DEPDC5 as a potential therapeutic target for epilepsy.

PubMed

Myers, Kenneth A; Scheffer, Ingrid E

2017-06-01

Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy. Areas covered: This review summarizes the mTOR pathway, including regulators and downstream effectors, emphasizing recent developments in the understanding of the complex role of the GATOR1 complex. We review the epilepsy types associated with mTOR overactivity, including tuberous sclerosis, polyhydramnios megalencephaly symptomatic epilepsy, cortical dysplasia, non-lesional focal epilepsy and post-traumatic epilepsy. Currently available mTOR inhibitors are discussed, primarily rapamycin analogs and ATP competitive mTOR inhibitors. Expert opinion: DEPDC5 is an attractive therapeutic target in focal epilepsy, as effects of DEPDC5 agonists would likely be anti-epileptogenic and more selective than currently available mTOR inhibitors. Therapeutic effects might be synergistic with certain existing dietary therapies, including the ketogenic diet.

Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis

DTIC Science & Technology

2016-07-01

5’-aat tat ttt ata tgg aat gag caa gta tgt ttt atc ata att gac cag ttc att tca agg acc ttc aaa aat ata cct acg aat tcg agc tcg ttt aaa c-3’), or...oTsc13 (5’-tta aga gtt cag att tgc ttt atg tgg tta ttc tgc tga agg tcc taa ttt att gac gtt gaa aaa taa agg cca cat agc gga tcc ccg ggt taa tta a-3...and oTsc14 (5’-ata aaa aaa att aat taa tga tgg caa ggc aca atc gta atc aat ctt tta att tag gac ttt tta tat gcc ctt atg gcg aat tcg agc tcg ttt aaa c

OPS MCC level B/C formulation requirements: Area targets and space volumes processor

NASA Technical Reports Server (NTRS)

Bishop, M. J., Jr.

1979-01-01

The level B/C mathematical specifications for the area targets and space volumes processor (ATSVP) are described. The processor is designed to compute the acquisition-of-signal (AOS) and loss-of-signal (LOS) times for area targets and space volumes. The characteristics of the area targets and space volumes are given. The mathematical equations necessary to determine whether the spacecraft lies within the area target or space volume are given. These equations provide a detailed model of the target geometry. A semianalytical technique for predicting the AOS and LOS time periods is disucssed. This technique was designed to bound the actual visibility period using a simplified target geometry model and unperturbed orbital motion. Functional overview of the ATSVP is presented and it's detailed logic flow is described.

7 CFR 600.5 - Area offices.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Area offices. 600.5 Section 600.5 Agriculture... AGRICULTURE GENERAL ORGANIZATION § 600.5 Area offices. Each area office is under the direction and supervision... for NRCS activities in the geographical area served by the area office. Usually the geographical area...

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Gulf of Maine off Seal Island... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger zone. A circular area with a radius of 1.5 nautical miles, having its center just easterly of Seal...

7 CFR 985.5 - Production area.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Production area. 985.5 Section 985.5 Agriculture... HANDLING OF SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Definitions § 985.5 Production area. Production area means all the area within the States of Washington, Idaho, Oregon, and that...

Increased hepatic mitochondrial FA oxidation reduces plasma and liver TG levels and is associated with regulation of UCPs and APOC-III in rats

PubMed Central

Lindquist, Carine; Bjørndal, Bodil; Rossmann, Christine Renate; Tusubira, Deusdedit; Svardal, Asbjørn; Røsland, Gro Vatne; Tronstad, Karl Johan; Hallström, Seth; Berge, Rolf Kristian

2017-01-01

Hepatic mitochondrial function, APOC-III, and LPL are potential targets for triglyceride (TG)-lowering drugs. After 3 weeks of dietary treatment with the compound 2-(tridec-12-yn-1-ylthio)acetic acid (1-triple TTA), the hepatic mitochondrial FA oxidation increased more than 5-fold in male Wistar rats. Gene expression analysis in liver showed significant downregulation of APOC-III and upregulation of LPL and the VLDL receptor. This led to lower hepatic (53%) and plasma (73%) TG levels. Concomitantly, liver-specific biomarkers related to mitochondrial biogenesis and function (mitochondrial DNA, citrate synthase activity, and cytochrome c and TFAM gene expression) were elevated. Interestingly, 1-triple TTA lowered plasma acetylcarnitine levels, whereas the concentration of β-hydroxybutyrate was increased. The hepatic energy state was reduced in 1-triple TTA-treated rats, as reflected by increased AMP/ATP and decreased ATP/ADP ratios, whereas the energy state remained unchanged in muscle and heart. The 1-triple TTA administration induced gene expression of uncoupling protein (UCP)2 and UCP3 in liver. In conclusion, the 1-triple TTA-mediated clearance of blood TG may result from lowered APOC-III production, increased hepatic LPL gene expression, mitochondrial FA oxidation, and (re)uptake of VLDL facilitating drainage of FAs to the liver for β-oxidation and production of ketone bodies as extrahepatic fuel. The possibility that UCP2 and UCP3 mediate a moderate degree of mitochondrial uncoupling should be considered. PMID:28473603

Large area thermal target board: An improvement to environmental effects and system parameters characterization

NASA Astrophysics Data System (ADS)

Watkins, Wendell R.; Bean, Brent L.; Munding, Peter D.

1994-06-01

Recent field tests have provided excellent opportunities to use a new characterization tool associated with the Mobile Imaging Spectroscopy Laboratory (MISL) of the Battlefield Environment Directorate, formerly the U.S. Army Atmospheric Sciences Laboratory. The MISL large area (1.8 by 1.8 m, uniform temperature, thermal target) was used for characterization and isolation of phenomena which impact target contrast. By viewing the target board from closeup and distant ranges simultaneously with the MISL thermal imagers, the inherent scene content could be calibrated and the degrading effects of atmospheric propagation could be isolated. The target board is equipped with several spatial frequency bar patterns, but only the largest 3.5-cycle full area bar pattern was used for the distant range of 1.6 km. The quantities measured with the target board include the inherent background change, the contrast transmission, and the atmospheric modulation transfer function. The MISL target board has a unique design which makes it lightweight with near perfect transition between the hot and cold portions of the bar pattern. The heated portion of the target is an elongated rectangular even which is tilted back at a 30 deg angle to form a 1.8 by 1.8 m square when viewed from the front. The cold bars we positioned in front of the heated oven surface and can be oriented in either the vertical or horizontal direction. The oven is mounted on a lightweight trailer for one- or two-man positioning. An attached metal and canvas structure is used to shield the entire target from both solar loading and cooling winds. The target board has a thin aluminum sheet front surface which is insulated from the oven's heating structure.

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

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

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).

Target surface area effects on hot electron dynamics from high intensity laser–plasma interactions

DOE PAGES

Zulick, C.; Raymond, A.; McKelvey, A.; ...

2016-06-15

Reduced surface area targets were studied using an ultra-high intensity femtosecond laser in order to determine the effect of electron sheath field confinement on electron dynamics. X-ray emission due to energetic electrons was imaged using a K α imaging crystal. Electrons were observed to travel along the surface of wire targets, and were slowed mainly by the induced fields. Targets with reduced surface areas were correlated with increased hot electron densities and proton energies. Furthermore, Hybrid Vlasov–Fokker–Planck simulations demonstrated increased electric sheath field strength in reduced surface area targets.

Abolition of Peroxiredoxin-5 Mitochondrial Targeting during Canid Evolution

PubMed Central

Van der Eecken, Valérie; Clippe, André; Dekoninck, Sophie; Goemaere, Julie; Walbrecq, Geoffroy; Van Veldhoven, Paul P.; Knoops, Bernard

2013-01-01

In human, the subcellular targeting of peroxiredoxin-5 (PRDX5), a thioredoxin peroxidase, is dependent on the use of multiple alternative transcription start sites and two alternative in-frame translation initiation sites, which determine whether or not the region encoding a mitochondrial targeting sequence (MTS) is translated. In the present study, the abolition of PRDX5 mitochondrial targeting in dog is highlighted and the molecular mechanism underlying the loss of mitochondrial PRDX5 during evolution is examined. Here, we show that the absence of mitochondrial PRDX5 is generalized among the extant canids and that the first events leading to PRDX5 MTS abolition in canids involve a mutation in the more 5′ translation initiation codon as well as the appearance of a STOP codon. Furthermore, we found that PRDX5 MTS functionality is maintained in giant panda and northern elephant seal, which are phylogenetically closely related to canids. Also, the functional consequences of the restoration of mitochondrial PRDX5 in dog Madin-Darby canine kidney (MDCK) cells were investigated. The restoration of PRDX5 mitochondrial targeting in MDCK cells, instead of protecting, provokes deleterious effects following peroxide exposure independently of its peroxidase activity, indicating that mitochondrial PRDX5 gains cytotoxic properties under acute oxidative stress in MDCK cells. Altogether our results show that, although mitochondrial PRDX5 cytoprotective function against oxidative stress has been clearly demonstrated in human and rodents, PRDX5 targeting to mitochondria has been evolutionary lost in canids. Moreover, restoration of mitochondrial PRDX5 in dog MDCK cells, instead of conferring protection against peroxide exposure, makes them more vulnerable. PMID:24023783

32 CFR 1602.5 - Area office staff.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Area office staff. 1602.5 Section 1602.5....5 Area office staff. The compensated employees, civilian and military, of the Selective Service System employed in an area office will be referred to as the area office staff. ...

32 CFR 1602.5 - Area office staff.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Area office staff. 1602.5 Section 1602.5....5 Area office staff. The compensated employees, civilian and military, of the Selective Service System employed in an area office will be referred to as the area office staff. ...

32 CFR 1602.5 - Area office staff.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Area office staff. 1602.5 Section 1602.5....5 Area office staff. The compensated employees, civilian and military, of the Selective Service System employed in an area office will be referred to as the area office staff. ...

32 CFR 1602.5 - Area office staff.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Area office staff. 1602.5 Section 1602.5....5 Area office staff. The compensated employees, civilian and military, of the Selective Service System employed in an area office will be referred to as the area office staff. ...

32 CFR 1602.5 - Area office staff.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Area office staff. 1602.5 Section 1602.5....5 Area office staff. The compensated employees, civilian and military, of the Selective Service System employed in an area office will be referred to as the area office staff. ...

Geothermal Target Areas in Colorado as Identified by Remote Sensing Techniques

DOE Data Explorer

Khalid Hussein

2012-02-01

This layer contains the areas identified as targets of potential geothermal activity. The Criteria used to identify the target areas include: hot/warm surface exposures modeled from ASTER/Landsat satellite imagery and geological characteristics, alteration mineral commonly associated with hot springs (clays, Si, and FeOx) modeled from ASTER and Landsat data, Colorado Geological Survey (CGS) known thermal hot springs/wells and heat-flow data points, Colorado deep-seated fault zones, weakened basement identified from isostatic gravity data, and Colorado sedimentary and topographic characteristics.

Triplet-triplet annihilation in highly efficient fluorescent organic light-emitting diodes: current state and future outlook.

PubMed

Kondakov, Denis Y

2015-06-28

range of current densities producing near-maximum TTA electroluminescence are the areas where future improvements would be most beneficial. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

pH-sensitive fluorescent sensors based on europium(III) complexes.

PubMed

Zhang, Xiaolin; Jiao, Yang; Jing, Xu; Wu, Hongmei; He, Guangjie; Duan, Chunying

2011-03-21

New europium(III) complexes Eu(TTA)(2)-DSQ and Eu(TTA)(3)-DR1 were designed and synthesized as new fluorescent pH probes (where HDSQ = 5-(dimethylamino)-N-(4-(2-((8-hydroxyquinolin-2-yl)methylene)hydrazinecarbonyl)phenyl)naphthalene-1-sulfonamide, DR1 = N(1)-(4-(dimethylamino)benzylidene)-N(2)-(rhodamine-6G) lactamethylene-diamine and TTA = thiophentrifluoroacetone). Eu(TTA)(2)-DSQ exhibited high sensitivity in monitoring pH changes in neutral aqueous solution with negligible background fluorescence. Eu(TTA)(3)-DR1 comprised a green light emitting Rhodamine 6G fluorophore and a Eu(III) moiety as the origin of red light. These pH-sensitive emitter components have pK(a) values of 5.0 and 7.2 respectively, and exhibit isolated protonated steps within one molecule. Luminescence titrations demonstrate that Eu(TTA)(3)-DR1 was able to detect pH values at both near neutral pH and acidic pH ranges, and was also able to detect pH in both cultured cells and in vivo.

25 CFR 33.5 - Area education functions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Area education functions. 33.5 Section 33.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION TRANSFER OF INDIAN EDUCATION FUNCTIONS § 33.5 Area education functions. A Bureau Area Education Programs Director shall perform those Bureau...

23 CFR 752.5 - Safety rest areas.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Safety rest areas. 752.5 Section 752.5 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT LANDSCAPE AND ROADSIDE DEVELOPMENT § 752.5 Safety rest areas. (a) Safety rest areas should provide facilities reasonably necessary...

23 CFR 752.5 - Safety rest areas.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Safety rest areas. 752.5 Section 752.5 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT LANDSCAPE AND ROADSIDE DEVELOPMENT § 752.5 Safety rest areas. (a) Safety rest areas should provide facilities reasonably necessary...

23 CFR 752.5 - Safety rest areas.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Safety rest areas. 752.5 Section 752.5 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT LANDSCAPE AND ROADSIDE DEVELOPMENT § 752.5 Safety rest areas. (a) Safety rest areas should provide facilities reasonably necessary...

23 CFR 752.5 - Safety rest areas.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 23 Highways 1 2012-04-01 2012-04-01 false Safety rest areas. 752.5 Section 752.5 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT LANDSCAPE AND ROADSIDE DEVELOPMENT § 752.5 Safety rest areas. (a) Safety rest areas should provide facilities reasonably necessary...

23 CFR 752.5 - Safety rest areas.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Safety rest areas. 752.5 Section 752.5 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT LANDSCAPE AND ROADSIDE DEVELOPMENT § 752.5 Safety rest areas. (a) Safety rest areas should provide facilities reasonably necessary...

25 CFR 33.5 - Area education functions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Area education functions. 33.5 Section 33.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION TRANSFER OF INDIAN EDUCATION FUNCTIONS § 33.5 Area education functions. A Bureau Area Education Programs Director shall perform those Bureau...

25 CFR 33.5 - Area education functions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Area education functions. 33.5 Section 33.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION TRANSFER OF INDIAN EDUCATION FUNCTIONS § 33.5 Area education functions. A Bureau Area Education Programs Director shall perform those Bureau...

25 CFR 33.5 - Area education functions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Area education functions. 33.5 Section 33.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION TRANSFER OF INDIAN EDUCATION FUNCTIONS § 33.5 Area education functions. A Bureau Area Education Programs Director shall perform those Bureau...

AN EARLY STAGE IN THE PLANT RECOLONIZATION OF A NUCLEAR TARGET AREA

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

Rickard, W.H.; Shields, L.M.

1963-01-01

Vegetational analyses were conducted three years postdetonation in a nuclear target area in a Grayia spinosa-Lycium andersonii community in Yucca Fiat, Nevada. Annual plants dominated the early stage of recolonization and were quantitatively more abundant in the disturbed areas than in an adjacent undisturbed shrub community. Ment zelia albicaulis and Chaenactis steviodes occurred in both disturbed and undisturbed areas, however; Mentzelia was more abundant in disturbed areas while Chaenactis was more abundant in the undisturbed community. Salsola kali was confined to disturbed areas while Phacelia vallismortae was more often encountered in the undisturbed community. The plant recolonization of a mechanicallymore » disturbed area was quantitatively and qualitatively more like that of the interior zone of the nuclear target area than less disturbed habitats. These data support a conclusion that soil displacement presents a more rigorous habitat for plant recolonization than disturbances created by the wider ranging destructive components of a nuclear detonation. (auth)« less

25 CFR 33.5 - Area education functions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true Area education functions. 33.5 Section 33.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION TRANSFER OF INDIAN EDUCATION FUNCTIONS § 33.5 Area education functions. A Bureau Area Education Programs Director shall perform those Bureau of...

The effects of figure/ground, perceived area, and target saliency on the luminosity threshold.

PubMed

Bonato, F; Cataliotti, J

2000-02-01

Observers adjusted the luminance of a target region until it began to appear self-luminous, or glowing. In Experiment 1, the target was either a face-shaped region (figure) or a non-face-shaped region (ground) of identical area that appeared to be the face's background. In Experiment 2, the target was a square or a trapezoid of identical area that appeared as a tilted rectangle. In Experiment 3, the target was a square surrounded by square, circular, or diamond-shaped elements. Targets that (1) were perceived as figures, (2) were phenomenally small in area, or (3) did not group well with other elements in the array because of shape appeared self-luminous at significantly lower luminance levels. These results indicate that like lightness perception, the luminosity threshold is influenced by perceptual organization and is not based on low-level retinal processes alone.

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

PubMed

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  < 0.05). Group 1 patients and group 3 data significantly differed in seed numbers ( P  < 0.01). Our results imply that extending the implantation 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.

7 CFR 925.5 - Production area.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 8 2012-01-01 2012-01-01 false Production area. 925.5 Section 925.5 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

7 CFR 925.5 - Production area.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Production area. 925.5 Section 925.5 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

7 CFR 925.5 - Production area.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 8 2014-01-01 2014-01-01 false Production area. 925.5 Section 925.5 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

7 CFR 925.5 - Production area.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 8 2013-01-01 2013-01-01 false Production area. 925.5 Section 925.5 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

7 CFR 925.5 - Production area.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Production area. 925.5 Section 925.5 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

Target vs. background discrimination using multispectral data in 1.5-14.5 micron

NASA Astrophysics Data System (ADS)

Cogliandro, Santo; Panizza, Marco; Castelli, Paola

1987-01-01

LOWTRAN V model calculations are compared to experimental spectral background radiance and spectral transmittance data in the 1.5 to 14.5-micron band, in order to identify the most important parameters affecting the discrimination of targets from background. Attention is accordingly given to the IR energy emitted by a reference plate at different values of temperature and emissivity vs various previously investigated backgrounds. Targets at near-ambient temperature are also considered.

Identification of clinical target areas in the brainstem of prion‐infected mice

PubMed Central

Mirabile, Ilaria; Jat, Parmjit S.; Brandner, Sebastian

2015-01-01

Aims While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas. Method We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset). Results We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre‐Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem. Conclusions Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre‐Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic Creutzfeldt–Jakob disease, we suggest that these nuclei represent key clinical target areas in prion diseases. PMID:25311251

Radiation damage calculations for the SINQ Target 5

NASA Astrophysics Data System (ADS)

Wechsler, Monroe S.; Lu, Wei; Dai, Yong

2003-03-01

Calculations are underway of radiation damage (production of displacements, helium, and hydrogen) at Target 5 of the SINQ spallation neutron source at the Paul Scherrer Institute in Switzerland. The target is bombarded by 575-MeV protons, and the spallation-neutron-producing target material is liquid lead. The calculations employ the Monte Carlo code MCNPX (version 2.3.0). The peak proton and neutron fluxes at the aluminum-alloy entrance window are determined to be about 1.9E14 protons/cm2s per mA of incident proton current and 2.4E13 neutrons/cm2s per mA. For a beam exposure of 10 Ahr, the peak damage sustained at the entrance window due to protons and neutrons combined is calculated to be 7.8 dpa, 2000 appmHe, and 4000 appmH. The significance of the damage results for the entrance window and components within Target 5 will be discussed.

Inverse Design of Low-Boom Supersonic Concepts Using Reversed Equivalent-Area Targets

NASA Technical Reports Server (NTRS)

Li, Wu; Rallabhand, Sriam

2011-01-01

A promising path for developing a low-boom configuration is a multifidelity approach that (1) starts from a low-fidelity low-boom design, (2) refines the low-fidelity design with computational fluid dynamics (CFD) equivalent-area (Ae) analysis, and (3) improves the design with sonic-boom analysis by using CFD off-body pressure distributions. The focus of this paper is on the third step of this approach, in which the design is improved with sonic-boom analysis through the use of CFD calculations. A new inverse design process for off-body pressure tailoring is formulated and demonstrated with a low-boom supersonic configuration that was developed by using the mixed-fidelity design method with CFD Ae analysis. The new inverse design process uses the reverse propagation of the pressure distribution (dp/p) from a mid-field location to a near-field location, converts the near-field dp/p into an equivalent-area distribution, generates a low-boom target for the reversed equivalent area (Ae,r) of the configuration, and modifies the configuration to minimize the differences between the configuration s Ae,r and the low-boom target. The new inverse design process is used to modify a supersonic demonstrator concept for a cruise Mach number of 1.6 and a cruise weight of 30,000 lb. The modified configuration has a fully shaped ground signature that has a perceived loudness (PLdB) value of 78.5, while the original configuration has a partially shaped aft signature with a PLdB of 82.3.

Restraint status improves the predictive value of motor vehicle crash criteria for pediatric trauma team activation.

PubMed

Bozeman, Andrew P; Dassinger, Melvin S; Recicar, John F; Smith, Samuel D; Rettiganti, Mallikarjuna R; Nick, Todd G; Maxson, Robert T

2012-12-01

Most trauma centers incorporate mechanistic criteria (MC) into their algorithm for trauma team activation (TTA). We hypothesized that characteristics of the crash are less reliable than restraint status in predicting significant injury and the need for TTA. We identified 271 patients (age, <15 y) admitted with a diagnosis of motor vehicle crash. Mechanistic criteria and restraint status of each patient were recorded. Both MC and MC plus restraint status were evaluated as separate measures for appropriately predicting TTA based on treatment outcomes and injury scores. Improper restraint alone predicted a need for TTA with an odds ratios of 2.69 (P = .002). MC plus improper restraint predicted the need for TTA with an odds ratio of 2.52 (P = .002). In contrast, the odds ratio when using MC alone was 1.65 (P = .16). When the 5 MC were evaluated individually as predictive of TTA, ejection, death of occupant, and intrusion more than 18 inches were statistically significant. Improper restraint is an independent predictor of necessitating TTA in this single-institution study. Copyright © 2012 Elsevier Inc. All rights reserved.

Impacts on terrestrial biodiversity of moving from a 2°C to a 1.5°C target

NASA Astrophysics Data System (ADS)

Smith, Pete; Price, Jeff; Molotoks, Amy; Warren, Rachel; Malhi, Yadvinder

2018-05-01

We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5-14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities. This article is part of the theme issue `The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.

33 CFR 334.120 - Delaware Bay off Milford Neck; naval aircraft bombing target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Delaware Bay off Milford Neck; naval aircraft bombing target area. 334.120 Section 334.120 Navigation and Navigable Waters CORPS OF....120 Delaware Bay off Milford Neck; naval aircraft bombing target area. (a) The danger zone. A circular...

33 CFR 334.120 - Delaware Bay off Milford Neck; naval aircraft bombing target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Delaware Bay off Milford Neck; naval aircraft bombing target area. 334.120 Section 334.120 Navigation and Navigable Waters CORPS OF....120 Delaware Bay off Milford Neck; naval aircraft bombing target area. (a) The danger zone. A circular...

Philippine protected areas are not meeting the biodiversity coverage and management effectiveness requirements of Aichi Target 11.

PubMed

Mallari, Neil Aldrin D; Collar, Nigel J; McGowan, Philip J K; Marsden, Stuart J

2016-04-01

Aichi Target 11 of the Convention on Biological Diversity urges, inter alia, that nations protect at least 17 % of their land, and that protection is effective and targets areas of importance for biodiversity. Five years before reporting on Aichi targets is due, we assessed the Philippines' current protected area system for biodiversity coverage, appropriateness of management regimes and capacity to deliver protection. Although protected estate already covers 11 % of the Philippines' land area, 64 % of its key biodiversity areas (KBAs) remain unprotected. Few protected areas have appropriate management and governance infrastructures, funding streams, management plans and capacity, and a serious mismatch exists between protected area land zonation regimes and conservation needs of key species. For the Philippines to meet the biodiversity coverage and management effectiveness elements of Aichi Target 11, protected area and KBA boundaries should be aligned, management systems reformed to pursue biodiversity-led targets and effective management capacity created.

9 CFR 72.5 - Area quarantined in Texas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Area quarantined in Texas. 72.5 Section 72.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF...) FEVER IN CATTLE § 72.5 Area quarantined in Texas. The area quarantined in Texas is the quarantined area...

MEK5-ERK5 Signaling in Cancer: Implications for Targeted Therapy

PubMed Central

Hoang, Van T.; Yan, Thomas J.; Cavanaugh, Jane E.; Flaherty, Patrick T.; Beckman, Barbara S.; Burow, Matthew E.

2017-01-01

Mitogen-activated protein kinases (MAPKs) regulate diverse cellular processes including proliferation, cell survival, differentiation, and apoptosis. While conventional MAPK constituents have well-defined roles in oncogenesis, the MAPK kinase 5-extracellular signal-regulated kinase 5 (MEK5-ERK5) pathway has only recently emerged in cancer research. In this review, we consider the MEK5 signaling cascade, focusing specifically on its involvement in drug resistance and regulation of aggressive cancer phenotypes. Moreover, we explore the role of MEK5 in tumorigenesis and metastatic progression, discussing the discrepancies in preclinical studies and assessing its viability as a therapeutic target for anti-cancer agents. PMID:28153789

Time to Appendectomy and Risk of Complicated Appendicitis and Adverse Outcomes in Children.

PubMed

Serres, Stephanie K; Cameron, Danielle B; Glass, Charity C; Graham, Dionne A; Zurakowski, David; Karki, Mahima; Anandalwar, Seema P; Rangel, Shawn J

2017-08-01

Management of appendicitis as an urgent rather than emergency procedure has become an increasingly common practice in children. Controversy remains as to whether this practice is associated with increased risk of complicated appendicitis and adverse events. To examine the association between time to appendectomy (TTA) and risk of complicated appendicitis and postoperative complications. In this retrospective cohort study using the Pediatric National Surgical Quality Improvement Program appendectomy pilot database, 2429 children younger than 18 years who underwent appendectomy within 24 hours of presentation at 23 children's hospitals from January 1, 2013, through December 31, 2014, were studied. The main exposure was TTA, defined as the time from emergency department presentation to appendectomy. Patients were further categorized into early and late TTA groups based on whether their TTA was shorter or longer than their hospital's median TTA. Exposures were defined in this manner to compare rates of complicated appendicitis within a time frame sensitive to each hospital's existing infrastructure and diagnostic practices. The primary outcome was complicated appendicitis documented at operation. The association between treatment delay and complicated appendicitis was examined across all hospitals by using TTA as a continuous variable and at the level of individual hospitals by using TTA as a categorical variable comparing outcomes between late and early TTA groups. Secondary outcomes included length of stay (LOS) and postoperative complications (incisional and organ space infections, percutaneous drainage procedures, unplanned reoperation, and hospital revisits). Of the 6767 patients who met the inclusion criteria, 2429 were included in the analysis (median age, 10 years; interquartile range, 8-13 years; 1467 [60.4%] male). Median hospital TTA was 7.4 hours (range, 5.0-19.2 hours), and 574 patients (23.6%) were diagnosed with complicated appendicitis (range, 5

Identification and Herc5-mediated ISGylation of novel target proteins.

PubMed

Takeuchi, Tomoharu; Inoue, Satoshi; Yokosawa, Hideyoshi

2006-09-22

ISG15, a protein containing two ubiquitin-like domains, is an interferon-stimulated gene product that functions in antiviral response and is conjugated to various cellular proteins (ISGylation) upon interferon stimulation. ISGylation occurs via a pathway similar to the pathway for ubiquitination that requires the sequential action of E1/E2/E3: the E1 (UBE1L), E2 (UbcH8), and E3 (Efp/Herc5) enzymes for ISGylation have been hitherto identified. In this study, we identified six novel candidate target proteins for ISGylation by a proteomic approach. Four candidate target proteins were demonstrated to be ISGylated in UBE1L- and UbcH8-dependent manners, and ISGylation of the respective target proteins was stimulated by Herc5. In addition, Herc5 was capable of binding with the respective target proteins. Thus, these results suggest that Herc5 functions as a general E3 ligase for protein ISGylation.

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false San Pablo Bay, Calif.; target... 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...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false San Pablo Bay, Calif.; target... 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...

Impacts on terrestrial biodiversity of moving from a 2°C to a 1.5°C target.

PubMed

Smith, Pete; Price, Jeff; Molotoks, Amy; Warren, Rachel; Malhi, Yadvinder

2018-05-13

We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5-14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities.This article is part of the theme issue 'The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'. © 2018 The Authors.

Impacts on terrestrial biodiversity of moving from a 2°C to a 1.5°C target

PubMed Central

Price, Jeff; Molotoks, Amy; Warren, Rachel

2018-01-01

We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5–14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities. This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'. PMID:29610386

5 CFR 351.402 - Competitive area.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Competitive area. 351.402 Section 351.402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.402 Competitive area. (a) Each agency shall establish competitive areas in which employees...

5 CFR 351.402 - Competitive area.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Competitive area. 351.402 Section 351.402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.402 Competitive area. (a) Each agency shall establish competitive areas in which employees...

5 CFR 351.402 - Competitive area.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Competitive area. 351.402 Section 351.402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.402 Competitive area. (a) Each agency shall establish competitive areas in which employees...

5 CFR 351.402 - Competitive area.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Competitive area. 351.402 Section 351.402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.402 Competitive area. (a) Each agency shall establish competitive areas in which employees...

5 CFR 351.402 - Competitive area.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Competitive area. 351.402 Section 351.402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.402 Competitive area. (a) Each agency shall establish competitive areas in which employees...

7 CFR 319.56-5 - Pest-free areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Pest-free areas. 319.56-5 Section 319.56-5 Agriculture..., DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Fruits and Vegetables § 319.56-5 Pest-free areas. As... provided that the fruits or vegetables originate from an area that is free of a specific pest or pests. In...

3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation.

PubMed

Sethi, Pallavi; Jyoti, Amar; Swindell, Elden P; Chan, Ryan; Langner, Ulrich W; Feddock, Jonathan M; Nagarajan, Radhakrishnan; O'Halloran, Thomas V; Upreti, Meenakshi

2015-11-01

An appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies. Existing in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Differential Neurotoxicity Related to Tetracycline Transactivator and TDP-43 Expression in Conditional TDP-43 Mouse Model of Frontotemporal Lobar Degeneration.

PubMed

Kukreja, L; Shahidehpour, R; Kim, G; Keegan, J; Sadleir, K R; Russell, T; Csernansky, J; Mesulam, M; Vassar, R J; Wang, L; Dong, H; Geula, C

2018-05-28

Frontotemporal lobar degeneration (FTLD) is among the most prevalent dementias of early-onset. Pathologically, FTLD presents with tauopathy or TAR DNA-binding protein 43 (TDP-43) proteinopathy. A biallelic mouse model of FTLD was produced on a mix FVB/129SVE background overexpressing wild-type human TDP-43 (hTDP-43) employing tetracycline transactivator (tTA), a system widely used in mouse models of neurological disorders. tTA activates hTDP-43 which is placed downstream of the tetracycline response element (TRE). The original study on this transgenic mouse found hippocampal degeneration following hTDP-43 expression, but did not account for independent effects of tTA protein. Here, we initially analyzed the neurotoxic effects of tTA in post-weaning age mice of either sex using immunostaining and area measurements of select brain regions. We observed tTA-dependent toxicity selectively in the hippocampus affecting the dentate gyrus significantly more than CA fields, whereas hTDP-43-dependent toxicity in bigenic mice occurred in most other cortical regions. Atrophy was associated with inflammation, activation of caspase-3 and loss of neurons. The atrophy associated with tTA expression was rescuable by tetracycline analog, doxycycline in the diet. MRI studies corroborated the patterns of atrophy. tTA-induced degeneration was strain-dependent and was rescued by moving the transgene onto a congenic C57BL/6 background. Despite significant hippocampal atrophy, behavioral tests in bigenic mice revealed no hippocampally mediated memory impairment. Significant atrophy in most cortical areas due solely to TDP-43 expression indicates that this mouse model remains useful for providing critical insight into co-occurrence of TDP-43 pathology, neurodegeneration and behavioral deficits in FTLD. SIGNIFICANCE STATEMENT The tTA expression system has been widely used in mice to model neurological disorders. The technique allows investigators to reversibly turn on or off disease causing

78 FR 35612 - Agency Information Collection Activities; Comment Request; Targeted Teacher Shortage Areas...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-13

... address the targeted teacher deferment provision of the Higher Education Act of 1965, as amended. The... DEPARTMENT OF EDUCATION [Docket No. ED-2013-ICCD-0076] Agency Information Collection Activities; Comment Request; Targeted Teacher Shortage Areas Nationwide Listing AGENCY: Office of Postsecondary...

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

Hagland, Hanne R.; Nilsson, Linn I.H.; Burri, Lena

Highlights: Black-Right-Pointing-Pointer We investigated mechanisms of mitochondrial regulation in rat hepatocytes. Black-Right-Pointing-Pointer Tetradecylthioacetic acid (TTA) was employed to activate mitochondrial oxidation. Black-Right-Pointing-Pointer Mitochondrial biogenesis and respiration were induced. Black-Right-Pointing-Pointer It was confirmed that PPAR target genes were induced. Black-Right-Pointing-Pointer The mechanism involved activation mTOR. -- Abstract: The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects,more » and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPAR{alpha}-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR.« less

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

PubMed Central

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

Enabling optical metrology on small 5×5μm2 in-cell targets to support flexible sampling and higher order overlay and CD control for advanced logic devices nodes

NASA Astrophysics Data System (ADS)

Salerno, Antonio; de la Fuente, Isabel; Hsu, Zack; Tai, Alan; Chang, Hammer; McNamara, Elliott; Cramer, Hugo; Li, Daoping

2018-03-01

In next generation Logic devices, overlay control requirements shrink to sub 2.5nm level on-product overlay. Historically on-product overlay has been defined by the overlay capability of after-develop in-scribe targets. However, due to design and dimension, the after development metrology targets are not completely representative for the final overlay of the device. In addition, they are confined to the scribe-lane area, which limits the sampling possibilities. To address these two issues, metrology on structures matching the device structure and which can be sampled with high density across the device is required. Conventional after-etch CDSEM techniques on logic devices present difficulties in discerning the layers of interest, potential destructive charging effects and finally, they are limited by the long measurement times[1] [2] [3] . All together, limit the sampling densities and making CDSEM less attractive for control applications. Optical metrology can overcome most of these limitations. Such measurement, however, does require repetitive structures. This requirement is not fulfilled by logic devices, as the features vary in pitch and CD over the exposure field. The solution is to use small targets, with a maximum pad size of 5x5um2 , which can easily be placed in the logic cell area. These targets share the process and architecture of the device features of interest, but with a modified design that replicates as close as possible the device layout, allowing for in-device metrology for both CD and Overlay. This solution enables measuring closer to the actual product feature location and, not being limited to scribe-lanes, it opens the possibility of higher-density sampling schemes across the field. In summary, these targets become the facilitator of in-device metrology (IDM), that is, enabling the measurements both in-device Overlay and the CD parameters of interest and can deliver accurate, high-throughput, dense and after-etch measurements for Logic

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

DTIC Science & Technology

2016-08-19

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 ...Science, University ofMichigan, AnnArbor,MI 48109-2099, USA E-mail: czulick@umich.edu Keywords: laser -plasma,mass-limited, fast electrons, sheath...field Abstract Reduced surface area targets were studied using an ultra-high intensity femtosecond laser in order to determine the effect of electron

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

Code of Federal Regulations, 2010 CFR

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...

A strontium-90 sequestrant for first-aid treatment of radiation emergency.

PubMed

Haratake, Mamoru; Hatanaka, Eisuke; Fuchigami, Takeshi; Akashi, Makoto; Nakayama, Morio

2012-01-01

In this study, hydrophilic porous polymer beads with phosphonic acid groups (PGMA-EGDMA-TTA-MP) were synthesized, and assessed as a radioactive strontium-90 sequestrant for the treatment of the radiation emergency. Strontium ions were rapidly absorbed into the blood from the gastrointestinal (GI) tract after oral administration to rats, and distributed to the target organ, i.e., bones. Over 40% of the administered strontium was absorbed into the blood, while the remainder was discharged in the feces within 48 h after the administration. When the PGMA-EGDMA-TTA-MP beads were administered to rats subsequent to the strontium solution, the strontium had accumulated less in the femur. Consequently, the oral administration of the PGMA-EGDMA-TTA-MP beads was effective in suppressing the absorption of strontium from the GI tract.

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

NASA Astrophysics Data System (ADS)

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.

G5G2.5 core-shell tecto-dendrimer specifically targets reactive glia in brain ischemia.

PubMed

Murta, Veronica; Schilrreff, Priscila; Rosciszewski, Gerardo; Morilla, Maria Jose; Ramos, Alberto Javier

2018-03-01

Secondary neuronal death is a serious stroke complication. This process is facilitated by the conversion of glial cells to the reactive pro-inflammatory phenotype that induces neurodegeneration. Therefore, regulation of glial activation is a compelling strategy to reduce brain damage after stroke. However, drugs have difficulties to access the CNS, and to specifically target glial cells. In the present work, we explored the use core-shell polyamidoamine tecto-dendrimer (G5G2.5 PAMAM) and studied its ability to target distinct populations of stroke-activated glial cells. We found that G5G2.5 tecto-dendrimer is actively engulfed by primary glial cells in a time- and dose-dependent manner showing high cellular selectivity and lysosomal localization. In addition, oxygen-glucose deprivation or lipopolysaccharides exposure in vitro and brain ischemia in vivo increase glial G5G2.5 uptake; not being incorporated by neurons or other cell types. We conclude that G5G2.5 tecto-dendrimer is a highly suitable carrier for targeted drug delivery to reactive glial cells in vitro and in vivo after brain ischemia. © 2017 International Society for Neurochemistry.

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Food and agricultural sciences areas targeted for... AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM Program Description § 3402.4 Food and agricultural sciences areas targeted for National Needs Graduate and...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Food and agricultural sciences areas targeted for... AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM Program Description § 3402.4 Food and agricultural sciences areas targeted for National Needs Graduate and...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 15 2011-01-01 2011-01-01 false Food and agricultural sciences areas targeted for... AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM Program Description § 3402.4 Food and agricultural sciences areas targeted for National Needs Graduate and...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 15 2012-01-01 2012-01-01 false Food and agricultural sciences areas targeted for... AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM Program Description § 3402.4 Food and agricultural sciences areas targeted for National Needs Graduate and...

Magnetic Field Effects on Triplet-Triplet Annihilation in Solutions: Modulation of Visible/NIR Luminescence.

PubMed

Mani, Tomoyasu; Vinogradov, Sergei A

2013-08-06

Photon upconversion based on sensitized triplet-triplet annihilation (TTA) presents interest for such areas as photovoltaics and imaging. Usually energy upconversion is observed as p -type delayed fluorescence from molecules whose triplet states are populated via energy transfer from a suitable triplet donor, followed by TTA. Magnetic field effects (MFE) on delayed fluorescence in molecular crystals are well known; however, there exist only a few examples of MFE on TTA in solutions, and all of them are limited to UV-emitting materials. Here we present MFE on TTA-mediated visible and near infrared (NIR) emission, sensitized by far-red absorbing metalloporphyrins in solutions at room temperature. In addition to visible delayed fluorescence from annihilator, we also observed NIR emission from the sensitizer, occurring as a result of triplet-triplet energy transfer back from annihilator, termed "delayed phosphorescence". This emission also exhibits MFE, but opposite in sign to the annihilator fluorescence.

33 CFR 334.60 - Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Harbor, Mass.; naval aircraft bombing target area. 334.60 Section 334.60 Navigation and Navigable Waters... REGULATIONS § 334.60 Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area. (a... bombing target hulk James Longstreet in Cape Cod Bay at latitude 41°49′46″, longitude 70°02′54″. (b) The...

33 CFR 334.60 - Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Harbor, Mass.; naval aircraft bombing target area. 334.60 Section 334.60 Navigation and Navigable Waters... REGULATIONS § 334.60 Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area. (a... bombing target hulk James Longstreet in Cape Cod Bay at latitude 41°49′46″, longitude 70°02′54″. (b) The...

Mesophotic depths as refuge areas for fishery-targeted species on coral reefs

NASA Astrophysics Data System (ADS)

Lindfield, Steven J.; Harvey, Euan S.; Halford, Andrew R.; McIlwain, Jennifer L.

2016-03-01

Coral reefs are subjected to unprecedented levels of disturbance with population growth and climate change combining to reduce standing coral cover and stocks of reef fishes. Most of the damage is concentrated in shallow waters (<30 m deep) where humans can comfortably operate and where physical disturbances are most disruptive to marine organisms. Yet coral reefs can extend to depths exceeding 100 m, potentially offering refuge from the threats facing shallower reefs. We deployed baited remote underwater stereo-video systems (stereo-BRUVs) at depths of 10-90 m around the southern Mariana Islands to investigate whether fish species targeted by fishing in the shallows may be accruing benefits from being at depth. We show that biomass, abundance and species richness of fishery-targeted species increased from shallow reef areas to a depth of 60 m, whereas at greater depths, a lack of live coral habitat corresponded to lower numbers of fish. The majority of targeted species were found to have distributions that ranged from shallow depths (10 m) to depths of at least 70 m, emphasising that habitat, not depth, is the limiting factor in their vertical distribution. While the gradient of abundance and biomass versus depth was steepest for predatory species, the first species usually targeted by fishing, we also found that fishery-targeted herbivores prevailed in similar biomass and species richness to 60 m. Compared to shallow marine protected areas, there was clearly greater biomass of fishery-targeted species accrued in mesophotic depths. Particularly some species typically harvested by depth-limited fishing methods (e.g., spearfishing), such as the endangered humphead wrasse Cheilinus undulatus, were found in greater abundance on deeper reefs. We conclude that mesophotic depths provide essential fish habitat and refuge for fishery-targeted species, representing crucial zones for fishery management and research into the resilience of disturbed coral reef ecosystems.

7 CFR 301.75-5 - Commercial citrus-producing areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Commercial citrus-producing areas. 301.75-5 Section... and Regulations § 301.75-5 Commercial citrus-producing areas. (a) The following are designated as commercial citrus-producing areas: American Samoa Arizona California Florida Guam Hawaii Louisiana Northern...

7 CFR 301.75-5 - Commercial citrus-producing areas.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Commercial citrus-producing areas. 301.75-5 Section... and Regulations § 301.75-5 Commercial citrus-producing areas. (a) The following are designated as commercial citrus-producing areas: American Samoa Arizona California Florida Guam Hawaii Louisiana Northern...

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

NASA Astrophysics Data System (ADS)

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.

33 CFR 334.1460 - Atlantic Ocean and Vieques Sound, in vicinity of Culebra Island; bombing and gunnery target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., in vicinity of Culebra Island; bombing and gunnery target area. 334.1460 Section 334.1460 Navigation...; bombing and gunnery target area. (a) The danger zone. From Punta Resaca on the north coast of Culebra at... danger zone is subject to use as a target area for bombing and gunnery practice. It will be open to...

33 CFR 334.1460 - Atlantic Ocean and Vieques Sound, in vicinity of Culebra Island; bombing and gunnery target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., in vicinity of Culebra Island; bombing and gunnery target area. 334.1460 Section 334.1460 Navigation...; bombing and gunnery target area. (a) The danger zone. From Punta Resaca on the north coast of Culebra at... danger zone is subject to use as a target area for bombing and gunnery practice. It will be open to...

