Targeting global protected area expansion for imperiled biodiversity.

Science.gov (United States)

Venter, Oscar; Fuller, Richard A; Segan, Daniel B; Carwardine, Josie; Brooks, Thomas; Butchart, Stuart H M; Di Marco, Moreno; Iwamura, Takuya; Joseph, Liana; O'Grady, Damien; Possingham, Hugh P; Rondinini, Carlo; Smith, Robert J; Venter, Michelle; Watson, James E M

2014-06-01

Governments have agreed to expand the global protected area network from 13% to 17% of the world's land surface by 2020 (Aichi target 11) and to prevent the further loss of known threatened species (Aichi target 12). These targets are interdependent, as protected areas can stem biodiversity loss when strategically located and effectively managed. However, the global protected area estate is currently biased toward locations that are cheap to protect and away from important areas for biodiversity. Here we use data on the distribution of protected areas and threatened terrestrial birds, mammals, and amphibians to assess current and possible future coverage of these species under the convention. We discover that 17% of the 4,118 threatened vertebrates are not found in a single protected area and that fully 85% are not adequately covered (i.e., to a level consistent with their likely persistence). Using systematic conservation planning, we show that expanding protected areas to reach 17% coverage by protecting the cheapest land, even if ecoregionally representative, would increase the number of threatened vertebrates covered by only 6%. However, the nonlinear relationship between the cost of acquiring land and species coverage means that fivefold more threatened vertebrates could be adequately covered for only 1.5 times the cost of the cheapest solution, if cost efficiency and threatened vertebrates are both incorporated into protected area decision making. These results are robust to known errors in the vertebrate range maps. The Convention on Biological Diversity targets may stimulate major expansion of the global protected area estate. If this expansion is to secure a future for imperiled species, new protected areas must be sited more strategically than is presently the case.

Low-density hydrocarbon foams for laser fusion targets: Progress report, 1986

International Nuclear Information System (INIS)

Chen, C.; Cook, R.C.; Haendler, B.L.; Hair, L.M.; Kong, F.M.; Letts, S.A.

1987-06-01

We describe progress made during 1986 in the development of direct-drive hydrocarbon foam targets for laser fusion. The foam materials are polystyrene and resorcinolformaldehyde. The processes for making the foams, their properties, characterization techniques, and the relationships of their properties to target specifications are presented. In the final section, we discuss statistical experimental design techniques that are being used to optimize the foams. 12 refs., 14 figs., 2 tabs

A closer look at urban transport. TERM 2013: transport indicators tracking progress towards environmental targets in Europe

Energy Technology Data Exchange (ETDEWEB)

Sanchez Vicente, A.

2013-12-01

The EEA works in the transport area to assess the impacts of the sector on the human health and the environment. This work also allows the EEA to monitor the progress of integrating transport and environmental policies, and informing the EU, EEA member countries and the public about such progress. This is achieved by the production of relevant indicators that track progress towards policy targets for transport related to the environment, as well as through the elaboration of periodic assessments that cover all transport modes and the impacts of transport on the environment. The annual TERM report aims to enable policymakers to gauge the progress of those policies aiming to improve the environmental performance of the transport system as a whole. TERM 2013, has two distinct parts. Part A provides an annual assessment of the EU's transport and environment policies based on the TERM-CSI, a selection of 12 indicators from the broader set of EEA transport indicators to enabling monitoring of the most important aspects of transport. Part B focuses on urban transport and its effects on the environment. (LN)

Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.

Science.gov (United States)

Feng, Shu; Shao, Longjiang; Yu, Wendong; Gavine, Paul; Ittmann, Michael

2012-07-15

Extensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. Effects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model. AZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors. Targeting FGFR signaling is a promising new approach to treating aggressive prostate cancer.

Optically pumped polarized 23Na vapor target for use in polarized ion source. Technical progress report

International Nuclear Information System (INIS)

Anderson, L.W.

1984-01-01

We are currently measuring relaxation times in an optically pumped 23 Na vapor target. Our research is directed toward improvements in the optically pumped Na vapor targets used for the production of polarized H - ions. In this progress report we review the properties of the optically pumped polarized H - ion source and especially the optically pumped Na vapor target employed in this source as well as discussing the progress of our research on relaxation times in an optically pumped Na vapor target. 30 references, 6 figures, 3 tables

Fast neutron dose equivalent rates in heavy ion target areas

Energy Technology Data Exchange (ETDEWEB)

Fulmer, C.B.; Butler, H.M.; Ohnesorge, W.F.; Mosko, S.W.

1978-01-01

At heavy ion accelerators, personnel access to areas near the target is sometimes important for successful performance of experiments. Radiation levels determine the amount of time that can be spent in these areas without exceeding maximum permissible exposures. Inasmuch as the fast neutrons contribute the major part of the Rem dose rates in these areas, knowledge of the fast neutron levels is important for planning permissive entry to target areas. Fast neutron dose rates were measured near thick medium mass targets bombarded with beams of C, N, O, and Ne ions. beam energies ranged from 3 to 16 MeV/amu. Dose rates (mrem/h) 1 meter from the target 90 degrees from the beam direction range from approx. 0.05 at MeV/amu to approx. 50 at 16 MeV/amu. These data should be helpful in planning permissive entry to heavy ion target areas.

Fast neutron dose equivalent rates in heavy ion target areas

International Nuclear Information System (INIS)

Fulmer, C.B.; Butler, H.M.; Ohnesorge, W.F.; Mosko, S.W.

1978-01-01

At heavy ion accelerators, personnel access to areas near the target is sometimes important for successful performance of experiments. Radiation levels determine the amount of time that can be spent in these areas without exceeding maximum permissible exposures. Inasmuch as the fast neutrons contribute the major part of the Rem dose rates in these areas, knowledge of the fast neutron levels is important for planning permissive entry to target areas. Fast neutron dose rates were measured near thick medium mass targets bombarded with beams of C, N, O, and Ne ions. beam energies ranged from 3 to 16 MeV/amu. Dose rates (mrem/h) 1 meter from the target 90 degrees from the beam direction range from approx. 0.05 at MeV/amu to approx. 50 at 16 MeV/amu. These data should be helpful in planning permissive entry to heavy ion target areas

Large area solid target neutron source

International Nuclear Information System (INIS)

Crawford, J.C.; Bauer, W.

1974-01-01

A potentially useful neutron source may result from the combination of a solid deuterium-tritium loaded target with the large area, high energy ion beams from ion sources being developed for neutral beam injection. The resulting neutron source would have a large radiating area and thus produce the sizable experimental volume necessary for future studies of bulk and synergistic surface radiation effects as well as experiments on engineering samples and small components. With a 200 keV D + T + beam and 40 kW/cm 2 power dissipation on a 200 cm 2 target spot, a total neutron yield of about 4 x 10 15 n/sec may be achieved. Although the useable neutron flux from this source is limited to 1 to 2 x 10 13 n/cm 2 /sec, this flux can be produced 3 cm in front of the target and over about 300 cm 3 of experimental volume. Problems of total power dissipation, sputtering, isotopic flushing and thermal dissociation are reviewed. Neutron flux profiles and potential experimental configurations are presented and compared to other neutron source concepts. (U.S.)

Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

Directory of Open Access Journals (Sweden)

Annie Schmid-Alliana

2018-01-01

Full Text Available Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on surrounding bone tissue. Lastly, we detail therapies for bone metastases. Due to poor prognosis for patients, the strategies mainly aim at reducing the impact of skeletal-related events on patients’ quality of life. However, recent advances have led to a better understanding of molecular mechanisms underlying bone metastases progression, and therefore of novel therapeutic targets.

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

Directory of Open Access Journals (Sweden)

Feng Jiang

2015-10-01

Full Text Available Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX, are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

Review of laser mega joule target area: Design and processes

International Nuclear Information System (INIS)

Geitzholz, M.; Lanternier, C.

2006-01-01

The Laser Mega Joule (LMJ) target area is currently designed to achieve ignition and significant fusion gain in laboratory. LMJ will be composed of 240 identical large 370 mm * 370 mm square laser beams. These beams will focus 2 mega-joules of energy at the wavelength of 351 nm on the center of an experiment chamber. Design studies for target equipment are well advanced, target chamber and target holder (concrete) works have already begun. A detailed overview of the target area equipment is presented: target chamber, frame, diagnostic inserter manipulator, final optic assembly, dual diagnostic and laser reference, non cryogenic target positioner. Recent technical and architectural choices are detailed including safety transfers and alignment processes (target, laser and diagnostic). All this target equipment allows us to optimize shot chrono-gram, from target metrology to the shot, including calibration process. (authors)

Inequities in utilization of maternal health interventions in Namibia: implications for progress towards MDG 5 targets

Directory of Open Access Journals (Sweden)

Kirigia Joses

2010-06-01

Full Text Available Abstract Background Inequities in the utilization of maternal health services impede progress towards the MDG 5 target of reducing the maternal mortality ratio by three quarters, between 1990 and 2015. In Namibia, despite increasing investments in the health sector, the maternal mortality ratio has increased from 271 per 100,000 live births in the period 1991-2000 to 449 per 100,000 live births in 1998-2007. Monitoring equity in the use of maternal health services is important to target scarce resources to those with more need and expedite the progress towards the MDG 5 target. The objective of this study is to measure socio-economic inequalities in access to maternal health services and propose recommendations relevant for policy and planning. Methods Data from the Namibia Demographic and Health Survey 2006-07 are analyzed for inequities in the utilization of maternal health. In measuring the inequities, rate-ratios, concentration curves and concentration indices are used. Results Regions with relatively high human development index have the highest rates of delivery by skilled health service providers. The rate of caesarean section in women with post secondary education is about seven times that of women with no education. Women in urban areas are delivered by skilled providers 30% more than their rural counterparts. The rich use the public health facilities 30% more than the poor for child delivery. Conclusion Most of the indicators such as delivery by trained health providers, delivery by caesarean section and postnatal care show inequities favoring the most educated, urban areas, regions with high human development indices and the wealthy. In the presence of inequities, it is difficult to achieve a significant reduction in the maternal mortality ratio needed to realize the MDG 5 targets so long as a large segment of society has inadequate access to essential maternal health services and other basic social services. Addressing inequities in

Improving privacy protection in the area of behavioural targeting

NARCIS (Netherlands)

Zuiderveen Borgesius, F.J.

2014-01-01

This PhD thesis discusses how European law could improve privacy protection in the area of behavioural targeting. Behavioural targeting, also referred to as online profiling, involves monitoring people’s online behaviour, and using the collected information to show people individually targeted

Progress Toward Heavy Ion IFE

International Nuclear Information System (INIS)

Meier, W.R.; Logan, B.G.; Waldron, W.L.; Sabbi, G.L.; Callahan-Miller, D.A.; Peterson, P.F.; Goodin, D.T.

2002-01-01

Successful development of Heavy Ion Fusion (HIF) will require scientific and technology advances in areas of targets, drivers and chambers. Design work on heavy ion targets indicates that high gain (60-130) may be possible with a -3-6 MJ driver depending on the ability to focus the beams to small spot sizes. Significant improvements have been made on key components of heavy ion drivers, including sources, injectors, insulators and ferromagnetic materials for long-pulse induction accelerator cells, solid-state pulsers, and superconducting quadrupole magnets. The leading chamber concept for HIF is the thick-liquid-wall HYLEE-II design, which uses an array of flibe jets to protect chamber structures from x-ray, debris, and neutron damage. Significant progress has been made in demonstrating the ability to create and control the types of flow needed to form the protective liquid blanket. Progress has also been made on neutron shielding for the final focus magnet arrays with predicted lifetimes now exceeding the life of the power plant. Safety analyses have been completed for the HYLEE-II design using state-of-the-art codes. Work also continues on target fabrication and injection for HE. A target injector experiment capable of > 5 Hz operation has been designed and construction will start in 2002. Methods for mass production of hohlraum targets are being evaluated with small-scale experiments and analyses. Progress in these areas will be reviewed

Progress toward heavy-ion IFE

International Nuclear Information System (INIS)

Meier, W.R.; Logan, B.G.; Waldron, W.L.; Sabbi, G.-L.; Callahan, D.A.; Peterson, P.F.; Goodin, D.T.

2002-01-01

Successful development of heavy-ion fusion (HIF) will require scientific and technology advances in areas of targets, drivers and chambers. Design work on heavy-ion targets indicates that high gain (60-130) may be possible with a ∼3-6 MJ driver depending on the ability to focus the beams to small spot sizes. Significant improvements have been made on key components of heavy-ion drivers, including sources, injectors, insulators and ferromagnetic materials for long-pulse induction accelerator cells, solid-state pulsers, and superconducting quadrupole magnets. The leading chamber concept for HIF is the thick-liquid-wall HYLIFE-II design, which uses an array of flibe jets to protect chamber structures from X-ray, debris, and neutron damage. Significant progress has been made in demonstrating the ability to create and control the types of flow needed to form the protective liquid blanket. Progress has also been made on neutron shielding for the final focus magnet arrays with predicted lifetimes now exceeding the life of the power plant. Safety analyses have been completed for the HYLIFE-II design using state-of-the-art codes. Work also continues on target fabrication and injection for HIF. A target injector experiment capable of >5 Hz operation has been designed and construction will start in 2002. Methods for mass-production of hohlraum targets are being evaluated with small-scale experiments and analyses. Progress in these areas will be reviewed

IMS Mitigation Target Areas - 2010 [ds673

Data.gov (United States)

California Natural Resource Agency — Mitigation Target Areas (MTA) were developed by the California Department of Fish and Game for the Interim Mitigation Strategy (IMS). The MTAs are an identification...

Consolidated progress report for 1976 on nuclear data activities in the NDS service area

International Nuclear Information System (INIS)

1977-10-01

A consolidated progress report for 1976 prepared for countries in the NDS service area. It is intended to encourage a closer relationship between Member States and provide for a wider circulation of unpublished progress reports from countries within the Nuclear Data Section service area

Target area for Nova upgrade: Containing ignition and beyond

International Nuclear Information System (INIS)

Tobin, M.T.; Smith, J.R.; Campbell, D.; Wong, D.K.; Sullivan, J.A.; Pendergrass, J.; Weinstein, B.; Klein, M.

1991-01-01

The Lawrence Livermore National Laboratory (LLNL) is developing a conceptual design for upgrading the Nova laser from ∼ 50 kJ to ∼ 1.8 MJ of laser energy at a wavelength of 351 nm. Anticipated target performance includes achieving ignition and possibly fusion yields to 20 MJ. The target area design represents a unique challenge since it will be operating in a regime where first wall ablation and optics damage are major issues for the first time in an ICF facility. Here we describe potential performance criteria for the facility and anticipated yield-dependent x-ray, neutron, shrapnel, and debris environments. We also briefly describe the different systems that make up the target area and discuss some of the design issues. The insignificant environmental impact Nova Upgrade (NU) operations is anticipated to have on the laboratory and surrounding area is discussed. Finally, alternate design options are described along with their potential benefits

Error Analysis of Fast Moving Target Geo-location in Wide Area Surveillance Ground Moving Target Indication Mode

Directory of Open Access Journals (Sweden)

Zheng Shi-chao

2013-12-01

Full Text Available As an important mode in airborne radar systems, Wide Area Surveillance Ground Moving Target Indication (WAS-GMTI mode has the ability of monitoring a large area in a short time, and then the detected moving targets can be located quickly. However, in real environment, many factors introduce considerable errors into the location of moving targets. In this paper, a fast location method based on the characteristics of the moving targets in WAS-GMTI mode is utilized. And in order to improve the location performance, those factors that introduce location errors are analyzed and moving targets are relocated. Finally, the analysis of those factors is proved to be reasonable by simulation and real data experiments.

Rare isotope accelerator—conceptual design of target areas

Science.gov (United States)

Bollen, Georg; Baek, Inseok; Blideanu, Valentin; Lawton, Don; Mantica, Paul F.; Morrissey, David J.; Ronningen, Reginald M.; Sherrill, Bradley S.; Zeller, Albert; Beene, James R.; Burgess, Tom; Carter, Kenneth; Carrol, Adam; Conner, David; Gabriel, Tony; Mansur, Louis; Remec, Igor; Rennich, Mark; Stracener, Dan; Wendel, Mark; Ahle, Larry; Boles, Jason; Reyes, Susana; Stein, Werner; Heilbronn, Lawrence

2006-06-01

The planned rare isotope accelerator facility RIA in the US would become the most powerful radioactive beam facility in the world. RIA's driver accelerator will be a device capable of providing beams from protons to uranium at energies of at least 400 MeV per nucleon, with beam power up to 400 kW. Radioactive beam production relies on both the in-flight separation of fast beam fragments and on the ISOL technique. In both cases the high beam power poses major challenges for target technology and handling and on the design of the beam production areas. This paper will give a brief overview of RIA and discuss aspects of ongoing conceptual design work for the RIA target areas.

Rare isotope accelerator - conceptual design of target areas

International Nuclear Information System (INIS)

Bollen, Georg; Baek, Inseok; Blideanu, Valentin; Lawton, Don; Mantica, Paul F.; Morrissey, David J.; Ronningen, Reginald M.; Sherrill, Bradley S.; Zeller, Albert; Beene, James R; Burgess, Tom; Carter, Kenneth; Carrol, Adam; Conner, David; Gabriel, Tony A; Mansur, Louis K; Remec, Igor; Rennich, Mark J; Stracener, Daniel W; Wendel, Mark W; Ahle, Larry; Boles, Jason; Reyes, Susana; Stein, Werner; Heilbronn, Lawrence

2006-01-01

The planned rare isotope accelerator facility RIA in the US would become the most powerful radioactive beam facility in the world. RIA's driver accelerator will be a device capable of providing beams from protons to uranium at energies of at least 400MeV per nucleon, with beam power up to 400 kW. Radioactive beam production relies on both the in-flight separation of fast beam fragments and on the ISOL technique. In both cases the high beam power poses major challenges for target technology and handling and on the design of the beam production areas. This paper will give a brief overview of RIA and discuss aspects of ongoing conceptual design work for the RIA target areas

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)

Theoretical Research Progress in High-Velocity/Hypervelocity Impact on Semi-Infinite Targets

Directory of Open Access Journals (Sweden)

Yunhou Sun

2015-01-01

Full Text Available With the hypervelocity kinetic weapon and hypersonic cruise missiles research projects being carried out, the damage mechanism for high-velocity/hypervelocity projectile impact on semi-infinite targets has become the research keystone in impact dynamics. Theoretical research progress in high-velocity/hypervelocity impact on semi-infinite targets was reviewed in this paper. The evaluation methods for critical velocity of high-velocity and hypervelocity impact were summarized. The crater shape, crater scaling laws and empirical formulae, and simplified analysis models of crater parameters for spherical projectiles impact on semi-infinite targets were reviewed, so were the long rod penetration state differentiation, penetration depth calculation models for the semifluid, and deformed long rod projectiles. Finally, some research proposals were given for further study.

MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1.

Science.gov (United States)

Wang, Yongxia; Zhang, Zheying; Wang, Jianqiang

2018-04-20

Breast cancer is the leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancer cases and has a poorer prognosis than other subtypes. Moreover, the treatment for breast cancer, especially for TNBC, remains unsatisfactory. Therefore, novel therapies are urgently needed. Microribonucleic acids (miRNAs) are a class of biomarkers and therapeutic targets in many types of cancers. In the present study, the expression of miR-384 was explored in GSE58606 and in fresh breast cancer tissues by qPCR. The results showed that miR-384 was decreased in breast cancer, especially in TNBC. The results of MTT, colony formation, soft agar, Transwell migration, wound healing and the tumorigenesis assay demonstranted that overexpression of miR-384 inhibited the proliferation and migration of breast cancer in vitro and in vivo; knockdown of miR-384 enhanced the proliferation and migration of breast cancer. In addition, luciferase assay showed that Activin A receptor type 1 (ACVR1) was a direct target of miR-384 and is involved in the inhibitory effects of miR-384 on breast cancer progression. Furthermore, this study indicated that ACVR1 activated the Wnt/β-catenin signaling pathway in breast cancer. In conclusion, our findings revealed functional and mechanistic links between miR-384 and ACVR1 in the progression of breast cancer. miR-384 not only plays an important role in the progression of breast cancer, but has promise as a potential therapeutic target for breast cancer especially for TNBC.

Setting a research agenda for progressive multiple sclerosis: the International Collaborative on Progressive MS.

Science.gov (United States)

Fox, Robert J; Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-11-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS.

Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS

Science.gov (United States)

Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-01-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS. PMID:22917690

Rare Isotope Accelerator - Conceptual Design of Target Areas

Energy Technology Data Exchange (ETDEWEB)

Bollen, Georg [Michigan State University, East Lansing; Baek, Inseok [Michigan State University, East Lansing; Blideanu, Valentin [CEA, Saclay, France; Lawton, Don [Michigan State University, East Lansing; Mantica, Paul F. [Michigan State University, East Lansing; Morrissey, David J. [Michigan State University, East Lansing; Ronningen, Reginald M. [Michigan State University, East Lansing; Sherrill, Bradley S. [Michigan State University, East Lansing; Zeller, Albert [Michigan State University, East Lansing; Beene, James R [ORNL; Burgess, Tom [Oak Ridge National Laboratory (ORNL); Carter, Kenneth [Oak Ridge National Laboratory (ORNL); Carrol, Adam [Oak Ridge National Laboratory (ORNL); Conner, David [ORNL; Gabriel, Tony A [ORNL; Mansur, Louis K [ORNL; Remec, Igor [ORNL; Rennich, Mark J [ORNL; Stracener, Daniel W [ORNL; Wendel, Mark W [ORNL; Ahle, Larry [Lawrence Livermore National Laboratory (LLNL); Boles, Jason [Lawrence Livermore National Laboratory (LLNL); Reyes, Susana [Lawrence Livermore National Laboratory (LLNL); Stein, Werner [Lawrence Livermore National Laboratory (LLNL); Heilbronn, Lawrence [Lawrence Berkeley National Laboratory (LBNL)

2006-01-01

The planned rare isotope accelerator facility RIA in the US would become the most powerful radioactive beam facility in the world. RIA s driver accelerator will be a device capable of providing beams from protons to uranium at energies of at least 400MeV per nucleon, with beam power up to 400 kW. Radioactive beam production relies on both the in-flight separation of fast beam fragments and on the ISOL technique. In both cases the high beam power poses major challenges for target technology and handling and on the design of the beam production areas. This paper will give a brief overview of RIA and discuss aspects of ongoing conceptual design work for the RIA target areas.

Rare isotope accelerator-conceptual design of target areas

Energy Technology Data Exchange (ETDEWEB)

Bollen, Georg [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824 (United States)]. E-mail: bollen@nscl.msu.edu; Baek, Inseok; Blideanu, Valentin; Lawton, Don; Mantica, Paul F.; Morrissey, David J.; Ronningen, Reginald M.; Sherrill, Bradley S.; Zeller, Albert [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824 (United States); Beene, James R.; Burgess, Tom; Carter, Kenneth; Carrol, Adam; Conner, David; Gabriel, Tony; Mansur, Louis; Remec, Igor; Rennich, Mark; Stracener, Dan; Wendel, Mark [Oak Ridge National Laboratory, Oak Ridge, TN 37830 (United States); Ahle, Larry; Boles, Jason; Reyes, Susana; Stein, Werner [Lawrence Livermore Laboratory, Livermore, CA 94550 (United States); Heilbronn, Lawrence [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States)

2006-06-23

The planned rare isotope accelerator facility RIA in the US would become the most powerful radioactive beam facility in the world. RIA's driver accelerator will be a device capable of providing beams from protons to uranium at energies of at least 400 MeV per nucleon, with beam power up to 400 kW. Radioactive beam production relies on both the in-flight separation of fast beam fragments and on the ISOL technique. In both cases the high beam power poses major challenges for target technology and handling and on the design of the beam production areas. This paper will give a brief overview of RIA and discuss aspects of ongoing conceptual design work for the RIA target areas.

Targeting epigenetics for the treatment of prostate cancer: recent progress and future directions.

Science.gov (United States)

Lin, Jianqing; Wang, Chenguang; Kelly, Wm Kevin

2013-06-01

Epigenetic aberrations contribute to prostate cancer carcinogenesis and disease progression. Efforts have been made to target DNA methyltransferase and histone deacetylases (HDACs) in prostate cancer and other solid tumors but have not had the success that was seen in the hematologic malignancies. Oral, less toxic, and more specific agents are being developed in solid tumors including prostate cancer. Combinations of epigenetic agents alone or with a targeted agent such as androgen receptor signaling inhibitors are promising approaches and will be discussed further. Copyright © 2013 Elsevier Inc. All rights reserved.

Particle beam fusion progress report, January-June 1980

International Nuclear Information System (INIS)

1981-05-01

An overview and technical summaries are given for research progress in each of the following general areas: (1) fusion target studies; (2) target experiments; (3) particle beam source theory; (4) diagnostics development; (5) particle beam experiments; (6) pulsed power research and development; (7) pulse power application; and (8) Electron Beam Fusion Accelerator project

Target experimental area and systems of the U.S. 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

1999-01-01

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 the authors 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

A biodiversity indicators dashboard: addressing challenges to monitoring progress towards the Aichi biodiversity targets using disaggregated global data.

Science.gov (United States)

Han, Xuemei; Smyth, Regan L; Young, Bruce E; Brooks, Thomas M; Sánchez de Lozada, Alexandra; Bubb, Philip; Butchart, Stuart H M; Larsen, Frank W; Hamilton, Healy; Hansen, Matthew C; Turner, Will R

2014-01-01

Recognizing the imperiled status of biodiversity and its benefit to human well-being, the world's governments committed in 2010 to take effective and urgent action to halt biodiversity loss through the Convention on Biological Diversity's "Aichi Targets". These targets, and many conservation programs, require monitoring to assess progress toward specific goals. However, comprehensive and easily understood information on biodiversity trends at appropriate spatial scales is often not available to the policy makers, managers, and scientists who require it. We surveyed conservation stakeholders in three geographically diverse regions of critical biodiversity concern (the Tropical Andes, the African Great Lakes, and the Greater Mekong) and found high demand for biodiversity indicator information but uneven availability. To begin to address this need, we present a biodiversity "dashboard"--a visualization of biodiversity indicators designed to enable tracking of biodiversity and conservation performance data in a clear, user-friendly format. This builds on previous, more conceptual, indicator work to create an operationalized online interface communicating multiple indicators at multiple spatial scales. We structured this dashboard around the Pressure-State-Response-Benefit framework, selecting four indicators to measure pressure on biodiversity (deforestation rate), state of species (Red List Index), conservation response (protection of key biodiversity areas), and benefits to human populations (freshwater provision). Disaggregating global data, we present dashboard maps and graphics for the three regions surveyed and their component countries. These visualizations provide charts showing regional and national trends and lay the foundation for a web-enabled, interactive biodiversity indicators dashboard. This new tool can help track progress toward the Aichi Targets, support national monitoring and reporting, and inform outcome-based policy-making for the protection of

A biodiversity indicators dashboard: addressing challenges to monitoring progress towards the Aichi biodiversity targets using disaggregated global data.

Directory of Open Access Journals (Sweden)

Xuemei Han

Full Text Available Recognizing the imperiled status of biodiversity and its benefit to human well-being, the world's governments committed in 2010 to take effective and urgent action to halt biodiversity loss through the Convention on Biological Diversity's "Aichi Targets". These targets, and many conservation programs, require monitoring to assess progress toward specific goals. However, comprehensive and easily understood information on biodiversity trends at appropriate spatial scales is often not available to the policy makers, managers, and scientists who require it. We surveyed conservation stakeholders in three geographically diverse regions of critical biodiversity concern (the Tropical Andes, the African Great Lakes, and the Greater Mekong and found high demand for biodiversity indicator information but uneven availability. To begin to address this need, we present a biodiversity "dashboard"--a visualization of biodiversity indicators designed to enable tracking of biodiversity and conservation performance data in a clear, user-friendly format. This builds on previous, more conceptual, indicator work to create an operationalized online interface communicating multiple indicators at multiple spatial scales. We structured this dashboard around the Pressure-State-Response-Benefit framework, selecting four indicators to measure pressure on biodiversity (deforestation rate, state of species (Red List Index, conservation response (protection of key biodiversity areas, and benefits to human populations (freshwater provision. Disaggregating global data, we present dashboard maps and graphics for the three regions surveyed and their component countries. These visualizations provide charts showing regional and national trends and lay the foundation for a web-enabled, interactive biodiversity indicators dashboard. This new tool can help track progress toward the Aichi Targets, support national monitoring and reporting, and inform outcome-based policy-making for the

Radiation Target Area Sample Environmental Chamber (RTASEC), Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Payload Systems Inc. proposes the Radiation Target Area Sample Environmental Chamber (RTASEC) as an innovative approach enabling radiobiologists to investigate the...

AA, radiation shielding curtain along the target area

CERN Multimedia

CERN PhotoLab

1980-01-01

At the far left is the beam tube for the high-intensity proton beam from the 26 GeV PS. The tube ends in a thin window and the proton beam continues in air through a hole in the shielding blocks (see also 8010308), behind which the target (see 7905091, 7905094)was located. After the target followed the magnetic horn, focusing the antiprotons, and the first part of the injection line with a proton dump. The antiprotons, deflected by a magnet, left the target area through another shielding wall, to make their way to the AA ring. Laterally, this sequence of components was shielded with movable, suspended, concrete blocks: the "curtain". Balasz Szeless, who had constructed it, is standing at its side.

Qualitative values of radioactivity, area and volumetric: Application on phantoms (target and background)

Energy Technology Data Exchange (ETDEWEB)

Abdel-Rahman Al-Shakhrah, Issa [Department of Physics, University of Jordan, Queen Rania Street, Amman (Jordan)], E-mail: issashak@yahoo.com

2009-04-15

The visualization of a lesion depends on the contrast between the lesion and surrounding background (T/B; (target/background) ratio). For imaging in vivo not only is the radioactivity in the target organ important, but so too is the ratio of radioactivity in the target versus that in the background. Nearly all studies reported in the literature have dealt with the surface index, as a standard factor to study the relationship between the target (tissue or organ) and the background. It is necessary to know the ratio between the volumetric activity of lesions (targets) and normal tissues (background) instead of knowing the ratio between the area activity, the volume index being a more realistic factor than the area index as the targets (tissues or organs) are real volumes that have surfaces. The intention is that this work should aid in approaching a quantitative relationship and differentiation between different tissues (target/background or abnormal/normal tissues). For the background, square regions of interest (Rios) (11x11 pixels in size) were manually drawn by the observer at locations far from the border of the plastic cylinder (simulated organ), while an isocontour region with 50% threshold was drawn automatically over the cylinder. The total number of counts and pixels in each of these regions was calculated. The relationship between different phantom parameters, cylinder (target) depth, area activity ratio (background/target, A(B/T)) and real volumetric activity ratio (background/target, V(B/T)), was demonstrated. Variations in the area and volumetric activity ratio values with respect to the depth were deduced. To find a realistic value of the ratio, calibration charts have been constructed that relate the area and real volumetric ratios as a function of depth of the tissues and organs. Our experiments show that the cross-sectional area of the cylinder (applying a threshold 50% isocontour) has a weak dependence on the activity concentrations of the

Qualitative values of radioactivity, area and volumetric: Application on phantoms (target and background)

International Nuclear Information System (INIS)

Abdel-Rahman Al-Shakhrah, Issa

2009-01-01

The visualization of a lesion depends on the contrast between the lesion and surrounding background (T/B; (target/background) ratio). For imaging in vivo not only is the radioactivity in the target organ important, but so too is the ratio of radioactivity in the target versus that in the background. Nearly all studies reported in the literature have dealt with the surface index, as a standard factor to study the relationship between the target (tissue or organ) and the background. It is necessary to know the ratio between the volumetric activity of lesions (targets) and normal tissues (background) instead of knowing the ratio between the area activity, the volume index being a more realistic factor than the area index as the targets (tissues or organs) are real volumes that have surfaces. The intention is that this work should aid in approaching a quantitative relationship and differentiation between different tissues (target/background or abnormal/normal tissues). For the background, square regions of interest (Rios) (11x11 pixels in size) were manually drawn by the observer at locations far from the border of the plastic cylinder (simulated organ), while an isocontour region with 50% threshold was drawn automatically over the cylinder. The total number of counts and pixels in each of these regions was calculated. The relationship between different phantom parameters, cylinder (target) depth, area activity ratio (background/target, A(B/T)) and real volumetric activity ratio (background/target, V(B/T)), was demonstrated. Variations in the area and volumetric activity ratio values with respect to the depth were deduced. To find a realistic value of the ratio, calibration charts have been constructed that relate the area and real volumetric ratios as a function of depth of the tissues and organs. Our experiments show that the cross-sectional area of the cylinder (applying a threshold 50% isocontour) has a weak dependence on the activity concentrations of the

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

Energy Technology Data Exchange (ETDEWEB)

Ovink, R.

2012-09-18

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

Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer.

Science.gov (United States)

Xiong, Ting; Liu, Xiao-Wang; Huang, Xue-Long; Xu, Xiong-Feng; Xie, Wei-Quan; Zhang, Su-Jun; Tu, Jian

2018-05-01

Diallyl disulfide (DADS), a volatile component of garlic oil, has various biological properties, including antioxidant, antiangiogenic and anticancer effects. The present study aimed to explore novel targets of DADS that may slow or stop the progression of breast cancer. First, xenograft tumor models were created by subcutaneously injecting MCF-7 and MDA-MB-231 breast cancer cells into nude mice. Subsequently, western blot analysis was performed to investigate the expression of tristetraprolin (TTP), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in the xenograft tumors, and cell cultures. Tablet cloning, Transwell and wound healing assays revealed that DADS treatment significantly inhibited the proliferation, invasion and migration of breast cancer cells. In addition, DADS treatment led to significant downregulation of uPA and MMP-9 protein expression, but significantly upregulated TTP expression in vivo and in vitro . Knocking down TTP expression using small interfering RNA reversed the aforementioned effects of DADS, which suggests TTP is a key target of DADS in inhibiting the progression of breast cancer.

Tilted bending magnet for SPS target area TCC2

CERN Multimedia

CERN PhotoLab

1976-01-01

A slow-extracted proton beam from the SPS goes to the underground target zone TCC2. The part of the primary beam which traverses target T4 is recuperated and transported over some 800 m, for further use in the North Area High Intensity facility (NAHIF). The curved and sloped trajectory required 4 of the bending magnets to be tilted. Here we see one of them being attended by Gilbert Françon in hall 867, ready for installation in TCC2.

Inhibition of prostate cancer osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and tumor neovasculature.

Science.gov (United States)

Mohamedali, Khalid A; Li, Zhi Gang; Starbuck, Michael W; Wan, Xinhai; Yang, Jun; Kim, Sehoon; Zhang, Wendy; Rosenblum, Michael G; Navone, Nora M

2011-04-15

A hallmark of prostate cancer (PCa) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that VEGF(121)/rGel targets osteoclast precursors and tumor neovasculature. Here we tested the hypothesis that targeting nontumor cells expressing these receptors can inhibit tumor progression in a clinically relevant model of osteoblastic PCa. Cells from MDA PCa 118b, a PCa xenograft obtained from a bone metastasis in a patient with castrate-resistant PCa, were injected into the femurs of mice. Osteoblastic progression was monitored following systemic administration of VEGF(121)/rGel. VEGF(121)/rGel was cytotoxic in vitro to osteoblast precursor cells. This cytotoxicity was specific as VEGF(121)/rGel internalization into osteoblasts was VEGF(121) receptor driven. Furthermore, VEGF(121)/rGel significantly inhibited PCa-induced bone formation in a mouse calvaria culture assay. In vivo, VEGF(121)/rGel significantly inhibited the osteoblastic progression of PCa cells in the femurs of nude mice. Microcomputed tomographic analysis revealed that VEGF(121)/rGel restored the bone volume fraction of tumor-bearing femurs to values similar to those of the contralateral (non-tumor-bearing) femurs. VEGF(121)/rGel significantly reduced the number of tumor-associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, VEGF(121)/rGel-treated mice had significantly less tumor burden than control mice. Our results thus indicate that VEGF(121)/rGel inhibits osteoblastic tumor progression by targeting angiogenesis, osteoclastogenesis, and bone formation. Targeting VEGF receptor (VEGFR)-1- or VEGFR-2-expressing cells is effective in controlling the osteoblastic progression of PCa in bone. These findings provide the basis for an effective multitargeted approach for metastatic PCa. ©2011 AACR.

Inhibition of prostate cancer osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and tumor neovasculature

Science.gov (United States)

Mohamedali, Khalid A.; Li, Zhi Gang; Starbuck, Michael W.; Wan, Xinhai; Yang, Jun; Kim, Sehoon; Zhang, Wendy; Rosenblum, Michael G.; Navone, Nora M.

2011-01-01

Purpose A hallmark of prostate cancer (PCa) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that VEGF121/rGel targets osteoclast precursors and tumor neovasculature. Here we tested the hypothesis that targeting non-tumor cells expressing these receptors can inhibit tumor progression in a clinically relevant model of osteoblastic PCa. Experimental Design Cells from MDA PCa 118b, a PCa xenograft obtained from a bone metastasis in a patient with castrate-resistant PCa, were injected into the femurs of mice. Osteoblastic progression was monitored following systemic administration of VEGF121/rGel. Results VEGF121/rGel was cytotoxic in vitro to osteoblast precursor cells. This cytotoxicity was specific as VEGF121/rGel internalization into osteoblasts was VEGF121 receptor driven. Furthermore, VEGF121/rGel significantly inhibited PCa-induced bone formation in a mouse calvaria culture assay. In vivo, VEGF121/rGel significantly inhibited the osteoblastic progression of PCa cells in the femurs of nude mice. Microcomputed tomography analysis revealed that VEGF121/rGel restored the bone volume fraction of tumor-bearing femurs to values similar to those of the contralateral (non–tumor bearing) femurs. VEGF121/rGel significantly reduced the number of tumor-associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, VEGF121/rGel-treated mice had significantly less tumor burden than control mice. Our results thus indicate that VEGF121/rGel inhibits osteoblastic tumor progression by targeting angiogenesis, osteoclastogenesis, and bone formation. Conclusions Targeting VEGFR-1 – or VEGFR-2–expressing cells is effective in controlling the osteoblastic progression of PCa in bone. These findings provide the basis for an effective multitargeted approach for metastatic PCa. PMID:21343372

En Face Spectral-Domain Optical Coherence Tomography for the Monitoring of Lesion Area Progression in Stargardt Disease.

Science.gov (United States)

Melillo, Paolo; Testa, Francesco; Rossi, Settimio; Di Iorio, Valentina; Orrico, Ada; Auricchio, Alberto; Simonelli, Francesca

2016-07-01

We investigated the progression of Stargardt disease (STGD1) over a multiyear follow-up by evaluating the macular lesion area as computed by an automatic algorithm from spectral-domain optical coherence tomography (SD-OCT). We reviewed medical records of STGD1 patients, with a clinical and molecular diagnosis of STGD1 at a single institution, who underwent best-corrected visual acuity (BCVA), fundus photography, SD-OCT, full-field electroretinography, and, when available, fundus autofluorescence (FAF). Regression models were fitted on the selected clinical parameters; in particular, on the macular lesion area computed by SD-OCT, to evaluate the disease progression over a multiyear follow-up. The comparison between SD-OCT and FAF, available for 22 patients, showed that macular lesion area, assessed by SD-OCT, significantly correlated with the area of absent FAF (P disease, showing a significant progression over the follow-up. Our findings suggest that the evaluation of macular lesion area by en face SD-OCT, together with FAF, could drive the choice of the most amenable candidates and the most suitable area to be treated in gene therapy clinical trials.

Empowerment Zones and Enterprise Districts - MDC_TargetUrbanAreaCorridor

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — A polygon feature class of Miami-Dade County, Targeted Urban Area Corridors. This coverage was created for the Office of Community & Economic Development (OCED)...

THE LOW BACKSCATTERING TARGETS CLASSIFICATION IN URBAN AREAS

Directory of Open Access Journals (Sweden)

L. Shi

2012-07-01

Full Text Available The Polarimetric and Interferometric Synthetic Aperture Radar (POLINSAR is widely used in urban area nowadays. Because of the physical and geometric sensitivity, the POLINSAR is suitable for the city classification, power-lines detection, building extraction, etc. As the new X-band POLINSAR radar, the china prototype airborne system, XSAR works with high spatial resolution in azimuth (0.1 m and slant range (0.4 m. In land applications, SAR image classification is a useful tool to distinguish the interesting area and obtain the target information. The bare soil, the cement road, the water and the building shadow are common scenes in the urban area. As it always exists low backscattering sign objects (LBO with the similar scattering mechanism (all odd bounce except for shadow in the XSAR images, classes are usually confused in Wishart-H-Alpha and Freeman-Durden methods. It is very hard to distinguish those targets only using the general information. To overcome the shortage, this paper explores an improved algorithm for LBO refined classification based on the Pre-Classification in urban areas. Firstly, the Pre-Classification is applied in the polarimetric datum and the mixture class is marked which contains LBO. Then, the polarimetric covariance matrix C3 is re-estimated on the Pre-Classification results to get more reliable results. Finally, the occurrence space which combining the entropy and the phase-diff standard deviation between HH and VV channel is used to refine the Pre-Classification results. The XSAR airborne experiments show the improved method is potential to distinguish the mixture classes in the low backscattering objects.

National Ignition Facility subsystem design requirements target area auxiliary subsystem SSDR 1.8.6

International Nuclear Information System (INIS)

Reitz, T.

1996-01-01

This Subsystem Design Requirement (SSDR) establishes the performance, design, development, and test requirements for the Target Area Auxiliary Subsystems (WBS 1.8.6), which is part of the NIF Target Experimental System (WBS 1.8). This document responds directly to the requirements detailed in NIF Target Experimental System SDR 003 document. Key elements of the Target Area Auxiliary Subsystems include: WBS 1.8.6.1 Local Utility Services; WBS 1.8.6.2 Cable Trays; WBS 1.8.6.3 Personnel, Safety, and Occupational Access; WBS 1.8.6.4 Assembly, Installation, and Maintenance Equipment; WBS 1.8.6.4.1 Target Chamber Service System; WBS 1.8.6.4.2 Target Bay Service Systems

Contractors Road Heavy Equipment Area SWMU 055 Corrective Measures Implementation Progress Report

Science.gov (United States)

Dorman, Lane

2015-01-01

This Corrective Measures Implementation (CMI) Progress Report, Revision 1, for Contractor's Road Heavy Equipment (CRHE) Area Solid Waste Management Unit (SWMU) Number 055 was prepared by Geosyntec Consultants (Geosyntec) for the National Aeronautics and Space Administration (NASA) under contract number NNK09CA02B, Delivery Order NNK09CA62D and Project Number PCN ENV-2324. This CMI Progress Report documents: (i) activities conducted as part of supplemental assessment activities completed from June 2009 through November 2014; (ii) Engineering Evaluation (EE) Advanced Data Packages (ADPs); and (iii) recommendations for future activities related to corrective measures at the Site.

Quantitative PET Imaging with Novel HER3 Targeted Peptides Selected by Phage Display to Predict Androgen Independent Prostate Cancer Progression

Science.gov (United States)

2017-08-01

Independent Prostate Cancer Progression PRINCIPAL INVESTIGATOR: Benjamin Larimer, PhD CONTRACTING ORGANIZATION: Massachusetts General Hospital Boston...3. DATES COVERED 1 Aug 2016 – 31 July 2017 4. TITLE AND SUBTITLE Cancer Progression 5a. CONTRACT NUMBER Quantitative PET Imaging with Novel HER3...Targeted Peptides Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression 5b. GRANT NUMBER W81XWH-16-1-0447 5c

A Biodiversity Indicators Dashboard: Addressing Challenges to Monitoring Progress towards the Aichi Biodiversity Targets Using Disaggregated Global Data

Science.gov (United States)

Han, Xuemei; Smyth, Regan L.; Young, Bruce E.; Brooks, Thomas M.; Sánchez de Lozada, Alexandra; Bubb, Philip; Butchart, Stuart H. M.; Larsen, Frank W.; Hamilton, Healy; Hansen, Matthew C.; Turner, Will R.

2014-01-01

Recognizing the imperiled status of biodiversity and its benefit to human well-being, the world's governments committed in 2010 to take effective and urgent action to halt biodiversity loss through the Convention on Biological Diversity's “Aichi Targets”. These targets, and many conservation programs, require monitoring to assess progress toward specific goals. However, comprehensive and easily understood information on biodiversity trends at appropriate spatial scales is often not available to the policy makers, managers, and scientists who require it. We surveyed conservation stakeholders in three geographically diverse regions of critical biodiversity concern (the Tropical Andes, the African Great Lakes, and the Greater Mekong) and found high demand for biodiversity indicator information but uneven availability. To begin to address this need, we present a biodiversity “dashboard” – a visualization of biodiversity indicators designed to enable tracking of biodiversity and conservation performance data in a clear, user-friendly format. This builds on previous, more conceptual, indicator work to create an operationalized online interface communicating multiple indicators at multiple spatial scales. We structured this dashboard around the Pressure-State-Response-Benefit framework, selecting four indicators to measure pressure on biodiversity (deforestation rate), state of species (Red List Index), conservation response (protection of key biodiversity areas), and benefits to human populations (freshwater provision). Disaggregating global data, we present dashboard maps and graphics for the three regions surveyed and their component countries. These visualizations provide charts showing regional and national trends and lay the foundation for a web-enabled, interactive biodiversity indicators dashboard. This new tool can help track progress toward the Aichi Targets, support national monitoring and reporting, and inform outcome-based policy-making for the

En Face Spectral-Domain Optical Coherence Tomography for the Monitoring of Lesion Area Progression in Stargardt Disease

Science.gov (United States)

Melillo, Paolo; Testa, Francesco; Rossi, Settimio; Di Iorio, Valentina; Orrico, Ada; Auricchio, Alberto; Simonelli, Francesca

2016-01-01

Purpose We investigated the progression of Stargardt disease (STGD1) over a multiyear follow-up by evaluating the macular lesion area as computed by an automatic algorithm from spectral-domain optical coherence tomography (SD-OCT). Methods We reviewed medical records of STGD1 patients, with a clinical and molecular diagnosis of STGD1 at a single institution, who underwent best-corrected visual acuity (BCVA), fundus photography, SD-OCT, full-field electroretinography, and, when available, fundus autofluorescence (FAF). Regression models were fitted on the selected clinical parameters; in particular, on the macular lesion area computed by SD-OCT, to evaluate the disease progression over a multiyear follow-up. Results The comparison between SD-OCT and FAF, available for 22 patients, showed that macular lesion area, assessed by SD-OCT, significantly correlated with the area of absent FAF (P disease, showing a significant progression over the follow-up. Our findings suggest that the evaluation of macular lesion area by en face SD-OCT, together with FAF, could drive the choice of the most amenable candidates and the most suitable area to be treated in gene therapy clinical trials. PMID:27409479

[Purification of 67Cu]. Progress report

International Nuclear Information System (INIS)

DeNardo, S.J.

1994-01-01

This report documents progress made in several areas of research and describes results which have not yet been published. These areas include: Purification of 67 Cu; Macrocyclic chelates for targeted therapy; Studies of biologic activation associated with molecular receptor increase and tumor response in ChL6/L6 protocol patients; Lym-1 single chain genetically engineered molecules; Analysis of molecular genetic coded messages to enhance tumor response; Human dosimetry and therapeutic human use radiopharmaceuticals; studies in phantoms; Quantitative SPECT; Preclinical studies; and Clinical studies

Progress on LMJ targets for ignition

Energy Technology Data Exchange (ETDEWEB)

Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Dattolo, E; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L, E-mail: catherine.cherfils@cea.f [CEA, DAM, DIF, F-91297 Arpajon (France)

2009-12-15

Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

Progress on LMJ targets for ignition

International Nuclear Information System (INIS)

Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Dattolo, E; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L

2009-01-01

Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

Science.gov (United States)

2009-01-01

Background Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Results Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (IL-8) and solute carrier family 1 (glial high affinity glutamate transporter), member 3 (SLC1A3), which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively). Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways. Conclusions Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies. PMID:20028558

Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

Directory of Open Access Journals (Sweden)

Triche Timothy

2009-12-01

Full Text Available Abstract Background Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Results Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (IL-8 and solute carrier family 1 (glial high affinity glutamate transporter, member 3 (SLC1A3, which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively. Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways. Conclusions Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies.

Harmonizing outdoor recreation and bird conservation targets in protected areas

NARCIS (Netherlands)

Pouwels, Rogier; Sierdsema, Henk; Foppen, Ruud P.B.; Henkens, René J.H.G.; Opdam, Paul F.M.; Eupen, van Michiel

2017-01-01

In protected areas managers have to achieve conservation targets while providing opportunities for outdoor recreation. This dual mandate causes conflicts in choosing between management options. Furthermore, the persistence of a protected species within the management unit often depends on how

A Small Disc Area Is a Risk Factor for Visual Field Loss Progression in Primary Open-Angle Glaucoma: The Glaucoma Stereo Analysis Study.

Science.gov (United States)

Kitaoka, Yasushi; Tanito, Masaki; Yokoyama, Yu; Nitta, Koji; Katai, Maki; Omodaka, Kazuko; Nakazawa, Toru

2018-01-01

The Glaucoma Stereo Analysis Study, a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We compared the associations of each parameter between the visual field loss progression group and no-progression group. The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. We divided the mean deviation (MD) slope values of all patients into the progression group (field progression and patient characteristics or each ONH parameter were analyzed with Spearman's rank correlation coefficient. The MD slope averages in the progression group and no-progression group were -0.58 ± 0.28 dB/year and 0.05 ± 0.26 dB/year, respectively. Among disc parameters, vertical disc width (diameter), disc area, cup area, and cup volume in the progression group were significantly less than those in the no-progression group. Logistic regression analysis revealed a significant association between the visual field progression and disc area (odds ratio 0.49/mm 2 disc area). A smaller disc area may be associated with more rapid glaucomatous visual field progression.

Using the Species-Area Relationship to Set Baseline Targets for Conservation

Directory of Open Access Journals (Sweden)

Philip Desmet

2004-12-01

Full Text Available This paper demonstrates how the power form of the Species-Area Relationship (SAR can be used to set conservation targets for land classes using biodiversity survey data. The log-transformation of the power model is a straight line; therefore, if one knows the average number of species recorded per survey site and can estimate the true species number present in the land class, using EstimateS software, it is possible to calculate the slope of the curve, or z-value. The z-value is the exponent in the power model and it can then be used to estimate the proportion of area required to represent a given proportion of species present in any land class. This application of the SAR is explored using phytosociological relevé data from South Africa's Succulent Karoo biome. We also provide suggestions for extrapolating the estimated z-values to other land classes within a bioregion that lack sufficient survey data, using the relationship between z-values and remotely determined landscape variables such as habitat diversity (topographic diversity and geographic location (latitude and longitude. The SAR predicts that for most Succulent Karoo vegetation types a conservation target of 10% of the land area would not be sufficient to conserve the majority of species. We also demonstrate that not all land classes are equal from a plant biodiversity perspective, so applying one target to all land classes in a region will lead to significant gaps and inefficiencies in any reserve network based on this universal target.

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

Science.gov (United States)

2010-07-01

... practice area, Mare Island Naval Shipyard, Vallejo. 334.1160 Section 334.1160 Navigation and Navigable... REGULATIONS § 334.1160 San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo. (a..., Mare Island Naval Shipyard, Vallejo, California, will conduct target practice in the area at intervals...

A review of progress towards radiative divertor

International Nuclear Information System (INIS)

Zagorski, Roman

1997-07-01

A solution of the problem of the power and particle exhaust from the next step tokamaks, will require new techniques which redistribute the power entering the SOL onto much larger surface area than conventional divertor design permits, while maintaining good impurity retention in divertor volume and allowing for efficient helium pumping. Progress made in developing such techniques is discussed. Status of the modelling studies of dynamic gas target divertor and impurity seeded radiating divertors is presented. Recent results of experiments on radiative and gas target divertors are reviewed

Bolder science needed now for protected areas.

Science.gov (United States)

Watson, James E M; Darling, Emily S; Venter, Oscar; Maron, Martine; Walston, Joe; Possingham, Hugh P; Dudley, Nigel; Hockings, Marc; Barnes, Megan; Brooks, Thomas M

2016-04-01

Recognizing that protected areas (PAs) are essential for effective biodiversity conservation action, the Convention on Biological Diversity established ambitious PA targets as part of the 2020 Strategic Plan for Biodiversity. Under the strategic goal to "improve the status of biodiversity by safeguarding ecosystems, species, and genetic diversity," Target 11 aims to put 17% of terrestrial and 10% of marine regions under PA status by 2020. Additionally and crucially, these areas are required to be of particular importance for biodiversity and ecosystem services, effectively and equitably managed, ecologically representative, and well-connected and to include "other effective area-based conservation measures" (OECMs). Whereas the area-based targets are explicit and measurable, the lack of guidance for what constitutes important and representative; effective; and OECMs is affecting how nations are implementing the target. There is a real risk that Target 11 may be achieved in terms of area while failing the overall strategic goal for which it is established because the areas are poorly located, inadequately managed, or based on unjustifiable inclusion of OECMs. We argue that the conservation science community can help establish ecologically sensible PA targets to help prioritize important biodiversity areas and achieve ecological representation; identify clear, comparable performance metrics of ecological effectiveness so progress toward these targets can be assessed; and identify metrics and report on the contribution OECMs make toward the target. By providing ecologically sensible targets and new performance metrics for measuring the effectiveness of both PAs and OECMs, the science community can actively ensure that the achievement of the required area in Target 11 is not simply an end in itself but generates genuine benefits for biodiversity. © 2016 Society for Conservation Biology.

A Small Disc Area Is a Risk Factor for Visual Field Loss Progression in Primary Open-Angle Glaucoma: The Glaucoma Stereo Analysis Study

Directory of Open Access Journals (Sweden)

Yasushi Kitaoka

2018-01-01

Full Text Available Purpose. The Glaucoma Stereo Analysis Study, a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX to assess various morphological parameters of the optic nerve head (ONH in glaucoma patients. We compared the associations of each parameter between the visual field loss progression group and no-progression group. Methods. The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. We divided the mean deviation (MD slope values of all patients into the progression group (<−0.3 dB/year and no-progression group (≧−0.3 dB/year. ONH morphological parameters were calculated with prototype analysis software. The correlations between glaucomatous visual field progression and patient characteristics or each ONH parameter were analyzed with Spearman’s rank correlation coefficient. Results. The MD slope averages in the progression group and no-progression group were −0.58 ± 0.28 dB/year and 0.05 ± 0.26 dB/year, respectively. Among disc parameters, vertical disc width (diameter, disc area, cup area, and cup volume in the progression group were significantly less than those in the no-progression group. Logistic regression analysis revealed a significant association between the visual field progression and disc area (odds ratio 0.49/mm2 disc area. Conclusion. A smaller disc area may be associated with more rapid glaucomatous visual field progression.

Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

National Research Council Canada - National Science Library

Worsham, Maria J; Raju, Usha; Chase, Gary; Lu, Mei

2004-01-01

.... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

National Research Council Canada - National Science Library

Worsham, Maria J; Raju, Usha; Lu, Mei

2006-01-01

.... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

Investigation on non-glass laser fusion targets: their fabrication, characterization, and transport. Charged Particle Research Laboratory report No. 2-81, progress report, June 1, 1980-January 31, 1981

International Nuclear Information System (INIS)

Kim, K.

1981-01-01

A summary is presented of the research progress made under LLNL Subcontract 8320003 for the period of June 1, 1980 through January 31, 1981. The main theme of the research has continued to be the development of techniques for fabricating, characterizing, and transporting laser fusion targets on a continuous basis. The target fabrication techniques are intended mainly for non-glass spherical shell targets, both cryogenic and non-cryogenic. Specifically, progress has been made in each of the following categories. (1) Investigation of liquid hydrogen behavior inside a spherical laser fusion target. (2) Development of automated target characterization scheme. (3) Study of cryogenic target fabrication scheme utilizing cold-gas-levitation and electric field positioning. (4) Development of a cryogenic target fabrication system based on target free-fall method. (5) Generation of hydrogen powder using electro-hydrodynamic spraying. (6) Study of target-charging techniques for application to contactless cryogenic target fabrication. (7) Development of hollow metal sphere production technique. A brief summary of the research progress made in each category is presented

Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.

Science.gov (United States)

Sedel, Frédéric; Bernard, Delphine; Mock, Donald M; Tourbah, Ayman

2016-11-01

Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Research progress on large-area perovskite thin films and solar modules

Directory of Open Access Journals (Sweden)

Zhichun Yang

2017-12-01

Full Text Available Organometal halide perovskites have exhibited a bright future as photovoltaic semiconductor in next generation solar cells due to their unique and promising physicochemical properties. Over the past few years, we have witnessed a tremendous progress of efficiency record evolution of perovskite solar cells (PSCs. Up to now, the highest efficiency record of PSCs has reached 22.1%; however, it was achieved at a very small device area of <0.1 cm2. With the device area increasing to mini-module scale, the efficiency record dropped dramatically. The inherent causes are mainly ascribed to inadequate quality control of large-area perovskite thin films and insufficient optimization of solar module design. In current stage of PSCs research and development, to overcome these two obstacles is in urgent need before this new technology could realize scale-up industrialization. Herein, we present an overview of recently developed strategies for preparing large-area perovskite thin films and perovskite solar modules (PSMs. At last, cost analysis and future application directions of PSMs have also been discussed.

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

Science.gov (United States)

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

2016-01-01

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

Decoding target distance and saccade amplitude from population activity in the macaque lateral intraparietal area (LIP

Directory of Open Access Journals (Sweden)

Frank Bremmer

2016-08-01

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

Quantitative PET Imaging with Novel HER3-Targeted Peptides Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression

Science.gov (United States)

2017-12-01

Independent Prostate Cancer Progression PRINCIPAL INVESTIGATOR: Benjamin Larimer, PhD CONTRACTING ORGANIZATION: Massachusetts General Hospital Boston...TYPE Final 3. DATES COVERED 1 Aug 2016 – 19 August 2017 Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression 5a...highly specific peptide that targets HER3 for prostate cancer imaging. The peptide was labeled with a PET imaging radionuclide and injected into mice

Methodology for estimation of potential for solar water heating in a target area

International Nuclear Information System (INIS)

Pillai, Indu R.; Banerjee, Rangan

2007-01-01

Proper estimation of potential of any renewable energy technology is essential for planning and promotion of the technology. The methods reported in literature for estimation of potential of solar water heating in a target area are aggregate in nature. A methodology for potential estimation (technical, economic and market potential) of solar water heating in a target area is proposed in this paper. This methodology links the micro-level factors and macro-level market effects affecting the diffusion or adoption of solar water heating systems. Different sectors with end uses of low temperature hot water are considered for potential estimation. Potential is estimated at each end use point by simulation using TRNSYS taking micro-level factors. The methodology is illustrated for a synthetic area in India with an area of 2 sq. km and population of 10,000. The end use sectors considered are residential, hospitals, nursing homes and hotels. The estimated technical potential and market potential are 1700 m 2 and 350 m 2 of collector area, respectively. The annual energy savings for the technical potential in the area is estimated as 110 kW h/capita and 0.55 million-kW h/sq. km. area, with an annual average peak saving of 1 MW. The annual savings is 650-kW h per m 2 of collector area and accounts for approximately 3% of the total electricity consumption of the target area. Some of the salient features of the model are the factors considered for potential estimation; estimation of electrical usage pattern for typical day, amount of electricity savings and savings during the peak load. The framework is general and enables accurate estimation of potential of solar water heating for a city, block. Energy planners and policy makers can use this framework for tracking and promotion of diffusion of solar water heating systems. (author)

Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Xiaopeng Ma

2017-01-01

Full Text Available Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future.

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

Science.gov (United States)

2010-01-01

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

Progress in chemical processing of LEU targets for 99Mo production - 1997

International Nuclear Information System (INIS)

Vandegrift, G.F.; Conner, C.; Sedlet, J.; Wygmans, D.G.; Wu, D.; Iskander, F.; Landsberger, S.

1997-01-01

Presented here are recent experimental results of our continuing development activities associated with converting current processes for producing fission-product 99 Mo from targets using high-enriched uranium (HEU) to low-enriched uranium (LEU). Studies were focused in four areas: (1) measuring the chemical behavior of iodine, rhodium, and silver in the LEU-modified Cintichem process, (2) performing experiments and calculations to assess the suitability of zinc fission barriers for LEU metal foil targets, (3) developing an actinide separations method for measuring alpha contamination of the purified 99 Mo product, and (4) developing a cooperation with Sandia National Laboratories and Los Alamos National Laboratory that will lead to approval by the U.S. Federal Drug Administration for production of 99 Mo from LEU targets. Experimental results continue to show the technical feasibility of converting current HEU processes to LEU. (author)

Progress in chemical treatment of LEU targets by the modified Cintichem process

International Nuclear Information System (INIS)

Wu, D.; Landsberger, S.; Vandegrift, G.F.

1996-01-01

Presented here are recent experimental results on tests of a modified Cintichem process for producing 99 Mo from low enriched uranium (LEU). Studies were focused in three areas: (1) testing the effects on 99 Mo recovery and purity of dissolving LEU foil in nitric acid alone, rather than in the sulfuric/nitric acid mixture currently used, (2) measuring decontamination factors for radionuclide impurities in each purification step, and (3) testing the effects on processing of adding barrier materials to the LEU metal-foil target. The experimental results show that switching from dissolving the target in the sulfuric/nitric mixture to using nitric acid alone should cause no significant difference in 99 Mo product yield or purity. Further, the results show that overall decontamination factors for gamma emitters in the LEU-target processing are high enough to meet the purity requirements for the 99 Mo product. The results also show that the selected barrier materials, Cu, Fe, and Ni, do not interfere with 99 Mo recovery and can be removed during chemical processing of the LEU target

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)

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

Science.gov (United States)

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

2016-05-01

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

Swedish Hard Rock Laboratory first evaluation of preinvestigations 1986-87 and target area characterization

International Nuclear Information System (INIS)

Gustafson, G.; Stanfors, R.; Wikberg, P.

1988-06-01

SKB plans to site an underground research laboratory in the Simpevarp area. A regional survey started in 1986 and an extensive programme for geology, geohydrology and hydrochemistry was carried through. This report gives an evaluation of all available data gathered from the start of the project up to the drilling of core boreholes in some target areas in the autumn of 1987. A descriptive geological-tectonic model on a regional scale is presented that is intended to constitute a basis for the hydrogeological modelling work. Preliminary rock mass descriptions are also presented on a more detailed scale for some minor parts of the area. It is recommended that the island Aespoe is the principal target area for the continued work on the Swedish Hard Rock Laboratory. (orig.)

Progress on LMJ targets for ignition

International Nuclear Information System (INIS)

Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Fremerye, P; Galmiche, D; Gauthier, P; Giorla, J; Lambert, F; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L

2010-01-01

Targets designed to produce ignition on the Laser MegaJoule are presented. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-shaped cocktail hohlraum. 1D and 2D robustness evaluations of these different targets shed light on critical points for ignition, that can be traded off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

Progress on LMJ targets for ignition

Energy Technology Data Exchange (ETDEWEB)

Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Fremerye, P; Galmiche, D; Gauthier, P; Giorla, J; Lambert, F; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L, E-mail: catherine.cherfils@cea.f [CEA, DAM, DIF, F-91297 Arpajon (France)

2010-08-01

Targets designed to produce ignition on the Laser MegaJoule are presented. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-shaped cocktail hohlraum. 1D and 2D robustness evaluations of these different targets shed light on critical points for ignition, that can be traded off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

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

Science.gov (United States)

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

2018-01-01

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

The FLUKA study of the secondary particles fluence in the AD-Antiproton Decelerator target area

CERN Document Server

Calviani, M

2014-01-01

In this paper we present Monte Carlo FLUKA simulations [1, 2] carried out to investigate the secondary particles fluence emerging from the antiproton production target and their spatial distribution in the AD target area. The detailed quantitative analysis has been performed for different positions along the magnet dog-leg as well as after the main collimator. These results allow tuning the position of the new beam current transformers (BCT) in the target area, in order to have a precise pulse-by-pulse evaluation of the intensity of negative particles injected in the AD-ring before the deceleration phase.

Uncovering SUMOylation Dynamics during Cell-Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein

DEFF Research Database (Denmark)

Schimmel, Joost; Eifler, Karolin; Sigurdsson, Jón Otti

2014-01-01

Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during cell......-cycle progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of cell-cycle progression and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M...... relieving FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during cell-cycle progression....

Status and progress of the RERTR program

International Nuclear Information System (INIS)

Travelli, A.

1996-01-01

The progress of the Reduced Enrichment Research and Test Reactor (RERTR) Program is described. The major events, findings, and activities of 1996 are reviewed after a brief summary of the results which the RERTR Program had achieved by the end of 1995 in collaboration with its many international partners. Significant progress has been made during the past year in each of the three areas that the delegates to last year's RERTR meeting chose to address, in their letter to President Clinton, as requiring special attention. (1) In the area of U.S. acceptance of spent fuel from foreign research reactors, a second shipment of 99 urgent-relief spent fuel elements was completed. The Final Environmental Impact Statement was published in February 1996, and the Record of Decision was published in May 1996. The first shipments under the Record of Decision, containing 280 spent fuel elements, were received at the Savannah River Site in September 1996. (2) In the area of advanced fuel development, adequate funding and guidance were received by the RERTR program in March 1996. Fuel development activities are now in progress, including procurement of equipment, screening of candidate materials, and preparations for the production of a first series of microplates. The first irradiations are planned to begin in the Advanced Test Reactor. in Idaho, during April 1997. (3) In the area of conversion of DOE research reactors, the RERTR program has been tasked by the Department of Energy to assess the feasibility of converting to LEU fuel each of the DOE research reactors which currently use HEU fuel. A preliminary assessment will be presented at this meeting. Significant progress has been made by the Russian RERTR program, which aims to develop and demonstrate within the next five years the technical means needed to convert Russian-supplied research reactors to LEU fuels. The study of an alternative LEU core for the FRM-II design has been extended to address, with excellent results

A review of global progress toward the Millennium Development Goal 1 Hunger Target.

Science.gov (United States)

Fanzo, Jessica C; Pronyk, Paul M

2011-06-01

The hunger component of the first Millennium Development Goal (MDG) aims to reduce the proportion of people who suffer from hunger by half between 1990 and 2015. In low- and middle-income countries, progress has been mixed, with approximately 925 million people hungry and 125 million and 195 million children underweight and stunted, respectively. To assess global progress on the hunger component of MDG1 and evaluate the success of interventions and country programs in reducing undernutrition. We review global progress on the hunger component of MDG1, examining experience from 40 community-based programs as well as national efforts to move interventions to scale drawn from the published and gray literature, alongside personal interviews with representatives of governments and development agencies. Based on this review, most strategies being implemented and scaled are focusing on treatment of malnutrition and rooted within the health sector. While critical, these programs generally address disease-related effects and emphasize the immediate determinants of undernutrition. Other major strategies to tackle undernutrition rely on the production of staple grains within the agriculture sector. These programs address hunger, as opposed to improving the quality of diets within communities. Strategies that adopt multisectoral programming as crucial to address longer-term determinants of undernutrition, such as poverty, gender equality, and functioning food and health systems, remain underdeveloped and under-researched. This review suggests that accelerating progress toward the MDG1 targets is less about the development of novel innovations and new technologies and more about putting what is already known into practice. Success will hinge on linking clear policies with effective delivery systems in working towards an evidence-based and contextually relevant multisectoral package of interventions that can rapidly be taken to scale.

Hotspots ampersand other hidden targets: Probability of detection, number, frequency and area

International Nuclear Information System (INIS)

Vita, C.L.

1994-01-01

Concepts and equations are presented for making probability-based estimates of the detection probability, and the number, frequency, and area of hidden targets, including hotspots, at a given site. Targets include hotspots, which are areas of extreme or particular contamination, and any object or feature that is hidden from direct visual observation--including buried objects and geologic or hydrologic details or anomalies. Being Bayesian, results are fundamentally consistent with observational methods. Results are tools for planning or interpreting exploration programs used in site investigation or characterization, remedial design, construction, or compliance monitoring, including site closure. Used skillfully and creatively, these tools can help streamline and expedite environmental restoration, reducing time and cost, making site exploration cost-effective, and providing acceptable risk at minimum cost. 14 refs., 4 figs

ISAC target operation with high proton currents

CERN Document Server

Dombsky, M; Schmor, P; Lane, M

2003-01-01

The TRIUMF-ISAC facility target stations were designed for ISOL target irradiations with up to 100 mu A proton beam currents. Since beginning operation in 1998, ISAC irradiation currents have progressively increased from initial values of approx 1 mu A to present levels of up to 40 mu A on refractory metal foil targets. In addition, refractory carbide targets have operated at currents of up to 15 mu A for extended periods. The 1-40 mu A operational regime is achieved by tailoring each target to the thermal requirements dictated by material properties such as beam power deposition, thermal conductivity and maximum operating temperature of the target material. The number of heat shields on each target can be varied in order to match the effective emissivity of the target surface for the required radiative power dissipation. Targets of different thickness, surface area and volume have been investigated to study the effect of diffusion and effusion delays on the yield of radioisotopes. For yields of short-lived p...

Tracking progress towards global drinking water and sanitation targets: A within and among country analysis.

Science.gov (United States)

Fuller, James A; Goldstick, Jason; Bartram, Jamie; Eisenberg, Joseph N S

2016-01-15

Global access to safe drinking water and sanitation has improved dramatically during the Millennium Development Goal (MDG) period. However, there is substantial heterogeneity in progress between countries and inequality within countries. We assessed countries' temporal patterns in access to drinking water and sanitation using publicly available data. We then classified countries using non-linear modeling techniques as having one of the following trajectories: 100% coverage, linear growth, linear decline, no change, saturation, acceleration, deceleration, negative acceleration, or negative deceleration. We further assessed the degree to which temporal profiles follow a sigmoidal pattern and how these patterns might vary within a given country between rural and urban settings. Among countries with more than 10 data points, between 15% and 38% showed a non-linear trajectory, depending on the indicator. Overall, countries' progress followed a sigmoidal trend, but some countries are making better progress and some worse progress than would be expected. We highlight several countries that are not on track to meet the MDG for water or sanitation, but whose access is accelerating, suggesting better performance during the coming years. Conversely, we also highlight several countries that have made sufficient progress to meet the MDG target, but in which access is decelerating. Patterns were heterogeneous and non-linearity was common. Characterization of these heterogeneous patterns will help policy makers allocate resources more effectively. For example, policy makers can identify countries that could make use of additional resources or might be in need of additional institutional capacity development to properly manage resources; this will be essential to meet the forthcoming Sustainable Development Goals. Copyright © 2015 Elsevier B.V. All rights reserved.

Cueing listeners to attend to a target talker progressively improves word report as the duration of the cue-target interval lengthens to 2,000 ms.

Science.gov (United States)

Holmes, Emma; Kitterick, Padraig T; Summerfield, A Quentin

2018-04-25

Endogenous attention is typically studied by presenting instructive cues in advance of a target stimulus array. For endogenous visual attention, task performance improves as the duration of the cue-target interval increases up to 800 ms. Less is known about how endogenous auditory attention unfolds over time or the mechanisms by which an instructive cue presented in advance of an auditory array improves performance. The current experiment used five cue-target intervals (0, 250, 500, 1,000, and 2,000 ms) to compare four hypotheses for how preparatory attention develops over time in a multi-talker listening task. Young adults were cued to attend to a target talker who spoke in a mixture of three talkers. Visual cues indicated the target talker's spatial location or their gender. Participants directed attention to location and gender simultaneously ("objects") at all cue-target intervals. Participants were consistently faster and more accurate at reporting words spoken by the target talker when the cue-target interval was 2,000 ms than 0 ms. In addition, the latency of correct responses progressively shortened as the duration of the cue-target interval increased from 0 to 2,000 ms. These findings suggest that the mechanisms involved in preparatory auditory attention develop gradually over time, taking at least 2,000 ms to reach optimal configuration, yet providing cumulative improvements in speech intelligibility as the duration of the cue-target interval increases from 0 to 2,000 ms. These results demonstrate an improvement in performance for cue-target intervals longer than those that have been reported previously in the visual or auditory modalities.

PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target

Science.gov (United States)

Li, Jiarong; Karaplis, Andrew C.; Huang, Dao C.; Siegel, Peter M.; Camirand, Anne; Yang, Xian Fang; Muller, William J.; Kremer, Richard

2011-01-01

Parathyroid hormone–related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer — it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention. PMID:22056386

TARGET - NEW PAYMENT SYSTEM FOR THE EURO AREA

Directory of Open Access Journals (Sweden)

ELENA VIOLETA DRĂGOI

2015-04-01

Full Text Available At EU level, the funds transfer systems have undergone significant changes starting with the introduction of euro. The launch of the euro, the emergence of new technologies, introduction of financial innovations and the globalization have led to reorganization of funds transfer systems` infrastructure. The paper aims to offer an analysis of actual payment system for Euro area, a trans-European funds transfer system with gross settlement in real-time for payments in euro TARGET- to increase economical and operational efficiency of payments and also to reduce the risks in the electronic funds transfer system by creating efficient and secure payment systems.

miR-630 targets IGF1R to regulate response to HER-targeting drugs and overall cancer cell progression in HER2 over-expressing breast cancer.

Science.gov (United States)

Corcoran, Claire; Rani, Sweta; Breslin, Susan; Gogarty, Martina; Ghobrial, Irene M; Crown, John; O'Driscoll, Lorraine

2014-03-24

While the treatment of HER2 over-expressing breast cancer with recent HER-targeted drugs has been highly effective for some patients, primary (also known as innate) or acquired resistance limits the success of these drugs. microRNAs have potential as diagnostic, prognostic and predictive biomarkers, as well as replacement therapies. Here we investigated the role of microRNA-630 (miR-630) in breast cancer progression and as a predictive biomarker for response to HER-targeting drugs, ultimately yielding potential as a therapeutic approach to add value to these drugs. We investigated the levels of intra- and extracellular miR-630 in cells and conditioned media from breast cancer cell lines with either innate- or acquired- resistance to HER-targeting lapatinib and neratinib, compared to their corresponding drug sensitive cell lines, using qPCR. To support the role of miR-630 in breast cancer, we examined the clinical relevance of this miRNA in breast cancer tumours versus matched peritumours. Transfection of miR-630 mimics and inhibitors was used to manipulate the expression of miR-630 to assess effects on response to HER-targeting drugs (lapatinib, neratinib and afatinib). Other phenotypic changes associated with cellular aggressiveness were evaluated by motility, invasion and anoikis assays. TargetScan prediction software, qPCR, immunoblotting and ELISAs, were used to assess miR-630's regulation of mRNA, proteins and their phosphorylated forms. We established that introducing miR-630 into cells with innate- or acquired- resistance to HER-drugs significantly restored the efficacy of lapatinib, neratinib and afatinib; through a mechanism which we have determined to, at least partly, involve miR-630's regulation of IGF1R. Conversely, we demonstrated that blocking miR-630 induced resistance/insensitivity to these drugs. Cellular motility, invasion, and anoikis were also observed as significantly altered by miR-630 manipulation, whereby introducing miR-630 into cells

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

Science.gov (United States)

2010-07-01

... degrees 09 minutes 26 seconds identified as Hannibal Target. (3) The regulations. Nonexplosive projectiles and bombs will be dropped at frequent intervals in the target areas. Hooper and Hannibal target areas...

Syndecans as modulators and potential pharmacological targets in cancer progression

Directory of Open Access Journals (Sweden)

Despoina eBarbouri

2014-02-01

Full Text Available Extracellular matrix (ECM components form a dynamic network of key importance for cell function and properties. Key macromolecules in this interplay are syndecans (SDCs, a family of transmembrane heparan sulfate proteoglycans (HSPGs. Specifically, heparan sulfate (HS chains with their different sulfation pattern have the ability to interact with growth factors and their receptors in tumor microenvironment, promoting the activation of different signaling cascades that regulate tumor cell behavior. The affinity of HS chains with ligands is altered during malignant conditions because of the modification of chain sequence/sulfation pattern. Furthermore, matrix degradation enzymes derived from the tumor itself or the tumor microenvironment, like heparanase and matrix metalloproteinases (MMPs, ADAM as well as ADΑMTS are involved in the cleavage of SDCs ectodomain at the HS and protein core level, respectively. Such released soluble syndecans shed syndecans in the extracellular matrix interact in an autocrine or paracrine manner with the tumor or/and stromal cells. Shed syndecans, upon binding to several matrix effectors, such as growth factors, chemokines and cytokines, have the ability to act as competitive inhibitors for membrane PGs, and modulate the inflammatory microenvironment of cancer cells. It is notable that syndecans and their soluble counterparts may affect either the behavior of cancer cells and/or their microenvironment during cancer progression. The importance of these molecules has been highlighted since HSPGs have been proposed as prognostic markers of solid tumors and hematopoietic malignancies. Going a step further down the line, the multi-actions of syndecans in many levels make them appealing as potential pharmacological targets, either by targeting directly the tumor or indirectly the adjacent stroma.

Conceptual design of a high current ISOL target area at TRIUMF

International Nuclear Information System (INIS)

Beveridge, J.L.; Buchmann, L.; Clark, G.S.; Sprenger, H.; Thorson, I.; Vincent, J.; D'Auria, J.M.; Dombsky, M.

1993-05-01

Two similar conceptual designs for the handling of highly activated components at the target area of a high current radioactive beam facility have been investigated. The proposed designs are sufficiently flexible that practical detailed designs could be realized. Personnel exposure to radiation during the handling procedures is expected to be minimal. (author) 3 refs., 4 figs

Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas

International Nuclear Information System (INIS)

Sadri, Navid; Zhang, Paul J.

2013-01-01

Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant chemotherapy employed in more advanced stage disease. However, in recent decades, there has been little progress in the average five-year survival for the majority of patients with high-grade soft tissue sarcomas, highlighting the need for improved targeted therapeutic agents. Clinical and preclinical studies demonstrate that tumor hypoxia and up-regulation of hypoxia-inducible factors (HIFs) is associated with decreased survival, increased metastasis, and resistance to therapy in soft tissue sarcomas. HIF-mediated gene expression regulates many critical aspects of tumor biology, including cell survival, metabolic programming, angiogenesis, metastasis, and therapy resistance. In this review, we discuss HIFs and HIF-mediated genes as potential prognostic markers and therapeutic targets in sarcomas. Many pharmacological agents targeting hypoxia-related pathways are in development that may hold therapeutic potential for treating both primary and metastatic sarcomas that demonstrate increased HIF expression

Progresses in optimization strategy for radiolabeled molecular probes targeting integrin αvβ3

International Nuclear Information System (INIS)

Chen Haojun; Wu Hua

2012-01-01

Tumor angiogenesis is critical in the growth, invasion and metastasis of malignant tumors. The integrins, which express on many types of tumor cells and activated vascular endothelial cells, play an important role in regulation of the tumor angiogenesis. RGD peptide, which contains Arg-Gly-Asp sequence, binds specifically to integrin α v β 3 . Therefore, the radiolabeled RGD peptides may have broad application prospects in radionuclide imaging and therapy. Major research interests include the selection of radionuclides, modification and improvement of RGD structures. In this article, we give a review on research progresses in optimization strategy for radiolabeled molecular probes targeting integrin α v β 3 . (authors)

Application effect of TEM sounding survey on prospecting and target area selection of sandstone-type uranium deposits

International Nuclear Information System (INIS)

He Jianguo; Liang Shanming; Zhao Cuiping

2006-01-01

Based on the results of transient electromagnetic (TEM) sounding survey during recent years regional geological reconnaissance with drilling (1:250000), the application effect of TEM sounding survey during regional reconnaissance is summarized in this paper. It is suggested that the data of TEM sounding are useful in judging hydrodynamic conditions of groundwater and determining favorable areas for uranium ore-formation; TEM sounding in large areas may be proper for prospecting in gobi-desert areas and be beneficial for regional reconnaissance and target area selection, and may reduce the target area and provide basis for further drilling program. It is of popularized significance in the prospecting for sandstone-type uranium deposits. (authors)

Targeted histology sampling from atypical small acinar proliferation area detected by repeat transrectal prostate biopsy

Directory of Open Access Journals (Sweden)

A. V. Karman

2017-01-01

Full Text Available Оbjective: to define the approach to the management of patients with the detected ASAP area.Materials and methods. In the time period from 2012 through 2015, 494 patients with previously negative biopsy and remaining suspicion of prostate cancer (PCa were examined. The patients underwent repeat 24-core multifocal prostate biopsy with taking additional tissue samples from suspicious areas detected by multiparametric magnetic resonance imaging and transrectal ultrasound. An isolated ASAP area was found in 127 (25. 7 % of the 494 examined men. All of them were offered to perform repeat target transrectal biopsy of this area. Targeted transrectal ultrasound guided biopsy of the ASAP area was performed in 56 (44.1 % of the 127 patients, 53 of them being included in the final analysis.Results. PCa was diagnosed in 14 (26.4 % of the 53 patients, their mean age being 64.4 ± 6.9 years. The average level of prostate-specific antigen (PSA in PCa patients was 6.8 ± 3.0 ng/ml, in those with benign lesions – 9.3 ± 6.5 ng/ml; the percentage ratio of free/total PSA with PCa was 16.2 ± 7,8 %, with benign lesions – 23.3 ± 7.7 %; PSA density in PCa patients was 0.14 ± 0.07 ng/ml/cm3, in those with benign lesions – 0.15 ± 0.12 ng/ml/cm3. Therefore, with ASAP area being detected in repeat prostate biopsy samples, it is advisable that targeted extended biopsy of this area be performed. 

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

Science.gov (United States)

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

2012-01-01

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

Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles

Science.gov (United States)

Hoang, David T; Iczkowski, Kenneth A; Kilari, Deepak; See, William; Nevalainen, Marja T

2017-01-01

Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms. PMID:27741508

Physical water scarcity metrics for monitoring progress towards SDG target 6.4 : An evaluation of indicator 6.4.2 “Level of water stress”

NARCIS (Netherlands)

Vanham, D.; Hoekstra, A. Y.; Wada, Y.; Bouraoui, F.; de Roo, A.; Mekonnen, M. M.; van de Bund, W. J.; Batelaan, O.; Pavelic, P.; Bastiaanssen, Wim G M; Kummu, M.; Rockström, J.; Liu, J.; Bisselink, B.; Ronco, P.; Pistocchi, A.; Bidoglio, G.

2018-01-01

Target 6.4 of the recently adopted Sustainable Development Goals (SDGs) deals with the reduction of water scarcity. To monitor progress towards this target, two indicators are used: Indicator 6.4.1 measuring water use efficiency and 6.4.2 measuring the level of water stress (WS). This paper aims to

Evaluation of fisher (Pekania pennanti) restoration in Olympic National Park and the Olympic Recovery Area: 2014 annual progress report

Science.gov (United States)

Happe, Patricia J.; Jenkins, Kurt J.; Kay, Thomas J.; Pilgrim, Kristy L.; Schwartz, Michael K.; Lewis, Jeffrey C.; Aubry, Keith B.

2015-01-01

With the translocation and release of 90 fishers (Pekania pennanti) from British Columbia to Olympic National Park during 2008–2010, the National Park Service and Washington Department of Fish and Wildlife accomplished the first phase of fisher restoration in Washington State. Beginning in 2013, we initiated a new research project to determine the current status of fishers on Washington’s Olympic Peninsula 3–5 years after the releases and evaluate the short-term success of the restoration program. Objectives of the study are to determine the current distribution of fishers and proportion of the recovery area that is currently occupied by fishers, determine several genetic characteristics of the reintroduced population, and determine reproductive success of the founding animals through genetic studies. During 2014, we continued working with a broad coalition of cooperating agencies, tribes, and nongovernmental organizations (NGO) to collect data on fisher distribution and genetics using noninvasive sampling methods. The primary sampling frame consisted of 157 24-square-kilometer hexagons (hexes) distributed across all major land ownerships within the Olympic Peninsula target survey area. In 2014 we expanded the study by adding 58 more hexes to an expanded study area in response to incidental fisher observations outside of the target area obtained in 2013; 49 hexes were added south and 9 to the east of the target area. During 2014, federal, state, tribal and NGO biologists and volunteers established three baited motion-sensing camera stations, paired with hair snaring devices, in 80 hexes; 69 in the targeted area 11 in the expansion areas. Each paired camera/hair station was left in place for approximately 6 weeks, with three checks on 2-week intervals. We documented fisher presence in 5 of the 80 hexagons, and identified 5 different fishers through a combination of microsatellite DNA analyses and camera detections. All fisher detections were in the target area

Greenhouse gas emission trends and projections in Europe 2011. Tracking progress towards Kyoto and 2020 targets

Energy Technology Data Exchange (ETDEWEB)

Busche, J.; Scheffler, M.; Graichen, V. (Umweltbundesamt, Vienna (Austria)) (and others)

2011-10-15

At the end of 2010, the EU-15 was on track to achieve its Kyoto target but three EU-15 Member States (Austria, Italy and Luxembourg) were not on track to meet their burden-sharing targets. These countries must therefore seriously consider further action to ensure compliance, in particular revising their plans on using flexible mechanisms. Among the EEA member countries outside the EU, Liechtenstein and Switzerland were not on track to achieve their Kyoto target at the end of 2009. All other European countries are on track to meet their targets, either based on domestic emissions only or with the assistance of Kyoto mechanisms. The economic recession had a significant impact on the EU's total greenhouse gas (GHG) emission trends but a more limited effect on progress towards Kyoto targets. This is because emissions in the sectors covered by the EU Emissions Trading Scheme (ETS), which were most affected by the crisis, do not affect Kyoto compliance once ETS caps have been set. With existing national measures, Member States do not project enough emission reductions for the EU to meet its unilateral 20 % reduction commitment in 2020. Additional measures currently planned by Member States will help further reduce emissions but will be insufficient to achieve the important emission cuts needed in the longer term. By 2020 Member States must enhance their efforts to reduce emissions in non-EU ETS sectors, such as the residential, transport or agriculture sectors, where legally binding national targets have been set under the EU's 2009 climate and energy package. (Author)

Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects

Science.gov (United States)

Ferraldeschi, R; Welti, J; Luo, J; Attard, G; de Bono, JS

2015-01-01

Androgen receptor (AR) signaling is a critical pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease. However, over time, most tumors become resistant to ADT. The view of castration-resistant prostate cancer (CRPC) has changed dramatically in the last several years. Progress in understanding the disease biology and mechanisms of castration resistance led to significant advancements and to paradigm shift in the treatment. Accumulating evidence showed that prostate cancers develop adaptive mechanisms for maintaining AR signaling to allow for survival and further evolution. The aim of this review is to summarize molecular mechanisms of castration resistance and provide an update in the development of novel agents and strategies to more effectively target the AR signaling pathway. PMID:24837363

Beams configuration design in target area with successive quadratic programming method

International Nuclear Information System (INIS)

Shi Zhiquan; Tan Jichun; Wei Xiaofeng; Man Jongzai; Zhang Xiaomin; Yuan Jing; Yuan Xiaodong

1998-01-01

The author describes the application of successive quadratic programming method (SQP) to design laser beam configuration in target area. Based on the requirement of ICF experiment physics, a math model of indirect-driver beam geometry is given. A 3D wire-frame is plotted, in which support lines represent 60 laser entireties and 240 turning points of support lines' segments stand for the spatial positions of reflectors

Technical Targets - A Tool to Support Strategic Planning in the Subsurface Contaminants Focus Area

International Nuclear Information System (INIS)

Looney, B.B.

2002-01-01

The Subsurface Contaminants Focus Area (SCFA) is supported by a lead laboratory consisting of technical representatives from DOE laboratories across the country. This broadly representative scientific group has developed and implemented a process to define Technical Targets to assist the SCFA in strategic planning and in managing their environmental research and development portfolio. At an initial meeting in Golden Colorado, an initial set of Technical Targets was identified using a rapid consensus based technical triage process. Thirteen Technical Targets were identified and described. Vital scientific and technical objectives were generated for each target. The targets generally fall into one of the following five strategic investment categories: Enhancing Environmental Stewardship, Eliminating Contaminant Sources, Isolating Contaminants, Controlling Contaminant Plumes, Enabling DOEs CleanUp Efforts. The resulting targets and the detail they comprise on what is, and what is not, needed to meet Environmental Management needs provide a comprehensive technically-based framework to assist in prioritizing future work and in managing the SCFA program

Salt Reduction Initiatives around the World - A Systematic Review of Progress towards the Global Target.

Science.gov (United States)

Trieu, Kathy; Neal, Bruce; Hawkes, Corinna; Dunford, Elizabeth; Campbell, Norm; Rodriguez-Fernandez, Rodrigo; Legetic, Branka; McLaren, Lindsay; Barberio, Amanda; Webster, Jacqui

2015-01-01

To quantify progress with the initiation of salt reduction strategies around the world in the context of the global target to reduce population salt intake by 30% by 2025. A systematic review of the published and grey literature was supplemented by questionnaires sent to country program leaders. Core characteristics of strategies were extracted and categorised according to a pre-defined framework. A total of 75 countries now have a national salt reduction strategy, more than double the number reported in a similar review done in 2010. The majority of programs are multifaceted and include industry engagement to reformulate products (n = 61), establishment of sodium content targets for foods (39), consumer education (71), front-of-pack labelling schemes (31), taxation on high-salt foods (3) and interventions in public institutions (54). Legislative action related to salt reduction such as mandatory targets, front of pack labelling, food procurement policies and taxation have been implemented in 33 countries. 12 countries have reported reductions in population salt intake, 19 reduced salt content in foods and 6 improvements in consumer knowledge, attitudes or behaviours relating to salt. The large and increasing number of countries with salt reduction strategies in place is encouraging although activity remains limited in low- and middle-income regions. The absence of a consistent approach to implementation highlights uncertainty about the elements most important to success. Rigorous evaluation of ongoing programs and initiation of salt reduction programs, particularly in low- and middle- income countries, will be vital to achieving the targeted 30% reduction in salt intake.

Salt Reduction Initiatives around the World - A Systematic Review of Progress towards the Global Target.

Directory of Open Access Journals (Sweden)

Kathy Trieu

Full Text Available To quantify progress with the initiation of salt reduction strategies around the world in the context of the global target to reduce population salt intake by 30% by 2025.A systematic review of the published and grey literature was supplemented by questionnaires sent to country program leaders. Core characteristics of strategies were extracted and categorised according to a pre-defined framework.A total of 75 countries now have a national salt reduction strategy, more than double the number reported in a similar review done in 2010. The majority of programs are multifaceted and include industry engagement to reformulate products (n = 61, establishment of sodium content targets for foods (39, consumer education (71, front-of-pack labelling schemes (31, taxation on high-salt foods (3 and interventions in public institutions (54. Legislative action related to salt reduction such as mandatory targets, front of pack labelling, food procurement policies and taxation have been implemented in 33 countries. 12 countries have reported reductions in population salt intake, 19 reduced salt content in foods and 6 improvements in consumer knowledge, attitudes or behaviours relating to salt.The large and increasing number of countries with salt reduction strategies in place is encouraging although activity remains limited in low- and middle-income regions. The absence of a consistent approach to implementation highlights uncertainty about the elements most important to success. Rigorous evaluation of ongoing programs and initiation of salt reduction programs, particularly in low- and middle- income countries, will be vital to achieving the targeted 30% reduction in salt intake.