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. 334.10 Section 334.10 Navigation and Navigable Waters CORPS... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger...

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. 334.10 Section 334.10 Navigation and Navigable Waters CORPS... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger...

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. 334.10 Section 334.10 Navigation and Navigable Waters CORPS... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger...

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. 334.10 Section 334.10 Navigation and Navigable Waters CORPS... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger...

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

PubMed Central

García-Avilés, Álvaro; Albert-Gascó, Héctor; Arnal-Vicente, Isabel; Elhajj, Ebtisam; Sanjuan-Arias, Julio; Sanchez-Perez, Ana María; Olucha-Bordonau, Francisco

2015-01-01

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 MPD administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered MPD doses (1.3, 2.7 and 5 mg/Kg) to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3 mg/Kg MPD; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum (MS), an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5 mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the MS the sparse tyrosine hydroxylase fibers 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. PMID:25852493

5-HT1a activation in PO/AH area induces therapeutic hypothermia in a rat model of intracerebral hemorrhage

PubMed Central

Liang, Tan; Chen, Qianwei; Li, Qiang; Li, Rongwei; Tang, Jun; Hu, Rong; Zhong, Jun; Ge, Hongfei; Liu, Xin; Hua, Feng

2017-01-01

Therapeutic hypothermia is widely applied as a neuroprotective measure on intracerebral hemorrhage (ICH). However, several clinical trials regarding physical hypothermia encountered successive failures because of its side-effects in recent years. Increasing evidences indicate that chemical hypothermia that targets hypothalamic 5-HT1a has potential to down-regulate temperature set point without major side-effects. Thus, this study examined the efficacy and safety of 5-HT1a stimulation in PO/AH area for treating ICH rats. First, the relationship between head temperature and clinical outcomes was investigated in ICH patients and rat models, respectively. Second, the expression and distribution of 5-HT1a receptor in PO/AH area was explored by using whole-cell patch and confocal microscopy. In the meantime, the whole-cell patch was subsequently applied to investigate the involvement of 5-HT1a receptors in temperature regulation. Third, we compared the efficacy between traditional PH and 5-HT1a activation-induced hypothermia for ICH rats. Our data showed that more severe perihematomal edema (PHE) and neurological deficits was associated with increased head temperature following ICH. 5-HT1a receptor was located on warm-sensitive neurons in PO/AH area and 8-OH-DPAT (5-HT1a receptor agonist) significantly enhanced the firing rate of warm-sensitive neurons. 8-OH-DPAT treatment provided a steadier reduction in brain temperature without a withdrawal rebound, which also exhibited a superior neuroprotective effect on ICH-induced neurological dysfunction, white matter injury and BBB damage compared with physical hypothermia. These findings suggest that chemical hypothermia targeting 5-HT1a receptor in PO/AH area could act as a novel therapeutic manner against ICH, which may provide a breakthrough for therapeutic hypothermia. PMID:29088731

2016 Waste Management Monitoring Report Area 3 and Area 5 Radioactive Waste Management Sites

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

Black, David

Environmental monitoring data are collected at and around the Area 3 and Area 5 Radioactive Waste Management Sites (RWMSs) within the Nevada National Security Site (NNSS). These data include direct radiation exposure, as well as radiation from the air, groundwater, meteorology, and vadose zone. This report summarizes the 2016 environmental data to provide an overall evaluation of RWMS performance and to support environmental compliance and performance assessment (PA) activities. Some of these data (e.g., radiation exposure, air, and groundwater) are presented in other reports, developed by National Security Technologies, LLC Direct radiation monitoring data indicate exposure levels at the RWMSsmore » are within the range of background levels measured at the NNSS. Slightly elevated exposure levels outside the Area 3 RWMS are attributed to nearby historical aboveground nuclear weapons tests. Air monitoring data show that tritium concentrations in water vapor and americium and plutonium concentrations in air particles are below Derived Concentration Standards for these radionuclides. Groundwater monitoring data indicate the groundwater in the uppermost aquifer beneath the Area 5 RWMS is not impacted by RWMS operations. Results of groundwater analysis from wells around the Area 5 RWMS were all below established investigation levels. Leachate samples collected from the leachate collection system at the mixed low-level waste cell were below established contaminant regulatory limits. During 2016, precipitation at the Area 3 RWMS was 8% below average, and precipitation at the Area 5 RWMS was 8% above average. Water balance measurements indicate that evapotranspiration from the vegetated weighing lysimeter dries the soil and prevents downward percolation of precipitation more effectively than evaporation as measured from the bare-soil weighing lysimeter. Vadose zone monitoring on Area 5 and Area 3 RWMS cell covers shows no evidence of precipitation percolating through the

Measuring the extent and effectiveness of protected areas as an indicator for meeting global biodiversity targets

PubMed Central

Chape, S; Harrison, J; Spalding, M; Lysenko, I

2005-01-01

There are now over 100 000 protected areas worldwide, covering over 12% of the Earth's land surface. These areas represent one of the most significant human resource use allocations on the planet. The importance of protected areas is reflected in their widely accepted role as an indicator for global targets and environmental assessments. However, measuring the number and extent of protected areas only provides a unidimensional indicator of political commitment to biodiversity conservation. Data on the geographic location and spatial extent of protected areas will not provide information on a key determinant for meeting global biodiversity targets: ‘effectiveness’ in conserving biodiversity. Although tools are being devised to assess management effectiveness, there is no globally accepted metric. Nevertheless, the numerical, spatial and geographic attributes of protected areas can be further enhanced by investigation of the biodiversity coverage of these protected areas, using species, habitats or biogeographic classifications. This paper reviews the current global extent of protected areas in terms of geopolitical and habitat coverage, and considers their value as a global indicator of conservation action or response. The paper discusses the role of the World Database on Protected Areas and collection and quality control issues, and identifies areas for improvement, including how conservation effectiveness indicators may be included in the database to improve the value of protected areas data as an indicator for meeting global biodiversity targets. PMID:15814356

Comparative elemental analysis of fine particulate matter (PM2.5) from industrial and residential areas in Greater Cairo-Egypt by means of a multi-secondary target energy dispersive X-ray fluorescence spectrometer

NASA Astrophysics Data System (ADS)

Shaltout, Abdallah A.; Hassan, Salwa K.; Karydas, Andreas G.; Zaki, Z. I.; Mostafa, Nasser Y.; Kregsamer, Peter; Wobrauschek, Peter; Streli, Christina

2018-07-01

Fine aerosol particles with aerodynamic diameter equal or <2.5 μm (PM2.5) have been collected from industrial and residential areas of Greater Cairo, Egypt during two different seasons namely; autumn 2014 and winter 2014/2015. Energy dispersive X-ray fluorescence (EDXRF) analysis utilizing polarization geometry and three different secondary targets (CaF2, Ge, and Mo) was employed for the quantitative analysis of eighteen (18) elements in PM2.5 samples. Light elements like Na and Mg was possible to be quantified, whereas detection limits in the range of few ng m-3 were attained for the most of the detected elements. Although, the average mass concentrations of the PM2.5 collected from the residential area (27 ± 7 μg m-3) is close to the annual mean limit value, a significant number of the collected samples (33%) presented higher average mass concentrations. For the industrial location, the average mass concentration is equal to 55 ± 19 μg m-3, exceeded twofold the annual mean limit value of the European Commission. Remarkably high elemental concentrations were determined for the most of the detected elements from the industrial area samples, clearly indicating the significant influence of anthropogenic activities. The present optimized EDXRF analysis offered significantly improved analytical range and limits of detection with respect to previous similar studies, thus enhancing our knowledge and understanding on the contribution of different pollution sources.

Projection of heat waves over China for eight different global warming targets using 12 CMIP5 models

NASA Astrophysics Data System (ADS)

Guo, Xiaojun; Huang, Jianbin; Luo, Yong; Zhao, Zongci; Xu, Ying

2017-05-01

Simulation and projection of the characteristics of heat waves over China were investigated using 12 CMIP5 global climate models and the CN05.1 observational gridded dataset. Four heat wave indices (heat wave frequency, longest heat wave duration, heat wave days, and high temperature days) were adopted in the analysis. Evaluations of the 12 CMIP5 models and their ensemble indicated that the multi-model ensemble could capture the spatiotemporal characteristics of heat wave variation over China. The inter-decadal variations of heat waves during 1961-2005 can be well simulated by multi-model ensemble. Based on model projections, the features of heat waves over China for eight different global warming targets (1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, and 5.0 °C) were explored. The results showed that the frequency and intensity of heat waves would increase more dramatically as the global mean temperature rise attained higher warming targets. Under the RCP8.5 scenario, the four China-averaged heat wave indices would increase from about 1.0 times/year, 2.5, 5.4, and 13.8 days/year to about 3.2 times/year, 14.0, 32.0, and 31.9 days/year for 1.5 and 5.0 °C warming targets, respectively. Those regions that suffer severe heat waves in the base climate would experience the heat waves with greater frequency and severity following global temperature rise. It is also noteworthy that the areas in which a greater number of severe heat waves occur displayed considerable expansion. Moreover, the model uncertainties exhibit a gradual enhancement with projected time extending from 2006 to 2099.

miR-151-5p, targeting chromatin remodeler SMARCA5, as a marker for the BRCAness phenotype

PubMed Central

Tommasi, Stefania; Pinto, Rosamaria; Danza, Katia; Pilato, Brunella; Palumbo, Orazio; Micale, Lucia; Summa, Simona De

2016-01-01

In recent years, the assessment of biomarkers useful for “precision medicine” has been a hot topic in research. The involvement of microRNAs in the pathogenesis of breast cancer has been highly investigated with the aim of being able to molecularly stratify this highly heterogeneous disease. Our aim was to identify microRNAs targeting DNA repair machinery, through Affymetrix GeneChip miRNA Arrays, in a cohort of BRCA-related and sporadic breast cancers. Moreover, we analyzed microRNA expression taking into account our previous results on the expression of PARP1, because of its importance in targeted therapy. miR-361-5p and miR-151-5p were found to be overexpressed in PARP1-upregulating BRCA-germline mutated and sporadic breast tumors. Pathway enrichment analysis was performed to identify potential target genes to be analyzed in the validation step in an independent cohort. Our results confirmed the overexpression of miR-151-5p and, interestingly, its role in the targeting of SMARCA5, a chromatin remodeler. This result was also confirmed in vitro, both through luciferase assay and by analyzing endogenous levels of SMARCA5 in MCF-7 cell lines using miR-151-5p mimic and inhibitor. In conclusion, our data showed the possibility of considering the overexpression of PARP1 and miR-151-5p as biomarkers useful to correctly treat sporadic breast cancers, which eventually could be considered as BRCAness tumors, with PARP-inhibitors. PMID:27385001

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River... Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U.S. Naval Air...) The regulations. (i) Through navigation of surface craft outside the target areas will be permitted at...

An Analysis of Determinants of Under-5 Mortality across Countries: Defining Priorities to Achieve Targets in Sustainable Developmental Goals.

PubMed

Acheampong, Michael; Ejiofor, Chukwudi; Salinas-Miranda, Abraham

2017-06-01

Objectives The end of the era of millennium development goals (MDGs) ushered in the sustainable development goals (SDGs) with a new target for the reduction of under-five mortality rates (U5MR). Although U5MR decreased globally, the reduction was insufficient to meet MDGs targets because significant socioeconomic inequities remain unaddressed across and within countries. Thus, further progress in achieving the new SDGs target will be hindered if there is no adequate prioritization of important socioeconomic, healthcare, and environmental factors. The objective of this study was to assess factors that account most for the differences in U5MR between countries around the globe. Methods We conducted an ordinary least squares (OLS) regression-based prioritization analysis of socioeconomic, healthcare, and environmental variables from 109 countries to understand which factors explain the differences in U5MR best. Results All indicators examined individually affected differences in U5MR between countries. However, the results of multivariate OLS regression showed that the most important factors that accounted for the differences were, in order: fertility rate, total health expenditure per capita, access to improved water and sanitation, and female employment rate. Conclusions To achieve the new global target for U5MR, policymakers must focus on certain priority areas, such as interventions that address access to affordable maternal healthcare services, educational programs for mothers, especially those who are adolescents, and safe drinking water and sanitation.

43 CFR 3101.5-3 - Alaska wildlife areas.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Alaska wildlife areas. 3101.5-3 Section... § 3101.5-3 Alaska wildlife areas. No lands within a refuge in Alaska open to leasing shall be available until the Fish and Wildlife Service has first completed compatability determinations. ...

43 CFR 3101.5-3 - Alaska wildlife areas.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Alaska wildlife areas. 3101.5-3 Section... § 3101.5-3 Alaska wildlife areas. No lands within a refuge in Alaska open to leasing shall be available until the Fish and Wildlife Service has first completed compatability determinations. ...

43 CFR 3101.5-3 - Alaska wildlife areas.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Alaska wildlife areas. 3101.5-3 Section... § 3101.5-3 Alaska wildlife areas. No lands within a refuge in Alaska open to leasing shall be available until the Fish and Wildlife Service has first completed compatability determinations. ...

43 CFR 3101.5-3 - Alaska wildlife areas.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Alaska wildlife areas. 3101.5-3 Section... § 3101.5-3 Alaska wildlife areas. No lands within a refuge in Alaska open to leasing shall be available until the Fish and Wildlife Service has first completed compatability determinations. ...

Small Molecule Screen for Candidate Antimalarials Targeting Plasmodium Kinesin-5*

PubMed Central

Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J.

2014-01-01

Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable “next generation” target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are “druggable.” One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease. PMID:24737313

Targeting the impact of agri-environmental policy - Future scenarios in two less favoured areas in Portugal.

PubMed

Jones, Nadia; Fleskens, Luuk; Stroosnijder, Leo

2016-10-01

Targeting agri-environmental measures (AEM) improves their effectiveness in the delivery of public goods, provided the necessary coordination with other incentives. In less favoured areas (LFA) measures focusing on the conservation of extensive farming contribute to sustainable land management in these areas. In this paper we investigate the implementation of a possible AEM supporting the improvement of permanent pastures coordinated with the extensive livestock and single farm payments actually in place. Through applying a spatially-explicit mixed integer optimisation model we simulate future land use scenarios for two less favoured areas in Portugal (Centro and Alentejo) considering two policy scenarios: a 'targeted AEM', and a 'non-targeted AEM'. We then compare the results with a 'basic policy' option (reflecting a situation without AEM). This is done with regard to landscape-scale effects on the reduction of fire hazard and erosion risk, as well as effects on farm income. The results show that an AEM for permanent pastures would be more cost-effective for erosion and fire hazard mitigation if implemented within a spatially targeted framework. However when cost-effectiveness is assessed with other indicators (e.g. net farm income and share of grazing livestock) 'non-targeted AEM' implementation delivers the best outcome in Alentejo. In Centro the implementation of an AEM involves important losses of income compared to the 'basic policy'. 'Targeted AEM' tends to favour farms in very marginal conditions, i.e. targeting is demonstrated to perform best in landscapes where spatial heterogeneity is higher. The results also show the risk of farm abandonment in the two studied less favoured areas: in all three scenarios more than 30% of arable land is deemed to be abandoned. Copyright © 2016 Elsevier Ltd. All rights reserved.

5 CFR 531.603 - Locality pay areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Locality pay areas. 531.603 Section 531.603 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY UNDER THE GENERAL SCHEDULE Locality-Based Comparability Payments § 531.603 Locality pay areas. (a) Locality rates of...

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

PubMed Central

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

Targeting LGR5 in Colorectal Cancer: therapeutic gold or too plastic?

PubMed

Morgan, R G; Mortensson, E; Williams, A C

2018-05-01

Leucine-rich repeat-containing G-protein coupled receptor (LGR5 or GPR49) potentiates canonical Wnt/β-catenin signalling and is a marker of normal stem cells in several tissues, including the intestine. Consistent with stem cell potential, single isolated LGR5 + cells from the gut generate self-organising crypt/villus structures in vitro termed organoids or 'mini-guts', which accurately model the parent tissue. The well characterised deregulation of Wnt/β-catenin signalling that occurs during the adenoma-carcinoma sequence in colorectal cancer (CRC) renders LGR5 an interesting therapeutic target. Furthermore, recent studies demonstrating that CRC tumours contain LGR5 + subsets and retain a degree of normal tissue architecture has heightened translational interest. Such reports fuel hope that specific subpopulations or molecules within a tumour may be therapeutically targeted to prevent relapse and induce long-term remissions. Despite these observations, many studies within this field have produced conflicting and confusing results with no clear consensus on the therapeutic value of LGR5. This review will recap the various oncogenic and tumour suppressive roles that have been described for the LGR5 molecule in CRC. It will further highlight recent studies indicating the plasticity or redundancy of LGR5 + cells in intestinal cancer progression and assess the overall merit of therapeutically targeting LGR5 in CRC.

MicroRNA-590-5p Inhibits Intestinal Inflammation by Targeting YAP.

PubMed

Yu, Minhao; Luo, Yang; Cong, Zhijie; Mu, Yifei; Qiu, Yier; Zhong, Ming

2018-04-18

Hippo signaling is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, survival, apoptosis, and stem cell self-renewal. In addition, Hippo signaling is profoundly implicated in intestinal regeneration and cancer. However, its roles in the pathogenesis of Crohn's disease (CD) remain largely unexplored. Quantitative real-time PCR was performed to identify the deregulated molecules in Hippo signaling. Expression of the highly upregulated Yes Associated Protein 1 (YAP) was subsequently examined by qRT-PCR, western blotting and immunohistochemistry in the intestinal tissues of CD patients and the colons of 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis mice. The miRNAs predicted to target YAP were explored by transfection of miR-590-5p mimics or inhibitors and analyzed by luciferase reporter assay. The role of the miR-590-5p/YAP axis in CD and colorectal cancer were studied in experimental colitis mice and colorectal cancer cell lines. YAP mRNA was significantly upregulated in intestinal epithelial cells in CD patients and TNBS-induced colitis mice. MiR-590-5p suppressed YAP expression by directly targeting the YAP 3'-untranslated region in Caco-2 cells and SW620 cells. Upregulation of miR-590-5p in colon reduced YAP level and its downstream targets in IECs. Treatment of miR-590-5p or YAP inhibitor Verteporfin alleviated experimental colitis. Targeting the miR-590-5p/YAP axis inhibited cell proliferation and invasiveness of CRC cells in vitro. Our results suggest that miR-590-5p inhibits intestinal inflammation in mouse colon and tumorigenesis of colorectal cancer cells by inhibiting YAP. The miR-590-5p/YAP axis may be an important novel mechanism in the pathogenesis of CD and colorectal cancer.

Thematic mapping of likely target areas for the occurence of cassiterite in the Serra do Mocambo (GO) granitic massifs using LANDSAT 2 digital imaging

NASA Technical Reports Server (NTRS)

Almeidofilho, R. (Principal Investigator)

1984-01-01

The applicability of LANDSAT/MSS images, enhanced by computer derived techniques, as essential tools in mineral research was investigated and the Serra do Mocambo granitic massif was used as illustration. Given the peculiar factors founded in this area, orbital imagery permitted the delineation of potential target areas of mineralization occurrences, associated to albitized/greisenized types. Follow up prospection for primary tin deposits in this granitic massif should be restricted to the delineated areas which are less than 5% of the total superficial area of the massif.

5 CFR 531.603 - Locality pay areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Locality pay areas. 531.603 Section 531.603 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY UNDER THE GENERAL SCHEDULE Locality-Based Comparability Payments § 531.603 Locality pay areas. (a) Locality rates of pay under this subpart shall be payable to...

Statistical methods for identifying and bounding a UXO target area or minefield

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

McKinstry, Craig A.; Pulsipher, Brent A.; Gilbert, Richard O.

2003-09-18

The sampling unit for minefield or UXO area characterization is typically represented by a geographical block or transect swath that lends itself to characterization by geophysical instrumentation such as mobile sensor arrays. New spatially based statistical survey methods and tools, more appropriate for these unique sampling units have been developed and implemented at PNNL (Visual Sample Plan software, ver. 2.0) with support from the US Department of Defense. Though originally developed to support UXO detection and removal efforts, these tools may also be used in current form or adapted to support demining efforts and aid in the development of newmore » sensors and detection technologies by explicitly incorporating both sampling and detection error in performance assessments. These tools may be used to (1) determine transect designs for detecting and bounding target areas of critical size, shape, and density of detectable items of interest with a specified confidence probability, (2) evaluate the probability that target areas of a specified size, shape and density have not been missed by a systematic or meandering transect survey, and (3) support post-removal verification by calculating the number of transects required to achieve a specified confidence probability that no UXO or mines have been missed.« less

Comparison of autogenous cancellous bone grafting and extracorporeal shock wave therapy on osteotomy healing in the tibial tuberosity advancement procedure in dogs. Radiographic densitometric evaluation.

PubMed

Barnes, K; Lanz, O; Werre, S; Clapp, K; Gilley, R

2015-01-01

To compare optical values in the osteotomy gap created after a tibial tuberosity advancement (TTA) treated with autogenous cancellous bone graft, extracorporeal shock wave therapy, a combination of autogenous cancellous bone graft and extracorporeal shock wave therapy, and absence of both autogenous cancellous bone graft and extracorporeal shock wave therapy using densitometry. Dogs that were presented for surgical repair of a cranial cruciate ligament rupture were randomly assigned to one of four groups: TTA with autogenous cancellous bone graft (TTA-G), TTA with autogenous cancellous bone graft and extracorporeal shock wave therapy (TTA-GS), TTA with extracorporeal shock wave therapy (TTA-S), and TTA with no additional therapy (TTA-O). Mediolateral radiographs at zero, four and eight weeks after surgery were evaluated to compare healing of the osteotomy gap via densitometry. An analysis of variance was used to compare the densitometric values between groups. At four weeks after surgery, a significant difference in osteotomy gap density was noted between TTA-GS (8.4 millimetres of aluminium equivalent [mmAleq]) and TTA-S (6.1 mmAleq), and between TTA-GS (8.4 mmAleq) and TTA-O (6.4 mmAleq). There were no significant differences noted between any groups at the eight week re-evaluation. There were no significant differences in the osteotomy gap density at eight weeks after surgery regardless of the treatment modality used. The combination of autogenous cancellous bone graft and extracorporeal shock wave therapy may lead to increased radiographic density of the osteotomy gap in the first four weeks after surgery. Densitometry using an aluminium step wedge is a feasible method for comparison of bone density after TTA in dogs.

Generation of Parametric Equivalent-Area Targets for Design of Low-Boom Supersonic Concepts

NASA Technical Reports Server (NTRS)

Li, Wu; Shields, Elwood

2011-01-01

A tool with an Excel visual interface is developed to generate equivalent-area (A(sub e)) targets that satisfy the volume constraints for a low-boom supersonic configuration. The new parametric Ae target explorer allows users to interactively study the tradeoffs between the aircraft volume constraints and the low-boom characteristics (e.g., loudness) of the ground signature. Moreover, numerical optimization can be used to generate the optimal A(sub e) target for given A(sub e) volume constraints. A case study is used to demonstrate how a generated low-boom Ae target can be matched by a supersonic configuration that includes a fuselage, wing, nacelle, pylon, aft pod, horizontal tail, and vertical tail. The low-boom configuration is verified by sonic-boom analysis with an off-body pressure distribution at three body lengths below the configuration

MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma.

PubMed

Fang, Feng; Chang, Rui-min; Yu, Lei; Lei, Xiong; Xiao, Shuai; Yang, Hao; Yang, Lian-Yue

2015-10-01

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying HCC progression are still not completely clear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of a metastasis-associated miRNA named miR-188-5p in HCC. miRNA array analysis was performed to search for metastasis-associated miRNAs in HCC. miR-188-5p expressions in tumor tissues and adjacent non-tumorous liver tissues of HCC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analyzed by Western blot and immunohistochemistry. Luciferase reporter assays was used to validate the target of miR-188-5p. The effect of miR-188-5p on HCC progression was studied in vitro and in vivo. miR-188-5p was significantly decreased in HCC and its expression levels were highly correlated with multiple nodules, microvascular invasion, overall and disease-free survival of HCC. Ectopic expression of miR-188-5p suppressed HCC cell proliferation and metastasis in vitro and in vivo. Fibroblast growth factor 5 (FGF5) was identified as a major target of miR-188-5p. Enforced expression of miR-188-5p inhibited the expression of FGF5 significantly and the restoration of FGF5 expression reversed the inhibitory effects of miR-188-5p on HCC cell proliferation and metastasis. These findings collectively demonstrate a tumor suppressor role of miR-188-5p in HCC progression via targeting FGF5, suggesting that miR-188-5p could serve as a potential prognostic biomarker and therapeutic target for HCC. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Mineral target areas in Nevada from geological analysis of LANDSAT-1 imagery

NASA Technical Reports Server (NTRS)

Abdel-Gawad, M.; Tubbesing, L.

1975-01-01

Geological analysis of LANDSAT-1 Scene MSS 1053-17540 suggests that certain known mineral districts in east-central Nevada frequently occur near faults or at faults or lineament intersections and areas of complex deformation and flexures. Seventeen (17) areas of analogous characteristics were identified as favorable targets for mineral exploration. During reconnaissance field trips eleven areas were visited. In three areas evidence was found of mining and/or prospecting not known before the field trips. In four areas favorable structural and alteration features were observed which call for more detailed field studies. In one of the four areas limonitic iron oxide samples were found in the regolith of a brecciated dolomite ridge. This area contains quartz veins, granitic and volcanic rocks and lies near the intersection of two linear fault structures identified in the LANDSAT-1 imagery. Semiquantitative spectroscopic analysis of selected portions of the samples showed abnormal contents of arsenic, molybdenum, copper, lead, zinc, and silver. These limonitic samples found were not in situ and further field studies are required to assess their source and significance.

Reducing the photo-bleaching effect of a new europium complex embedded in styrene butadiene copolymer

NASA Astrophysics Data System (ADS)

Jiménez, G. Lesly; Reyes-Rodríguez, J. L.; Padilla, Isela; Alarcón-Flores, G.; Falcony, C.

2018-02-01

A highly luminescent europium complex obtained with two different ligands, succinimide (SI) and 2-thenoyltrifluoroacetone (TTA) , was synthetized with different TTA concentrations. The photoluminescence (PL) emission from these materials corresponds to the characteristic inter-electronic energy level transitions of the Eu3+ ions. However, the excitation spectrum is strongly dependent on the presence of TTA, having an optimum response when 0.75 mmol of this compound is added to the EuL3(H2O)3 complex. The quantum yield obtained by these powders were around 72 % ± 1.7 % indicating an optimum sensitization of these complex. The EuL3 TTA complex with the best PL properties was embedded in a styrene butadiene copolymer (SBC) film, produced by the drop casting method, obtaining similar PL behavior at different concentrations, the highest intensity was observed at 1.2% (w/v) of EuL3 TTA complex and the quantum yield of these composite films was 60.5 % ± 2 % . These films were exposed to continuous UV irradiation and after 141 h no photo-bleaching effect was observed in contrast with the EuL3 TTA complex that exhibited a noticeable photoluminescence intensity degradation at much shorter exposure times. Both the Eu-complexes and the composite films were characterized by FT-IR, XRD, SEM and fluorescence spectroscopy.

Locomotor adaptability in persons with unilateral transtibial amputation.

PubMed

Darter, Benjamin J; Bastian, Amy J; Wolf, Erik J; Husson, Elizabeth M; Labrecque, Bethany A; Hendershot, Brad D

2017-01-01

Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb.

Efficacy of a two-tiered trauma team activation protocol in a Norwegian trauma centre.

PubMed

Rehn, M; Lossius, H M; Tjosevik, K E; Vetrhus, M; Østebø, O; Eken, T

2012-02-01

A registry-based analysis revealed imprecise informal one-tiered trauma team activation (TTA) in a primary trauma centre. A two-tiered TTA protocol was introduced and analysed to examine its impact on triage precision and resource utilization. Interhospital transfers and patients admitted by non-healthcare personnel were excluded. Undertriage was defined as the fraction of major trauma victims (New Injury Severity Score over 15) admitted without TTA. Overtriage was the fraction of TTA without major trauma. Of 1812 patients, 768 had major trauma. Overall undertriage was reduced from 28·4 to 19·1 per cent (P < 0·001) after system revision. Overall overtriage increased from 61·5 to 71·6 per cent, whereas the mean number of skilled hours spent per overtriaged patient was reduced from 6·5 to 3·5 (P < 0·001) and the number of skilled hours spent per major trauma victim was reduced from 7·4 to 7·1 (P < 0·001). Increasing age increased risk for undertriage and decreased risk for overtriage. Falls increased risk for undertriage and decreased risk for overtriage, whereas motor vehicle-related accidents showed the opposite effects. Patients triaged to a prehospital response involving an anaesthetist had less chance of both undertriage and overtriage. A two-tiered TTA protocol was associated with reduced undertriage and increased overtriage, while trauma team resource consumption was reduced. NCT00876564 (http://www.clinicaltrials.gov). Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... damage caused by projectiles, bombs, missiles, or Naval or Coast Guard vessels to fishing structures or... and bombs will be dropped at frequent intervals in the target areas. Hooper and Hannibal target areas...

Detectability of geothermal areas using Skylab X-5 data

NASA Technical Reports Server (NTRS)

Siegal, B. S.; Kahle, A. B.; Goetz, A. F. H.; Gillespie, A. R.; Abrams, M. J.

1975-01-01

The results are presented of a study which was undertaken to determine if data from a single near-noon pass of Skylab could be used to detect geothermal areas. The size and temperature requirements for a geothermally heated area to be seen by Skylab S-192 MSS X-5 thermal sensor were calculated. This sensor obtained thermal data with the highest spatial resolution of any nonmilitary satellite system. Only very large hot areas could be expected to be unambiguously recognized with a single data set from this instrument. The study area chosen was The Geysers geothermal field in Sonoma County, California, the only geothermal area of significant size scanned by Skylab. Unfortunately, 95% of the Skylab thermal channel data was acquired within 3 hours of local noon. For The Geysers area only daytime X-5 data were available. An analysis of the thermal channel data (10.2 to 12.5 um) revealed that ground temperatures determined by Skylab were normally distributed. No anomalous hot spots were apparent. Computer enhancement techniques were used to delineate the hottest 100 and 300 ground areas (pixel, 75 m by 75 m) within the study region. It was found that the Skylab MSS with the X-5 thermal detector does not have sufficient spatial resolution to locate unambiguously from daytime data any but the largest and hottest convectively created geothermal features, which in general are prominent enough to have been previously recognized.

3D Long-Range Triplet Migration in a Water-Stable Metal-Organic Framework for Upconversion-Based Ultralow-Power in Vivo Imaging.

PubMed

Park, Jihye; Xu, Ming; Li, Fuyou; Zhou, Hong-Cai

2018-04-25

Triplet-triplet annihilation upconversion (TTA-UC) has gained increasing attention because it allows for harvesting of low-energy photons in the solar spectrum with high efficiency in relevant applications including solar cells and bioimaging. However, the utilization of conventional TTA-UC systems for low-power bioapplications is significantly hampered by their general incompatibility and low efficiency in aqueous media. Herein we report a metal-organic framework (MOF) as a biocompatible nanoplatform for TTA-UC to realize low-power in vivo imaging. Our MOF consists of a porphyrinic sensitizer in an anthracene-based Zr-MOF as a TTA-UC platform. In particular, closely aligned chromophores in the MOF facilitate a long-range 3D triplet diffusion of 1.6 μm allowing efficient energy migration in water. The tunable ratio between sensitizer and annihilator by our synthetic method also allows an optimization of the system for maximized TTA-UC efficiency in water at a very low excitation power density. Consequently, the low-power imaging of lymph node in a live mouse was successfully demonstrated with an excellent signal-to-noise ratio (SNR > 30 at 5 mW cm -2 ).

Enhancing teen pregnancy prevention in local communities: capacity building using the interactive systems framework.

PubMed

Duffy, Jennifer L; Prince, Mary Severson; Johnson, Erin E; Alton, Forrest L; Flynn, Shannon; Faye, Amy Mattison; Padgett, Polly Edwards; Rollison, Chris; Becker, Dana; Hinzey, Angela L

2012-12-01

Getting To Outcomes (GTO), an innovative framework for planning, implementing, evaluating, and sustaining interventions has been shown to be effective in helping community-based organizations (CBOs) introduce science-based approaches into their prevention work. However, the Interactive Systems Framework (ISF) suggests that adopting innovations like GTO requires a significant amount of capacity building through training and technical assistance (T/TA). In this study, 11 CBOs and three schools in South Carolina entered into a 3 year program of intense and proactive T/TA based on the ISF to learn how to apply an adaptation of GTO (Promoting Science-Based Approaches-Getting To Outcomes, PSBA-GTO) to their teen pregnancy prevention programs. Using semi-structured interviews, the partnering organizations were assessed at three points in time, pre-T/TA, 12 months, and post T/TA (30 months) for their performance of the steps of GTO in their work. The seven organizations which participated in T/TA until the end of the project received an average of 76 h of TA and 112 h of training per organization. Interview results showed increased performance of all 10 steps of PSBA-GTO by these organizations when conducting their teen pregnancy programs. These results suggest targeted and proactive T/TA can successfully bridge the gap between research and practice by using a three part delivery system, as prescribed in the ISF, which relies on an intermediary prevention support system to ensure accurate and effective translation of research to the everyday work of community-based practitioners.

How Do Vision and Hearing Impact Pedestrian Time-to-Arrival Judgments?

PubMed Central

Roper, JulieAnne M.; Hassan, Shirin E.

2014-01-01

Purpose To determine how accurate normally-sighted male and female pedestrians were at making time-to-arrival (TTA) judgments of approaching vehicles when using just their hearing or both their hearing and vision. Methods Ten male and 14 female subjects with confirmed normal vision and hearing estimated the TTA of approaching vehicles along an unsignalized street under two sensory conditions: (i) using both habitual vision and hearing; and (ii) using habitual hearing only. All subjects estimated how long the approaching vehicle would take to reach them (ie the TTA). The actual TTA of vehicles was also measured using custom made sensors. The error in TTA judgments for each subject under each sensory condition was calculated as the difference between the actual and estimated TTA. A secondary timing experiment was also conducted to adjust each subject’s TTA judgments for their “internal metronome”. Results Error in TTA judgments changed significantly as a function of both the actual TTA (p<0.0001) and sensory condition (p<0.0001). While no main effect for gender was found (p=0.19), the way the TTA judgments varied within each sensory condition for each gender was different (p<0.0001). Females tended to be as accurate under either condition (p≥0.01) with the exception of TTA judgments made when the actual TTA was two seconds or less and eight seconds or longer, during which the vision and hearing condition was more accurate (p≤0.002). Males made more accurate TTA judgments under the hearing only condition for actual TTA values five seconds or less (p<0.0001), after which there were no significant differences between the two conditions (p≥0.01). Conclusions Our data suggests that males and females use visual and auditory information differently when making TTA judgments. While the sensory condition did not affect the females’ accuracy in judgments, males initially tended to be more accurate when using their hearing only. PMID:24509543

Environmental Stewardship: It's Only Natural. Kerr Lake State Recreation Area: An Environmental Education Learning Experience Designed for Grades 3-5.

ERIC Educational Resources Information Center

Ayers, Scott; Speed, John

This activity guide, developed to provide hands-on environmental education activities geared to Kerr Lake State Recreation Area in North Carolina, is targeted for grades 3, 4, and 5 and meets curriculum objectives of the standard course of study established by the North Carolina Department of Public Instruction. Three types of activities are…

Differential contributions to the interception of occluded ballistic trajectories by the temporoparietal junction, area hMT/V5+, and the intraparietal cortex.

PubMed

Delle Monache, Sergio; Lacquaniti, Francesco; Bosco, Gianfranco

2017-09-01

The ability to catch objects when transiently occluded from view suggests their motion can be extrapolated. Intraparietal cortex (IPS) plays a major role in this process along with other brain structures, depending on the task. For example, interception of objects under Earth's gravity effects may depend on time-to-contact predictions derived from integration of visual signals processed by hMT/V5+ with a priori knowledge of gravity residing in the temporoparietal junction (TPJ). To investigate this issue further, we disrupted TPJ, hMT/V5+, and IPS activities with transcranial magnetic stimulation (TMS) while subjects intercepted computer-simulated projectile trajectories perturbed randomly with either hypo- or hypergravity effects. In experiment 1 , trajectories were occluded either 750 or 1,250 ms before landing. Three subject groups underwent triple-pulse TMS (tpTMS, 3 pulses at 10 Hz) on one target area (TPJ | hMT/V5+ | IPS) and on the vertex (control site), timed at either trajectory perturbation or occlusion. In experiment 2 , trajectories were entirely visible and participants received tpTMS on TPJ and hMT/V5+ with same timing as experiment 1 tpTMS of TPJ, hMT/V5+, and IPS affected differently the interceptive timing. TPJ stimulation affected preferentially responses to 1-g motion, hMT/V5+ all response types, and IPS stimulation induced opposite effects on 0-g and 2-g responses, being ineffective on 1-g responses. Only IPS stimulation was effective when applied after target disappearance, implying this area might elaborate memory representations of occluded target motion. Results are compatible with the idea that IPS, TPJ, and hMT/V5+ contribute to distinct aspects of visual motion extrapolation, perhaps through parallel processing. NEW & NOTEWORTHY Visual extrapolation represents a potential neural solution to afford motor interactions with the environment in the face of missing information. We investigated relative contributions by temporoparietal junction

MicroRNA-142-5p contributes to Hashimoto's thyroiditis by targeting CLDN1.

PubMed

Zhu, Jin; Zhang, Yuehua; Zhang, Weichen; Zhang, Wei; Fan, Linni; Wang, Lu; Liu, Yixiong; Liu, Shasha; Guo, Ying; Wang, Yingmei; Yi, Jun; Yan, Qingguo; Wang, Zhe; Huang, Gaosheng

2016-06-08

MicroRNAs have the potential as diagnostic biomarkers and therapeutic targets in autoimmune diseases. However, very limited studies have evaluated the expression of microRNA profile in thyroid gland related to Hashimoto's thyroiditis (HT). MicroRNA microarray expression profiling was performed and validated by quantitative RT-PCR. The expression pattern of miR-142-5p was detected using locked nucleic acid-in situ hybridization. The target gene was predicted and validated using miRNA targets prediction database, gene expression analysis, quantitative RT-PCR, western blot, and luciferase assay. The potential mechanisms of miR-142-5p were studied using immunohistochemistry, immunofluorescence, and quantitative assay of thyrocyte permeability. Thirty-nine microRNAs were differentially expressed in HT (Fold change ≥2, P < 0.05) and miR-142-5p, miR-142-3p, and miR-146a were only high expression in HT thyroid gland (P < 0.001). miR-142-5p, which was expressed at high levels in injured follicular epithelial cells, was also detected in HT patient serum and positively correlated with thyroglobulin antibody (r ≥ 0.6, P < 0.05). Furthermore, luciferase assay demonstrated CLDN1 was the direct target gene of miR-142-5p (P < 0.05), and Immunohistochemical staining showed a reverse expression patterns with miR-142-5p and CLDN1. Overexpression of miR-142-5p in thyrocytes resulted in reducing of the expression of claudin-1 both in mRNA and protein level (P = 0.032 and P = 0.009 respectively) and increasing the permeability of thyrocytes monolayer (P < 0.01). Our findings indicate a previously unrecognized mechanism that miR-142-5p, targeting CLDN1, plays an important role in HT pathogenesis.

LWIR hyperspectral change detection for target acquisition and situation awareness in urban areas

NASA Astrophysics Data System (ADS)

Dekker, Rob J.; Schwering, Piet B. W.; Benoist, Koen W.; Pignatti, Stefano; Santini, Federico; Friman, Ola

2013-05-01

This paper studies change detection of LWIR (Long Wave Infrared) hyperspectral imagery. Goal is to improve target acquisition and situation awareness in urban areas with respect to conventional techniques. Hyperspectral and conventional broadband high-spatial-resolution data were collected during the DUCAS trials in Zeebrugge, Belgium, in June 2011. LWIR data were acquired using the ITRES Thermal Airborne Spectrographic Imager TASI-600 that operates in the spectral range of 8.0-11.5 μm (32 band configuration). Broadband data were acquired using two aeroplanemounted FLIR SC7000 MWIR cameras. Acquisition of the images was around noon. To limit the number of false alarms due to atmospheric changes, the time interval between the images is less than 2 hours. Local co-registration adjustment was applied to compensate for misregistration errors in the order of a few pixels. The targets in the data that will be analysed in this paper are different kinds of vehicles. Change detection algorithms that were applied and evaluated are Euclidean distance, Mahalanobis distance, Chronochrome (CC), Covariance Equalisation (CE), and Hyperbolic Anomalous Change Detection (HACD). Based on Receiver Operating Characteristics (ROC) we conclude that LWIR hyperspectral has an advantage over MWIR broadband change detection. The best hyperspectral detector is HACD because it is most robust to noise. MWIR high spatial-resolution broadband results show that it helps to apply a false alarm reduction strategy based on spatial processing.

MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5.

PubMed

Li, T K; Yin, K; Chen, Z; Bao, Y; Zhang, S X

2017-03-08

Ras association domain family member 5 (RASSF5), a member of the Ras association domain family, induces cell apoptosis by phosphorylating FOXO3a, which triggers target gene BIM (pro-apoptotic factor) activation. MiR-214 is overexpressed in oral cancer tissue, indicating its possible involvement in oral cancer pathogenesis. Bioinformatics analysis has revealed a complimentary sequence between miR-214 and the 3'-UTR of RASSF5 mRNA. However, whether miR-124 regulates RASSF5 in oral cancer remains poorly understood. We aimed to investigate the role of miR-214 in RASSF5 expression regulation in oral cancer. Tumor and paracarcinoma tissues were obtained from 48 oral cancer patients to examine miR-214 and RASSF5 expression. The relationship between miR-214 and RASSF5 was investigated by dual luciferase reporter gene assay. Oral cancer KB cells were cultured in vitro and divided into inhibitor NC, miR-214 inhibitor, Scramble-pMD18, RASSF5-pMD18, and miR-214 inhibitor + RASSF5-pMD18 groups. Caspase 3 activity, cell apoptosis, and total protein expression were measured by spectrophotometry, flow cytometry, and western blot, respectively. MiR-214 expression was significantly increased, while that of RASSF5 decreased in oral cancer tumor tissues compared to paracarcinoma tissues. Luciferase assay showed that miR-214 suppressed RASSF5 expression by targeting its 3'-UTR. Down-regulation of miR-214 and/or enhancement of RASSF5 expression markedly increased FOXO3a phosphorylation, BIM expression, caspase 3 activity, and apoptosis. In conclusion, miR-214 expression was elevated and RASSF5 was down-regulated in oral cancer. Moreover, miR-214 regulated KB cell apoptosis through targeted inhibition of RASSF5 expression, FOXO3a phosphorylation, and BIM expression, suggesting its possible application as a novel therapeutic oral cancer target.

33 CFR 334.1470 - Caribbean Sea and Vieques Sound, in vicinity of Eastern Vieques; bombing and gunnery target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Caribbean Sea and Vieques Sound, in vicinity of Eastern Vieques; bombing and gunnery target area. 334.1470 Section 334.1470 Navigation...; bombing and gunnery target area. (a) The danger zone. From Punta Conejo on the south coast of Vieques at...