Integrating Biodiversity and Ecosystem Services in the Post-2015 Development Agenda: Goal Structure, Target Areas and Means of Implementation

Directory of Open Access Journals (Sweden)

Paul L. Lucas

2013-12-01

Full Text Available The United Nations’ discussions on defining a new set of post-2015 development goals focus on poverty eradication and sustainable development. Biodiversity and ecosystem services are essential for poverty eradication, which is also one of the foundations of the Strategic Plan for Biodiversity of the Convention on Biological Diversity (CBD. Based on an assessment of current proposals of goals and targets, and a quantitative pathway analysis to meet long term biodiversity and food security goals, this paper discusses how biodiversity and ecosystem services can be integrated into a broad set of goals and targets, and concludes with relevant target areas and means of implementation for which specific targets need to be defined. Furthermore, it responds to the call of the CBD to consider the Strategic Plan for Biodiversity and the related Aichi biodiversity targets in the post-2015 development agenda. The paper’s analysis identifies three overlapping but also supplemental ways to integrate biodiversity and ecosystem services in the post-2015 agenda: integrated goals, goals addressing earth system functioning and goals addressing environmental limits. It further concludes seven target areas to be included under the goals to address biodiversity and ecosystem services in the context of food and agriculture: access to food, demand for agricultural products, sustainable intensification, ecosystem fragmentation, protected areas, essential ecosystem services and genetic diversity. The Strategic Plan for Biodiversity provides a good basis for integrating biodiversity and ecosystem services in the post-2015 development agenda. Many Aichi targets address the proposed target areas and the means of implementation discussed, while they need to be complemented with targets that specifically address human well-being, as well as institutions and governance.

Overview of US heavy-ion fusion progress and plans

International Nuclear Information System (INIS)

Logan, G.; Bieniosek, F.; Celata, C.; Henestroza, E.; Kwan, J.; Lee, E.P.; Leitner, M.; Prost, L.; Roy, P.; Seidl, P.A.; Eylon, S.; Vay, J.-L.; Waldron, W.; Yu, S.; Barnard, J.; Callahan, D.; Cohen, R.; Friedman, A.; Grote, D.; Kireeff Covo, M.; Meier, W.R.; Molvik, A.; Lund, S.; Davidson, R.; Efthimion, P.; Gilson, E.; Grisham, L.; Kaganovich, I.; Qin, H.; Startsev, E.; Rose, D.; Welch, D.; Olson, C.; Kishek, R.; O'Shea, P.; Haber, I.

2005-01-01

Significant experimental and theoretical progress has been made in the US heavy-ion fusion program on high-current sources, injectors, transport, final focusing, chambers and targets for high-energy density physics (HEDP) and inertial fusion energy (IFE) driven by induction linac accelerators. One focus of present research is the beam physics associated with quadrupole focusing of intense, space-charge dominated heavy-ion beams, including gas and electron cloud effects at high currents, and the study of long-distance-propagation effects such as emittance growth due to field errors in scaled experiments. A second area of emphasis in present research is the introduction of background plasma to neutralize the space charge of intense heavy-ion beams and assist in focusing the beams to a small spot size. In the near future, research will continue in the above areas, and a new area of emphasis will be to explore the physics of neutralized beam compression and focusing to high intensities required to heat targets to high-energy density conditions as well as for inertial fusion energy

Enhanced surveillance program FY97 accomplishments. Progress report

Energy Technology Data Exchange (ETDEWEB)

Mauzy, A. [ed.; Laake, B. [comp.

1997-10-01

This annual report is one volume of the Enhanced Surveillance Program (ESP) FY97 Accomplishments. The complete accomplishments report consists of 11 volumes. Volume 1 includes an ESP overview and a summary of selected unclassified FY97 program highlights. Volume 1 specifically targets a general audience, reflecting about half of the tasks conducted in FY97 and emphasizing key program accomplishments and contributions. The remaining volumes of the accomplishments report are classified, organized by program focus area, and present in technical detail the progress achieved in each of the 104 FY97 program tasks. Focus areas are as follows: pits; high explosives; organics; dynamics; diagnostics; systems; secondaries; nonnuclear materials; nonnuclear components; and Surveillance Test Program upgrades.

Progress in target materials for high-efficiency X-ray backlight

International Nuclear Information System (INIS)

Du Ai; Zhou Bin; Li Longxiang; Zhu Xiurong; Li Yu'nong; Shen Jun; Gao Guohua; Zhang Zhihua; Wu Guangming

2012-01-01

The composition, microstructure and density of the target materials are the key parameters to determinate the photon energy and intensity of the laser-induced X-ray backlight. Thus the classification of backlight targets, the preparation of target materials and the interaction between targets and high power laser were introduced in this paper. Underdense targets were more competitive than traditional dense targets among the backlight targets. Nano-structured foam targets, which could be classified into nanofiber targets and aerogel targets, were regarded as novel high-efficiency underdense targets. Nanofiber, which was commonly prepared via electro spinning and thermal treatment, exhibited good formability and high concentration of emission atoms; while aerogel, which was prepared via sol-gel processes and supercritical fluid drying, possesses the advantages of homogeneous microstructure and theoretically high conversion efficiency, but accompanied with the disadvantages of complex synthetic processes and low concentration of emission atoms. To prepare monolithic aerogels with low density and high concentration of emission atoms via combined sol-gel theories may be the better design for the development of the laser-induced X-ray backlight. (authors)

Geothermal resource areas database for monitoring the progress of development in the United States

Energy Technology Data Exchange (ETDEWEB)

Lawrence, J.D.; Lepman, S.R.; Leung, K.; Phillips, S.L.

1981-01-01

The Geothermal Resource Areas Database (GRAD) and associated data system provide broad coverage of information on the development of geothermal resources in the United States. The system is designed to serve the information requirements of the National Progress Monitoring System. GRAD covers development from the initial exploratory phase through plant construction and operation. Emphasis is on actual facts or events rather than projections and scenarios. The selection and organization of data are based on a model of geothermal development. Subjects in GRAD include: names and addresses, leases, area descriptions, geothermal wells, power plants, direct use facilities, and environmental and regulatory aspects of development. Data collected in the various subject areas are critically evaluated, and then entered into an on-line interactive computer system. The system is publically available for retrieval and use. The background of the project, conceptual development, software development, and data collection are described here. Appendices describe the structure of the database in detail.

In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis.

Science.gov (United States)

Latham, Antony M; Kankanala, Jayakanth; Fearnley, Gareth W; Gage, Matthew C; Kearney, Mark T; Homer-Vanniasinkam, Shervanthi; Wheatcroft, Stephen B; Fishwick, Colin W G; Ponnambalam, Sreenivasan

2014-01-01

Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small molecule kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues. We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis. We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro. This novel synthetic molecule has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery.

microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2.

Science.gov (United States)

Nie, Jing; Liu, Lin; Zheng, Wei; Chen, Lin; Wu, Xin; Xu, Yingxin; Du, Xiaohui; Han, Weidong

2012-01-01

Deregulated microRNAs participate in carcinogenesis and cancer progression, but their roles in cancer development remain unclear. In this study, miR-365 expression was found to be downregulated in human colon cancer tissues as compared with that in matched non-neoplastic mucosa tissues, and its downregulation was correlated with cancer progression and poor survival in colon cancer patients. Functional studies revealed that restoration of miR-365 expression inhibited cell cycle progression, promoted 5-fluorouracil-induced apoptosis and repressed tumorigenicity in colon cancer cell lines. Furthermore, bioinformatic prediction and experimental validation were used to identify miR-365 target genes and indicated that the antitumor effects of miR-365 were probably mediated by its targeting and repression of Cyclin D1 and Bcl-2 expression, thus inhibiting cell cycle progression and promoting apoptosis. These results suggest that downregulation of miR-365 in colon cancer may have potential applications in prognosis prediction and gene therapy in colon cancer patients.

U.C. Davis high energy particle physics research: Technical progress report -- 1990

Energy Technology Data Exchange (ETDEWEB)

NONE

1990-12-31

Summaries of progress made for this period is given for each of the following areas: (1) Task A--Experiment, H1 detector at DESY; (2) Task C--Experiment, AMY detector at KEK; (3) Task D--Experiment, fixed target detectors at Fermilab; (4) Task F--Experiment, PEP detector at SLAC and pixel detector; (5) Task B--Theory, particle physics; and (6) Task E--Theory, particle physics.

An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

Science.gov (United States)

Aleksandrova, I. V.; Bazdenkov, S. V.; Chtcherbakov, V. I.; Gromov, A. I.; Koresheva, E. R.; Koshelev, E. A.; Osipov, I. E.; Yaguzinskiy, L. S.

2004-04-01

Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets.

An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

International Nuclear Information System (INIS)

Aleksandrova, I V; Bazdenkov, S V; Chtcherbakov, V I; Gromov, A I; Koresheva, E R; Koshelev, E A; Osipov, I E; Yaguzinskiy, L S

2004-01-01

Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets

Progress in the chemistry of chromium(V) doping agents used in polarized target materials

International Nuclear Information System (INIS)

Krumpolc, M.; Hill, D.; Struhrmann, H.B.

1990-01-01

We wish to report progress in two areas of the chromium (V)-based doping agents: Two commonly used chromium (V) complexes, I and II, have been synthesized in perdeuterated form (i.e., all hydrogens replaced by deuterium). They are sodium bis(2-ethyl-2-deuteroxy-butyrato)oxochromate(V)monodeuterate, IV, (acronym EDBA-Cr(V)), and sodium bis(2-deuteroxy-2-methylpropionato)oxochromate(V), III, (acronym DMPA-Cr(V)). A synthetic route leading to the preparation of stable, chromium(III)-free solutions of chromium(V) in diols (1,2-ethanediol/ethylene glycol/and 1,2-propanediol/propylene glycol/) has been outlined

The Research Progress of Targeted Drug Delivery Systems

Science.gov (United States)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Progress in inertial fusion

International Nuclear Information System (INIS)

Hogan, W.; Storm, E.

1985-10-01

The requirements for high gain in inertial confinement are given in terms of target implosion requirements. Results of experimental studies of the laser/target interaction and of the dynamics of laser implosion. A report of the progress of advanced laser development is also presented. 3 refs., 8 figs., 1 tab

Low-Cost Radar Sensors for Personnel Detection and Tracking in Urban Areas

Science.gov (United States)

2007-01-31

progress on the reserach grant "Low-Cost Radar Sensors for Personnel Detection and Tracking in Urban Areas" during the period 1 May 2005 - 31 December...The limitations of the proposed system resulting from DOA ambiguity of multiple moving targets are studied. 2. METHODOLOGY Our radar receiver

Evaluation of fisher (Pekania pennanti) restoration in Olympic National Park and the Olympic Recovery Area: 2015 final annual progress report

Science.gov (United States)

Happe, Patricia J.; Jenkins, Kurt J.; Kay, Thomas J.; Pilgrim, Kristie; Schwartz, Michael K; Lewis, Jeffrey C.; Aubry, Keith B.

2016-01-01

With the translocation and release of 90 fishers (Pekania pennanti) from British Columbia to Olympic National Park during 2008–2010, the National Park Service (NPS) and Washington Department of Fish and Wildlife (WDFW) accomplished the first phase of fisher restoration in Washington State. Beginning in 2013, we initiated a new research project to determine the current status of fishers on Washington’s Olympic Peninsula 3–8 years after the releases and evaluate the short-term success of the restoration program. Objectives of the study are to determine the current distribution of fishers and proportion of the recovery area that is currently occupied by fishers, determine several genetic characteristics of the reintroduced population, and determine reproductive success of the founding animals through genetic studies. During 2015, we continued working with a broad coalition of cooperating agencies, tribes, and nongovernmental organizations (NGO) to collect data on fisher distribution and genetics using noninvasive sampling methods. The primary sampling frame consisted of 157 24-km2 hexagons (hexes) distributed across all major land ownerships within the Olympic Peninsula target survey area. In 2014 we expanded the study by adding 58 more hexes to an expanded study area in response to incidental fisher observations outside of the target area obtained in 2013; 49 hexes were added south and 9 to the east of the target area. During 2015, Federal, State, Tribal and NGO biologists and volunteers established three Distributioned motion-sensing camera stations, paired with hair snaring devices, in 87 hexes; 75 in the targeted area and 12 in the expansion areas. Each paired camera/hair station was left in place for approximately 6 weeks, with three checks on 2-week intervals. We documented fisher presence in 7 of the 87 hexagons. Four fishers were identified through microsatellite DNA analyses. The 4 identified fishers included 1 of the original founding population of 90

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

Science.gov (United States)

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

2018-03-01

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

Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention

Science.gov (United States)

Liskay, R.Michael

2014-01-01

Although Apc mutation is widely considered an initiating event in colorectal cancer, little is known about the earliest stages of tumorigenesis following sporadic Apc loss. Therefore, we have utilized a novel mouse model that facilitates the sporadic inactivation of Apc via frameshift reversion of Cre in single, isolated cells and subsequently tracks the fates of Apc-deficient intestinal cells. Our results suggest that consistent with Apc being a ‘gatekeeper’, loss of Apc early in life during intestinal growth leads to adenomas or increased crypt fission, manifested by fields of mutant but otherwise normal-appearing crypts. In contrast, Apc loss occurring later in life has minimal consequences, with mutant crypts being less prone to either increased crypt fission or adenoma formation. Using the stem cell-specific Lgr5-CreER mouse, we generated different sized fields of Apc-deficient crypts via independent recombination events and found that field size correlates with progression to adenoma. To evaluate this early stage prior to adenoma formation as a therapeutic target, we examined the chemopreventive effects of sulindac on Apc-deficient occult crypt fission. We found that sulindac treatment started early in life inhibits the morphologically occult spread of Apc-deficient crypts and thus reduces adenoma numbers. Taken together these results suggest that: (i) earlier Apc loss promotes increased crypt fission, (ii) a field of Apc-deficient crypts, which can form via occult crypt fission or independent neighboring events, is an important intermediate between loss of Apc and adenoma formation and (iii) normal-appearing Apc-deficient crypts are potential unappreciated targets for cancer screening and chemoprevention. PMID:23996931

Overview of U.S. heavy ion fusion progress and plans

International Nuclear Information System (INIS)

Logan, G.; Bieniosek, F.; Celata, C.; Henestroza, E.; Kwan, J; Lee, E.P.; Leitner, M.; Prost, L.; Roy, P.; Seidl, P.A.; Eylon, S.; Vay, J.-L.; Waldron, W.; Yu, S.; Barnard, J.; Callahan, D.; Cohen, R.; Friedman, A.; Grote, D.; Kireeff Covo, M.; Meier, W.R.; Molvik, A.; Lund, S.; Davidson, R.; Efthimion, P.; Gilson, E.; Grisham, L.; Kaganovich, I.; Qin, H.; Startsev, E.; Rose, D.; Welch, D.; Olson, C.; Kishek, R.; O'Shea, P.; Haber, I.

2004-01-01

Significant experimental and theoretical progress has been made in the U.S. heavy ion fusion program on high-current sources, injectors, transport, final focusing, chambers and targets for high energy density physics (HEDP) and inertial fusion energy (IFE) driven by induction linac accelerators. One focus of present research is the beam physics associated with quadrupole focusing of intense, space-charge dominated heavy-ion beams, including gas and electron cloud effects at high currents, and the study of long-distance-propagation effects such as emittance growth due to field errors in scaled experiments. A second area of emphasis in present research is the introduction of background plasma to neutralize the space charge of intense heavy ion beams and assist in focusing the beams to a small spot size. In the near future, research will continue in the above areas, and a new area of emphasis will be to explore the physics of neutralized beam compression and focusing to high intensities required to heat targets to high energy density conditions as well as for inertial fusion energy

Streamlined Approach for Environmental Restoration (SAFER) Plan for Corrective Action Unit 408: Bomblet Target Area Tonopah Test Range (TTR), Nevada, Revision 1

Energy Technology Data Exchange (ETDEWEB)

Mark Krauss

2010-03-01

This Streamlined Approach for Environmental Restoration Plan addresses the actions needed to achieve closure of Corrective Action Unit (CAU) 408, Bomblet Target Area (TTR). Corrective Action Unit 408 is located at the Tonopah Test Range and is currently listed in Appendix III of the Federal Facility Agreement and Consent Order. Corrective Action Unit 408 comprises Corrective Action Site TA-55-002-TAB2, Bomblet Target Areas. Clean closure of CAU 408 will be accomplished by removal of munitions and explosives of concern within seven target areas and potential disposal pits. The target areas were used to perform submunitions related tests for the U.S. Department of Energy (DOE). The scope of CAU 408 is limited to submunitions released from DOE activities. However, it is recognized that the presence of other types of unexploded ordnance and munitions may be present within the target areas due to the activities of other government organizations. The CAU 408 closure activities consist of: • Clearing bomblet target areas within the study area. • Identifying and remediating disposal pits. • Collecting verification samples. • Performing radiological screening of soil. • Removing soil containing contaminants at concentrations above the action levels. Based on existing information, contaminants of potential concern at CAU 408 include unexploded submunitions, explosives, Resource Conservation Recovery Act metals, and depleted uranium. Contaminants are not expected to be present in the soil at concentrations above the action levels; however, this will be determined by radiological surveys and verification sample results.

Streamlined Approach for Environmental Restoration (SAFER) Plan for Corrective Action Unit 408: Bomblet Target Area Tonopah Test Range (TTR), Nevada, Revision 1

International Nuclear Information System (INIS)

Krauss, Mark

2010-01-01

This Streamlined Approach for Environmental Restoration Plan addresses the actions needed to achieve closure of Corrective Action Unit (CAU) 408, Bomblet Target Area (TTR). Corrective Action Unit 408 is located at the Tonopah Test Range and is currently listed in Appendix III of the Federal Facility Agreement and Consent Order. Corrective Action Unit 408 comprises Corrective Action Site TA-55-002-TAB2, Bomblet Target Areas. Clean closure of CAU 408 will be accomplished by removal of munitions and explosives of concern within seven target areas and potential disposal pits. The target areas were used to perform submunitions related tests for the U.S. Department of Energy (DOE). The scope of CAU 408 is limited to submunitions released from DOE activities. However, it is recognized that the presence of other types of unexploded ordnance and munitions may be present within the target areas due to the activities of other government organizations. The CAU 408 closure activities consist of: (1) Clearing bomblet target areas within the study area. (2) Identifying and remediating disposal pits. (3) Collecting verification samples. (4) Performing radiological screening of soil. (5) Removing soil containing contaminants at concentrations above the action levels. Based on existing information, contaminants of potential concern at CAU 408 include unexploded submunitions, explosives, Resource Conservation Recovery Act metals, and depleted uranium. Contaminants are not expected to be present in the soil at concentrations above the action levels; however, this will be determined by radiological surveys and verification sample results.

Setting Ambitious yet Achievable Targets Using Probabilistic Projections: Meeting Demand for Family Planning.

Science.gov (United States)

Kantorová, Vladimíra; New, Jin Rou; Biddlecom, Ann; Alkema, Leontine

2017-09-01

In 2015, governments adopted 17 internationally agreed goals to ensure progress and well-being in the economic, social, and environmental dimensions of sustainable development. These new goals present a challenge for countries to set empirical targets that are ambitious yet achievable and that can account for different starting points and rates of progress. We used probabilistic projections of family planning indicators, based on a global data set and Bayesian hierarchical modeling, to generate illustrative targets at the country level. Targets were defined as the percentage of demand for family planning satisfied with modern contraceptive methods where a country has at least a 10 percent chance of reaching the target by 2030. National targets for 2030 ranged from below 50 percent of demand satisfied with modern contraceptives (for three countries in Africa) to above 90 percent (for 41 countries from all major areas of the world). The probabilistic approach also identified countries for which a global fixed target value of 75 percent demand satisfied was either unambitious or has little chance of achievement. We present the web-based Family Planning Estimation Tool (FPET) enabling national decision makers to compute and assess targets for meeting family planning demand. © 2017 The Population Council, Inc.

Recent advances in indirect drive ICF target physics

International Nuclear Information System (INIS)

Hammel, B.A.

2002-01-01

The National Ignition Facility (NIF), currently under construction, will be used for the study of ignition physics in inertially confined targets, as well as basic and applied research in the field of high energy density science. In preparing for ignition on the NIF, the Lawrence Livermore National Laboratory's Inertial Confinement Fusion Program, in collaboration with Los Alamos National Laboratory (LANL), Sandia National Laboratory (SNL), the Laboratory for Laser Energetics (LLE), General Atomics (GA), and the Commissariat a l'Energie Atomique (CEA), is working to refine ignition designs, develop improved experimental methods, and fabricate and test cryogenic targets required for ignition. This paper will briefly review NIF construction progress, and summarize advances in these areas. (author)

In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis.

Directory of Open Access Journals (Sweden)

Antony M Latham

Full Text Available Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small molecule kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues.We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2 and cyclin-dependent kinase 1 (CDK1. This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis.We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro. This novel synthetic molecule has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery.

Antagonism of EG-VEGF Receptors as Targeted Therapy for Choriocarcinoma Progression In Vitro and In Vivo.

Science.gov (United States)

Traboulsi, Wael; Sergent, Frédéric; Boufettal, Houssine; Brouillet, Sophie; Slim, Rima; Hoffmann, Pascale; Benlahfid, Mohammed; Zhou, Qun Y; Balboni, Gianfranco; Onnis, Valentina; Bolze, Pierre A; Salomon, Aude; Sauthier, Philippe; Mallet, François; Aboussaouira, Touria; Feige, Jean J; Benharouga, Mohamed; Alfaidy, Nadia

2017-11-15

Purpose: Choriocarcinoma (CC) is the most malignant gestational trophoblastic disease that often develops from complete hydatidiform moles (CHM). Neither the mechanism of CC development nor its progression is yet characterized. We recently identified endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as a novel key placental growth factor that controls trophoblast proliferation and invasion. EG-VEGF acts via two receptors, PROKR1 and PROKR2. Here, we demonstrate that EG-VEGF receptors can be targeted for CC therapy. Experimental Design: Three approaches were used: (i) a clinical investigation comparing circulating EG-VEGF in control ( n = 20) and in distinctive CHM ( n = 38) and CC ( n = 9) cohorts, (ii) an in vitro study investigating EG-VEGF effects on the CC cell line JEG3, and (iii) an in vivo study including the development of a novel CC mouse model, through a direct injection of JEG3-luciferase into the placenta of gravid SCID-mice. Results: Both placental and circulating EG-VEGF levels were increased in CHM and CC (×5) patients. EG-VEGF increased JEG3 proliferation, migration, and invasion in two-dimensional (2D) and three-dimensional (3D) culture systems. JEG3 injection in the placenta caused CC development with large metastases compared with their injection into the uterine horn. Treatment of the animal model with EG-VEGF receptor's antagonists significantly reduced tumor development and progression and preserved pregnancy. Antibody-array and immunohistological analyses further deciphered the mechanism of the antagonist's actions. Conclusions: Our work describes a novel preclinical animal model of CC and presents evidence that EG-VEGF receptors can be targeted for CC therapy. This may provide safe and less toxic therapeutic options compared with the currently used multi-agent chemotherapies. Clin Cancer Res; 23(22); 7130-40. ©2017 AACR . ©2017 American Association for Cancer Research.

MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1.

Science.gov (United States)

Qian, Lu; Zhang, Wanggang; Lei, Bo; He, Aili; Ye, Lianhong; Li, Xingzhou; Dong, Xin

2016-11-01

The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays. Luciferase assay confirmed that Notch1 was a target gene of miR-101, and western blotting showed that miR-101 suppressed the expression of Notch1 at the protein level. Moreover, functional restoration assays revealed that Notch1 mediates the effects of miR-101 on Jurkat cell proliferation, apoptosis and invasion. miR-101 enhanced the sensitivity of Jurkat cells to the chemotherapeutic agent adriamycin. Taken together, our results show for the first time that miR-101 acts as a tumor suppressor in T-cell acute lymphoblastic leukaemia and it could enhance chemotherapeutic sensitivity. Furthermore, Notch1 was identified to be a novel target of miR-101. This study indicates that miR-101 may represent a potential therapeutic target for T-cell acute lymphoblastic leukemia intervention.

Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress

NARCIS (Netherlands)

Lammers, Twan Gerardus Gertudis Maria; Kiessling, F.; Hennink, W.E.; Storm, Gerrit

2012-01-01

Abstract Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells,

MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma

International Nuclear Information System (INIS)

Wang, Maomao; Deng, Xiaodong; Ying, Qi; Jin, Tingyan; Li, Ming; Liang, Chong

2015-01-01

MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan–Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan–Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas. - Highlights: • MiR-224 expression is correlates with prognosis in meningioma patients. • ERG2 is a novel downstream target of miR-224. • MiR-224 suppressed cell growth and enhanced apoptosis in IOMM-Lee and CH157 cells. • MiR-224 is an upstream regulator of the ERG2

Targeting Glutamatergic Signaling and the PI3 Kinase Pathway to Halt Melanoma Progression

Directory of Open Access Journals (Sweden)

Stephen A. Rosenberg

2015-02-01

Full Text Available Our group has previously reported that the majority of human melanomas (>60% express the metabotropic glutamate receptor 1 (GRM1 and that the glutamate release inhibitor riluzole, a drug currently used to treat amyotrophic lateral sclerosis, can induce apoptosis in GRM1-expressing melanoma cells. Our group previously reported that in vitro riluzole treatment reduces cell growth in three-dimensional (3D soft agar colony assays by 80% in cells with wildtype phosphoinositide 3-kinase (PI3K pathway activation. However, melanoma cell lines harboring constitutive activating mutations of the PI3K pathway (PTEN and NRAS mutations showed only a 35% to 40% decrease in colony formation in soft agar in the presence of riluzole. In this study, we have continued our preclinical studies of riluzole and its effect on melanoma cells alone and in combination with inhibitors of the PI3 kinase pathway: the AKT inhibitor, API-2, and the mammalian target of rapamycin (mTOR inhibitor, rapamycin. We modeled these combinatorial therapies on various melanoma cell lines in 3D and 2D systems and in vivo. Riluzole combined with mTOR inhibition is more effective at halting melanoma anchorage-independent growth and xenograft tumor progression than either agent alone. PI3K signaling changes associated with this combinatorial treatment shows that 3D (nanoculture modeling of cell signaling more closely resembles in vivo signaling than monolayer models. Riluzole combined with mTOR inhibition is effective at halting tumor cell progression independent of BRAF mutational status. This makes this combinatorial therapy a potentially viable alternative for metastatic melanoma patients who are BRAF WT and are therefore ineligible for vemurafenib therapy.

Influence of the Target Vessel on the Location and Area of Maximum Skin Dose during Percutaneous Coronary Intervention

International Nuclear Information System (INIS)

Chida, K.; Fuda, K.; Kagaya, Y.; Saito, H.; Takai, Y.; Kohzuki, M.; Takahash i, S.; Yamada, S.; Zuguchi, M.

2007-01-01

Background: A number of cases involving radiation-associated patient skin injury attributable to percutaneous coronary intervention (PCI) have been reported. Knowledge of the location and area of the patient's maximum skin dose (MSD) in PCI is necessary to reduce the risk of skin injury. Purpose: To determine the location and area of the MSD in PCI, and separately analyze the effects of different target vessels. Material and Methods: 197 consecutive PCI procedures were studied, and the location and area of the MSD were calculated by a skin-dose mapping software program: Caregraph. The target vessels of the PCI procedures were divided into four groups based on the American Heart Association (AHA) classification. Results: The sites of the MSD for AHA no.1-3, AHA no.4, and AHA no.11-15 were located mainly on the right back skin, the lower right or center back skin, and the upper back skin areas, respectively, whereas the MSD sites for the AHA no. 5-10 PCI were widely spread. The MSD area for the AHA no. 4 PCI was larger than that for the AHA no. 11-15 PCI (P<0.0001). Conclusion: Although the radiation associated with PCI can be widely spread and variable, we observed a tendency regarding the location and area of the MSD when we separately analyzed the data for different target vessels. We recommend the use of a smaller radiation field size and the elimination of overlapping fields during PCI

Targeting Nanomedicine to Brain Tumors: Latest Progress and Achievements.

Science.gov (United States)

Van't Root, Moniek; Lowik, Clemens; Mezzanotte, Laura

2017-01-01

Targeting nanomedicine to brain tumors is hampered by the heterogeneity of brain tumors and the blood brain barrier. These represent the main reasons of unsuccessful treatments. Nanomedicine based approaches hold promise for improved brain tissue distribution of drugs and delivery of combination therapies. In this review, we describe the recent advancements and latest achievements in the use of nanocarriers, virus and cell-derived nanoparticles for targeted therapy of brain tumors. We provide successful examples of nanomedicine based approaches for direct targeting of receptors expressed in brain tumor cells or modulation of pathways involved in cell survival as well as approaches for indirect targeting of cells in the tumor stroma and immunotherapies. Although the field is at its infancy, clinical trials involving nanomedicine based approaches for brain tumors are ongoing and many others will start in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Adaptive block online learning target tracking based on super pixel segmentation

Science.gov (United States)

Cheng, Yue; Li, Jianzeng

2018-04-01

Video target tracking technology under the unremitting exploration of predecessors has made big progress, but there are still lots of problems not solved. This paper proposed a new algorithm of target tracking based on image segmentation technology. Firstly we divide the selected region using simple linear iterative clustering (SLIC) algorithm, after that, we block the area with the improved density-based spatial clustering of applications with noise (DBSCAN) clustering algorithm. Each sub-block independently trained classifier and tracked, then the algorithm ignore the failed tracking sub-block while reintegrate the rest of the sub-blocks into tracking box to complete the target tracking. The experimental results show that our algorithm can work effectively under occlusion interference, rotation change, scale change and many other problems in target tracking compared with the current mainstream algorithms.

Semiautomatic Segmentation of Rim Area Focal Hyperautofluorescence Predicts Progression of Geographic Atrophy Due to Dry Age-Related Macular Degeneration.

Science.gov (United States)

Allingham, Michael J; Nie, Qing; Lad, Eleonora M; Izatt, Daniel J; Mettu, Priyatham S; Cousins, Scott W; Farsiu, Sina

2016-04-01

To develop image analysis software usable by nonexpert graders to segment geographic atrophy (GA) from dry AMD and to quantify rim area focal hyperautofluorescence (RAFH) surrounding GA on fundus autofluorescence (FAF) images. To compare the GA progression predictions based on RAFH with those of a validated qualitative classification system. Retrospective analysis of serial FAF images from 49 eyes of 30 subjects with GA was performed using MATLAB-based software (MathWorks, Natick, MA, USA). Correlation between RAFH and progression of GA was analyzed using Spearman correlation. Comparisons of lesion growth rate between RAFH tertiles used generalized estimating equations and Kruskal-Wallis testing. Interobserver variability in lesion size, growth rate and RAFH were compared between two expert and one nonexpert grader using Bland-Altman statistics. Rim area focal hyperautofluorescence was positively correlated with GA progression rate (ρ = 0.49, P < 0.001). Subjects in the middle or highest RAFH tertile were at greater risk of progression (P = 0.005 and P = 0.001, respectively). Mean difference in RAFH was 0.012 between expert and -0.005 to 0.017 between expert and nonexperts. Mean difference in lesion size (mm2) was 0.11 between expert and -0.29 to 0.41 between expert and nonexperts. Mean difference in lesion growth rate (mm2/mo) was 0.0098 between expert and -0.027 to 0.037 between expert and nonexperts. Risk stratification based on RAFH tertile was 96% identical across all graders. Our semiautomated image analysis software facilitates stratification of progression risk based on RAFH and enabled a nonexpert grader with minimal training to obtain results comparable to expert graders. Predictions based on RAFH were similar to those of a validated qualitative classification system.

MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1

Energy Technology Data Exchange (ETDEWEB)

Tian, Zhijie [School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500 (China); Jiang, Hequn [The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041 (China); Liu, Ying; Huang, Yong [School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500 (China); Xiong, Xin [Laboratory Research Center, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016 (China); Wu, Hongwei, E-mail: hongweiwu2118@sina.com [The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041 (China); Dai, Xiaozhen, E-mail: xiaozhendai2012@163.com [School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500 (China); Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing 400044 (China); Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY (United States)

2016-05-01

MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as critical gene regulators by targeting mRNAs for translational repression or degradation. In this study, we showed that the expression level of miR-133b was decreased, while Sirt1 mRNA expression levels were increased in hepatocellular carcinoma (HCC) and cell lines, and we identified Sirt1 as a novel direct target of miR-133b. The over-expression of miR-133b suppressed Sirt1 expression. In addition, miR-133b over-expression resulted in attenuating HCC cell proliferation and invasion together with apoptosis increase in vitro. HepG2 cell transplantation revealed that up-regulation of miR-133b could inhibit HCC tumor genesis in vivo. Forced expression of Sirt1 partly rescued the effect of miR-133b in vitro. Furthermore, our study showed that miR-133b over-expression or Sirt1 down-regulation elevated E-cadherin expression, and repressed glypican-3 (GPC3) and the anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1) expression. The inhibition of GPC3 expression repressed Bcl-2, Bcl-xL, and Mcl-1 expression, and elevated E-cadherin expression. Moreover, the Sirt1 up-regulation resulted in increases in HCC cell proliferation and invasion together with decreases apoptosis, and increases in the cytosolic accumulation and nuclear translocation of the transcription factor β-catenin in vitro. But the effect of Sirt1 up-regulation was partly reversed by GPC3 down-regulation in vitro. Taken together, these findings provide insight into the role and mechanism of miR-133b in regulating HCC cell proliferation, invasion and apoptosis via the miR-133b/Sirt1/GPC3/Wnt β-catenin axis, and miR-133b may serve as a potential therapeutic target in HCC in the future. - Highlights: • Sirt1 is a direct target of miR-133b in HCC. • miR-133b over-expression suppresses HCC progression in vitro and in vivo. • Sirt1 restoration reverses the effect of miR-133b over-expression on HCC cells. • GPC3 down-regulation reverses

MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1

International Nuclear Information System (INIS)

Tian, Zhijie; Jiang, Hequn; Liu, Ying; Huang, Yong; Xiong, Xin; Wu, Hongwei; Dai, Xiaozhen

2016-01-01

MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as critical gene regulators by targeting mRNAs for translational repression or degradation. In this study, we showed that the expression level of miR-133b was decreased, while Sirt1 mRNA expression levels were increased in hepatocellular carcinoma (HCC) and cell lines, and we identified Sirt1 as a novel direct target of miR-133b. The over-expression of miR-133b suppressed Sirt1 expression. In addition, miR-133b over-expression resulted in attenuating HCC cell proliferation and invasion together with apoptosis increase in vitro. HepG2 cell transplantation revealed that up-regulation of miR-133b could inhibit HCC tumor genesis in vivo. Forced expression of Sirt1 partly rescued the effect of miR-133b in vitro. Furthermore, our study showed that miR-133b over-expression or Sirt1 down-regulation elevated E-cadherin expression, and repressed glypican-3 (GPC3) and the anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1) expression. The inhibition of GPC3 expression repressed Bcl-2, Bcl-xL, and Mcl-1 expression, and elevated E-cadherin expression. Moreover, the Sirt1 up-regulation resulted in increases in HCC cell proliferation and invasion together with decreases apoptosis, and increases in the cytosolic accumulation and nuclear translocation of the transcription factor β-catenin in vitro. But the effect of Sirt1 up-regulation was partly reversed by GPC3 down-regulation in vitro. Taken together, these findings provide insight into the role and mechanism of miR-133b in regulating HCC cell proliferation, invasion and apoptosis via the miR-133b/Sirt1/GPC3/Wnt β-catenin axis, and miR-133b may serve as a potential therapeutic target in HCC in the future. - Highlights: • Sirt1 is a direct target of miR-133b in HCC. • miR-133b over-expression suppresses HCC progression in vitro and in vivo. • Sirt1 restoration reverses the effect of miR-133b over-expression on HCC cells. • GPC3 down-regulation reverses

Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.

Science.gov (United States)

Bojadzic, Damir; Buchwald, Peter

2018-05-30

Protein-protein interactions (PPIs) that are part of the costimulatory and coinhibitory (immune checkpoint) signaling are critical for adequate T cell response and are important therapeutic targets for immunomodulation. Biologics targeting them have already achieved considerable clinical success in the treatment of autoimmune diseases or transplant recipients (e.g., abatacept, belatacept, and belimumab) as well as cancer (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab). In view of such progress, there have been only relatively limited efforts toward developing small-molecule PPI inhibitors (SMPPIIs) targeting these cosignaling interactions, possibly because they, as all other PPIs, are difficult to target by small molecules and were not considered druggable. Nevertheless, substantial progress has been achieved during the last decade. SMPPIIs proving the feasibility of such approaches have been identified through various strategies for a number of cosignaling interactions including CD40-CD40L, OX40-OX40L, BAFFR-BAFF, CD80-CD28, and PD-1-PD-L1s. Here, after an overview of the general aspects and challenges of SMPPII-focused drug discovery, we review them briefly together with relevant structural, immune-signaling, physicochemical, and medicinal chemistry aspects. While so far only a few of these SMPPIIs have shown activity in animal models (DRI-C21045 for CD40-D40L, KR33426 for BAFFR-BAFF) or reached clinical development (RhuDex for CD80-CD28, CA-170 for PD-1-PD-L1), there is proof-of-principle evidence for the feasibility of such approaches in immunomodulation. They can result in products that are easier to develop/manufacture and are less likely to be immunogenic or encounter postmarket safety events than corresponding biologics, and, contrary to them, can even become orally bioavailable. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Key Biodiversity Areas in the Indo-Burma Hotspot: Process, Progress and Future Directions

Directory of Open Access Journals (Sweden)

A.W. Tordoff

2012-08-01

Full Text Available Key Biodiversity Areas (KBAs provide geographic targets for the expansion of protected area coverage, and identify sites for urgent conservation action. Identification of KBAs in the Indo-Burma Hotspot was undertaken during 2003, for a region of analysis comprising Cambodia, Lao PDR, Myanmar (Burma, Thailand and Vietnam, plus parts of southern China. The starting point was information on 282 Important Bird Areas identified by BirdLife International and collaborators. These data were then overlaid with point locality data on globally threatened mammals, reptiles, amphibians, freshwater fish and plants, with additional KBAs identified as required. Through this process, a total of 438 KBAs were identified, covering 258,085km2 or 11.5 percent of the region of analysis. Only 58 percent of the KBAs are wholly or partly included within protected areas, suggesting that there may be a need for further expansion of protected area networks, particularly in Myanmar and Vietnam. The criteria for KBA identification are triggered by 812 species, of which 23 are believed only to occur at a single KBA globally. The KBAs have proven to be a useful conservation priority setting tool in Indo-Burma, helping to guide investments by various donors and application of environmental safeguard policies by international financial institutions. There are fewer examples of KBAs being used to guide expansion of protected area systems in Indo-Burma. In large part, this is because the period of rapid expansion of protected areas in most hotspot countries predated the KBA identification process, and political support for further significant expansion is currently limited.

Renewable energy progress and biofuels sustainability

Energy Technology Data Exchange (ETDEWEB)

Hamelinck, C.; De Lovinfosse, I.; Koper, M.; Beestermoeller, C.; Nabe, C.; Kimmel, M.; Van den Bos, A.; Yildiz, I.; Harteveld, M. [Ecofys Netherlands, Utrecht (Netherlands); Ragwitz, M.; Steinhilber, S. [Fraunhofer Institut fuer System- und Innovationsforschung ISI, Karlsruhe (Germany); Nysten, J.; Fouquet, D. [Becker Buettner Held BBH, Munich (Germany); Resch, G.; Liebmann, L.; Ortner, A.; Panzer, C. [Energy Economics Group EEG, Vienna University of Technology, Vienna (Austria); Walden, D.; Diaz Chavez, R.; Byers, B.; Petrova, S.; Kunen, E. [Winrock International, Brussels (Belgium); Fischer, G.

2013-03-15

On 27 March 2013, the European Commission published its first Renewable Energy Progress Report under the framework of the 2009 Renewable Energy Directive. Since the adoption of this directive and the introduction of legally binding renewable energy targets, most Member States experienced significant growth in renewable energy consumption. 2010 figures indicate that the EU as a whole is on its trajectory towards the 2020 targets with a renewable energy share of 12.7%. Moreover, in 2010 the majority of Member States already reached their 2011/2012 interim targets set in the Directive. However, as the trajectory grows steeper towards the end, more efforts will still be needed from the Member States in order to reach the 2020 targets. With regard to the EU biofuels and bioliquids sustainability criteria, Member States' implementation of the biofuels scheme is considered too slow. In accordance with the reporting requirements set out in the 2009 Directive on Renewable Energy, every two years the European Commission publishes a Renewable Energy Progress Report. The report assesses Member States' progress in the promotion and use of renewable energy along the trajectory towards the 2020 renewable energy targets. The report also describes the overall renewable energy policy developments in each Member State and their compliance with the measures outlined in the Directive and the National Renewable Energy Action Plans. Moreover, in accordance with the Directive, it reports on the sustainability of biofuels and bioliquids consumed in the EU and the impacts of this consumption. A consortium led by Ecofys was contracted by the European Commission to perform support activities concerning the assessment of progress in renewable energy and sustainability of biofuels.

Renewable energy progress and biofuels sustainability

Energy Technology Data Exchange (ETDEWEB)

Hamelinck, C.; De Lovinfosse, I.; Koper, M.; Beestermoeller, C.; Nabe, C.; Kimmel, M.; Van den Bos, A.; Yildiz, I.; Harteveld, M. [Ecofys Netherlands, Utrecht (Netherlands); Ragwitz, M.; Steinhilber, S. [Fraunhofer Institut fuer System- und Innovationsforschung ISI, Karlsruhe (Germany); Nysten, J.; Fouquet, D. [Becker Buettner Held BBH, Munich (Germany); Resch, G.; Liebmann, L.; Ortner, A.; Panzer, C. [Energy Economics Group EEG, Vienna University of Technology, Vienna (Austria); Walden, D.; Diaz Chavez, R.; Byers, B.; Petrova, S.; Kunen, E. [Winrock International, Brussels (Belgium); Fischer, G.

2013-03-15

On 27 March 2013, the European Commission published its first Renewable Energy Progress Report under the framework of the 2009 Renewable Energy Directive. Since the adoption of this directive and the introduction of legally binding renewable energy targets, most Member States experienced significant growth in renewable energy consumption. 2010 figures indicate that the EU as a whole is on its trajectory towards the 2020 targets with a renewable energy share of 12.7%. Moreover, in 2010 the majority of Member States already reached their 2011/2012 interim targets set in the Directive. However, as the trajectory grows steeper towards the end, more efforts will still be needed from the Member States in order to reach the 2020 targets. With regard to the EU biofuels and bioliquids sustainability criteria, Member States' implementation of the biofuels scheme is considered too slow. In accordance with the reporting requirements set out in the 2009 Directive on Renewable Energy, every two years the European Commission publishes a Renewable Energy Progress Report. The report assesses Member States' progress in the promotion and use of renewable energy along the trajectory towards the 2020 renewable energy targets. The report also describes the overall renewable energy policy developments in each Member State and their compliance with the measures outlined in the Directive and the National Renewable Energy Action Plans. Moreover, in accordance with the Directive, it reports on the sustainability of biofuels and bioliquids consumed in the EU and the impacts of this consumption. A consortium led by Ecofys was contracted by the European Commission to perform support activities concerning the assessment of progress in renewable energy and sustainability of biofuels.

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

Science.gov (United States)

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

2015-01-01

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

Evaluation of the geologic relations and seismotectonic stability of the Yucca Mountain Area Nevada Nuclear Waste Site Investigation (NNWSI). Progress report, 30 September 1994

Energy Technology Data Exchange (ETDEWEB)

NONE

1994-12-31

This report dated 30 September 1994 provides a summary of progress for the project {open_quotes}Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI){close_quotes}. This progress report was preceded by the progress report for the year from 1 October 1992 to 30 September 1993. This report summarizes the geologic and seismotectonic studies conducted at Yucca Mountain during the contract period including Quaternary tectonics, an evaluation of mineral resource potential of the area, caldera geology, and volcano-tectonic activity at and near the site. A report of basinal studies conducted during the contract period is also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

Targeted therapies in the treatment of urothelial cancers.

Science.gov (United States)

Aragon-Ching, Jeanny B; Trump, Donald L

2017-07-01

Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

Abnormal cortical synaptic plasticity in primary motor area in progressive supranuclear palsy.

Science.gov (United States)

Conte, Antonella; Belvisi, Daniele; Bologna, Matteo; Ottaviani, Donatella; Fabbrini, Giovanni; Colosimo, Carlo; Williams, David R; Berardelli, Alfredo

2012-03-01

No study has yet investigated whether cortical plasticity in primary motor area (M1) is abnormal in patients with progressive supranuclear palsy (PSP). We studied M1 plasticity in 15 PSP patients and 15 age-matched healthy subjects. We used intermittent theta-burst stimulation (iTBS) to investigate long-term potentiation (LTP) and continuous TBS (cTBS) to investigate long-term depression (LTD)-like cortical plasticity in M1. Ten patients underwent iTBS again 1 year later. We also investigated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in M1 with paired-pulse transcranial magnetic stimulation, tested H reflex from upper limb flexor muscles before and after iTBS, and measured motor evoked potential (MEP) input-output (I/O) curves before and after iTBS. iTBS elicited a significantly larger MEP facilitation after iTBS in patients than in healthy subjects. Whereas in healthy subjects, cTBS inhibited MEP, in patients it significantly facilitated MEPs. In patients, SICI was reduced, whereas ICF was normal. H reflex size remained unchanged after iTBS. Patients had steeper MEP I/O slopes than healthy subjects at baseline and became even more steeper after iTBS only in patients. The iTBS-induced abnormal MEP facilitation in PSP persisted at 1-year follow-up. In conclusion, patients with PSP have abnormal M1 LTP/LTD-like plasticity. The enhanced LTP-like cortical synaptic plasticity parallels disease progression.

Progress and perspectives on targeting nanoparticles for brain drug delivery

Directory of Open Access Journals (Sweden)

Huile Gao

2016-07-01

Full Text Available Due to the ability of the blood–brain barrier (BBB to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier (BBTB, and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.

Progress and perspectives on targeting nanoparticles for brain drug delivery

Institute of Scientific and Technical Information of China (English)

Huile Gao

2016-01-01

Due to the ability of the blood–brain barrier(BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier(BBTB), and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.

M402, a novel heparan sulfate mimetic, targets multiple pathways implicated in tumor progression and metastasis.

Directory of Open Access Journals (Sweden)

He Zhou

Full Text Available Heparan sulfate proteoglycans (HSPGs play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1α, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis.

Trends and projections in Europe 2013. Tracking progress towards Europe's climate and energy targets until 2020

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-10-01

This report provide an assessment of the progress of the EU and European countries towards achieving their climate mitigation and energy policy objectives. These targets include international commitments pursuant the KP and the EU 2020 commitment to reduce by 20 % greenhouse gas (GHG) emissions compared to 1990, to create 20 % of energy consumption from renewables and to increase energy efficiency by 20 %. The assessment is based on GHG data for the period 2008-2012, including recent estimates of proxy 2012 GHG emissions, GHG projections until 2020 submitted by Member States in 2013, as well as energy statistics until 2011. (Author)

Tracking progress toward global polio eradication--worldwide, 2009-2010.

Science.gov (United States)

2011-04-15

Since the Global Polio Eradication Initiative (GPEI) began in 1988, progress has been tracked by 1) surveillance comprised of detection and investigation of cases of acute flaccid paralysis (AFP), coupled with environmental surveillance (sewage testing) in selected areas, and 2) timely testing of fecal specimens in accredited laboratories to identify polioviruses. The sensitivity of AFP case detection and the timeliness of AFP investigations are monitored with performance indicators. Polioviruses are isolated and characterized by the Global Polio Laboratory Network (GPLN). This report assesses the quality of polio surveillance and the timeliness of poliovirus isolation reporting and characterization worldwide during 2009--2010. During that period, 77% of countries affected by wild poliovirus (WPV) met national performance standards for AFP surveillance; underperforming subnational areas were identified in two of four countries with reestablished WPV transmission and in 13 of 22 countries with WPV outbreaks. Targets for timely GPLN reporting of poliovirus isolation results were met in five World Health Organization (WHO) regions in 2009 and in four of six regions in 2010; targets for timely poliovirus characterization were met in four WHO regions in 2009 and in five regions in 2010. Monitoring of surveillance performance indicators at subnational levels continues to be critical to identifying surveillance gaps that might allow WPV circulation to be missed in certain areas or subpopulations. To achieve polio eradication, efforts are needed to further strengthen AFP surveillance, implement targeted environmental surveillance, and ensure that GPLN quality is maintained.

Multi-target molecular imaging and its progress in research and application

International Nuclear Information System (INIS)

Tang Ganghua

2011-01-01

Multi-target molecular imaging (MMI) is an important field of research in molecular imaging. It includes multi-tracer multi-target molecular imaging(MTMI), fusion-molecule multi-target imaging (FMMI), coupling-molecule multi-target imaging (CMMI), and multi-target multifunctional molecular imaging(MMMI). In this paper,imaging modes of MMI are reviewed, and potential applications of positron emission tomography MMI in near future are discussed. (author)

St. Louis Area Earthquake Hazards Mapping Project - A Progress Report-November 2008

Science.gov (United States)

Karadeniz, D.; Rogers, J.D.; Williams, R.A.; Cramer, C.H.; Bauer, R.A.; Hoffman, D.; Chung, J.; Hempen, G.L.; Steckel, P.H.; Boyd, O.L.; Watkins, C.M.; McCallister, N.S.; Schweig, E.

2009-01-01

St. Louis has experienced minor earthquake damage at least 12 times in the past 200 years. Because of this history and its proximity to known active earthquake zones, the St. Louis Area Earthquake Hazards Mapping Project (SLAEHMP) is producing digital maps that show variability of earthquake hazards, including liquefaction and ground shaking, in the St. Louis area. The maps will be available free via the internet. Although not site specific enough to indicate the hazard at a house-by-house resolution, they can be customized by the user to show specific areas of interest, such as neighborhoods or transportation routes. Earthquakes currently cannot be predicted, but scientists can estimate how strongly the ground is likely to shake as the result of an earthquake. Earthquake hazard maps provide one way of conveying such estimates. The U.S. Geological Survey (USGS), which produces earthquake hazard maps for the Nation, is working with local partners to develop detailed maps for urban areas vulnerable to strong ground shaking. These partners, which along with the USGS comprise the SLAEHMP, include the Missouri University of Science and Technology-Rolla (Missouri S&T), Missouri Department of Natural Resources (MDNR), Illinois State Geological Survey (ISGS), Saint Louis University, Missouri State Emergency Management Agency, and URS Corporation. Preliminary hazard maps covering a test portion of the 29-quadrangle St. Louis study area have been produced and are currently being evaluated by the SLAEHMP. A USGS Fact Sheet summarizing this project was produced and almost 1000 copies have been distributed at several public outreach meetings and field trips that have featured the SLAEHMP (Williams and others, 2007). In addition, a USGS website focusing on the SLAEHMP, which provides links to project results and relevant earthquake hazard information, can be found at: http://earthquake.usgs.gov/regional/ceus/urban_map/st_louis/index.php. This progress report summarizes the

Targeting androgen receptor and JunD interaction for prevention of prostate cancer progression.

Science.gov (United States)

Mehraein-Ghomi, Farideh; Kegel, Stacy J; Church, Dawn R; Schmidt, Joseph S; Reuter, Quentin R; Saphner, Elizabeth L; Basu, Hirak S; Wilding, George

2014-05-01

Multiple studies show that reactive oxygen species (ROS) play a major role in prostate cancer (PCa) development and progression. Previously, we reported an induction of Spermidine/Spermine N(1) -Acetyl Transferase (SSAT) by androgen-activated androgen receptor (AR)-JunD protein complex that leads to over-production of ROS in PCa cells. In our current research, we identify small molecules that specifically block AR-JunD in this ROS-generating metabolic pathway. A high throughput assay based on Gaussia Luciferase reconstitution was used to identify inhibitors of the AR-JunD interaction. Selected hits were further screened using a fluorescence polarization competitor assay to eliminate those that bind to the AR Ligand Binding Domain (LBD), in order to identify molecules that specifically target events downstream to androgen activation of AR. Eleven molecules were selected for studies on their efficacy against ROS generation and growth of cultured human PCa cells by DCFH dye-oxidation assay and DNA fluorescence assay, respectively. In situ Proximity Ligation Assay (PLA), SSAT promoter-luciferase reporter assay, and western blotting of apoptosis and cell cycle markers were used to study mechanism of action of the lead compound. Selected lead compound GWARJD10 with EC(50) 10 μM against ROS production was shown to block AR-JunD interaction in situ as well as block androgen-induced SSAT gene expression at IC(50) 5 μM. This compound had no effect on apoptosis markers, but reduced cyclin D1 protein level. Inhibitor of AR-JunD interaction, GWARJD10 shows promise for prevention of progression of PCa at an early stage of the disease by blocking growth and ROS production. © 2014 Wiley Periodicals, Inc.

Collaborative 3D Target Tracking in Distributed Smart Camera Networks for Wide-Area Surveillance

Directory of Open Access Journals (Sweden)

Xenofon Koutsoukos

2013-05-01

Full Text Available With the evolution and fusion of wireless sensor network and embedded camera technologies, distributed smart camera networks have emerged as a new class of systems for wide-area surveillance applications. Wireless networks, however, introduce a number of constraints to the system that need to be considered, notably the communication bandwidth constraints. Existing approaches for target tracking using a camera network typically utilize target handover mechanisms between cameras, or combine results from 2D trackers in each camera into 3D target estimation. Such approaches suffer from scale selection, target rotation, and occlusion, drawbacks typically associated with 2D tracking. In this paper, we present an approach for tracking multiple targets directly in 3D space using a network of smart cameras. The approach employs multi-view histograms to characterize targets in 3D space using color and texture as the visual features. The visual features from each camera along with the target models are used in a probabilistic tracker to estimate the target state. We introduce four variations of our base tracker that incur different computational and communication costs on each node and result in different tracking accuracy. We demonstrate the effectiveness of our proposed trackers by comparing their performance to a 3D tracker that fuses the results of independent 2D trackers. We also present performance analysis of the base tracker along Quality-of-Service (QoS and Quality-of-Information (QoI metrics, and study QoS vs. QoI trade-offs between the proposed tracker variations. Finally, we demonstrate our tracker in a real-life scenario using a camera network deployed in a building.

Identification of the target areas to be resected in patients with non-bullous emphysema by using gas and perfusion SPECT images

International Nuclear Information System (INIS)

Sugi, Kazuro; Ueda, Kazuhiro; Fujita, Nobuhiro; Nawata, Kouichi; Kaneda, Yoshikazu; Nawata, Sumihiko; Esato, Kensuke

1997-01-01

Significant improvement of pulmonary function after the volume reduction surgery has been reported in patients with bullous emphysema. However, there has been no successful report in patients with non-bullous emphysema. The reason of failure in patients with non-bullous emphysema should lie mainly on the difficulty to identify the target areas to be resected. We describe how to identify the target areas in the patients with non-bullous emphysema by using gas and perfusion single-photon emission computed tomography (SPECT). Twelve patients with non-bullous emphysema were studied by 133 Xe gas and 99m Tc MAA SPECT, which revealed that abnormal retention and low perfusion areas were located in the apex of the upper lobe and the basal segment of the lower lobe. The resections were performed thoracoscopically focused on the target areas by hockey-stick shape resection in the upper lobe and spiral shape resection in the lower lobe without deformity formation of the residual lung. Slight but significant improvement in the pulmonary functions was observed after the surgery in patients with non-bullous emphysema. The Xe gas and Tc MAA SPECT were useful procedures to identify the target areas to be resected in patients with non-bullous emphysema. (author)

The LLNL [Lawrence Livermore National Laboratory] ICF [Inertial Confinement Fusion] Program: Progress toward ignition in the Laboratory

International Nuclear Information System (INIS)

Storm, E.; Batha, S.H.; Bernat, T.P.; Bibeau, C.; Cable, M.D.; Caird, J.A.; Campbell, E.M.; Campbell, J.H.; Coleman, L.W.; Cook, R.C.; Correll, D.L.; Darrow, C.B.; Davis, J.I.; Drake, R.P.; Ehrlich, R.B.; Ellis, R.J.; Glendinning, S.G.; Haan, S.W.; Haendler, B.L.; Hatcher, C.W.; Hatchett, S.P.; Hermes, G.L.; Hunt, J.P.; Kania, D.R.; Kauffman, R.L.; Kilkenny, J.D.; Kornblum, H.N.; Kruer, W.L.; Kyrazis, D.T.; Lane, S.M.; Laumann, C.W.; Lerche, R.A.; Letts, S.A.; Lindl, J.D.; Lowdermilk, W.H.; Mauger, G.J.; Montgomery, D.S.; Munro, D.H.; Murray, J.R.; Phillion, D.W.; Powell, H.T.; Remington, B.R.; Ress, D.B.; Speck, D.R.; Suter, L.J.; Tietbohl, G.L.; Thiessen, A.R.; Trebes, J.E.; Trenholme, J.B.; Turner, R.E.; Upadhye, R.S.; Wallace, R.J.; Wiedwald, J.D.; Woodworth, J.G.; Young, P.M.; Ze, F.

1990-01-01

The Inertial Confinement Fusion (ICF) Program at the Lawrence Livermore National Laboratory (LLNL) has made substantial progress in target physics, target diagnostics, and laser science and technology. In each area, progress required the development of experimental techniques and computational modeling. The objectives of the target physics experiments in the Nova laser facility are to address and understand critical physics issues that determine the conditions required to achieve ignition and gain in an ICF capsule. The LLNL experimental program primarily addresses indirect-drive implosions, in which the capsule is driven by x rays produced by the interaction of the laser light with a high-Z plasma. Experiments address both the physics of generating the radiation environment in a laser-driven hohlraum and the physics associated with imploding ICF capsules to ignition and high-gain conditions in the absence of alpha deposition. Recent experiments and modeling have established much of the physics necessary to validate the basic concept of ignition and ICF target gain in the laboratory. The rapid progress made in the past several years, and in particular, recent results showing higher radiation drive temperatures and implosion velocities than previously obtained and assumed for high-gain target designs, has led LLNL to propose an upgrade of the Nova laser to 1.5 to 2 MJ (at 0.35 μm) to demonstrate ignition and energy gains of 10 to 20 -- the Nova Upgrade

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

Science.gov (United States)

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

2017-05-01

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

Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels.

Science.gov (United States)

Wilkinson, Trevor C I

2016-06-15

The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Vertical displacement of the brain and the target area during open stereotaxic neurosurgery

International Nuclear Information System (INIS)

Wester, K.; Kraekenes, J.

2001-01-01

During stereotaxic thalamotomies, we observed that the brain surface was sinking. The study was carried out to investigate to what extent the target area also was displaced and how this would affect the accuracy of the stereotaxic procedure. In 12 thalamotomies, with the patients operated on in the sitting position, we found that the cortical surface sank 0-9 (mean 5) mm during the operation. The vertical co-ordinate of the thalamic target was consequently adjusted per-operatively, and the electrodes were advanced on additional distance of 1-5.5 (mean 3.5) mm in an attempt to compensate for the assumed sinking of the target. This per-operative adjustment was based on the surgeon's experience and the results of macro-stimulation studies. The exact location of the thalamotomy lesion, and thereby the accuracy of the adjustment, was evaluated on 3 months postoperative CT scans. These showed that the intended target was hit with a sufficient degree of accuracy in all the patients, although the vertical co-ordinate had been slightly over-adjusted, as the center of the lesion on the average was located 1 mm below the intended location. Thus, if the vertical position had not been adjusted, the lesion would on the average have been located 2.5 mm too high compared with the intended target. Patients undergoing thalamotomy and other stereotaxic procedures, where a high degree of accuracy is needed, should be operated on in the sitting position. At the thalamic level, the vertical displacement of the target should be adjusted for by additional advancement of the stereotaxic probe. On average, this compensatory adjustment should be about half the per-operative sinking of the cortical surface. (author)

The role of digital health in making progress toward Sustainable Development Goal (SDG) 3 in conflict-affected populations.

Science.gov (United States)

Asi, Yara M; Williams, Cynthia

2018-06-01

The progress of the Millennium Development Goals (MDGs) shows that sustained global action can achieve success. Despite the unprecedented achievements in health and education, more than one billion people, many of them in conflict-affected areas, were unable to reap the benefits of the MDG gains. The recently developed Sustainable Development Goals (SDGs) are even more ambitious then their predecessor. SDG 3 prioritizes health and well-being for all ages in specific areas such as maternal mortality, communicable diseases, mental health, and healthcare workforce. However, without a shift in the approach used for conflict-affected areas, the world's most vulnerable people risk being left behind in global development yet again. We must engage in meaningful discussions about employing innovative strategies to address health challenges fragile, low-resource, and often remote settings. In this paper, we will argue that to meet the ambitious health goals of SDG 3, digital health can help to bridge healthcare gaps in conflict-affected areas. First, we describe the health needs of populations in conflict-affected environments, and how they overlap with the SDG 3 targets. Secondly, we discuss how digital health can address the unique needs of conflict-affected areas. Finally, we evaluate the various challenges in deploying digital technologies in fragile environments, and discuss potential policy solutions. Persons in conflict-affected areas may benefit from the diffusive nature of digital health tools. Innovations using cellular technology or cloud-based solutions overcome physical barriers. Additionally, many of the targets of SDG 3 could see significant progress if efficacious education and outreach efforts were supported, and digital health in the form of mHealth and telehealth offers a relatively low-resource platform for these initiatives. Lastly, lack of data collection, especially in conflict-affected or otherwise fragile states, was one of the primary limitations of

Multiple Target Laser Designator (MTLD)

Science.gov (United States)

2007-03-01

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

Tight junctions: a barrier to the initiation and progression of breast cancer?

LENUS (Irish Health Repository)

Brennan, Kieran

2010-01-01

Breast cancer is a complex and heterogeneous disease that arises from epithelial cells lining the breast ducts and lobules. Correct adhesion between adjacent epithelial cells is important in determining the normal structure and function of epithelial tissues, and there is accumulating evidence that dysregulated cell-cell adhesion is associated with many cancers. This review will focus on one cell-cell adhesion complex, the tight junction (TJ), and summarize recent evidence that TJs may participate in breast cancer development or progression. We will first outline the protein composition of TJs and discuss the functions of the TJ complex. Secondly we will examine how alterations in these functions might facilitate breast cancer initiation or progression; by focussing on the regulatory influence of TJs on cell polarity, cell fate and cell migration. Finally we will outline how pharmacological targeting of TJ proteins may be useful in limiting breast cancer progression. Overall we hope to illustrate that the relationship between TJ alterations and breast cancer is a complex one; but that this area offers promise in uncovering fundamental mechanisms linked to breast cancer progression.

Androgen receptor activation: a prospective therapeutic target for bladder cancer?

Science.gov (United States)

Mizushima, Taichi; Tirador, Kathleen A; Miyamoto, Hiroshi

2017-03-01

Patients with non-muscle-invasive or muscle-invasive bladder cancer undergoing surgery and currently available conventional therapy remain having a high risk of tumor recurrence or progression, respectively. Novel targeted molecular therapy is therefore expected to improve patient outcomes. Meanwhile, substantially higher incidence of bladder cancer in men has prompted research on androgen-mediated androgen receptor (AR) signaling in this malignancy. Indeed, preclinical evidence has suggested that AR signaling plays an important role in urothelial carcinogenesis and tumor outgrowth as well as resistance to some of the currently available conventional non-surgical therapies. Areas covered: We summarize and discuss available data suggesting the involvement of AR and its potential downstream targets in the development and progression of bladder cancer. Associations between AR signaling and sensitivity to cisplatin/doxorubicin or bacillus Calmette-Guérin treatment are also reviewed. Expert opinion: AR activation is likely to correlate with the promotion of urothelial carcinogenesis and cancer outgrowth as well as resistance to conventional therapies. Molecular therapy targeting the AR may thus provide effective chemopreventive and therapeutic approaches for urothelial cancer. Accordingly, bladder cancer can now be considered as an endocrine-related neoplasm. Clinical application of various anti-AR therapies available for AR-dependent prostate cancer to bladder cancer patients is anticipated.

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

Science.gov (United States)

2016-08-19

Science, University ofMichigan, AnnArbor,MI 48109-2099, USA E-mail: czulick@umich.edu Keywords: laser- plasma ,mass-limited, fast electrons , sheath...New J. Phys. 18 (2016) 063020 doi:10.1088/1367-2630/18/6/063020 PAPER Target surface area effects on hot electron dynamics from high intensity laser... plasma interactions CZulick, ARaymond,AMcKelvey, VChvykov, AMaksimchuk, AGRThomas, LWillingale, VYanovsky andKKrushelnick Center forUltrafast Optical

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

Energy Technology Data Exchange (ETDEWEB)

Mark Krauss

2010-09-01

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

Advances in targeted delivery of small interfering RNA using simple bioconjugates

DEFF Research Database (Denmark)

Nielsen, Christoffer; Kjems, Jørgen; Sorensen, Kristine Rothaus

2014-01-01

with a targeting moiety, in a simple bioconjugate construct. We discuss the use of different types of targeting moieties, as well as the different conjugation strategies employed for preparing these bioconjugate constructs that deliver the siRNA to target cells. We focus especially on the in-built or passive......Introduction: Development of drugs based on RNA interference by small interfering RNA (siRNA) has been progressing slowly due to a number of challenges associated with the in vivo behavior of siRNA. A central problem is controlling siRNA delivery to specific cell types. Here, we review existing...... literature on one type of strategy for solving the issue of cell-specific delivery of siRNA, namely delivering the siRNA as part of simple bioconjugate constructs. Areas covered: This review presents current experience from strategies aimed at targeting siRNA to specific cell types, by associating the siRNA...

Tumor Progression Locus 2 (Tpl2 Kinase as a Novel Therapeutic Target for Cancer: Double-Sided Effects of Tpl2 on Cancer

Directory of Open Access Journals (Sweden)

Hye Won Lee

2015-02-01

Full Text Available Tumor progression locus 2 (Tpl2 is a mitogen-activated protein kinase (MAPK kinase kinase (MAP3K that conveys various intra- and extra-cellular stimuli to effector proteins of cells provoking adequate adoptive responses. Recent studies have elucidated that Tpl2 is an indispensable signal transducer as an MAP3K family member in diverse signaling pathways that regulate cell proliferation, survival, and death. Since tumorigenesis results from dysregulation of cellular proliferation, differentiation, and apoptosis, Tpl2 participates in many decisive molecular processes of tumor development and progression. Moreover, Tpl2 is closely associated with cytokine release of inflammatory cells, which has crucial effects on not only tumor cells but also tumor microenvironments. These critical roles of Tpl2 in human cancers make it an attractive anti-cancer therapeutic target. However, Tpl2 contradictorily works as a tumor suppressor in some cancers. The double-sided effects of Tpl2 originate from the specific upstream and downstream signaling environment of each tumor, since Tpl2 interacts with various signaling components. This review summarizes recent studies concerning the possible roles of Tpl2 in human cancers and considers its possibility as a therapeutic target, against which novel anti-cancer agents could be developed.

Nitrate | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Sunburn | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Larval abundances of rockfishes that were historically targeted by fishing increased over 16 years in association with a large marine protected area.

Science.gov (United States)

Thompson, Andrew R; Chen, Dustin C; Guo, Lian W; Hyde, John R; Watson, William

2017-09-01

Marine protected areas (MPAs) can facilitate recovery of diminished stocks by protecting reproductive adults. To effectively augment fisheries, however, reproductive output must increase within the bounds of MPAs so that larvae can be exported to surrounding areas and seed the region. In response to dramatic declines of rockfishes ( Sebastes spp.) in southern California by the late 1990s two large MPAs, the Cowcod Conservation Areas (CCAs), were established in 2001. To evaluate whether the CCAs affected rockfish productivity we evaluated the dynamics of 8 species that were, and 7 that were not, historically targeted by fishing. Abundances of 6/8 targeted and 4/7 non-targeted species increased regionally from 1998 to 2013. These upturns were probably affected by environmental conditions in addition to changes in fishing pressure as the presence of most species correlated negatively with temperature, and temperature was lower than the historic average in 11/15 years. Seventy-five per cent of the targeted, but none of the non-targeted species increased at a greater rate inside than outside the CCAs while controlling for environmental factors. Results indicate that management actions, coupled with favourable environmental conditions, facilitated the resurgence of multiple rockfish species that were targeted by intense fishing effort for decades.

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

Science.gov (United States)

Mavridis, Ioannis N

2017-12-11

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

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

Directory of Open Access Journals (Sweden)

Ioannis N. Mavridis

2017-12-01

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

Federal Facility Agreement progress report

Energy Technology Data Exchange (ETDEWEB)

1993-10-01

The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas.

Federal Facility Agreement progress report

International Nuclear Information System (INIS)

1993-10-01

The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas

Target diagnostic system for the National Ignition Facility (NIF)

International Nuclear Information System (INIS)

Leeper, R.J.; Chandler, G.A.; Cooper, G.W.; Derzon, M.S.

1996-01-01

A review of recent progress on the design of a diagnostic system proposed for ignition target experiments on the National Ignition Facility (NIF) will be presented. This diagnostic package contains an extensive suite of optical, x-ray, gamma-ray, and neutron diagnostics that enable measurements of the performance of both direct and indirect driven NIF targets. The philosophy used in designing all of the diagnostics in the set has emphasized redundant and independent measurement of fundamental physical quantities relevant to the operation of the NIF target. A unique feature of these diagnostics is that they are being designed to be capable of operating, in the high radiation, EMP, and debris backgrounds expected on the NIF facility. The diagnostic system proposed can be categorized into three broad areas: laser characterization, hohlraum characterization, and capsule performance diagnostics. The operating principles of a representative instrument from each class of diagnostic employed in this package will be summarized and illustrated with data obtained in recent prototype diagnostic tests

Changes in muscle cross-sectional area, muscle force, and jump performance during 6 weeks of progressive whole-body vibration combined with progressive, high intensity resistance training

Science.gov (United States)

Rosenberger, A.; Beijer, Å.; Johannes, B.; Schoenau, E.; Mester, J.; Rittweger, J.; Zange, J.

2017-01-01

Objectives: We hypothesized that progressive whole-body vibration (WBV) superimposed to progressive high intensity resistance training has greater effects on muscle cross-sectional area (CSA), muscle force of leg muscles, and jump performance than progressive high intensity resistance training alone. Methods: Two groups of healthy male subjects performed either 6 weeks of Resistive Vibration Exercise (RVE, squats and heel raises with WBV, n=13) or Resistive Exercise (RE, squats and heel raises without WBV, n=13). Squats under RVE required indispensable weight loading on the forefoot to damp harmful vibrations to the head. Time, intervention, and interaction effects were analyzed. Results: After 6 weeks of training, knee extensor CSA, isometric knee extension force, and counter movement jump height increased equally in both groups (time effect, P<0.001, P≤0.02, and P≤0.03, respectively), whereas only in RVE ankle plantar flexor CSA and isometric ankle plantar flexion force reached significance or a tendency, respectively, (time effect, P=0.015 and P=0.069, respectively; intervention effect also for the latter, P=0.006). Drop jump contact time did significantly more improve in RVE (interaction effect, P=0.042). Conclusions: RVE showed better training effects than RE only in plantar flexor muscles. RVE seems to be suitable in professional sports with a special focus on calf muscles. PMID:28574410

Tracking progress toward global polio eradication, 2010-2011.

Science.gov (United States)

2012-04-20

In January 2012, polio eradication was declared a "programmatic emergency for global public health" by the Executive Board of the World Health Organization (WHO). Since the Global Polio Eradication Initiative (GPEI) began in 1988, progress has been tracked by surveillance of acute flaccid paralysis (AFP) cases and testing of linked stool specimens for polioviruses (PVs) in WHO-accredited Global Polio Laboratory Network (GPLN) laboratories, complemented by sewage testing (environmental surveillance) in selected areas. Monitoring AFP surveillance quality at national and subnational administrative levels using standard performance indicators identifies potential gaps where PV circulation might go undetected; monitoring specimen transport and laboratory reporting timeliness identifies areas where reporting delays could lead to late response, permitting ongoing transmission. This report provides an assessment of 2010-2011 performance indicators for AFP surveillance at national and subnational levels in polio-affected countries and laboratory reporting at the regional level, updated from 2009-2010. Overall, 16 (62%) of 26 countries with circulating wild PV (WPV) met national AFP surveillance indicator targets during both 2010 and 2011. All three countries with reestablished WPV transmission and 16 of 19 countries with WPV outbreaks had substantial proportions (>20%) of their respective populations living in areas with underperforming surveillance during 2010 or 2011. Targets for timely reporting of PV isolation and type characterization results were met in three of six WHO regions in 2010 and five regions in 2011. To achieve polio eradication, efforts are needed to improve AFP surveillance and laboratory performance.

Polarized few-nucleon targets: new developments

International Nuclear Information System (INIS)

Haeusser, O.

1992-09-01

We discuss recent improvements in producing polarized few-nucleon targets for nuclear and particle physics experiments. The emphasis is on progress with polarized gas targets intended for experiments at electron and proton storage rings. (author) 54 refs., 1 tab

Polarized few-nucleon targets: new developments

Energy Technology Data Exchange (ETDEWEB)

Haeusser, O

1992-09-01

We discuss recent improvements in producing polarized few-nucleon targets for nuclear and particle physics experiments. The emphasis is on progress with polarized gas targets intended for experiments at electron and proton storage rings. (author) 54 refs., 1 tab.

Implication of the displacement of the T1 primary target in the west area at the CERN SPS

CERN Document Server

Gatignon, L

1999-01-01

As soon as the transfer line T12 for proton injection into the LHC must be installed, the T1 primary target has to be at least partly dismantled, as its shielding would block the passage of the beam. Even though the installation of T12 is only foreseen for later, in view of sharing of workload related to the SLI project, it is preferred to move the primary production target T1 for the West Area to its new position already in the shutdown 1999/2000. The new position of the target requires major modifications of support structures in TCC6, of the transfer line towards T1 and of a more than 500 metres long section of the H3 secondary beam in the West Area, all to be completed in the 1999/2000 shutdown. To allow the work to be finished in time, part of it (including some civil engineering in TT4) is already done in the 1998/99 shutdown. In this memo the necessary modifications are described, cost estimates are given and a planning is provided.

The U.S. RERTR program status and progress

International Nuclear Information System (INIS)

Travelli, A.

1998-01-01

The progress of the Reduced Enrichment Research and Test Reactor (RERTR) Program since its inception in 1978 is described. A brief summary of the results which the RERTR Program had achieved by the end of 1996 in collaboration with its many international partners is followed by a detailed review of the major events, findings, and activities of 1997. Significant progress has been made during the past year. In the area of U.S. acceptance of spent fuel from foreign research reactors, several shipments have taken place and additional are being planned. Intense fuel development activities are in progress, including procurement of equipment, screening of candidate materials, and production of microplates. Irradiation of the first series of microplates began in August 1997 in the Advanced Test Reactor, in Idaho. Progress has been made in the Russian RERTR program, which aims to develop and demonstrate within five years the technical means needed to convert Russian-supplied research reactors to LEU fuels. The study of an alternative LEU core for the FRM-II design has been extended to address, with favorable results, controversial performance issues which were raised at last year's meeting. Progress was also made on several aspects of producing molybdenum-99 from fission targets utilizing LEU instead of HEU. Various types of targets and processes are being pursued, with FDA approval of an LEU process projected to occur within two years. The feasibility of LEU Fuel conversion for three important DOE research reactors (BMRR, HFBR, and HFIR) has been evaluated by the RERTR program. In spite of the many momentous events which have occurred during the intervening years, and the excellent progress achieved, the most important challenges that the RERTR program faces today are not very different in type from those that were faced during the first RERTR meeting. Now, as then, the most important task is to develop new LEU fuels satisfying requirements which cannot be satisfied by any

The U.S. RERTR Program. Status and progress

International Nuclear Information System (INIS)

Travelli, A.

1997-01-01

The progress of the Reduced Enrichment Research and Test Reactor (RERTR) Program since its inception in 1978 is described. A brief summary of the results which the RERTR Program had achieved by the end of 1996 in collaboration with its many international partners is followed by a detailed review of the major events, findings, and activities of 1997. Significant progress has been made during the past year. In the area of U.S. acceptance of spent fuel from foreign research reactors, several shipments have taken place and additional are being planned. Intense fuel development activities are in progress, including procurement of equipment, screening of candidate materials, and production of microplates. Irradiation of the first series of microplates began in August 1997 in the Advanced Test Reactor, in Idaho. Progress has been made in the Russian RERTR program, which aims to develop and demonstrate within five years the technical means needed to convert Russian-supplied research reactors to LEU fuels. The study of an alternative LEU core for the FRM-II design has been extended to address, with favorable results, controversial performance issues which were raised at last year's meeting. Progress was also made on several aspects of producing molybdenum-99 from fission targets utilizing LEU instead of HEU. Various types of targets and processes are being pursued, with FDA approval of an LEU process projected to occur within two years. The feasibility of LEU fuel conversion for three important DOE research reactors (BMRR, HFBR, and HFIR) has been evaluated by the RERTR program. In spite of the many momentous events which have occurred during the intervening years, and the excellent progress achieved, the most important challenges that the RERTR program faces today are not very different in type from those that were faced during the first RERTR meeting. Now, as then, the most important task is to develop new LEU fuels satisfying requirements which cannot be satisfied by any

Evaluation of the geologic relations and seismotectonic stability of the Yucca Mountain Area Nevada Nuclear Waste Site Investigations (NNWSI). Progress report, October 1, 1991--September 30, 1992

Energy Technology Data Exchange (ETDEWEB)

NONE

1992-09-30

This report dated 30 September 1992 provides a summary of progress for the project {open_quotes}Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI){close_quotes}. This progress report was preceded by the progress report for the year from 1 October 1990 to 30 September 1991. This report summarizes the geologic and seismotectonic studies conducted at Yucca Mountain during the contract period including Quaternary tectonics, an evaluation of mineral resource potential of the area, caldera geology, and volcano-tectonic activity at and near the site. A report of basinal studies conducted during the contract period is also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

Progress In Magnetized Target Fusion Driven by Plasma Liners

Science.gov (United States)

Thio, Francis Y. C.; Kirkpatrick, Ronald C.; Knapp, Charles E.; Cassibry, Jason; Eskridge, Richard; Lee, Michael; Smith, James; Martin, Adam; Wu, S. T.; Schmidt, George;

The neural basis of monitoring goal progress

Directory of Open Access Journals (Sweden)

Yael eBenn

2014-09-01

Full Text Available The neural basis of progress monitoring has received relatively little attention compared to other sub-processes that are involved in goal directed behavior such as motor control and response inhibition. Studies of error-monitoring have identified the dorsal anterior cingulate cortex (dACC as a structure that is sensitive to conflict detection, and triggers corrective action. However, monitoring goal progress involves monitoring correct as well as erroneous events over a period of time. In the present research, 20 healthy participants underwent fMRI while playing a game that involved monitoring progress towards either a numerical or a visuo-spatial target. The findings confirmed the role of the dACC in detecting situations in which the current state may conflict with the desired state, but also revealed activations in the frontal and parietal regions, pointing to the involvement of processes such as attention and working memory in monitoring progress over time. In addition, activation of the cuneus was associated with monitoring progress towards a specific target presented in the visual modality. This is the first time that activation in this region has been linked to higher-order processing of goal-relevant information, rather than low-level anticipation of visual stimuli. Taken together, these findings identify the neural substrates involved in monitoring progress over time, and how these extend beyond activations observed in conflict and error monitoring.

[50 years of hepatology - from therapeutic nihilism to targeted therapies].

Science.gov (United States)

Manns, Michael P

2013-04-01

Over the past 50 years significant progress has been made in the whole field of hepatology. Part of this is translation of basic research (biochemistry, immunology, virology, molecular biology and others) into clinical hepatology. This enabled us to understand more about the pathogenesis of liver diseases and led to the discovery of the five major hepatotropic viruses, the identification of hepatocellular autoantigens, and to the development of specific therapies for chronic hepatitis B, C and D. In addition, the molecular basis of most genetic liver diseases has been identified. Significant progress was made in the development of medical therapies for various liver diseases with different underlying etiologies. Surgery significantly contributed to the progress in the management of liver diseases; examples are laparoscopic cholecystectomy and the development of liver transplantation. A multimodal therapeutic algorithm has been established for the therapy of hepatocelluar carcinoma (HCC); with Sorafenib "targeted therapy" has entered the area of HCC. The progress made over the last 50 years not only led to an aetiological differentiation of acute and chronic liver diseases but also to specific therapies based on the identification and understanding of the underlying etiology. © Georg Thieme Verlag KG Stuttgart · New York.

Estimasi kebutuhan spektrum untuk memenuhi target rencana pita lebar Indonesia di wilayah perkotaan [The estimation of spectrum requirements to meet the target of Indonesia broadband plan in urban area

Directory of Open Access Journals (Sweden)

Kasmad Ariansyah

2015-12-01

Full Text Available Pemerintah Indonesia telah mengesahkan Rencana Pita Lebar Indonesia menjelang akhir tahun 2014. Dokumen tersebut berisi panduan dan arah pembangunan pita lebar nasional dan berisi berisi target-target pencapaian berkelanjutan antara tahun 2014-2019. Terkait target capaian pita lebar nirkabel, ketersediaan dan kecukupan spektrum frekuensi merupakan salah satu hal yang sangat penting.  Studi ini dilakukan untuk mengestimasi kebutuhan spektrum frekuensi dalam rangka memenuhi target capaian Rencana Pita Lebar Indonesia khususnya layanan pita lebar nirkabel di wilayah perkotaan. DKI Jakarta dipilih sebagai sampel wilayah perkotaan. Analisis dilakukan dengan menghitung luas cakupan BTS, mengestimasi jumlah potensi pengguna, mengestimasi kebutuhan spektrum dan membandingkannya dengan spektrum yang sudah dialokasikan untuk mendapatkan jumlah kekurangan spektrum. 3G dan 4G diasumsikan sebagai teknologi yang digunakan untuk memenuhi sasaran pita lebar bergerak. Hasil analisis menunjukkan pada rentang tahun 2016-2019 akan terjadi kekurangan spektrum di wilayah perkotaan sebesar 2x234,5 MHz sampai dengan 2x240,5MHz (untuk mode FDD atau sebesar 313 MHz sampai dengan 321 MHz (untuk mode TDD. Spektrum frekuensi merupakan sumber daya yang reusable, dengan mengasumsikan kebutuhan spektrum di perdesaan lebih rendah dibanding kebutuhan di perkotaan, maka estimasi ini dapat pula digunakan untuk menggambarkan kebutuhan spektrum di Indonesia secara keseluruhan.*****Indonesian government has issued Indonesia Broadband Plan (IBP at the end of 2014. IBP provides guidance and direction for the development of national broadband and contains targets in the period of 2014 to 2019. Relating to wireless broadband target, the availability and the adequacy of spectrum is very important. This study was conducted to estimate the spectrum requirements to meet the Indonesia broadband plan target especially the target of mobile broadband in urban area. DKI Jakarta was taken as

Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

Science.gov (United States)

Zhai, Shiyan; Song, Genxin; Qin, Yaochen; Ye, Xinyue; Lee, Jay

2017-01-01

This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.

Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

Directory of Open Access Journals (Sweden)

Shiyan Zhai

Full Text Available This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.

Scales of Progress

Science.gov (United States)

Jung, Lee Ann

2018-01-01

What is Goal Attainment Scaling? In this article, Lee Ann Jung defines it as a way to measure a student's progress toward an individualized goal. Instead of measuring a skill at a set time (for instance, on a test or other assignment), Goal Attainment Scaling tracks the steps a student takes over the course of a year in a targeted skill. Together,…

Progressive universalism? The impact of targeted coverage on health care access and expenditures in Peru.

Science.gov (United States)

Neelsen, Sven; O'Donnell, Owen

2017-12-01

Like other countries seeking a progressive path to universalism, Peru has attempted to reduce inequalities in access to health care by granting the poor entitlement to tax-financed basic care without charge. We identify the impact of this policy by comparing the target population's change in health care utilization with that of poor adults already covered through employment-based insurance. There are positive effects on receipt of ambulatory care and medication that are largest among the elderly and the poorest. The probability of getting formal health care when sick is increased by almost two fifths, but the likelihood of being unable to afford treatment is reduced by more than a quarter. Consistent with the shallow coverage offered, there is no impact on use of inpatient care. Neither is there any effect on average out-of-pocket health care expenditure, but medical spending is reduced by up to 25% in the top quarter of the distribution. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Progress on large area GEMs (VCI 2010)

CERN Document Server

Villa, Marco; Alfonsi, Matteo; Brock, Ian; Croci, Gabriele; David, Eric; de Oliveira, Rui; Ropelewski, Leszek; Taureg, Hans; van Stenis, Miranda

2011-01-01

The Gas Electron Multiplier (GEM) manufacturing technique has recently evolved to allow the production of large area GEMs. A novel approach based on single mask photolithography eliminates the mask alignment issue, which limits the dimensions in the traditional double mask process. Moreover, a splicing technique overcomes the limited width of the raw material. Stretching and handling issues in large area GEMs have also been addressed. Using the new improvements it was possible to build a prototype triple-GEM detector of ~ 2000 cm2 active area, aimed at an application for the TOTEM T1 upgrade. Further refinements of the single mask technique give great control over the shape of the GEM holes and the size of the rims, which can be tuned as needed. In this framework, simulation studies can help to understand the GEM behavior depending on the hole shape.

NCI Dictionary | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Custom Report | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Fat Consumption | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Alcohol Consumption | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

Science.gov (United States)

Hill, Rebecca M; Kuijper, Sanne; Lindsey, Janet C; Petrie, Kevin; Schwalbe, Ed C; Barker, Karen; Boult, Jessica K R; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L; Poon, Evon; Robinson, Simon P; Ruddle, Ruth; Raynaud, Florence I; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W; Wharton, Stephen B; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J; Weiss, William A; Chesler, Louis; Clifford, Steven C

2015-01-12

We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Progressive Abduction Loading Therapy with Horizontal-Plane Viscous Resistance Targeting Weakness and Flexion Synergy to Treat Upper Limb Function in Chronic Hemiparetic Stroke: A Randomized Clinical Trial.

Science.gov (United States)

Ellis, Michael D; Carmona, Carolina; Drogos, Justin; Dewald, Julius P A

2018-01-01

Progressive abduction loading therapy has emerged as a promising exercise therapy in stroke rehabilitation to systematically target the loss of independent joint control (flexion synergy) in individuals with chronic moderate/severe upper-extremity impairment. Preclinical investigations have identified abduction loading during reaching exercise as a key therapeutic factor to improve reaching function. An augmentative approach may be to additionally target weakness by incorporating resistance training to increase constitutive joint torques of reaching with the goal of improving reaching function by "overpowering" flexion synergy. The objective was, therefore, to determine the therapeutic effects of horizontal-plane viscous resistance in combination with progressive abduction loading therapy. 32 individuals with chronic hemiparetic stroke were randomly allocated to two groups. The two groups had equivalent baseline characteristics on all demographic and outcome metrics including age (59 ± 11 years), time poststroke (10.1 ± 7.6 years), and motor impairment (Fugl-Meyer, 26.7 ± 6.5 out of 66). Both groups received therapy three times/week for 8 weeks while the experimental group included additional horizontal-plane viscous resistance. Quantitative standardized progression of the intervention was achieved using a robotic device. The primary outcomes of reaching distance and velocity under maximum abduction loading and secondary outcomes of isometric strength and a clinical battery were measured at pre-, post-, and 3 months following therapy. There was no difference between groups on any outcome measure. However, for combined groups, there was a significant increase in reaching distance (13.2%, effect size; d  = 0.56) and velocity (13.6%, effect size; d  = 0.27) at posttesting that persisted for 3 months and also a significant increase in abduction, elbow extension, and external rotation strength at posttesting that did not persist 3�

Progress report 1982

International Nuclear Information System (INIS)

Paul, H.

1983-01-01

This progress report describes the scientific work and research results done by the institute for experimental physics, atom and nuclear physics of the Johannes-Kepler-Universitaet Linz in the period of 1982. The covered subject areas are ionization by cations, investigations of surface areas by light ions, measurement of stopping power in solids, data acquisition and aerosol physics. (A.N.)

TARGET Research Goals

Science.gov (United States)

TARGET researchers use various sequencing and array-based methods to examine the genomes, transcriptomes, and for some diseases epigenomes of select childhood cancers. This “multi-omic” approach generates a comprehensive profile of molecular alterations for each cancer type. Alterations are changes in DNA or RNA, such as rearrangements in chromosome structure or variations in gene expression, respectively. Through computational analyses and assays to validate biological function, TARGET researchers predict which alterations disrupt the function of a gene or pathway and promote cancer growth, progression, and/or survival. Researchers identify candidate therapeutic targets and/or prognostic markers from the cancer-associated alterations.

Quantification of plaque area and characterization of plaque biochemical composition with atherosclerosis progression in ApoE/LDLR(-/-) mice by FT-IR imaging.

Science.gov (United States)

Wrobel, Tomasz P; Mateuszuk, Lukasz; Kostogrys, Renata B; Chlopicki, Stefan; Baranska, Malgorzata

2013-11-07

In this work the quantitative determination of atherosclerotic lesion area (ApoE/LDLR(-/-) mice) by FT-IR imaging is presented and validated by comparison with atherosclerotic lesion area determination by classic Oil Red O staining. Cluster analysis of FT-IR-based measurements in the 2800-3025 cm(-1) range allowed for quantitative analysis of the atherosclerosis plaque area, the results of which were highly correlated with those of Oil Red O histological staining (R(2) = 0.935). Moreover, a specific class obtained from a second cluster analysis of the aortic cross-section samples at different stages of disease progression (3, 4 and 6 months old) seemed to represent the macrophages (CD68) area within the atherosclerotic plaque.