33 CFR 334.1470 - Caribbean Sea and Vieques Sound, in vicinity of Eastern Vieques; bombing and gunnery target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Caribbean Sea and Vieques Sound, in vicinity of Eastern Vieques; bombing and gunnery target area. 334.1470 Section 334.1470 Navigation...; bombing and gunnery target area. (a) The danger zone. From Punta Conejo on the south coast of Vieques at...

Measurement of energy deposited by charged particle beams in composite targets. [0. 5 to 28. 5 GeV

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

Crase, K.; Farley, W.E.; Kruger, H.

1977-11-03

The energies deposited in composite targets by proton beams from 0.8 to 28.5 GeV energy and by an electron beam at 0.5 GeV energy were measured. The targets consisted of various thicknesses of /sup 238/U shower plates backed by a composite detector plate consisting of a 5-cm-thick CH/sub 2/ moderator and a 0.635-cm /sup 238/U plate. The spacing between the shower and detector plates was varied to allow different spreading of the shower between plates. Passive detectors (thermoluminescence dosimeters, Lexan fission track recorders, photographic emulsions, and removable /sup 238/U pieces) were used to measure the fission-fragment dose and the nonfissionmore » dose at various depths and radial positions in the targets. Plots and numerical values of the measured doses are presented for comparison with computer code calculations. To provide a basis for comparison of the effects of different particle beam energies, data along the beam axes are presented as specific dose (cal/g per incident integrated kJ/cm/sup 2/). In general, the higher the incident proton energy, the larger is the dose in the back of the target relative to that in the front.« less

Endoscopic Endonasal Transsphenoidal Approach

PubMed Central

Cappabianca, Paolo; Alfieri, Alessandra; Colao, Annamaria; Ferone, Diego; Lombardi, Gaetano; de Divitiis, Enrico

1999-01-01

The outcome of endoscopic endonasal transsphenoidal surgery in 10 patients with pituitary adenomas was compared with that of traditional transnasal transsphenoidal approach (TTA) in 20 subjects. Among the 10 individuals subjected to “pure endoscopy,” 2 had a microadenoma, 1 an intrasellar macroadenoma, 4 had a macroadenoma with suprasellar expansion, 2 had a macroadenoma with supra-parasellar expansion, and 1 a residual tumor; 5 had acromegaly and 5 had a nonfunctioning adenoma (NFA). Among the patients subjected to TTA, 4 had a microadenoma, 2 had an intrasellar macroadenoma, 6 had a macroadenoma with suprasellar expansion, 4 had a macroadenoma with supra-parasellar expansion, and 4 had a residual tumor; 9 patients had acromegaly, 1 hyperprolactinemia, 1 Cushing's disease, and 9 a NFA. At the macroscopic evaluation, tumor removal was total (100%) after endoscopy in 9 patients and after TTA in 14 patients. Six months after surgery, magnetic resonance imaging (MRI) confirmed the total tumor removal in 21 of 23 patients (91.3%). Circulating growth hormone (GH) and insulin-like growth factor-I (IGF-I) significantly decreased 6 months after surgery in all 14 acromegalic patients: normalization of plasma IGF-I levels was obtained in 4 of 5 patients after the endoscopic procedure and in 4 of 9 patients after TTA. Before surgery, pituitary hormone deficiency was present in 14 out of 30 patients: pituitary function improved in 4 patients, remaining unchanged in the other 10 patients. Visual field defects were present before surgery in 4 patients, and improved in all. Early surgical results in the group of 10 patients who underwent endoscopic pituitary tumor removal were at least equivalent to those of standard TTA, with excellent postoperative course. Postsurgical hospital stay was significantly shorter (3.1 ± 0.4 vs. 6.2 ± 0.3 days, p < 0.001) after endoscopy as compared to TTA. ImagesFigure 1Figure 2 PMID:17171126

Effects of nandrolone decanoate on time to consolidation of bone defects resulting from osteotomy for tibial tuberosity advancement.

PubMed

Marques, Danilo R C; Marques, Danilo; Ibanez, Jose F; Freitas, Itallo B; Hespanha, Ana C; Monteiro, Juliana F; Eggert, Mayara; Becker, Amanda

2017-09-12

Experimental study. The aim of this study was to evaluate the effect of nandrolone decanoate (ND) on the time taken for bone consolidation in dogs undergoing tibial tuberosity advancement surgery (TTA). Seventeen dogs that underwent TTA surgery were randomly divided into two groups: group C (TTA; 9 stifles), and group TTA+ND (TTA and systemic administration of ND; 8 stifles). Three observers (two radiologists and an orthopaedic surgeon), assessed bone consolidation by visual inspection of serial radiographs at intervals of 21 days following surgery. There were no differences in median weight and age between groups, nor between the medians of the variables right and left stifle. Only weight and age values were normally distributed. The other variables, right and left stifle and time to consolidation, showed non-normal distribution. Meniscal injury was present in all animals in group C and all animals in group TTA+ND. There was a significant difference between time to consolidation in groups C and TTA+ND (p <0.05). One animal in the group TTA+ND showed increased libido. Kappa agreement among observers on radiographs was 0.87. Administration of ND reduces time to bone consolidation in dogs undergoing TTA.

Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor- Associated...3. DATES COVERED 31 Aug 2015 - 30 Aug 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting MEK5 Enhances Radiosensitivity of Human Prostate...therapeutic modality for the treatment of human prostate cancer. However, tumors often demonstrate resistance to ionizing radiation and continue to

46 CFR 30.10-5a - Cargo area-TB/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Cargo area-TB/ALL. 30.10-5a Section 30.10-5a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5a Cargo area—TB/ALL. The term cargo area means that part of a vessel that includes the cargo tanks and...

46 CFR 30.10-5a - Cargo area-TB/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Cargo area-TB/ALL. 30.10-5a Section 30.10-5a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5a Cargo area—TB/ALL. The term cargo area means that part of a vessel that includes the cargo tanks and...

46 CFR 30.10-5a - Cargo area-TB/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Cargo area-TB/ALL. 30.10-5a Section 30.10-5a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5a Cargo area—TB/ALL. The term cargo area means that part of a vessel that includes the cargo tanks and...

46 CFR 30.10-5a - Cargo area-TB/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Cargo area-TB/ALL. 30.10-5a Section 30.10-5a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5a Cargo area—TB/ALL. The term cargo area means that part of a vessel that includes the cargo tanks and...

46 CFR 30.10-5a - Cargo area-TB/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Cargo area-TB/ALL. 30.10-5a Section 30.10-5a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5a Cargo area—TB/ALL. The term cargo area means that part of a vessel that includes the cargo tanks and...

Effect of tibial tuberosity advancement on femorotibial contact mechanics and stifle kinematics.

PubMed

Kim, Stanley E; Pozzi, Antonio; Banks, Scott A; Conrad, Bryan P; Lewis, Daniel D

2009-01-01

Objective- To evaluate the effects of tibial tuberosity advancement (TTA) on femorotibial contact mechanics and 3-dimensional kinematics in cranial cruciate ligament (CrCL)-deficient stifles of dogs. Study Design- In vitro biomechanical study. Animals- Unpaired pelvic limbs from 8 dogs, weighing 28-35 kg. Methods- Digital pressure sensors placed subjacent to the menisci were used to measure femorotibial contact force, contact area, peak and mean contact pressure, and peak pressure location with the limb under an axial load of 30% body weight and a stifle angle of 135 degrees . Three-dimensional static poses of the stifle were obtained using a Microscribe digitizing arm. Each specimen was tested under normal, CrCL-deficient, and TTA-treated conditions. Repeated measures analysis of variance with a Tukey post hoc test (P<.05) was used for statistical comparison. Results- Significant disturbances to all measured contact mechanic parameters were evident after CrCL transection, which corresponded to marked cranial tibial subluxation and internal tibial rotation in the CrCL-deficient stifle. No significant differences in any contact mechanic and kinematic parameters were detected between normal and TTA-treated stifles. Conclusion- TTA eliminates craniocaudal stifle instability during simulated weight-bearing and concurrently restores femorotibial contact mechanics to normal. Clinical Relevance- TTA may mitigate the progression of stifle osteoarthritis in dogs afflicted with CrCL insufficiency by eliminating cranial tibial thrust while preserving the normal orientation of the proximal tibial articulating surface.

9 CFR 72.5 - Area quarantined in Texas.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Area quarantined in Texas. 72.5 Section 72.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BOVINE BABESIOSIS...

Dynamic Nucleolar Targeting of Dengue Virus Polymerase NS5 in Response to Extracellular pH

PubMed Central

Fraser, Johanna E.; Rawlinson, Stephen M.; Heaton, Steven M.

2016-01-01

ABSTRACT The nucleolar subcompartment of the nucleus is increasingly recognized as an important target of RNA viruses. Here we document for the first time the ability of dengue virus (DENV) polymerase, nonstructural protein 5 (NS5), to accumulate within the nucleolus of infected cells and to target green fluorescent protein (GFP) to the nucleolus of live transfected cells. Intriguingly, NS5 exchange between the nucleus and nucleolus is dynamically modulated by extracellular pH, responding rapidly and reversibly to pH change, in contrast to GFP alone or other nucleolar and non-nucleolar targeted protein controls. The minimal pH-sensitive nucleolar targeting region (pHNTR), sufficient to target GFP to the nucleolus in a pH-sensitive fashion, was mapped to NS5 residues 1 to 244, with mutation of key hydrophobic residues, Leu-165, Leu-167, and Val-168, abolishing pHNTR function in NS5-transfected cells, and severely attenuating DENV growth in infected cells. This is the first report of a viral protein whose nucleolar targeting ability is rapidly modulated by extracellular stimuli, suggesting that DENV has the ability to detect and respond dynamically to the extracellular environment. IMPORTANCE Infections by dengue virus (DENV) threaten 40% of the world's population yet there is no approved vaccine or antiviral therapeutic to treat infections. Understanding the molecular details that govern effective viral replication is key for the development of novel antiviral strategies. Here, we describe for the first time dynamic trafficking of DENV nonstructural protein 5 (NS5) to the subnuclear compartment, the nucleolus. We demonstrate that NS5's targeting to the nucleolus occurs in response to acidic pH, identify the key amino acid residues within NS5 that are responsible, and demonstrate that their mutation severely impairs production of infectious DENV. Overall, this study identifies a unique subcellular trafficking event and suggests that DENV is able to detect and respond

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... 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) The danger zone. A sector in San Pablo Bay adjacent to the westerly shore of Mare Island with a radius...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... 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) The danger zone. A sector in San Pablo Bay adjacent to the westerly shore of Mare Island with a radius...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... 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) The danger zone. A sector in San Pablo Bay adjacent to the westerly shore of Mare Island with a radius...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River... Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River, Maryland, danger zones. (a) Aerial firing range—(1) The danger zone. The waters...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River... Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River, Maryland, danger zones. (a) Aerial firing range—(1) The danger zone. The waters...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River... Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River, Maryland, danger zones. (a) Aerial firing range—(1) The danger zone. The waters...

Memory Enhancement by Targeting Cdk5 Regulation of NR2B

PubMed Central

Plattner, Florian; Hernandéz, Adan; Kistler, Tara M.; Pozo, Karine; Zhong, Ping; Yuen, Eunice Y.; Tan, Chunfeng; Hawasli, Ammar H.; Cooke, Sam F.; Nishi, Akinori; Guo, Ailan; Wiederhold, Thorsten; Yan, Zhen; Bibb, James A.

2014-01-01

SUMMARY Many psychiatric and neurological disorders are characterized by learning and memory deficits, for which cognitive enhancement is considered a valid treatment strategy. The N-methyl-D-aspartate receptor (NMDAR) is a prime target for the development of cognitive enhancers due to its fundamental role in learning and memory. In particular, the NMDAR subunit NR2B improves synaptic plasticity and memory when over-expressed in neurons. However, NR2B regulation is not well understood and no therapies potentiating NMDAR function have been developed. Here, we show that serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5). Cdk5-dependent NR2B phosphorylation is regulated by neuronal activity and controls the receptor’s cell surface expression. Disrupting NR2B-Cdk5 interaction using a small interfering peptide (siP) increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation in vivo. Our results reveal a novel regulatory mechanism critical to NR2B function that can be targeted for the development of cognitive enhancers. PMID:24607229

Red-light-controllable liquid-crystal soft actuators via low-power excited upconversion based on triplet-triplet annihilation.

PubMed

Jiang, Zhen; Xu, Ming; Li, Fuyou; Yu, Yanlei

2013-11-06

A red-light-controllable soft actuator has been achieved, driven by low-power excited triplet-triplet annihilation-based upconversion luminescence (TTA-UCL). First, a red-to-blue TTA-based upconversion system with a high absolute quantum yield of 9.3 ± 0.5% was prepared by utilizing platinum(II) tetraphenyltetrabenzoporphyrin (PtTPBP) as the sensitizer and 9,10-bis(diphenylphosphoryl)anthracene (BDPPA) as the annihilator. In order to be employed as a highly effective phototrigger of photodeformable cross-linked liquid-crystal polymers (CLCPs), the PtTPBP&BDPPA system was incorporated into a rubbery polyurethane film and then assembled with an azotolane-containing CLCP film. The generating assembly film bent toward the light source when irradiated with a 635 nm laser at low power density of 200 mW cm(-2) because the TTA-UCL was effectively utilized by the azotolane moieties in the CLCP film, inducing their trans-cis photoisomerization and an alignment change of the mesogens via an emission-reabsorption process. It is the first example of a soft actuator in which the TTA-UCL is trapped and utilized to create photomechanical effect. Such advantages of using this novel red-light-controllable soft actuator in potential biological applications have also been demonstrated as negligible thermal effect and its excellent penetration ability into tissues. This work not only provides a novel photomanipulated soft actuation material system based on the TTA-UCL technology but also introduces a new technological application of the TTA-based upconversion system in photonic devices.

Nevada National Security Site 2013 Waste Management Monitoring Report Area 3 and Area 5 Radioactive Waste Management Site

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

Hudson, D. B.

Environmental monitoring data are collected at and around the Area 3 and Area 5 Radioactive Waste Management Sites (RWMSs) within the Nevada National Security Site (NNSS). These data are associated with radiation exposure, air, groundwater, meteorology, and vadose zone. This report summarizes the 2013 environmental data to provide an overall evaluation of RWMS performance and to support environmental compliance and performance assessment (PA) activities. Some of these data (e.g., radiation exposure, air, and groundwater) are presented in other reports (National Security Technologies, LLC, 2013; 2014a; 2014b). Direct radiation monitoring data indicate exposure levels at the RWMSs are within the rangemore » of background levels measured at the NNSS. Slightly elevated exposure levels outside the Area 3 RWMS are attributed to nearby historical aboveground nuclear weapons tests. Air monitoring data show tritium concentrations in water vapor and americium and plutonium concentrations in air particles are close to detection limits and background levels. The measured levels of radionuclides in air particulates and moisture are below Derived Concentration Standards for these radionuclides. Groundwater monitoring data indicate the groundwater in the uppermost aquifer beneath the Area 5 RWMS is not impacted by RWMS operations. Results of groundwater analysis from wells around the Area 5 RWMS were all below established investigation levels. Leachate samples collected from the leachate collection system at the mixed low-level waste cell were below established contaminant regulatory limits. The 105.8 millimeters (mm) (4.17 inches [in.]) of precipitation at the Area 3 RWMS during 2013 is 30% below the average of 150.3 mm (5.92 in.), and the 117.5 mm (4.63 in.) of precipitation at the Area 5 RWMS during 2013 is 5% below the average of 123.6 mm (4.86 in.). Water balance measurements indicate that evapotranspiration from the vegetated weighing lysimeter dries the soil and prevents

Development and Characterization of Novel Bioluminecent Systems

DTIC Science & Technology

2013-07-01

Ppy I108R. The following primers and their respective reverse compliments were used: Y447E, 5´- CT TTA ATT AAA TAC AAA GGA GAG CAG GTG GCC CCC GCT G...3´ [EcoRV] and I108R, 5´- GGA GTT GCA GTG GCG CCC GCG AAC GAC CGT TAT AAT GAA CGT-3´ [KasI] (bold represents the mutated codons, underlined...primers and their respective reverse compliments: Y447C, 5´- G AAG TCT TTA ATA AAA TAC AAA GGA TGT CAG GTG GCC CCC GCT G -3´ [PacI] and I108C, 5´- GGA

Flaviviridae virus nonstructural proteins 5 and 5A mediate viral immune evasion and are promising targets in drug development.

PubMed

Chen, Shun; Yang, Chao; Zhang, Wei; Mahalingam, Suresh; Wang, Mingshu; Cheng, Anchun

2018-05-06

Infections with viruses in the Flaviviridae family have a vast global and economic impact because of the high morbidity and mortality. The pathogenesis of Flaviviridae infections is very complex and not fully understood because these viruses can inhibit multiple immune pathways including the complement system, NK cells, and IFN induction and signalling pathways. The non-structural (NS) 5 and 5A proteins of Flaviviridae viruses are highly conserved and play an important role in resisting host immunity through various evasion mechanisms. This review summarizes the strategies used by the NS5 and 5A proteins of Flaviviridae viruses for evading the innate immune response by inhibiting pattern recognition receptor (PRR) signalling pathways (TLR/MyD88, IRF7), suppressing interferon (IFN) signalling pathways (IFN-γRs, STAT1, STAT2), and impairing the function of IFN-stimulated genes (ISGs) (e.g. protein kinase R [PKR], oligoadenylate synthase [OAS]). All of these immune evasion mechanisms depend on the interaction of NS5 or NS5A with cellular proteins, such as MyD88 and IRF7, IFN-αRs, IFN-γRs, STAT1, STAT2, PKR and OAS. NS5 is the most attractive target for the discovery of broad spectrum compounds against Flaviviridae virus infection. The methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) activities of NS5 are the main therapeutic targets for antiviral drugs against Flaviviridae virus infection. Based on our site mapping, the sites involved in immune evasion provide some potential and promising targets for further novel antiviral therapeutics. Copyright © 2018 Elsevier Inc. All rights reserved.

7 CFR 301.75-5 - Commercial citrus-producing areas.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Commercial citrus-producing areas. 301.75-5 Section 301.75-5 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Citrus Canker Notice of Quarantine...

7 CFR 301.75-5 - Commercial citrus-producing areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Commercial citrus-producing areas. 301.75-5 Section 301.75-5 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Citrus Canker Notice of Quarantine...

5 CFR 591.206 - How does OPM establish COLA areas?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false How does OPM establish COLA areas? 591... Allowances § 591.206 How does OPM establish COLA areas? (a) OPM designates, within nonforeign areas, areas where agencies pay employees a COLA by virtue of living costs that are substantially higher than those...

5 CFR 591.206 - How does OPM establish COLA areas?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false How does OPM establish COLA areas? 591... Allowances § 591.206 How does OPM establish COLA areas? (a) OPM designates, within nonforeign areas, areas where agencies pay employees a COLA by virtue of living costs that are substantially higher than those...

5 CFR 591.206 - How does OPM establish COLA areas?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false How does OPM establish COLA areas? 591... Allowances § 591.206 How does OPM establish COLA areas? (a) OPM designates, within nonforeign areas, areas where agencies pay employees a COLA by virtue of living costs that are substantially higher than those...

5 CFR 591.206 - How does OPM establish COLA areas?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false How does OPM establish COLA areas? 591... Allowances § 591.206 How does OPM establish COLA areas? (a) OPM designates, within nonforeign areas, areas where agencies pay employees a COLA by virtue of living costs that are substantially higher than those...

5 CFR 591.206 - How does OPM establish COLA areas?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false How does OPM establish COLA areas? 591... Allowances § 591.206 How does OPM establish COLA areas? (a) OPM designates, within nonforeign areas, areas where agencies pay employees a COLA by virtue of living costs that are substantially higher than those...

Prediction of target genes for miR-140-5p in pulmonary arterial hypertension using bioinformatics methods.

PubMed

Li, Fangwei; Shi, Wenhua; Wan, Yixin; Wang, Qingting; Feng, Wei; Yan, Xin; Wang, Jian; Chai, Limin; Zhang, Qianqian; Li, Manxiang

2017-12-01

The expression of microRNA (miR)-140-5p is known to be reduced in both pulmonary arterial hypertension (PAH) patients and monocrotaline-induced PAH models in rat. Identification of target genes for miR-140-5p with bioinformatics analysis may reveal new pathways and connections in PAH. This study aimed to explore downstream target genes and relevant signaling pathways regulated by miR-140-5p to provide theoretical evidences for further researches on role of miR-140-5p in PAH. Multiple downstream target genes and upstream transcription factors (TFs) of miR-140-5p were predicted in the analysis. Gene ontology (GO) enrichment analysis indicated that downstream target genes of miR-140-5p were enriched in many biological processes, such as biological regulation, signal transduction, response to chemical stimulus, stem cell proliferation, cell surface receptor signaling pathways. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis found that downstream target genes were mainly located in Notch, TGF-beta, PI3K/Akt, and Hippo signaling pathway. According to TF-miRNA-mRNA network, the important downstream target genes of miR-140-5p were PPI, TGF-betaR1, smad4, JAG1, ADAM10, FGF9, PDGFRA, VEGFA, LAMC1, TLR4, and CREB. After thoroughly reviewing published literature, we found that 23 target genes and seven signaling pathways were truly inhibited by miR-140-5p in various tissues or cells; most of these verified targets were in accordance with our present prediction. Other predicted targets still need further verification in vivo and in vitro .

Role of TAF12 in the Increased VDR Activity in Paget’s Disease of Bone

DTIC Science & Technology

2013-10-01

and 5’‐GCC AAA TGC AGT TTA AGC TCT GCT‐3’ (antisense). The gene‐specific primers for mouse b‐actin were 5’‐GGC CGT ACC ACT GGC ATC GTG ATG‐ 3...cycles. The gene‐specific primers for CYP24A1 mRNA were 5’‐CGG GTG GAC CAT TTA CAA CTC GG‐3’ (sense) and 5’‐CTC AAC AGG CTC ATT GTC TGT GG‐3’ (antisense...The gene specific designing primers for b‐actinwere 5’‐ GTG CGT GAC ATC AAA GAG‐3’ (sense) and 5’‐GCC ACA GGA TTC CAT ACC‐3’ (antisense). The

Europium (III) Organic Complexes in Porous Boron Nitride Microfibers: Efficient Hybrid Luminescent Material

NASA Astrophysics Data System (ADS)

Lin, Jing; Feng, Congcong; He, Xin; Wang, Weijia; Fang, Yi; Liu, Zhenya; Li, Jie; Tang, Chengchun; Huang, Yang

2016-09-01

We report the design and synthesis of a novel kind of organic-inorganic hybrid material via the incorporation of europium (III) β-diketonate complexes (Eu(TTA)3, TTA = 2-thenoyltrifluoroacetone) into one-dimensional (1D) porous boron nitride (BN) microfibers. The developed Eu(TTA)3@BN hybrid composites with typical 1D fibrous morphology exhibit bright visible red-light emission on UV illumination. The confinement of Eu(TTA)3 within pores of BN microfibers not only decreases the aggregation-caused quenching in solid Eu(TTA)3, but also improves their thermal stabilities. Moreover, The strong interactions between Eu(TTA)3 and porous BN matrix result in an interesting energy transfer process from BN host to TTA ligand and TTA ligand to Eu3+ ions, leading to the remarkable increase of red emission. The synthetic approach should be a very promising strategy which can be easily expanded to other hybrid luminescent materials based on porous BN.

Europium (III) Organic Complexes in Porous Boron Nitride Microfibers: Efficient Hybrid Luminescent Material

PubMed Central

Lin, Jing; Feng, Congcong; He, Xin; Wang, Weijia; Fang, Yi; Liu, Zhenya; Li, Jie; Tang, Chengchun; Huang, Yang

2016-01-01

We report the design and synthesis of a novel kind of organic-inorganic hybrid material via the incorporation of europium (III) β-diketonate complexes (Eu(TTA)3, TTA = 2-thenoyltrifluoroacetone) into one-dimensional (1D) porous boron nitride (BN) microfibers. The developed Eu(TTA)3@BN hybrid composites with typical 1D fibrous morphology exhibit bright visible red-light emission on UV illumination. The confinement of Eu(TTA)3 within pores of BN microfibers not only decreases the aggregation-caused quenching in solid Eu(TTA)3, but also improves their thermal stabilities. Moreover, The strong interactions between Eu(TTA)3 and porous BN matrix result in an interesting energy transfer process from BN host to TTA ligand and TTA ligand to Eu3+ ions, leading to the remarkable increase of red emission. The synthetic approach should be a very promising strategy which can be easily expanded to other hybrid luminescent materials based on porous BN. PMID:27687246

The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma

PubMed Central

Keller, Alexandra; Wingelhofer, Bettina; Peter, Barbara; Bauer, Karin; Berger, Daniela; Gamperl, Susanne; Reifinger, Martin; Cerny-Reiterer, Sabine; Moriggl, Richard; Willmann, Michael; Valent, Peter; Hadzijusufovic, Emir

2018-01-01

Background Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma. Materials and Methods We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI-1. Results Activated JAK2 and STAT5 were detected in both cell lines. The drugs applied were found to inhibit proliferation and survival in these cells with the following rank-order of potency: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol. Moreover, synergistic anti-neoplastic effects were obtained by combining pimozide with KIT-targeting drugs (toceranib, masitinib, nilotinib, midostaurin) in NI-1 cells. Conclusion The JAK2/STAT5 pathway is a novel potential target of therapy in canine mastocytoma. PMID:28397975

Nevada National Security Site 2012 Waste Management Monitoring Report Area 3 and Area 5 Radioactive Waste Management Site

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

Hudson, David B.

2013-09-10

Environmental monitoring data are collected at and around the Area 3 and Area 5 Radioactive Waste Management Sites (RWMSs) at the Nevada National Security Site (NNSS). These data are associated with radiation exposure, air, groundwater, meteorology, and vadose zone. This report summarizes the 2012 environmental data to provide an overall evaluation of RWMS performance and to support environmental compliance and performance assessment (PA) activities. Some of these data (e.g., radiation exposure, air, and groundwater) are presented in other reports (National Security Technologies, LLC, 2012; 2013a; 2013b). Direct radiation monitoring data indicate exposure levels at the RWMSs are within the rangemore » of background levels measured at the NNSS. Slightly elevated exposure levels outside the Area 3 RWMS are attributed to nearby historical aboveground nuclear weapons tests. Air monitoring data show tritium concentrations in water vapor and americium and plutonium concentrations in air particles are only slightly above detection limits and background levels. The measured levels of radionuclides in air particulates and moisture are below Derived Concentration Standards for these radionuclides. Groundwater monitoring data indicate the groundwater in the uppermost aquifer beneath the Area 5 RWMS is not impacted by RWMS operations. Results of groundwater analysis from wells around the Area 5 RWMS were all below established investigation levels. Leachate samples collected from the leachate collection system at the mixed low-level waste cell were below established contaminant regulatory limits. The 133.9 millimeters (mm) (5.27 inches [in.]) of precipitation at the Area 3 RWMS during 2012 is 12% below the average of 153.0 mm (6.02 in.), and the 137.6 mm (5.42 in.) of precipitation at the Area 5 RWMS during 2012 is 11% below the average of 122.4 mm (4.82 in.). Water balance measurements indicate that evapotranspiration from the vegetated weighing lysimeter dries the soil and

Effect of cranial cruciate ligament deficiency, tibial plateau leveling osteotomy, and tibial tuberosity advancement on contact mechanics and alignment of the stifle in flexion.

PubMed

Kim, Stanley E; Pozzi, Antonio; Banks, Scott A; Conrad, Bryan P; Lewis, Daniel D

2010-04-01

To assess contact mechanics and 3-dimensional (3-D) joint alignment in cranial cruciate ligament (CCL)-deficient stifles before and after tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA) with the stifle in 90 degrees of flexion. In vitro biomechanical study. Cadaveric pelvic limb pairs (n=8) from dogs weighing 28-35 kg. Contralateral limbs were assigned to receive TPLO or TTA. Digital pressure sensors were used to measure femorotibial contact area, peak and mean contact pressure, and peak pressure location with the limb under a load of 30% body weight and stifle flexion angle of 90 degrees . 3-D poses were obtained using a Microscribe digitizer. Specimens were tested under normal, CCL deficient, and treatment conditions. Significant disturbances in alignment were not observed after CCL transection, although medial contact area was 10% smaller than normal (P=.003). There were no significant differences in contact mechanics or alignment between normal and TTA conditions; TPLO induced 6 degrees varus angulation (P<.001), 26% decrease in lateral peak pressure (P=.027), and 18% increase in medial mean pressure (P=.008) when compared with normal. Cranial tibial subluxation is nominal in CCL-deficient stifles loaded in flexion. Stifle alignment and contact mechanics are not altered by TTA, whereas TPLO causes mild varus and a subsequent increase in medial compartment loading. Cranial tibial subluxation of CCL-deficient stifles may not occur during postures that load the stifle in flexion. The significance of minor changes in loading patterns after TPLO is unknown.

19 F(α,n) thick target yield from 3.5 to 10.0 MeV

DOE PAGES

Norman, E.B.; Chupp, T.E.; Lesko, K.T.; ...

2015-09-01

Using a target of PbF2, the thick-target yield from the 19F(α,n) reaction was measured from Eα=3.5–10 MeV. From these results, we infer the thick-target neutron yields from targets of F2 and UF6 over this same alpha-particle energy range.

Computerized pediatric telephone triage and advice programs at children's hospitals: operating and financial characteristics.

PubMed

Melzer, S M; Poole, S R

1999-08-01

To describe the operating characteristics, financial performance, and perceived value of computerized children's hospital-based telephone triage and advice (TTA) programs. A written survey of all 32 children's hospital-based TTA programs in the United States that used the same proprietary pediatric TTA software product for at least 6 months. The expense, revenues, and perceived value of children's hospital-based TTA programs. Of 30 programs (94%) responding, 27 (90%) were eligible for the study and reported on their experience with nearly 1.3 million TTA calls over a 12-month period. Programs provided pediatric TTA services for 1560 physicians, serving an average of 82 physicians (range, 10-340 physicians) and answering 38880 calls (range, 8500-140000 calls) annually. The mean call duration was 11.3 minutes and the estimated mean total expense per call was $12.45. Of programs charging fees for TTA services, 16 (59%) used a per-call fee and 7 (26%) used a monthly service fee. All respondents indicated that fees did not cover all associated costs. Telephone triage and advice programs, when examined on a stand-alone basis, were all operating with annual deficits (mean, $447000; median, $325000; range, $74000-$1.3 million), supported by the sponsoring children's hospitals and their companion programs. Using a 3-point Likert scale, the TTA program managers rated the value of the TTA program very highly as a mechanism for marketing to physicians (2.85) and increasing physician (2.92) and patient (2.80) satisfaction. Children's hospital-based TTA programs operate at substantial financial deficits. Ongoing support of these programs may derive from the perception that they are a valuable mechanism for marketing and increase patient and physician satisfaction. Children's hospitals should develop strategies to ensure the long-term financial viability of TTA programs or they may have to discontinue these services.

Using Landsat Surface Reflectance Data as a Reference Target for Multiswath Hyperspectral Data Collected Over Mixed Agricultural Rangeland Areas

DOE PAGES

McCann, Cooper; Repasky, Kevin S.; Morin, Mikindra; ...

2017-07-25

Low-cost flight-based hyperspectral imaging systems have the potential to provide important information for ecosystem and environmental studies as well as aide in land management. To realize this potential, methods must be developed to provide large-area surface reflectance data allowing for temporal data sets at the mesoscale. This paper describes a bootstrap method of producing a large-area, radiometrically referenced hyperspectral data set using the Landsat surface reflectance (LaSRC) data product as a reference target. The bootstrap method uses standard hyperspectral processing techniques that are extended to remove uneven illumination conditions between flight passes, allowing for radiometrically self-consistent data after mosaicking. Throughmore » selective spectral and spatial resampling, LaSRC data are used as a radiometric reference target. Advantages of the bootstrap method include the need for minimal site access, no ancillary instrumentation, and automated data processing. Data from two hyperspectral flights over the same managed agricultural and unmanaged range land covering approximately 5.8 km 2 acquired on June 21, 2014 and June 24, 2015 are presented. As a result, data from a flight over agricultural land collected on June 6, 2016 are compared with concurrently collected ground-based reflectance spectra as a means of validation.« less

Using Landsat Surface Reflectance Data as a Reference Target for Multiswath Hyperspectral Data Collected Over Mixed Agricultural Rangeland Areas

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

McCann, Cooper; Repasky, Kevin S.; Morin, Mikindra

Low-cost flight-based hyperspectral imaging systems have the potential to provide important information for ecosystem and environmental studies as well as aide in land management. To realize this potential, methods must be developed to provide large-area surface reflectance data allowing for temporal data sets at the mesoscale. This paper describes a bootstrap method of producing a large-area, radiometrically referenced hyperspectral data set using the Landsat surface reflectance (LaSRC) data product as a reference target. The bootstrap method uses standard hyperspectral processing techniques that are extended to remove uneven illumination conditions between flight passes, allowing for radiometrically self-consistent data after mosaicking. Throughmore » selective spectral and spatial resampling, LaSRC data are used as a radiometric reference target. Advantages of the bootstrap method include the need for minimal site access, no ancillary instrumentation, and automated data processing. Data from two hyperspectral flights over the same managed agricultural and unmanaged range land covering approximately 5.8 km 2 acquired on June 21, 2014 and June 24, 2015 are presented. As a result, data from a flight over agricultural land collected on June 6, 2016 are compared with concurrently collected ground-based reflectance spectra as a means of validation.« less

Measurement of the distribution of radiation in the area surrounding the target mass using optically stimulated luminescence technique.

PubMed

Tanır, A Güneş; Yedek, Hatice; Koç, Kemal; Bölükdemir, M Hicabi

2017-01-01

The scattered doses received by the area surrounding the target that has been subjected to x-rays were investigated. Two experiments were carried out: 1- Al 2 O 3 : C was used as dosimeter and the luminescence counts was measured using both the RisØ TL/OSL system and an ion chamber. 2- BeO aliquots were used and the counts were read using the IBEOX/OSL system. According to the results, the doses absorbed by the area surrounding the target are significantly amount. Copyright © 2016 Elsevier Ltd. All rights reserved.

75 FR 53969 - Office of Community Services: Notice To Award an Expansion Supplement

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-02

... related to job creation and new initiatives that target careers in energy efficiency and other...; and (3) collects, develops, and disseminates resources related to job creation and careers related to... through professional consultations and peer assistance sessions; and online toolkit(s). The T/TA CAP will...

Biochemical Characterisation of TSC1 and TSC2 Variants Identified in Patients with Tuberous Sclerosis Complex

DTIC Science & Technology

2010-07-01

G-3¶) and TSC1 reverse (5¶-GCG GGT ACC TTA GCT GTG TTC ATG AGT CTC-3¶). Subsequently, an mCherry tag was inserted N-terminally in pcDNA3.1-TSC1 to...primer pair mCherry forward (5¶-GCG TCT AGA ACC ATG GTG AGC AAG GGC GA-3¶) and mCherry reverse (5¶-GCG GCT AGC CTT GTA CAG CTC GTC CAT GCC-3¶). The...5¶-GAT GAG ATC CGC ACC CTC TGA GAC CAG CTG CTT TTA CTG CAC AAC-3¶; TSC1R692X reverse: 5¶-GTT GTG CAG TAA AAG CAG CTG GTC TCA GAG GGT GCG GAT CTC ATC

Evaluation of Genomic Instability in the Abnormal Prostate

DTIC Science & Technology

2007-12-01

Mehrotra, J., Varde, S., Wang, H., Chiu, H., Vargo, J., Gray , K., Nagle, R.B., Neri, J.R., Mazumder, A. (2007) Prostate 68, 152-60. Appendix A...GSTP-1 Reverse 5’-GCC CCA ATA CTA AAT CAC GAC G-3’ GSTP-1 Probe 5’-6-FAM-CGG TCG ACG TTC GGG GTG TAG CG-6-TAMSp-3’ RassF1A Forward 5’-GCG TTG AAG...GAA CCA AAA CGC TCC CCA T-3’ APC Reverse 5’-TTA TAT GTC GGT TAC GTG CGT TTA TAT-3’ APC Probe 5’-6-FAM-CCC GTC GAA AAC CCG CCG ATT A-6-TAMSp-3

5. Photocopy of photograph showing target tracking radar from 'Procedures ...

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

5. Photocopy of photograph showing target tracking radar from 'Procedures and Drills for the NIKE Hercules Missile Battery,' Department of the Army Field Manual, FM-44-82 from Institute for Military History, Carlisle Barracks, Carlisle, PA, 1959 - NIKE Missile Battery PR-79, East Windsor Road south of State Route 101, Foster, Providence County, RI

miR-758-5p regulates cholesterol uptake via targeting the CD36 3'UTR.

PubMed

Li, Bi-Rong; Xia, Lin-Qin; Liu, Jing; Liao, Lin-Ling; Zhang, Yang; Deng, Min; Zhong, Hui-Juan; Feng, Ting-Ting; He, Ping-Ping; Ouyang, Xin-Ping

2017-12-09

miR-758-3p plays an important role via regulting ABCA1-mediated cholesterol efflux in atherosclerosis. However, the mechanism of miR-758-5p in cholesterol metabolism is still unclear. Here, we revealed that miR-758-5p decreased total cholesterol accumulation in THP-1 macrophage derived foam cells through markedly reducing cholesterol uptake, and no effect on the cholesterol efflux. Interestingly, computational analysis suggests that CD36 may be a target gene of miR-758-5p. Our study further demonstrated that miR-758-5p decreased CD36 expression at both protein and mRNA levels via targeting the CD36 3'UTR in THP-1 macrophage derived foam cells. The present present study concluded that miR-758-5p decreases lipid accumulation of foam cell via regulating CD36-mediated the cholesterol uptake. Therefore, targeting miR-758-5p may offer a promising strategy to treat atherosclerotic vascular disease. Copyright © 2017. Published by Elsevier Inc.

Photon energy upconverting nanopaper: a bioinspired oxygen protection strategy.

PubMed

Svagan, Anna J; Busko, Dmitry; Avlasevich, Yuri; Glasser, Gunnar; Baluschev, Stanislav; Landfester, Katharina

2014-08-26

The development of solid materials which are able to upconvert optical radiation into photons of higher energy is attractive for many applications such as photocatalytic cells and photovoltaic devices. However, to fully exploit triplet-triplet annihilation photon energy upconversion (TTA-UC), oxygen protection is imperative because molecular oxygen is an ultimate quencher of the photon upconversion process. So far, reported solid TTA-UC materials have focused mainly on elastomeric matrices with low barrier properties because the TTA-UC efficiency generally drops significantly in glassy and semicrystalline matrices. To overcome this limit, for example, combine effective and sustainable annihilation upconversion with exhaustive oxygen protection of dyes, we prepare a sustainable solid-state-like material based on nanocellulose. Inspired by the structural buildup of leaves in Nature, we compartmentalize the dyes in the liquid core of nanocellulose-based capsules which are then further embedded in a cellulose nanofibers (NFC) matrix. Using pristine cellulose nanofibers, a sustainable and environmentally friendly functional nanomaterial with ultrahigh barrier properties is achieved. Also, an ensemble of sensitizers and emitter compounds are encapsulated, which allow harvesting of the energy of the whole deep-red sunlight region. The films demonstrate excellent lifetime in synthetic air (20.5/79.5, O2/N2)-even after 1 h operation, the intensity of the TTA-UC signal decreased only 7.8% for the film with 8.8 μm thick NFC coating. The lifetime can be further modulated by the thickness of the protective NFC coating. For comparison, the lifetime of TTA-UC in liquids exposed to air is on the level of seconds to minutes due to fast oxygen quenching.

MicroRNA-490-5p inhibits proliferation of bladder cancer by targeting c-Fos

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

Li, Shiqi; Xu, Xianglai; Xu, Xin

2013-11-29

Highlights: •We examined the level of miR-490-5p in bladder cancer tissues and three cancer cell lines. •We are the first to show the function of miR-490-5p in bladder cancer. •We demonstrate c-Fos may be a target of miR-490-5p. -- Abstract: MicroRNAs (miRNAs) are non-protein-coding sequences that play a crucial role in tumorigenesis by negatively regulating gene expression. Here, we found that miR-490-5p is down-regulated in human bladder cancer tissue and cell lines compared to normal adjacent tissue and a non-malignant cell line. To better characterize the function of miR-490-5p in bladder cancer, we over-expressed miR-490-5p in bladder cancer cell linesmore » with chemically synthesized mimics. Enforced expression of miR-490-5p in bladder cancer cells significantly inhibited the cell proliferation via G1-phase arrest. Further studies found the decreased c-Fos expression at both mRNA and protein levels and Luciferase reporter assays demonstrated that c-Fos is a direct target of miR-490-5p in bladder cancer. These findings indicate miR-490-5p to be a novel tumor suppressor of bladder cancer cell proliferation through targeting c-Fos.« less

Synergies and trade-offs in achieving global biodiversity targets.

PubMed

Di Marco, Moreno; Butchart, Stuart H M; Visconti, Piero; Buchanan, Graeme M; Ficetola, Gentile F; Rondinini, Carlo

2016-02-01

After their failure to achieve a significant reduction in the global rate of biodiversity loss by 2010, world governments adopted 20 new ambitious Aichi biodiversity targets to be met by 2020. Efforts to achieve one particular target can contribute to achieving others, but different targets may sometimes require conflicting solutions. Consequently, lack of strategic thinking might result, once again, in a failure to achieve global commitments to biodiversity conservation. We illustrate this dilemma by focusing on Aichi Target 11. This target requires an expansion of terrestrial protected area coverage, which could also contribute to reducing the loss of natural habitats (Target 5), reducing human-induced species decline and extinction (Target 12), and maintaining global carbon stocks (Target 15). We considered the potential impact of expanding protected areas to mitigate global deforestation and the consequences for the distribution of suitable habitat for >10,000 species of forest vertebrates (amphibians, birds, and mammals). We first identified places where deforestation might have the highest impact on remaining forests and then identified places where deforestation might have the highest impact on forest vertebrates (considering aggregate suitable habitat for species). Expanding protected areas toward locations with the highest deforestation rates (Target 5) or the highest potential loss of aggregate species' suitable habitat (Target 12) resulted in partially different protected area network configurations (overlapping with each other by about 73%). Moreover, the latter approach contributed to safeguarding about 30% more global carbon stocks than the former. Further investigation of synergies and trade-offs between targets would shed light on these and other complex interactions, such as the interaction between reducing overexploitation of natural resources (Targets 6, 7), controlling invasive alien species (Target 9), and preventing extinctions of native

SEDIMENT HABITAT ASSESSMENT FOR TARGETED NEAR-COASTAL AREAS OF THE GULF OF MEXICO: A SUMMARY

EPA Science Inventory

Lewis, Michael A. In press. Sediment Habitat Assessment for Targeted Near-Coastal Areas of the Gulf of Mexico: A Summary. In: Estuarine Indicators Workshop Proceedings. CRC Press, Boca Raton, FL. 25 p. (ERL,GB 1201).

Sediment chemical and biological quality is summarized ...

7 CFR 301.89-5 - Movement of regulated articles from regulated areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Movement of regulated articles from regulated areas. 301.89-5 Section 301.89-5 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... § 301.89-5 Movement of regulated articles from regulated areas. (a) Any regulated article may be moved...

Time-to-Antibiotic Administration as a Quality of Care Measure in Children with Febrile Neutropenia: A Survey of Pediatric Oncology Centers

PubMed Central

McCavit, Timothy L.; Winick, Naomi

2011-01-01

Time-to-antibiotic administration (TTA) has been suggested as a quality-of-care (QOC) measure for pediatric oncology patients with febrile neutropenia (FN). Unknown, however, is to what extent pediatric oncology centers utilize TTA. Therefore, we designed and administered an electronic survey (68% response rate) of programs in the Children's Oncology Group to assess TTA utilization. Nearly half of respondents track TTA. Most reported using a benchmark of less than 60 minutes from arrival. TTA is a commonly used QOC measure for pediatric FN despite an absence of studies establishing its validity and a lack of data supporting its impact on outcomes of FN. PMID:21509930

Assessing protected area effectiveness using surrounding (buffer) areas environmentally similar to the target area.

PubMed

Mas, Jean-François

2005-06-01

Many studies are based on the assumption that an area and its surrounding (buffer) area present similar environmental conditions and can be compared. For example, in order to assess the effectiveness of a protected area, the land use/cover changes are compared inside the park with its surroundings. However, the heterogeneity in spatial variables can bias this assessment: we have shown that most of the protected areas in Mexico present significant environmental differences between their interior and their surroundings. Therefore, a comparison that aims at assessing the effectiveness of conservation strategies, must be cautioned. In this paper, a simple method which allows the generation of a buffer area that presents similar conditions with respect to a set of environmental variables is presented. The method was used in order to assess the effectiveness of the Calakmul Biosphere Reserve, a protected area located in the south-eastern part of Mexico. The annual rate of deforestation inside the protected area, the standard buffer area (based upon distance from the protected area only) and the similar buffer area (taking into account distance along with some environmental variables) were 0.3, 1.3 and 0.6%, respectively. These results showed that the protected area was effective in preventing land clearing, but that the comparison with the standard buffer area gave an over-optimistic vision of its effectiveness.

Effect of area ratio on the performance of a 5.5:1 pressure ratio centrifugal impeller

NASA Technical Reports Server (NTRS)

Schumann, L. F.; Clark, D. A.; Wood, J. R.

1986-01-01

A centrifugal impeller which was initially designed for a pressure ratio of approximately 5.5 and a mass flow rate of 0.959 kg/sec was tested with a vaneless diffuser for a range of design point impeller area ratios from 2.322 to 2.945. The impeller area ratio was changed by successively cutting back the impeller exit axial width from an initial value of 7.57 mm to a final value of 5.97 mm. In all, four separate area ratios were tested. For each area ratio a series of impeller exit axial clearances was also tested. Test results are based on impeller exit surveys of total pressure, total temperature, and flow angle at a radius 1.115 times the impeller exit radius. Results of the tests at design speed, peak efficiency, and an exit tip clearance of 8 percent of exit blade height show that the impeller equivalent pressure recovery coefficient peaked at a design point area ratio of approximately 2.748 while the impeller aerodynamic efficiency peaked at a lower value of area ratio of approximately 2.55. The variation of impeller efficiency with clearance showed expected trends with a loss of approximately 0.4 points in impeller efficiency for each percent increase in exit axial tip clearance for all impellers tested.

Target and beam-target spin asymmetries in exclusive π+ and π- electroproduction with 1.6- to 5.7-GeV electrons

NASA Astrophysics Data System (ADS)

Bosted, P. E.; Biselli, A. S.; Careccia, S.; Dodge, G.; Fersch, R.; Guler, N.; Kuhn, S. E.; Pierce, J.; Prok, Y.; Zheng, X.; Adhikari, K. P.; Adikaram, D.; Akbar, Z.; Amaryan, M. J.; Anefalos Pereira, S.; Asryan, G.; Avakian, H.; Badui, R. A.; Ball, J.; Baltzell, N. A.; Battaglieri, M.; Batourine, V.; Bedlinskiy, I.; Boiarinov, S.; Briscoe, W. J.; Bültmann, S.; Burkert, V. D.; Cao, T.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Chetry, T.; Ciullo, G.; Clark, L.; Colaneri, L.; Cole, P. L.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; Deur, A.; Djalali, C.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Filippi, A.; Fleming, J. A.; Forest, T. A.; Fradi, A.; Garçon, M.; Gevorgyan, N.; Ghandilyan, Y.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Gleason, C.; Gohn, W.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guo, L.; Hafidi, K.; Hanretty, C.; Harrison, N.; Hattawy, M.; Heddle, D.; Hicks, K.; Holtrop, M.; Hughes, S. M.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joo, K.; Joosten, S.; Keller, D.; Khandaker, M.; Kim, W.; Klein, A.; Klein, F. J.; Kubarovsky, V.; Kuleshov, S. V.; Lanza, L.; Lenisa, P.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Markov, N.; McCracken, M. E.; McKinnon, B.; Meyer, C. A.; Minehart, R.; Mirazita, M.; Mokeev, V.; Movsisyan, A.; Munevar, E.; Munoz Camacho, C.; Nadel-Turonski, P.; Net, L. A.; Ni, A.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Peng, P.; Phelps, W.; Pisano, S.; Pogorelko, O.; Price, J. W.; Procureur, S.; Protopopescu, D.; Puckett, A. J. R.; Raue, B. A.; Ripani, M.; Rizzo, A.; Rosner, G.; Rossi, P.; Roy, P.; Sabatié, F.; Salgado, C.; Schumacher, R. A.; Seder, E.; Sharabian, Y. G.; Simonyan, A.; Skorodumina, Iu.; Smith, G. D.; Sparveris, N.; Stankovic, Ivana; Stepanyan, S.; Strakovsky, I. I.; Strauch, S.; Sytnik, V.; Taiuti, M.; Tian, Ye; Torayev, B.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Weinstein, L. B.; Wood, M. H.; Zachariou, N.; Zana, L.; Zhang, J.; Zhao, Z. W.; Zonta, I.; CLAS Collaboration

2016-11-01

Beam-target double-spin asymmetries and target single-spin asymmetries in exclusive π+ and quasiexclusive π- electroproduction were obtained from scattering of 1.6- to 5.7-GeV longitudinally polarized electrons from longitudinally polarized protons (for π+) and deuterons (for π-) using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The kinematic range covered is 1.1 5 GeV2 , with good angular coverage in the forward hemisphere. The asymmetry results were divided into approximately 40 000 kinematic bins for π+ from free protons and 15 000 bins for π- production from bound nucleons in the deuteron. The present results are found to be in reasonable agreement with fits to previous world data for W <1.7 GeV and Q2<0.5 GeV2 , with discrepancies increasing at higher values of Q2, especially for W >1.5 GeV. Very large target-spin asymmetries are observed for W >1.6 GeV. When combined with cross-section measurements, the present results can provide powerful constraints on nucleon resonance amplitudes at moderate and large values of Q2, for resonances with masses as high as 2.3 GeV.

Target and beam-target spin asymmetries in exclusive π + and π - electroproduction with 1.6- to 5.7-GeV electrons

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

Bosted, P. E.; Biselli, A. S.; Careccia, S.

Beam-target double-spin asymmetries and target single-spin asymmetries in exclusive pi(+) and quasiexclusive pi(-) electroproduction were obtained from scattering of 1.6- to 5.7-GeV longitudinally polarized electrons from longitudinally polarized protons (for pi(+)) and deuterons (for pi(-)) using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The kinematic range covered is 1.1 < W < 2.6 GeV and 0.05 < Q(2) < 5 GeV2, with good angular coverage in the forward hemisphere. The asymmetry results were divided into approximately 40 000 kinematic bins for pi(+) from free protons and 15 000 bins for pi(-) production from bound nucleons in the deuteron.more » The present results are found to be in reasonable agreement with fits to previous world data for W < 1.7 GeV and Q(2) < 0.5 GeV2, with discrepancies increasing at higher values of Q(2), especially for W > 1.5 GeV. Very large target-spin asymmetries are observed for W > 1.6 GeV. When combined with cross-section measurements, the present results can provide powerful constraints on nucleon resonance amplitudes at moderate and large values of Q(2), for resonances with masses as high as 2.3 GeV.« less

Evaluation of a Powered Ankle-Foot Prosthesis during Slope Ascent Gait

PubMed Central

2016-01-01

Passive prosthetic feet lack active plantarflexion and push-off power resulting in gait deviations and compensations by individuals with transtibial amputation (TTA) during slope ascent. We sought to determine the effect of active ankle plantarflexion and push-off power provided by a powered prosthetic ankle-foot (PWR) on lower extremity compensations in individuals with unilateral TTA as they walked up a slope. We hypothesized that increased ankle plantarflexion and push-off power would reduce compensations commonly observed with a passive, energy-storing-returning prosthetic ankle-foot (ESR). We compared the temporal spatial, kinematic, and kinetic measures of ten individuals with TTA (age: 30.2 ± 5.3 yrs) to matched abled-bodied (AB) individuals during 5° slope ascent. The TTA group walked with an ESR and separately with a PWR. The PWR produced significantly greater prosthetic ankle plantarflexion and push-off power generation compared to an ESR and more closely matched AB values. The PWR functioned similar to a passive ESR device when transitioning onto the prosthetic limb due to limited prosthetic dorsiflexion, which resulted in similar deviations and compensations. In contrast, when transitioning off the prosthetic limb, increased ankle plantarflexion and push-off power provided by the PWR contributed to decreased intact limb knee extensor power production, lessening demand on the intact limb knee. PMID:27977681

Evaluation of a Powered Ankle-Foot Prosthesis during Slope Ascent Gait.

PubMed

Rábago, Christopher A; Aldridge Whitehead, Jennifer; Wilken, Jason M

2016-01-01

Passive prosthetic feet lack active plantarflexion and push-off power resulting in gait deviations and compensations by individuals with transtibial amputation (TTA) during slope ascent. We sought to determine the effect of active ankle plantarflexion and push-off power provided by a powered prosthetic ankle-foot (PWR) on lower extremity compensations in individuals with unilateral TTA as they walked up a slope. We hypothesized that increased ankle plantarflexion and push-off power would reduce compensations commonly observed with a passive, energy-storing-returning prosthetic ankle-foot (ESR). We compared the temporal spatial, kinematic, and kinetic measures of ten individuals with TTA (age: 30.2 ± 5.3 yrs) to matched abled-bodied (AB) individuals during 5° slope ascent. The TTA group walked with an ESR and separately with a PWR. The PWR produced significantly greater prosthetic ankle plantarflexion and push-off power generation compared to an ESR and more closely matched AB values. The PWR functioned similar to a passive ESR device when transitioning onto the prosthetic limb due to limited prosthetic dorsiflexion, which resulted in similar deviations and compensations. In contrast, when transitioning off the prosthetic limb, increased ankle plantarflexion and push-off power provided by the PWR contributed to decreased intact limb knee extensor power production, lessening demand on the intact limb knee.

Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles.

PubMed

Wang, Yichao; Li, Puwang; Chen, Lijue; Gao, Weimin; Zeng, Fanbo; Kong, Ling Xue

2015-02-01

The incorporation of a high percentage of targeting molecules into drug delivery system is one of the important methods for improving efficacy of targeting therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic acid (FA) as targeting molecule have a low targeting efficiency due to a low FA conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of 46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro experiments, an IC₅₀ of 5.69 µg/mL has been achieved for 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which only have an IC₅₀ of 22.9 and 14.17 µg/mL, respectively. The fluorescent microscopy images showed that nanoparticles with FA are largely taken up by HT-29 cancer cells and the targeting nanoparticles have more affinity to cancer cells than the pure drugs and untreated nanoparticles. Therefore, the 1, 3-diaminopropane can facilitate the conjugation of FA to PLGA to form a novel polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be a highly efficient system for specific delivery of drugs to cancer cells.

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation.

PubMed

Valencia-Torres, Lourdes; Olarte-Sánchez, Cristian M; Lyons, David J; Georgescu, Teodora; Greenwald-Yarnell, Megan; Myers, Martin G; Bradshaw, Christopher M; Heisler, Lora K

2017-06-01

Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT 2C R) is a target for the treatment of human obesity. Mechanistically, 5-HT 2C Rs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HT 2C Rs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice. We found that the 5-HT 2C R agonist lorcaserin significantly reduced both ad libitum chow intake and PR responding for chocolate pellets and increased c-fos expression in VTA 5-HT 2C R expressing γ-aminobutyric acid (GABA) neurons, but not 5-HT 2C R expressing dopamine (DA) neurons. We next adopted a chemogenetic approach using a 5-HT 2C R CRE line to clarify the function of subset of 5-HT 2C receptor expressing VTA neurons in the modulation of appetite and food-motivated behavior. Activation of VTA 5-HT 2C receptor expressing neurons significantly reduced ad libitum chow intake, operant responding for chocolate pellets, and the incentive value of food. In contrast, chemogenetic inhibition of VTA 5-HT 2C receptor expressing neurons had no effect on the feeding behavior. These results indicate that activation of the subpopulation of 5-HT 2C R neurons within the VTA is sufficient to significantly reduce homeostatic feeding and effort-based intake of palatable food, and that this subset has an inhibitory role in motivational processes. These findings are relevant to the treatment of obesity.

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

PubMed Central

Valencia-Torres, Lourdes; Olarte-Sánchez, Cristian M; Lyons, David J; Georgescu, Teodora; Greenwald-Yarnell, Megan; Myers, Martin G; Bradshaw, Christopher M; Heisler, Lora K

2017-01-01

Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT2CR) is a target for the treatment of human obesity. Mechanistically, 5-HT2CRs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HT2CRs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice. We found that the 5-HT2CR agonist lorcaserin significantly reduced both ad libitum chow intake and PR responding for chocolate pellets and increased c-fos expression in VTA 5-HT2CR expressing γ-aminobutyric acid (GABA) neurons, but not 5-HT2CR expressing dopamine (DA) neurons. We next adopted a chemogenetic approach using a 5-HT2CRCRE line to clarify the function of subset of 5-HT2C receptor expressing VTA neurons in the modulation of appetite and food-motivated behavior. Activation of VTA 5-HT2C receptor expressing neurons significantly reduced ad libitum chow intake, operant responding for chocolate pellets, and the incentive value of food. In contrast, chemogenetic inhibition of VTA 5-HT2C receptor expressing neurons had no effect on the feeding behavior. These results indicate that activation of the subpopulation of 5-HT2CR neurons within the VTA is sufficient to significantly reduce homeostatic feeding and effort-based intake of palatable food, and that this subset has an inhibitory role in motivational processes. These findings are relevant to the treatment of obesity. PMID:27882999

Nevada National Security Site 2011 Waste Management Monitoring Report, Area 3 and Area 5 Radioactive Waste Management Site

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

NSTec Environmental Management

2012-07-31

Environmental monitoring data are collected at and around the Area 3 and Area 5 Radioactive Waste Management Sites (RWMSs) at the Nevada National Security Site (NNSS). These data are associated with radiation exposure, air, groundwater, meteorology, and vadose zone. This report summarizes the 2011 environmental data to provide an overall evaluation of RWMS performance and to support environmental compliance and performance assessment (PA) activities. Some of these data (e.g., radiation exposure, air, and groundwater) are presented in other reports. Direct radiation monitoring data indicate exposure levels at the RWMSs are within the range of background levels measured at the NNSS.more » Slightly elevated exposure levels outside the Area 3 RWMS are attributed to nearby historical aboveground nuclear weapons tests. Air monitoring data show tritium concentrations in water vapor and americium and plutonium concentrations in air particles are only slightly above detection limits and background levels. The measured levels of radionuclides in air particulates and moisture are below derived concentration guides for these radionuclides. During the last 2 weeks of March 2011, gamma spectroscopy results for air particles showed measurable activities of iodine-131 (131I), cesium-134 (134Cs), and cesium-137 (137Cs). These results are attributed to the release of fission products from the damaged Fukushima Daiichi power plant in Japan. The remaining gamma spectroscopy results for air particulates collected at the Area 3 and Area 5 RWMS were below minimum detectable concentrations. Groundwater monitoring data indicate the groundwater in the uppermost aquifer beneath the Area 5 RWMS is not impacted by RWMS operations. Results of groundwater analysis from wells around the Area 5 RWMS were all below established investigation levels. The 86.3 millimeters (mm) (3.40 inches [in.]) of precipitation at the Area 3 RWMS during 2011 is 44% below the average of 154.1 mm (6.07 in.), and the

WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors

PubMed Central

Anastas, Jamie N.; Kulikauskas, Rima M.; Tamir, Tigist; Rizos, Helen; Long, Georgina V.; von Euw, Erika M.; Yang, Pei-Tzu; Chen, Hsiao-Wang; Haydu, Lauren; Toroni, Rachel A.; Lucero, Olivia M.; Chien, Andy J.; Moon, Randall T.

2014-01-01

About half of all melanomas harbor a mutation that results in a constitutively active BRAF kinase mutant (BRAFV600E/K) that can be selectively inhibited by targeted BRAF inhibitors (BRAFis). While patients treated with BRAFis initially exhibit measurable clinical improvement, the majority of patients eventually develop drug resistance and relapse. Here, we observed marked elevation of WNT5A in a subset of tumors from patients exhibiting disease progression on BRAFi therapy. WNT5A transcript and protein were also elevated in BRAFi-resistant melanoma cell lines generated by long-term in vitro treatment with BRAFi. RNAi-mediated reduction of endogenous WNT5A in melanoma decreased cell growth, increased apoptosis in response to BRAFi challenge, and decreased the activity of prosurvival AKT signaling. Conversely, overexpression of WNT5A promoted melanoma growth, tumorigenesis, and activation of AKT signaling. Similarly to WNT5A knockdown, knockdown of the WNT receptors FZD7 and RYK inhibited growth, sensitized melanoma cells to BRAFi, and reduced AKT activation. Together, these findings suggest that chronic BRAF inhibition elevates WNT5A expression, which promotes AKT signaling through FZD7 and RYK, leading to increased growth and therapeutic resistance. Furthermore, increased WNT5A expression in BRAFi-resistant melanomas correlates with a specific transcriptional signature, which identifies potential therapeutic targets to reduce clinical BRAFi resistance. PMID:24865425

Missing marine protected area (MPA) targets: How the push for quantity over quality undermines sustainability and social justice.

PubMed

De Santo, Elizabeth M

2013-07-30

International targets for marine protected areas (MPAs) and networks of MPAs set by the World Summit on Sustainable Development and United Nations Convention on Biological Diversity failed to meet their 2012 deadline and have been extended to 2020. Whilst targets play an important role in building momentum for conservation, they are also responsible for the recent designation of several extremely large no-take MPAs, which pose significant long-term monitoring and enforcement challenges. This paper critically examines the effectiveness of MPA targets, focusing on the underlying risks to achieving Millennium Development Goals posed by the global push for quantity versus quality of MPAs. The observations outlined in this paper have repercussions for international protected area politics with respect to (1) the science-policy interface in environmental decision-making, and (2) social justice concerns in global biodiversity conservation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nevada National Security Site 2015 Waste Management Monitoring Report Area 3 and Area 5 Radioactive Waste Management Sites

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

Black, David; Hudson, David

Environmental monitoring data are collected at and around the Area 3 and Area 5 Radioactive Waste Management Sites (RWMSs) within the Nevada National Security Site (NNSS). These data include direct radiation exposure, as well as radiation from the air, groundwater, meteorology, and vadose zone. This report summarizes the 2015 environmental data to provide an overall evaluation of RWMS performance and to support environmental compliance and performance assessment (PA) activities. Some of these data (e.g., radiation exposure, air, and groundwater) are presented in other reports developed by National Security Technologies, LLC. Direct radiation monitoring data indicate exposure levels at the RWMSsmore » are within the range of background levels measured at the NNSS. Slightly elevated exposure levels outside the Area 3 RWMS are attributed to nearby historical aboveground nuclear weapons tests. Air monitoring data show that tritium concentrations in water vapor and americium and plutonium concentrations in air particles are below Derived Concentration Standards for these radionuclides. Groundwater monitoring data indicate the groundwater in the uppermost aquifer beneath the Area 5 RWMS is not impacted by RWMS operations. Results of groundwater analysis from wells around the Area 5 RWMS were all below established investigation levels. Leachate samples collected from the leachate collection system at the mixed low-level waste cell were below established contaminant regulatory limits. During 2015, precipitation at the Area 3 RWMS was 0.9% above average, and precipitation at the Area 5 RWMS was 25% above average. Water balance measurements indicate that evapotranspiration from the vegetated weighing lysimeter dries the soil and prevents downward percolation of precipitation more effectively than evaporation as measured from the bare-soil weighing lysimeter. The 1.8 inches of precipitation in September reached the lowest sensors at 180 cm on the Cell 5S and 5N covers

PRMT5 as a druggable target for glioblastoma therapy.

PubMed

Banasavadi-Siddegowda, Yeshavanth Kumar; Welker, Alessandra M; An, Min; Yang, Xiaozhi; Zhou, Wei; Shi, Guqin; Imitola, Jaime; Li, Chenglong; Hsu, Sigmund; Wang, Jiang; Phelps, Mitch; Zhang, Jianying; Beattie, Christine E; Baiocchi, Robert; Kaur, Balveen

2018-05-18

In spite of standard multimodal therapy consisting of surgical resection followed by radiation and concurrent chemotherapy, prognosis for glioblastoma (GBM) patients remains poor. The identification of both differentiated and undifferentiated "stem cell like" populations in the tumor highlights the significance of finding novel targets that affect the heterogeneous tumor cell population. Protein arginine methyltransferase 5 (PRMT5) is one such candidate gene whose nuclear expression correlates with poor survival and has been reported to be required for survival of differentiated GBM cells and self-renewal of undifferentiated GBM cells. In the current study we screened the specificity and efficacy of 4 novel PRMT5 inhibitors in the treatment of GBM. Efficacies of these inhibitors were screened using an in vitro GBM neurosphere model and an in vivo intracranial zebrafish model of glioma. Standard molecular biology methods were employed to investigate changes in cell cycle, growth, and senescence. In vitro and in vivo studies revealed that among the 4 PRMT5 inhibitors, treatment of GBM cells with compound 5 (CMP5) mirrored the effects of PRMT5 knockdown wherein it led to apoptosis of differentiated GBM cells and drove undifferentiated primary patient derived GBM cells into a nonreplicative senescent state. In vivo antitumor efficacy combined with the specificity of CMP5 underscores the importance of developing it for translation.

Retrieval of AOD and PM2.5 Concentrations over Urban Areas of Shenyang City using MODIS Data

NASA Astrophysics Data System (ADS)

Wang, Z.

2016-12-01

Atmospheric aerosols play an important part in the Earth's radiation balance as well as global climate change, aerosols also have very important impact on environment as well as human and other organisms' health, PM2.5 and other small particle aerosols, can enter bronchi directly, thus causing bronchitis, cardiovascular disease, asthma and so on.Detection of AOD by satellite and remote sensing is currently one of the hotest issues , diffierent from the traditional monitoring method, this method has much more advantanges, for emample wide area coverage, fast and convenient etc. So it is possible for people to know the regional changes of AOD real time over large area. Now, detection aerosol by RS technology has reached a high level in marine and dense vegetation land areas, but result is not ideal for urban areas, the higher surface reflectance in urban areas is a bottleneck of AOD retrieval. Focus on the high surface reflectance and low accuracy of the AOD products of urban areas, this paper propose an algorithm coupled with surface reflectance to get red band surface reflectance, based on Dens Dark Vegetation algorithm and geometrical optics model theory, to distinguish urban reflectivity from other targets. Considering the appropriate aerosol model which adapt to season and other proper parameters, this paper uses 6S model to establish look-up table, thus retrieve AOD for urban as well as other high reflectance areas. This paper take Shenyang region as pilot area, then retrieve the AOD and PM2.5 concentration of Shenyang in 2015 based on MODIS data, thus get 1km resolution distribution map, and then analyzed the results in spatial, intensity and temporal. At last, real-time monitoring data from the ground monitor station is used to verify the outcome, the results have good accuracy and the the correlation reached 0.9004 when the weather is sunny. The research shows that this algorithm has relatively higher precision and certain universality. This method has

T-type calcium channel antagonism decreases motivation for nicotine and blocks nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine.

PubMed

Uslaner, Jason M; Vardigan, Joshua D; Drott, Jason M; Uebele, Victor N; Renger, John J; Lee, Ariel; Li, Zhaoxia; Lê, A D; Hutson, Pete H

2010-10-15

Recent evidence suggests an involvement of T-type calcium channels in the effects of drugs of abuse. We examined the influence of the novel, potent, and selective T-type calcium channel antagonist [2-(4-cyclopropylphenyl)-N-((1R)-1-{5-[2,2,2-trifluoroethyl]oxo}pyridine-2-yl)ethyl]acetamide] (TTA-A2) (.3, 1, or 3 mg/kg) on motivation for nicotine, as measured by nicotine self-administration on a progressive ratio (PR) schedule, and nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine delivery (n = 11 or 12 Long Evans rats/group). Furthermore, we examined the specificity of the TTA-A2 effects by characterizing its influence on PR responding for food (in the absence or presence of nicotine-potentiated responding), food- versus nicotine-induced cue-potentiated reinstatement for a response previously reinforced by food administration (n = 11 or 12 Wistar Hannover rats/group), and its ability to induce a conditioned place aversion. TTA-A2 dose-dependently decreased self-administration of nicotine on a PR schedule and the ability of both nicotine and a cue paired with nicotine to reinstate responding. The effects were specific for nicotine's incentive motivational properties, as TTA-A2 did not influence responding for food on a PR schedule but did attenuate the ability of nicotine to potentiate responding for food. Likewise, TTA-A2 did not alter food-induced cue-potentiated reinstatement for a response previously reinforced by food but did decrease nicotine-induced cue-potentiated reinstatement. Finally, TTA-A2 did not produce an aversive state, as indicated by a lack of ability to induce conditioned place aversion. These data suggest that T-type calcium channel antagonists have potential for alleviating nicotine addiction by selectively decreasing the incentive motivational properties of nicotine. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Ecological Risk Assessment of Munitions Compounds on Coral and Coral Reef Health

DTIC Science & Technology

2014-01-01

C308R Porites lobata Maunalua Bay, Oahu, HI K5 TAG GTG GGG AAT CAA ACG GC C307F C309F Porites lobata La Perouse, Maui, HI 3-3 GCT GGC TTA CAG...GGA ATT TTA ACT TCA AGC 24 41.7% 54°C 2.08 Kb this work Porites mtDNA cobR A GAT TCT CTT TGC GCA GTG GCA TAG G 25 52.0% 59°C this work Porites mtDNA...47.6% 52°C 2.14 Kb this work Porites mtDNA nad5(5’)R K CCA ACT GTG CAG ACT TTC CAA CC 23 52.2% 57°C this work References and further reading

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

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

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 •more » 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

Target and beam-target spin asymmetries in exclusive π + and π – electroproduction with 1.6- to 5.7-GeV electrons

DOE PAGES

Bosted, P. E.; Biselli, A. S.; Careccia, S.; ...

2016-11-01

Here, beam-target double-spin asymmetries and target single-spin asymmetries in exclusive π + and quasiexclusive π – electroproduction were obtained from scattering of 1.6- to 5.7-GeV longitudinally polarized electrons from longitudinally polarized protons (for π +) and deuterons (for π –) using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The kinematic range covered is 1.1 < W < 2.6 GeV and 0.05 < Q 2 < 5GeV 2, with good angular coverage in the forward hemisphere. The asymmetry results were divided into approximately 40 000 kinematic bins for π + from free protons and 15 000 bins for πmore » – production from bound nucleons in the deuteron. The present results are found to be in reasonable agreement with fits to previous world data for W < 1.7 GeV and Q 2 < 0.5GeV 2, with discrepancies increasing at higher values of Q 2, especially for W > 1.5 GeV. Very large target-spin asymmetries are observed for W > 1.6 GeV. When combined with cross-section measurements, the present results can provide powerful constraints on nucleon resonance amplitudes at moderate and large values of Q 2, for resonances with masses as high as 2.3 GeV.« less

Down-regulated let-7b-5p represses glycolysis metabolism by targeting AURKB in asthenozoospermia.

PubMed

Zhou, Ran; Zhang, Yan; Du, Guizhen; Han, Li; Zheng, Sinian; Liang, Jian; Huang, Xiaomin; Qin, Yufeng; Wu, Wei; Chen, Minjian; Wu, Di; Song, Ling; Fu, Guangbo; Lv, Shuyan; Xia, Yankai; Lu, Chuncheng; Wang, Xinru

2018-07-15

Glycolysis, through anaerobic respiration, can supply energy for human sperm motility. MicroRNAs (miRNAs) could participate in the glycolytic pathway through regulating target genes. To investigate the potential role of glycolysis-related miRNAs in asthenozoospermia, TaqMan Low Density Array (TLDA) was used to screen potentially functional miRNAs, and seven glycolysis-related miRNAs were isolated to be related to asthenozoospermia. After qRT-PCR validation, only one seminal plasma miRNA, let-7b-5p, was found significantly decreased in severe asthenozoospermia cases compared with healthy controls. To further understand whether let-7b-5p is involved in asthenozoospermia by regulating the glycolytic pathway, we carried out gain-and-loss function study of let-7b-5p in GC-2 cells and detected the glycolytic activities. Our results showed that knocking down let-7b-5p could inhibit glycolytic activities. Besides, we also found overexpressed Aurkb (a target gene of let-7b-5p) could recapitulate the effects of knocking down let-7b-5p. Our findings indicated that low expression of let-7b-5p could repress glycolysis in asthenozoospermia by targeting AURKB. Copyright © 2018 Elsevier B.V. All rights reserved.

Metabotropic glutamate receptor 5 as a potential target for smoking cessation.

PubMed

Chiamulera, Cristiano; Marzo, Claudio Marcello; Balfour, David J K

2017-05-01

Most habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor. Relapse rates, however, remain high, and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. The purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. Imaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. Although mGluR5 NAMs attenuate most of the key facets of nicotine dependence, they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many "off-target" effects to be used clinically. However, newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence.

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

PubMed

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.

Effective targeting of STAT5-mediated survival in myeloproliferative neoplasms using ABT-737 combined with rapamycin

PubMed Central

Li, Geqiang; Miskimen, Kristy L.; Wang, Zhengqi; Xie, Xiu Yan; Tse, William; Gouilleux, Fabrice; Moriggl, Richard; Bunting, Kevin D.

2010-01-01

Signal transducer and activator of transcription-5 (STAT5) is a critical transcription factor for normal hematopoiesis and its sustained activation is associated with hematologic malignancy. A persistently active mutant of STAT5 (STAT5aS711F) associates with Grb2 associated binding protein 2 (Gab2) in myeloid leukemias and promotes growth in vitro through AKT activation. Here we have retrovirally transduced wild-type or Gab2−/− mouse bone marrow cells expressing STAT5aS711F and transplanted into irradiated recipient mice to test an in vivo myeloproliferative disease (MPD) model. To target Gab2-independent AKT/mTOR activation, wild-type mice were treated separately with rapamycin. In either case, mice lacking Gab2 or treated with rapamycin displayed attenuated myeloid hyperplasia and modestly improved survival, but the effects were not cytotoxic and were reversible. To improve upon this approach, in vitro targeting of STAT5-mediated AKT/mTOR using rapamycin was combined with inhibition of the STAT5 direct target genes bcl-2 and bcl-XL using ABT-737. Striking synergy with both drugs was observed in mouse BaF3 cells expressing STAT5aS711F, TEL-JAK2, or BCR-ABL and in the relatively single agent-resistant human BCR-ABL positive K562 cell line. Therefore, targeting distinct STAT5 mediated survival signals, e.g. bcl-2/bcl-XL and AKT/mTOR may be an effective therapeutic approach for human myeloproliferative neoplasms. PMID:20535152

Antisense oligonucleotides targeting translation inhibitory elements in 5' UTRs can selectively increase protein levels.

PubMed

Liang, Xue-Hai; Sun, Hong; Shen, Wen; Wang, Shiyu; Yao, Joyee; Migawa, Michael T; Bui, Huynh-Hoa; Damle, Sagar S; Riney, Stan; Graham, Mark J; Crooke, Rosanne M; Crooke, Stanley T

2017-09-19

A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs. Levels of human RNASEH1, LDLR, and ACP1 and of mouse ACP1 and ARF1 were increased up to 2.7-fold in different cell types and species upon treatment with chemically modified ASOs targeting 5' UTR inhibitory regions in the mRNAs encoding these proteins. The activities of ASOs in enhancing translation were sequence and position dependent and required helicase activity. The ASOs appear to improve the recruitment of translation initiation factors to the target mRNA. Importantly, ASOs targeting ACP1 mRNA significantly increased the level of ACP1 protein in mice, suggesting that this approach has therapeutic and research potentials. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Large benefits to marine fisheries of meeting the 1.5°C global warming target.

PubMed

Cheung, William W L; Reygondeau, Gabriel; Frölicher, Thomas L

2016-12-23

Translating the Paris Agreement to limit global warming to 1.5°C above preindustrial level into impact-related targets facilitates communication of the benefits of mitigating climate change to policy-makers and stakeholders. Developing ecologically relevant impact-related targets for marine ecosystem services, such as fisheries, is an important step. Here, we use maximum catch potential and species turnover as climate-risk indicators for fisheries. We project that potential catches will decrease by more than 3 million metric tons per degree Celsius of warming. Species turnover is more than halved when warming is lowered from 3.5° to 1.5°C above the preindustrial level. Regionally, changes in maximum catch potential and species turnover vary across ecosystems, with the biggest risk reduction in the Indo-Pacific and Arctic regions when the Paris Agreement target is achieved. Copyright © 2016, American Association for the Advancement of Science.

Target research on tumor biology characteristics of mir-155-5p regulation on gastric cancer cell.

PubMed

Feng, Jun-an

2016-03-01

After the mir-155-5p over expressed in gastric cancer cells, the expression profile chip was adopted to screen its target genes. Some of the intersection of target genes were selected based on the bioinformatics prediction, in order to study the mechanism of its function and role of research. Affymetrix eukaryotic gene expression spectrum was conducted to screen mir-155-5p regulated genetic experiment. Western blot technique was employed to detect and screen the protein expression of target genes. Mimics was transfected in BGC-823 of gastric cancer cells. Compared with mimics-nc group and mock group, the mRNA expression quantities of SMAD1, STAT1, CAB39, CXCR4 and CA9 were significantly lower. After the gastric cancer cells BGC-823 and MKN-45 had been transfected by mimics, compared with mimics-nc (MNC) group and mock (MOCK) group, it was decreased for the protein expression of SMAD1, STAT1 and CAB39 in mimics (MIMICS) group. The verification of qRT-PCR demonstrated that SMAD1, STAT1, CAB39, CXCR4 and CA9 were the predicted target genes and target proteins of mir-155-5p, the over expression of mir-155-5p could enable the decreasing of its expression level in gastric cancer cells MKN-45 and BGC-823.

Guide for geometric design and operational factors that impact truck use of toll roads.

DOT National Transportation Integrated Search

2010-09-01

Texas has approximately 300 miles of toll roads, predominantly in the three largest and : most congested urban areas of Austin, Dallas, and Houston. The Texas Turnpike Authority : (TTA) Division of the Texas Department of Transportation (TxDOT) and t...

Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development.

PubMed

Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

2013-05-28

The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5-PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5-PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders.

48 CFR 52.226-5 - Restrictions on Subcontracting Outside Disaster or Emergency Area.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Subcontracting Outside Disaster or Emergency Area. 52.226-5 Section 52.226-5 Federal Acquisition Regulations... CLAUSES Text of Provisions and Clauses 52.226-5 Restrictions on Subcontracting Outside Disaster or Emergency Area. As prescribed in 26.206(c), insert the following clause: Restrictions on Subcontracting...

48 CFR 52.226-5 - Restrictions on Subcontracting Outside Disaster or Emergency Area.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Subcontracting Outside Disaster or Emergency Area. 52.226-5 Section 52.226-5 Federal Acquisition Regulations... CLAUSES Text of Provisions and Clauses 52.226-5 Restrictions on Subcontracting Outside Disaster or Emergency Area. As prescribed in 26.206(c), insert the following clause: Restrictions on Subcontracting...

48 CFR 52.226-5 - Restrictions on Subcontracting Outside Disaster or Emergency Area.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Subcontracting Outside Disaster or Emergency Area. 52.226-5 Section 52.226-5 Federal Acquisition Regulations... CLAUSES Text of Provisions and Clauses 52.226-5 Restrictions on Subcontracting Outside Disaster or Emergency Area. As prescribed in 26.206(c), insert the following clause: Restrictions on Subcontracting...

48 CFR 52.226-5 - Restrictions on Subcontracting Outside Disaster or Emergency Area.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Subcontracting Outside Disaster or Emergency Area. 52.226-5 Section 52.226-5 Federal Acquisition Regulations... CLAUSES Text of Provisions and Clauses 52.226-5 Restrictions on Subcontracting Outside Disaster or Emergency Area. As prescribed in 26.206(c), insert the following clause: Restrictions on Subcontracting...

48 CFR 52.226-5 - Restrictions on Subcontracting Outside Disaster or Emergency Area.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Subcontracting Outside Disaster or Emergency Area. 52.226-5 Section 52.226-5 Federal Acquisition Regulations... CLAUSES Text of Provisions and Clauses 52.226-5 Restrictions on Subcontracting Outside Disaster or Emergency Area. As prescribed in 26.206(c), insert the following clause: Restrictions on Subcontracting...

Abnormal temperature dependent behaviors of intersystem crossing and triplet-triplet annihilation in organic planar heterojunction devices

NASA Astrophysics Data System (ADS)

Xiang, Jie; Chen, Yingbing; Yuan, De; Jia, Weiyao; Zhang, Qiaoming; Xiong, Zuhong

2016-09-01

Anomalous temperature dependent magneto-electroluminescence was observed at low and high magnetic field strength from organic planar heterojunction devices incorporated common phosphorescent host materials of N,N'-dicarbazolyl-3,5-benzene (mCP) or 4,4'-N,N'-dicarbazole-biphenyl (CBP) as an emissive layer. We found that intersystem crossing became stronger with decreasing temperature and that triplet-triplet annihilation (TTA) occurred at room temperature but ceased at low temperature. Analyses of the electroluminescence spectra of these devices and their temperature dependences indicated that the population of exciplex states increased at low temperature, which caused the abnormal behavior of intersystem crossing. Additionally, long lifetime of the excitons within mCP or CBP layer may allow TTA to occur at room temperature, while the reduced population of excitons at low temperature may account for the disappearance of TTA even though the excitons had increased lifetime.

Methane mitigation shows significant benefits towards achieving the 1.5 degree target.

NASA Astrophysics Data System (ADS)

Collins, W.; Webber, C.; Cox, P. M.; Huntingford, C.; Lowe, J. A.; Sitch, S.

2017-12-01

Most analyses of allowable carbon emissions to achieve the 1.5 degree target implicitly assume that the ratio of CO2 to non-CO2 greenhouse gases remains near constant, and that all radiative forcing factors have similar impacts on land and ocean carbon storage. Here we determine how plausible reductions in methane emissions will make the carbon targets more feasible. We account for the latest estimates of the methane radiative effect as well as the indirect effects of methane on ozone. We particularly address the differing effects of methane and CO2 mitigation on the land carbon storage including via reduced concentrations of surface ozone. The methodology uses an intermediate complexity climate model (IMOGEN) coupled to a land surface model (JULES) which represents the details of the terrestrial carbon cycle. The carbon emissions inputs to IMOGEN are varied to find allowable pathways consistent with the Paris 1.5 K or 2.0 K targets. The IMOGEN physical parameters are altered to represent the climate characteristics of 38 CMIP5 models (such as climate sensitivity) to provide bounds on the range of allowable CO2 emissions. We examine the effects of three different methane mitigation options that are broadly consistent with the ranges in the SSP scenarios: little mitigation, cost-optimal mitigation, and maximal mitigation. The land and ocean carbon storage increases with methane mitigation, allowing more flexibility in CO2 emission reduction. This is mostly since CO2 fertilisation is reduced less with high methane mitigation, with a small contribution from reduced plant damage with lower surface ozone levels.

9 CFR 73.5 - Interstate shipment of undiseased cattle from quarantined area; when permitted.

Code of Federal Regulations, 2010 CFR

2010-01-01

... cattle from quarantined area; when permitted. 73.5 Section 73.5 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS SCABIES IN CATTLE § 73.5 Interstate shipment of undiseased cattle from quarantined area; when permitted. Cattle of any herd in any quarantined area, which herd is not...

2-Aryl-5-carboxytetrazole as a New Photoaffinity Label for Drug Target Identification

PubMed Central

2016-01-01

Photoaffinity labels are powerful tools for dissecting ligand–protein interactions, and they have a broad utility in medicinal chemistry and drug discovery. Traditional photoaffinity labels work through nonspecific C–H/X–H bond insertion reactions with the protein of interest by the highly reactive photogenerated intermediate. Herein, we report a new photoaffinity label, 2-aryl-5-carboxytetrazole (ACT), that interacts with the target protein via a unique mechanism in which the photogenerated carboxynitrile imine reacts with a proximal nucleophile near the target active site. In two distinct case studies, we demonstrate that the attachment of ACT to a ligand does not significantly alter the binding affinity and specificity of the parent drug. Compared with diazirine and benzophenone, two commonly used photoaffinity labels, in two case studies ACT showed higher photo-cross-linking yields toward their protein targets in vitro based on mass spectrometry analysis. In the in situ target identification studies, ACT successfully captured the desired targets with an efficiency comparable to the diazirine. We expect that further development of this class of photoaffinity labels will lead to a broad range of applications across target identification, and validation and elucidation of the binding site in drug discovery. PMID:27740749

2-Aryl-5-carboxytetrazole as a New Photoaffinity Label for Drug Target Identification.

PubMed

Herner, András; Marjanovic, Jasmina; Lewandowski, Tracey M; Marin, Violeta; Patterson, Melanie; Miesbauer, Laura; Ready, Damien; Williams, Jon; Vasudevan, Anil; Lin, Qing

2016-11-09

Photoaffinity labels are powerful tools for dissecting ligand-protein interactions, and they have a broad utility in medicinal chemistry and drug discovery. Traditional photoaffinity labels work through nonspecific C-H/X-H bond insertion reactions with the protein of interest by the highly reactive photogenerated intermediate. Herein, we report a new photoaffinity label, 2-aryl-5-carboxytetrazole (ACT), that interacts with the target protein via a unique mechanism in which the photogenerated carboxynitrile imine reacts with a proximal nucleophile near the target active site. In two distinct case studies, we demonstrate that the attachment of ACT to a ligand does not significantly alter the binding affinity and specificity of the parent drug. Compared with diazirine and benzophenone, two commonly used photoaffinity labels, in two case studies ACT showed higher photo-cross-linking yields toward their protein targets in vitro based on mass spectrometry analysis. In the in situ target identification studies, ACT successfully captured the desired targets with an efficiency comparable to the diazirine. We expect that further development of this class of photoaffinity labels will lead to a broad range of applications across target identification, and validation and elucidation of the binding site in drug discovery.

5. VIEW OF BERYLLIUM PROCESSING AREA, ROLLING MILL. BERYLLIUM FORMING ...

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

5. VIEW OF BERYLLIUM PROCESSING AREA, ROLLING MILL. BERYLLIUM FORMING BEGAN IN SIDE A OF THE BUILDING IN 1962. (11/5/73) - Rocky Flats Plant, Uranium Rolling & Forming Operations, Southeast section of plant, southeast quadrant of intersection of Central Avenue & Eighth Street, Golden, Jefferson County, CO

Involvement of miR-485-5p in hepatocellular carcinoma progression targeting EMMPRIN.