MicroRNA-202 inhibits tumor progression by targeting LAMA1 in esophageal squamous cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Meng, Xiangrui, E-mail: xiangruimengzz@163.com [Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou 450000, Henan Province (China); Chen, Xiaoqi [Department of Digestion and Oncology, The First Affiliated Hospital of Henan Uninversity of TCM, 19 Renmin Road, Zhengzhou 450000, Henan Province (China); Lu, Peng [Department of Gastrointestinal Surgery, The People' s Hospital of Zhengzhou, 33 Huanghe Road, Zhengzhou 450000, Henan Province (China); Ma, Wang; Yue, Dongli; Song, Lijie; Fan, Qingxia [Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou 450000, Henan Province (China)

2016-05-13

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies in the gastrointestinal tract. Emerging studies have indicated that microRNAs (miRNAs) are strongly implicated in the development and progression of ESCC. Here, we focused on the function and the underlying molecular mechanism of miR-202 in ESCC. The results showed that miR-202 was significantly down-regulated in ESCC tissues and cell lines. Overexpression of miR-202 in ECa-109 and KYSE-510 cells markedly suppressed cell proliferation and cell migration, and induced cell apoptosis. Furthermore, laminin α1 (LAMA1) expression was frequently positive in ESCC tissues and inversely correlated with miR-202 expression. Then we demonstrated that miR-202 targeted 3'-untranslated region (UTR) of LAMA1 and inhibited its protein expression. Additionally, LAMA1 overexpression rescued the proliferation inhibition and cell apoptosis elevation induced by miR-202. MiR-202 also inhibited the protein expression of p-FAK and p-Akt, which were all reversed by LAMA1 overexpression. Taken together, these findings suggest that miR-202 may function as a novel tumor suppressor in ESCC by repressing cell proliferation and migration, and its biological effects may attribute the inhibition of LAMA1-mediated FAK-PI3K-Akt signaling. - Highlights: • Expression of miR-202 was decreased in ESCC tissues and cell lines. • MiR-202 overexpression inhibited ESCC cell growth and induced apoptosis. • MiR-202 directly targeted LAMA1 in ESCC. • The LAMA1-FAK-PI3K signaling mediated the suppressive role of miR-202.

Investigation on fabrication and positioning of cryogenic shell laser fusion targets. Annual report, October 1, 1977--November 30, 1978

International Nuclear Information System (INIS)

Kim, K.

1978-01-01

The research has been directed toward fabrication and positioning of cryogenic shell laser fusion targets, with particular emphasis on the development of a scheme which would allow for continuous fabrication, inspection, and delivery of the targets. Specifically, progress has been made in each of the following areas: (1) fabrication of a uniform layer of solid DT inside a glass microshell using a combination of helium gas jets and a heater wire; (2) levitation-freezing of a DT-filled glass microshell as a method for fabricating and positioning a cryogenic shell target; (3) a target fabrication system intended for continuous fabrication, inspection, and delivery of cryogenic targets; and (4) development of diagnostics for inspection, recording, and analysis of a solid DT layer inside a glass microshell, and for observing the parameters controlling the target freezing process

Progress and prospects for indirect drive ICF

International Nuclear Information System (INIS)

Lindl, J.D.

1992-08-01

During the past few years, a great deal of progress has been made toward demonstrating the requirements for ignition and high gain ICF targets. Because of this progress, the 1990 National Academy of Science (NAS) and Fusion Policy Advisory Committee (FPAC) reviews recommended that the US National ICF Program focus on the physics of ignition. Subject to successful completion of a series of experiments to be carried out on the Nova laser at Lawrence Livermore National Laboratory (LLNL), these reviews advocated construction of a 1 to 2 MJ glass laser, whose purpose would be demonstration of ignition and modest-gain ICF targets within about a decade. The LLNL proposal for this National Ignition Facility, which was endorsed by the NAS and FPAC as the most timely and cost effective path to this goal, is referred to as the ''Nova Upgrade.'' This paper reviews recent progress on the Nova laser and the performance expected with the Nova Upgrade

Progress report 1981

International Nuclear Information System (INIS)

Chalupka, A.; Dirninger, G.

1982-01-01

The progress report describes the scientific work and research results of the institute for radium research and nuclear physics of the Austrian Academy of Sciences for the period of 1981. The progress report covers the subject areas of nuclear theory, nuclear model calculations, experimental nuclear physics and neutron involved reactions, medium energy physics, instrumentation and detectors, evaluation of nuclear data and numerical data processing, dating, applications in medicine, dosimetry and environmental studies. A list of publications of this institute is given. (A.N.)

Progress report 1982

International Nuclear Information System (INIS)

Chalupka, A.; Wild, E.; Dirninger, G.

1983-01-01

The progress report describes the scientific work and research results of the institute for radium research and nuclear physics of the Austrian Academy of Sciences for the period of 1982. The progress report covers the subject areas of nuclear theory, nuclear model calculations, experimental nuclear physics and neutron involved reactions, medium energy physics, instrumentation and detectors, evaluation of nuclear data and numerical data processing, dating, applications in medicine, dosimetry and environmental studies. A list of publications of this institute is given. (A.N.)

Progress on the WOM (Wavelength-shifting optical module) development for IceCube

Energy Technology Data Exchange (ETDEWEB)

Hebecker, Dustin [DESY Zeuthen (Germany)

2015-07-01

For ongoing studies for the extension of the IceCube neutrino observatory to low energies (PINGU) and high energies the noise rate of the optical modules should be decreased and the effective area increased in order to improve energy resolution and overall sensitivity. The WOM (Wavelength-shifting optical module) targets this points by expanding the capture area while decreasing the size of the PMT and thus decreasing the noise rate. Photons are first captured in an organic wavelength-shifting material (WLS) that is coated on light guiding material to guide the light to two smaller PMTs. This allows to achieve a very large collection area and reduces the noise to the order of 10 Hz in comparison to 600-800 Hz (IceCube DOM). The progress on the necessary WLS paint development and substrate selection will be presented. Also a brief status / outlook on the prototype assembly will be given.

Continuing progress on a lattice QCD software infrastructure

International Nuclear Information System (INIS)

Joo, B

2008-01-01

We report on the progress of the software effort in the QCD application area of SciDAC. In particular, we discuss how the software developed under SciDAC enabled the aggressive exploitation of leadership computers, and we report on progress in the area of QCD software for multi-core architectures

Evaluation of pressure drop across area changes during blowdown. Quarterly progress report for period ending June 30, 1976

International Nuclear Information System (INIS)

Weisman, J.

1976-11-01

Transient pressure drops across abrupt area changes are being determined in a series of blowdown experiments. These tests are being conducted with Freon 113 as the test fluid in a well instrumented apparatus. During this period, test runs were obtained with the first abrupt expansion test section. Test data from two typical runs are included in this report. Additional progress was made in developing the computer programs which were to be used in analyzing this data but funding of this analytical effort has been suspended

Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma.

Science.gov (United States)

Pritchard, Eleanor M; Dyer, Michael A; Guy, R Kiplin

2016-01-01

While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors.

Static nuclear polarisation and polarised targets

International Nuclear Information System (INIS)

Heeringa, W.

1984-12-01

Recent progress and status of statically polarised nuclear targets are reviewed. Special attention is given to polarised 1 H and 3 He. An important quantity in the determination of the target polarisation is the thermal gradient over the target sample. The dependence of this gradient on heat input, sample geometry, and thermal conductivity of the sample is discussed. Possibilities of performing experiments with proton beams are indicated. (orig.) [de

Tertiary particle production and target optimization of the H2 beam line in the SPS North Area

CERN Document Server

AUTHOR|(CDS)2079540; Tellander, Felix; CERN. Geneva. ATS Department

2016-01-01

In this note, the tertiary particle yield from secondary targets of different materials placed at the ‘filter’ position of the H2 beam line of SPS North Area are presented. The production is studied for secondary beams of different momenta in the range of 50-250 GeV/c. More specifically, we studied six different targets: two copper cylinders with a radius of 40 mm and lengths of 100 and 300 mm, one solid tungsten cylinder with a radius of 40 mm and a length of 150 mm and three polyethylene cylinders with radius of 40 mm and lengths of 550, 700 and 1000 mm. Eight different momenta of the secondary beam (50, 60, 70, 100, 120, 150, 200 and 250 GeV/c) as well as two different physics lists (QGSP_BIC and FTFP_BERT) have been extensively studied. The purpose of this study is (a) to optimize (using the appropriate filter target) the particle production from the secondary targets as demanded by the experiments (b) investigate the proton production (with respect to the pion production) in the produced tertiary bea...

Truck-mounted Area-wide Application of Pyriproxyfen Targeting Aedes aegypti and Aedes albopictus in Northeast Florida

Science.gov (United States)

2014-12-01

TRUCK-MOUNTED AREA-WIDE APPLICATION OF PYRIPROXYFEN TARGETING AEDES AEGYPTI AND AEDES ALBOPICTUS IN NORTHEAST FLORIDA1 CARL W. DOUD,2,3 ANTHONY M...truck-mounted ultra-low volume applications of pyriproxyfen against Aedes aegypti larvae in artificial water containers and wild adult Ae. albopictus...larval control, Aedes aegypti, Aedes albopictus INTRODUCTION Aedes albopictus (Skuse) (Asian tiger mosquito) and Ae. aegypti (L.) (yellow fever

HIV/AIDS National Strategic Plans of Sub-Saharan African countries: an analysis for gender equality and sex-disaggregated HIV targets.

Science.gov (United States)

Sherwood, Jennifer; Sharp, Alana; Cooper, Bergen; Roose-Snyder, Beirne; Blumenthal, Susan

2017-12-01

National Strategic Plans (NSPs) for HIV/AIDS are country planning documents that set priorities for programmes and services, including a set of targets to quantify progress toward national and international goals. The inclusion of sex-disaggregated targets and targets to combat gender inequality is important given the high disease burden among young women and adolescent girls in Sub-Saharan Africa, yet no comprehensive gender-focused analysis of NSP targets has been performed. This analysis quantitatively evaluates national HIV targets, included in NSPs from eighteen Sub-Saharan African countries, for sex-disaggregation. Additionally, NSP targets aimed at reducing gender-based inequality in health outcomes are compiled and inductively coded to report common themes. On average, in the eighteen countries included in this analysis, 31% of NSP targets include sex-disaggregation (range 0-92%). Three countries disaggregated a majority (>50%) of their targets by sex. Sex-disaggregation in data reporting was more common for targets related to the early phases of the HIV care continuum: 83% of countries included any sex-disaggregated targets for HIV prevention, 56% for testing and linkage to care, 22% for improving antiretroviral treatment coverage, and 11% for retention in treatment. The most common target to reduce gender inequality was to prevent gender-based violence (present in 50% of countries). Other commonly incorporated target areas related to improving women's access to family planning, human and legal rights, and decision-making power. The inclusion of sex-disaggregated targets in national planning is vital to ensure that programmes make progress for all population groups. Improving the availability and quality of indicators to measure gender inequality, as well as evaluating programme outcomes by sex, is critical to tracking this progress. This analysis reveals an urgent need to set specific and separate targets for men and women in order to achieve an equitable

HIV/AIDS National Strategic Plans of Sub-Saharan African countries: an analysis for gender equality and sex-disaggregated HIV targets

Science.gov (United States)

Sherwood, Jennifer; Sharp, Alana; Cooper, Bergen; Roose-Snyder, Beirne; Blumenthal, Susan

2017-01-01

Abstract National Strategic Plans (NSPs) for HIV/AIDS are country planning documents that set priorities for programmes and services, including a set of targets to quantify progress toward national and international goals. The inclusion of sex-disaggregated targets and targets to combat gender inequality is important given the high disease burden among young women and adolescent girls in Sub-Saharan Africa, yet no comprehensive gender-focused analysis of NSP targets has been performed. This analysis quantitatively evaluates national HIV targets, included in NSPs from eighteen Sub-Saharan African countries, for sex-disaggregation. Additionally, NSP targets aimed at reducing gender-based inequality in health outcomes are compiled and inductively coded to report common themes. On average, in the eighteen countries included in this analysis, 31% of NSP targets include sex-disaggregation (range 0–92%). Three countries disaggregated a majority (>50%) of their targets by sex. Sex-disaggregation in data reporting was more common for targets related to the early phases of the HIV care continuum: 83% of countries included any sex-disaggregated targets for HIV prevention, 56% for testing and linkage to care, 22% for improving antiretroviral treatment coverage, and 11% for retention in treatment. The most common target to reduce gender inequality was to prevent gender-based violence (present in 50% of countries). Other commonly incorporated target areas related to improving women’s access to family planning, human and legal rights, and decision-making power. The inclusion of sex-disaggregated targets in national planning is vital to ensure that programmes make progress for all population groups. Improving the availability and quality of indicators to measure gender inequality, as well as evaluating programme outcomes by sex, is critical to tracking this progress. This analysis reveals an urgent need to set specific and separate targets for men and women in order to achieve

Avian leukosis virus subgroup J promotes cell proliferation and cell cycle progression through miR-221 by targeting CDKN1B.

Science.gov (United States)

Ren, Chaoqi; Yu, Mengmeng; Zhang, Yao; Fan, Minghui; Chang, Fangfang; Xing, Lixiao; Liu, Yongzhen; Wang, Yongqiang; Qi, Xiaole; Liu, Changjun; Zhang, Yanping; Cui, Hongyu; Li, Kai; Gao, Li; Pan, Qing; Wang, Xiaomei; Gao, Yulong

2018-04-23

Avian leukosis virus subgroup J (ALV-J), a highly oncogenic retrovirus, causes leukemia-like proliferative diseases in chickens. microRNAs post-transcriptionally suppress targets and are involved in the development of various tumors. We previously showed that miR-221 is upregulated in ALV-J-induced tumors. In this study, we analyzed the possible function of miR-221 in ALV-J tumorigenesis. The target validation system showed that CDKN1B is a target of miR-221 and is downregulated in ALV-J infection. As CDKN1B arrests the cell cycle and regulates its progression, we analyzed the proliferation of ALV-J-infected DF-1 cells. ALV-J-infection-induced DF1 cell derepression of G1/S transition and overproliferation required high miR-221 expression followed by CDKN1B downregulation. Cell cycle pathway analysis showed that ALV-J infection induced DF-1 cell overproliferation via the CDKN1B-CDK2/CDK6 pathway. Thus, miR-221 may play an important role in ALV-J-induced aggressive growth of DF-1 cells; these findings have expanded our insights into the mechanism underlying ALV-J infection and tumorigenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

[Research progress on remote sensing of ecological and environmental changes in the Three Gorges Reservoir area, China].

Science.gov (United States)

Teng, Ming-jun; Zeng, Li-xiong; Xiao, Wen-fa; Zhou, Zhi-xiang; Huang, Zhi-lin; Wang, Peng-cheng; Dian, Yuan-yong

2014-12-01

The Three Gorges Reservoir area (TGR area) , one of the most sensitive ecological zones in China, has dramatically changes in ecosystem configurations and services driven by the Three Gorges Engineering Project and its related human activities. Thus, understanding the dynamics of ecosystem configurations, ecological processes and ecosystem services is an attractive and critical issue to promote regional ecological security of the TGR area. The remote sensing of environment is a promising approach to the target and is thus increasingly applied to and ecosystem dynamics of the TGR area on mid- and macro-scales. However, current researches often showed controversial results in ecological and environmental changes in the TGR area due to the differences in remote sensing data, scale, and land-use/cover classification. Due to the complexity of ecological configurations and human activities, challenges still exist in the remote-sensing based research of ecological and environmental changes in the TGR area. The purpose of this review was to summarize the research advances in remote sensing of ecological and environmental changes in the TGR area. The status, challenges and trends of ecological and environmental remote-sensing in the TGR area were further discussed and concluded in the aspect of land-use/land-cover, vegetation dynamics, soil and water security, ecosystem services, ecosystem health and its management. The further researches on the remote sensing of ecological and environmental changes were proposed to improve the ecosystem management of the TGR area.

Recent Progress on Data-Based Optimization for Mineral Processing Plants

Directory of Open Access Journals (Sweden)

Jinliang Ding

2017-04-01

Full Text Available In the globalized market environment, increasingly significant economic and environmental factors within complex industrial plants impose importance on the optimization of global production indices; such optimization includes improvements in production efficiency, product quality, and yield, along with reductions of energy and resource usage. This paper briefly overviews recent progress in data-driven hybrid intelligence optimization methods and technologies in improving the performance of global production indices in mineral processing. First, we provide the problem description. Next, we summarize recent progress in data-based optimization for mineral processing plants. This optimization consists of four layers: optimization of the target values for monthly global production indices, optimization of the target values for daily global production indices, optimization of the target values for operational indices, and automation systems for unit processes. We briefly overview recent progress in each of the different layers. Finally, we point out opportunities for future works in data-based optimization for mineral processing plants.

Search for neutrino oscillations and measurements of neutrino-nucleus cross sections. Technical progress report, 16 January 1985-15 October 1985

International Nuclear Information System (INIS)

Koetke, D.D.

1985-01-01

Progress is reported in these areas: work done at LANL on experiment E764, including beam line modification, new target installation, system testing, on-line software development, beam tuning, and data acquisition; neutrino Monte Carlo program development; flux calculations for the DC modified torroidal pion focussing device for the low energy decay-in-flight neutrino source; and prototype preparation for a large modular segmented detector

Dynamics in the global protected-area estate since 2004.

Science.gov (United States)

Lewis, Edward; MacSharry, Brian; Juffe-Bignoli, Diego; Harris, Nyeema; Burrows, Georgina; Kingston, Naomi; Burgess, Neil D

2017-11-23

Nations of the world have committed to a number of goals and targets to address the global environmental challenges humanity faces. Protected areas have for centuries been a key strategy in conservation and play a major role in addressing current challenges. The most important tool used to track progress on protected area commitments is the World Database on Protected Areas (WDPA). Periodic assessments of the world's protected area estate show steady growth over the last two decades. However, the current method, which uses the latest version of the WDPA, does not show the true dynamic nature of protected areas over time, nor does it provide information on sites removed from the WDPA. In reality, this methodology can only show growth or remain stable. This paper presents a novel approach to assess protected area change over time using twelve temporally distinct versions of the WDPA that quantify area added, and removed, from the WDPA annually from 2004 to 2016. Results show that both the narrative of continual protected area growth and the counter-narrative of protected area removal are overly simplistic. The former because growth has been almost entirely marine and the latter because we demonstrate that some areas removed are re-protected in later years. Analysis indicates that, on average, 2.5 million km 2 is added to the WDPA annually and 1.1 million km 2 is removed. Reasons for the inclusion and removal of protected areas in the WDPA database are explored and discussed. To meet the 17% land coverage component of Aichi Biodiversity Target 11 by 2020, which stands at 14.7% in 2016, the world will either need to reduce the rate of protected area removal or increase the rate of protected area designation and addition to the WDPA. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or without adalimumab effectively reduces MRI synovitis, osteitis and tenosynovitis and halts structural damage progression in early rheumatoid arthritis

DEFF Research Database (Denmark)

Axelsen, Mette Bjørndal; Eshed, Iris; Hørslev-Petersen, Kim

2014-01-01

To investigate whether a treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid injections suppresses MRI inflammation and halts structural damage progression in patients with early rheumatoid arthritis (ERA), and whether adalimumab provides an additional effect....

Monitoring Ground Deformation of Subway Area during the Construction Based on the Method of Multi-Temporal Coherent Targets Analysis

Science.gov (United States)

Zhang, L.; Wu, J.; Zhao, J.; Yuan, M.

2018-04-01

Multi-temporal coherent targets analysis is a high-precision and high-spatial-resolution monitoring method for urban surface deformation based on Differential Synthetic Aperture Radar (DInSAR), and has been successfully applied to measure land subsidence, landslide and strain accumulation caused by fault movement and so on. In this paper, the multi-temporal coherent targets analysis is used to study the settlement of subway area during the period of subway construction. The eastern extension of Shanghai Metro Line. 2 is taking as an example to study the subway settlement during the construction period. The eastern extension of Shanghai Metro Line. 2 starts from Longyang Road and ends at Pudong airport. Its length is 29.9 kilometers from east to west and it is a key transportation line to the Pudong Airport. 17 PalSAR images during 2007 and 2010 are applied to analyze and invert the settlement of the buildings nearby the subway based on the multi-temporal coherent targets analysis. But there are three significant deformation areas nearby the Line 2 between 2007 and 2010, with maximum subsidence rate up to 30 mm/y in LOS. The settlement near the Longyang Road station and Chuansha Town are both caused by newly construction and city expansion. The deformation of the coastal dikes suffer from heavy settlement and the rate is up to -30 mm/y. In general, the area close to the subway line is relatively stable during the construction period.

Addressing key science and technology issues for IFE chambers, target fabrication and target injection

International Nuclear Information System (INIS)

Meier, W.R.; Goodin, D.T.; Nobile, A.

2003-01-01

Significant progress has been made in the development of high repetition rate chambers, target fabrication and injection for inertial fusion energy (IFE) for both heavy ion and laser drivers. Research is being conducted in a coordinated manner by national laboratories, universities and industry. This paper provides an overview of U.S. research activities and discusses how interface considerations (such as beam propagation and target survival during injection) impact design choices. (author)

Heparan Sulfate and Heparanase as Modulators of Breast Cancer Progression

Directory of Open Access Journals (Sweden)

Angélica M. Gomes

2013-01-01

Full Text Available Breast cancer is defined as a cancer originating in tissues of the breast, frequently in ducts and lobules. During the last 30 years, studies to understand the biology and to treat breast tumor improved patients’ survival rates. These studies have focused on genetic components involved in tumor progression and on tumor microenvironment. Heparan sulfate proteoglycans (HSPGs are involved in cell signaling, adhesion, extracellular matrix assembly, and growth factors storage. As a central molecule, HSPG regulates cell behavior and tumor progression. HS accompanied by its glycosaminoglycan counterparts regulates tissue homeostasis and cancer development. These molecules present opposite effects according to tumor type or cancer model. Studies in this area may contribute to unveil glycosaminoglycan activities on cell dynamics during breast cancer exploring these polysaccharides as antitumor agents. Heparanase is a potent tumor modulator due to its protumorigenic, proangiogenic, and prometastatic activities. Several lines of evidence indicate that heparanase is upregulated in all human sarcomas and carcinomas. Heparanase seems to be related to several aspects regulating the potential of breast cancer metastasis. Due to its multiple roles, heparanase is seen as a target in cancer treatment. We will describe recent findings on the function of HSPGs and heparanase in breast cancer behavior and progression.

Prostate Cancer Treatment | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Prostate Cancer Screening | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Bladder Cancer Treatment | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Red Meat Consumption | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Kidney Cancer Treatment | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Secondhand Smoke Exposure | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Colorectal Cancer Treatment | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Colorectal Cancer Screening | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Sun-Protective Behavior | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Cervical Cancer Screening | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Geothermal Progress Monitor report No. 5. Progress report, June 1981

Energy Technology Data Exchange (ETDEWEB)

1981-01-01

Updated information is presented on activities and progress in the areas of electric power plants, direct heat applications, deep well drilling, leasing of federal lands, legislative and regulatory actions, research and development, and others. Special attention is given in this report to 1980 highlights, particularly in the areas of electric and direct heat uses, drilling, and the Federal lands leasing program. This report also includes a summary of the DOE FY 1982 geothermal budget request to Congress.

Streamlined Approach for Environmental Restoration Plan for Corrective Action Unit 408: Bomblet Target Area, Tonopah Test Range, Nevada

International Nuclear Information System (INIS)

NSTec Environmental Management

2006-01-01

This Streamlined Approach for Environmental Restoration Plan provides the details for the closure of Corrective Action Unit (CAU) 408, Bomblet Target Area. CAU 408 is located at the Tonopah Test Range and is currently listed in Appendix III of the Federal Facility Agreement and Consent Order of 1996. One Corrective Action Site (CAS) is included in CAU 408: (lg b ullet) CAS TA-55-002-TAB2, Bomblet Target Areas Based on historical documentation, personnel interviews, process knowledge, site visits, aerial photography, multispectral data, preliminary geophysical surveys, and the results of data quality objectives process (Section 3.0), clean closure will be implemented for CAU 408. CAU 408 closure activities will consist of identification and clearance of bomblet target areas, identification and removal of depleted uranium (DU) fragments on South Antelope Lake, and collection of verification samples. Any soil containing contaminants at concentrations above the action levels will be excavated and transported to an appropriate disposal facility. Based on existing information, contaminants of potential concern at CAU 408 include explosives. In addition, at South Antelope Lake, bomblets containing DU were tested. None of these contaminants is expected to be present in the soil at concentrations above the action levels; however, this will be determined by radiological surveys and verification sample results. The corrective action investigation and closure activities have been planned to include data collection and hold points throughout the process. Hold points are designed to allow decision makers to review the existing data and decide which of the available options are most suitable. Hold points include the review of radiological, geophysical, and analytical data and field observations

Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

Science.gov (United States)

Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

2014-11-21

In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

Progress on the IPNS Enriched Uranium Booster Target

International Nuclear Information System (INIS)

Knox, A.E.; Carpenter, J.M.; Bailey, J.L.

1986-09-01

We describe the Enriched Uranium Booster Target designed for use in Argonne's Intense Pulsed Neutron Source. This report contains a general description of the system, and descriptions of the thermal-hydraulic and loss-of-coolant accident analyses, of the neutronic, criticality and power density calculations, of the assessment of radiation and thermal cycling growth, and of the disk fabrication methods. We also describe the calculations of radionuclide buildup and the related hazards analysis and our calculations of the temperature and stress profiles in the disks, and briefly allude to considerations of security and safeguards

Prismatic displacement effect of progressive multifocal glasses on reaction time and accuracy in elderly people.

Science.gov (United States)

Ellison, Ashton C; Campbell, A John; Robertson, M Clare; Sanderson, Gordon F

2014-01-01

Multifocal glasses (bifocals, trifocals, and progressives) increase the risk of falling in elderly people, but how they do so is unclear. To explain why glasses with progressive addition lenses increase the risk of falls and whether this can be attributed to false projection, this study aimed to 1) map the prismatic displacement of a progressive lens, and 2) test whether this displacement impaired reaction time and accuracy. The reaction times of healthy ≥75-year-olds (31 participants) were measured when grasping for a bar and touching a black line. Participants performed each test twice, wearing their progressives and new, matched single vision (distance) glasses in random order. The line and bar targets were positioned according to the maximum and minimum prismatic displacement effect through the progressive lens, mapped using a focimeter. Progressive spectacle lenses have large areas of prismatic displacement in the central visual axis and edges. Reaction time was faster for progressives compared with single vision glasses with a centrally-placed horizontal grab bar (mean difference 101 ms, P=0.011 [repeated measures analysis]) and a horizontal black line placed 300 mm below center (mean difference 80 ms, P=0.007). There was no difference in accuracy between the two types of glasses. Older people appear to adapt to the false projection of progressives in the central visual axis. This adaptation means that swapping to new glasses or a large change in prescription may lead to a fall. Frequently updating glasses may be more beneficial.

Particle-beam-fusion progress report, July 1979 through December 1979

International Nuclear Information System (INIS)

1981-01-01

The following chapters are included in this semi-annual progress report: (1) fusion target studies, (2) target experiments, (3) particle-beam source developments, (4) particle beam experiments, (5) pulsed power, (6) pulsed power applications, and (7) electron beam fusion accelerator project

Investigation on cryogenic laser fusion targets: fabrication, characterization, and transport. Annual report, December 1, 1978-November 30, 1979

International Nuclear Information System (INIS)

Kim, K.

1979-01-01

The research has been directed toward fabrication, characterization, and positioning of cryogenic shell laser fusion targets, with particular emphasis on the development of a scheme which would allow for continuous fabrication, inspection, and delivery of the targets. Specifically, progress has been made in the following areas: (1) Fabrication of a uniform spherical shell of DT-condensate using a cold-wall target-freezing-cell. (2) Fabrication of a uniform spherical shell of liquid DT using a room-temperature wall target-freezing-cell. (3) Support-free cryogenic target fabrication using cold-gas-levitation. (4) Continuous fabrication of cryogenic targets using free-fall method. (5) Automatic characterization of DT-layer uniformity. (6) Sorting of DT-filled glass microshells using an interference microscope. (7) Development of an a-c interference microscope for accurate characterization of moving targets. (8) Development of a machine which is capable of producing a continuous stream of uniform DT spheres of controllable sizes. (9) Theoretical study on the behavior of liquid hydrogen contained in a spherical shell

Progress report, Physics Division

International Nuclear Information System (INIS)

1986-03-01

This report reviews events and progress in the following areas: development of the TASCC facility; experimental and theoretical nuclear physics research; radionuclide standardization; condensed matter research; applied mathematics; and computer facility operation

National Ignition Facility subsystem design requirements laser and target area building (LTAB) SSDR 1.2.2.1

International Nuclear Information System (INIS)

Kempel, P.; Hands, J.

1996-01-01

This Subsystem Design Requirements (SSDR) document establishes the performance, design, and verification requirements for the conventional building systems and subsystems of the Laser and Target Area Building (LTAB), including those that house and support the operation of high-energy laser equipment and the operational flow of personnel and materials throughout the facility. This SSDR addresses the following subsystems associated with the LTAB: Building structural systems for the Target Bay, Switchyards, Diagnostic Building, Decontamination Area, Laser Bays, Capacitor Bays and Operations Support Area, and the necessary space associated with building-support equipment; Architectural building features associated with housing the space and with the operational cleanliness of the functional operation of the facilities; Heating, Ventilating, and Air Conditioning (HVAC) systems for maintaining a clean and thermally stable ambient environment within the facilities; Plumbing systems that provide potable water and sanitary facilities for the occupants, plus stormwater drainage for transporting rainwater; Fire Protection systems that guard against fire damage to the facilities and their contents; Material handling systems for transporting personnel and heavy materials within the building areas; Mechanical process piping systems for liquids and gases that provide cooling and other service to experimental laser equipment and components; Electrical power and grounding systems that provide service and standby power to building and experimental equipment, including lighting distribution and communications systems for the facilities; Instrumentation and control systems that ensure the safe operation of conventional facilities systems, such as those listed above. Detailed requirements for building subsystems that are not addressed in this document (such as specific sizes, locations, or capacities) are included in detail-level NIP Project Interface Control Documents (ICDS)

A comparison of machine learning techniques for detection of drug target articles.

Science.gov (United States)

Danger, Roxana; Segura-Bedmar, Isabel; Martínez, Paloma; Rosso, Paolo

2010-12-01

Important progress in treating diseases has been possible thanks to the identification of drug targets. Drug targets are the molecular structures whose abnormal activity, associated to a disease, can be modified by drugs, improving the health of patients. Pharmaceutical industry needs to give priority to their identification and validation in order to reduce the long and costly drug development times. In the last two decades, our knowledge about drugs, their mechanisms of action and drug targets has rapidly increased. Nevertheless, most of this knowledge is hidden in millions of medical articles and textbooks. Extracting knowledge from this large amount of unstructured information is a laborious job, even for human experts. Drug target articles identification, a crucial first step toward the automatic extraction of information from texts, constitutes the aim of this paper. A comparison of several machine learning techniques has been performed in order to obtain a satisfactory classifier for detecting drug target articles using semantic information from biomedical resources such as the Unified Medical Language System. The best result has been achieved by a Fuzzy Lattice Reasoning classifier, which reaches 98% of ROC area measure. Copyright © 2010 Elsevier Inc. All rights reserved.

Automated alignment of the Advanced Radiographic Capability (ARC) target area at the National Ignition Facility

Science.gov (United States)

Roberts, Randy S.; Awwal, Abdul A. S.; Bliss, Erlan S.; Heebner, John E.; Leach, Richard R.; Orth, Charles D.; Rushford, Michael C.; Lowe-Webb, Roger R.; Wilhelmsen, Karl C.

2015-09-01

The Advanced Radiographic Capability (ARC) at the National Ignition Facility (NIF) is a petawatt-class, short-pulse laser system designed to provide x-ray backlighting of NIF targets. ARC uses four NIF beamlines to produce eight beamlets to create a sequence of eight images of an imploding fuel capsule using backlighting targets and diagnostic instrumentation. ARC employs a front end that produces two pulses, chirps the pulses out to 2 ns, and then injects the pulses into the two halves of each of four NIF beamlines. These pulses are amplified by NIF pre- and main amplifiers and transported to compressor vessels located in the NIF target area. The pulses are then compressed and pointed into the NIF target chamber where they impinge upon an array of backlighters. The interaction of the ARC laser pulses and the backlighting material produces bursts of high-energy x-rays that illuminate an imploding fuel capsule. The transmitted x-rays are imaged by diagnostic instrumentation to produce a sequence of radiograph images. A key component of the success of ARC is the automatic alignment system that accomplishes the precise alignment of the beamlets to avoid damaging equipment and to ensure that the beamlets are directed onto the tens-of-microns scale backlighters. In this paper, we describe the ARC automatic alignment system, with emphasis on control loops used to align the beampaths. We also provide a detailed discussion of the alignment image processing, because it plays a critical role in providing beam centering and pointing information for the control loops.

Tracking Clean Energy Progress 2013

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-06-01

Tracking Clean Energy Progress 2013 (TCEP 2013) examines progress in the development and deployment of key clean energy technologies. Each technology and sector is tracked against interim 2020 targets in the IEA Energy Technology Perspectives 2012 2°C scenario, which lays out pathways to a sustainable energy system in 2050. Stark message emerge: progress has not been fast enough; large market failures are preventing clean energy solutions from being taken up; considerable energy efficiency remains untapped; policies need to better address the energy system as a whole; and energy-related research, development and demonstration need to accelerate. Alongside these grim conclusions there is positive news. In 2012, hybrid-electric vehicle sales passed the 1 million mark. Solar photovoltaic systems were being installed at a record pace. The costs of most clean energy technologies fell more rapidly than anticipated.

Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis

Directory of Open Access Journals (Sweden)

Jessica A. Bernard

2017-01-01

Full Text Available Prospective longitudinal evaluation of adolescents at ultra-high-risk (UHR for the development of psychosis enables an enriched neurodevelopmental perspective of disease progression in the absence of many of the factors that typically confound research with formally psychotic patients (antipsychotic medications, drug/alcohol dependence. The cerebellum has been linked to cognitive dysfunction and symptom severity in schizophrenia and recent work from our team suggests that it is a promising target for investigation in UHR individuals as well. However, the cerebellum and cerebello-thalamo-cortical networks have not been investigated developmentally or with respect to disease progression in this critical population. Further, to date, the types of longitudinal multimodal connectivity studies that would substantially inform our understanding of this area have not yet been conducted. In the present investigation 26 UHR and 24 healthy control adolescents were administered structured clinical interviews and scanned at baseline and then again at 12-month time points to investigate both functional and structural connectivity development of cerebello-thalamo-cortical networks in conjunction with symptom progression. Our results provide evidence of abnormal functional and structural cerebellar network development in the UHR group. Crucially, we also found that cerebello-thalamo-cortical network development and connectivity at baseline are associated with positive symptom course, suggesting that cerebellar networks may be a biomarker of disease progression. Together, these findings provide support for neurodevelopmental models of psychotic disorders and suggest that the cerebellum and respective networks with the cortex may be especially important for elucidating the pathophysiology of psychosis and highlighting novel treatment targets.

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

Science.gov (United States)

Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

2010-09-01

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

Progress Toward Regional Measles Elimination - Worldwide, 2000-2016.

Science.gov (United States)

Dabbagh, Alya; Patel, Minal K; Dumolard, Laure; Gacic-Dobo, Marta; Mulders, Mick N; Okwo-Bele, Jean-Marie; Kretsinger, Katrina; Papania, Mark J; Rota, Paul A; Goodson, James L

2017-10-27

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan, † with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive programmatic actions, securing political commitment, and raising

LIFE: Recent Developments and Progress

International Nuclear Information System (INIS)

Anklam, T.M.

2011-01-01

Test results from the NIF show excellent progress toward achieving ignition. Experiments designed to verify coupling of the laser energy to the fusion target have shown that the efficiency meets that needed for ignition. Several tests with the cryogenic targets needed for ignition have been performed, and world-record neutron output produced. The National Ignition Campaign is on schedule to meet its 2012 ignition milestone, with the next phase in the campaign due to start later this month. It has been a busy and very productive year. The NIF is in full 24/7 operations and has progressed markedly in the path toward ignition. The long-standing goal of the National Ignition Campaign to demonstrate ignition by the end of FY 2012 is on track. The LIFE plant design has matured considerably, and a delivery plan established based on close interactions with vendors. National-level reviews of fusion are underway, and are due to present initial findings later this year. A value proposition has been drafted for review. The LIFE project is ready to move into the delivery phase.

The Argonne laser-driven D target: Recent developments and progress

International Nuclear Information System (INIS)

Fedchak, J.A.; Bailey, K.; Cummings, W.J.

1997-01-01

The first direct measurements of nuclear tensor polarization p zz in a laser-driven polarized D target have been performed at Argonne. We present p zz and electron polarization P e data taken at a magnetic field of 600 G in the optical pumping cell. These results are highly indicative that spin-temperature equilibrium is achieved in the system. To prevent spin relaxation of D and K atoms as well as the molecular recombination of D atoms, the walls of the laser-driven D target are coated with organosilane compounds. We discuss a new coating technique, the open-quotes afterwashclose quotes, developed at Argonne which has yielded stable atomic fraction results when the coating is exposed to K. We also present new coating techniques for glass and Cu substrates

Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway

Energy Technology Data Exchange (ETDEWEB)

Yao, Jingjing [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China); Xu, Chen [Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433 (China); Department of Orthopedics, Changzheng Hospital Affiliated to Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003 (China); Fang, Ziyu; Li, Yaoming [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China); Liu, Houqi; Wang, Yue [Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433 (China); Translational Medicine Center, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433 (China); Xu, Chuanliang [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China); Sun, Yinghao, E-mail: sunyh@medmail.com.cn [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China)

2016-05-20

Abstracts: MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibit apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-5p, which could target to the 3′UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. -- Highlights: •miR-182-5p is the mostly up-regulated miRNA in Chinese prostate cancer. •miR-182-5p is regulated by androgen receptor. •miR-182-5p promotes prostate cancer progression. •miR-182-5p regulates ARRDC3/ITGB4 pathway.

Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway

International Nuclear Information System (INIS)

Yao, Jingjing; Xu, Chen; Fang, Ziyu; Li, Yaoming; Liu, Houqi; Wang, Yue; Xu, Chuanliang; Sun, Yinghao

2016-01-01

Abstracts: MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibit apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-5p, which could target to the 3′UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. -- Highlights: •miR-182-5p is the mostly up-regulated miRNA in Chinese prostate cancer. •miR-182-5p is regulated by androgen receptor. •miR-182-5p promotes prostate cancer progression. •miR-182-5p regulates ARRDC3/ITGB4 pathway.

Are area-based initiatives able to improve area safety in deprived areas? A quasi-experimental evaluation of the Dutch District Approach.

Science.gov (United States)

Kramer, Daniëlle; Jongeneel-Grimen, Birthe; Stronks, Karien; Droomers, Mariël; Kunst, Anton E

2015-07-28

Numerous area-based initiatives have been implemented in deprived areas across Western-Europe with the aim to improve the socio-economic and environmental conditions in these areas. Only few of these initiatives have been scientifically evaluated for their impact on key social determinants of health, like perceived area safety. Therefore, this study aimed to assess the impact of a Dutch area-based initiative called the District Approach on trends in perceived area safety and underlying problems in deprived target districts. A quasi-experimental design was used. Repeated cross-sectional data on perceived area safety and underlying problems were obtained from the National Safety Monitor (2005-2008) and its successor the Integrated Safety Monitor (2008-2011). Study population consisted of 133,522 Dutch adults, including 3,595 adults from target districts. Multilevel logistic regression analyses were performed to assess trends in self-reported general safety, physical order, social order, and non-victimization before and after the start of the District Approach mid-2008. Trends in target districts were compared with trends in various control groups. Residents of target districts felt less safe, perceived less physical and social order, and were victimized more often than adults elsewhere in the Netherlands. For non-victimization, target districts showed a somewhat more positive change in trend after the start of the District Approach than the rest of the Netherlands or other deprived districts. Differences were only statistically significant in women, older adults, and lower educated adults. For general safety, physical order, and social order, there were no differences in trend change between target districts and control groups. Results suggest that the District Approach has been unable to improve perceptions of area safety and disorder in deprived areas, but that it did result in declining victimization rates.

Where to Go Next? Identifying Target Areas in the North Atlantic for Future Seafloor Mapping Initiatives

Science.gov (United States)

Woelfl, A. C.; Jencks, J.; Johnston, G.; Varner, J. D.; Devey, C. W.

2017-12-01

Human activities are rapidly expanding into the oceans, yet detailed bathymetric maps do not exist for most of the seafloor that would permit governments to formulate sensible usage rules. Changing this situation will require an enormous international mapping effort. To ensure that this effort is directed towards the regions most in need of mapping, we need to know which areas have already been mapped and which areas are potentially most interesting. Despite various mapping efforts in recent years, large parts of the Atlantic still lack detailed bathymetric information. To successfully plan for future mapping efforts to fill these gaps, knowledge of current data coverage is imperative to avoid duplication of effort. While certain datasets are publically available online (e.g. NOAA's NCEI, EMODnet, IHO-DCDB, LDEO's GMRT), many are not. However, with the limited information we do have at hand, the question remains, where should we map next? And what criteria should we take into account? In 2016, a study was taken on as part of the efforts of the International Atlantic Seabed Mapping Working Group (ASMIWG). The ASMIWG, established by the Tri-Partite Galway Statement Implementation Committee, was tasked to develop a cohesive seabed mapping strategy for the Atlantic Ocean. The aim of our study was to develop a reproducible process for identifying and evaluating potential target areas within the North Atlantic that represent suitable sites for future bathymetric surveys. The sites were selected by applying a GIS-based suitability analysis that included specific user group-based parameters of the marine environment. Furthermore, information regarding current data coverage were gathered to take into account in the selection process. The results reveal the suitability of sites within the North Atlantic based on the selected criteria. Three potential target sites should be seen as flexible suggestions for future mapping initiatives rather than a rigid, defined set of areas

Research progress on osteoarthritis treatment mechanisms.

Science.gov (United States)

Gu, Yun-Tao; Chen, Jian; Meng, Zhu-Long; Ge, Wan-Yu; Bian, Yang-Yang; Cheng, Shao-Wen; Xing, Chen-Kun; Yao, Jiang-Ling; Fu, Jian; Peng, Lei

2017-09-01

Osteoarthritis is a common disease and is frequently encountered in the older population; the incidence rises sharply with age. It is estimated that more than 360 million people suffer from OA. However, the pathogenesis of osteoarthritis remains unclear, and we cannot effectively prevent the progression of OA. The aim of this review was to explore the molecular markers and signaling pathways that induce chondrocyte apoptosis in OA. We searched, using the key words osteoarthritis, chondrocyte apoptosis, autophagy, endoplasmic reticulum stress, molecular targets, and biomarkers, in PubMed, Web of Science, and Google Scholar from 1994 to 2017. We also reviewed the signaling pathways and molecular markers associated with chondrocyte apoptosis and approaches aimed at inhibiting the apoptosis-inducing mechanism to at least delay the progression of cartilage degeneration in OA. This article provides an overview of targeted therapies and the related signaling pathways in OA. Copyright © 2017. Published by Elsevier Masson SAS.

Progress towards a high-gain and robust target design for heavy ion fusion

Energy Technology Data Exchange (ETDEWEB)

Henestroza, Enrique; Grant Logan, B. [Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

2012-07-15

Recently [E. Henestroza et al., Phys. Plasmas 18, 032702 (2011)], a new inertial-fusion target configuration, the X-target, using one-sided axial illumination has been explored. This class of target uses annular and solid-profile heavy ion beams to compress and ignite deuterium-tritium (DT) fuel that fills the interior of metal cases that have side-view cross sections in the shape of an 'X.' X-targets using all-DT-filled metal cases imploded by three annular ion beams resulted in fuel densities of {approx}50 g/cm{sup 3} at peak compression, and fusion gains of {approx}50, comparable to heavy ion driven hohlraum targets [D. A. Callahan-Miller and M. Tabak, Phys. Plasmas 7, 2083 (2000)]. This paper discusses updated X-target configurations that incorporate inside the case a propellant (plastic) and a pusher (aluminum) surrounding the DT fuel. The updated configurations are capable of assembling higher fuel areal densities {approx}2 g/cm{sup 2} using two annular beams to implode the target to peak DT densities {approx}100 g/cm{sup 3}, followed by a fast-ignition solid ion beam which heats the high-density fuel to thermonuclear temperatures in {approx}200 ps to start the burn propagation, obtaining gains of {approx}300. These targets have been modeled using the radiation-hydrodynamics code HYDRA [M. M. Marinak et al., Phys. Plasmas 8, 2275 (2001)] in two- and three- dimensions to study the properties of the implosion as well as the ignition and burn propagation phases. At typical Eulerian mesh resolutions of a few microns, the aluminum-DT interface shows negligible Rayleigh-Taylor (RT) and Richtmyer-Meshkov instability growth; also, the shear flow of the DT fuel as it slides along the metal X-target walls, which drives the RT and Kelvin Helmholtz instabilities, does not have a major effect on the burning rate. An analytic estimate of the RT instability process at the Al-DT interface shows that the aluminum spikes generated during the pusher deceleration phase

Beta-Zone parapapillary atrophy and the velocity of glaucoma progression.