PubMed

Sun, Xiangjun; Liu, Yonglei; Li, Ming; Wang, Mingchun; Wang, Yutong

2015-05-01

EMMPRIN plays important roles in cancer development, which includes EMMPRIN 1, 2, 3, and 4 isoforms. EMMPRIN2 is the main component in human cancers, but its regulation by miRNAs is still unclear. In this study, we will investigate the mechanism of EMMPRIN regulation in hepatocellular carcinoma (HCC) by miRNAs. Through RT-PCR, we found that EMMPRIN2 was the main isoform in HCC cells. EMMPRIN2 was down-regulated significantly by predicted miRNAs and miR-485-5p was one of the miRNA that regulated EMMPRIN in HCC cell lines. It was verified that EMMPRIN was a target gene of miR-485-5p by using luciferase analysis assay. We found that miR-485-5p was significantly downregulated in HCC tissues and that its expression was inversely correlated with the TNM stage and metastasis in HCC samples. Results of cellular functions in HCC showed that miR-485-5p could inhibit cell proliferation and metastasis. Additionally, miR-485-5p overexpression suppressed HCC growth in vivo by down-regulation of EMMPRIN. Our study for the first time demonstrated that miR-485-5p represses HCC invasive and metastatic capacities by targeting EMMPRIN expression. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

MicroRNA-106a-5p facilitates human glioblastoma cell proliferation and invasion by targeting adenomatosis polyposis coli protein

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

Li, Dazhi; Wang, Zengliang; Chen, Zigui

The invasive behavior of glioblastoma multiforme (GBM) cells is an important reason for its poor prognosis. Tumor cells acquire an ability to digest the extracellular matrix and infiltrate the adjacent normal tissue during invasion. Restraining GBM invasion by changing effector molecules can significantly improve the patient's prognosis. MiRNAs are involved in multiple biological functions via suppressing target genes. In this study, we found that miR-106a-5p expression was high in GBM tissues and cells. The data showed an inverse correlation in GBM tissues between the levels of miR-106a-5p and adenomatosis polyposis coli (APC) mRNAs.Additionally, ectopic expression of miR-106a-5pfacilitated the invasion ofmore » GBM cells whereas inhibition of miR-106a-5p expression weakened the invasive ability. Numerous transcription factors are downstream effectors of the Wnt/β-catenin pathway. Target prediction databases and luciferase data showed that APC is a new direct target of miR-106a-5p. Importantly, westernblot assays demonstrated that miR-106a-5p can reduce APC protein level and enhance target proteins of Wnt/β-catenin pathway. Thus, we hypothesize that miR-106a-5p directly targets APC, resulting in the activation of Wnt/β-catenin pathway. Our results suggest that miR-106a-5p is involved in the invasive behavior of GBM cells and by targeting APC and activating Wnt/β-catenin pathway, it provides a theoretical basis for developing potential clinical strategies. - Highlights: • miR-106a-5p is upregulated in human glioblastoma. • Upregulation of miR-106a-5p promotes glioma cell proliferation and invasion. • miR-106a-5p inactivates the Wnt/β-catenin pathway by directly targeting APC.« less

Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

DTIC Science & Technology

2015-11-01

increased PhScN potency as a result of preventing endoproteolytic degradation. Finally, the in vivo lung extravasation and colonization data, as well as...successful colonization are late stages in breast cancer progression that are ultimately fatal. Hence, prevention of extravasation which leads to colony...Award Number: TITLE: “Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma

Assessment of target detection limits in hyperspectral data

NASA Astrophysics Data System (ADS)

Gross, W.; Boehler, J.; Schilling, H.; Middelmann, W.; Weyermann, J.; Wellig, P.; Oechslin, R.; Kneubuehler, M.

2015-10-01

Hyperspectral remote sensing data can be used for civil and military applications to detect and classify target objects that cannot be reliably separated using broadband sensors. The comparably low spatial resolution is compensated by the fact that small targets, even below image resolution, can still be classified. The goal of this paper is to determine the target size to spatial resolution ratio for successful classification of different target and background materials. Airborne hyperspectral data is used to simulate data with known mixture ratios and to estimate the detection threshold for given false alarm rates. The data was collected in July 2014 over Greding, Germany, using airborne aisaEAGLE and aisaHAWK hyperspectral sensors. On the ground, various target materials were placed on natural background. The targets were four quadratic molton patches with an edge length of 7 meters in the colors black, white, grey and green. Also, two different types of polyethylene (camouflage nets) with an edge length of approximately 5.5 meters were deployed. Synthetic data is generated from the original data using spectral mixtures. Target signatures are linearly combined with different background materials in specific ratios. The simulated mixtures are appended to the original data and the target areas are removed for evaluation. Commonly used classification algorithms, e.g. Matched Filtering, Adaptive Cosine Estimator are used to determine the detection limit. Fixed false alarm rates are employed to find and analyze certain regions where false alarms usually occur first. A combination of 18 targets and 12 backgrounds is analyzed for three VNIR and two SWIR data sets of the same area.

MiR-20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells.

PubMed

Huang, Dabing; Bian, Geng; Pan, Yueyin; Han, Xinghua; Sun, Yubei; Wang, Yong; Shen, Guodong; Cheng, Min; Fang, Xiang; Hu, Shilian

2017-01-01

MicroRNAs (miRNAs) was reported to be involved in cancer radio-resistance, which remains a major obstacle for effective cancer therapy. The differently expressed miRNAs were detected by RNA-seq experiment in nasopharyngeal cancer (NPC) cells. MiR-20a-5p was selected as our target, which was subject to finding its target gene Rab27B via bioinformatics analysis. The qRT-PCR, western blot and the luciferase reporter assays were performed to confirm Rab27B as the target of miR-20a-5p. In addition, the roles of miR-20a-5p in NPC radio-resistance were detected by transfection of either miR-20a-5p-mimic or miR-20a-5p-antagomiR. The involvement of Rab27B with NPC radio-resistance was also detected by the experiments with siRNA-mediated repression of Rab27B or over-expression of GFP-Rab27B. Wound healing and invasion assays were performed to detect the roles of both miR-20a-5p and Rab27B. MiR-20a-5p promotes NPC radio-resistance. We identified that its target gene Rab27B negatively correlates with miR-20a-5p-mediated NPC radio-resistance by systematic studies of a radio-sensitive (CNE-2) and resistant (CNE-1) NPC cell lines. Repression of Rab27B by siRNA suppresses cell apoptosis and passivates CNE-2 cells, whereas over-expression of Rab27B triggered cell apoptosis and sensitizes CNE-1 cells. MiR-20a-5p and its target gene Rab27B might be involved in the NPC radio-resistance. Thus the key players and regulators involved in this pathway might be the potential targets for developing effective therapeutic strategies against NPC.

The Poughkeepsie Survey. A Report on Employment and Unemployment in a "Target Area" under the Model Cities Program.

ERIC Educational Resources Information Center

Kuper, Irvin, Ed.

Located in the heart of the Mid-Hudson area, Poughkeepsie is in one of the fastest growing regions of New York State, but the city itself has grown very little in the last five decades. The local Model Cities agency has created a target area which includes most of the older part of the city. In July 1967, the population was 35,970. A total of…

The stimulus integration area for horizontal vergence.

PubMed

Allison, Robert S; Howard, Ian P; Fang, Xueping

2004-06-01

Over what region of space are horizontal disparities integrated to form the stimulus for vergence? The vergence system might be expected to respond to disparities within a small area of interest to bring them into the range of precise stereoscopic processing. However, the literature suggests that disparities are integrated over a fairly large parafoveal area. We report the results of six experiments designed to explore the spatial characteristics of the stimulus for vergence. Binocular eye movements were recorded using magnetic search coils. Each dichoptic display consisted of a central target stimulus that the subject attempted to fuse, and a competing stimulus with conflicting disparity. In some conditions the target was stationary, providing a fixation stimulus. In other conditions, the disparity of the target changed to provide a vergence-tracking stimulus. The target and competing stimulus were combined in a variety of conditions including those in which (1) a transparent textured-disc target was superimposed on a competing textured background, (2) a textured-disc target filled the centre of a competing annular background, and (3) a small target was presented within the centre of a competing annular background of various inner diameters. In some conditions the target and competing stimulus were separated in stereoscopic depth. The results are consistent with a disparity integration area with a diameter of about 5 degrees. Stimuli beyond this integration area can drive vergence in their own right, but they do not appear to be summed or averaged with a central stimulus to form a combined disparity signal. A competing stimulus had less effect on vergence when separated from the target by a disparity pedestal. As a result, we propose that it may be more useful to think in terms of an integration volume for vergence rather than a two-dimensional retinal integration area.

Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

DTIC Science & Technology

2015-11-01

systemic therapy to prevent breast cancer bone colony progression. Figure 6. Colocalization of Ac-PhscNGGK-Bio with DiI in lung– extravasated SUM149PT cells...breast cancer progression that are ultimately fatal. Hence, prevention of extravasation which leads to colony formation would increase life...1 Award Number: W81XWH-12-1-0097 TITLE: “Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site

The Roots of Alzheimer's Disease: Are High-Expanding Cortical Areas Preferentially Targeted?†.

PubMed

Fjell, Anders M; Amlien, Inge K; Sneve, Markus H; Grydeland, Håkon; Tamnes, Christian K; Chaplin, Tristan A; Rosa, Marcello G P; Walhovd, Kristine B

2015-09-01

Alzheimer's disease (AD) is regarded a human-specific condition, and it has been suggested that brain regions highly expanded in humans compared with other primates are selectively targeted. We calculated shared and unique variance in the distribution of AD atrophy accounted for by cortical expansion between macaque and human, affiliation to the default mode network (DMN), ontogenetic development and normal aging. Cortical expansion was moderately related to atrophy, but a critical discrepancy was seen in the medial temporo-parietal episodic memory network. Identification of "hotspots" and "coldspots" of expansion across several primate species did not yield compelling evidence for the hypothesis that highly expanded regions are specifically targeted. Controlling for distribution of atrophy in aging substantially attenuated the expansion-AD relationship. A path model showed that all variables explained unique variance in AD atrophy but were generally mediated through aging. This supports a systems-vulnerability model, where critical networks are subject to various negative impacts, aging in particular, rather than being selectively targeted in AD. An alternative approach is suggested, focused on the interplay of the phylogenetically old and preserved medial temporal lobe areas with more highly expanded association cortices governed by different principles of plasticity and stability. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

MiR-188-5p suppresses gastric cancer cell proliferation and invasion via targeting ZFP91.

PubMed

Peng, Yuping; Shen, Xuning; Jiang, Honggang; Chen, Zhiheng; Wu, Jiaming; Zhu, Yi; Zhou, Yuan; Li, Jin

2018-02-22

MicroRNAs (miRNAs) have been demonstrated to be essential regulators in the development and progression of various cancers. The role of miR-188-5p in gastric cancer has not been determined. In this study, we found that the expression of miR-188-5p was downregulated in gastric cancer (GC) tissues compared with adjacent normal tissues. And lowly expressed miR-188-5p was significantly associated with lymph node metastasis and advanced TNM stage. Moreover, overexpression of miR-188-5p significantly inhibited GC cell proliferation, migration and invasion but promoted cellular apoptosis. In mechanism, we identified transcription factor ZFP91 as a target gene of miR-188-5p in GC. We found that miR-188-5p overexpression significantly inhibited the expression of ZFP91 in GC cell lines. And there was an inversely correlation between the expression of miR-188-5p and ZFP91 in GC tissues. What's more, we found that restoration of ZFP91 in miR-188-5poverexpressed MGC-803 and SGC-7901 cells promoted cell proliferation, migration and invasion. Finally, we also showed that overexpression of miR-188-5p inhibited tumor growth in vivo. Taken together, our findings indicated that miR-188-5p serves as a tumor suppressor in human gastric cancer by targeting ZFP91, suggesting that miR-188-5p might be a promising therapeutic target for GC treatment.

CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer.

PubMed

Svensson, Susanne; Abrahamsson, Annelie; Rodriguez, Gabriela Vazquez; Olsson, Anna-Karin; Jensen, Lasse; Cao, Yihai; Dabrosin, Charlotta

2015-08-15

Novel therapeutic targets of estrogen receptor (ER)-positive breast cancers are urgently needed because current antiestrogen therapy causes severe adverse effects, nearly 50% of patients are intrinsically resistant, and the majority of recurrences have maintained ER expression. We investigated the role of estrogen-dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models. For in vivo sampling of human chemokines, microdialysis was used in breast cancers of women or normal human breast tissue before and after tamoxifen therapy. Estrogen exposure and targeted therapies were assessed in immune competent PyMT murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. Cancer cell dissemination was investigated using zebrafish. ER(+) cancers in women produced high levels of extracellular CCL2 and CCL5 in vivo, which was associated with infiltration of tumor-associated macrophages. In experimental breast cancer, estradiol enhanced macrophage influx and angiogenesis through increased release of CCL2, CCL5, and vascular endothelial growth factor. These effects were inhibited by anti-CCL2 or anti-CCL5 therapy, which resulted in potent inhibition of cancer growth. In addition, estradiol induced a protumorigenic activation of the macrophages. In a zebrafish model, macrophages increased cancer cell dissemination via CCL2 and CCL5 in the presence of estradiol, which was inhibited with anti-CCL2 and anti-CCL5 treatment. Our findings shed new light on the mechanisms underlying the progression of ER(+) breast cancer and indicate the potential of novel therapies targeting CCL2 and CCL5 pathways. ©2015 American Association for Cancer Research.

Palmitoylation-dependent CDKL5–PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development

PubMed Central

Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

2013-01-01

The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5–PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5–PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders. PMID:23671101

Rational Design of a Lanthanide-Based Complex Featuring Different Single-Molecule Magnets.

PubMed

Pointillart, F; Guizouarn, T; Lefeuvre, B; Golhen, S; Cador, O; Ouahab, L

2015-11-16

The rational synthesis of the 2-{1-methylpyridine-N-oxide-4,5-[4,5-bis(propylthio)tetrathiafulvalenyl]-1H-benzimidazol-2-yl}pyridine ligand (L) is described. It led to the tetranuclear complex [Dy4(tta)12(L)2] (Dy-Dy2-Dy) after coordination reaction with the precursor Dy(tta)3⋅2 H2O (tta(-) = 2-thenoyltrifluoroacetonate). The X-ray structure of Dy-Dy2-Dy can be described as two terminal mononuclear units bridged by a central antiferromagnetically coupled dinuclear complex. The terminal N2O6 and central O8 environments are described as distorted square antiprisms. The ac magnetism measurements revealed a strong out-of-phase signal of the magnetic susceptibility with two distinct sets of data. The high- and low-frequency components were attributed to the two terminal mononuclear single-molecule magnets (SMMs) and the central dinuclear SMM, respectively. A magnetic hysteresis loop was detected at very low temperature. From both structural and magnetic points of view, the tetranuclear SMM Dy-Dy2-Dy is a self-assembly of two known mononuclear SMMs bridged by a known dinuclear SMM. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

7 CFR 759.5 - Secretarial disaster area determination and notification process.

Code of Federal Regulations, 2013 CFR

2013-01-01

... § 759.5 Secretarial disaster area determination and notification process. (a) U.S. Drought Monitor. With respect to drought and without requiring an LAR: (1) If any portion of a county is physically located in an area with a Drought Monitor Intensity Classification value of D3 (drought-extreme) or higher...

7 CFR 759.5 - Secretarial disaster area determination and notification process.

Code of Federal Regulations, 2014 CFR

2014-01-01

... § 759.5 Secretarial disaster area determination and notification process. (a) U.S. Drought Monitor. With respect to drought and without requiring an LAR: (1) If any portion of a county is physically located in an area with a Drought Monitor Intensity Classification value of D3 (drought-extreme) or higher...

Analysis of the phosphorescent dye concentration dependence of triplet-triplet annihilation in organic host-guest systems

NASA Astrophysics Data System (ADS)

Zhang, L.; van Eersel, H.; Bobbert, P. A.; Coehoorn, R.

2016-10-01

Using a novel method for analyzing transient photoluminescence (PL) experiments, a microscopic description is obtained for the dye concentration dependence of triplet-triplet annihilation (TTA) in phosphorescent host-guest systems. It is demonstrated that the TTA-mechanism, which could be a single-step dominated process or a diffusion-mediated multi-step process, can be deduced for any given dye concentration from a recently proposed PL intensity analysis. A comparison with the results of kinetic Monte Carlo simulations provides the TTA-Förster radius and shows that the TTA enhancement due to triplet diffusion can be well described in a microscopic manner assuming Förster- or Dexter-type energy transfer.

Triplet diffusion leads to triplet-triplet annihilation in organic phosphorescent emitters

NASA Astrophysics Data System (ADS)

Zhang, Yifan; Forrest, Stephen R.

2013-12-01

In organic materials, triplet-triplet annihilation (TTA) can be dominated by triplet diffusion or triplet-to-triplet energy transfer. Here, we discuss the diffusion and transfer dominated mechanisms in the context of photoluminescence (PL) transient measurements from thin films of archetype phosphorescent organic light emitters based on Ir and Pt complexes. We find that TTA in these emitters is controlled by diffusion due to a Dexter-type exchange interaction, suggesting triplet radiative decay and TTA are independent processes. Minimizing the PL and absorption spectral overlap in phosphorescent emitters can lead to a significantly decreased TTA rate, and thus suppressed efficiency roll-off in phosphorescent organic light emitting diodes at high brightness.

MicroRNA-134-5p promotes high glucose-induced podocyte apoptosis by targeting bcl-2

PubMed Central

Qian, Xiaoxiao; Tan, Juan; Liu, Ling; Chen, Sheng; You, Na; Yong, Huijuan; Pan, Minglin; You, Qiang; Ding, Dafa; Lu, Yibing

2018-01-01

Podocyte apoptosis is a typical early feature of diabetic nephropathy (DN), with loss of nephrin integrity contributing to increased proteinuria in patients with DN. Emerging evidence shows that microRNAs (miRNAs) play vital roles in the pathogenesis of DN. Thus, we aimed to further elucidate the role of miRNAs in podocyte apoptosis in DN. We used db/db and db/m mice maintained under a continuous feeding regime for 12 weeks. Using microarray analysis, we found several miRNAs potentially related to podocyte apoptosis. In addition, we cultured a conditionally immortalized human podocyte cell line in 30 mM D-glucose and found that miR-134-5p was upregulated in both db/db mice and high-glucose (HG)-treated podocytes. Upregulation of miR-134-5p was accompanied by podocyte apoptosis and downregulation of nephrin. Inhibition of miR-134-5p produced the opposite effect. Dual-luciferase reporter assays showed that miR-134-5p directly targeted the 3’-untranslated region of the B-cell lymphoma-2 gene (BCL2), and further study confirmed an increase in bcl-2 protein level in HG-treated podocytes transfected with anti-miR-134-5p. Knockdown of BCL2 impeded the antiapoptotic effect of anti-miR-134-5p. Finally, we found that miR-134-5p might regulate apoptosis in db/db mice and podocytes by targeting BCL2. Taken together, our findings suggest that miR-134-5p promotes podocyte apoptosis under HG conditions by targeting BCL2. Our study provides a meaningful approach to interpret the mechanisms of action of miRNAs involved in DN. PMID:29636888

Bipolar molecular composites: a new class of high-electron-mobility organic solids

NASA Astrophysics Data System (ADS)

Lin, Liang-Bih; Jenekhe, Samson A.; Borsenberger, Paul M.

1997-10-01

We describe high electron mobility in organic solids in the form of bipolar molecular composites of N,N'-bis(1,2-dimethylpropyl)-1,4,5,8-naphthalenetetracarboxylic diimide (NTDI) and tri-p-tolylaniine (TTA). The electron mobility in the NTDI/TTA composites is ~2 x 10 cm2/Vs, which is a factor of 4 to 6 higher than in pure NTDI and isone of the highest values reported for disordered organic solids. The field and temperature dependencies of the charge mobility can be described using the disorder formalism due to Bassler and co-workers, which provides an estimation of the energy width σ of the hopping site manifold. Analysis of the data gave σ=0.081 and 0.060 eV for the electron and hole mobilities in a NTDI/TTA composite of 0.5510.45 molar ratio. The energetic disorder for electron transport in the bipolar composites is substantially lower than for pure NTDI, which is 0.093 eV. The results suggest that the observed enhancement arises from a substantial reduction of energetic disorder in the electron transport manifold of the bipolar composites. The reduction of energetic disorder may be due to intermolecular charge transfer between NTDI and TTA. Such a charge transfer could stabilize the electron transport manifold by better charge delocalization, and consequently, less energetic disorder. Another possible reason for the observed enhanced electron mobility is the reduction of NTDI dimers that can act as carrier traps by the presence of TTA molecules in the bipolar composites. These results also suggest that bipolar composites represent a promising new class of high electron mobility organic solids.

Pediatric emergency department triage-based pain guideline utilizing intranasal fentanyl: Effect of implementation.

PubMed

Schoolman-Anderson, Kristin; Lane, Roni D; Schunk, Jeff E; Mecham, Nancy; Thomas, Richard; Adelgais, Kathleen

2018-01-16

Pain management guidelines in the emergency department (ED) may reduce time to analgesia administration (TTA). Intranasal fentanyl (INF) is a safe and effective alternative to intravenous opiates. The effect of an ED pain management guideline providing standing orders for nurse-initiated administration of intranasal fentanyl (INF) is not known. The objective of this study was to determine the impact of a pediatric ED triage-based pain protocol utilizing intranasal fentanyl (INF) on time to analgesia administration (TTA) and patient and parent satisfaction. This was a prospective study of patients 3-17 years with an isolated orthopedic injury presenting to a pediatric ED before and after instituting a triage-based pain guideline allowing for administration of INF by triage nurses. Our primary outcome was median TTA and secondary outcomes included the proportion of patients who received INF for pain, had unnecessary IV placement, and patient and parent satisfaction. We enrolled 132 patients; 72 pre-guideline, 60 post-guideline. Demographics were similar between groups. Median TTA was not different between groups (34.5 min vs. 33 min, p = .7). Utilization of INF increased from 41% pre-guideline to 60% post-guideline (p = .01) and unnecessary IV placement decreased from 24% to 0% (p = .002). Patients and parents preferred the IN route for analgesia administration. A triage-based pain protocol utilizing INF did not reduce TTA, but did result in increased INF use, decreased unnecessary IV placement, and was preferred by patients and parents to IV medication. INF is a viable analgesia alternative for children with isolated extremity injuries. Copyright © 2018. Published by Elsevier Inc.

Development and Pre-Clinical Evaluation of a Novel Prostate-Restricted Replication Competent Adenovirus-AD-IU-1

DTIC Science & Technology

2006-05-01

CTCTGTTTGTGGA A A A TT TTA A A CTA CTGGTTTA A TTT CT TTA TTGGTTGTA A TA TGA CTA TTTTA CGTCA TA TA A CA A TTTTTA TT GTTTGT TA A A TGA CTTTA TTGTTTGTC A...radiotracer 1 was 0.8–1.2 Ci /mmol at end of synthesis (EOS). In comparison with the results reported in the literature,[15,25,33,34] several improvements in...99%, and the chemical purity of radiotracer 1 was 93%. The average (n ¼ 3–5) specific radio- activity of radiotracer 1 was 0.8–1.2 Ci /mmol at EOS

5. TETHERED MINUTEMAN MISSILE LAUNCH, TEST AREA 1100. Original is ...

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

5. TETHERED MINUTEMAN MISSILE LAUNCH, TEST AREA 1-100. Original is a color print. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Leuhman Ridge near Highways 58 & 395, Boron, Kern County, CA

5. INTERIOR, STORAGE AREA AT WESTERN END, FROM SOUTH OF ...

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

5. INTERIOR, STORAGE AREA AT WESTERN END, FROM SOUTH OF LOADING DOCK WELL, LOOKING NORTH. - Oakland Naval Supply Center, Coffee Roasting Plant, East of Fourth Street, between J & K, Oakland, Alameda County, CA

The Changing Face of Hepatitis C: Recent Advances on HCV Inhibitors Targeting NS5A

PubMed

Rai, Diwakar; Wang, Liu; Jiang, Xuemei; Zhan, Peng; Jia, Haiyong; De Clercq, Erik; Liu, Xinyong

2015-05-05

Current treatment for HCV infections consists of approved direct acting antivirals (DAAs), viz. the protease inhibitors (boceprevir, telaprevir, and simeprevir), NS5B polymerase inhibitors (sofosbuvir) and NS5A inhibitor (ledipasvir) in combination with pegylated interferon α and ribavirin). These treatments have made a great improvement in the treatment of chronic HCV infections in recent years, but their adverse side effects, emergence of resistant mutants, high cost, and increased pill burden have limited their clinical use. Recently, with the increasing knowledge in understanding the HCV life cycle, more targets have been recognized. NS5A protein plays a critical role in assembly of infectious HCV particles and offering potential for HCV therapies. Therefore, discovery and development of novel DAAs targeting NS5A with novel mechanisms of action, is of great necessity to improve the quality of existing HCV treatments. In the present review, we discuss recent advances with NS5A inhibitors with potent anti-HCV activity, and the potential for the development of HCV NS5A inhibitors to combat HCV infections.

miR-1271 promotes non-small-cell lung cancer cell proliferation and invasion via targeting HOXA5

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

Wang, Yongfang; Xu, Lianhong; Jiang, Lixin, E-mail: jianglx66766@163.com

2015-03-13

MicroRNAs (miRNAs) are short, non-coding RNAs (∼22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating numerous target genes at posttranscriptional level. However, the role of microRNAs in lung cancer, particularly non-small-cell lung cancer (NSCLC), has remained elusive. In this study, two microRNAs, miR-1271 and miR-628, and their predicted target genes were identified differentially expressed in NSCLC by analyzing the miRNA and mRNA expression data from NSCLC tissues and their matching normal controls. miR-1271 and its target gene HOXA5 were selected for further investigation. CCK-8 proliferation assay showed that the cell proliferation was promoted by miR-1271more » in NSCLC cells, while miR-1271 inhibitor could significantly inhibited the proliferation of NSCLC cells. Interestingly, migration and invasion assay indicated that overexpression of miR-1271 could significantly promoted the migration and invasion of NSCLC cells, whereas miR-1271 inhibitor could inhibited both cell migration and invasion of NSCLC cells. Western blot showed that miR-1271 suppressed the protein level of HOXA5, and luciferase assays confirmed that miR-1271 directly bound to the 3'untranslated region of HOXA5. This study indicated indicate that miR-1271 regulates NSCLC cell proliferation and invasion, via the down-regulation of HOXA5. Thus, miR-1271 may represent a potential therapeutic target for NSCLC intervention. - Highlights: • Overexpression of miR-1271 promoted proliferation and invasion of NSCLC cells. • miR-1271 inhibitor inhibited the proliferation and invasion of NSCLC cells. • miR-1271 targets 3′ UTR of HOXA5 in NSCLC cells. • miR-1271 negatively regulates HOXA5 in NSCLC cells.« less

5. Roof Truss Above Service Area, Roof Truss Above Ward, ...

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

5. Roof Truss Above Service Area, Roof Truss Above Ward, Roof Framing Axonometric - National Home for Disabled Volunteer Soldiers - Battle Mountain Sanitarium, Ward 4, 500 North Fifth Street, Hot Springs, Fall River County, SD

5. GENERAL VIEW OF GARAGE AREA FROM WEST; STEPS TO ...

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

5. GENERAL VIEW OF GARAGE AREA FROM WEST; STEPS TO WEST FRONT ENTRANCE VISABLE TO THE RIGHT - Isaac N. Hagan House, Kentuck Knob, U.S. Route 40 vicinity (Stewart Township), Chalkhill, Fayette County, PA

50 CFR 697.26 - EEZ Nearshore Management Area 5 Trap Waiver.

Code of Federal Regulations, 2013 CFR

2013-10-01

... permit under this section may engage in trap fishing for black sea bass in EEZ Nearshore Management Area... applicable to lobster and black sea bass fishing. (1) A vessel issued a permit under this section may retain... sea bass permits under § 648.4(a)(7)(i) of this chapter may request an Area 5 Trap Waiver Permit...

50 CFR 697.26 - EEZ Nearshore Management Area 5 Trap Waiver.

Code of Federal Regulations, 2014 CFR

2014-10-01

... permit under this section may engage in trap fishing for black sea bass in EEZ Nearshore Management Area... applicable to lobster and black sea bass fishing. (1) A vessel issued a permit under this section may retain... sea bass permits under § 648.4(a)(7)(i) of this chapter may request an Area 5 Trap Waiver Permit...

50 CFR 697.26 - EEZ Nearshore Management Area 5 Trap Waiver.

Code of Federal Regulations, 2012 CFR

2012-10-01

... permit under this section may engage in trap fishing for black sea bass in EEZ Nearshore Management Area... applicable to lobster and black sea bass fishing. (1) A vessel issued a permit under this section may retain... sea bass permits under § 648.4(a)(7)(i) of this chapter may request an Area 5 Trap Waiver Permit...

5. WEST MEZZANINE, LOOKING NORTH, AREA PREVIOUSLY CONTAINED HIGH TENSION ...

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

5. WEST MEZZANINE, LOOKING NORTH, AREA PREVIOUSLY CONTAINED HIGH TENSION BUS AND SWITCHING EQUIPMENT FOR BUILDINGS L1 AND L2 - Portland General Electric Company, Lincoln Substation, 1841 Southeast Water Street, Portland, Multnomah County, OR

Proton acceleration to above 5.5 MeV by interaction of 1017 W/cm2 laser pulse with H2O nano-wire targets

NASA Astrophysics Data System (ADS)

Schleifer, E.; Bruner, N.; Eisenmann, S.; Botton, M.; Pikuz, S. A., Jr.; Faenov, A. Y.; Gordon, D.; Zigler, A.

2011-05-01

Compact sources of high energy protons (50-500MeV) are expected to be key technology in a wide range of scientific applications 1-8. Particularly promising is the target normal sheah acceleration (TNSA) scheme 9,10, holding record level of 67MeV protons generated by a peta-Watt laser 11. In general, laser intensity exceeding 1018 W/cm2 is required to produce MeV level protons. Enhancing the energy of generated protons using compact laser sources is very attractive task nowadays. Recently, nano-scale targets were used to accelerate ions 12,13. Here we report on the first generation of 5.5-7.5MeV protons by modest laser intensities (4.5 × 1017 W/cm2) interacting with H2O nano-wires (snow) deposited on a Sapphire substrate. In this setup, the plasma near the tip of the nano-wire is subject to locally enhanced laser intensity with high spatial gradients, and confined charge separation is obtained. Electrostatic fields of extremely high intensities are produced, and protons are accelerated to MeV-level energies. Nano-wire engineered targets will relax the demand of peak energy from laser based sources.

Comparison of the boomerang wire vascular access management system versus manual compression alone during percutaneous diagnostic and interventional cardiovascular procedures: The boomerang™ wire vascular access management trial II.

PubMed

Goswami, Nilesh J; Smalling, Ronnie G; Sinha, Shantanu; Gammon, Roger S; Ramaiah, Venkatesh G

2016-01-01

To evaluate the use of the Boomerang™ Wire as an adjunct to manual compression (MC) in patients requiring diagnostic (Dx) or interventional (Ix) percutaneous procedures. MC remains the standard of care for closure of femoral artery access sites. Adjunctive use of a device to facilitate closure, reduce time to hemostasis (TTH) and ambulation (TTA) without increasing complication rates could reduce costs and hospital resource demands. The Boomerang™ Trial was a prospective, multicenter, randomized, controlled trial comparing use of the Boomerang™ wire, (Cardiva Medical, Sunnyvale, CA) in conjunction with MC versus MC alone to achieve hemostasis in Dx and Ix patients undergoing percutaneous procedures requiring femoral artery access. Endpoints included TTH, TTA, major, and minor access-site related complications. Subjects were randomized 3:1, Boomerang versus MC. No minor or major device-related adverse events were reported. Nondevice related complication rates were 3 (0.9%) in the Boomerang arm (n = 327) and 1 (0.8%) in MC arm (n = 123). Mean TTH for Boomerang vs. MC was 11.2 ± 4.3 vs. 23.2 ± 11 min for Dx (P < 0.0001) and 13.9 ± 5.4 vs. 38.4 ± 57.3 min for Ix patients (P < 0.0001). Mean TTA for Boomerang vs. MC was 3.3 ± 3.0 vs. 4.5 ± 2.0 hr (P < 0.0001)for Dx and 5.4 ± 3.3 vs. 6.8 ± 3.2 hr (P < 0.0001) for Ix patients. Boomerang™ use, in conjunction with MC, was associated with low rates of complications and demonstrated that Boomerang™ as an adjunct to MC can significantly decrease TTH and TTA after both Dx and Ix procedures. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

MicroRNA-361-5p Inhibits Cancer Cell Growth by Targeting CXCR6 in Hepatocellular Carcinoma.

PubMed

Sun, Jian-Jun; Chen, Guo-Yong; Xie, Zhan-Tao

2016-01-01

A growing body of evidence supports the notion that MicroRNAs (miRNAs) function as key regulators of tumorigenesis. In the present study, the expression and roles of miRNA-361-5p were explored in hepatocellular carcinoma (HCC). Quantitative real-time PCR was used to detect the expression miR-361-5p in HCC tissues and pair-matched adjacent normal tissues. MTT and BrdU assays were used to identify the role of miR-361-5p in the regulation of proliferation and invasion of HCC cells. Using bioinformatics analysis, luciferase reporter assays and Western blots were used to identify the molecular target of miR-361-5p. nude mice were used to detect the anti-tumor role of miR-361-5p in vivo. miR-361-5p was down-regulated in HCC tissues in comparison to adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-361-5p suppressed proliferation and invasion of HCC cells. Chemokine (C-X-C Motif) receptor 6 (CXCR6) was identified as a target of miR-361-5p. Indeed, knockdown of CXCR6 photocopied, while overexpression of CXCR6 largely attenuated the anti-proliferative effect of miR-361-5p. More importantly, in vivo studies demonstrated that forced expression of miR-361-5p significantly inhibited tumor growth in the nude mice. Our results indicate that miR-361-5p acts as a tumor suppressor and might serve as a novel therapeutic target for the treatment of HCC patients. © 2016 The Author(s) Published by S. Karger AG, Basel.

Operationalization of the wilderness targets of the German NSBD

Treesearch

Albert Reif

2015-01-01

The German government's National Strategy on Biological Diversity (NSBD) aims at protecting its biodiversity in a broad sense. The NSBD calls for 5% of Germany's forest land area to be permanently set aside for natural forest protection, i.e., natural processes taking place, and as a second target, for 2% of Germany's land area to become "wilderness...

NLRC5/MHC class I transactivator is a target for immune evasion in cancer

PubMed Central

Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B.; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A.; Lizee, Gregory A.; Kobayashi, Koichi S.

2016-01-01

Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as “NLRC5” [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8+ cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers. PMID:27162338

NLRC5/MHC class I transactivator is a target for immune evasion in cancer.

PubMed

Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A; Lizee, Gregory A; Kobayashi, Koichi S

2016-05-24

Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as "NLRC5" [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8(+) cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers.

5. GLACIER POINT ROAD VIEW AT SENTINEL DOME PARKING AREA. ...

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

5. GLACIER POINT ROAD VIEW AT SENTINEL DOME PARKING AREA. LOOKING E. GIS: N-37 42 43.8 / W-119 35 12.1 - Glacier Point Road, Between Chinquapin Flat & Glacier Point, Yosemite Village, Mariposa County, CA

Is the zero emission requirement aligned with 2.0°C and 1.5°C stabilization targets?

NASA Astrophysics Data System (ADS)

Tanaka, K.; O'Neill, B. C.

2016-12-01

The Paris Agreement stipulates that the global warming be stabilized at well below 2°C and eventually 1.5°C above pre-industrial levels. While the landmark agreement has led to a wide range of associated analyses, less attention has been paid to another mitigation target in Paris: cut the net greenhouse gas emissions to zero during the second half of this century. This study explores how such an emission target may guide us to achieve the temperature target. We found that, if the emission target is met by 2060, the most likely outcome is that the warming will peak at slightly above 2°C and decline below 1.5°C by the early 22nd century. This corresponds roughly to the temperature target; however, it is important to realize that the warming inevitably exceeds 1.5°C temporarily. On the contrary, if delayed by 2100, the warming reaches as high as 4°C until it starts to fall. Furthermore, net negative CO2 emissions are implicitly required for the emission target, the intensity of which depends on unabatable anthropogenic non-CO2 greenhouse gas emissions as well as the emission metric used to equate greenhouse gas emissions on the basis of CO2.

miR-491-5p suppresses cell growth and invasion by targeting Notch3 in nasopharyngeal carcinoma.

PubMed

Zhang, Qi; Li, Qiang; Xu, Tao; Jiang, Hui; Xu, Lin-Gen

2016-06-01

MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in Southern China. miR-491-5p has been implicated in multiple types of cancer; however, its biological role and underlying mechanism in NPC have not been fully explored. In the present study, we found that miR-491-5p was downregulated in NPC tissues and cell lines compared with the corresponding normal counterparts. Overexpression of miR-491-5p significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA target prediction algorithms and reporter assays, we showed that miR-491-5p suppressed Notch3 expression both at the mRNA and protein level through directly targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of Notch3 significantly reversed the tumor-suppressive effects of miR‑491-5p. Taken together, the present study reveals a mechanistic link between miR-491-5p and Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a therapeutic target for NPC.

Preparation and characterisation of isotopically enriched Ta2O5 targets for nuclear astrophysics studies

NASA Astrophysics Data System (ADS)

Caciolli, A.; Scott, D. A.; Di Leva, A.; Formicola, A.; Aliotta, M.; Anders, M.; Bellini, A.; Bemmerer, D.; Broggini, C.; Campeggio, M.; Corvisiero, P.; Depalo, R.; Elekes, Z.; Fülöp, Zs.; Gervino, G.; Guglielmetti, A.; Gustavino, C.; Gyürky, Gy.; Imbriani, G.; Junker, M.; Marta, M.; Menegazzo, R.; Napolitani, E.; Prati, P.; Rigato, V.; Roca, V.; Rolfs, C.; Rossi Alvarez, C.; Somorjai, E.; Salvo, C.; Straniero, O.; Strieder, F.; Szücs, T.; Terrasi, F.; Trautvetter, H. P.; Trezzi, D.

2012-10-01

The direct measurement of reaction cross-sections at astrophysical energies often requires the use of solid targets of known thickness, isotopic composition, and stoichiometry that are able to withstand high beam currents for extended periods of time. Here, we report on the production and characterisation of isotopically enriched Ta2O5 targets for the study of proton-induced reactions at the Laboratory for Underground Nuclear Astrophysics facility of the Laboratori Nazionali del Gran Sasso. The targets were prepared by anodisation of tantalum backings in enriched water (up to 66% in 17O and up to 96% in 18O. Special care was devoted to minimising the presence of any contaminants that could induce unwanted background reactions with the beam in the energy region of astrophysical interest. Results from target characterisation measurements are reported, and the conclusions for proton capture measurements with these targets are drawn.

Biotechnological engineering of heparin/heparan sulphate: a novel area of multi-target drug discovery.

PubMed

Rusnati, Marco; Oreste, Pasqua; Zoppetti, Giorgio; Presta, Marco

2005-01-01

Heparin is a sulphated glycosaminoglycan currently used as an anticoagulant and antithrombotic drug. It consists largely of 2-O-sulphated IdoA not l&r arrow N, 6-O-disulphated GlcN disaccharide units. Other disaccharides containing unsulphated IdoA or GlcA and N-sulphated or N-acetylated GlcN are also present as minor components. This heterogeneity is more pronounced in heparan sulphate (HS), where the low-sulphated disaccharides are the most abundant. Heparin/HS bind to a variety of biologically active polypeptides, including enzymes, growth factors and cytokines, and viral proteins. This capacity can be exploited to design multi-target heparin/HS-derived drugs for pharmacological interventions in a variety of pathologic conditions besides coagulation and thrombosis, including neoplasia and viral infection. The capsular K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor N-acetyl heparosan. The possibility of producing K5 polysaccharide derivatives by chemical and enzymatic modifications, thus generating heparin/HS-like compounds, has been demonstrated. These K5 polysaccharide derivatives are endowed with different biological properties, including anticoagulant/antithrombotic, antineoplastic, and anti-AIDS activities. Here, the literature data are discussed and the possible therapeutic implications for this novel class of multi-target "biotechnological heparin/HS" molecules are outlined.

Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south-western Uganda.

PubMed

Ndyomugyenyi, Richard; Magnussen, Pascal; Lal, Sham; Hansen, Kristian; Clarke, Siân E

2016-09-01

To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children <5 years of age receiving appropriately targeted treatment with artemisinin-based combination therapy (ACT), vs. presumptive treatment. Cluster-randomized trials were conducted in two contrasting areas of moderate-to-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (i) presumptive clinical diagnosis of malaria [control arm] and (ii) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm], with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving artemether-lumefantrine or rectal artesunate, and patients with no malaria parasites not given ACT. In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (<200 parasites/μl) was identified as a potential concern. When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within

Time-Tag Generation Script

NASA Technical Reports Server (NTRS)

Jackson, Dan E.

2010-01-01

Time-Tag Generation Script (TTaGS) is an application program, written in the AWK scripting language, for generating commands for aiming one Ku-band antenna and two S-band antennas for communicating with spacecraft. TTaGS saves between 2 and 4 person-hours per every 24 hours by automating the repetitious process of building between 150 and 180 antenna-control commands. TTaGS reads a text database of communication satellite schedules and a text database of satellite rise and set times and cross-references items in the two databases. It then compares the scheduled start and stop with the geometric rise and set to compute the times to execute antenna control commands. While so doing, TTaGS determines whether to generate commands for guidance, navigation, and control computers to tell them which satellites to track. To help prevent Ku-band irradiation of the Earth, TTaGS accepts input from the user about horizon tolerance and accordingly restricts activation and effects deactivation of the transmitter. TTaGS can be modified easily to enable tracking of additional satellites and for such other tasks as reading Sun-rise/set tables to generate commands to point the solar photovoltaic arrays of the International Space Station at the Sun.

Evapotranspiration Cover for the 92-Acre Area Retired Mixed Waste Pits, Area 5 Waste Management Division, Nevada National Security Site, Final CQA Report

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

NSTec Environmental Management; The Delphi Groupe, Inc.; J. A. Cesare and Associates, Inc.

The report is the Final Construction Quality Assurance (CQA) Report for the 92-Acrew Evapotranspiration Cover, Area 5 Waste Management Division Retired Mixed Waste Pits, Nevada National Security Site, Nevada, for the period of January 20, 2011, to January 31, 2012 The Area 5 RWMS uses engineered shallow-land burial cells to dispose of packaged waste. The 92-Acre Area encompasses the southern portion of the Area 5 RWMS, which has been designated for the first final closure operations. This area contains 13 Greater Confinement Disposal (GCD) boreholes, 16 narrow trenches, and 9 broader pits. With the exception of two active pits (P03more » and P06), all trenches and pits in the 92-Acre Area had operational covers approximately 2.4 meters thick, at a minimum, in most areas when this project began. The units within the 92-Acre Area are grouped into the following six informal categories based on physical location, waste types and regulatory requirements: (1) Pit 3 Mixed Waste Disposal Unit (MWDU); (2) Corrective Action Unit (CAU) 111; (3) CAU 207; (4) Low-level waste disposal units; (5) Asbestiform low-level waste disposal units; and (6) One transuranic (TRU) waste trench.« less

Evaluation of target acquisition difficulty using recognition distance to measure required retinal area

NASA Astrophysics Data System (ADS)

Nilsson, Thomy H.

2001-09-01

The psychophysical method of limits was used to measure the distance at which observers could distinguish military vehicles photographed in natural landscapes. Obtained from the TNO-TM Search_2 dataset, these pictures either were rear-projected 35-mm slides or were presented on a computer monitor. Based on the rationale that more difficult vehicle targets would require more visual pathways for recognition, difficult of acquisition was defined in terms of the relative retinal area required for recognition. Relative retinal area was derived from the inverse square of the recognition distance of a particular vehicle relative to the distance of the vehicle that could be seen furthest away. Results are compared with data on the time required to find the vehicles in these pictures. These comparison indicate recognition distance thresholds can be a suitable means of defining standards for the effectiveness of vital graphic information; and the two methods are complementary with respect to distinguishing different degrees of acquisition difficulty, and together may provide a means to measure the total information processing required for recognition.

Catastrophic Declines in Wilderness Areas Undermine Global Environment Targets.

PubMed

Watson, James E M; Shanahan, Danielle F; Di Marco, Moreno; Allan, James; Laurance, William F; Sanderson, Eric W; Mackey, Brendan; Venter, Oscar

2016-11-07

Humans have altered terrestrial ecosystems for millennia [1], yet wilderness areas still remain as vital refugia where natural ecological and evolutionary processes operate with minimal human disturbance [2-4], underpinning key regional- and planetary-scale functions [5, 6]. Despite the myriad values of wilderness areas-as critical strongholds for endangered biodiversity [7], for carbon storage and sequestration [8], for buffering and regulating local climates [9], and for supporting many of the world's most politically and economically marginalized communities [10]-they are almost entirely ignored in multilateral environmental agreements. This is because they are assumed to be relatively free from threatening processes and therefore are not a priority for conservation efforts [11, 12]. Here we challenge this assertion using new comparable maps of global wilderness following methods established in the original "last of the wild" analysis [13] to examine the change in extent since the early 1990s. We demonstrate alarming losses comprising one-tenth (3.3 million km 2 ) of global wilderness areas over the last two decades, particularly in the Amazon (30%) and central Africa (14%). We assess increases in the protection of wilderness over the same time frame and show that these efforts are failing to keep pace with the rate of wilderness loss, which is nearly double the rate of protection. Our findings underscore an immediate need for international policies to recognize the vital values of wilderness and the unprecedented threats they face and to underscore urgent large-scale, multifaceted actions needed to maintain them. Copyright © 2016 Elsevier Ltd. All rights reserved.

5. EXTERIOR OF NORTH SIDE SHOWING ENCLOSED FRONT PORCH AREA, ...

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

5. EXTERIOR OF NORTH SIDE SHOWING ENCLOSED FRONT PORCH AREA, ALUMINUM SLIDING GLASS WINDOW GLAZING REPLACEMENTS, AND RAILING FOR STAIRS TO BASEMENT. VIEW TO SOUTHWEST. - Bishop Creek Hydroelectric System, Plant 4, Worker Cottage, Bishop Creek, Bishop, Inyo County, CA

Vault Area (original section), east corridor, Vault No. 5, showing ...

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

Vault Area (original section), east corridor, Vault No. 5, showing inner set of doors on vault - Fort McNair, Film Store House, Fort Lesley J. McNair, P Street between Third & Fourth Streets, Southwest, Washington, District of Columbia, DC

Epstein-Barr virus miR-BART20-5p regulates cell proliferation and apoptosis by targeting BAD.

PubMed

Kim, Hyoji; Choi, Hoyun; Lee, Suk Kyeong

2015-01-28

Although Epstein-Barr virus (EBV) BamHI A rightward transcript (BART) microRNAs (miRNAs) are ubiquitously expressed in EBV-associated tumors, the role of most BART miRNAs is unclear. In this study, we showed that Bcl-2-associated death promoter (BAD) expression was significantly lower in EBV-infected AGS-EBV cells than in EBV-negative AGS cells and investigated whether BART miRNAs target BAD. Using bioinformatics analysis, five BART miRNAs showing seed match with the 3' untranslated region (3'-UTR) of BAD were selected. Of these, only miR-BART20-5p reduced BAD expression when individually transfected into AGS cells. A luciferase assay revealed that miR-BART20-5p directly targets BAD. The expression of BAD mRNA and protein was decreased by miR-BART20-5p and increased by an inhibitor of miR-BART20-5p. PE-Annexin V staining and cell proliferation assays showed that miR-BART20-5p reduced apoptosis and enhanced cell growth. Furthermore, miR-BART20-5p increased chemoresistance to 5-fluorouracil and docetaxel. Our data suggest that miR-BART20-5p contributes to tumorigenesis of EBV-associated gastric carcinoma by directly targeting the 3'-UTR of BAD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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.

Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

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

Constanzo, Julie; Paquette, Benoit; Charest, Gabriel

2015-05-15

Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brainmore » were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife.« less

microRNA-145 regulates the RLR signaling pathway in miiuy croaker after poly(I:C) stimulation via targeting MDA5.

PubMed

Han, Jingjing; Sun, Yuena; Song, Weihua; Xu, Tianjun

2017-03-01

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that participate in diverse biological processes via degrading the target mRNAs or repressing translation. In this study, the regulation of miRNA to the RLR (RIG-I-like receptor) signaling pathway by degrading the target mRNAs was researched in miiuy croaker. MDA5, a microRNA-145-5p (miR-145-5p) putative target gene, was predicted by bioinformatics, and the target sites from the 3'untranslated region of MDA5 transcripts were confirmed using luciferase reporter assays. Pre-miR-145 was more effective in inhibiting MDA5 than miR-145-5p mimic, and the effect was dose- and time-dependent. The expression patterns of miR-145-5p and MDA5 were analyzed in liver and kidney from miiuy croaker. Results implied that miR-145-5p may function via degrading the MDA5 mRNAs, thereby regulating the RLR signaling pathway. Studies on miR-145-5p will enrich knowledge of its functions in immune response regulation in fish, as well as offer a basis for regulatory networks that are composed of numerous miRNAs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Airborne surveys of USA urban areas at 121.5/243 MHz

NASA Technical Reports Server (NTRS)

Taylor, R. E.; Hill, J. S.

1979-01-01

In situ, aircraft flight measurements were made in 1976 and 1977 by NASA of the radio-frequency environment over USA urban areas within the emergency distress search and rescue frequency bands at 121.5 and 243.0 MHz. This paper analyzes test results reported previously for USA East Coast and Midwest flight surveys; presented also are test results obtained in May 1977 for the USA West Coast during the NASA, ASSESS-II, Space Shuttle/Spacelab simulation aircraft flights. The USA West Coast flight include data at 121.5/243 MHz during an extensive series of aircraft passes for the Los Angeles urban area. The USA East Coast/Midwest measurements show correlation with population count.

Statistical Algorithms for Designing Geophysical Surveys to Detect UXO Target Areas

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

O'Brien, Robert F.; Carlson, Deborah K.; Gilbert, Richard O.

2005-07-29

The U.S. Department of Defense is in the process of assessing and remediating closed, transferred, and transferring military training ranges across the United States. Many of these sites have areas that are known to contain unexploded ordnance (UXO). Other sites or portions of sites are not expected to contain UXO, but some verification of this expectation using geophysical surveys is needed. Many sites are so large that it is often impractical and/or cost prohibitive to perform surveys over 100% of the site. In that case, it is particularly important to be explicit about the performance required of the survey. Thismore » article presents the statistical algorithms developed to support the design of geophysical surveys along transects (swaths) to find target areas (TAs) of anomalous geophysical readings that may indicate the presence of UXO. The algorithms described here determine 1) the spacing between transects that should be used for the surveys to achieve a specified probability of traversing the TA, 2) the probability of both traversing and detecting a TA of anomalous geophysical readings when the spatial density of anomalies within the TA is either uniform (unchanging over space) or has a bivariate normal distribution, and 3) the probability that a TA exists when it was not found by surveying along transects. These algorithms have been implemented in the Visual Sample Plan (VSP) software to develop cost-effective transect survey designs that meet performance objectives.« less

Statistical Algorithms for Designing Geophysical Surveys to Detect UXO Target Areas

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

O'Brien, Robert F.; Carlson, Deborah K.; Gilbert, Richard O.

2005-07-28

The U.S. Department of Defense is in the process of assessing and remediating closed, transferred, and transferring military training ranges across the United States. Many of these sites have areas that are known to contain unexploded ordnance (UXO). Other sites or portions of sites are not expected to contain UXO, but some verification of this expectation using geophysical surveys is needed. Many sites are so large that it is often impractical and/or cost prohibitive to perform surveys over 100% of the site. In such cases, it is particularly important to be explicit about the performance required of the surveys. Thismore » article presents the statistical algorithms developed to support the design of geophysical surveys along transects (swaths) to find target areas (TAs) of anomalous geophysical readings that may indicate the presence of UXO. The algorithms described here determine (1) the spacing between transects that should be used for the surveys to achieve a specified probability of traversing the TA, (2) the probability of both traversing and detecting a TA of anomalous geophysical readings when the spatial density of anomalies within the TA is either uniform (unchanging over space) or has a bivariate normal distribution, and (3) the probability that a TA exists when it was not found by surveying along transects. These algorithms have been implemented in the Visual Sample Plan (VSP) software to develop cost-effective transect survey designs that meet performance objectives.« less

Phosphorodiamidate morpholino targeting the 5' untranslated region of the ZIKV RNA inhibits virus replication.

PubMed

Popik, Waldemar; Khatua, Atanu; Hildreth, James E K; Lee, Benjamin; Alcendor, Donald J

2018-06-01

Zika virus (ZIKV) infection has been associated with microcephaly in infants. Currently there is no treatment or vaccine. Here we explore the use of a morpholino oligonucleotide targeted to the 5' untranslated region (5'-UTR) of the ZIKV RNA to prevent ZIKV replication. Morpholino DWK-1 inhibition of ZIKV replication in human glomerular podocytes was examined by qRT-PCR, reduction in ZIKV genome copy number, western blot analysis, immunofluorescence and proinflammatory cytokine gene expression. Podocytes pretreated with DWK-1 showed reduced levels of both viral mRNA and ZIKV E protein expression compared to controls. We observed suppression in proinflammatory gene expression for IFN-β (interferon β) RANTES (regulated on activation, normal T cell expressed and secreted), MIP-1α (macrophage inflammatory protein-1α), TNF-α (tumor necrosis factor-α) and IL1-α (interleukin 1-α) in ZIKV-infected podocytes pretreated with DWK-1. Morpholino DWK-1 targeting the ZIKV 5'-UTR effectively inhibits ZIKV replication and suppresses ZIKV-induced proinflammatory gene expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of Scd5, a protein phosphatase-1 targeting protein, in phosphoregulation of Sla1 during endocytosis

PubMed Central

Chi, Richard J.; Torres, Onaidy T.; Segarra, Verónica A.; Lansley, Tanya; Chang, Ji Suk; Newpher, Thomas M.; Lemmon, Sandra K.

2012-01-01

Summary Phosphorylation regulates assembly and disassembly of proteins during endocytosis. In yeast, Prk1 and Ark1 phosphorylate factors after vesicle internalization leading to coat disassembly. Scd5, a protein phosphatase-1 (PP1)-targeting subunit, is proposed to regulate dephosphorylation of Prk1/Ark1 substrates to promote new rounds of endocytosis. In this study we analyzed scd5-PP1Δ2, a mutation causing impaired PP1 binding. scd5-PP1Δ2 caused hyperphosphorylation of several Prk1 endocytic targets. Live-cell imaging of 15 endocytic components in scd5-PP1Δ2 revealed that most factors arriving before the invagination/actin phase of endocytosis had delayed lifetimes. Severely affected were early factors and Sla2 (Hip1R homolog), whose lifetime was extended nearly fourfold. In contrast, the lifetime of Sla1, a Prk1 target, was extended less than twofold, but its cortical recruitment was significantly reduced. Delayed Sla2 dynamics caused by scd5-PP1Δ2 were suppressed by SLA1 overexpression. This was dependent on the LxxQxTG repeats (SR) of Sla1, which are phosphorylated by Prk1 and bind Pan1, another Prk1 target, in the dephosphorylated state. Without the SR, Sla1ΔSR was still recruited to the cell surface, but was less concentrated in cortical patches than Pan1. sla1ΔSR severely impaired endocytic progression, but this was partially suppressed by overexpression of LAS17, suggesting that without the SR region the SH3 region of Sla1 causes constitutive negative regulation of Las17 (WASp). These results demonstrate that Scd5/PP1 is important for recycling Prk1 targets to initiate new rounds of endocytosis and provide new mechanistic information on the role of the Sla1 SR domain in regulating progression to the invagination/actin phase of endocytosis. PMID:22825870

MARK1 is a Novel Target for miR-125a-5p: Implications for Cell Migration in Cervical Tumor Cells.

PubMed

Natalia, Martinez-Acuna; Alejandro, Gonzalez-Torres; Virginia, Tapia-Vieyra Juana; Alvarez-Salas, Luis Marat

2018-01-01

Aberrant miRNA expression is associated with the development of several diseases including cervical cancer. Dysregulation of miR-125a-5p is present in a plethora of tumors, but its role in cervical cancer is not well understood. The aim was to analyze the expression profile of miR-125a-5p in tumor and immortal cell lines with further target prediction, validation and function analysis. MiR-125a-5p expression was determined by real-time RT-PCR from nine cervical cell lines. In silico tools were used to find target transcripts with an miR-125-5p complementary site within the 3'UTR region. Further target selection was based on gene ontology annotation and ΔG analysis. Target validation was performed by transfection of synthetic miR-125a-5p mimics and luciferase assays. Functional evaluation of miR-125a-5p on migration was performed by transwell migration assays. Differential miR-125a-5p expression was observed between immortal and tumor cells regardless of the human papillomavirus (HPV) content. Thermodynamic and ontological analyses showed Microtubule-Affinity-Regulating Kinase1 (MARK1) as a putative target for miR-125a-5p. An inverse correlation was observed among miR-125a-5p expression and MARK1 protein levels in tumor but not in immortal cells. Luciferase assays showed direct miR-125a-5p regulation over MARK1 through recognition of a predicted target site within the 3'-UTR. HeLa and C-33A cervical tumor cells enhanced migration after transfection with miR-125a-5p mimics and stimulation of cell migration was reproduced by siRNA-mediated inhibition of MARK1. The results showed MARK1 as a novel functional target for miR-125a-5p with implications on cell migration of tumor cervical cancer cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enhanced anticancer efficacy and tumor targeting through folate-PEG modified nanoliposome loaded with 5-fluorouracil

NASA Astrophysics Data System (ADS)

Le, Van Minh; Tran Nho, Trung Duc; Trieu Ly, Hai; Vo, Thanh Sang; Dung Nguyen, Hoang; Thu Huong Phung, Thi; Zou, Aihua; Liu, Jianwen

2017-03-01

Cancer targeted therapies have attracted considerable attention over the past year. Recently, 5-fluouracil (5-FU), which has high toxicity to normal cells and short half-life associated with rapid metabolism, is one of the most commonly used therapies in the treatment of cancer. In this study the folic acid-conjugated pegylated nanoliposomes were synthesized and then loaded into them with 5-FU to improve the anti-tumor efficacy. The average size of liposomes (LPs) was about 52.7 nm which was identified by TEM. In the liposome uptake studies, the level uptake of folate-conjugated liposomes has increased compared to non-conjugated LPs according to LPs concentration, incubation time and presence of concentration of free folic acid (FA). The MTT assay and apoptotic test were carried out in HCT116 and MCF-7 cells for 24 or 48 h. The results revealed that the folate-PEG modified 5-Fu loaded nanoliposomes had strong cytotoxicity to cancer cell compared to pure 5-FU or PEG modified 5-FU loaded liposomes in a concentration- and time-dependent manner, and mainly enhanced the cancer cell death through folate-mediated endocytosis. Hence, the folate-PEG modified nanoliposome is a potential targeted drug-delivery system for the treatment of FR-positive cancers.

Preclinical Assessment of CAR T-Cell Therapy Targeting the Tumor Antigen 5T4 in Ovarian Cancer

PubMed Central

Owens, Gemma L.; Sheard, Victoria E.; Kalaitsidou, Milena; Blount, Daniel; Lad, Yatish; Cheadle, Eleanor J.; Edmondson, Richard J.; Kooner, Gurdeep; Gilham, David E.

2018-01-01

Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome both quantitative and qualitative shortfalls of the host immune system relating to the detection and subsequent destruction of tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step in the ability to utilize CAR T cells for the treatment of cancer. The 5T4 is a tumor-associated antigen which is expressed on the cell surface of most solid tumors including ovarian cancer. Matched blood and tumor samples were collected from 12 patients with ovarian cancer; all tumors were positive for 5T4 expression by immunohistochemistry. Patient T cells were effectively transduced with 2 different anti-5T4 CAR constructs which differed in their affinity for the target antigen. Co-culture of CAR T cells with matched autologous tumor disaggregates resulted in antigen-specific secretion of IFN-gamma. Furthermore, assessment of the efficacy of anti-5T4 CAR T cells in a mouse model resulted in therapeutic benefit against established ovarian tumors. These results demonstrate proof of principle that 5T4 is an attractive target for immune intervention in ovarian cancer and that patient T cells engineered to express a 5T4-specific CAR can recognize and respond physiologically to autologous tumor cells. PMID:29239915

5 CFR 532.317 - Use of data from the nearest similar area.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REGULATIONS PREVAILING RATE SYSTEMS Determining Rates for Principal Types of Positions § 532.317 Use of data... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Use of data from the nearest similar area... subpart, analyze and use the acceptable data from the nearest similar wage area together with the data...

5 CFR 532.317 - Use of data from the nearest similar area.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REGULATIONS PREVAILING RATE SYSTEMS Determining Rates for Principal Types of Positions § 532.317 Use of data... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Use of data from the nearest similar area... subpart, analyze and use the acceptable data from the nearest similar wage area together with the data...

Blockade of T-type calcium channels prevents tonic-clonic seizures in a maximal electroshock seizure model.

PubMed

Sakkaki, Sophie; Gangarossa, Giuseppe; Lerat, Benoit; Françon, Dominique; Forichon, Luc; Chemin, Jean; Valjent, Emmanuel; Lerner-Natoli, Mireille; Lory, Philippe

2016-02-01

T-type (Cav3) calcium channels play important roles in neuronal excitability, both in normal and pathological activities of the brain. In particular, they contribute to hyper-excitability disorders such as epilepsy. Here we have characterized the anticonvulsant properties of TTA-A2, a selective T-type channel blocker, in mouse. Using the maximal electroshock seizure (MES) as a model of tonic-clonic generalized seizures, we report that mice treated with TTA-A2 (0.3 mg/kg and higher doses) were significantly protected against tonic seizures. Although no major change in Local Field Potential (LFP) pattern was observed during the MES seizure, analysis of the late post-ictal period revealed a significant increase in the delta frequency power in animals treated with TTA-A2. Similar results were obtained for Cav3.1-/- mice, which were less prone to develop tonic seizures in the MES test, but not for Cav3.2-/- mice. Analysis of extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and c-Fos expression revealed a rapid and elevated neuronal activation in the hippocampus following MES clonic seizures, which was unchanged in TTA-A2 treated animals. Overall, our data indicate that TTA-A2 is a potent anticonvulsant and that the Cav3.1 isoform plays a prominent role in mediating TTA-A2 tonic seizure protection. Copyright © 2015. Published by Elsevier Ltd.

Dust Removal Target on 'Vera Rubin Ridge'

NASA Image and Video Library

2017-11-01

This image from the Mars Hand Lens Imager (MAHLI) camera on NASA's Curiosity Mars rover shows effects of using the rover's wire-bristled Dust Removal Tool (DRT) on a rock target called "Christmas Cove." The tool brushed an area about 2.5 inches (6 centimeters) across on Sept. 16, 2017, during the 1,118th Martian day, or sol of Curiosity's work on Mars. MAHLI took this image later the same sol. Both DRT and MAHLI are on the turret of tools at the end of Curiosity's arm. The site is partway up "Vera Rubin Ridge" on lower Mount Sharp, in an area where reconnaissance imaging with science filters revealed variability in indications of the mineral hematite. Removing dust from part of the Christmas Cove target was part of an experiment to check whether dust is subduing the apparent indications of hematite in some of the area's bedrock. The brushed area's purplish tint in this MAHLI image, accentuated even more when observed with science filters of the rover's Mast Camera, is characteristic of fine-grained hematite. Brushing of this target also exposed details in the fine layering and bright veins within the bedrock of this part of Vera Rubin Ridge. The image is oriented so that sunlight comes from upper left. Layers are lower (older) toward lower right. https://photojournal.jpl.nasa.gov/catalog/PIA22064

miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

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

Zhang, Yunda; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102; Xu, Guoxing

miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasionmore » while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. - Highlights: • miR-411-5p is downregulated in breast cancer tissues and cell lines. • miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro. • GRB2 is a direct target of miR-411-5p in breast cancer. • GRB2 is overexpressed in breast cancer and associates with disease outcome. • miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.« less

Organization of area hV5/MT+ in subjects with homonymous visual field defects.

PubMed

Papanikolaou, Amalia; Keliris, Georgios A; Papageorgiou, T Dorina; Schiefer, Ulrich; Logothetis, Nikos K; Smirnakis, Stelios M

2018-04-06

Damage to the primary visual cortex (V1) leads to a visual field loss (scotoma) in the retinotopically corresponding part of the visual field. Nonetheless, a small amount of residual visual sensitivity persists within the blind field. This residual capacity has been linked to activity observed in the middle temporal area complex (V5/MT+). However, it remains unknown whether the organization of hV5/MT+ changes following early visual cortical lesions. We studied the organization of area hV5/MT+ of five patients with dense homonymous defects in a quadrant of the visual field as a result of partial V1+ or optic radiation lesions. To do so, we developed a new method, which models the boundaries of population receptive fields directly from the BOLD signal of each voxel in the visual cortex. We found responses in hV5/MT+ arising inside the scotoma for all patients and identified two possible sources of activation: 1) responses might originate from partially lesioned parts of area V1 corresponding to the scotoma, and 2) responses can also originate independent of area V1 input suggesting the existence of functional V1-bypassing pathways. Apparently, visually driven activity observed in hV5/MT+ is not sufficient to mediate conscious vision. More surprisingly, visually driven activity in corresponding regions of V1 and early extrastriate areas including hV5/MT+ did not guarantee visual perception in the group of patients with post-geniculate lesions that we examined. This suggests that the fine coordination of visual activity patterns across visual areas may be an important determinant of whether visual perception persists following visual cortical lesions. Copyright © 2018 Elsevier Inc. All rights reserved.

Potential proteins targeted by let-7f-5p in HeLa cells.

PubMed

Wang, Yu; Chen, Xiujuan; Zhang, Yi; Song, Jiandong

2017-07-24

MicroRNAs are a class of small, endogenous, non-coding RNAs mediating posttranscriptional gene silencing. The current authors hypothesized that let-7f-5p is likely involved in cell invasion and proliferation by regulating the expression of target genes. The current study combined let-7f-5p with iTRAQ to assess its effect on gene expression in HeLa cells. Results indicated that 164 proteins were expressed at different levels in HeLa cells overexpressing let-7f-5p and negative controls and that 172 proteins were expressed at different levels in let-7f-5p-silenced HeLa cells and negative controls. Results indicated that let-7f-5p may suppress insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in HeLa cells.

PVT1-derived miR-1207-5p promotes breast cancer cell growth by targeting STAT6.

PubMed

Yan, Chen; Chen, Yaqing; Kong, Weiwei; Fu, Liya; Liu, Yunde; Yao, Qingjuan; Yuan, Yuhua

2017-05-01

Accumulating evidence indicates that ectopic expression of non-coding RNAs are responsible for breast cancer progression. Increased non-coding RNA PVT1, the host gene of microRNA-1207-5p (miR-1207-5p), has been associated with breast cancer proliferation. However, how PVT1 functions in breast cancer is still not clear. In this study, we show a PVT1-derived microRNA, miR-1207-5p, that promotes the proliferation of breast cancer cells by directly regulating STAT6. We first confirm the positive correlated expression pattern between PVT1 and miR-1207-5p by observing consistent induced expression by estrogen, and overexpression in breast cancer cell lines and breast cancer patient specimens. Moreover, silence of PVT1 also decreased miR-1207-5p expression. Furthermore, increased miR-1207-5p expression promoted, while decreased miR-1207-5p expression suppressed, cell proliferation, colony formation, and cell cycle progression in breast cancer cell lines. Mechanistically, a novel target of miR-1207-5p, STAT6, was identified by a luciferase reporter assay. Overexpression of miR-1207-5p decreased the levels of STAT6, which activated CDKN1A and CDKN1B to regulate the cell cycle. We also confirmed the reverse correlation of miR-1207-5p and STAT6 expression levels in breast cancer samples. Therefore, our findings reveal that PVT1-derived miR-1207-5p promotes the proliferation of breast cancer cells by targeting STAT6, which in turn controls CDKN1A and CDKN1B expression. These findings suggest miR-1207-5p might be a potential target for breast cancer therapy. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Design, Synthesis and Evaluation of Novel 2,5,6-Trisubstituted Benzimidazoles Targeting FtsZ as Antitubercular Agents

PubMed Central

Park, Bora; Awasthi, Divya; Chowdhury, Soumya R.; Melief, Eduard H.; Kumar, Kunal; Knudson, Susan E.; Slayden, Richard A.; Ojima, Iwao

2014-01-01

Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63–12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM. PMID:24726304

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

NASA Astrophysics Data System (ADS)

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

miR-192 suppresses T follicular helper cell differentiation by targeting CXCR5 in childhood asthma.

PubMed

Zhang, Defeng; Wu, Yuanbo; Sun, Gengyun

2018-05-01

The aim of this study was to investigate the role of miR-192 in differentiation of T follicular helper cells in childhood asthma. Blood samples were taken from eighteen children with acute asthma attacks and fifteen healthy children (HC). Quantitative real-time PCR and Western blotting were used to detect the expression levels of miR-192, C-X-C chemokine receptor type 5 (CXCR5), B-cell lymphoma 6 (BCL-6) and inducible T-cell costimulator (ICOS). The flow cytometry was performed to detect the proportion of CD4 + CXCR5+ Tfh cells on CD4 + T lymphocytes. The enzyme-linked immunosorbent assay (ELISA) was carried out to determine the plasma concentrations of total IgE and IL-21. The effect of miR-192 on the T follicular helper cells differentiation by targeting CXCR5 was determined by dual-luciferase reporter assay. Children with asthma had lower levels of miR-192 than HC. The proportion of CD4 + CXCR + Tfh cells was significantly higher in the acute asthma group than HC. Similarly, the plasma concentration of total IgE and IL-21 in the acute group markedly increased compared with the HC, and IgE concentration was positively correlated with the proportion of CD4 + CXCR5 + Tfh cells. Furthermore, the expression levels of CXCR5, Bcl-6 and ICOS were significantly higher in the acute group than in the HC. While the proportion of CD4 + CXCR5 + Tfh cells, IL-21, CXCR5, Bcl-6 and ICOS were obviously lower in the CD4 + T cells transfected with miR-192 plasmid than that in miR-192 + CXCR5 group and control group. In conclusion, miR-192 blocks the activation pathway of Tfh cells by targeting CXCR5, which is a reasonable cellular target for therapeutic intervention.

2016 Targeted AirShed Grant Program - Closed Announcement FY 2016

EPA Pesticide Factsheets

Targeted Air Shed Grant Program proposal for FY 2016. The overall goal of the program is to reduce air pollution in the Nation’s areas with the highest levels of ozone and PM2.5 ambient air concentrations.

Setting conservation targets for sandy beach ecosystems

NASA Astrophysics Data System (ADS)

Harris, Linda; Nel, Ronel; Holness, Stephen; Sink, Kerry; Schoeman, David

2014-10-01

Representative and adequate reserve networks are key to conserving biodiversity. This begs the question, how much of which features need to be placed in protected areas? Setting specifically-derived conservation targets for most ecosystems is common practice; however, this has never been done for sandy beaches. The aims of this paper, therefore, are to propose a methodology for setting conservation targets for sandy beach ecosystems; and to pilot the proposed method using data describing biodiversity patterns and processes from microtidal beaches in South Africa. First, a classification scheme of valued features of beaches is constructed, including: biodiversity features; unique features; and important processes. Second, methodologies for setting targets for each feature under different data-availability scenarios are described. From this framework, targets are set for features characteristic of microtidal beaches in South Africa, as follows. 1) Targets for dune vegetation types were adopted from a previous assessment, and ranged 19-100%. 2) Targets for beach morphodynamic types (habitats) were set using species-area relationships (SARs). These SARs were derived from species richness data from 142 sampling events around the South African coast (extrapolated to total theoretical species richness estimates using previously-established species-accumulation curve relationships), plotted against the area of the beach (calculated from Google Earth imagery). The species-accumulation factor (z) was 0.22, suggesting a baseline habitat target of 27% is required to protect 75% of the species. This baseline target was modified by heuristic principles, based on habitat rarity and threat status, with final values ranging 27-40%. 3) Species targets were fixed at 20%, modified using heuristic principles based on endemism, threat status, and whether or not beaches play an important role in the species' life history, with targets ranging 20-100%. 4) Targets for processes and 5

NCRP Program Area Committee 5: Environmental Radiation and Radioactive Waste Issues.

PubMed

Chen, S Y; Napier, Bruce

2016-02-01

Program Area Committee 5 of the National Council on Radiation Protection and Measurements (NCRP) focuses its activities on environmental radiation and radioactive waste issues. The Committee completed a number of reports in these subject areas, most recently NCRP Report No. 175, Decision Making for Late-Phase Recovery from Major Nuclear or Radiological Incidents. Historically this Committee addressed emerging issues of the nation pertaining to radioactivity or radiation in the environment or radioactive waste issues due either to natural origins or to manmade activities.

Geometric Model for Tracker-Target Look Angles and Line of Slight Distance

DTIC Science & Technology

2015-10-20

412TW-PA-15239 Geometric Model for Tracker -Target Look Angles and Line of Slight Distance DANIEL T. LAIRD AIR FORCE TEST CENTER EDWARDS...15 – 23 OCT 15 4. TITLE AND SUBTITLE Geometric Model for Tracker -Target Look Angles and Line of Slight Distance 5a. CONTRACT...include area code) 661-277-8615 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 GEOMETRIC MODEL FOR TRACKER -TARGET LOOK ANGLES

Forecasting the progress towards the target of Millennium Development Goal 1C in children under 5 years of age in Bangladesh.

PubMed

Hasan, Md Tanvir; Soares Magalhaes, Ricardo J; Williams, Gail M; Mamun, Abdullah A

2015-07-01

To estimate the average annual rates of reduction of stunting, underweight and wasting for the period 1996 to 2011, and to evaluate whether Bangladesh will be expected to achieve the target of Millennium Development Goal 1C of reducing the prevalence of underweight by half by 2015. We used five nationwide, cross-sectional, Demographic and Health Survey data sets to estimate prevalence of undernutrition defined by stunting, underweight and wasting among children under 5 years of age using the WHO child growth standards. We then computed the average annual rates of reduction of prevalence of undernutrition using the formula derived by UNICEF. Finally, we projected the prevalence of undernutrition for the year 2015 using the estimated average annual rates of reduction. Nationwide covering Bangladesh. Children under 5 years of age (n 28,941). The prevalence of stunting decreased by 18.8% (from 60.0% to 41.2%), underweight by 16.0% (from 52.2% to 36.2%) and wasting by 5.1% (from 20.6% to 15.5%) during 1996 to 2011. The overall average annual rates of reduction were 2.84%, 2.69 % and 2.47%, respectively, for stunting, underweight and wasting. We forecast that in 2015, the prevalence of stunting, underweight and wasting will be 36.7%, 32.5% and 14.0%, respectively, at the national level. The prevalence of undernutrition is likely to remain high in rural areas, in the Sylhet division and in the poorest wealth quintile. Bangladesh is likely to achieve the Millennium Development Goal 1C target of reducing the prevalence of underweight by half by 2015. However, it is falling behind in reducing stunting and further investment is needed to reduce individual, household and environmental determinants of stunting in Bangladesh.

5. METAL SHOP ROOM (AREA 108 ON PLAN CA236R36). Looking ...

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

5. METAL SHOP ROOM (AREA 108 ON PLAN CA-236-R-36). Looking northeast. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-A Terminal Room, Test Area 1-120, north end of Jupiter Boulevard, Boron, Kern County, CA

Targeting of GLUT1-GLUT5 chimeric proteins in the polarized cell line Caco-2.

PubMed

Inukai, K; Takata, K; Asano, T; Katagiri, H; Ishihara, H; Nakazaki, M; Fukushima, Y; Yazaki, Y; Kikuchi, M; Oka, Y

1997-04-01

Caco-2, a human differentiated intestinal epithelial cell line, is a promising model for investigating the mechanism of polarized targeting of apical and basolateral membrane proteins. We stably transfected rat GLUT5 cDNA and rabbit GLUT1 cDNA into Caco-2 cells with an expression vector. Immunohistochemical study revealed that the GLUT5 protein expressed was localized at apical membranes and that the GLUT1 expressed was present primarily in the basolateral membranes of cells grown on permeable support. Next, to investigate the domain responsible for determining apical vs. basolateral sorting in glucose transporters, we prepared several GLUT1-GLUT5 chimeric cDNAs and transfected them into Caco-2 cells. A GLUT1 [N terminus approximately sixth transmembrane domain (TM6)]-GLUT5 [intracellular loop (IL) approximately C terminus] chimera was observed exclusively at the apical membrane, while GLUT1 (N terminus approximately IL)-GLUT5 (TM7 approximately C terminus) and GLUT1 (N terminus approximately TM12)-GLUT5 (C-terminal domain) chimeras were observed mainly at the basolateral membrane, a localization similar to that of GLUT1. Moreover, using a recombinant adenovirus expression system, we expressed a GLUT5 (N terminus approximately TM6)-GLUT1(IL)-GLUT5(TM7 approximately C-terminus) chimera, which was observed at the basolateral membrane. Based on these results, the C-terminal domain does not determine isoform-specific targeting of GLUT1 and GLUT5. Rather, it is the intracellular loop in glucose transporters that appears to play a pivotal role in apical-basolateral sorting signals in Caco-2 cells.

Transient receptor potential canonical 4 and 5 proteins as targets in cancer therapeutics.

PubMed

Gaunt, Hannah J; Vasudev, Naveen S; Beech, David J

2016-10-01

Novel approaches towards cancer therapy are urgently needed. One approach might be to target ion channels mediating Ca 2+ entry because of the critical roles played by Ca 2+ in many cell types, including cancer cells. There are several types of these ion channels, but here we address those formed by assembly of transient receptor potential canonical (TRPC) proteins, particularly those which involve two closely related members of the family: TRPC4 and TRPC5. We focus on these proteins because recent studies point to roles in important aspects of cancer: drug resistance, transmission of drug resistance through extracellular vesicles, tumour vascularisation, and evoked cancer cell death by the TRPC4/5 channel activator (-)-englerin A. We conclude that further research is both justified and necessary before these proteins can be considered as strong targets for anti-cancer cell drug discovery programmes. It is nevertheless already apparent that inhibitors of the channels would be unlikely to cause significant adverse effects, but, rather, have other effects which may be beneficial in the context of cancer and chemotherapy, potentially including suppression of innate fear, visceral pain and pathological cardiac remodelling.

MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ

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

Yuan, Jian; Xiao, Gelei; The Institute of Skull Base Surgery & Neuro-oncology at Hunan, Changsha, Hunan 410008

Highlights: • Expression of miR-125a-5p is inversely correlated with that of TAZ in glioma cells. • MiR-125a-5p represses TAZ expression in glioma cells. • MiR-125a-5p directly targets the 3′ UTR of TAZ mRNA and promotes its degradation. • MiR-125a-5p represses CTGF and survivin via TAZ, and inhibits glioma cell growth. • MiR-125a-5p inhibits the stem cell features of HFU-251 MG cells. - Abstract: Glioblastoma (GBM) is the most lethal brain tumor due to the resistance to conventional therapies, such as radiotherapy and chemotherapy. TAZ, an important mediator of the Hippo pathway, was found to be up-regulated in diverse cancers, includingmore » in GBM, and plays important roles in tumor initiation and progression. However, little is known about the regulation of TAZ expression in tumors. In this study, we found that miR-125a-5p is an important regulator of TAZ in glioma cells by directly targeting the TAZ 3′ UTR. MiR-125a-5p levels are inversely correlated with that of TAZ in normal astrocytes and a panel of glioma cell lines. MiR-125a-5p represses the expression of TAZ target genes, including CTGF and survivin, and inhibits cell proliferation and induces the differentiation of GBM cells; whereas over-expression of TAZ rescues the effects of miR-125a-5p. This study revealed a mechanism for TAZ deregulation in glioma cells, and also demonstrated a tumor suppressor role of miR-125a-5p in glioblastoma cells.« less

Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents.

PubMed

Park, Bora; Awasthi, Divya; Chowdhury, Soumya R; Melief, Eduard H; Kumar, Kunal; Knudson, Susan E; Slayden, Richard A; Ojima, Iwao

2014-05-01

Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM. Copyright © 2014 Elsevier Ltd. All rights reserved.

Causal evidence for frontal involvement in memory target maintenance by posterior brain areas during distracter interference of visual working memory

PubMed Central

Feredoes, Eva; Heinen, Klaartje; Weiskopf, Nikolaus; Ruff, Christian; Driver, Jon

2011-01-01

Dorsolateral prefrontal cortex (DLPFC) is recruited during visual working memory (WM) when relevant information must be maintained in the presence of distracting information. The mechanism by which DLPFC might ensure successful maintenance of the contents of WM is, however, unclear; it might enhance neural maintenance of memory targets or suppress processing of distracters. To adjudicate between these possibilities, we applied time-locked transcranial magnetic stimulation (TMS) during functional MRI, an approach that permits causal assessment of a stimulated brain region's influence on connected brain regions, and evaluated how this influence may change under different task conditions. Participants performed a visual WM task requiring retention of visual stimuli (faces or houses) across a delay during which visual distracters could be present or absent. When distracters were present, they were always from the opposite stimulus category, so that targets and distracters were represented in distinct posterior cortical areas. We then measured whether DLPFC-TMS, administered in the delay at the time point when distracters could appear, would modulate posterior regions representing memory targets or distracters. We found that DLPFC-TMS influenced posterior areas only when distracters were present and, critically, that this influence consisted of increased activity in regions representing the current memory targets. DLPFC-TMS did not affect regions representing current distracters. These results provide a new line of causal evidence for a top-down DLPFC-based control mechanism that promotes successful maintenance of relevant information in WM in the presence of distraction. PMID:21987824

miR-9 and miR-140-5p target FoxP2 and are regulated as a function of the social context of singing behavior in zebra finches.

PubMed

Shi, Zhimin; Luo, Guanzheng; Fu, Lijuan; Fang, Zhide; Wang, XiuJie; Li, XiaoChing

2013-10-16

Mutations in the FOXP2 gene cause speech and language impairments, accompanied by structural and functional abnormalities in brain regions underlying speech-related sensory-motor processing, including the striatum and cerebellum. The sequence and expression patterns of FOXP2 are highly conserved among higher vertebrates. In the zebra finch brain, FoxP2 is expressed in Area X, a striatal nucleus required for vocal learning, and reduced FoxP2 expression impairs dendritic development and vocal learning. The FoxP2 gene encodes a transcription factor that controls the expression of many downstream genes. However, how FOXP2 gene expression is regulated is not clearly understood. miRNAs regulate gene expression post-transcriptionally by targeting the 3'-untranslated regions (UTRs) of mRNAs, leading to translational suppression or mRNA degradation. In this study, we identified miR-9 and miR-140-5p as potential regulators of the FoxP2 gene. We show that both miR-9 and miR-140-5p target specific sequences in the FoxP2 3'-UTR and downregulate FoxP2 protein and mRNA expression in vitro. We also show that the expression of miR-9 and miR-140-5p in Area X of the zebra finch brain is regulated during song development in juvenile zebra finches. We further show that in adult zebra finches the expression of miR-9 and miR-140-5p in Area X is regulated as a function of the social context of song behavior in males singing undirected songs. Our findings reveal a post-transcriptional mechanism that regulates FoxP2 expression and suggest that social vocal behavior can influence the basal ganglia circuit controlling vocal learning via a miRNA-FoxP2 gene regulatory network.

miR-9 and miR-140-5p Target FoxP2 and Are Regulated as a Function of the Social Context of Singing Behavior in Zebra Finches

PubMed Central

Shi, Zhimin; Luo, Guanzheng; Fu, Lijuan; Fang, Zhide; Wang, XiuJie

2013-01-01

Mutations in the FOXP2 gene cause speech and language impairments, accompanied by structural and functional abnormalities in brain regions underlying speech-related sensory-motor processing, including the striatum and cerebellum. The sequence and expression patterns of FOXP2 are highly conserved among higher vertebrates. In the zebra finch brain, FoxP2 is expressed in Area X, a striatal nucleus required for vocal learning, and reduced FoxP2 expression impairs dendritic development and vocal learning. The FoxP2 gene encodes a transcription factor that controls the expression of many downstream genes. However, how FOXP2 gene expression is regulated is not clearly understood. miRNAs regulate gene expression post-transcriptionally by targeting the 3′-untranslated regions (UTRs) of mRNAs, leading to translational suppression or mRNA degradation. In this study, we identified miR-9 and miR-140-5p as potential regulators of the FoxP2 gene. We show that both miR-9 and miR-140-5p target specific sequences in the FoxP2 3′-UTR and downregulate FoxP2 protein and mRNA expression in vitro. We also show that the expression of miR-9 and miR-140-5p in Area X of the zebra finch brain is regulated during song development in juvenile zebra finches. We further show that in adult zebra finches the expression of miR-9 and miR-140-5p in Area X is regulated as a function of the social context of song behavior in males singing undirected songs. Our findings reveal a post-transcriptional mechanism that regulates FoxP2 expression and suggest that social vocal behavior can influence the basal ganglia circuit controlling vocal learning via a miRNA-FoxP2 gene regulatory network. PMID:24133256

Preliminary Quantification of Image Color Gradient on Genesis Concentrator Silicon Carbine Target 60001

NASA Technical Reports Server (NTRS)

Allton, J. H.; Calaway, M. J.; Rodriquez, M. C.

2008-01-01

The Genesis spacecraft concentrator was a device to focus solar wind ions onto a 6-cm diameter target area, thus concentrating the solar wind by 20X [1]. The target area was comprised of 4 quadrants held in place by a gold-coated stainless steel "cross" (Fig. 1). To date, two SiC and one chemical vapor deposited (CVD) quadrants have been imaged at 5X using a Leica DM-6000M in autoscan mode. Complete imaging of SiC sample 60001 required 1036 images. The mosaic of images is shown in Fig. 2 and position of analyzed areas in Fig. 3. This mosaic imaging is part of the curatorial documentation of surface condition and mapping of contamination. Higher magnification (50X) images of selected areas of the target and individual contaminant particles are compiled into reports which may be requested from the Genesis Curator [2].