Science.gov (United States)

Teng, Christopher C; De Moraes, Carlos Gustavo V; Prata, Tiago S; Tello, Celso; Ritch, Robert; Liebmann, Jeffrey M

2010-05-01

Beta-Zone parapapillary atrophy (PPA) occurs more commonly in eyes with glaucoma. Rates of glaucomatous visual field (VF) progression in eyes with and without beta-zone PPA at the time of baseline assessment were compared. Retrospective, comparative study. Two hundred forty-five patients from the New York Glaucoma Progression Study. Subjects with glaucomatous optic neuropathy and repeatable VF loss were assessed for eligibility. Eyes with a Heidelberg Retina Tomograph II (HRT) examination, at least 5 visual field tests after the HRT in either eye, optic disc photographs, and Zone PPA was defined as a region of chorioretinal atrophy with visible sclera and choroidal vessels adjacent to the optic disc. Global rates of VF progression were determined by automated pointwise linear regression analysis. Univariate analysis included age, gender, ethnicity, central corneal thickness (CCT), refractive error, baseline mean deviation, baseline intraocular pressure (IOP), mean IOP, IOP fluctuation, disc area, rim area, rim area-to-disc area ratio, beta-zone PPA area, beta-zone PPA area-to-disc area ratio, and presence or absence of beta-zone PPA. The relationship between beta-zone PPA and the rate and risk of glaucoma progression. Two hundred forty-five eyes of 245 patients (mean age, 69.6+/-12.3 years) were enrolled. The mean follow-up was 4.9+/-1.4 years and the mean number of VFs after HRT was 9.3+/-2.7. beta-Zone PPA was present in 146 eyes (65%). Eyes with beta-zone PPA progressed more rapidly (-0.84+/-0.8 dB/year) than eyes without it (-0.51+/-0.6 dB/year; Pzone PPA (HR, 2.59; P1.5 dB/year; P = 0.08) global rates of progression occurred more commonly in eyes with beta-zone PPA than in eyes without it. Thinner CCT (zone PPA (kappa = 0.13). Eyes with beta-zone PPA are at increased risk for glaucoma progression and warrant close clinical surveillance. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Immunotherapy Targets in Pediatric Cancer

International Nuclear Information System (INIS)

Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

2012-01-01

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer.

Immunotherapy Targets in Pediatric Cancer

Energy Technology Data Exchange (ETDEWEB)

Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal, E-mail: rimas.orentas@nih.gov, E-mail: mackallc@mail.nih.gov [Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)

2012-01-30

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer.

Restoration for the future: endpoints, targets, and indicators of progress and success

Science.gov (United States)

Daniel C. Dey; Callie Jo. Schweitzer

2014-01-01

Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly described and quantitative endpoints and intermediary targets are needed to...

Therapeutic targeting of the p53 pathway in cancer stem cells

Science.gov (United States)

Prabhu, Varun V.; Allen, Joshua E.; Hong, Bo; Zhang, Shengliang; Cheng, Hairong; El-Deiry, Wafik S.

2013-01-01

Introduction Cancer stem cells are a high profile drug target for cancer therapeutics due to their indispensable role in cancer progression, maintenance, and therapeutic resistance. Restoring wild-type p53 function is an attractive new therapeutic approach for the treatment of cancer due to the well-described powerful tumor suppressor function of p53. As emerging evidence intimately links p53 and stem cell biology, this approach also provides an opportunity to target cancer stem cells. Areas covered Therapeutic approaches to restore the function of wild-type p53, cancer and normal stem cell biology in relation to p53, and the downstream effects of p53 on cancer stem cells. Expert opinion The restoration of wild-type p53 function by targeting p53 directly, its interacting proteins, or its family members holds promise as a new class of cancer therapies. This review examines the impact that such therapies may have on normal and cancer stem cells based on the current evidence linking p53 signaling with these populations. PMID:22998602

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

Uncovering Direct Targets of MiR-19a Involved in Lung Cancer Progression.

Directory of Open Access Journals (Sweden)

Kumiko Yamamoto

Full Text Available Micro RNAs (miRNAs regulate the expression of target genes posttranscriptionally by pairing incompletely with mRNA in a sequence-specific manner. About 30% of human genes are regulated by miRNAs, and a single miRNA is capable of reducing the production of hundreds of proteins by means of incomplete pairing upon miRNA-mRNA binding. Lately, evidence implicating miRNAs in the development of lung cancers has been emerging. In particular, miR-19a, which is highly expressed in malignant lung cancer cells, is considered the key miRNA for tumorigenesis. However, its direct targets remain underreported. In the present study, we focused on six potential miR-19a target genes selected by miRNA target prediction software. To evaluate these genes as direct miR-19a target genes, we performed luciferase, pull-down, and western blot assays. The luciferase activity of plasmids with each miR-19a-binding site was observed to decrease, while increased luciferase activity was observed in the presence of anti-miR-19a locked nucleic acid (LNA. The pull-down assay showed biotinylated miR-19a to bind to AGO2 protein and to four of six potential target mRNAs. Western blot analysis showed that the expression levels of the four genes changed depending on treatment with miR-19a mimic or anti-miR-19a-LNA. Finally, FOXP1, TP53INP1, TNFAIP3, and TUSC2 were identified as miR-19a targets. To examine the function of these four target genes in lung cancer cells, LK79 (which has high miR-19a expression and A549 (which has low miR-19a expression were used. The expression of the four target proteins was higher in A549 than in LK79 cells. The four miR-19a target cDNA expression vectors suppressed cell viability, colony formation, migration, and invasion of A549 and LK79 cells, but LK79 cells transfected with FOXP1 and TP53INP1 cDNAs showed no difference compared to the control cells in the invasion assay.

A review on primary progressive aphasia

Directory of Open Access Journals (Sweden)

Gabriel C Léger

2007-01-01

Full Text Available Gabriel C Léger1,2, Nancy Johnson31Neurology Service, Hôtel-Dieu du Centre Hospitalier de l’Univertité de Montréal, Montréal, Québec, Canada; 2Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; 3Cognitive Neurology and Alzheimer’s Disease Center, Department of Psychiatry and Behavioral Science, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Primary progressive aphasia (PPA is a neurodegenerative disease of insidious onset presenting with progressive isolated loss of language function, without significant impairment in other cognitive domains. Current diagnostic criteria require the language dysfunction to remain isolated for at least two years, and to remain the salient feature as the disease progresses, usually to involve other domains such as behavior, executive functions, and judgment. Although PPA in its early stages can usually be differentiated from probable Alzheimer’s disease (PRAD and the behavioral variant of frontotemporal lobar degeneration by the absence of significant changes in memory and behavior, and the preservation of activities daily living, progression of the disease often leads to deficits more consistent with the latter. Underlying etiologies remain heterogeneous: the neuropathological characteristics associated with frontotemporal lobar degeneration, cortocobasal degeneration, and motor neuron disease are usually found. There is a strong genetic susceptibility with affliction of first-degree relatives with similar disease in up to 40 to 50% in some series. Pathogenic mutations in genes coding for the proteins tau and progranulin have been isolated. These are leading to a better understanding of the neuropathological mechanisms and hopefully targeted disease-modifying therapy. Current therapy is limited to improving mood symptoms and targeting behavior changes as they develop. Referral to specialized centers where speech therapy, counseling, and education

Hot target assembly at 14 UD Pelletron Accelerator Facility, BARC- TIFR, Mumbai

International Nuclear Information System (INIS)

Sharma, S.C.; Ramjilal; Ninawe, N.G.; Bhagwat, P.V.; Ahmeabadhai, P.; Kain, V.

2005-01-01

BARC-TIFR 14 UD Pelletron Accelerator Facility at Mumbai is operational since 1989 with progressively increased efficiency. The accelerator has been serving as major facility for heavy ion based research in India. There is an increased demand for high current proton beam, especially on heated targets for reactor physics based experiments. A proton beam setup is commissioned in the tower area of the existing facility itself, which provide proton beam of energy 2 MeV to 26 MeV with maximum 3 μA current. This setup is being used to produce radioisotopes and tracer packets. Proton beam of few MeV in μA current range is also needed to study radiation effects on metals at higher temperature, for use in reactors. For this purpose a hot target assembly has been designed and is being currently used at the Pelletron Accelerator

Targeted nanoparticles for colorectal cancer

DEFF Research Database (Denmark)

Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

2016-01-01

Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

US Food Industry Progress During the National Salt Reduction Initiative: 2009-2014.

Science.gov (United States)

Curtis, Christine J; Clapp, Jenifer; Niederman, Sarah A; Ng, Shu Wen; Angell, Sonia Y

2016-10-01

To assess the US packaged food industry's progress from 2009 to 2014, when the National Salt Reduction Initiative had voluntary, category-specific sodium targets with the goal of reducing sodium in packaged and restaurant foods by 25% over 5 years. Using the National Salt Reduction Initiative Packaged Food Database, we assessed target achievement and change in sales-weighted mean sodium density in top-selling products in 61 food categories in 2009 (n = 6336), 2012 (n = 6898), and 2014 (n = 7396). In 2009, when the targets were established, no categories met National Salt Reduction Initiative 2012 or 2014 targets. By 2014, 26% of categories met 2012 targets and 3% met 2014 targets. From 2009 to 2014, the sales-weighted mean sodium density declined significantly in almost half of all food categories (43%; 26/61 categories). Overall, sales-weighted mean sodium density declined significantly (by 6.8%; P industry progress was modest. The US Food and Drug Administration's proposed voluntary targets will be an important step in achieving more substantial sodium reductions.

Protected area gap analysis of important bird areas in Tanzania

DEFF Research Database (Denmark)

Sritharan, Shakthi; Burgess, Neil David

2012-01-01

Analyses of gaps in protected area (PA) coverage of species distributions have been carried out extensively for the past two decades, aiming to better locate new PAs and conserve species. In this study, progress to close gaps in the protection of the Important Bird Areas (IBAs) of Tanzania...

Annual Progress report - General Task

International Nuclear Information System (INIS)

Wesnousky, S.G.

1993-01-01

This report provides a summary of progress for the project open-quotes Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI).close quotes A similar report was previously provided for the period of 1 October 1991 to 30 September 1992. The report initially covers the activities of the General Task and is followed by sections that describe the progress of the other ongoing tasks

Early detection of emphysema progression

DEFF Research Database (Denmark)

Gorbunova, Vladlena; Jacobs, Sander S A M; Lo, Pechin

2010-01-01

Emphysema is one of the most widespread diseases in subjects with smoking history. The gold standard method for estimating the severity of emphysema is a lung function test, such as forced expiratory volume in first second (FEV1). However, several clinical studies showed that chest CT scans offer...... more sensitive estimates of emphysema progression. The standard CT densitometric score of emphysema is the relative area of voxels below a threshold (RA). The RA score is a global measurement and reflects the overall emphysema progression. In this work, we propose a framework for estimation of local...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.

Directory of Open Access Journals (Sweden)

Amanda Worker

Full Text Available Parkinson's disease (PD, Multiple System Atrophy (MSA and Progressive Supranuclear Palsy (PSP are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features.High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0. Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group.Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology.These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients.

Dual-Functional Nanoparticles Targeting CXCR4 and Delivering Antiangiogenic siRNA Ameliorate Liver Fibrosis.

Science.gov (United States)

Liu, Chun-Hung; Chan, Kun-Ming; Chiang, Tsaiyu; Liu, Jia-Yu; Chern, Guann-Gen; Hsu, Fu-Fei; Wu, Yu-Hsuan; Liu, Ya-Chi; Chen, Yunching

2016-07-05

The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy.

Preliminary performance and ICF target experiments with Nova

International Nuclear Information System (INIS)

Drake, R.P.

1985-11-01

In December 1984, the Nova facility fired all ten laser arms, converted the output 1.05 micron energy to 0.35 micron light, and focused the 0.35 micron light through a 4 mm pinhole in the ten-beam target chamber. Since that time, a two-beam target chamber has been added, the performance of the laser evaluated, and preparation has been made for target experiments. This paper summarizes the performance of Nova and describes progress and plans for target experiments

Podoplanin - an emerging cancer biomarker and therapeutic target.

Science.gov (United States)

Krishnan, Harini; Rayes, Julie; Miyashita, Tomoyuki; Ishii, Genichiro; Retzbach, Edward P; Sheehan, Stephanie A; Takemoto, Ai; Chang, Yao-Wen; Yoneda, Kazue; Asai, Jun; Jensen, Lasse; Chalise, Lushun; Natsume, Atsushi; Goldberg, Gary S

2018-03-25

Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts (CAFs), and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition (EMT), migration, invasion, metastasis, and inflammation. Antibodies, CAR-T cells, biologics, and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer including glioma, squamous cell carcinoma, mesothelioma, and melanoma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

MicroRNA-144-3p suppresses gastric cancer progression by inhibiting epithelial-to-mesenchymal transition through targeting PBX3

International Nuclear Information System (INIS)

Li, Butian; Zhang, Shengping; Shen, Hao; Li, Chenglong

2017-01-01

MicroRNAs are aberrantly expressed in a wide variety of human cancers. The present study aims to elucidate the effects and molecular mechanisms of miR-144-3p that underlie gastric cancer (GC) development. It was observed that miR-144-3p expression was significantly decreased in GC tissues compared to that in paired non-tumor tissues; moreover, its expression was lower in tissues of advanced stage and larger tumor size, as well as in lymph node metastasis tissues compared to that in control groups. miR-144-3p expression was associated with depth of invasion (P = 0.030), tumor size (P = 0.047), lymph node metastasis (P = 0.047), and TNM stage (P = 0.048). Additionally, miR-144-3p significantly inhibited proliferation, migration, and invasion in GC cells. It also reduced F-actin expression and suppressed epithelial-to-mesenchymal transition (EMT) in GC cells. Furthermore, pre-leukemia transcription factor 3 (PBX3) was a direct target gene of miR-144-3p. PBX3 was overexpressed in GC tissues and promoted EMT in GC cells. The effects of miR-144-3p mimics or inhibitors on cell migration, invasion, and proliferation were reversed by PBX3 overexpression or downregulation respectively. These results suggest that miR-144-3p suppresses GC progression by inhibiting EMT through targeting PBX3. - Highlights: • miR-144-3p is downregulated in gastric cancer tissues and associated with malignant clinical factors. • miR-144-3p inhibits proliferation, migration, and invasion in gastric cancer cells. • PBX3 is a direct target of miR-144-3p and promotes EMT in gastric cancer. • miR-144-3p suppresses EMT in gastric cancer by regulating PBX3.

Progress towards the development of SH2 domain inhibitors.

Science.gov (United States)

Kraskouskaya, Dziyana; Duodu, Eugenia; Arpin, Carolynn C; Gunning, Patrick T

2013-04-21

Src homology 2 (SH2) domains are 100 amino acid modular units, which recognize and bind to tyrosyl-phosphorylated peptide sequences on their target proteins, and thereby mediate intracellular protein-protein interactions. This review summarizes the progress towards the development of synthetic agents that disrupt the function of the SH2 domains in different proteins as well as the clinical relevance of targeting a specific SH2 domain. Since 1986, SH2 domains have been identified in over 110 human proteins, including kinases, transcription factors, and adaptor proteins. A number of these proteins are over-activated in many diseases, including cancer, and their function is highly dependent on their SH2 domain. Thus, inhibition of a protein's function through disrupting that of its SH2 domain has emerged as a promising approach towards the development of novel therapeutic modalities. Although targeting the SH2 domain is a challenging task in molecular recognition, the progress reported here demonstrates the feasibility of such an approach.

Target salt 2025: a global overview of national programs to encourage the food industry to reduce salt in foods.

Science.gov (United States)

Webster, Jacqui; Trieu, Kathy; Dunford, Elizabeth; Hawkes, Corinna

2014-08-21

Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce salt. A systematic review of the literature was supplemented by key informant questionnaires to inform categorization of the initiatives. Fifty nine food industry salt reduction programs were identified. Thirty eight countries had targets for salt levels in foods and nine countries had introduced legislation for some products. South Africa and Argentina have both introduced legislation limiting salt levels across a broad range of foods. Seventeen countries reported reductions in salt levels in foods-the majority in bread. While these trends represent progress, many countries have yet to initiate work in this area, others are at early stages of implementation and further monitoring is required to assess progress towards achieving the global target.

Radar automatic target recognition (ATR) and non-cooperative target recognition (NCTR)

CERN Document Server

Blacknell, David

2013-01-01

The ability to detect and locate targets by day or night, over wide areas, regardless of weather conditions has long made radar a key sensor in many military and civil applications. However, the ability to automatically and reliably distinguish different targets represents a difficult challenge. Radar Automatic Target Recognition (ATR) and Non-Cooperative Target Recognition (NCTR) captures material presented in the NATO SET-172 lecture series to provide an overview of the state-of-the-art and continuing challenges of radar target recognition. Topics covered include the problem as applied to th

Hydrogen storage - are we making progress?

International Nuclear Information System (INIS)

Blair, L.; Milliken, J.; Satyapal, S.

2004-01-01

'Full text:' The efficient storage of hydrogen in compact, lightweight systems that allow greater than 300-mile range has been identified as one of the major technical challenges facing the practical commercialization of fuel cell power systems for light-duty vehicles. Following the hydrogen vision announced by President Bush in his 2003 State of the Union address, the U.S. Department of Energy issued a Grand Challenge, soliciting ideas from universities, national laboratories, and industry. DOE's National Hydrogen Storage Project, an aggressive and innovative research program focused on materials R and D, will be launched in Fiscal Year 2005. An intensive effort is also underway in the private sector, both in the U.S. and abroad, to meet the challenging on-board hydrogen storage requirements. A historical perspective of hydrogen storage research and development will be provided and the current DOE technical targets for hydrogen storage systems will be discussed. The state-of-the-art in hydrogen storage will be summarized and recent progress assessed. Finally future research directions and areas of technical emphasis will be described. (author)

Development of annular targets for 99Mo production

International Nuclear Information System (INIS)

Conner, C.; Lewandowski, E.F.; Snelgrove, J.L.; Liberatore, M.W.; Walker, D.E.; Wiencek, T.C.; McGann, D.J.; Hofman, G.L.; Vandegrift, G.F.

1999-01-01

During 1999, significant progress was made in the development of a low-enriched uranium (LEU) target for production of 99 Mo. Successful conversion requires an inexpensive, reliable target. To keep the target geometry the same when changing from high-enriched uranium (HEU) to LEU targets, a denser form of uranium is required in order to increase the amount of uranium per target by a factor of approximately five. Targets containing LEU in the form of a metal foil are being developed for producing 99 Mo from the fissioning of 235 U. A new annular target was developed this year, and seven targets were irradiated in the Indonesian RSG-GAS reactor. Results of development of this annular target and its performance during irradiation are described. (author)

Financial Burden of Cancer Care | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Fungicides transport in runoff from vineyard plot and catchment: contribution of non-target areas.

Science.gov (United States)

Lefrancq, Marie; Payraudeau, Sylvain; García Verdú, Antonio Joaquín; Maillard, Elodie; Millet, Maurice; Imfeld, Gwenaël

2014-04-01

Surface runoff and erosion during the course of rainfall events are major processes of pesticides transport from agricultural land to aquatic ecosystem. These processes are generally evaluated either at the plot or the catchment scale. Here, we compared at both scales the transport and partitioning in runoff water of two widely used fungicides, i.e., kresoxim-methyl (KM) and cyazofamid (CY). The objective was to evaluate the relationship between fungicides runoff from the plot and from the vineyard catchment. The results show that seasonal exports for KM and CY at the catchment were larger than those obtained at the plot. This underlines that non-target areas within the catchment largely contribute to the overall load of runoff-associated fungicides. Estimations show that 85 and 62 % of the loads observed for KM and CY at the catchment outlet cannot be explained by the vineyard plots. However, the partitioning of KM and CY between three fractions, i.e., the suspended solids (>0.7 μm) and two dissolved fractions (i.e., between 0.22 and 0.7 µm and plot scales enable to evaluate the sources areas of pesticide off-site transport.

Biomedical research with cyclotron produced radionuclides. Progress report, February 1, 1981-December 31, 1981

International Nuclear Information System (INIS)

Laughlin, J.S.

1981-09-01

Progress is reported in the following areas: evaluation of chemotherapeutic regimens in solid tumors using 13 N-labelled amino acids; organ imaging with 13 N-labelled L-amino acids; imaging with 111 In-labelled-autologous platelets; synthesis and biological studies of 111 In-labelled ammonia and L-amino acids; synthesis and evaluation for pancreatic imaging of 11 C-labelled amino acides; radioisotope monitoring of myocardiol function; synthesis of 11 C-labelled precursor compounds; reduction of radiation exposure through automation and remote control; development of an anhydrous 18 F target; evaluation of radiolabelled 5-fluorouracils for scintigraphy; and methods of data analysis, modeling, and unproving instrumentation for positron-emission tomography

Progression of Stargardt Disease as Determined by Fundus Autofluorescence in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 9).

Science.gov (United States)

Strauss, Rupert W; Muñoz, Beatriz; Ho, Alexander; Jha, Anamika; Michaelides, Michel; Cideciyan, Artur V; Audo, Isabelle; Birch, David G; Hariri, Amir H; Nittala, Muneeswar G; Sadda, SriniVas; West, Sheila; Scholl, Hendrik P N

2017-11-01

Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease. To describe the yearly progression rate of atrophic lesions in the retrospective Progression of Stargardt Disease study. A multicenter retrospective cohort study was conducted at tertiary referral centers in the United States and Europe. A total of 251 patients aged 6 years or older at baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 centers between August 2, 2013, and December 12, 2014; of these patients, 215 had at least 2 gradable fundus autofluorescence images with atrophic lesion(s) present in at least 1 eye. Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence were quantified by a reading center. Progression rates were estimated from linear mixed models with time as the independent variable. Yearly rate of progression using the growth of atrophic lesions measured by fundus autofluorescence. A total of 251 participants (458 study eyes) were enrolled. Images from 386 eyes of 215 participants (126 females and 89 males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9 [13.3] years) showed atrophic lesions present on at least 2 visits and were graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224 eyes (123 female participants and 101 male participants; mean [SD] age, 33.0 [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were included in the estimation of the progression of the area of DDAF. At the first visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2 (2.7) mm2. The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm2. Mean progression of DDAF was 0.51 mm2/y (95% CI, 0.42-0.61 mm2/y), and of total decreased fundus autofluorescence was 0.35 mm2/y (95% CI, 0.28-0.43 mm2/y). Rates of

Short-term changes in arterial inflammation predict long-term changes in atherosclerosis progression

Energy Technology Data Exchange (ETDEWEB)

Joseph, Philip [Massachusetts General Hospital and Harvard Medical School, Cardiology Division and Cardiac MR PET CT Program, Boston, MA (United States); McMaster University, Population Health Research Institute, Department of Medicine, and Department of Radiology, Hamilton, ON (Canada); Ishai, Amorina; Tawakol, Ahmed [Massachusetts General Hospital and Harvard Medical School, Cardiology Division and Cardiac MR PET CT Program, Boston, MA (United States); Mani, Venkatesh [Icahn School of Medicine at Mount Sinai School of Medicine, Translational and Molecular Imaging Institute and Department of Radiology, New York, NY (United States); Kallend, David [The Medicines Company, Parsippany, NJ (United States); Rudd, James H.F. [University of Cambridge, Division of Cardiovascular Medicine, Cambridge (United Kingdom); Fayad, Zahi A. [Icahn School of Medicine at Mount Sinai School of Medicine, Translational and Molecular Imaging Institute and Department of Radiology, New York, NY (United States); Icahn School of Medicine at Mount Sinai School of Medicine, Hess CSM Building Floor TMII, Rm S1-104, Translational and Molecular Imaging Institute and Department of Radiology, New York, NY (United States)

2017-01-15

It remains unclear whether changes in arterial wall inflammation are associated with subsequent changes in the rate of structural progression of atherosclerosis. In this sub-study of the dal-PLAQUE clinical trial, multi-modal imaging was performed using 18-fludeoxyglucose (FDG) positron emission tomography (PET, at 0 and 6 months) and magnetic resonance imaging (MRI, at 0 and 24 months). The primary objective was to determine whether increasing FDG uptake at 6 months predicted atherosclerosis progression on MRI at 2 years. Arterial inflammation was measured by the carotid FDG target-to-background ratio (TBR), and atherosclerotic plaque progression was defined as the percentage change in carotid mean wall area (MWA) and mean wall thickness (MWT) on MRI between baseline and 24 months. A total of 42 participants were included in this sub-study. The mean age of the population was 62.5 years, and 12 (28.6 %) were women. In participants with (vs. without) any increase in arterial inflammation over 6 months, the long-term changes in both MWT (% change MWT: 17.49 % vs. 1.74 %, p = 0.038) and MWA (% change MWA: 25.50 % vs. 3.59 %, p = 0.027) were significantly greater. Results remained significant after adjusting for clinical and biochemical covariates. Individuals with no increase in arterial inflammation over 6 months had no significant structural progression of atherosclerosis over 24 months as measured by MWT (p = 0.616) or MWA (p = 0.373). Short-term changes in arterial inflammation are associated with long-term structural atherosclerosis progression. These data support the concept that therapies that reduce arterial inflammation may attenuate or halt progression of atherosclerosis. (orig.)

Short-term changes in arterial inflammation predict long-term changes in atherosclerosis progression

International Nuclear Information System (INIS)

Joseph, Philip; Ishai, Amorina; Tawakol, Ahmed; Mani, Venkatesh; Kallend, David; Rudd, James H.F.; Fayad, Zahi A.

2017-01-01

It remains unclear whether changes in arterial wall inflammation are associated with subsequent changes in the rate of structural progression of atherosclerosis. In this sub-study of the dal-PLAQUE clinical trial, multi-modal imaging was performed using 18-fludeoxyglucose (FDG) positron emission tomography (PET, at 0 and 6 months) and magnetic resonance imaging (MRI, at 0 and 24 months). The primary objective was to determine whether increasing FDG uptake at 6 months predicted atherosclerosis progression on MRI at 2 years. Arterial inflammation was measured by the carotid FDG target-to-background ratio (TBR), and atherosclerotic plaque progression was defined as the percentage change in carotid mean wall area (MWA) and mean wall thickness (MWT) on MRI between baseline and 24 months. A total of 42 participants were included in this sub-study. The mean age of the population was 62.5 years, and 12 (28.6 %) were women. In participants with (vs. without) any increase in arterial inflammation over 6 months, the long-term changes in both MWT (% change MWT: 17.49 % vs. 1.74 %, p = 0.038) and MWA (% change MWA: 25.50 % vs. 3.59 %, p = 0.027) were significantly greater. Results remained significant after adjusting for clinical and biochemical covariates. Individuals with no increase in arterial inflammation over 6 months had no significant structural progression of atherosclerosis over 24 months as measured by MWT (p = 0.616) or MWA (p = 0.373). Short-term changes in arterial inflammation are associated with long-term structural atherosclerosis progression. These data support the concept that therapies that reduce arterial inflammation may attenuate or halt progression of atherosclerosis. (orig.)

Progress in Establishment of Fission Mo Production Technology in Korea

International Nuclear Information System (INIS)

Lee, Jun Sig

2013-01-01

Research activities have been made in both the development of the fission Mo production process and the designing of the production facility that will be established at Kijang, Korea including a new research reactor in 2017. Progress in the process development for target preparation, target dissolution, Mo extraction, and purification has been made. It is also a great concern to minimize the radioactive wastes or at least to generate the wastes in readily treatable forms in the project. After series of cold experiments, the target dissolution and solution formulation for a column operation are optimized. Progress in the design of the production facility has been made. Two trains of hot cells including the waste storages have been proposed for the alternative operation of the facility. A radioisotope production facility is designed to locate next to the fission Mo production building to provide a simpler and easier handling pathway of the products

Evaluation of the geologic relations and seismotectonic stability of the Yucca Mountain area Nevada Nuclear Waste site investigation (NNWSI). Progress report, October 1, 1992--September 30, 1993

International Nuclear Information System (INIS)

1993-01-01

This report provides a summary of progress for the project open-quotes Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI).close quotes A similar report was previously provided for the period of 1 October 1991 to 30 September 1992. The report initially covers the activities of the General Task and is followed by sections that describe the progress of the other ongoing Tasks. This report summarizes the geologic and seismotectonic studies conducted at Yucca Mountain during the contract period including Quaternary tectonics, an evaluation of mineral resource potential of the area, caldera geology, and volcano-tectonic activity at and near the site. A report of basinal studies conducted during the contract period is also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database

Evaluation of the geologic relations and seismotectonic stability of the Yucca Mountain area Nevada Nuclear Waste site investigation (NNWSI). Progress report, October 1, 1992--September 30, 1993

Energy Technology Data Exchange (ETDEWEB)

NONE

1993-09-30

This report provides a summary of progress for the project {open_quotes}Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI).{close_quotes} A similar report was previously provided for the period of 1 October 1991 to 30 September 1992. The report initially covers the activities of the General Task and is followed by sections that describe the progress of the other ongoing Tasks. This report summarizes the geologic and seismotectonic studies conducted at Yucca Mountain during the contract period including Quaternary tectonics, an evaluation of mineral resource potential of the area, caldera geology, and volcano-tectonic activity at and near the site. A report of basinal studies conducted during the contract period is also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

Progress Report Phase I: Use, access, and fire/fuels management attitudes and preferences of user groups concerning the Valles Caldera National Preserve (VCNP) and adjacent areas

Science.gov (United States)

Kurt F. Anschuetz; Carol B. Raish

2010-01-01

This document represents a progress report of activities completed during Phase I of the study titled, Use, Access, and Fire/Fuels Management Attitudes and Preferences of User Groups Concerning the Valles Caldera National Preserve (VCNP) and Adjacent Areas, and the preliminary findings of this work.

Tracking Progress in Carbon Capture and Storage

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-09-06

At the second Clean Energy Ministerial in Abu Dhabi, April 2011 (CEM 2), the Carbon Capture, Use and Storage Action Group (CCUS AG) presented seven substantive recommendations to Energy Ministers on concrete, near-term actions to accelerate global carbon capture and storage (CCS) deployment. Twelve CCUS AG governments agreed to advance progress against the 2011 recommendations by the third Clean Energy Ministerial (London, 25-26 April 2012) (CEM 3). Following CEM 2, the CCUS AG requested the IEA and the Global CCS Institute to report on progress made against the 2011 recommendations at CEM 3. Tracking Progress in Carbon Capture and Storage: International Energy Agency/Global CCS Institute report to the third Clean Energy Ministerial responds to that request. The report considers a number of key questions. Taken as a whole, what advancements have committed CCUS AG governments made against the 2011 recommendations since CEM 2? How can Energy Ministers continue to drive progress to enable CCS to fully contribute to climate change mitigation? While urgent further action is required in all areas, are there particular areas that are currently receiving less policy attention than others, where efforts could be redoubled? The report concludes that, despite developments in some areas, significant further work is required. CCS financing and industrial applications continue to represent a particularly serious challenge.

[Research progress on ebola virus glycoprotein].

Science.gov (United States)

Ding, Guo-Yong; Wang, Zhi-Yu; Gao, Lu; Jiang, Bao-Fa

2013-03-01

Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans and there are no effective therapeutic or prophylactic treatments available. The glycoprotein (GP) of EBOV is a transmembrane envelope protein known to play multiple functions including virus attachment and entry, cell rounding and cytotoxicity, down-regulation of host surface proteins, and enhancement of virus assembly and budding. GP is the primary target of protective immunity and the key target for developing neutralizing antibodies. In this paper, the research progress on genetic structure, pathogenesis and immunogenicity of EBOV GP in the last 5 years is reviewed.

Using the Malcolm Baldrige "are we making progress" survey for organizational self-assessment and performance improvement.

Science.gov (United States)

Shields, Judith A; Jennings, Jerry L

2013-01-01

A national healthcare company applied the Malcolm Baldrige Criteria for Performance Excellence and its "Are We Making Progress?" survey as an annual organizational self-assessment to identify areas for improvement. For 6 years, Liberty Healthcare Corporation reviewed the survey results on an annual basis to analyze positive and negative trends, monitor company progress toward targeted goals and develop new initiatives to address emerging areas for improvement. As such, the survey provided a simple and inexpensive methodology to gain useful information from employees at all levels and from multiple service sites and business sectors. In particular, it provided a valuable framework for assessing and improving the employees' commitment to the company's mission and values, high standards and ethics, quality of work, and customer satisfaction. The methodology also helped the company to incorporate the philosophy and principles of continuous quality improvement in a unified fashion. Corporate and local leadership used the same measure to evaluate the performance of individual programs relative to each other, to the company as a whole, and to the "best practices" standard of highly successful companies that received the Malcolm Baldrige National Quality Award. © 2012 National Association for Healthcare Quality.

Graphite targets at LAMPF

International Nuclear Information System (INIS)

Brown, R.D.; Grisham, D.L.

1983-01-01

Rotating polycrystalline and stationary pyrolytic graphite target designs for the LAMPF experimental area are described. Examples of finite element calculations of temperatures and stresses are presented. Some results of a metallographic investigation of irradiated pyrolytic graphite target plates are included, together with a brief description of high temperature bearings for the rotating targets

Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment

Science.gov (United States)

Willis, Rudolph E.

2016-01-01

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis. PMID:27649156

Taking stock of Myanmar's progress toward the health-related Millennium Development Goals: current roadblocks, paths ahead.

Science.gov (United States)

Saw, Yu Mon; Win, Khine Lae; Shiao, Laura Wen-Shuan; Thandar, Moe Moe; Amiya, Rachel M; Shibanuma, Akira; Tun, Soe; Jimba, Masamine

2013-09-11

Myanmar is a developing country with considerable humanitarian needs, rendering its pursuit of the Millennium Development Goals (MDGs) an especially high priority. Yet progress to date remains under-examined on key fronts. Particularly within the three health-related MDGs (MDGs 4, 5, and 6), the limited data reported point to patchy levels of achievement. This study was undertaken to provide an overview and assessment of Myanmar's progress toward the health-related MDGs, along with possible solutions for accelerating health-related development into 2015 and beyond. The review highlights off-track progress in the spheres of maternal and child health (MDGs 4 and 5). It also shows Myanmar's achievements toward MDG 6 targets--in the areas of HIV/AIDS, malaria, and tuberculosis. Such achievements are especially notable in that Myanmar has been receiving the lowest level of official development assistance among all of the least developed countries in Asia. However, to make similar progress in MDGs 4 and 5, Myanmar needs increased investment and commitment in health. Toward moving forward with the post-2015 development agenda, Myanmar's government also needs to take the lead in calling for attention from the World Health Organization and its global development partners to address the stagnation in health-related development progress within the country. In particular, Myanmar's government should invest greater efforts into health system strengthening to pave the road to universal health coverage.

Evaluation of Australian soup manufacturer compliance with national sodium reduction targets.

Science.gov (United States)

Levi, Rebecca; Probst, Yasmine; Crino, Michelle; Dunford, Elizabeth

2018-04-01

Packaged foods dominate Australia's food supply and are important contributors to nutrition-related disease. To help address this problem, the Food and Health Dialogue (FHD) was launched in 2009, setting voluntary sodium reduction targets for various categories of packaged foods. The aim of this study was to examine the food industry's progress and compliance with the FHD sodium reduction targets for soup products. Nutritional information was collected from product labels of all soup products available from four major Australian supermarkets annually between 2011 and 2014. Products were assigned to categories in line with those in the FHD. The proportion of soup products meeting sodium reduction targets was examined by (i) soup category; (ii) FHD participant status; and (iii) manufacturer. A 6% reduction in sodium levels in soups overall was found from 2011 to 2014 (P = 0.002). Significant reductions were observed for FHD participants (P < 0.05 for all) but not for non-participants. In 2014, 67% dry soups and 76% of wet soups met national sodium reduction targets. Despite the majority of soup products meeting the sodium reduction targets specified by the FHD, re-evaluation of the targets may be required to further reduce sodium levels in soups. Manufacturers participating in the FHD are likely to be driving sodium reductions in the Australian soup market, further highlighting the need for continued government leadership in this area to ensure all manufacturers are actively involved in the process. © 2017 Dietitians Association of Australia.

Improved Discriminability of Spatiotemporal Neural Patterns in Rat Motor Cortical Areas as Directional Choice Learning Progresses

Directory of Open Access Journals (Sweden)

Hongwei eMao

2015-03-01

Full Text Available Animals learn to choose a proper action among alternatives to improve their odds of success in food foraging and other activities critical for survival. Through trial-and-error, they learn correct associations between their choices and external stimuli. While a neural network that underlies such learning process has been identified at a high level, it is still unclear how individual neurons and a neural ensemble adapt as learning progresses. In this study, we monitored the activity of single units in the rat medial and lateral agranular (AGm and AGl, respectively areas as rats learned to make a left or right side lever press in response to a left or right side light cue. We noticed that rat movement parameters during the performance of the directional choice task quickly became stereotyped during the first 2-3 days or sessions. But learning the directional choice problem took weeks to occur. Accompanying rats’ behavioral performance adaptation, we observed neural modulation by directional choice in recorded single units. Our analysis shows that ensemble mean firing rates in the cue-on period did not change significantly as learning progressed, and the ensemble mean rate difference between left and right side choices did not show a clear trend of change either. However, the spatiotemporal firing patterns of the neural ensemble exhibited improved discriminability between the two directional choices through learning. These results suggest a spatiotemporal neural coding scheme in a motor cortical neural ensemble that may be responsible for and contributing to learning the directional choice task.

Limited-area short-range ensemble predictions targeted for heavy rain in Europe

Directory of Open Access Journals (Sweden)

K. Sattler

2005-01-01

Full Text Available Inherent uncertainties in short-range quantitative precipitation forecasts (QPF from the high-resolution, limited-area numerical weather prediction model DMI-HIRLAM (LAM are addressed using two different approaches to creating a small ensemble of LAM simulations, with focus on prediction of extreme rainfall events over European river basins. The first ensemble type is designed to represent uncertainty in the atmospheric state of the initial condition and at the lateral LAM boundaries. The global ensemble prediction system (EPS from ECMWF serves as host model to the LAM and provides the state perturbations, from which a small set of significant members is selected. The significance is estimated on the basis of accumulated precipitation over a target area of interest, which contains the river basin(s under consideration. The selected members provide the initial and boundary data for the ensemble integration in the LAM. A second ensemble approach tries to address a portion of the model-inherent uncertainty responsible for errors in the forecasted precipitation field by utilising different parameterisation schemes for condensation and convection in the LAM. Three periods around historical heavy rain events that caused or contributed to disastrous river flooding in Europe are used to study the performance of the LAM ensemble designs. The three cases exhibit different dynamic and synoptic characteristics and provide an indication of the ensemble qualities in different weather situations. Precipitation analyses from the Deutsche Wetterdienst (DWD are used as the verifying reference and a comparison of daily rainfall amounts is referred to the respective river basins of the historical cases.

The Research Progress of SiRNA Targeting Notch1 on Tumor Cells: A Mini Review of the State of the Art

Directory of Open Access Journals (Sweden)

Lanfen Huo

2016-09-01

Full Text Available Notch signaling is a highly conserved signaling pathway, playing an important role in a variety of cell differentiation, development and regulation. Notch signaling includes Notch1-4; Notch1 gene encodes Notch1 signaling that can shorten cell cycle, enhance cell proliferation, inhibit cell differentiation, and promote apoptosis. Mutation and overexpression of the Notch1 gene may induce tumorigenesis, which plays an important role in the development of tumors across a variety of signaling pathways. Currently, using RNA interference technology (RNAi synthesizing small interference RNA (siRNA targeting Notch1 gene（siNotch1）has become a hot topic, and clinical application of gene silencing has also obtained a certain therapeutic effect. In this paper, the application of Notch1 gene silencing in tumor progress was reviewed.

Shock ignition: a brief overview and progress in the design of robust targets

International Nuclear Information System (INIS)

Atzeni, S; Marocchino, A; Schiavi, A

2015-01-01

Shock ignition is a laser direct-drive inertial confinement fusion (ICF) scheme in which the stages of compression and hot spot formation are partly separated. The fuel is first imploded at a lower velocity than in conventional ICF, reducing the threats due to Rayleigh–Taylor instability. Close to stagnation, an intense laser spike drives a strong converging shock, which contributes to hot spot formation. This paper starts with a brief overview of the theoretical studies, target design and experimental results on shock ignition. The second part of the paper illustrates original work aiming at the design of robust targets and computation of the relevant gain curves. Following Chang et al (2010 Phys. Rev. Lett. 104 135002) a safety factor for high gain, ITF* (analogous to the ignition threshold factor ITF introduced by Clark et al (2008 Phys. Plasmas 15 056305)), is evaluated by means of parametric 1D simulations with artificially reduced reactivity. SI designs scaled as in Atzeni et al (2013 New J. Phys. 15 045004) are found to have nearly the same ITF*. For a given target, such ITF* increases with implosion velocity and laser spike power. A gain curve with a prescribed ITF* can then be simply generated by upscaling a reference target with that value of ITF*. An interesting option is scaling in size by reducing the implosion velocity to keep the ratio of implosion velocity to self-ignition velocity constant. At a given total laser energy, targets with higher ITF* are driven to higher implosion velocity and achieve a somewhat lower gain. However, a 1D gain higher than 100 is achieved at an (incident) energy below 1 MJ, an implosion velocity below 300 km s −1 and a peak incident power below 400 TW. 2D simulations of mispositioned targets show that targets with a higher ITF* indeed tolerate larger displacements. (paper)

Progress on LEU very high density fuel and target development in Argentina

International Nuclear Information System (INIS)

Balart, S.; Cabot, P.; Calzetta, O.; Duran, A.; Garces, J.; Hermida, J.D.; Manzini, A.; Pasqualini, E.; Taboada, H.

2006-01-01

Since last RRFM meeting, CNEA has continued on new LEU fuel and target development activities. Main goals are the plan to convert our RA-6 reactor from HEU to a new LEU core, to get a comprehensive understanding of U-Mo/Al compounds phase formation in dispersed and monolithic fuels, to develop possible solutions to VHD dispersed and monolithic fuels technical problems, to optimize techniques to recover U from silicide scrap samples as cold test for radiowaste separation for final conditioning of silicide spent fuels. and to improve the diffusion of LEU target and radiochemical technology for radioisotope production. Future plans include: - Completion of the RA-6 reactor conversion to LEU; - Improvement on fuel development and production facilities to implement new technologies, including NDT techniques to assess bonding quality; - Irradiation of miniplates and full scale fuel assembly at RA-3 and plans to perform irradiation on higher power and temperature regime reactors; - Optimization of LEU target and radiochemical techniques for radioisotope production. (author)

Minimizing scatter-losses during pre-heat for magneto-inertial fusion targets

Science.gov (United States)

Geissel, Matthias; Harvey-Thompson, Adam J.; Awe, Thomas J.; Bliss, David E.; Glinsky, Michael E.; Gomez, Matthew R.; Harding, Eric; Hansen, Stephanie B.; Jennings, Christopher; Kimmel, Mark W.; Knapp, Patrick; Lewis, Sean M.; Peterson, Kyle; Schollmeier, Marius; Schwarz, Jens; Shores, Jonathon E.; Slutz, Stephen A.; Sinars, Daniel B.; Smith, Ian C.; Speas, C. Shane; Vesey, Roger A.; Weis, Matthew R.; Porter, John L.

2018-02-01

The size, temporal and spatial shape, and energy content of a laser pulse for the pre-heat phase of magneto-inertial fusion affect the ability to penetrate the window of the laser-entrance-hole and to heat the fuel behind it. High laser intensities and dense targets are subject to laser-plasma-instabilities (LPI), which can lead to an effective loss of pre-heat energy or to pronounced heating of areas that should stay unexposed. While this problem has been the subject of many studies over the last decades, the investigated parameters were typically geared towards traditional laser driven Inertial Confinement Fusion (ICF) with densities either at 10% and above or at 1% and below the laser's critical density, electron temperatures of 3-5 keV, and laser powers near (or in excess of) 1 × 1015 W/cm2. In contrast, Magnetized Liner Inertial Fusion (MagLIF) [Slutz et al., Phys. Plasmas 17, 056303 (2010) and Slutz and Vesey, Phys. Rev. Lett. 108, 025003 (2012)] currently operates at 5% of the laser's critical density using much thicker windows (1.5-3.5 μm) than the sub-micron thick windows of traditional ICF hohlraum targets. This article describes the Pecos target area at Sandia National Laboratories using the Z-Beamlet Laser Facility [Rambo et al., Appl. Opt. 44(12), 2421 (2005)] as a platform to study laser induced pre-heat for magneto-inertial fusion targets, and the related progress for Sandia's MagLIF program. Forward and backward scattered light were measured and minimized at larger spatial scales with lower densities, temperatures, and powers compared to LPI studies available in literature.

Land substitution effects of biofuel side products and implications on the land area requirement for EU 2020 biofuel targets

International Nuclear Information System (INIS)

Ozdemir, Enver Doruk; Haerdtlein, Marlies; Eltrop, Ludger

2009-01-01

The provision of biofuels today is based on energy crops rather than residual biomass, which results in the requirement of agricultural land area. The side products may serve as animal feed and thus prevent cultivation of other feedstock and the use of corresponding land area. These effects of biofuel provision have to be taken into account for a comprising assessment of land area requirement for biofuel provision. Between 18.5 and 21.1 Mio. hectares (ha) of land area is needed to meet the EU 2020 biofuel target depending on the biofuel portfolio when substitution effects are neglected. The utilization of the bioethanol side products distiller's dried grain and solubles (DDGS) and pressed beet slices may save up to 0.7 Mio. ha of maize cultivation area in the EU. The substitution effect due to the utilization of biodiesel side products (oil cakes of rape, palm and soy) as animal feed may account for up to 7.1 Mio. ha of soy cultivation area in Brazil. The results show that the substitution of land area due to use of side products might ease the pressures on land area requirement considerably and should therefore not be neglected in assessing the impacts of biofuel provision worldwide.

Transforming a low value coastal area into a high value natural and recreational area

NARCIS (Netherlands)

Ritzen, M.J.

2004-01-01

The coastal zone in the Netherlands takes a very peculiar place in the discussion about sustainability in the Netherlands. Large areas are left unused and they remain low cost value areas due to the lack of progressive decision-making. These areas have a low value in economic, recreational and

Neonatal tetanus elimination in Pakistan: progress and challenges.

Science.gov (United States)

Lambo, Jonathan A; Nagulesapillai, Tharsiya

2012-12-01

Pakistan is one of the 34 countries that have not achieved the neonatal tetanus (NT) global elimination target set by the World Health Organization (WHO). NT, caused by Clostridium tetani, is a highly fatal infection of the neonatal period. It is one of the most underreported diseases and remains a major but preventable cause of neonatal and infant mortality in many developing countries. In 1989, the World Health Assembly called for the elimination of NT by 1995, and since then considerable progress has been made using the following strategies: clean delivery practices, routine tetanus toxoid (TT) immunization of pregnant women, and immunization of all women of childbearing age with three doses of TT vaccine in high-risk areas during supplementary immunization campaigns. This review presents the activities, progress, and challenges in achieving NT elimination in Pakistan. A review of the literature found TT vaccination coverage in Pakistan ranged from 60% to 74% over the last decade. Low vaccination coverage, the main driver for NT in Pakistan, is due to many factors, including demand failure for TT vaccine resulting from inadequate knowledge of TT vaccine among reproductive age females and inadequate information about the benefits of TT provided by health care workers and the media. Other factors linked to low vaccination coverage include residing in rural areas, lack of formal education, poor knowledge about place and time to get vaccinated, and lack of awareness about the importance of vaccination. A disparity exists in TT vaccination coverage and antenatal care between urban and rural areas due to access and utilization of health care services. NT reporting is incomplete, as cases from the private sector and rural areas are underreported. To successfully eliminate NT, women of reproductive age must be made aware of the benefits of TT vaccine, not only to themselves, but also to their families. Effective communication strategies for TT vaccine delivery and

Measuring impact of protected area management interventions: current and future use of the Global Database of Protected Area Management Effectiveness.

Science.gov (United States)

Coad, Lauren; Leverington, Fiona; Knights, Kathryn; Geldmann, Jonas; Eassom, April; Kapos, Valerie; Kingston, Naomi; de Lima, Marcelo; Zamora, Camilo; Cuardros, Ivon; Nolte, Christoph; Burgess, Neil D; Hockings, Marc

2015-11-05

Protected areas (PAs) are at the forefront of conservation efforts, and yet despite considerable progress towards the global target of having 17% of the world's land area within protected areas by 2020, biodiversity continues to decline. The discrepancy between increasing PA coverage and negative biodiversity trends has resulted in renewed efforts to enhance PA effectiveness. The global conservation community has conducted thousands of assessments of protected area management effectiveness (PAME), and interest in the use of these data to help measure the conservation impact of PA management interventions is high. Here, we summarize the status of PAME assessment, review the published evidence for a link between PAME assessment results and the conservation impacts of PAs, and discuss the limitations and future use of PAME data in measuring the impact of PA management interventions on conservation outcomes. We conclude that PAME data, while designed as a tool for local adaptive management, may also help to provide insights into the impact of PA management interventions from the local-to-global scale. However, the subjective and ordinal characteristics of the data present significant limitations for their application in rigorous scientific impact evaluations, a problem that should be recognized and mitigated where possible. © 2015 The Authors.

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.

A fuzzy logic expert system for evaluating policy progress towards sustainability goals.

Science.gov (United States)

Cisneros-Montemayor, Andrés M; Singh, Gerald G; Cheung, William W L

2017-12-16

Evaluating progress towards environmental sustainability goals can be difficult due to a lack of measurable benchmarks and insufficient or uncertain data. Marine settings are particularly challenging, as stakeholders and objectives tend to be less well defined and ecosystem components have high natural variability and are difficult to observe directly. Fuzzy logic expert systems are useful analytical frameworks to evaluate such systems, and we develop such a model here to formally evaluate progress towards sustainability targets based on diverse sets of indicators. Evaluation criteria include recent (since policy enactment) and historical (from earliest known state) change, type of indicators (state, benefit, pressure, response), time span and spatial scope, and the suitability of an indicator in reflecting progress toward a specific objective. A key aspect of the framework is that all assumptions are transparent and modifiable to fit different social and ecological contexts. We test the method by evaluating progress towards four Aichi Biodiversity Targets in Canadian oceans, including quantitative progress scores, information gaps, and the sensitivity of results to model and data assumptions. For Canadian marine systems, national protection plans and biodiversity awareness show good progress, but species and ecosystem states overall do not show strong improvement. Well-defined goals are vital for successful policy implementation, as ambiguity allows for conflicting potential indicators, which in natural systems increases uncertainty in progress evaluations. Importantly, our framework can be easily adapted to assess progress towards policy goals with different themes, globally or in specific regions.

The rationale for targeting the LOX family in cancer

DEFF Research Database (Denmark)

Barker, Holly E; Cox, Thomas R; Erler, Janine T

2012-01-01

The therapeutic targeting of extracellular proteins is becoming hugely attractive in light of evidence implicating the tumour microenvironment as pivotal in all aspects of tumour initiation and progression. Members of the lysyl oxidase (LOX) family of proteins are secreted by tumours and are the ......The therapeutic targeting of extracellular proteins is becoming hugely attractive in light of evidence implicating the tumour microenvironment as pivotal in all aspects of tumour initiation and progression. Members of the lysyl oxidase (LOX) family of proteins are secreted by tumours...... and are the subject of much effort to understand their roles in cancer. In this Review we discuss the roles of members of this family in the remodelling of the tumour microenvironment and their paradoxical roles in tumorigenesis and metastasis. We also discuss how targeting this family of proteins might lead to a new...... avenue of cancer therapeutics....

Exploration of the medical periodic table: towards new targets.

Science.gov (United States)

Barry, Nicolas P E; Sadler, Peter J

2013-06-07

Metallodrugs offer potential for unique mechanisms of drug action based on the choice of the metal, its oxidation state, the types and number of coordinated ligands and the coordination geometry. We discuss recent progress in identifying new target sites and elucidating the mechanisms of action of anti-cancer, anti-bacterial, anti-viral, anti-parasitic, anti-inflammatory, and anti-neurodegenerative agents, as well as in the design of metal-based diagnostic agents. Progress in identifying and defining target sites has been accelerated recently by advances in proteomics, genomics and metal speciation analysis. Examples of metal compounds and chelating agents (enzyme inhibitors) currently in clinical use, clinical trials or preclinical development are highlighted.

Microtubule affinity-regulating kinases are potential druggable targets for Alzheimer's disease.

Science.gov (United States)

Annadurai, Narendran; Agrawal, Khushboo; Džubák, Petr; Hajdúch, Marián; Das, Viswanath

2017-11-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects normal functions of the brain. Currently, AD is one of the leading causes of death in developed countries and the only one of the top ten diseases without a means to prevent, cure, or significantly slow down its progression. Therefore, newer therapeutic concepts are urgently needed to improve survival and the quality of life of AD patients. Microtubule affinity-regulating kinases (MARKs) regulate tau-microtubule binding and play a crucial role in neurons. However, their role in hyperphosphorylation of tau makes them potential druggable target for AD therapy. Despite the relevance of MARKs in AD pathogenesis, only a few small molecules are known to have anti-MARK activity and not much has been done to progress these compounds into therapeutic candidates. But given the diverse role of MARKs, the specificity of novel inhibitors is imperative for their successful translation from bench to bedside. In this regard, a recent co-crystal structure of MARK4 in association with a pyrazolopyrimidine-based inhibitor offers a potential scaffold for the development of more specific MARK inhibitors. In this manuscript, we review the biological role of MARKs in health and disease, and draw attention to the largely unexplored area of MARK inhibitors for AD.

MiR-155 modulates the progression of neuropathic pain through targeting SGK3.

Science.gov (United States)

Liu, Shaoxing; Zhu, Bo; Sun, Yan; Xie, Xianfeng

2015-01-01

This study aimed to illustrate the potential effects of miR-155 in neuropathic pain and its potential mechanism. Spragure-Dawley (SD) rats were used for neuropathic pain model of bilateral chronic constriction injury (bCCI) construction. Effects of miR-155 expression on pain threshold of mechanical stimuli (MWT), paw withdrawal threshold latency (PMTL) and cold threshold were analyzed. Target for miR-155 was analyzed using bioinformatics methods. Moreover, effects of miR-155 target gene expression on pain thresholds were also assessed. Compared with the controls and sham group, miR-155 was overexpressed in neuropathic pain rats (P<0.05), but miR-155 slicing could significantly decreased the pain thresholds (P<0.05). Serum and glucocorticoid regulated protein kinase 3 (SGK3) was predicted as the target gene for miR-155, and miR-155 expression was negatively correlated to SGK3 expression. Furthermore, SGK3 overexpression could significantly decreased the pain thresholds which was the same as miR-155 (P<0.05). Moreover, miR-155 slicing and SGK3 overexpression could significantly decrease the painthreshold. The data presented in this study suggested that miR-155 slicing could excellently alleviate neuropathic pain in rats through targeting SGK3 expression. miR-155 may be a potential therapeutic target for neuropathic pain treatment.

Molecular targeted therapy for advanced gastric cancer.

Science.gov (United States)

Kim, Jong Gwang

2013-03-01

Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.

Low Impact Development for Industrial Areas

Science.gov (United States)

2015-07-01

copper gutters can also be significant sources of metal pollutants. Other studies indicate that vehicle disc brake pads and car tires can be a...industrial areas to develop the performance criteria for LID systems that specifically targeted these areas. Areas targeted include scrap metal recycling

Geothermal progress monitor. Progress report No. 3, March-April 1980

Energy Technology Data Exchange (ETDEWEB)

1980-01-01

Progress is reviewed in the following areas: electric uses; direct heat uses; drilling activities; exploration; leases; outreach and technical assistance; feasibility studies and application demonstrations; geothermal loan guarantee program; general activities; R and D activities; legal, institutional, and regulatory activities; environmental activities; and state, local, and private sector activities. Also included are a list of reports and publications and a directory of individuals in the geothermal community. (MHR)

Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area.

Directory of Open Access Journals (Sweden)

Alvaro eGarcía-Aviles

2015-03-01

Full Text Available Methylphenidate (MPD is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD. Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if methylphenidate administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered methylphenidate doses (1.3; 2.7 and 5mg/Kg to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3mg/Kg methylphenidate; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum, an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the medial septum the sparse tyrosine hydroxylase fibres did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons.

Phyllodes tumors with and without fibroadenoma-like areas display distinct genomic features and may evolve through distinct pathways.

Science.gov (United States)

Pareja, Fresia; Geyer, Felipe C; Kumar, Rahul; Selenica, Pier; Piscuoglio, Salvatore; Ng, Charlotte K Y; Burke, Kathleen A; Edelweiss, Marcia; Murray, Melissa P; Brogi, Edi; Weigelt, Britta; Reis-Filho, Jorge S

2017-01-01

Breast fibroepithelial lesions (fibroadenomas and phyllodes tumors) are underpinned by recurrent MED12 exon 2 mutations, which are more common in fibroadenomas and benign phyllodes tumors. TERT promoter hotspot mutations have been documented in phyllodes tumors, and found to be more frequent in borderline and malignant lesions. Several lines of evidence suggest that a subset of phyllodes tumors might arise from fibroadenomas. Here we sought to investigate the genetic differences between phyllodes tumors with fibroadenoma-like areas vs. those without. We retrieved data for 16 borderline/ malignant phyllodes tumors, including seven phyllodes tumors with fibroadenoma-like areas and nine phyllodes tumors without fibroadenoma-like areas, which had been previously subjected to targeted capture massively parallel sequencing. Whilst MED12 exon 2 mutations were significantly more frequent in tumors with fibroadenoma-like areas (71 vs. 11%), an enrichment in genetic alterations targeting bona fide cancer genes was found in those without fibroadenoma-like areas, in particular in EGFR mutations and amplifications (78 vs. 14%). No significant difference in the frequency of TERT genetic alterations was observed (71% in cases with fibroadenoma-like areas vs 56% in those without fibroadenoma-like areas). Our data suggest that the development of phyllodes tumors might follow two different evolutionary pathways: a MED12 -mutant pathway that involves the progression from a fibroadenoma to a malignant phyllodes tumor; and a MED12 -wild-type pathway, where malignant phyllodes tumors arise de novo through the acquisition of genetic alterations targeting cancer genes. Additional studies are warranted to confirm our observations and define whether the outcome differs between both pathways.

Prismatic displacement effect of progressive multifocal glasses on reaction time and accuracy in elderly people

Directory of Open Access Journals (Sweden)

Ellison AC

2014-05-01

Full Text Available Ashton C Ellison, A John Campbell, M Clare Robertson, Gordon F SandersonDunedin School of Medicine, Department of Medicine, Dunedin, New ZealandBackground: Multifocal glasses (bifocals, trifocals, and progressives increase the risk of falling in elderly people, but how they do so is unclear. To explain why glasses with progressive addition lenses increase the risk of falls and whether this can be attributed to false projection, this study aimed to 1 map the prismatic displacement of a progressive lens, and 2 test whether this displacement impaired reaction time and accuracy.Methods: The reaction times of healthy ≥75-year-olds (31 participants were measured when grasping for a bar and touching a black line. Participants performed each test twice, wearing their progressives and new, matched single vision (distance glasses in random order. The line and bar targets were positioned according to the maximum and minimum prismatic displacement effect through the progressive lens, mapped using a focimeter.Results: Progressive spectacle lenses have large areas of prismatic displacement in the central visual axis and edges. Reaction time was faster for progressives compared with single vision glasses with a centrally-placed horizontal grab bar (mean difference 101 ms, P=0.011 [repeated measures analysis] and a horizontal black line placed 300 mm below center (mean difference 80 ms, P=0.007. There was no difference in accuracy between the two types of glasses.Conclusion: Older people appear to adapt to the false projection of progressives in the central visual axis. This adaptation means that swapping to new glasses or a large change in prescription may lead to a fall. Frequently updating glasses may be more beneficial.Keywords: fall prevention, false projection, stored visual spatial information

Radioactive target and source development at Argonne National Laboratory

International Nuclear Information System (INIS)

Greene, J.P.; Ahmad, I.; Thomas, G.E.

1992-01-01

An increased demand for low-level radioactive targets has created the need for a laboratory dedicated to the production of these foils. A description is given of the radioactive target produced as well as source development work being performed at the Physics Division target facility of Argonne National Laboratory (ANL). Highlights include equipment used and the techniques employed. In addition, some examples of recent source preparation are given as well as work currently in progress

Research progress in role of iron overload in non-alcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

LI Guangming

2013-12-01

Full Text Available Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD. The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iron overload and lipid metabolism, and relationship between type of iron deposition and liver damage; the significance of iron overload in the diagnosis and treatment of NAFLD is discussed from iron overload as a new marker of risk stratification and potential therapeutic target in NAFLD. It is currently considered that iron overload, whether the cause or result of NAFLD progression, will promote the progression of NAFLD once it occurs; as a new marker of risk stratification and potential therapeutic target in NAFLD, iron load is worthy of further study.

Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.

Science.gov (United States)

Pu, Wei-Ling; Sun, Li-Kang; Gao, Xiu-Mei; Rüegg, Curzio; Cuendet, Muriel; Hottiger, Micheal O; Zhou, Kun; Miao, Lin; Zhang, Yun-Sha; Gebauer, Margaret

2017-10-01

Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.

Target support for inertial confinement fusion

International Nuclear Information System (INIS)

Schultz, K.R.

1995-08-01

General Atomics (GA) plays an important industrial support role for the US Inertial Confinement Fusion (ICF) program in the area of target technology. This includes three major activities: target fabrication support, target handling systems development, and target chamber design. The work includes target fabrication for existing ICF experiments, target and target system development for future experiments, and target research and target chamber design for experiments on future machines, such as the National Ignition Facility (NIF)

Medicaid Coverage of Tobacco Dependency Treatments | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

UV Exposure and Sun Protective Practices | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Smoke-free Workplace Rules and Laws | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Cryogenic polarized-target facility. Progress report, July 1, 1981-June 30, 1982

International Nuclear Information System (INIS)

Gould, C.R.; Haase, D.G.

1982-01-01

The goal of this three-year research project is to build a cryogenically polarized target facility for measuring total neutron cross sections for polarized neutrons incident on polarized nuclei. The components of the system have been assembled at TUNL during the current contract period. These include the dilution-refrigerator support assembly, the dilution-refrigerator itself, the dewar, the beam line, the shielding cave for the neutron source, and the neutron-detector shield and rolling-cart assembly. The dilution refrigerator is presently undergoing testing at liquid-nitrogen and liquid-helium temperatures. Experiments with aluminum and copper targets are scheduled for the coming contract period

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

Science.gov (United States)

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

2017-08-18

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

The "Conveyor Belt Effect": A Re-Assessment of the Impact of National Targets for Lifelong Learning.

Science.gov (United States)

Gorard, Stephen; Selwyn, Neil; Rees, Gareth

Although the National Targets for Education and Training in England and Wales include indicators for lifelong learning, and the progress towards the targets set for these indicators has been lauded by politicians and other observers, much of this apparent progress is actually accounted for by changes in these same indicators. However, once the…

Using the Nova target chamber for high-yield targets

International Nuclear Information System (INIS)

Pitts, J.H.

1987-01-01

The existing 2.2-m-radius Nova aluminum target chamber, coated and lined with boron-seeded carbon shields, is proposed for use with 1000-MJ-yield targets in the next laser facility. The laser beam and diagnostic holes in the target chamber are left open and the desired 10 -2 Torr vacuum is maintained both inside and outside the target chamber; a larger target chamber room is the vacuum barrier to the atmosphere. The hole area available is three times that necessary to maintain a maximum fluence below 12 J/cm 2 on optics placed at a radius of 10 m. Maximum stress in the target chamber wall is 73 MPa, which complies with the intent of the ASME Pressure Vessel Code. However, shock waves passing through the inner carbon shield could cause it to comminute. We propose tests and analyses to ensure that the inner carbon shield survives the environment. 13 refs

Targeting Alternative Sites on the Androgen Receptor to Treat Castration-Resistant Prostate Cancer

Directory of Open Access Journals (Sweden)

Paul S. Rennie

2013-06-01

Full Text Available Recurrent, metastatic prostate cancer continues to be a leading cause of cancer-death in men. The androgen receptor (AR is a modular, ligand-inducible transcription factor that regulates the expression of genes that can drive the progression of this disease, and as a consequence, this receptor is a key therapeutic target for controlling prostate cancer. The current drugs designed to directly inhibit the AR are called anti-androgens, and all act by competing with androgens for binding to the androgen/ligand binding site. Unfortunately, with the inevitable progression of the cancer to castration resistance, many of these drugs become ineffective. However, there are numerous other regulatory sites on this protein that have not been exploited therapeutically. The regulation of AR activity involves a cascade of complex interactions with numerous chaperones, co-factors and co-regulatory proteins, leading ultimately to direct binding of AR dimers to specific DNA androgen response elements within the promoter and enhancers of androgen-regulated genes. As part of the family of nuclear receptors, the AR is organized into modular structural and functional domains with specialized roles in facilitating their inter-molecular interactions. These regions of the AR present attractive, yet largely unexploited, drug target sites for reducing or eliminating androgen signaling in prostate cancers. The design of small molecule inhibitors targeting these specific AR domains is only now being realized and is the culmination of decades of work, including crystallographic and biochemistry approaches to map the shape and accessibility of the AR surfaces and cavities. Here, we review the structure of the AR protein and describe recent advancements in inhibiting its activity with small molecules specifically designed to target areas distinct from the receptor’s androgen binding site. It is anticipated that these new classes of anti-AR drugs will provide an additional

Biomedical research with cyclotron produced radionuclides. Progress report, February 1, 1981-December 31, 1981

Energy Technology Data Exchange (ETDEWEB)

Laughlin, J.S.

1981-09-01

Progress is reported in the following areas: evaluation of chemotherapeutic regimens in solid tumors using /sup 13/N-labelled amino acids; organ imaging with /sup 13/N-labelled L-amino acids; imaging with /sup 111/In-labelled-autologous platelets; synthesis and biological studies of /sup 111/In-labelled ammonia and L-amino acids; synthesis and evaluation for pancreatic imaging of /sup 11/C-labelled amino acides; radioisotope monitoring of myocardiol function; synthesis of /sup 11/C-labelled precursor compounds; reduction of radiation exposure through automation and remote control; development of an anhydrous /sup 18/F target; evaluation of radiolabelled 5-fluorouracils for scintigraphy; and methods of data analysis, modeling, and unproving instrumentation for positron-emission tomography. (EDB)

Targeting vaccines to dendritic cells

DEFF Research Database (Denmark)

Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

2002-01-01

delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC....... to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC...

Progress report for a research program in computational physics: Progress report, January 1, 1988-December 31, 1988

International Nuclear Information System (INIS)

Guralnik, G.S.

1988-01-01

The project of this progress report are all ultimately concerned with various aspects of numerical simulations of lattice gauge theories. These aspects include algorithms, machines, theoretical studies and actual simulations. We made progress in four general areas: studies of new algorithms, determination of the SU(3) β-function, studies of the finite temperature QCD phase transition in the presence of fermions, and the calculation of hadronic matrix elements. We will describe each of these in turn. 7 refs

Ranking EU progress on road safety : 11th road safety Performance Index (PIN) report.

NARCIS (Netherlands)

Adminaite, D. Jost, G. Stipdonk, H. & Ward, H.

2017-01-01

In 2010, the European Union renewed its commitment to improve road safety by setting a target of reducing road deaths by 50% by 2020, compared to 2010 levels. This target followed an earlier target set in 2001 to halve road deaths by 2010. Since 2014, progress has virtually ground to a halt. 2016

Technological aspects of cryogenic laser-fusion targets

International Nuclear Information System (INIS)

Musinski, D.L.; Henderson, T.M.; Simms, R.J.; Pattinson, T.R.; Jacobs, R.B.

1980-01-01

Most current laser-fusion targets consist of hollow spherical glass shells which have been filled with a mixture of gaseous deuterium-tritium fuel. Theoretical considerations suggest that optimum yields can be obtained from these targets if the fuel is condensed as a uniform liquid or solid layer on the inner surface of the glass shell at the time it is irradiated. In principle, this can be accomplished in a straightforward way by cooling the target below the condensation or freezing point of the fuel. In practice, cryogenic targets can appear in routine laser experiments only when the necessary cryogenic technology is reliably integrated into experimental target chambers. Significant progress has been made recently in this field. The authors will discuss the scientific basis and the various technological features of a system which has allowed the successful irradiation of uniform solid-fuel-layer targets

Consolidated progress report for 1975 on nuclear data activities in the NDS service area: Argentina, Bangladesh, Brazil, Bulgaria, Hungary, India, Iran, Iraq, Israel, Pakistan, Poland, Romania, South Africa, Yugoslavia

International Nuclear Information System (INIS)

1976-01-01

A consolidated progress report for 1975 on nuclear data activities in the NDS service area is presented for the following countries: Argentina, Bangladesh, Brazil, Bulgaria, Hungary, India, Iran, Iraq, Israel, Pakistan, Poland, Romania, South Africa, Yugoslavia

Mesoscale Assessment of CO2 Storage Potential and Geological Suitability for Target Area Selection in the Sichuan Basin

Directory of Open Access Journals (Sweden)

Yujie Diao

2017-01-01

Full Text Available In China, south of the Yangtze River, there are a large number of carbon sources, while the Sichuan Basin is the largest sedimentary basin; it makes sense to select the targets for CO2 geological storage (CGUS early demonstration. For CO2 enhanced oil and gas, coal bed methane recovery (CO2-EOR, EGR, and ECBM, or storage in these depleted fields, the existing oil, gas fields, or coal seams could be the target areas in the mesoscale. This paper proposed a methodology of GIS superimposed multisource information assessment of geological suitability for CO2 enhanced water recovery (CO2-EWR or only storage in deep saline aquifers. The potential per unit area of deep saline aquifers CO2 storage in Central Sichuan is generally greater than 50 × 104 t/km2 at P50 probability level, with Xujiahe group being the main reservoir. CO2 storage potential of depleted gas fields is 53.73 × 108 t, while it is 33.85 × 108 t by using CO2-EGR technology. This paper recommended that early implementation of CGUS could be carried out in the deep saline aquifers and depleted gas fields in the Sichuan Basin, especially that of the latter because of excellent traps, rich geological data, and well-run infrastructures.

Development of target ion source systems for radioactive beams at GANIL

Energy Technology Data Exchange (ETDEWEB)

Bajeat, O., E-mail: bajeat@ganil.fr [GANIL, BP 55027, 14076 CAEN Cedex 05 (France); Delahaye, P. [GANIL, BP 55027, 14076 CAEN Cedex 05 (France); Couratin, C. [GANIL, BP 55027, 14076 CAEN Cedex 05 (France); LPC Caen, 6 bd Maréchal Juin, 14050 CAEN Cedex (France); Dubois, M.; Franberg-Delahaye, H.; Henares, J.L.; Huguet, Y.; Jardin, P.; Lecesne, N.; Lecomte, P.; Leroy, R.; Maunoury, L.; Osmond, B.; Sjodin, M. [GANIL, BP 55027, 14076 CAEN Cedex 05 (France)

2013-12-15

Highlights: • For Spiral 1, a febiad ion source has been connected to a graphite target. • For Spiral 2, an oven made with a carbon resistor is under development. • We made some measurement of effusion in the Spiral 2 target. • A laser ion source is under construction. -- Abstract: The GANIL facility (Caen, France) is dedicated to the acceleration of heavy ion beams including radioactive beams produced by the Isotope Separation On-Line (ISOL) method at the SPIRAL1 facility. To extend the range of radioactive ion beams available at GANIL, using the ISOL method two projects are underway: SPIRAL1 upgrade and the construction of SPIRAL2. For SPIRAL1, a new target ion source system (TISS) using the VADIS FEBIAD ion source coupled to the SPIRAL1 carbon target will be tested on-line by the end of 2013 and installed in the cave of SPIRAL1 for operation in 2015. The SPIRAL2 project is under construction and is being design for using different production methods as fission, fusion or spallation reactions to cover a large area of the chart of nuclei. It will produce among others neutron rich beams obtained by the fission of uranium induced by fast neutrons. The production target made from uranium carbide and heated at 2000 °C will be associated with several types of ion sources. Developments currently in progress at GANIL for each of these projects are presented.

Urban-rural demarcation within a metropolitan area: a methodology for using small area disaggregation

CSIR Research Space (South Africa)

Green, Cheri A

2008-04-01

Full Text Available There is ongoing debate with regard to the levels of service provision in urban and rural areas. However, progress with respect to the delivery of planned services can only be efficiently and equitably measured once benchmarks for different areas...

Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

Energy Technology Data Exchange (ETDEWEB)

Bajenova, Olga, E-mail: o.bazhenova@spbu.ru [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Chaika, Nina [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Tolkunova, Elena; Davydov-Sinitsyn, Alexander [Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064 (Russian Federation); Gapon, Svetlana [Boston Children' s Hospital, Boston, MA 02115 (United States); Thomas, Peter [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); O’Brien, Stephen [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation)

2014-06-10

Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.

Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

International Nuclear Information System (INIS)

Bajenova, Olga; Chaika, Nina; Tolkunova, Elena; Davydov-Sinitsyn, Alexander; Gapon, Svetlana; Thomas, Peter; O’Brien, Stephen

2014-01-01

Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein

Parameter measurement of target

International Nuclear Information System (INIS)

Gao Dangzhong

2001-01-01

The progress of parameter measurement of target (ICF-15) in 1999 are presented, including the design and contract of the microsphere equator profiler, the precise air bearing manufacturing, high-resolution X-ray image of multi-layer shells and the X-ray photos processed with special image and data software, some plastic shells measured in precision of 0.3 μm, the high-resolution observation and photograph system of 'dew-point method', special fixture of target and its temperature distribution measuring, the dew-point temperature and fuel gas pressure of shells measuring with internal pressure of 5 - 15 (x10 5 ) Pa D 2 and wall thickness of 1.5∼3 μm

Progress Report 1985-1986

International Nuclear Information System (INIS)

1987-01-01

The research directions in the Physics Institute of Universidade Federal do Rio Grande do Sul are presented. The progress reports cavied out in the follow areas are presented: perturbed angular correlation; Moessbauer spectroscopy; ion implantation; magnetism and electronic transport; microelectronics; condensed matter theory; quantum field theory; plasma physics; nuclear physics; astronomy and astrophysics; and instrumentation. (M.C.K.) [pt

Research and development on optically pumped polarized ion sources. Technical progress report, February 1, 1985-January 31, 1986

International Nuclear Information System (INIS)

Anderson, L.W.

1985-07-01

During the past year we have studied the relaxation times in an optically pumped 23 Na vapor target, studied the effects of radiation trapping on the polarization in a Na vapor target, and have studied the effects of spin exchange collisions on a beam of fast H 0 atoms as they pass through a polarized alkali target. This research is directed toward improvements in the optically pumped Na or other alkali vapor targets used for the production of polarized H - ions. In this progress report we review the properties of the optically pumped polarized H - ion source as well as discussing the progress of our research on optically pumped Na or other alkali vapor targets. 81 refs., 9 figs

Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets

Science.gov (United States)

Siles-Lucas, Mar; Casulli, Adriano; Cirilli, Roberto

2018-01-01

Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways. PMID:29677189

Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets.

Directory of Open Access Journals (Sweden)

Mar Siles-Lucas

2018-04-01

Full Text Available Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways.

Progress in converting 99Mo production from high-to-low-enriched uranium - 1999

International Nuclear Information System (INIS)

Snelgrove, J.L.; Vandegrift, G.F.; Conner, C.; Wiencek, T.C.; Hofman, G.L.

1999-01-01

Over this past year, extraordinary progress has been made in executing our charter to assist in converting Mo-99 production worldwide from HEU to LEU. Building on the successful development of the experimental LEU-foil target, we have designed a new, economical irradiation target. We have also successfully demonstrated, in collaboration with BATAN in Indonesia, that LEU can be substituted for HEU in the Cintichem target without loss of product yield or purity; in fact, conversion may make economic sense. We are interacting with a number of commercial producers - we have begun active collaborations with the CNEA and ANSTO; we are working to define the scope of collaborations with MDS Nordion and Mallinckrodt; and IRE has offered its services to irradiate and test a target at the appropriate time. Conversion of the CNEA process is on schedule. Other papers presented at this meeting will present specific results on the demonstration of the LEU-modified Cintichem process, the development of the new target, and progress in converting the CNEA process. (author)

The contribution of transport to air quality. TERM 2012: transport indicators tracking progress towards environmental targets in Europe

Energy Technology Data Exchange (ETDEWEB)

Sanchez Vicente, A.; Pastorello, C.; Foltescu, V.L. [and others

2012-11-15

TERM 2012 (Transport and Environment Reporting Mechanism) presents the most relevant and up to date information on the main issues regarding transport and environment in Europe, particularly in areas with specific policy targets such as greenhouse gas emissions and energy consumption, transport demand levels, noise and other issues. It also offers an overview of the transport sector's impact on air pollutant emissions and air quality. It discusses the contributions made by all modes of transport to direct air pollutant emissions and also to 'secondary' air pollutants formed in the atmosphere. Alongside the recently published Air quality in Europe - 2012 report, TERM 2012 aims to inform the European Commission's review of the Thematic Strategy on Air Pollution. (Author)

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)

Underreporting of high-risk water and sanitation practices undermines progress on global targets.

Science.gov (United States)

Vedachalam, Sridhar; MacDonald, Luke H; Shiferaw, Solomon; Seme, Assefa; Schwab, Kellogg J

2017-01-01

Water and sanitation indicators under the Millennium Development Goals failed to capture high-risk practices undertaken on a regular basis. In conjunction with local partners, fourteen rounds of household surveys using mobile phones with a customized open-source application were conducted across nine study geographies in Asia and Africa. In addition to the main water and sanitation facilities, interviewees (n = 245,054) identified all water and sanitation options regularly used for at least one season of the year. Unimproved water consumption and open defecation were targeted as high-risk practices. We defined underreporting as the difference between the regular and main use of high-risk practices. Our estimates of high-risk practices as the main option matched the widely accepted Demographic and Health Surveys (DHS) estimates within the 95% confidence interval. However, estimates of these practices as a regular option was far higher than the DHS estimates. Across the nine geographies, median underreporting of unimproved water use was 5.5%, with a range of 0.5% to 13.9%. Median underreporting of open defecation was much higher at 9.9%, with a range of 2.7% to 11.5%. This resulted in an underreported population of 25 million regularly consuming unimproved water and 50 million regularly practicing open defecation. Further examination of data from Ethiopia suggested that location and socio-economic factors were significant drivers of underreporting. Current global monitoring relies on a framework that considers the availability and use of a single option to meet drinking water and sanitation needs. Our analysis demonstrates the use of multiple options and widespread underreporting of high-risk practices. Policies based on current monitoring data, therefore, fail to consider the range of challenges and solutions to meeting water and sanitation needs, and result in an inflated sense of progress. Mobile surveys offer a cost-effective and innovative platform to rapidly

Progress in the last decade in our understanding of primary progressive aphasia

Directory of Open Access Journals (Sweden)

Ratnavalli Ellajosyula

2010-10-01

Full Text Available Primary progressive aphasia (PPA is a focal neurodegeneration of the brain affecting the language network. Patients can have isolated language impairment for years without impairment in other areas. PPA is classified as primary progressive nonfluent aphasia (PNFA, semantic dementia (SD, and logopenic aphasia, which have distinct patterns of atrophy on neuroimaging. PNFA and SD are included under frontotemporal lobar degenerations. PNFA patients have effortful speech with agrammatism, which is frequently associated with apraxia of speech and demonstrate atrophy in the left Broca′s area and surrounding region on neuroimaging. Patients with SD have dysnomia with loss of word and object (or face meaning with asymmetric anterior temporal lobe atrophy. Logopenic aphasics have word finding difficulties with frequent pauses in conversation, intact grammar, and word comprehension but impaired repetition for sentences. The atrophy is predominantly in the left posterior temporal and inferior parietal regions. Recent studies have described several progranulin mutations on chromosome 17 in PNFA. The three clinical syndromes have a less robust relationship to the underlying pathology, which is heterogeneous and includes tauopathy, ubiquitinopathy, Pick′s disease, corticobasal degeneration, progressive supranuclear palsy, and Alzheimer′s disease. Recent studies, however, seem to indicate that a better characterization of the clinical phenotype (apraxic, agrammatic, semantic, logopenic, jargon increases the predictive value of the underlying pathology. Substantial advances have been made in our understanding of PPAs but developing new biomarkers is essential in making accurate causative diagnoses in individual patients. This is critically important in the development and evaluation of disease-modifying drugs.

Progress of radiolabelled bombesin in diagnosis and treatment of prostate cancer

International Nuclear Information System (INIS)

Xing Yan; Zhao Jihua

2010-01-01

Studies show that high expression of bombesin exist in the face of many kind of tumors such as prostate cancer, so bombesin and its receptor can be used as target in radionuclide receptor imaging and targeted therapy of tumor, and become the focus of prostate cancer research. This article reviews the progress of radiolabelled bombesin in prostate cancer imaging and therapy. (authors)

Overview of progress on the improvement projects for the LANSCE accelerator and target facilities

International Nuclear Information System (INIS)

Macek, R.J.; Browne, J.; Brun, T.; Donahue, J.B.; Fitzgerald, D.H.; Hoffman, E.; Pynn, R.; Schriber, S.; Weinacht, D.

1997-01-01

Three projects have been initiated since 1994 to improve the performance of the accelerator and target facilities for the Los Alamos Neutron Science Center (LANSCE). The LANSCE Reliability Improvement Project (LRIP) was separated into two phases. Phase 1, completed in 1995, targeted near-term improvements to beam reliability and availability that could be completed in one-year's time. Phase 2, now underway and scheduled for completion in May 1998, consists of two projects: (a) implementation of direct H-injection for the Proton Storage Ring (PSR) and (b) an upgrade of the target/moderator system for the short pulse spallation neutron (SPSS) source. The latter will reduce the target change-out time from about 10 months to about three weeks. The third project, the SPSS Enhancement Project, is aimed at increasing the PSR output beam current to 200 microA at 30 Hz and providing up to seven new neutron scattering instruments

Developing conservation targets in social-ecological systems

Directory of Open Access Journals (Sweden)

Phillip S. Levin

2015-12-01

Full Text Available The development of targets is foundational in conservation. Although progress has been made in setting targets, the diverse linkages among ecological and social components make target setting for coupled social-ecological systems extremely challenging. Developing integrated social-ecological targets is difficult because it forces policy makers to consider how management actions propagate throughout social-ecological systems, and because ultimately it is society, not scientists, that defines targets. We developed an interdisciplinary approach for identifying management targets and illustrate this approach using an example motivated by Puget Sound, USA. Our approach blends ecological modeling with empirical social science to articulate trade-offs and reveal societal preferences for different social-ecological states. The framework aims to place information in the hands of decision makers and promote discussion in the appropriate forums. Our ultimate objective is to encourage the informed participation of citizens in the development of social-ecological targets that reflect their values while also protecting key ecosystem attributes.

Cyclooxygenase as a target for chemoprevention in colorectal cancer: lost cause or a concept coming of age?

LENUS (Irish Health Repository)

Doherty, Glen A

2009-02-01

COX-2 is upregulated at an early stage in colorectal carcinogenesis and generates prostaglandins, which promote cancer cell proliferation, impair apoptosis and enhance angiogenesis, promoting tumour growth and metastasis. There are ample data from animal models and human studies to demonstrate enhanced tumour progression associated with COX-2 activity in cancer cells. Conversely, NSAIDs including aspirin inhibit COX-2 and, therefore, have anti-neoplastic properties. There has been sustained interest in COX-2 as a chemopreventive target in colorectal cancer (CRC) and although both aspirin and COX-2 selective NSAIDs have demonstrated efficacy, adverse effects have limited their widespread adoption. In particular, evidence of the cardiovascular effects of COX-2 selective inhibitors has led to questioning of the suitability of COX-2 as a target for chemoprevention. This review examines the basis for targeting COX-2 in CRC chemoprevention, evaluates the efficacy and safety of the approach and examines future strategies in this area.

Lot quality assurance sampling for monitoring coverage and quality of a targeted condom social marketing programme in traditional and non-traditional outlets in India.

Science.gov (United States)

Piot, Bram; Mukherjee, Amajit; Navin, Deepa; Krishnan, Nattu; Bhardwaj, Ashish; Sharma, Vivek; Marjara, Pritpal

2010-02-01

This study reports on the results of a large-scale targeted condom social marketing campaign in and around areas where female sex workers are present. The paper also describes the method that was used for the routine monitoring of condom availability in these sites. The lot quality assurance sampling (LQAS) method was used for the assessment of the geographical coverage and quality of coverage of condoms in target areas in four states and along selected national highways in India, as part of Avahan, the India AIDS initiative. A significant general increase in condom availability was observed in the intervention area between 2005 and 2008. High coverage rates were gradually achieved through an extensive network of pharmacies and particularly of non-traditional outlets, whereas traditional outlets were instrumental in providing large volumes of condoms. LQAS is seen as a valuable tool for the routine monitoring of the geographical coverage and of the quality of delivery systems of condoms and of health products and services in general. With a relatively small sample size, easy data collection procedures and simple analytical methods, it was possible to inform decision-makers regularly on progress towards coverage targets.

Fast neutron dosimetry. Progress report, 1 July 1983-30 June 1984

International Nuclear Information System (INIS)

Attix, F.H.

1984-08-01

Progress was made in several anticipated areas and a few rather unexpected ones. Development and testing of the hemispherical LET was completed. At Wisconsin and at the Rotating Target Neutron Source-Model I, Lawrence Livermore National Laboratory (LLNL), this counter was used to measure LET spectra in lead, carbon, and A-150 plastic. An anticipated design goal to directly measure kerma by particle type was met. Alpha-particle production and kerma in carbon were measured at several neutron energies from 14.1- to 15-MeV neutron energy. To supplement these kerma factor measurements, carbon and A-150 plastic kerma factor calculations were performed in the same neutron energy regions. Various microscopic cross sections were used in this effort to study the observed energy dependence. Calculations of LET spectra for A-150 plastic and carbon were also carried out

Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

Science.gov (United States)

Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

2015-01-01

Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

Towards a green economy in Europe. EU environmental policy targets and objectives 2010-2050

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-07-15

The 'green economy' has emerged as a priority in policy debate in recent years. But what does the concept mean in practice and how can decision-makers measure progress towards this strategic goal? This report provides some answers, presenting a detailed overview of the key objectives and targets in EU environmental policy and legislation for the period 2010-2050. It focuses on selected environmental and resource policy areas, specifically: energy; greenhouse gas (GHG) emissions and ozone-depleting substances; air quality and air pollution; transport sector emissions of greenhouse gases and air pollutants; waste; water; sustainable consumption and production (SCP); chemicals; biodiversity and land use. (Author)

Interleukin-30: A novel microenvironmental hallmark of prostate cancer progression.

Science.gov (United States)

Di Carlo, Emma

2014-01-01

Metastatic prostate cancer is a leading cause of cancer-related death in men worldwide. We have recently discovered that IL-30 shapes the microenvironment of prostate cancer and tumor-draining lymph nodes to favor tumor progression. IL-30 supports tumor growth in vitro, and IL-30 expression in prostate cancer patients is associated with high tumor grade and metastatic stage of disease. Thus, IL-30 may constitute a valuable target for modern therapeutic approaches to hamper prostate cancer progression.

Progress toward fusion with light ions

International Nuclear Information System (INIS)

1980-01-01

New results in target design, beam generation and transport, and pulse power technology have led to a program shift stressing light ion-driven inertial confinement fusion. According to present estimates, a gain ten fusion pellet will require at least one megajoule and approx. 100 TW power input. Progress in ion sources has resulted in beam power density of approx. 1 TW/cm 2 , a factor of ten increase over the last year, and cylindrical implosion experiments have been performed. Other experiments have demonstrated the ability to transport ion and electron beams with high efficiency and have confirmed numerical predictions on the properties of beam transport channels converging at a target. These developments together with improvements in pulse power technology allow us to project that the 72 beam, 100 TW Particle Beam Fusion Accelerator, PBFA-II will attain target output energy equal to stored energy in the accelerator

Report of the workshop on polarized target materials

International Nuclear Information System (INIS)

Court, G.R.; Crabb, D.G.; Fernow, R.C.; Fitzgerald, D.H.; Gray, S.W.; Hill, D.A.; Jarmer, J.J.; Krisch, A.D.; Krumpolic, M.; Niinikoski, T.O.

1978-01-01

The workshop concentrated on an examination of: radiation damage in polarized target materials, a survey of clean target materials, and dynamic polarization results with the new stable Cr(V) complexes. In addition to the normal polarized target experts with backgrounds in high energy physics, low temperature physics and solid state physics, scientists with strong backgrounds in various areas of chemistry and radiation damage physics were included, as these areas were quite crucial to the workshop goals. However, it is clear that much closer collaboration with experts in these areas will be necessary to find polarized target materials that allow more precise experiments on high P 2 perpendicular processes and inclusive processes

High Yield F-18 Target for KOTRON-13 Cyclotron

International Nuclear Information System (INIS)

Lee, W. K.; Song, J. Y.; Park, J. Y.; Jung, K. I.; Chae, S. K.

2009-01-01

Currently the domestic radiation market for medical diagnosis witnesses a high increase of the use of PET/CT for the purpose of cancer diagnosis, and the cases of cancer diagnosis using PET/CT increase by geometric progression every year. In case of domestic practice, full body scan is taken by using FDG medical isotope medicines mainly using F-18, but the necessity of various medical radioactive isotopes according to each medical purpose is increasing. F-18 output yield is directly proportional to energy of protons and beam current, and has correlation with heat production rate in case of target and decides the function of target in accordance with the efficiency of a cooling device. At present, in case of most F-18 target, when one irradiates beam in O-18 water of about 0.2∼5mL, one has to apply heat of over 300W, a high thermal energy per unit area is irradiated in target, which is easily damaged, and it has limitation in beam current. Currently, in case of commercial target, about 2,000W beam current is the maximum value, and in case of double-grid target developed by Korea Institute of Radiological and Medical Sciences in 2004, it was designed to stand up to about 1,000W theoretically, but in reality it can irradiate lower beam current than this because of the shortage of cooling efficiency. In general, the irradiation strength to produce radioactive isotopes given in the heat emission by target substance currently is limited to 50μA against target substance irradiated in 1.6mL. However, current KOTRON-13 cyclotron can accelerate proton beam with a high scope of strength marking 100μA thru 120μA by a continuous development. Therefore, it doesn't fully function compared with that of proton beam of KOTRON-13 cyclotron. The solution about this is to get over the problem of cooling target substance of cavity in the production system of radioactive isotopes. Especially, one has to develop the method to cool target substance, and provide higher F-18 yield than

Gender differences in the progression of target organ damage in patients with increased insulin resistance: the LOD-DIABETES study.