Synthesis, characterization, and luminescent properties of Eu3+ dipyridophenazine functionalized complexes for potential bioimaging applications

NASA Astrophysics Data System (ADS)

Beasley, Jeremy

Luminescent properties of lanthanide complexes possess unique characteristics that make them good candidates for possible bioimaging agents and have inspired research initiatives to further explore these materials. However, the toxicity of these metals limits their applications as in-vivo bioimaging agents. One solution that eliminates the toxic effects is to encase these lanthanide complexes in silica. This project was designed to probe the variation in the fluorescence properties of a highly luminescent europium (III) complex, utilizing a fluorinated â-diketonate ligand (thenoyltrifluoroacetone (tta)), upon the substitution of the solvent molecules by various functionalized dipyrido[3,2-a:2',3'-c]phenazine (DPPZ) ligands. A method for covalently attaching, or occluding complexes in silica nanoparticles were also included in the project design. The structure and properties of the functionalized DPPZ ligands and their respective complexes were determined by FT-IR, 1H-NMR, UV-Vis, and fluorescence spectroscopy techniques. UV excitation of the complexes resulted in red luminescence (~ 614 nm) characteristic of trivalent europium ions. The differences in luminescence properties of the complexes are rationalized in terms of the electronic features of the different functionalized DPPZ ligands. The higher overall quantum yield of the un-functionalized DPPZ complex, Eu(tta)3DPPZ (Q.Y.= 7.68 +/- 0.06 %), and the low overall quantum yield observed for Eu(tta)3DPPZ-COOEt (Q.Y.= 1.08 +/- 0.05%), Eu(tta) 3DPPZ-Si (Q.Y.= 0.65+/- 0.04%), Eu(tta)3DPPZ-COOH (Q.Y.= 0.61+/- 0.07 %), Eu(tta)3DPPZ-CH3 (Q.Y.= 0.59+/-0.02 %) are rationalized in terms of how electron donating or withdrawing groups affect their respective ligand-to-metal energy transfer efficiencies. Eu(tta) 3DPPZ was the only complex to show enhanced luminescent properties capable of potential applications in biomedical imaging.

Beyond cysteine: recent developments in the area of targeted covalent inhibition.

PubMed

Mukherjee, Herschel; Grimster, Neil P

2018-05-29

Over the past decade targeted covalent inhibitors have undergone a renaissance due to the clinical validation and regulatory approval of several small molecule therapeutics that are designed to irreversibly modify their target protein. Invariably, these compounds rely on the serendipitous placement of a cysteine residue proximal to the small molecule binding site; while this strategy has afforded numerous successes, it necessarily limits the number of proteins that can be targeted by this approach. This drawback has led several research groups to develop novel methodologies that target non-cysteine residues for covalent modification. Herein, we survey the current literature of warheads that covalently modify non-cysteine amino acids in proteins. Copyright © 2018 Elsevier Ltd. All rights reserved.

Target size analysis of serotonin 5-HT/sub 1/ and 5-HT/sub 2/ receptors in bovine brain membranes

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

Nishino, N.; Tanaka, C.

1985-09-23

Freeze-dried crude synaptic membranes prepared from bovine cerebral cortex and striatum were exposed to high energy gamma ray from the source of /sup 60/Co. The size of serotonin 5-HT/sub 1/ receptors labeled by (/sup 3/H)serotonin and that of 5-HT/sub 2/ receptors labeled by (/sup 3/H)spiperone or (/sup 3/H)ketanserin was determined by target size analyses. The values were 57,000 daltons, 145,000 daltons and 152,000 daltons for the cerebral cortex and 56,000 daltons, 141,000 daltons and 150,000 daltons for the striatum, respectively. The estimated sizes were deduced by reference to enzyme standards with known molecular masses and which were irradiated in parallel.more » These results demonstrate that the molecular entities in situ for 5-HT/sub 1/ receptors are distinct from those for 5-HT/sub 2/ receptors, thus supporting data on the existence of two distinct populations of serotonin receptors, hitherto evidenced physiopharmacologically.« less

Comparison of Hourly PM2.5 Observations Between Urban and Suburban Areas in Beijing, China.

PubMed

Yao, Ling; Lu, Ning; Yue, Xiafang; Du, Jia; Yang, Cundong

2015-09-29

Hourly PM2.5 observations collected at 12 stations over a 1-year period are used to identify variations between urban and suburban areas in Beijing. The data demonstrates a unique monthly variation form, as compared with other major cities. Urban areas suffer higher PM2.5 concentration (about 92 μg/m³) than suburban areas (about 77 μg/m³), and the average PM2.5 concentration in cold season (about 105 μg/m³) is higher than warm season (about 78 μg/m³). Hourly PM2.5 observations exhibit distinct seasonal, diurnal and day-of-week variations. The diurnal variation of PM2.5 is observed with higher concentration at night and lower value at daytime, and the cumulative growth of nighttime (22:00 p.m. in winter) PM2.5 concentration maybe due to the atmospheric stability. Moreover, annual average PM2.5 concentrations are about 18 μg/m³ higher on weekends than weekdays, consistent with driving restrictions on weekdays. Additionally, the nighttime peak in weekdays (21:00 p.m.) is one hour later than weekends (20:00 p.m.) which also shows the evidence of human activity. These observed facts indicate that the variations of PM2.5 concentration between urban and suburban areas in Beijing are influenced by complex meteorological factors and human activities.

Comparison of Hourly PM2.5 Observations Between Urban and Suburban Areas in Beijing, China

PubMed Central

Yao, Ling; Lu, Ning; Yue, Xiafang; Du, Jia; Yang, Cundong

2015-01-01

Hourly PM2.5 observations collected at 12 stations over a 1-year period are used to identify variations between urban and suburban areas in Beijing. The data demonstrates a unique monthly variation form, as compared with other major cities. Urban areas suffer higher PM2.5 concentration (about 92 μg/m3) than suburban areas (about 77 μg/m3), and the average PM2.5 concentration in cold season (about 105 μg/m3) is higher than warm season (about 78 μg/m3). Hourly PM2.5 observations exhibit distinct seasonal, diurnal and day-of-week variations. The diurnal variation of PM2.5 is observed with higher concentration at night and lower value at daytime, and the cumulative growth of nighttime (22:00 p.m. in winter) PM2.5 concentration maybe due to the atmospheric stability. Moreover, annual average PM2.5 concentrations are about 18 μg/m3 higher on weekends than weekdays, consistent with driving restrictions on weekdays. Additionally, the nighttime peak in weekdays (21:00 p.m.) is one hour later than weekends (20:00 p.m.) which also shows the evidence of human activity. These observed facts indicate that the variations of PM2.5 concentration between urban and suburban areas in Beijing are influenced by complex meteorological factors and human activities. PMID:26426035

43 CFR 5.2 - Areas administered by the Bureau of Indian Affairs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Areas administered by the Bureau of Indian Affairs. 5.2 Section 5.2 Public Lands: Interior Office of the Secretary of the Interior MAKING PICTURES... be scrupulously observed. (c) Use of Indian lands. If the filming of pictures or the making of...

43 CFR 5.2 - Areas administered by the Bureau of Indian Affairs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Areas administered by the Bureau of Indian Affairs. 5.2 Section 5.2 Public Lands: Interior Office of the Secretary of the Interior MAKING PICTURES... be scrupulously observed. (c) Use of Indian lands. If the filming of pictures or the making of...

43 CFR 5.2 - Areas administered by the Bureau of Indian Affairs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Areas administered by the Bureau of Indian Affairs. 5.2 Section 5.2 Public Lands: Interior Office of the Secretary of the Interior MAKING PICTURES... be scrupulously observed. (c) Use of Indian lands. If the filming of pictures or the making of...

Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system

PubMed Central

Wang, Xiaolong; Yu, Honghao; Lei, Anmin; Zhou, Jiankui; Zeng, Wenxian; Zhu, Haijing; Dong, Zhiming; Niu, Yiyuan; Shi, Bingbo; Cai, Bei; Liu, Jinwang; Huang, Shuai; Yan, Hailong; Zhao, Xiaoe; Zhou, Guangxian; He, Xiaoling; Chen, Xiaoxu; Yang, Yuxin; Jiang, Yu; Shi, Lei; Tian, Xiue; Wang, Yongjun; Ma, Baohua; Huang, Xingxu; Qu, Lei; Chen, Yulin

2015-01-01

Recent advances in the study of the CRISPR/Cas9 system have provided a precise and versatile approach for genome editing in various species. However, the applicability and efficiency of this method in large animal models, such as the goat, have not been extensively studied. Here, by co-injection of one-cell stage embryos with Cas9 mRNA and sgRNAs targeting two functional genes (MSTN and FGF5), we successfully produced gene-modified goats with either one or both genes disrupted. The targeting efficiency of MSTN and FGF5 in cultured primary fibroblasts was as high as 60%, while the efficiency of disrupting MSTN and FGF5 in 98 tested animals was 15% and 21% respectively, and 10% for double gene modifications. The on- and off-target mutations of the target genes in fibroblasts, as well as in somatic tissues and testis of founder and dead animals, were carefully analyzed. The results showed that simultaneous editing of several sites was achieved in large animals, demonstrating that the CRISPR/Cas9 system has the potential to become a robust and efficient gene engineering tool in farm animals, and therefore will be critically important and applicable for breeding. PMID:26354037

42 CFR 5.3 - Procedures for designation of health professional(s) shortage areas.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Procedures for designation of health professional(s... SERVICES GENERAL PROVISIONS DESIGNATION OF HEALTH PROFESSIONAL(S) SHORTAGE AREAS § 5.3 Procedures for designation of health professional(s) shortage areas. (a) Using data available to the Department from national...

5 CFR 532.219 - Criteria for establishing nonappropriated fund wage areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Criteria for establishing nonappropriated fund wage areas. 532.219 Section 532.219 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PREVAILING RATE SYSTEMS Prevailing Rate Determinations § 532.219 Criteria for...

5 CFR 532.211 - Criteria for establishing appropriated fund wage areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Criteria for establishing appropriated fund wage areas. 532.211 Section 532.211 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PREVAILING RATE SYSTEMS Prevailing Rate Determinations § 532.211 Criteria for...

Targeted Blockage of Signal Transducer and Activator of Transcription 5 Signaling Pathway with Decoy Oligodeoxynucleotides Suppresses Leukemic K562 Cell Growth

PubMed Central

Wang, Xiaozhong; Zeng, Jianming; Shi, Mei; Zhao, Shiqiao; Bai, Weijun; Cao, Weixi; Tu, Zhiguang; Huang, Zonggan

2011-01-01

The protein signal transducer and activator of transcription 5 (STAT5) of the JAK/STAT pathway is constitutively activated because of its phosphorylation by tyrosine kinase activity of fusion protein BCR-ABL in chronic myelogenous leukemia (CML) cells. This study investigated the potential therapeutic effect of STAT5 decoy oligodeoxynucleotides (ODN) using leukemia K562 cells as a model. Our results showed that transfection of 21-mer-long STAT5 decoy ODN into K562 cells effectively inhibited cell proliferation and induced cell apoptosis. Further, STAT5 decoy ODN downregulated STAT5 targets bcl-xL, cyclinD1, and c-myc at both mRNA and protein levels in a sequence-specific manner. Collectively, these data demonstrate the therapeutic effect of blocking the STAT5 signal pathway by cis-element decoy for cancer characterized by constitutive STAT5 activation. Thus, our study provides support for STAT5 as a potential target downstream of BCR-ABL for CML treatment and helps establish the concept of targeting STAT5 by decoy ODN as a novel therapy approach for imatinib-resistant CML. PMID:21091189

Platinum in PM2.5 of the metropolitan area of Mexico City.

PubMed

Morton-Bermea, Ofelia; Amador-Muñoz, Omar; Martínez-Trejo, Lida; Hernández-Álvarez, Elizabeth; Beramendi-Orosco, Laura; García-Arreola, María Elena

2014-10-01

The increase in platinum (Pt) in the airborne particulate matter with size ≤2.5 µm (PM2.5) in urban environments may be interpreted as result of the abrasion and deterioration of automobile catalyst. Nowadays, about four million vehicles in Mexico City use catalytic converters, which means that their impact should be considered. In order to evaluate the contribution of Pt to environmental pollution of the metropolitan area of Mexico City (MAMC), airborne PM2.5 was collected at five different sites in the urban area (NW, NE, C, SW, SE) in 2011 during April (dry-warm season), August (rainy season) and December (dry-cold season). Analytical determinations were carried out using a ICP-MS with a collision cell and kinetic energy discrimination. The analytical and instrument performance was evaluated with standard road dust reference material (BCR-723). Median Pt concentration in the analyzed particulate was is 38.4 pg m(-3) (minimal value 1 pg m(-3) maximal value 79 pg m(-3)). Obtained Pt concentrations are higher than those reported for other urban areas. Spatial variation shows that SW had Pt concentration significantly higher than NW and C only. Seasonal variation shows that Pt median was higher in rainy season than in both dry seasons. A comparison of these results with previously reported data of PM10 from 1991 and 2003 in the same studied area shows a worrying increase in the concentration of Pt in the air environment of MAMC.

A Novel Method for Gene-Specific Enhancement of Protein Translation by Targeting 5’UTRs of Selected Tumor Suppressors

PubMed Central

Master, Adam; Wójcicka, Anna; Giżewska, Kamilla; Popławski, Piotr; Williams, Graham R.; Nauman, Alicja

2016-01-01

Background Translational control is a mechanism of protein synthesis regulation emerging as an important target for new therapeutics. Naturally occurring microRNAs and synthetic small inhibitory RNAs (siRNAs) are the most recognized regulatory molecules acting via RNA interference. Surprisingly, recent studies have shown that interfering RNAs may also activate gene transcription via the newly discovered phenomenon of small RNA-induced gene activation (RNAa). Thus far, the small activating RNAs (saRNAs) have only been demonstrated as promoter-specific transcriptional activators. Findings We demonstrate that oligonucleotide-based trans-acting factors can also specifically enhance gene expression at the level of protein translation by acting at sequence-specific targets within the messenger RNA 5’-untranslated region (5’UTR). We designed a set of short synthetic oligonucleotides (dGoligos), specifically targeting alternatively spliced 5’UTRs in transcripts expressed from the THRB and CDKN2A suppressor genes. The in vitro translation efficiency of reporter constructs containing alternative TRβ1 5’UTRs was increased by up to more than 55-fold following exposure to specific dGoligos. Moreover, we found that the most folded 5’UTR has higher translational regulatory potential when compared to the weakly folded TRβ1 variant. This suggests such a strategy may be especially applied to enhance translation from relatively inactive transcripts containing long 5’UTRs of complex structure. Significance This report represents the first method for gene-specific translation enhancement using selective trans-acting factors designed to target specific 5’UTR cis-acting elements. This simple strategy may be developed further to complement other available methods for gene expression regulation including gene silencing. The dGoligo-mediated translation-enhancing approach has the potential to be transferred to increase the translation efficiency of any suitable target gene

5 CFR 591.215 - Where does OPM collect prices in the COLA and DC areas?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Where does OPM collect prices in the COLA... Areas Cost-Of-Living Allowances § 591.215 Where does OPM collect prices in the COLA and DC areas? (a) Survey areas. Each COLA area has one survey area, except Hawaii County, HI, and the U.S. Virgin Islands...

5 CFR 591.215 - Where does OPM collect prices in the COLA and DC areas?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Where does OPM collect prices in the COLA... Areas Cost-Of-Living Allowances § 591.215 Where does OPM collect prices in the COLA and DC areas? (a) Survey areas. Each COLA area has one survey area, except Hawaii County, HI, and the U.S. Virgin Islands...

5 CFR 591.215 - Where does OPM collect prices in the COLA and DC areas?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Where does OPM collect prices in the COLA... Areas Cost-Of-Living Allowances § 591.215 Where does OPM collect prices in the COLA and DC areas? (a) Survey areas. Each COLA area has one survey area, except Hawaii County, HI, and the U.S. Virgin Islands...

Effects of the 'Consumer Game' on Learning and Attitudes of Selected Seventh Grade Students in A Target-Area School.

ERIC Educational Resources Information Center

Cohen, Karen C.

The following report describes one teacher's use of the Consumer Game in a class of seventh grade students in a target area school. These students were not highly motivated and displayed poor attitudes toward school, and it was hoped that a game experience might interest them. Despite unusual administrative conditions, the game appears to have…

Proteomic profile of Mycobacterium tuberculosis after eupomatenoid-5 induction reveals potential drug targets.

PubMed

Ghiraldi-Lopes, Luciana D; Campanerut-Sá, Paula Az; Meneguello, Jean E; Seixas, Flávio Av; Lopes-Ortiz, Mariana A; Scodro, Regiane Bl; Pires, Claudia Ta; da Silva, Rosi Z; Siqueira, Vera Ld; Nakamura, Celso V; Cardoso, Rosilene F

2017-08-01

We investigated a proteome profile, protein-protein interaction and morphological changes of Mycobacterium tuberculosis after different times of eupomatenoid-5 (EUP-5) induction to evaluate the cellular response to the drug-induced damages. The bacillus was induced to sub-minimal inhibitory concentration of EUP-5 at 12 h, 24 h and 48 h. The proteins were separated by 2D gel electrophoresis, identified by LC/MS-MS. Scanning electron microscopy and Search Tool for the Retrieval of Interacting Genes/Proteins analyses were performed. EUP-5 impacts mainly in M. tuberculosis proteins of intermediary metabolism and interactome suggests a multisite disturbance that contributes to bacilli death. Scanning electron microscopy revealed the loss of bacillary form. Some of the differentially expressed proteins have the potential to be drug targets such as citrate synthase (Rv0896), phosphoglycerate kinase (Rv1437), ketol-acid reductoisomerase (Rv3001c) and ATP synthase alpha chain (Rv1308).

Molecular targets for flavivirus drug discovery

PubMed Central

Sampath, Aruna; Padmanabhan, R.

2009-01-01

Flaviviruses are a major cause of infectious disease in humans. Dengue virus causes an estimated 50 million cases of febrile illness each year, including an increasing number of cases of hemorrhagic fever. West Nile virus, which recently spread from the Mediterranean basin to the Western Hemisphere, now causes thousands of sporadic cases of encephalitis annually. Despite the existence of licensed vaccines, yellow fever, Japanese encephalitis and tick-borne encephalitis also claim many thousands of victims each year across their vast endemic areas. Antiviral therapy could potentially reduce morbidity and mortality from flavivirus infections, but no effective drugs are currently available. This article introduces a collection of papers in Antiviral Research on molecular targets for flavivirus antiviral drug design and murine models of dengue virus disease that aims to encourage drug development efforts. After reviewing the flavivirus replication cycle, we discuss the envelope glycoprotein, NS3 protease, NS3 helicase, NS5 methyltransferase and NS5 RNA-dependent RNA polymerase as potential drug targets, with special attention being given to the viral protease. The other viral proteins are the subject of individual articles in the journal. Together, these papers highlight current status of drug discovery efforts for flavivirus diseases and suggest promising areas for further research. PMID:18796313

2015 Targeted AirShed Grant Program Grant - Closed Announcement FY 2015

EPA Pesticide Factsheets

Targeted Air Shed Grant Program proposal for FY 2015. The overall goal of the program is to reduce air pollution in the Nation’s areas with the highest levels of ozone and PM2.5 ambient air concentrations.

A community-engaged approach to select geographic areas for interventions to reduce health disparities.

PubMed

Cromley, Ellen; Kleinman, Lawrence C; Ramos, Michelle A; Arniella, Guedy; Viswanathan, Nalini; Garel, Mischka; Horowitz, Carol R

2011-01-01

While neighborhood-based approaches to eliminate health disparities are on the rise, there is little guidance on how researchers may engage with community partners to select geographic areas for interventions to reduce health disparities. We aimed to identify a small geographic area to target interventions to improve diabetes-related outcomes. We describe lessons learned from a community-engaged approach to specify the geographic area of focus. A community-academic partnership of more than 20 organizations collaborated to develop and employ a 5-stage process to specify a target area for diabetes preventions and control activities. A coalition with local knowledge and ties to the community can develop criteria and direct a process leading to selection of a geographic area, increased research capacity, and strengthened relationships among partners. A participatory approach can be effective in defining a geographic area for targeting interventions to reduce health disparities.

Coastal flood implications of 1.5°C, 2°C and 2.5°C global mean temperature stabilization targets for small island nations

NASA Astrophysics Data System (ADS)

Rasmussen, D.; Buchanan, M. K.; Kopp, R. E.; Oppenheimer, M.

2017-12-01

Sea-level rise (SLR) is magnifying the frequency and severity of flooding in coastal regions. The rate and amount of global-mean SLR is a function of the trajectory of the global mean surface temperature (GMST). Therefore, temperature stabilization targets (e.g., 1.5°C or 2°C, as from the Paris Agreement) have important implications for regulating coastal flood risk. Quantifying the differences in the impact from SLR between these and other GMST stabilization targets is necessary for assessing the benefits and harms of mitigation goals. Low-lying small island nations are particularly vulnerable to inundation and coastal flooding from SLR because building protective and resilient infrastructure may not be physically or economically feasible. For small island nations, keeping GMST below a specified threshold may be the only option for maintaining habitability. Here, we assess differences in the return levels of coastal floods for small island nations between 1.5°C, 2.0°C, and 2.5°C GMST stabilization. We employ probabilistic, localized SLR projections and long-term hourly tide gauge records to construct estimates of local flood risk. We then estimate the number of small island nations' inhabitants at risk for permanent inundation under different GMST stabilization targets.

Atmospheric PM2.5 Mercury in the Metropolitan Area of Mexico City.

PubMed

Morton-Bermea, Ofelia; Garza-Galindo, Rodrigo; Hernández-Álvarez, Elizabeth; Ordoñez-Godínez, Sara L; Amador-Muñoz, Omar; Beramendi-Orosco, Laura; Miranda, Javier; Rosas-Pérez, Irma

2018-04-01

In this study, atmospheric mercury concentration in airborne particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM 2.5 ) was analyzed by ICP-MS. Samples were collected in the Mexico City Metropolitan Area (MCMA), during 2013, in five locations, Northwest, Northeast (NE), Central, Southwest and Southeast, along three seasons: dry warm, rainy, and dry cold (DC). It can be observed that NE shows the highest mercury concentration (p < 0.05), where pollution events were identified. The seasonal distribution shows that samples collected during DC present the highest concentration (p < 0.05). These results are in agreement with the distribution of important mercury industrial sources located in the northern urban area as well with the temperature and wind conditions during 2013. The comparison of data obtained in this work with those of similar previous studies clearly indicates a decrease, between 2006 and 2013, of mercury content in PM 2.5 collected in MCMA.

Dual combination therapy targeting DR5 and EMMPRIN in pancreatic adenocarcinoma.

PubMed

Kim, Hyunki; Zhai, Guihua; Samuel, Sharon L; Rigell, Christopher J; Umphrey, Heidi R; Rana, Samir; Stockard, Cecil R; Fineberg, Naomi S; Zinn, Kurt R

2012-02-01

The goal of the study was to assess the efficacy of combined extracellular matrix metalloprotease inducer (EMMPRIN)- and death receptor 5 (DR5)-targeted therapy for pancreatic adenocarcinoma in orthotopic mouse models with multimodal imaging. Cytotoxicity of anti-EMMPRIN antibody and anti-DR5 antibody (TRA-8) in MIA PaCa-2 and PANC-1 cell lines was measured by ATPlite assay in vitro. The distributions of Cy5.5-labeled TRA-8 and Cy3-labeled anti-EMMPRIN antibody in the 2 cell lines were analyzed by fluorescence imaging in vitro. Groups 1 to 12 of severe combined immunodeficient mice bearing orthotopic MIA PaCa-2 (groups 1-8) or PANC-1 (groups 9-12) tumors were used for in vivo studies. Dynamic contrast-enhanced-MRI was applied in group 1 (untreated) or group 2 (anti-EMMPRIN antibody). The tumor uptake of Tc-99m-labeled TRA-8 was measured in group 3 (untreated) and group 4 (anti-EMMPRIN antibody). Positron emission tomography/computed tomography imaging with (18)F-FDG was applied in groups 5 to 12. Groups 5 to 8 (or groups 9 to 12) were untreated or treated with anti-EMMPRIN antibody, TRA-8, and combination, respectively. TRA-8 showed high killing efficacy for both MIA PaCa-2 and PANC-1 cells in vitro, but additional anti-EMMPRIN treatment did not improve the cytotoxicity. Cy5.5-TRA-8 formed cellular caps in both the cell lines, whereas the maximum signal intensity was correlated with TRA-8 cytotoxicity. Anti-EMMPRIN therapy significantly enhanced the tumor delivery of the MR contrast agent, but not Tc-99m-TRA-8. Tumor growth was significantly suppressed by the combination therapy, and the additive effect of the combination was shown in both MIA PaCa-2 and PANC-1 tumor models.

Structural Insights Into the Recognition of Peroxisomal Targeting Signal 1 By Trypanosoma Brucei Peroxin 5

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

Sampathkumar, P.; Roach, C.; Michels, P.A.M.

2009-05-27

Glycosomes are peroxisome-like organelles essential for trypanosomatid parasites. Glycosome biogenesis is mediated by proteins called 'peroxins,' which are considered to be promising drug targets in pathogenic Trypanosomatidae. The first step during protein translocation across the glycosomal membrane of peroxisomal targeting signal 1 (PTS1)-harboring proteins is signal recognition by the cytosolic receptor peroxin 5 (PEX5). The C-terminal PTS1 motifs interact with the PTS1 binding domain (P1BD) of PEX5, which is made up of seven tetratricopeptide repeats. Obtaining diffraction-quality crystals of the P1BD of Trypanosoma brucei PEX5 (TbPEX5) required surface entropy reduction mutagenesis. Each of the seven tetratricopeptide repeats appears to havemore » a residue in the alpha(L) conformation in the loop connecting helices A and B. Five crystal structures of the P1BD of TbPEX5 were determined, each in complex with a hepta- or decapeptide corresponding to a natural or nonnatural PTS1 sequence. The PTS1 peptides are bound between the two subdomains of the P1BD. These structures indicate precise recognition of the C-terminal Leu of the PTS1 motif and important interactions between the PTS1 peptide main chain and up to five invariant Asn side chains of PEX5. The TbPEX5 structures reported here reveal a unique hydrophobic pocket in the subdomain interface that might be explored to obtain compounds that prevent relative motions of the subdomains and interfere selectively with PTS1 motif binding or release in trypanosomatids, and would therefore disrupt glycosome biogenesis and prevent parasite growth.« less

Altered RECQL5 expression in urothelial bladder carcinoma increases cellular proliferation and makes RECQL5 helicase activity a novel target for chemotherapy

PubMed Central

Patterson, Karl; Arya, Lovleen; Bottomley, Sarah; Morgan, Susan; Cox, Angela; Catto, James; Bryant, Helen E.

2016-01-01

RECQ helicases are a family of enzymes with both over lapping and unique functions. Functional autosomal recessive loss of three members of the family BLM, WRN and RECQL4, results in hereditary human syndromes characterized by cancer predisposition and premature aging, but despite the finding that RECQL5 deficient mice are cancer prone, no such link has been made to human RECQL5. Here we demonstrate that human urothelial carcinoma of the bladder (UCC) has increased expression of RECQL5 compared to normal bladder tissue and that increasing RECQL5 expression can drive proliferation of normal bladder cells and is associated with poor prognosis. Further, by expressing a helicase dead RECQL5 and by depleting bladder cancer cells of RECQL5 we show that inhibition of RECQL5 activity has potential as a new target for treatment of UCC. PMID:27764811

Exciplex-Sensitized Triplet-Triplet Annihilation in Heterojunction Organic Thin-Film.

PubMed

Lin, Bo-Yen; Easley, Connor J; Chen, Chia-Hsun; Tseng, Po-Chen; Lee, Ming-Zer; Sher, Pin-Hao; Wang, Juen-Kai; Chiu, Tien-Lung; Lin, Chi-Feng; Bardeen, Christopher J; Lee, Jiun-Haw

2017-03-29

A new concept for organic light-emitting diodes (OLEDs) is presented, which is called exciplex-sensitized triplet-triplet annihilation (ESTTA). The exciplex formed at the organic heterojunction interface of 4,4',4″-tris(N-3-methyphenyl-N-phenyl-amino) triphenylamine and 9,10-bis(2'-naphthyl) anthracene (ADN) is used to sensitize the triplet-triplet annihilation (TTA) process on the ADN molecules. This results in a turn-on voltage (2.2 V) of the blue emission from the OLED below the bandgap (2.9 eV). From the transient electroluminescence measurement, blue emission totally came from the TTA process without direct recombination on the ADN molecules. The blue singlet exciton from the TTA process can be quenched by energy transfer to the exciplex, as revealed by transient photoluminescence measurements. This can be prevented by blocking the energy transfer path and improving the radiative recombination rate of blue emission. With the insertion of the "triplet diffusion and singlet blocking (TDSB)" layer and the incorporation of the dopant material, an ESTTA-OLED with external quantum efficiency of 5.1% was achieved, which consists of yellow and blue emission coming from the exciplex and ESTTA process, respectively.

Tibial Tuberosity Anteromedialization for Patellofemoral Chondral Disease: Prognostic Factors.

PubMed

Rosso, Federica; Rossi, Roberto; Governale, Giorgio; Marmotti, Antongiulio; Cherubini, Valeria; Cottino, Umberto; Bonasia, Davide Edoardo

2017-06-01

Tibial tuberosity anteromedialization (TTA) is a well-established treatment option for patellofemoral chondral disease that is resistant to nonoperative treatment. However, the prognostic factors of this procedure are unknown. To analyze the prognostic factors correlated with the midterm outcomes of TTA for patellofemoral chondral disease and determine the survivorship. Case series; Level of evidence, 4. Indications of TTA for chondral disease included skeletal maturity, age <65 years, TTA with or without lateral release, and (3) minimum 2-year follow-up. Exclusion criteria were (1) previous knee surgeries, (2) previous patellar dislocations, (3) inflammatory/rheumatic conditions, (4) major combined procedures other than lateral release, (5) focal chondral lesions amenable to cartilage repair, and (6) severe trochlear dysplasia. The patients were prospectively evaluated radiographically and clinically using the Western Ontario and McMaster Universities Osteoarthritis Index-Short-Form (WOMAC-SF) and Kujala scores. Different clinical and radiological data were collected (preoperative, intraoperative, and postoperative) and correlated with the outcomes using multiple logistic regression. The Kaplan-Meier survivorship was also evaluated. From January 2003 to December 2013, among 76 eligible patients, 69 patients (78 knees, 74.4% female) were included, with a mean follow-up of 67.9 ± 34.5 months (range, 24-163 months) and a mean age at the time of surgery of 43.5 ± 16.1 years. The mean preoperative WOMAC-SF (17.8 ± 5.3) and Kujala (49.3 ± 15.6) scores significantly ( P < .001) improved after surgery (WOMAC-SF: 6.6 ± 6.9; Kujala: 74.2 ± 20.5). The patients graded their operated knee as 7.2 ± 2.1 of 10 points, on average, and stated that they would undergo the surgery again in 58

A Tracking Analyst for large 3D spatiotemporal data from multiple sources (case study: Tracking volcanic eruptions in the atmosphere)

NASA Astrophysics Data System (ADS)

Gad, Mohamed A.; Elshehaly, Mai H.; Gračanin, Denis; Elmongui, Hicham G.

2018-02-01

This research presents a novel Trajectory-based Tracking Analyst (TTA) that can track and link spatiotemporally variable data from multiple sources. The proposed technique uses trajectory information to determine the positions of time-enabled and spatially variable scatter data at any given time through a combination of along trajectory adjustment and spatial interpolation. The TTA is applied in this research to track large spatiotemporal data of volcanic eruptions (acquired using multi-sensors) in the unsteady flow field of the atmosphere. The TTA enables tracking injections into the atmospheric flow field, the reconstruction of the spatiotemporally variable data at any desired time, and the spatiotemporal join of attribute data from multiple sources. In addition, we were able to create a smooth animation of the volcanic ash plume at interactive rates. The initial results indicate that the TTA can be applied to a wide range of multiple-source data.

Bioimaging of Nucleolin Aptamer-Containing 5-(N-benzylcarboxyamide)-2′-deoxyuridine More Capable of Specific Binding to Targets in Cancer Cells

PubMed Central

Lee, Kyue Yim; Kang, Hyungu; Ryu, Sung Ho; Lee, Dong Soo; Lee, Jung Hwan; Kim, Soonhag

2010-01-01

Chemically modified nucleotides have been developed and applied into SELEX procedure to find a novel type of aptamers to fit with targets of interest. In this study, we directly performed chemical modification of 5-(N-benzylcarboxyamide)-2′-deoxyuridine (called 5-BzdU) in the AS1411 aptamer, which binds to the nucleolin protein expressed in cancer cells. Forty-seven compounds of AS1411-containing Cy3-labeled 5-BzdU (called Cy3-(5-BzdU)-modified-AS1411) were synthesized by randomly substituting thymidines one to twelve in AS1411 with Cy3-labeled 5-BzdU. Both statistically quantified fluorescence measurements and confocal imaging analysis demonstrated at least three potential compounds of interest: number 12, 29 and 41 that significantly increased the targeting affinity to cancer cells but no significant activity from normal healthy cells. These results suggest that the position and number of substituents in AS1411 are critical parameters to improve the aptamer function. In this study, we demonstrated that chemical modification of the existing aptamers enhanced the binding and targeting affinity to targets of interest without additional SELEX procedures. PMID:20204158

Effect of Förster-mediated triplet-polaron quenching and triplet-triplet annihilation on the efficiency roll-off of organic light-emitting diodes

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

Eersel, H. van; Bobbert, P. A.; Janssen, R. A. J.

2016-04-28

We report the results of a systematic study of the interplay of triplet-polaron quenching (TPQ) and triplet-triplet annihilation (TTA) on the efficiency roll-off of organic light-emitting diodes (OLEDs) with increasing current density. First, we focus on OLEDs based on the green phosphorescent emitter tris[2-phenylpyridine]iridium(III) (Ir(ppy){sub 3}) and the red phosphorescent dye platinum octaethylporphyrin. It is found that the experimental data can be reproduced using kinetic Monte Carlo (kMC) simulations within which TPQ and TTA are due to a nearest-neighbor (NN) interaction, or due to a more long-range Förster-type process. Furthermore, we find a subtle interplay between TPQ and TTA: decreasingmore » the contribution of one process can increase the contribution of the other process, so that the roll-off is not significantly reduced. Furthermore, we find that just analyzing the shape of the roll-off is insufficient for determining the relative role of TPQ and TTA. Subsequently, we investigate the wider validity of this picture using kMC simulations for idealized but realistic symmetric OLEDs, with an emissive layer containing a small concentration of phosphorescent dye molecules in a matrix material. Whereas for NN-interactions the roll-off can be reduced when the dye molecules act as shallow hole and electron traps, we find that such an approach becomes counterproductive for long-range TTA and TPQ. Developing well-founded OLED design rules will thus require that more quantitative information is available on the rate and detailed mechanism of the TPQ and TTA processes.« less

Effect of Förster-mediated triplet-polaron quenching and triplet-triplet annihilation on the efficiency roll-off of organic light-emitting diodes

NASA Astrophysics Data System (ADS)

van Eersel, H.; Bobbert, P. A.; Janssen, R. A. J.; Coehoorn, R.

2016-04-01

We report the results of a systematic study of the interplay of triplet-polaron quenching (TPQ) and triplet-triplet annihilation (TTA) on the efficiency roll-off of organic light-emitting diodes (OLEDs) with increasing current density. First, we focus on OLEDs based on the green phosphorescent emitter tris[2-phenylpyridine]iridium(III) (Ir(ppy)3) and the red phosphorescent dye platinum octaethylporphyrin. It is found that the experimental data can be reproduced using kinetic Monte Carlo (kMC) simulations within which TPQ and TTA are due to a nearest-neighbor (NN) interaction, or due to a more long-range Förster-type process. Furthermore, we find a subtle interplay between TPQ and TTA: decreasing the contribution of one process can increase the contribution of the other process, so that the roll-off is not significantly reduced. Furthermore, we find that just analyzing the shape of the roll-off is insufficient for determining the relative role of TPQ and TTA. Subsequently, we investigate the wider validity of this picture using kMC simulations for idealized but realistic symmetric OLEDs, with an emissive layer containing a small concentration of phosphorescent dye molecules in a matrix material. Whereas for NN-interactions the roll-off can be reduced when the dye molecules act as shallow hole and electron traps, we find that such an approach becomes counterproductive for long-range TTA and TPQ. Developing well-founded OLED design rules will thus require that more quantitative information is available on the rate and detailed mechanism of the TPQ and TTA processes.

Long Term Functional Outcome of Tibial Tuberosity Advancement vs. Tibial Plateau Leveling Osteotomy and Extracapsular Repair in a Heterogeneous Population of Dogs.

PubMed

Krotscheck, Ursula; Nelson, Samantha A; Todhunter, Rory J; Stone, Marisa; Zhang, Zhiwu

2016-02-01

To determine a long term function of tibial tuberosity advancement (TTA) for treatment of ruptured cranial cruciate ligament (CCL) in dogs, and to compare this to the long term function of previously reported tibial plateau leveling osteotomy (TPLO), extracapsular reconstruction (ECR), and a population of normal dogs. Prospective clinical trial. Dogs with unilateral ruptured CCL treated with TTA (n = 14), TPLO (n = 15), and ECR (n = 23), and normal adult dogs (control, n = 80). Force plate gait analysis was performed at 1 time point for the normal control group and preoperatively, and at 2 and 8 weeks and 6 and 12 months postoperatively for the treatment groups. Using serial force plates, symmetry indices (SI) were calculated between the operated and unoperated pelvic limbs for peak vertical force (PVF), contact time (CT), and vertical impulse (VI). Ground reaction forces (GRF) of the treatment and control group were compared using a general linear model. Walk SI for dogs with TTA were not significantly different from the control group at 12 months postoperatively. At the trot, neither TTA nor ECR achieved normal GRF. SI of the TPLO group were not different from the normal control group by 6-12 months postoperatively. At the walk, TTA achieves normal function by 12 months; however, at the trot TTA is indistinguishable from ECR. TPLO resulted in operated limb function that was similar to the control population by 6-12 months postoperatively at the walk and the trot. © Copyright 2016 by The American College of Veterinary Surgeons.

Technical advance: stringent control of transgene expression in Arabidopsis thaliana using the Top10 promoter system

NASA Technical Reports Server (NTRS)

Love, J.; Scott, A. C.; Thompson, W. F.; Brown, C. S. (Principal Investigator)

2000-01-01

We show that the tightly regulated tetracycline-sensitive Top10 promoter system (Weinmann et al. Plant J. 1994, 5, 559-569) is functional in Arabidopsis thaliana. A pure breeding A. thaliana line (JL-tTA/8) was generated which expressed a chimeric fusion of the tetracycline repressor and the activation domain of Herpes simplex virus (tTA), from a single transgenic locus. Plants from this line were crossed with transgenics carrying the ER-targeted green fluorescent protein coding sequence (mGFP5) under control of the Top10 promoter sequence. Progeny from this cross displayed ER-targeted GFP fluorescence throughout the plant, indicating that the tTA-Top10 promoter interaction was functional in A. thaliana. GFP expression was repressed by 100 ng ml-1 tetracycline, an order of magnitude lower than the concentration used previously to repress expression in Nicotiana tabacum. Moreover, the level of GFP expression was controlled by varying the concentration of tetracycline in the medium, allowing a titred regulation of transgenic activity that was previously unavailable in A. thaliana. The kinetics of GFP activity were determined following de-repression of the Top10:mGFP5 transgene, with a visible ER-targeted GFP signal appearing from 24 to 48 h after de-repression.

The 5-HT7 receptor as a potential target for treating drug and alcohol abuse

PubMed Central

Hauser, Sheketha R.; Hedlund, Peter B.; Roberts, Amanda J.; Sari, Youssef; Bell, Richard L.; Engleman, Eric A.

2015-01-01

Alcohol and drug abuse take a large toll on society and affected individuals. However, very few effective treatments are currently available to treat alcohol and drug addiction. Basic and clinical research has begun to provide some insights into the underlying neurobiological systems involved in the addiction process. Several neurotransmitter pathways have been implicated and distinct reward neurocircuitry have been proposed—including the mesocorticolimbic dopamine (MCL-DA) system and the extended amygdala. The serotonin (5-HT) neurotransmitter system is of particular interest and multiple 5-HT receptors are thought to play significant roles in alcohol and drug self-administration and the development of drug dependence. Among the 5-HT receptors, the 5-HT7 receptor is currently undergoing characterization as a potential target for the treatment of several psychiatric disorders. Although this receptor has received only limited research regarding addictive behaviors, aspects of its neuroanatomical, biochemical, physiological, pharmacological, and behavioral profiles suggest that it could play a key role in the addiction process. For instance, genomic studies in humans have suggested a link between variants in the gene encoding the 5-HT7 receptor and alcoholism. Recent behavioral testing using high-affinity antagonists in mice and preliminary tests with alcohol-preferring rats suggest that this receptor could mediate alcohol consumption and/or reinforcement and play a role in seeking/craving behavior. Interest in the development of new and more selective pharmacological agents for this receptor will aid in examining the 5-HT7 receptor as a novel target for treating addiction. PMID:25628528

Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity.

PubMed

Ding, Baoyue; Wu, Xin; Fan, Wei; Wu, Zhaoyong; Gao, Jing; Zhang, Wei; Ma, Lulu; Xiang, Wang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2011-01-01

The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma.

Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity

PubMed Central

Ding, Baoyue; Wu, Xin; Fan, Wei; Wu, Zhaoyong; Gao, Jing; Zhang, Wei; Ma, Lulu; Xiang, Wang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2011-01-01

Background The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. Methods The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Results Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. Conclusion The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma. PMID:21976975

Bolder science needed now for protected areas.

PubMed

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.

In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5.

PubMed

Arya, Hemant; Syed, Safiulla Basha; Singh, Sorokhaibam Sureshkumar; Ampasala, Dinakar R; Coumar, Mohane Selvaraj

2017-06-16

Understanding the molecular mode of action of natural product is a key step for developing drugs from them. In this regard, this study is aimed to understand the molecular-level interactions of chemical constituents of Clerodendrum colebrookianum Walp., with anti-hypertensive drug targets using computational approaches. The plant has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets-Rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and phosphodiesterase 5 (PDE5). Docking studies showed that three chemical constituents (acteoside, martinoside, and osmanthuside β6) out of 21 reported from the plant to interact with the anti-hypertensive drug targets with good glide score. In addition, they formed H-bond interactions with the key residues Met156/Met157 of ROCK I/ROCK II and Gln817 of PDE5. Further, molecular dynamics (MD) simulation of protein-ligand complexes suggest that H-bond interactions between acteoside/osmanthuside β6 and Met156/Met157 (ROCK I/ROCK II), acteoside and Gln817 (PDE5) were stable. The present investigation suggests that the anti-hypertensive activity of the plant is due to the interaction of acteoside and osmanthuside β6 with ROCK and PDE5 drug targets. The identified molecular mode of binding of the plant constituents could help to design new drugs to treat hypertension.

Targeting IL-5Rα with antibody-conjugates reveals a strategy for imaging and therapy for invasive bladder cancer.

PubMed

Paquette, Michel; Vilera-Perez, Luis-Guillermo; Beaudoin, Simon; Ekindi-Ndongo, Nadia; Boudreaut, Pierre-Luc; Bonin, Marc-Andre; Battista, Marie-Claude; Bentourkia, M'hamed; Lopez, Angel F; Lecomte, Roger; Marsault, Eric; Guérin, Brigitte; Sabbagh, Robert; Leyton, Jeffrey V

2017-01-01

Despite the high interest and concern due to an increasing incidence and death rate, patients who develop muscle invasive bladder cancer (MIBC) have few options available. However, the past decade has produced many candidate bladder tumor-specific markers but further development of these markers is still needed for creating effective targeted medications to solve this urgent need. Interleukin-5 receptor α-subunit (IL-5Rα) has recently been reported to be involved in MIBC progression. Thus, we aimed to validate IL-5Rα as a target for antibody-conjugates to better manage patients with MIBC. Patients were recruited and their tumors were processed for IL-5Rα immunohistochemical analysis. NOD/SCID mice were also heterotopically implanted with the human MIBC HT-1376 and HT-B9 cell lines and established xenografts immunohistochemically evaluated for IL-5Rα and compared against patient tumors. Using the mAb A14, an antibody-drug conjugate (ADC) and a radiolabeled immunoconjugate (RIC) were developed by conjugating to vinblastine and to the positron emitter copper-64 ( 64 Cu), respectively. As a proof-of-concept for ADC and RIC efficacy, in vitro cytotoxicity and in vivo positron emission tomography (PET) imaging in tumor-bearing mice were performed, respectively. In addition, as rapid internalization and accumulation are important components for effective antibody-conjugates, we evaluated these aspects in response to IL-5 and 64 Cu-A14 treatments. Our findings suggest that although IL-5Rα protein expression is preferentially increased in MIBC, it is rapid IL-5Rα-mediated internalization allowing vinblastine-A14 to have cytotoxic activity and 64 Cu-A14 to detect MIBC tumors in vivo . This is the first report to elucidate the potential of IL-5Rα as an attractive MIBC target for antibody-conjugate applications.

Targeting IL-5Rα with antibody-conjugates reveals a strategy for imaging and therapy for invasive bladder cancer

PubMed Central

Vilera-Perez, Luis-Guillermo; Beaudoin, Simon; Ekindi-Ndongo, Nadia; Boudreaut, Pierre-Luc; Bonin, Marc-Andre; Battista, Marie-Claude; Bentourkia, M'hamed; Lopez, Angel F.; Lecomte, Roger; Marsault, Eric; Sabbagh, Robert; Leyton, Jeffrey V.

2017-01-01

ABSTRACT Despite the high interest and concern due to an increasing incidence and death rate, patients who develop muscle invasive bladder cancer (MIBC) have few options available. However, the past decade has produced many candidate bladder tumor-specific markers but further development of these markers is still needed for creating effective targeted medications to solve this urgent need. Interleukin-5 receptor α-subunit (IL-5Rα) has recently been reported to be involved in MIBC progression. Thus, we aimed to validate IL-5Rα as a target for antibody-conjugates to better manage patients with MIBC. Patients were recruited and their tumors were processed for IL-5Rα immunohistochemical analysis. NOD/SCID mice were also heterotopically implanted with the human MIBC HT-1376 and HT-B9 cell lines and established xenografts immunohistochemically evaluated for IL-5Rα and compared against patient tumors. Using the mAb A14, an antibody-drug conjugate (ADC) and a radiolabeled immunoconjugate (RIC) were developed by conjugating to vinblastine and to the positron emitter copper-64 (64Cu), respectively. As a proof-of-concept for ADC and RIC efficacy, in vitro cytotoxicity and in vivo positron emission tomography (PET) imaging in tumor-bearing mice were performed, respectively. In addition, as rapid internalization and accumulation are important components for effective antibody-conjugates, we evaluated these aspects in response to IL-5 and 64Cu-A14 treatments. Our findings suggest that although IL-5Rα protein expression is preferentially increased in MIBC, it is rapid IL-5Rα-mediated internalization allowing vinblastine-A14 to have cytotoxic activity and 64Cu-A14 to detect MIBC tumors in vivo. This is the first report to elucidate the potential of IL-5Rα as an attractive MIBC target for antibody-conjugate applications. PMID:29123949

miR-885-5p upregulation promotes colorectal cancer cell proliferation and migration by targeting suppressor of cytokine signaling.

PubMed

Su, Meng; Qin, Baoli; Liu, Fang; Chen, Yuze; Zhang, Rui

2018-07-01

The aim of the present study was to investigate the role of microRNA (miR)-885-5p in colorectal cancer cell proliferation and migration, and to determine the possible underlying molecular mechanisms. The expression of miR-885-5p in colorectal cancer tissue and cells was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of three suppressor of cytokine signaling (SOCS) factors were detected by RT-qPCR and western blotting. The effects of miR-885-5p on tumor cell proliferation and migration were studied using MTT and Transwell assays, respectively. Additionally, the expression levels of epithelial-mesenchymal transition (EMT)-related proteins (N-cadherin, E-cadherin, vimentin and Snail) were detected by RT-qPCR and western blot analysis. Furthermore, the target of miR-885-5p was predicted and confirmed using a luciferase reporter assay. miR-885-5p was demonstrated to be upregulated and SOCS was downregulated in colorectal cancer tissue, and cells. miR-885-5p suppression significantly inhibited tumor cell proliferation and migration, promoted E-cadherin expression, and inhibited the expression levels of N-cadherin, vimentin and Snail. Further studies showed that SOCS5, SOCS6 and SOCS7 were direct targets of miR-885-5p. The results suggest that miR-885-5p suppression inhibited cell proliferation and migration, and the EMT process by targeting SOCS5, SOCS6 and SOCS7 genes in colorectal cancer. miR-885-5p and SOCS may be used for the diagnosis and treatment of colorectal cancer.

Cytocompatible chitosan-graft-mPEG-based 5-fluorouracil-loaded polymeric nanoparticles for tumor-targeted drug delivery.

PubMed

Antoniraj, M Gover; Ayyavu, Mahesh; Henry, Linda Jeeva Kumari; Nageshwar Rao, Goutham; Natesan, Subramanian; Sundar, D Sathish; Kandasamy, Ruckmani

2018-03-01

Biodegradable materials like chitosan (CH) and methoxy polyethylene glycol (mPEG) are widely being used as drug delivery carriers for various therapeutic applications. In this study, copolymer (CH-g-mPEG) of CH and carboxylic acid terminated mPEG was synthesized by carbodiimide-mediated acid amine reaction. The resultant hydrophilic copolymer was characterized by Fourier transform infrared spectroscopy and 1 H NMR studies, revealing its relevant functional bands and proton peaks, respectively. Blank polymeric nanoparticles (B-PNPs) and 5-fluorouracil loaded polymeric nanoparticles (5-FU-PNPs) were formulated by ionic gelation method. Furthermore, folic acid functionalized FA-PNPs and FA-5-FU-PNPs were prepared for folate receptor-targeted drug delivery. FA-5-FU-PNPs were characterized by particle size, zeta potential, and in vitro drug release studies, resulting in 197.7 nm, +29.9 mv, and sustained drug release of 88% in 24 h, respectively. Cytotoxicity studies were performed for FA-PNPs and FA-5-FU-PNPs in MCF-7 cell line, which exhibited a cell viability of 80 and 41%, respectively. In vitro internalization studies were carried out for 5-FU-PNPs and FA-5-FU-PNPs which demonstrated increased cellular uptake of FA-5-FU-PNPs by receptor-mediated transport. Significant (p < .01) reduction (1.5-fold) of reactive oxygen species (ROS) accumulation was observed in lipopolysaccharides-stimulated RAW264.7 macrophages, revealing its potent antioxidant property. From the obtained results, it is concluded that folic acid functionalization of 5-FU-PNPs is an ideal approach for sustained and targeted drug delivery, thereby influencing better therapeutic effect.

The Effect of a Microprocessor Prosthetic Foot on Function and Quality of Life in Transtibial Amputees Who Are Limited Community Ambulators

DTIC Science & Technology

with greater range of motion and active power, will translate into improved functional performance, ambulatory safety (risk of falls) and quality of... life in trans-tibial amputees (TTA) who function as limited community ambulators. We will assess these outcomes in 54 veterans with TTA by randomizing

Plasmon-Enhanced Sub-Bandgap Photocatalysis via Triplet-Triplet Annihilation Upconversion for Volatile Organic Compound Degradation.

PubMed

Kim, Hyoung-Il; Weon, Seunghyun; Kang, Homan; Hagstrom, Anna L; Kwon, Oh Seok; Lee, Yoon-Sik; Choi, Wonyong; Kim, Jae-Hong

2016-10-18

This study demonstrates the first reported photocatalytic decomposition of an indoor air pollutant, acetaldehyde, using low-energy, sub-bandgap photons harnessed through sensitized triplet-triplet annihilation (TTA) upconversion (UC). To utilize low-intensity noncoherent indoor light and maximize photocatalytic activity, we designed a plasmon-enhanced sub-bandgap photocatalyst device consisting of two main components: (1) TTA-UC rubbery polymer films containing broad-band plasmonic particles (Ag-SiO 2 ) to upconvert sub-bandgap photons, and (2) nanodiamond (ND)-loaded WO 3 as a visible-light photocatalyst composite. Effective decomposition of acetaldehyde was achieved using ND/WO 3 (E g = 2.8 eV) coupled with TTA-UC polymer films that emit blue photons (λ Em = 425 nm, 2.92 eV) upconverted from green photons (λ Ex = 532 nm, 2.33 eV), which are wasted in most environmental photocatalysis. The overall photocatalytic efficiency was amplified by the broad-band surface plasmon resonance of AgNP-SiO 2 particles incorporated into the TTA-UC films.

An Improved Compressive Sensing and Received Signal Strength-Based Target Localization Algorithm with Unknown Target Population for Wireless Local Area Networks.

PubMed

Yan, Jun; Yu, Kegen; Chen, Ruizhi; Chen, Liang

2017-05-30

In this paper a two-phase compressive sensing (CS) and received signal strength (RSS)-based target localization approach is proposed to improve position accuracy by dealing with the unknown target population and the effect of grid dimensions on position error. In the coarse localization phase, by formulating target localization as a sparse signal recovery problem, grids with recovery vector components greater than a threshold are chosen as the candidate target grids. In the fine localization phase, by partitioning each candidate grid, the target position in a grid is iteratively refined by using the minimum residual error rule and the least-squares technique. When all the candidate target grids are iteratively partitioned and the measurement matrix is updated, the recovery vector is re-estimated. Threshold-based detection is employed again to determine the target grids and hence the target population. As a consequence, both the target population and the position estimation accuracy can be significantly improved. Simulation results demonstrate that the proposed approach achieves the best accuracy among all the algorithms compared.

MicroRNA-139-5p acts as a tumor suppressor by targeting ELTD1 and regulating cell cycle in glioblastoma multiforme

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

Dai, Shouping; Wang, Xianjun; Li, Xiao

MicroRNA-139-5p was identified to be significantly down-regulated in glioblastoma multiform (GBM) by miRNA array. In this report we aimed to clarify its biological function, molecular mechanisms and direct target gene in GBM. Twelve patients with GBM were analyzed for the expression of miR-139-5p by quantitative RT-PCR. miR-139-5p overexpression was established by transfecting miR-139-5p-mimic into U87MG and T98G cells, and its effects on cell proliferation were studied using MTT assay and colony formation assays. We concluded that ectopic expression of miR-139-5p in GBM cell lines significantly suppressed cell proliferation and inducing apoptosis. Bioinformatics coupled with luciferase and western blot assays alsomore » revealed that miR-139-5p suppresses glioma cell proliferation by targeting ELTD1 and regulating cell cycle. - Highlights: • miR-139-5p is downregulated in GBM. • miR-139-5p regulates cell proliferation through inducing apoptosis. • miR-139-5p regulates glioblastoma tumorigenesis by targeting 3′UTR of ELTD1. • miR-139-5p is involved in cell cycle regulation.« less

Triplet-triplet annihilation photon-upconversion: towards solar energy applications.

PubMed

Gray, Victor; Dzebo, Damir; Abrahamsson, Maria; Albinsson, Bo; Moth-Poulsen, Kasper

2014-06-14

Solar power production and solar energy storage are important research areas for development of technologies that can facilitate a transition to a future society independent of fossil fuel based energy sources. Devices for direct conversion of solar photons suffer from poor efficiencies due to spectrum losses, which are caused by energy mismatch between the optical absorption of the devices and the broadband irradiation provided by the sun. In this context, photon-upconversion technologies are becoming increasingly interesting since they might offer an efficient way of converting low energy solar energy photons into higher energy photons, ideal for solar power production and solar energy storage. This perspective discusses recent progress in triplet-triplet annihilation (TTA) photon-upconversion systems and devices for solar energy applications. Furthermore, challenges with evaluation of the efficiency of TTA-photon-upconversion systems are discussed and a general approach for evaluation and comparison of existing systems is suggested.

Beyond the binding site: in vivo identification of tbx2, smarca5 and wnt5b as molecular targets of CNBP during embryonic development.

PubMed

Armas, Pablo; Margarit, Ezequiel; Mouguelar, Valeria S; Allende, Miguel L; Calcaterra, Nora B

2013-01-01

CNBP is a nucleic acid chaperone implicated in vertebrate craniofacial development, as well as in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human muscle diseases. CNBP is highly conserved among vertebrates and has been implicated in transcriptional regulation; however, its DNA binding sites and molecular targets remain elusive. The main goal of this work was to identify CNBP DNA binding sites that might reveal target genes involved in vertebrate embryonic development. To accomplish this, we used a recently described yeast one-hybrid assay to identify DNA sequences bound in vivo by CNBP. Bioinformatic analyses revealed that these sequences are G-enriched and show high frequency of putative G-quadruplex DNA secondary structure. Moreover, an in silico approach enabled us to establish the CNBP DNA-binding site and to predict CNBP putative targets based on gene ontology terms and synexpression with CNBP. The direct interaction between CNBP and candidate genes was proved by EMSA and ChIP assays. Besides, the role of CNBP upon the identified genes was validated in loss-of-function experiments in developing zebrafish. We successfully confirmed that CNBP up-regulates tbx2b and smarca5, and down-regulates wnt5b gene expression. The highly stringent strategy used in this work allowed us to identify new CNBP target genes functionally important in different contexts of vertebrate embryonic development. Furthermore, it represents a novel approach toward understanding the biological function and regulatory networks involving CNBP in the biology of vertebrates.

Beyond the Binding Site: In Vivo Identification of tbx2, smarca5 and wnt5b as Molecular Targets of CNBP during Embryonic Development

PubMed Central

Mouguelar, Valeria S.; Allende, Miguel L.; Calcaterra, Nora B.

2013-01-01

CNBP is a nucleic acid chaperone implicated in vertebrate craniofacial development, as well as in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human muscle diseases. CNBP is highly conserved among vertebrates and has been implicated in transcriptional regulation; however, its DNA binding sites and molecular targets remain elusive. The main goal of this work was to identify CNBP DNA binding sites that might reveal target genes involved in vertebrate embryonic development. To accomplish this, we used a recently described yeast one-hybrid assay to identify DNA sequences bound in vivo by CNBP. Bioinformatic analyses revealed that these sequences are G-enriched and show high frequency of putative G-quadruplex DNA secondary structure. Moreover, an in silico approach enabled us to establish the CNBP DNA-binding site and to predict CNBP putative targets based on gene ontology terms and synexpression with CNBP. The direct interaction between CNBP and candidate genes was proved by EMSA and ChIP assays. Besides, the role of CNBP upon the identified genes was validated in loss-of-function experiments in developing zebrafish. We successfully confirmed that CNBP up-regulates tbx2b and smarca5, and down-regulates wnt5b gene expression. The highly stringent strategy used in this work allowed us to identify new CNBP target genes functionally important in different contexts of vertebrate embryonic development. Furthermore, it represents a novel approach toward understanding the biological function and regulatory networks involving CNBP in the biology of vertebrates. PMID:23667590

Combined targeting of STAT3 and STAT5: a novel approach to overcome drug resistance in chronic myeloid leukemia.

PubMed

Gleixner, Karoline V; Schneeweiss, Mathias; Eisenwort, Gregor; Berger, Daniela; Herrmann, Harald; Blatt, Katharina; Greiner, Georg; Byrgazov, Konstantin; Hoermann, Gregor; Konopleva, Marina; Waliul, Islam; Cumaraswamy, Abbarna A; Gunning, Patrick T; Maeda, Hiroshi; Moriggl, Richard; Deininger, Michael; Lion, Thomas; Andreeff, Michael; Valent, Peter

2017-09-01

In chronic myeloid leukemia, resistance against BCR-ABL1 tyrosine kinase inhibitors can develop because of BCR-ABL1 mutations, activation of additional pro-oncogenic pathways, and stem cell resistance. Drug combinations covering a broad range of targets may overcome resistance. CDDO-Me (bardoxolone methyl) is a drug that inhibits the survival of leukemic cells by targeting different pro-survival molecules, including STAT3. We found that CDDO-Me inhibits proliferation and survival of tyrosine kinase inhibitor-resistant BCR-ABL1 + cell lines and primary leukemic cells, including cells harboring BCR-ABL1 T315I or T315I + compound mutations. Furthermore, CDDO-Me was found to block growth and survival of CD34 + /CD38 - leukemic stem cells (LSC). Moreover, CDDO-Me was found to produce synergistic growth-inhibitory effects when combined with BCR-ABL1 tyrosine kinase inhibitors. These drug-combinations were found to block multiple signaling cascades and molecules, including STAT3 and STAT5. Furthermore, combined targeting of STAT3 and STAT5 by shRNA and STAT5-targeting drugs also resulted in synergistic growth-inhibition, pointing to a new efficient concept of combinatorial STAT3 and STAT5 inhibition. However, CDDO-Me was also found to increase the expression of heme-oxygenase-1, a heat-shock-protein that triggers drug resistance and cell survival. We therefore combined CDDO-Me with the heme-oxygenase-1 inhibitor SMA-ZnPP, which also resulted in synergistic growth-inhibitory effects. Moreover, SMA-ZnPP was found to sensitize BCR-ABL1 + cells against the combination 'CDDO-Me+ tyrosine kinase inhibitor'. Together, combined targeting of STAT3, STAT5, and heme-oxygenase-1 overcomes resistance in BCR-ABL1 + cells, including stem cells and highly resistant sub-clones expressing BCR-ABL1 T315I or T315I-compound mutations. Whether such drug-combinations are effective in tyrosine kinase inhibitor-resistant patients with chronic myeloid leukemia remains to be elucidated. Copyright

Propagation Characteristics in an Underground Shopping Area for 5GHz-band Wireless Access Systems

NASA Astrophysics Data System (ADS)

Itokawa, Kiyohiko; Kita, Naoki; Sato, Akio; Matsue, Hideaki; Mori, Daisuke; Watanabe, Hironobu

5-GHz band wireless access systems, such as the RLAN (Radio Local Area Network) system of IEEE802.11a, HiperLAN/2, HiSWANa and AWA, are developed and provide transmission rates over 20 Mbps for indoor use. Those 5-GHz access systems are expected to extend service areas from the office to the so-called “hot-spot" in public areas. Underground shopping malls are one of the anticipated service areas for such a nomadic wireless access service. Broadband propagation characteristics are required for radio zone design in an underground mall environment despite previous results obtained by narrow band measurements. This paper presents results of an experimental study on the propagation characteristics for broadband wireless access systems in an underground mall environment. First, broadband propagation path loss is measured and formulated considering human body shadowing. A ray trace simulation is used to clarify the basic propagation mechanism in such a closed environment. Next, a distance dependency of the delay spread during a crowded time period, rush hour, is found to be at most 65 nsec, which is under the permitted maximum value of the present 5-GHz systems. Finally, above propagation characteristics support the result of transmission test carried out by using AWA equipment.

Constraints on global temperature target overshoot

NASA Astrophysics Data System (ADS)

MacMartin, D. G.; Ricke, K.; Millar, R.

2016-12-01

The climate science and policy communities are beginning to assess the feasibility and potential benefits of limiting global warming to 1.5°C or 2°C. Understanding the dependence of the magnitude and duration of possible temporary exceedance (i.e., "overshoot") of these targets on sustainable energy decarbonization futures and carbon dioxide (CO2) removal rates will be an important contribution of the scientific community to this policy discussion. Drawing upon results from the mitigation literature and the IPCC Working Group 3 (WG3) scenario database, we examine the global mean temperature implications of differing independent pathways for the decarbonization of global energy supply and the implementation of negative emissions technologies. We find that within the range of decarbonization and negative emissions futures considered by WG3, the most ambitious rates of both decarbonization and deployment of negative emissions technologies are required to avoid overshoot of 1.5°C. The magnitude of temperature overshoot is more sensitive to the rate of decarbonization, but limiting the duration of overshoot to less than two centuries will require ambitious deployment of both decarbonization and negative emissions technology. The dependencies of temperature overshoots properties upon currently untested negative emissions technologies suggests that it will be important to assess how climate impacts depend on the magnitude and duration of overshoot, not just long term residual warming. As a new round of research proceeds with a 1.5°C threshold in mind, it will be important to understand the drivers behind various global temperature linked impacts and how these are influenced by both the duration and magnitude of a temporary overshoot of the target. This understanding will allow policy makers to better link climate policy goals to specific technological needs. Figure: Magnitude and duration of 1.5°C temperature target overshoot for "likely" range of climate response

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

USGS Publications Warehouse

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

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

NASA Astrophysics Data System (ADS)

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.

Construction of METHFR shRNA/5-fluorouracil co-loaded folate-targeted chitosan polymeric nanoparticles and its anti-carcinoma effect on gastric cells growth

NASA Astrophysics Data System (ADS)

Xin, Lin; Fan, Ji-Chang; Le, Yi-Guan; Zeng, Fei; Cheng, Hua; Hu, Xiao-yun; Cao, Jia-Qing

2016-05-01

PEGylated and folate-targeted chitosan polymeric nanoparticles (FPNs) for the treatment of gastric carcinoma were prepared successfully. OQC-anchored folate conjugates were synthesized and used in assembling FPNs nano-system for enhancing intracellular uptake against folate receptor overexpressing cancer cells. The results indicated that folate-targeted chitosan polymeric nanoparticles (CPNs) can reverse drug-resistant SGC-7901 cells of 5-fluorouracil (5-FU) compared with non-targeted CPNs. Increased therapeutic efficiency of 5-FU/METHFR shRNA co-loaded PNs were also tested in SGC-7901 cells and compaed with 5-FU or METHFR shRNA in solution, which was associated with increased cell inhibition function for single drug group and synergistic effects of 5-FU and METHFR shRNA at 2.0 µg/mL FPNs concentration. In addition, the cell accumulation levels of 5-FU in SGC-7901 cells was time dependent for these nanoparticles. FPNs (effective diameter: 83.2 ± 1.1 nm; polydispersity index: 0.193) could significantly boost cellular accumulation of 5-FU and overcome the drug efflux mechanism of MDR than 5-FU-loaded NPNs and 5-FU in solution. In conclusion, ligand-targeted PNs can be used as a potentially effective drug delivery system.

Increased importance of methane reduction for a 1.5 degree target

NASA Astrophysics Data System (ADS)

Collins, William J.; Webber, Christopher P.; Cox, Peter M.; Huntingford, Chris; Lowe, Jason; Sitch, Stephen; Chadburn, Sarah E.; Comyn-Platt, Edward; Harper, Anna B.; Hayman, Garry; Powell, Tom

2018-04-01

To understand the importance of methane on the levels of carbon emission reductions required to achieve temperature goals, a processed-based approach is necessary rather than reliance on the transient climate response to emissions. We show that plausible levels of methane (CH4) mitigation can make a substantial difference to the feasibility of achieving the Paris climate targets through increasing the allowable carbon emissions. This benefit is enhanced by the indirect effects of CH4 on ozone (O3). Here the differing effects of CH4 and CO2 on land carbon storage, including the effects of surface O3, lead to an additional increase in the allowable carbon emissions with CH4 mitigation. We find a simple robust relationship between the change in the 2100 CH4 concentration and the extra allowable cumulative carbon emissions between now and 2100 (0.27 ± 0.05 GtC per ppb CH4). This relationship is independent of modelled climate sensitivity and precise temperature target, although later mitigation of CH4 reduces its value and thus methane reduction effectiveness. Up to 12% of this increase in allowable emissions is due to the effect of surface ozone. We conclude early mitigation of CH4 emissions would significantly increase the feasibility of stabilising global warming below 1.5 °C, alongside having co-benefits for human and ecosystem health.

Micro-channel-based high specific power lithium target

NASA Astrophysics Data System (ADS)

Mastinu, P.; Martın-Hernández, G.; Praena, J.; Gramegna, F.; Prete, G.; Agostini, P.; Aiello, A.; Phoenix, B.

2016-11-01

A micro-channel-based heat sink has been produced and tested. The device has been developed to be used as a Lithium target for the LENOS (Legnaro Neutron Source) facility and for the production of radioisotope. Nevertheless, applications of such device can span on many areas: cooling of electronic devices, diode laser array, automotive applications etc. The target has been tested using a proton beam of 2.8MeV energy and delivering total power shots from 100W to 1500W with beam spots varying from 5mm2 to 19mm2. Since the target has been designed to be used with a thin deposit of lithium and since lithium is a low-melting-point material, we have measured that, for such application, a specific power of about 3kW/cm2 can be delivered to the target, keeping the maximum surface temperature not exceeding 150° C.

NHSA Position Paper: The Design of a Head Start Training and Technical Assistance System.

ERIC Educational Resources Information Center

NHSA Journal, 1994

1994-01-01

This position paper examines the current Head Start training and technical assistance (TTA) system and proposes specific improvements. These include the creation of regional TTA offices, the use of satellite and interactive communications technology, and a reevaluation of the role of teaching centers, national training contracts, and Head Start…

US EPA Nonattainment Areas and Designations-Annual PM2.5 (1997 NAAQS)

EPA Pesticide Factsheets

This web service contains the following layers: PM2.5 Annual 1997 NAAQS State Level and PM2.5 Annual 1997 NAAQS National . It also contains the following tables: maps99.FRED_MAP_VIEWER.%fred_area_map_data and maps99.FRED_MAP_VIEWER.%fred_area_map_view. Full FGDC metadata records for each layer may be found by clicking the layer name at the web service endpoint (https://gispub.epa.gov/arcgis/rest/services/OAR_OAQPS/NAA1997PM25Annual/MapServer) and viewing the layer description.These layers identify areas in the U.S. where air pollution levels have not met the National Ambient Air Quality Standards (NAAQS) for criteria air pollutants and have been designated nonattainment?? areas (NAA). The data are updated weekly from an OAQPS internal database. However, that does not necessarily mean the data have changed. The EPA Office of Air Quality Planning and Standards (OAQPS) has set National Ambient Air Quality Standards for six principal pollutants, which are called criteria pollutants. Under provisions of the Clean Air Act, which is intended to improve the quality of the air we breathe, EPA is required to set National Ambient Air Quality Standards for six common air pollutants. These commonly found air pollutants (also known as criteria pollutants) are found all over the United States. They are particle pollution (often referred to as particulate matter), ground-level ozone, carbon monoxide, sulfur oxides, nitrogen oxides, and lead. For each criteria pollutant, there

Geological structure and ore mineralization of the South Sopchinsky and Gabbro-10 massifs and the Moroshkovoe Lake target, Monchegorsk area, Kola Peninsula, Russia

NASA Astrophysics Data System (ADS)

Pripachkin, Pavel V.; Rundkvist, Tatyana V.; Miroshnikova, Yana A.; Chernyavsky, Alexey V.; Borisenko, Elena S.

2016-12-01

The South Sopchinsky massif (SSM), Gabbro-10 (G-10) massif, and Moroshkovoe Lake (ML) target Monchegorsk area, Kola Peninsula, are located at the junction of the Monchepluton and Monchetundra layered intrusions. The intrusions were studied in detail as they are targets for platinum-group element (PGE) mineralization. The rocks in these targets comprise medium- to coarse-grained mesocratic to leucocratic gabbronorites, medium-grained mesocratic to melanocratic norites and pyroxenites, and various veins mainly comprising norite, plagioclase-amphibole-magnetite rocks, and quartz-magnetite rocks. The veins contain Ni-Cu-PGE mineralization associated with magnetite and chromite. In all targets, the contacts between gabbronorite and norite-pyroxenite are undulating, and the presence of magmatic (intrusive) breccias suggests that these rocks formed through mingling of two distinct magmatic pulses. In places, the gabbronorites clearly crosscut the modal layering of the norites and pyroxenites. Trace element data indicate that the gabbronorites have similar compositions to rocks of the upper part of the Monchetundra intrusion, whereas the norites and pyroxenites resemble rocks from the lower to intermediate stratigraphic levels of the Monchepluton, such as in the Nude-Poaz and Sopcha massifs. Sulfide mineralization in the studied targets principally consists of secondary bornite, millerite, and chalcopyrite. In contrast, the primary sulfide assemblage within the layered sequence of the adjacent Monchepluton is characterized by pentlandite, chalcopyrite, and pyrrhotite. Therefore, the mineralization in the studied targets is interpreted to be of a contact style. We argue that the studied area represents the contact zone between gabbronorites of the Monchetundra intrusion and norites and pyroxenites of the Monchepluton. In addition, the rocks were overprinted by postmagmatic veining and remobilization of contact style sulfide and PGE mineralization.

Improving Photovoltaic Performance of a Fused-Ring Azepinedione Copolymer via a D-A-A Design.

PubMed

Zhang, Honghong; Li, Ting; Xiao, Zuo; Lei, Zhongli; Ding, Liming

2018-04-01

Two conjugated copolymer donors, PTTABDT and PBTTABDT, based on a fused-ring azepinedione acceptor unit, 5-(2-octyldodecyl)-4H-thieno[2',3':4,5]thieno[3,2-c]thieno[2',3':4,5]thieno[2,3-e]azepine-4,6(5H)-dione (TTA), are prepared. PTTABDT possesses a conventional donor-acceptor (D-A) structure with one TTA in the repeat unit, while PBTTABDT has a D-A-A structure with two TTAs in the repeat unit. Compared with PTTABDT, PBTTABDT shows a deeper highest occupied molecular orbital (HOMO) level, a narrower bandgap, and a higher hole mobility, and exhibits better performance in bulk heterojunction solar cells. Power conversion efficiencies of 6.18% and 7.81% are achieved from PTTABDT:PC 71 BM and PBTTABDT:PC 71 BM solar cells, respectively. The higher performance of PBTTABDT:PC 71 BM solar cells results from the enhanced open-circuit voltage (V oc ) and short-circuit current density (  J sc ). © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identifying hydrologically sensitive areas using LiDAR DEMs to mitigate critical source areas of diffuse pollution: development and application

NASA Astrophysics Data System (ADS)

Thomas, Ian; Jordan, Phil; Mellander, Per-Erik; Fenton, Owen; Shine, Oliver; hUallacháin, Daire Ó.; Creamer, Rachel; McDonald, Noeleen; Dunlop, Paul; Murphy, Paul

2016-04-01

Identifying critical source areas (CSAs) of diffuse pollution in agricultural catchments requires the accurate identification of hydrologically sensitive areas (HSAs) at highest propensity for generating surface runoff and transporting pollutants such as phosphorus (P). A new GIS-based HSA Index is presented that identifies HSAs at the sub-field scale. It uses a soil topographic index (STI) and accounts for the hydrological disconnection of overland flow via topographic impediment from flow sinks such as hedgerows and depressions. High resolution (0.25-2 m) LiDAR Digital Elevation Models (DEMs) are utilised to capture these microtopographic controls on flow pathways and hydrological connectivity. The HSA Index was applied to four agricultural catchments (~7.5-12 km2) with contrasting topography and soil types. Catchment HSA sizes were estimated using high resolution rainfall-quickflow measurements during saturated winter storm events in 2009-2014, and mapped using the HSA Index. HSA sizes ranged from 1.6-3.4% of the catchment area during median storm events and 2.9-8.5% during upper quartile events depending on whether well or poorly drained soils dominated, which validated HSA Index value distributions. Total flow sink volume capacities ranged from 8,298-59,584 m3 and caused 8.5-24.2% of overland-flow-generating-areas and 16.8-33.4% of catchment areas to become hydrologically disconnected from the open drainage channel network. HSA maps identified 'delivery points' along surface runoff pathways where transported pollutants such as P are delivered to the open drainage network. Using these as proposed locations for targeting mitigation measures such as riparian buffer strips (RBS) reduced costs compared to blanket implementation within an example agri-environment scheme by 66% and 91% over 1 and 5 years respectively, which included LiDAR DEM acquisition costs. Considering that HSAs are often the dominant P CSA factor in agricultural catchments and can override

p21 Activated Kinase 5 Activates Raf-1 and Targets it to Mitochondria

PubMed Central

Wu, Xiaochong; Carr, Heather S.; Dan, Ippeita; Ruvolo, Peter P.; Frost, Jeffrey A.

2008-01-01

Raf-1 is an important effector of Ras mediated signaling and is a critical regulator of the ERK/MAPK pathway. Raf-1 activation is controlled in part by phosphorylation on multiple residues, including an obligate phosphorylation site at serine 338. Previously PAK1 and casein kinase II have been implicated as serine 338 kinases. To identify novel kinases that phosphorylate this site, we tested the ability of group II PAKs (PAKs 4-6) to control serine 338 phosphorylation. We observed that all group II PAKs were efficient serine 338 kinases, although only PAK1 and PAK5 significantly stimulated Raf-1 kinase activity. We also showed that PAK5 forms a tight complex with Raf-1 in the cell, but not A-Raf or B-Raf. Importantly, we also demonstrated that the association of Raf-1 with PAK5 targets a subpopulation of Raf-1 to mitochondria. These data indicate that PAK5 is a potent regulator of Raf-1 activity and may control Raf-1 dependent signaling at the mitochondria. PMID:18465753

CaV3.1 isoform of T-type calcium channels supports excitability of rat and mouse ventral tegmental area neurons.

PubMed

Tracy, Matthew E; Tesic, Vesna; Stamenic, Tamara Timic; Joksimovic, Srdjan M; Busquet, Nicolas; Jevtovic-Todorovic, Vesna; Todorovic, Slobodan M

2018-03-23

Recent data have implicated voltage-gated calcium channels in the regulation of the excitability of neurons within the mesolimbic reward system. While the attention of most research has centered on high voltage L-type calcium channel activity, the presence and role of the low voltage-gated T-type calcium channel (T-channels) has not been well explored. Hence, we investigated T-channel properties in the neurons of the ventral tegmental area (VTA) utilizing wild-type (WT) rats and mice, Ca V 3.1 knock-out (KO) mice, and TH-eGFP knock-in (KI) rats in acute horizontal brain slices of adolescent animals. In voltage-clamp experiments, we first assessed T-channel activity in WT rats with characteristic properties of voltage-dependent activation and inactivation, as well as characteristic crisscrossing patterns of macroscopic current kinetics. T-current kinetics were similar in WT mice and WT rats but T-currents were abolished in Ca V 3.1 KO mice. In ensuing current-clamp experiments, we observed the presence of hyperpolarization-induced rebound burst firing in a subset of neurons in WT rats, as well as dopaminergic and non-dopaminergic neurons in TH-eGFP KI rats. Following the application of a pan-selective T-channel blocker TTA-P2, rebound bursting was significantly inhibited in all tested cells. In a behavioral assessment, the acute locomotor increase induced by a MK-801 (Dizocilpine) injection in WT mice was abolished in Ca V 3.1 KO mice, suggesting a tangible role for 3.1 T-type channels in drug response. We conclude that pharmacological targeting of Ca V 3.1 isoform of T-channels may be a novel approach for the treatment of disorders of mesolimbic reward system. Copyright © 2018. Published by Elsevier Ltd.

Retrospective Analysis of Dose Titration and Serum Testosterone Level Assessments in Patients Treated With Topical Testosterone.

PubMed

Muram, David; Kaltenboeck, Anna; Boytsov, Natalie; Hayes-Larson, Eleanor; Ivanova, Jasmina; Birnbaum, Howard G; Swindle, Ralph

2015-11-01

Patterns of care following topical testosterone agent (TTA) initiation are poorly understood. This study aimed to characterize care following TTA initiation and compare results between patients with and without a serum testosterone (T) assay within 30 days before and including TTA initiation. Adult men (N=4,146) initiating TTAs from January 1, 2011, to March 31, 2012, were identified from a commercially insured database. Patients were included if they initiated at recommended starting dose (RSD) and had ≥12 and ≥6 months of continuous eligibility preinitiation (baseline) and postinitiation (study period), respectively. Patients were stratified by preinitiation T assay. Maintenance dose attainment month was determined using unadjusted generalized estimating equations regression to compare dose relative to RSD month by month. Outcomes included maintenance dose attainment month, time to stopping of index TTA refills or a claim for nonindex testosterone replacement therapy (TRT), and proportion of patients with study period T assay or diagnosis of hypogonadism (HG) or another low testosterone condition, and were compared using chi-square and Wilcoxon rank-sum tests for categorical and continuous variables, respectively. Maintenance dose was attained in Month 4 postinitiation, at 115.2% of RSD. Approximately 46% of patients had a preinitiation T assay; these men were more likely to receive a diagnosis of HG or another low testosterone condition, to have a follow-up T assay, to continue treatment by filling a nonindex TRT, and less likely to stop refilling treatment with their index TTA. Differences in care following TTA initiation suggest that preinitiation T assays (i.e., guideline-based care) may be helpful in ensuring treatment benefits. © The Author(s) 2014.

5 CFR 532.307 - Determinating whether a dominant industry exists in a wage area.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Determinating whether a dominant industry... § 532.307 Determinating whether a dominant industry exists in a wage area. (a) The chairperson of the... written report concerning the existence of specialized industries within the wage area. (3) The report of...

5 CFR 532.307 - Determinating whether a dominant industry exists in a wage area.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Determinating whether a dominant industry... § 532.307 Determinating whether a dominant industry exists in a wage area. (a) The chairperson of the... written report concerning the existence of specialized industries within the wage area. (3) The report of...

5 CFR 532.307 - Determinating whether a dominant industry exists in a wage area.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Determinating whether a dominant industry... § 532.307 Determinating whether a dominant industry exists in a wage area. (a) The chairperson of the... written report concerning the existence of specialized industries within the wage area. (3) The report of...

5 CFR 532.307 - Determinating whether a dominant industry exists in a wage area.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Determinating whether a dominant industry... § 532.307 Determinating whether a dominant industry exists in a wage area. (a) The chairperson of the... written report concerning the existence of specialized industries within the wage area. (3) The report of...

Thermochromic VO2 Films Deposited by RF Magnetron Sputtering Using V2O3 or V2O5 Targets

NASA Astrophysics Data System (ADS)

Shigesato, Yuzo; Enomoto, Mikiko; Odaka, Hidehumi

2000-10-01

Thermochromic monoclinic-tetragonal VO2 films were successfully deposited on glass substrates with high reproducibility by rf magnetron sputtering using V2O3 or V2O5 targets. In the case of reactive sputtering using a V-metal target, the VO2 films could be obtained only under the very narrow deposition conditions of the “transition region” where the deposition rate decreases drastically with increasing oxygen gas flow rate. In the case of a V2O3 target, polycrystalline VO2 films with a thickness of 400 to 500 nm were obtained by the introduction of oxygen gas [O2/(Ar+O2)=1--1.5%], whereas hydrogen gas [H2/(Ar+H2)=2.5--10%] was introduced in the case of a V2O5 target. Furthermore, the VO2 films were successfully grown heteroepitaxially on a single-crystal sapphire [α-Al2O3(001)] substrate, where the epitaxial relationship was confirmed to be VO2(010)[100]\\parallelAl2O3(001)[100], [010], [\\bar{1}\\bar{1}0] by an X-ray diffraction pole figure measurement. The resistivity ratio between semiconductor and metal phases for the heteroepitaxial VO2 films was much larger than the ratio of the polycrystalline films on glass substrates under the same deposition conditions.

Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

PubMed

Liu, Shuo; Niger, Corinne; Koh, Eugene Y; Stains, Joseph P

2015-01-01

Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs) could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis)-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases like

43 CFR 5.1 - Areas administered by U.S. Fish and Wildlife Service or National Park Service.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Wildlife Service or National Park Service. 5.1 Section 5.1 Public Lands: Interior Office of the Secretary... JURISDICTION OF THE DEPARTMENT OF THE INTERIOR § 5.1 Areas administered by U.S. Fish and Wildlife Service or... track made on any area administered by the U.S. Fish and Wildlife Service or the National Park Service...

43 CFR 5.1 - Areas administered by U.S. Fish and Wildlife Service or National Park Service.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Wildlife Service or National Park Service. 5.1 Section 5.1 Public Lands: Interior Office of the Secretary... JURISDICTION OF THE DEPARTMENT OF THE INTERIOR § 5.1 Areas administered by U.S. Fish and Wildlife Service or... track made on any area administered by the U.S. Fish and Wildlife Service or the National Park Service...

43 CFR 5.1 - Areas administered by U.S. Fish and Wildlife Service or National Park Service.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Wildlife Service or National Park Service. 5.1 Section 5.1 Public Lands: Interior Office of the Secretary... JURISDICTION OF THE DEPARTMENT OF THE INTERIOR § 5.1 Areas administered by U.S. Fish and Wildlife Service or... track made on any area administered by the U.S. Fish and Wildlife Service or the National Park Service...

Tumor Targeting and Pharmacokinetics of a Near-Infrared Fluorescent-Labeled δ-Opioid Receptor Antagonist Agent, Dmt-Tic-Cy5.

PubMed

Huynh, Amanda Shanks; Estrella, Veronica; Stark, Valerie E; Cohen, Allison S; Chen, Tingan; Casagni, Todd J; Josan, Jatinder S; Lloyd, Mark C; Johnson, Joseph; Kim, Jongphil; Hruby, Victor J; Vagner, Josef; Morse, David L

2016-02-01

Fluorescence molecular imaging can be employed for the development of novel cancer targeting agents. Herein, we investigated the pharmacokinetics (PK) and cellular uptake of Dmt-Tic-Cy5, a delta-opioid receptor (δOR) antagonist-fluorescent dye conjugate, as a tumor-targeting molecular imaging agent. δOR expression is observed normally in the CNS, and pathologically in some tumors, including lung liver and breast cancers. In vitro, in vivo, and ex vivo experiments were conducted to image and quantify the fluorescence signal associated with Dmt-Tic-Cy5 over time using in vitro and intravital fluorescence microscopy and small animal fluorescence imaging of tumor-bearing mice. We observed specific retention of Dmt-Tic-Cy5 in tumors with maximum uptake in δOR-expressing positive tumors at 3 h and observable persistence for >96 h; clearance from δOR nonexpressing negative tumors by 6 h; and systemic clearance from normal organs by 24 h. Live-cell and intravital fluorescence microscopy demonstrated that Dmt-Tic-Cy5 had sustained cell-surface binding lasting at least 24 h with gradual internalization over the initial 6 h following administration. Dmt-Tic-Cy5 is a δOR-targeted agent that exhibits long-lasting and specific signal in δOR-expressing tumors, is rapidly cleared from systemic circulation, and is not retained in non-δOR-expressing tissues. Hence, Dmt-Tic-Cy5 has potential as a fluorescent tumor imaging agent.