Science.gov (United States)

Gómez-Marcos, Manuel Ángel; Recio-Rodríguez, José Ignacio; Gómez-Sánchez, Leticia; Agudo-Conde, Cristina; Rodríguez-Sanchez, Emiliano; Maderuelo-Fernandez, JoseAngel; Gomez-Sanchez, Marta; García-Ortiz, Luís

2015-10-01

The purpose of this study was to analyze the evolution of vascular, cardiac and renal target organ damage (TOD) in patients with increased insulin resistance over a 3.5 year follow-up and to investigate gender difference and factors that influence its progression. We performed a prospective observational study involving 112 patients (71 men, 41 women) who were followed for 3.5 years. Measurements included blood pressure, blood glucose, lipids, smoking, body mass index (BMI) and HOMA-Ir Vascular TOD included carotid intima-media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index (ABI). Cardiac TOD included Cornell voltage-duration product and Sokolow. Renal TOD included creatinine, glomerular filtration and albumin/creatinine ratio. The IMT increased in both genders. Each year, the IMT increased 0.005 mm in men and 0.011 in women and the PWV 0.024 and 0.020 m/sec, respectively. The highest increase was in women with type 2 diabetes mellitus, who had an increase in TOD carotid (40%), PWV (24%) and renal TOD (20 %). Multiple regression analysis, after adjusting for age and gender, showed a negative association between duration since diabetes diagnosis and ABI (β = -0.006; p = 0.017) and between BMI and glomerular filtration (β = -0.813; p = 0.014). HbA1c was positively associated with PWV (β = 0.501; p = 0.014). This study showed that the progression of vascular and renal TOD differs by gender. The increase in vascular and renal TOD was higher in women, especially in diabetic women. The PWV increase showed a positive association with mean HbA1c levels during the follow-up. Glomerular filtration was associated with BMI and the ABI was associated with duration since type 2 diabetes mellitus diagnosis. Clinical Trials.gov Identifier NCT01065155.

Apoptosis: Targets in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Kalthoff Holger

2003-01-01

Full Text Available Abstract Pancreatic adenocarcinoma is characterized by poor prognosis, because of late diagnosis and lack of response to chemo- and/or radiation therapies. Resistance to apoptosis mainly causes this insensitivity to conventional therapies. Apoptosis or programmed cell death is a central regulator of tissue homeostasis. Certain genetic disturbances of apoptotic signaling pathways have been found in carcinomas leading to tumor development and progression. In the past few years, the knowledge about the complex pathways of apoptosis has strongly increased and new therapeutic approaches based on this knowledge are being developed. This review will focus on the role of apoptotic proteins contributing to pancreatic cancer development and progression and will demonstrate possible targets to influence this deadly disease.

Progress of the RERTR programme in 1999

International Nuclear Information System (INIS)

Travelli, A.

1999-01-01

This paper describes the progress achieved by the Reduced Enrichment for Research and Test Reactors (RERTR) Program in collaboration with its many international partners during 1999 and discusses planned activities for the coming year. The past year was characterized by exceptionally important accomplishments and events for the RERTR program. - Three additional shipments containing 1,006 spent fuel assemblies from foreign research reactors were accepted by the U.S. Altogether, 3,237 spent fuel assemblies from foreign research reactors have been received by the U.S. under the acceptance policy. - Postirradiation examinations of the first two batches of microplates revealed good irradiation behavior of U-6Mo, and excellent irradiation behavior of U-Mo alloys with higher Mo content or with small Ru additions. Irradiation of a new batch of microplates to investigate the behavior of these fuels at high temperatures is scheduled to begin in October 1999. These materials hold the promise of achieving the program goal of developing LEU research reactor fuels with uranium densities in the 8-9 g /cm 3 range. - Progress on irradiation testing and safety analyses was made in the Russian RERTR program, which aims to develop and demonstrate the technical means needed to convert Russian supplied research reactors to LEU fuels. - The U.S. Government has decided to aggressively pursue, in cooperation with the Russian Government, eventual conversion of three Russian plutonium production reactors to the use of low-enriched UO 2 -Al dispersion fuel. This effort is now proceeding, with assistance from RERTR personnel. - At the request of the German government, the RERTR program has addressed the performance of a new alternative LEU FRM-II core design that could be installed in the same building structure erected for the current 20 MW HEU design with the same 50-day fuel life. The results have been favorable. - Significant improvements were made in the design of an LEU metal-foil target

Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

Science.gov (United States)

Arrue, Lily; Ratjen, Lars

2017-12-07

The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

BAF57 Modulation of Androgen Receptor Action and Prostate Cancer Progression

National Research Council Canada - National Science Library

Link, Kevin A

2006-01-01

Given the requirement of the AR activation pathway for prostate cancer growth and progression, it is necessary to identify alternative means of targeting this pathway for the treatment of prostate cancer...

PROPOSING AN INTEGRATIVE-PROGRESSIVE MODEL IN HANDLING TROUBLED INDONESIAN OVERSEAS WORKERS IN THE TRANSIT AREA (A SOCIO-LEGAL RESEARCH IN TANJUNG PINANG CITY, KEPULAUAN RIAU PROVINCE

Directory of Open Access Journals (Sweden)

Rina Shahriyani Shahrullah

2015-12-01

Full Text Available Tanjung Pinang City of the Riau Islands Province (Provinsi Kepulauan Riau is a transit area for the troubled Indonesian overseas workers from Singapore and Malaysia. The Indonesian National Board for the Placement and Protection of Indonesian Workers (Badan Nasional Penempatan dan Perlindungan Tenaga Kerja Indonesia/BNP2TKI reported that 15,105 troubled Indonesian overseas workers were deported from January to November 2014 via Tanjung Pinang City.  Previous research revealed that citizens of Tanjung Pinang City criticized the treatments given by the local government to the deported workers by reason that they were not the citizens of the Riau Islands Province, yet the local government has to provide shelters and funds prior to returning them to their home towns. The treatments for the deported workers in the transit area have also raised pros and cons among the stakeholders who are in charge of handling the deported workers. This circumstance may not occur if a special regional regulation of the Riau Islands Province has been issued to govern the troubled Indonesian overseas workers in the transit area.  Due to this vacuum of law, this research aims to establish a mechanism in handling the deported workers in the transit area by designing an integrative-progressive model which can be adopted by the stakeholders. The model is to link the legal and non- legal issues and as well as to provide the collaborative mechanisms for the stakeholders based on the approaches of the integrative and progressive legal theory.

The Progress of the HIRFL-CSR Project and the Commissioning of the Cluster Target

International Nuclear Information System (INIS)

Cai Xiaohong; Lu Rongchun; Shao Caojie; Ruan, Fangfang; Yu, Deyang; Li Mingsheng; Torpokov, D K; Shestakov, Yu V; Sadykov, Rs; Zevakov, S A; Xia Jiawen; Zhan Wenlong

2007-01-01

HIRFL-CSR, a new cooler-storage-ring project, is the post-acceleration system of the Heavy Ion Research Facility in Lanzhou (HIRFL) consisting of a main ring (CSRm) and an experimental ring (CSRe). The construction of the HIRFL-CSR complex is nearing completion. The stored beam in the CSRm has been observed. Recently, the stored beam was accelerated from 7 MeV/u to 30 MeV/u. The cluster target is located in one straight section of the CSRe providing cluster jet targets of inert gases and small molecular gases. The cluster target has been finished and the results of the test running are presented

The regional metallogenesis and optimum selection of prospecting target for superlarge uranium deposit in metallogenic area of erguna

International Nuclear Information System (INIS)

Luo Yi; Wang Zhengbang; Hou Huiqun; Zhou Dean; Qi Fucheng; Xiao Xiangping

1995-06-01

The study area, an activation zone of the median Massif in Xingmeng geosynclinal area, geologically underwent the multiple tectono-magmatic reworking of granitizations during Shinagan, Caledonia and Hercynian periods and of continental rift volcanism in the Mesozoic-Cenozoic era. It is an important potential area for uranium metallogenesis in volcanic basin in North China. The study identifies that four stages of uranium preconcentration and three phases of hydrothermal superimposed-reworking uranium metallogenesis occurred along with the regional geological elevation process. Studies on the U-Pb isotope and induced fission track of various kinds of basement rocks from the area indicate that the basement composed of crustal source remelting type Caledonian and Hercynian granites is favourable for uranium metallogenesis in volcanic basin, and that the late Jurassic intermediate-acid volcano-rock directly act as the source of uranium and that Cretaceous-Tertiary extension-rift basalt magmatic activation supply an important hydrothermal reworking condition for the uranium metallogenesis in volcanic basin. Based on comparative study on the metallogenetic conditions of typical large-scale volcanic uranium deposits at home and abroad, nine prospecting criteria are summarized, the polygenetic mixing hydrothermal uranium metallogenetic model for penetrable volcano-collapse basin is presented, and the main prospecting targets of uranium deposits are pointed out. (2 figs.)

Chance, purpose, and progress in evolution and christianity.

Science.gov (United States)

Mix, Lucas J; Masel, Joanna

2014-08-01

Evolutionary biology has a complex relationship with ideas of chance, purpose, and progress. Probability plays a subtle role; strikingly, founding figures in statistics were motivated by evolutionary questions. The findings of evolutionary biology have been used both in support of narratives of progress, and in their deconstruction. Likewise, professional biologists bring to their scientific work a set of preconceptions about chance and progress, grounded in their philosophical, religious, and/or political views. From the religious side, questions of purpose are ever-present. We explore this interplay in five broad categories: chance, progress, intelligence, eugenics, and the evolution of religious practices, each the subject of a semester long symposium. The intellectual influence of evolutionary biology has had a broad societal impact in these areas. Based on our experience, we draw attention to a number of relevant facts that, while accepted by experts in their respective fields, may be unfamiliar outside them. We list common areas of miscommunication, including specific examples and discussing causes: sometimes semantics and sometimes more substantive knowledge barriers. We also make recommendations for those attempting similar dialogue. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Taking stock of Myanmar’s progress toward the health-related Millennium Development Goals: current roadblocks, paths ahead

Science.gov (United States)

2013-01-01

Myanmar is a developing country with considerable humanitarian needs, rendering its pursuit of the Millennium Development Goals (MDGs) an especially high priority. Yet progress to date remains under-examined on key fronts. Particularly within the three health-related MDGs (MDGs 4, 5, and 6), the limited data reported point to patchy levels of achievement. This study was undertaken to provide an overview and assessment of Myanmar’s progress toward the health-related MDGs, along with possible solutions for accelerating health-related development into 2015 and beyond. The review highlights off-track progress in the spheres of maternal and child health (MDGs 4 and 5). It also shows Myanmar’s achievements toward MDG 6 targets – in the areas of HIV/AIDS, malaria, and tuberculosis. Such achievements are especially notable in that Myanmar has been receiving the lowest level of official development assistance among all of the least developed countries in Asia. However, to make similar progress in MDGs 4 and 5, Myanmar needs increased investment and commitment in health. Toward moving forward with the post-2015 development agenda, Myanmar’s government also needs to take the lead in calling for attention from the World Health Organization and its global development partners to address the stagnation in health-related development progress within the country. In particular, Myanmar’s government should invest greater efforts into health system strengthening to pave the road to universal health coverage. PMID:24025845

Autophagy and Mis-targeting of Therapeutic Enzyme in Skeletal Muscle in Pompe Disease

Science.gov (United States)

Fukuda, Tokiko; Ahearn, Meghan; Roberts, Ashley; Mattaliano, Robert J.; Zaal, Kristien; Ralston, Evelyn; Plotz, Paul H.; Raben, Nina

2009-01-01

Enzyme replacement therapy (ERT) became a reality for patients with Pompe disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a deficiency of glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). The therapy, which relies on receptor-mediated endocytosis of recombinant human GAA (rhGAA), appears to be effective in cardiac muscle, but less so in skeletal muscle. We have previously shown a profound disturbance of the lysosomal degradative pathway (autophagy) in therapy-resistant muscle of GAA knockout mice (KO). Our findings here demonstrate a progressive age-dependent autophagic build-up in addition to enlargement of glycogen-filled lysosomes in multiple muscle groups in the KO. Trafficking and processing of the therapeutic enzyme along the endocytic pathway appear to be affected by the autophagy. Confocal microscopy of live single muscle fibers exposed to fluorescently labeled rhGAA indicates that a significant portion of the endocytosed enzyme in the KO was trapped as a partially processed form in the autophagic areas instead of reaching its target – the lysosomes. A fluid-phase endocytic marker was similarly mis-targeted and accumulated in vesicular structures within the autophagic areas. These findings may explain why ERT often falls short of reversing the disease process, and point to new avenues for the development of pharmacological intervention. PMID:17008131

The UK fuel poverty strategy: 5th annual progress report 2007

International Nuclear Information System (INIS)

2007-12-01

This fifth annual progress report details government progress in 2007 in tackling fuel poverty and movement towards targets. The United Kingdom were the first country in the world to recognise the issue of fuel poverty and to put in place measures to tackle the issue, including spending 20 billion pounds sterling on benefits and programmes since the year 2000. The report covers progress to date, schemes and initiatives to tackle fuel poverty, the energy market and looks ahead to the future. Progress and development of the schemes across the devolved nations are also considered. This report is the first to publish the Government's proposals for the Carbon Emissions Reduction Target (CERT) priority group, which were laid before Parliament on 5th December 2007. This report is the first to present the fuel poverty figures for 2005, and shows the effects of rising energy prices. The Government continues to take action to ensure that the energy market is working properly, and to encourage reform in the EU on energy market liberalisation - this should reduce pressure on prices. Those in fuel poverty have much to gain by switching supplier and this report outlines the action taken by Ofgem and Energywatch to encourage this

Implementing inflation targeting regimes: The case of Poland

OpenAIRE

Gottschalk, Jan; Moore, David

1999-01-01

This paper assesses the prospects for the new Polish monetary policy strategy of inflation targeting. Regarding the general requirements for implementing an inflation targeting strategy it appears that Poland has made sufficient progress in reducing fiscal dominance and hardening budget constraints. The paper also finds that the exchange rate has played a dominant role as a policy instrument, with the linkages between the short-term interest rate and inflation remaining unclear. Given this un...

Rexin-G, a targeted genetic medicine for cancer.

Science.gov (United States)

Gordon, Erlinda M; Hall, Frederick L

2010-05-01

Rexin-G, a tumor-targeted retrovector bearing a cytocidal cyclin G1 construct, is the first targeted gene therapy vector to gain fast track designation and orphan drug priorities for multiple cancer indications in the US. This review describes the major milestones in the clinical development of Rexin-G: from the molecular cloning and characterization of the human cyclin G1 proto-oncogene in 1994, to the design of the first knockout constructs and genetic engineering of the targeted delivery system from 1995 to 1997, through the initial proofs-of-concept, molecular pharmacology and toxicology studies of Rexin-G in preclinical cancer models from 1997 to 2001, to the pioneering clinical studies in humans from 2002 to 2004, which--together with the advancements in bioprocess development of high-potency clinical grade vectors circa 2005 - 2006--led to the accelerated approval of Rexin-G for all solid tumors by the Philippine FDA in 2007 and the rapid progression of clinical studies from 2007 to 2009 to the cusp of pivotal Phase III trials in the US. In recording the development of Rexin-G as a novel form of targeted biological therapy, this review also highlights important aspects of vector design engineering which served to overcome the physiological barriers to gene delivery as it addresses the key regulatory issues involved in the development of a targeted gene therapy product. Progressive clinical development of Rexin-G demonstrates the potential safety and efficacy of targeted genetic medicine, while validating the design engineering of the molecular biotechnology platform.

Annual progress report

International Nuclear Information System (INIS)

Russek, A.

1975-06-01

Progress has been made in calculation of cross-sections for dielectronic and radiative recombination when hot electrons are incident on partially stripped impurity ions. Calculations were completed for the cases of 1 keV and 10 keV electrons incident on ions of arbitrary Z with ionization state consistent with a 1 keV plasma temperature. It was found that dielectronic recombination dominates radiative recombination by a factor of 100 at 1 keV incident electron energy to a factor of 1000 at 10 keV incident electron energy. The work is now being extended to other plasma temperatures and is being improved by more accurate calculation of the matrix elements involved. Progress was also made in the calculation of accurate bremsstrahlung and higher order radiative processes which also occur when hot electrons are incident on partially stripped impurity ions. Formal expressions for the matrix elements have been obtained for cross-sections in a fully relativistic partial wave analysis for bremsstrahlung radiation both with and without electron excitation of the target ion. Final evaluation now awaits the evaluation of the relativistic radial integrals involved in these matrix elements. (U.S.)

Plutonium Focus Area research and development plan. Revision 1

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-11-01

The Department of Energy (DOE) committed to a research and development program to support the technology needs for converting and stabilizing its nuclear materials for safe storage. The R and D Plan addresses five of the six material categories from the 94-1 Implementation Plan: plutonium (Pu) solutions, plutonium metals and oxides, plutonium residues, highly enriched uranium, and special isotopes. R and D efforts related to spent nuclear fuel (SNF) stabilization were specifically excluded from this plan. This updated plan has narrowed the focus to more effectively target specific problem areas by incorporating results form trade studies. Specifically, the trade studies involved salt; ash; sand, slag, and crucible (SS and C); combustibles; and scrub alloy. The plan anticipates possible disposition paths for nuclear materials and identifies resulting research requirements. These requirements may change as disposition paths become more certain. Thus, this plan represents a snapshot of the current progress and will continue to be updated on a regular basis. The paper discusses progress in safeguards and security, plutonium stabilization, special isotopes stabilization, highly-enriched uranium stabilization--MSRE remediation project, storage technologies, engineered systems, core technology, and proposed DOE/Russian technology exchange projects.

Plutonium Focus Area research and development plan. Revision 1

International Nuclear Information System (INIS)

1996-11-01

The Department of Energy (DOE) committed to a research and development program to support the technology needs for converting and stabilizing its nuclear materials for safe storage. The R and D Plan addresses five of the six material categories from the 94-1 Implementation Plan: plutonium (Pu) solutions, plutonium metals and oxides, plutonium residues, highly enriched uranium, and special isotopes. R and D efforts related to spent nuclear fuel (SNF) stabilization were specifically excluded from this plan. This updated plan has narrowed the focus to more effectively target specific problem areas by incorporating results form trade studies. Specifically, the trade studies involved salt; ash; sand, slag, and crucible (SS and C); combustibles; and scrub alloy. The plan anticipates possible disposition paths for nuclear materials and identifies resulting research requirements. These requirements may change as disposition paths become more certain. Thus, this plan represents a snapshot of the current progress and will continue to be updated on a regular basis. The paper discusses progress in safeguards and security, plutonium stabilization, special isotopes stabilization, highly-enriched uranium stabilization--MSRE remediation project, storage technologies, engineered systems, core technology, and proposed DOE/Russian technology exchange projects

Nanoparticle-Based Drug Delivery for Therapy of Lung Cancer: Progress and Challenges

Directory of Open Access Journals (Sweden)

Anish Babu

2013-01-01

Full Text Available The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment.

BAF57 Modulation of Androgen Receptor Action and Prostate Cancer Progression

National Research Council Canada - National Science Library

Link, Kevin A

2007-01-01

Given the requirement of the androgen receptor (AR) activation pathway for prostate cancer growth and progression, it is necessary to identify alternative means of targeting this pathway for the treatment of prostate cancer...

Proceedings of the twelfth target fabrication specialists` meeting

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-04-01

Research in fabrication for inertial confinement fusion (ICF) comprises at least three broad categories: targets for high energy density physics on existing drivers, ignition capsule fabrication, and cryogenic fuel layer formation. The latter two are being pursued primarily for the National Ignition Facility (NIF). Scientists from over 14 laboratories, universities, and businesses contributed over 100 papers on all aspects of ICF target fabrication. The NIF is well along in construction and photos of poured concrete and exposed steel added to the technical excitement. It was clear from the meeting that there has been significant progress toward the fabrication of an ignition target for NIF and that new techniques are resulting in higher quality targets for high energy density research.

Proceedings of the twelfth target fabrication specialists' meeting

International Nuclear Information System (INIS)

1999-01-01

Research in fabrication for inertial confinement fusion (ICF) comprises at least three broad categories: targets for high energy density physics on existing drivers, ignition capsule fabrication, and cryogenic fuel layer formation. The latter two are being pursued primarily for the National Ignition Facility (NIF). Scientists from over 14 laboratories, universities, and businesses contributed over 100 papers on all aspects of ICF target fabrication. The NIF is well along in construction and photos of poured concrete and exposed steel added to the technical excitement. It was clear from the meeting that there has been significant progress toward the fabrication of an ignition target for NIF and that new techniques are resulting in higher quality targets for high energy density research

Theoretical nuclear structure. Progress report for 1997

International Nuclear Information System (INIS)

Nazarewicz, W.; Strayer, M.R.

1997-01-01

This research effort is directed toward theoretical support and guidance for the fields of radioactive ion beam physics, gamma-ray spectroscopy, and the interface between nuclear structure and nuclear astrophysics. The authors report substantial progress in all these areas. One measure of progress is publications and invited material. The research described here has led to more than 25 papers that are published, accepted, or submitted to refereed journals, and to 25 invited presentations at conferences and workshops

Polarized target physics at the Bonn electron accelerators

International Nuclear Information System (INIS)

Meyer, W.

1988-12-01

At the BONN 2.5 GeV electron synchrotron experiments with polarized nucleon targets have a long tradition. Starting with measurements of the target asymmetry in single pion photoproduction off polarized protons, resp. neutrons, the experiments have been concentrated on photodisintegration measurements of polarized deuterons. Parallel to these activities a considerable progress in the field of the target technology, e.g. cryogenics and target materials, has been made, by which all the measurements have profitted enormously. Especially the development of the new target material ammonia has allowed the first use of a polarized deuteron (ND 3 ) target in an intense electron beam. The construction of a frozen spin target, which will be used in combination with a tagged polarized photon beam, makes a new generation of polarized target experiments in photon induced reactions possible. Together with electron scattering off polarized deuterons and neutrons they will be a main activity in the physics program at the new stretcher accelerator ELSA in BONN. (orig.)

Use of fundus autofluorescence images to predict geographic atrophy progression.

Science.gov (United States)

Bearelly, Srilaxmi; Khanifar, Aziz A; Lederer, David E; Lee, Jane J; Ghodasra, Jason H; Stinnett, Sandra S; Cousins, Scott W

2011-01-01

Fundus autofluorescence imaging has been shown to be helpful in predicting progression of geographic atrophy (GA) secondary to age-related macular degeneration. We assess the ability of fundus autofluorescence imaging to predict rate of GA progression using a simple categorical scheme. Subjects with GA secondary to age-related macular degeneration with fundus autofluorescence imaging acquired at least 12 months apart were included. Rim area focal hyperautofluorescence was defined as percentage of the 500-μm-wide margin bordering the GA that contained increased autofluorescence. Rim area focal hyperautofluorescence on baseline fundus autofluorescence images was assessed and categorized depending on the extent of rim area focal hyperautofluorescence (Category 1: ≤33%; Category 2: between 33 and 67%; Category 3: ≥67%). Total GA areas at baseline and follow-up were measured to calculate change in GA progression. Forty-five eyes of 45 subjects were included; average duration of follow-up was 18.5 months. Median growth rates differed among categories of baseline rim area focal hyperautofluorescence (P = 0.01 among Categories 1, 2, and 3; P = 0.008 for Category 1 compared with Category 3, Jonckheere-Terpstra test). A simple categorical scheme that stratifies the amount of increased autofluorescence in the 500-μm margin bordering GA may be used to differentiate faster and slower progressors.

HER-2 as a Progression Factor and Therapeutic Target in Breast Cancer

National Research Council Canada - National Science Library

1999-01-01

...). We had observed previously that upon reduction of llER-2 in MCF-7 cells by ribozyme-targeting estradiol lost its ability to induce anchorage- independent colony formation in soft agar of the tumor cell...

FY2016 Lightweight Materials Annual Progress Report

Energy Technology Data Exchange (ETDEWEB)

None, None

2017-10-31

The Lightweight Materials research and development (R&D) area within the DOE Vehicle Technologies Office (VTO) provides support and guidance for many cutting-edge automotive technologies under development. Research focuses on addressing critical barriers to commercializing lightweight materials for passenger and commercial vehicles. This report describes the progress made on the research and development projects funded by the Lightweight Materials area.

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study.

Directory of Open Access Journals (Sweden)

Vijay R Varma

2018-01-01

Full Text Available The metabolic basis of Alzheimer disease (AD is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression.Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180 assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA (N = 44, mean age = 81.33, % female = 36.36 from AD (N = 15, control (CN; N = 14, and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15 participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes-sphingolipids and glycerophospholipids-that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer's Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63 and preclinical (BLSA (N = 207, mean age = 78.68, % female = 42.63 AD, in which we tested their associations with magnetic resonance imaging (MRI measures of AD-related brain atrophy, cerebrospinal fluid (CSF biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study

Science.gov (United States)

Oommen, Anup M.; Varma, Sudhir; Casanova, Ramon; An, Yang; O’Brien, Richard; Pletnikova, Olga; Kastenmueller, Gabi; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Thambisetty, Madhav

2018-01-01

Background The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. Methods and findings Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and “asymptomatic Alzheimer’s disease” (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes—sphingolipids and glycerophospholipids—that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer’s Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that

Targeted therapy in lung and breast cancer: a big deal

OpenAIRE

Caffarra, Cristina

2015-01-01

Great strides have been done in treating cancer. For decades, the hallmark of medical treatment for cancer has been intravenous cytotoxic chemotherapy which targets all dividing cells. In the last ten years the identification of different driver oncogenic mutations has allowed the development of targeted drugs. Targeted cancer therapies are based on the use of drugs that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. The ...

The potential of AR-V7 as a therapeutic target.

Science.gov (United States)

Uo, Takuma; Plymate, Stephen R; Sprenger, Cynthia C

2018-03-01

The androgen receptor variant AR-V7 is gaining attention as a potential predictive marker for as well as one of the resistance mechanisms to the most current anti-androgen receptor (AR) therapies in castration-resistant prostate cancer (CRPC). Accordingly, development of next-generation drugs that directly or indirectly target AR-V7 signaling is urgently needed. Areas covered: We review proposed mechanisms of drug resistance in relation to AR-V7 status, the mechanisms of generation of AR-V7, and its transcriptome, cistrome, and interactome. Pharmacological agents that interfere with these processes are being developed to counteract pan AR and AR-V7-specific signaling. Also, we address the current status of the preclinical and clinical studies targeting AR-V7 signaling. Expert opinion: AR-V7 is considered a true therapeutic target, however, it remains to be determined if AR-V7 is a principal driver or merely a bystander requiring heterodimerization with co-expressed full-length AR or other variants to drive CRPC progression. While untangling AR-V7 biology, multiple strategies are being developed to counteract drug resistance, including selective blockade of AR-V7 signaling as well as inhibition of pan-AR signaling. Ideally anti-AR therapies will be combined with agents preventing activation and enrichment of AR negative tumor cells that are otherwise depressed by AR activity axis.

Progress towards novel adenosine receptor therapeutics gleaned from the recent patent literature.

Science.gov (United States)

Press, Neil J; Fozard, John R

2010-08-01

The principle of treating disease with selective adenosine receptor ligands has been demonstrated with drugs on the market, while the lesser understood receptor subtypes are still being probed with new and drug-like pharmaceutical tools. The field of adenosine receptor research is, therefore, highly important as an emerging and proven point of intervention in disease. From 2008 to 2009, > 120 primary patent applications have claimed adenosine receptor ligands, which we analyze by applicant and target. Particularly significant disclosures are described in detail, paying particular attention to the biological data marshalled to support the case. The first published disclosure of new compounds, compound uses or drug targets is often in the patent literature, which can be difficult to trawl, interpret and verify as it is not subject to peer review. We have critically reviewed this area and share our conclusions regarding progress, trends and identification of early tool compounds or compounds of potential clinical significance ahead of peer-reviewed publication. Adenosine receptor research is a thriving field with continuing claims of exciting new compounds with high specificity and intriguing examples of new uses for such ligands.

Recent progresses in biomedical applications of aptamer-functionalized systems.

Science.gov (United States)

Ding, Fei; Gao, Yangguang; He, Xianran

2017-09-15

Aptamers, known as "chemical antibodies" are screened via a combinational technology of systematic evolution of ligands by exponential enrichment (SELEX). Due to their specific targeting ability, high binding affinity, low immunogenicity and easy modification, aptamer-functionalized systems have been extensively applied in various fields and exhibit favorable results. However, there is still a long way for them to be commercialized, and few aptamer-functionalized systems have yet successfully entered clinical and industrial use. Thus, it is necessary to overview the recent research progresses of aptamer-functionalized systems for the researchers to improve or design novel and better aptamer-functionalized systems. In this review, we first introduce the recent progresses of aptamer-functionalized systems' applications in biosensing, targeted drug delivery, gene therapy and cancer cell imaging, followed by a discussion of the challenges faced with extensive applications of aptamer-functionalized systems and speculation of the future prospects of them. Copyright © 2017 Elsevier Ltd. All rights reserved.

TASCC Division progress report

International Nuclear Information System (INIS)

Hardy, J.C.

1992-10-01

The TASCC (Tandem Accelerator-Superconducting Cyclotron) facility is devoted to developing and providing beams for an experimental program of basic nuclear research. Beam was on target for 2901 hours during the period of interest. The cyclotron provided beam for 524 hours, and tandem beams were used for a total of 3940 hours. The most exciting experimental result was the first evidence of a rotational band with the characteristics of hyperdeformation: a ridge-valley structure in 152 Dy. This progress report details experimental results and instrumentation and facility development over the period. (L.L.) (refs., tabs., figs.)

Muddled mechanisms: recent progress towards antimalarial target identification [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Rachel L. Edwards

2016-10-01

Full Text Available In the past decade, malaria rates have plummeted as a result of aggressive infection control measures and the adoption of artemisinin-based combination therapies (ACTs. However, a potential crisis looms ahead. Treatment failures to standard antimalarial regimens have been reported in Southeast Asia, and devastating consequences are expected if resistance spreads to the African continent. To prevent a potential public health emergency, the antimalarial arsenal must contain therapeutics with novel mechanisms of action (MOA. An impressive number of high-throughput screening (HTS campaigns have since been launched, identifying thousands of compounds with activity against one of the causative agents of malaria, Plasmodium falciparum. Now begins the difficult task of target identification, for which studies are often tedious, labor intensive, and difficult to interpret. In this review, we highlight approaches that have been instrumental in tackling the challenges of target assignment and elucidation of the MOA for hit compounds. Studies that apply these innovative techniques to antimalarial target identification are described, as well as the impact of the data in the field.

Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin-mediated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin.

Science.gov (United States)

Liu, Chuanxia; Feng, Xiaoxia; Wang, Baixiang; Wang, Xinhua; Wang, Chaowei; Yu, Mengfei; Cao, Guifen; Wang, Huiming

2018-03-01

Bone marrow mesenchymal stem cells (BMMSC) have been shown to be recruited to the tumor microenvironment and exert a tumor-promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor-promoting effect of BMMSC on head and neck cancer (HNC) are not clear. In this study, we investigated Periostin (POSTN) and its roles in the tumor-promoting effect of BMMSC on HNC. In vitro analysis of HNC cells cultured in BMMSC-conditioned media (MSC-CM) showed that MSC-CM significantly promoted cancer progression by enhancing cell proliferation, migration, epithelial-mesenchymal transformation (EMT), and altering expression of cell cycle regulatory proteins and inhibition of apoptosis. Moreover, MSC-CM promoted the expression of POSTN and POSTN promoted HNC progression through the activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. In a murine model of HNC, we found that BMMSC promoted tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical sample analysis further confirmed that the expression of POSTN and N-cadherin were correlated with pathological grade and lymph node metastasis of HNC. In conclusion, this study indicated that BMMSC promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN-mediated PI3K/Akt/mTOR activation. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Recent Progress and Development of Crystal Structure Analysis of Enzymes and Other Proteins

Science.gov (United States)

Tanokura, Masaru; Nagata, Koji; Miyazono, Ken-Ichi; Miyakawa, Takuya; Okai, Masahiko

Structural biology has made tremendous progress in this decade. Here we briefly introduce the Target Proteins Research Program, a national project promoted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. The program aims to reveal the structure and function of proteins that are of great importance in both academic research and industrial application. We also summarize the results of structure-function analyses of (i) transcriptional regulatory proteins useful for the breading of drought and heat stress tolerant crops, (ii) useful enzymes for the production of chiral compounds, and (iii) useful enzymes for the degradation of environmental pollution substances. These results can be utilized in various areas of industries, to enhance food production, to improve the efficiency of pharmaceutical compound production, and to promote the bioremediation of contaminated soil and water.

Deep kernel learning method for SAR image target recognition

Science.gov (United States)

Chen, Xiuyuan; Peng, Xiyuan; Duan, Ran; Li, Junbao

2017-10-01

With the development of deep learning, research on image target recognition has made great progress in recent years. Remote sensing detection urgently requires target recognition for military, geographic, and other scientific research. This paper aims to solve the synthetic aperture radar image target recognition problem by combining deep and kernel learning. The model, which has a multilayer multiple kernel structure, is optimized layer by layer with the parameters of Support Vector Machine and a gradient descent algorithm. This new deep kernel learning method improves accuracy and achieves competitive recognition results compared with other learning methods.

Heavy-ion-fusion-science: summary of US progress

International Nuclear Information System (INIS)

Yu, S.S.; Logan, B.G.; Barnard, J.J.; Bieniosek, F.M.; Briggs, R.J.; Cohen, R.H.; Coleman, J.E.; Davidson, R.C.; Friedman, A.; Gilson, E.P.; Grisham, L.R.; Grote, D.P.; Henestroza, E.; Kaganovich, I.D.; Covo, M. Kireeff; Kishek, R.A.; Kwan, J.W.; Lee, E.P.; Leitner, M.A.; Lund, S.M.; Molvik, A.W.; Olson, C.L.; Qin, H.; Roy, P.K.; Sefkow, A.; Seidl, P.A.; Startsev, E.A.; Vay, J-L.; Waldron, W.L.; Welch, D.R.

2007-01-01

Over the past two years noteworthy experimental and theoretical progress has been made towards the top-level scientific question for the US programme on heavy-ion-fusion-science and high energy density physics: 'How can heavy-ion beams be compressed to the high intensity required to create high energy density matter and fusion conditions?' New results in transverse and longitudinal beam compression, high-brightness transport and beam acceleration will be reported. Central to this campaign is final beam compression. With a neutralizing plasma, we demonstrated transverse beam compression by an areal factor of over 100 and longitudinal compression by a factor of > 50. We also report on the first demonstration of simultaneous transverse and longitudinal beam compression in plasma. High beam brightness is key to high intensity on target, and detailed experimental and theoretical studies on the effect of secondary electrons on beam brightness degradation are reported. A new accelerator concept for near-term low-cost target heating experiments was invented, and the predicted beam dynamics validated experimentally. We show how these scientific campaigns have created new opportunities for interesting target experiments in the warm dense matter regime. Finally, we summarize progress towards heavy-ion fusion, including the demonstration of a compact driver-size high-brightness ion injector. For all components of our high intensity campaign, the new results have been obtained via tightly coupled efforts in experiments, simulations and theory

Rural:urban inequalities in post 2015 targets and indicators for drinking-water

Energy Technology Data Exchange (ETDEWEB)

Bain, R.E.S. [The Water Institute at UNC, University of North Carolina at Chapel Hill, NC (United States); Wright, J.A. [Geography and Environment, University of Southampton, Southampton (United Kingdom); Christenson, E. [The Water Institute at UNC, University of North Carolina at Chapel Hill, NC (United States); Bartram, J.K., E-mail: jbartram@unc.edu [The Water Institute at UNC, University of North Carolina at Chapel Hill, NC (United States)

2014-08-15

Disparities in access to drinking water between rural and urban areas are pronounced. Although use of improved sources has increased more rapidly in rural areas, rising from 62% in 1990 to 81% in 2011, the proportion of the rural population using an improved water source remains substantially lower than in urban areas. Inequalities in coverage are compounded by disparities in other aspects of water service. Not all improved sources are safe and evidence from a systematic review demonstrates that water is more likely to contain detectable fecal indicator bacteria in rural areas. Piped water on premises is a service enjoyed primarily by those living in urban areas so differentiating amongst improved sources would exacerbate rural:urban disparities yet further. We argue that an urban bias may have resulted due to apparent stagnation in urban coverage and the inequity observed between urban and peri-urban areas. The apparent stagnation at around 95% coverage in urban areas stems in part from relative population growth – over the last two decades more people gained access to improved water in urban areas. There are calls for setting higher standards in urban areas which would exacerbate the already extreme rural disadvantage. Instead of setting different targets, health, economic, and human rights perspectives, We suggest that the focus should be kept on achieving universal access to safe water (primarily in rural areas) while monitoring progress towards higher service levels, including greater water safety (both in rural and urban areas and among different economic strata)

Rural:urban inequalities in post 2015 targets and indicators for drinking-water.

Science.gov (United States)

Bain, R E S; Wright, J A; Christenson, E; Bartram, J K

2014-08-15

Disparities in access to drinking water between rural and urban areas are pronounced. Although use of improved sources has increased more rapidly in rural areas, rising from 62% in 1990 to 81% in 2011, the proportion of the rural population using an improved water source remains substantially lower than in urban areas. Inequalities in coverage are compounded by disparities in other aspects of water service. Not all improved sources are safe and evidence from a systematic review demonstrates that water is more likely to contain detectable fecal indicator bacteria in rural areas. Piped water on premises is a service enjoyed primarily by those living in urban areas so differentiating amongst improved sources would exacerbate rural:urban disparities yet further. We argue that an urban bias may have resulted due to apparent stagnation in urban coverage and the inequity observed between urban and peri-urban areas. The apparent stagnation at around 95% coverage in urban areas stems in part from relative population growth - over the last two decades more people gained access to improved water in urban areas. There are calls for setting higher standards in urban areas which would exacerbate the already extreme rural disadvantage. Instead of setting different targets, health, economic, and human rights perspectives, We suggest that the focus should be kept on achieving universal access to safe water (primarily in rural areas) while monitoring progress towards higher service levels, including greater water safety (both in rural and urban areas and among different economic strata). Copyright © 2014 Elsevier B.V. All rights reserved.

Rural:urban inequalities in post 2015 targets and indicators for drinking-water

International Nuclear Information System (INIS)

Bain, R.E.S.; Wright, J.A.; Christenson, E.; Bartram, J.K.

2014-01-01

Disparities in access to drinking water between rural and urban areas are pronounced. Although use of improved sources has increased more rapidly in rural areas, rising from 62% in 1990 to 81% in 2011, the proportion of the rural population using an improved water source remains substantially lower than in urban areas. Inequalities in coverage are compounded by disparities in other aspects of water service. Not all improved sources are safe and evidence from a systematic review demonstrates that water is more likely to contain detectable fecal indicator bacteria in rural areas. Piped water on premises is a service enjoyed primarily by those living in urban areas so differentiating amongst improved sources would exacerbate rural:urban disparities yet further. We argue that an urban bias may have resulted due to apparent stagnation in urban coverage and the inequity observed between urban and peri-urban areas. The apparent stagnation at around 95% coverage in urban areas stems in part from relative population growth – over the last two decades more people gained access to improved water in urban areas. There are calls for setting higher standards in urban areas which would exacerbate the already extreme rural disadvantage. Instead of setting different targets, health, economic, and human rights perspectives, We suggest that the focus should be kept on achieving universal access to safe water (primarily in rural areas) while monitoring progress towards higher service levels, including greater water safety (both in rural and urban areas and among different economic strata)

Technology strategy for gas technologies; Technology Target Areas; TTA8 Gas Technology

Energy Technology Data Exchange (ETDEWEB)

2008-07-01

TTA8 - Gas technologies points out the various routes Norway can follow to capitalise on the vast resources of natural gas that will be produced in the years to come by developing a strong technology and competence platform. A broad view is taken for the value creation having as basis the continued gas export from NCS to Europe, but also a strong focus on development of gas resources in other parts of the world. The latter can also be seen as part of international positioning for upstream resources and does also include involvements in projects, and export of technology and products. The TTA has structured the analysis into 3 main areas: Gas transport and processing (pipeline, LNG, other); Gas conversion to fuels, chemicals and materials; CO{sub 2} management. In this report, for each of these areas, scenarios based on a gap analysis are presented. One of the key goals has been to identify pacing and emerging technologies for the next 20 years. Based on this, technologies have been mapped according to importance for future competitiveness and technology ambitions. This also includes primary funding responsibilities (public and/or industry). The road map below reflects the key issues in the proposed strategy. The base level of the figure explains areas that will have to be pursued to maintain Norway's role as a key gas and gas technology provider. The second layer represents near term options and possibilities with a reasonable risk profile that could further enhance the Norwegian position given the resources and drive to further develop this industry. As the top layer we have selected some of our 'dreams', what we may achieve if a progressive approach is followed with a strongly innovation based policy. It is acknowledged by the TTA that Norway cannot be a leading technology player in all aspects of the gas value chain. For some technologies we should be an active player and developer, whilst for other technologies we should become a competent buyer and user. This

Technology strategy for gas technologies; Technology Target Areas; TTA8 Gas Technology

Energy Technology Data Exchange (ETDEWEB)

2008-07-01

TTA8 - Gas technologies points out the various routes Norway can follow to capitalise on the vast resources of natural gas that will be produced in the years to come by developing a strong technology and competence platform. A broad view is taken for the value creation having as basis the continued gas export from NCS to Europe, but also a strong focus on development of gas resources in other parts of the world. The latter can also be seen as part of international positioning for upstream resources and does also include involvements in projects, and export of technology and products. The TTA has structured the analysis into 3 main areas: Gas transport and processing (pipeline, LNG, other); Gas conversion to fuels, chemicals and materials; CO{sub 2} management. In this report, for each of these areas, scenarios based on a gap analysis are presented. One of the key goals has been to identify pacing and emerging technologies for the next 20 years. Based on this, technologies have been mapped according to importance for future competitiveness and technology ambitions. This also includes primary funding responsibilities (public and/or industry). The road map below reflects the key issues in the proposed strategy. The base level of the figure explains areas that will have to be pursued to maintain Norway's role as a key gas and gas technology provider. The second layer represents near term options and possibilities with a reasonable risk profile that could further enhance the Norwegian position given the resources and drive to further develop this industry. As the top layer we have selected some of our 'dreams', what we may achieve if a progressive approach is followed with a strongly innovation based policy. It is acknowledged by the TTA that Norway cannot be a leading technology player in all aspects of the gas value chain. For some technologies we should be an active player and developer, whilst for other technologies we should become a competent buyer

Reference Structures: Stagnation, Progress, and Future Challenges.

Science.gov (United States)

Greenberg, Jane

1997-01-01

Assesses the current state of reference structures in online public access catalogs (OPACs) in a framework defined by stagnation, progress, and future challenges. Outlines six areas for reference structure development. Twenty figures provide illustrations. (AEF)

Quantifying progress toward a conservation assessment for all plants.

Science.gov (United States)

Bachman, Steven P; Nic Lughadha, Eimear M; Rivers, Malin C

2018-06-01

The Global Strategy for Plant Conservation (GSPC) set an ambitious target to achieve a conservation assessment for all known plant species by 2020. We consolidated digitally available plant conservation assessments and reconciled their scientific names and assessment status to predefined standards to provide a quantitative measure of progress toward this target. The 241,919 plant conservation assessments generated represent 111,824 accepted land plant species (vascular plants and bryophytes, not algae). At least 73,081 and up to 90,321 species have been assessed at the global scale, representing 21-26% of known plant species. Of these plant species, at least 27,148 and up to 32,542 are threatened. Eighty plant families, including some of the largest, such as Asteraceae, Orchidaceae, and Rubiaceae, are underassessed and should be the focus of assessment effort if the GSPC target is to be met by 2020. Our data set is accessible online (ThreatSearch) and is a baseline that can be used to directly support other GSPC targets and plant conservation action. Although around one-quarter of a million plant assessments have been compiled, the majority of plants are still unassessed. The challenge now is to build on this progress and redouble efforts to document conservation status of unassessed plants to better inform conservation decisions and conserve the most threatened species. © 2017 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

Alcohol consumption and prostate cancer incidence and progression

DEFF Research Database (Denmark)

Brunner, Clair; Davies, Neil M; Martin, Richard M

2017-01-01

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this stud...... consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression....

An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression

Science.gov (United States)

2017-10-01

targeting of critical androgen receptor -604 coregulator interactions in prostate cancer . Nature communications 4, 1923, 605 doi:10.1038/ncomms2912 (2013...AWARD NUMBER: W81XWH-16-1-0474 TITLE: An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression PRINCIPAL INVESTIGATOR...14 Sep 2017 4. Title An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression 5a. CONTRACT NUMBER 5b. GRANT NUMBER

Target assignment for security officers to K targets (TASK)

International Nuclear Information System (INIS)

Rowland, J.R.; Shelton, K.W.; Stunkel, C.B.

1983-02-01

A probabilistic algorithm is developed to provide an optimal Target Assignment for Security officers to K targets (TASK) using a maximin criterion. Under the assumption of only a limited number (N) of security officers, the TASK computer model determines deployment assignments which maximize the system protection against sabotage by an adversary who may select any link in the system, including the weakest, for the point of attack. Applying the TASK model to a hypothetical nuclear facility containing a nine-level building reveals that aggregate targets covering multiple vital areas should be utilized to reduce the number of possible target assignments to a value equal to or only slightly larger than N. The increased probability that a given aggregate target is covered by one or more security officers offsets the slight decrease in interruption probability due to its occurring earlier in the adversary's path. In brief, the TASK model determines the optimal maximin deployment strategy for limited numbers of security officers and calculates a quantitative measure of the resulting system protection

ECTRIMS/ACTRIMS 2017: Closing in on neurorepair in progressive multiple sclerosis.

Science.gov (United States)

Kremer, David; Küry, Patrick; Hartung, Hans-Peter

2018-04-01

While there is now a multitude of potent medications for relapsing-remitting multiple sclerosis (RRMS), effective therapies targeting neurodegeneration in progressive multiple sclerosis types are still lacking. Stimulation of neurorepair in this disease remains a pathogenetically defined treatment goal. However, therapeutic progress is slowed by the still inadequate tool set to capture "regeneration/repair" in MS and to define appropriate outcomes in clinical trials. In this review, we discuss studies investigating promising regenerative agents for progressive MS which were recently presented during the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)/Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017 meeting in Paris.