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

PubMed

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

2013-06-01

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

MicroRNA-187 regulates gastric cancer progression by targeting the tumor suppressor CRMP1

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

Ren, Lian; Li, Fang; Di, Maojun

Aberrant expression of microRNAs contributes to the initiation and progression of numerous human cancers. The underlying effects and molecular mechanisms of microRNA-187 (miR-187) in gastric cancer (GC) remain unclear. The present study reports that miR-187 was significantly overexpressed in GC tissues compared to that in non-tumor tissues and was associated with malignant clinical factors such as depth of invasion (P = 0.005), tumor size (P = 0.024), lymph node metastasis (P = 0.048), and TNM stage (P = 0.035). Additionally, miR-187 promoted tumor growth in vivo, and significantly increased migration, invasion, and proliferation, but inhibited apoptosis in GC cells. It was found that collapsin response mediator protein 1 (CRMP1),more » a tumor suppressor, was a direct downstream target of miR-187 in GC. Furthermore, CRMP1 silencing resulted in similar effects on cell proliferation, migration, and apoptosis as those of miR-187 overexpressing GC cells. Additionally, the effects of miR-187 inhibitor on cell migration and cell apoptosis were reversed by CRMP1 downregulation. In summary, miR-187 promotes tumor progression by regulating CRMP1 expression in GC and may thus be a potential prognostic marker and a therapeutic target in GC. - Highlights: • miR-187 was significantly overexpressed in GC tissues and associated with malignant clinical factors. • miR-187 significantly increased migration, invasion, and proliferation, but inhibited apoptosis in GC cells. • CRMP1 tumor suppressor is a direct target of miR-187 in GC. • Overexpression of miR-187 promoted GC progression by targeting tumor suppressor gene CRMP1.« less

The Role of BPTF in Melanoma Progression and in Response to BRAF-Targeted Therapy

PubMed Central

Dar, Altaf A.; Nosrati, Mehdi; Bezrookove, Vladimir; de Semir, David; Majid, Shahana; Thummala, Suresh; Sun, Vera; Tong, Schuyler; Leong, Stanley P. L.; Minor, David; Billings, Paul R.; Soroceanu, Liliana; Debs, Robert; Miller, James R.; Sagebiel, Richard W.

2015-01-01

Background: Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we explore the oncogenic effects of BPTF in melanoma. Methods: The consequences of differential expression of BPTF were explored using shRNA-mediated knockdown in several melanoma cell lines. Immunoblotting was used to assess the expression of various proteins regulated by BPTF. The functional role of BPTF in melanoma progression was investigated using assays of colony formation, invasion, cell cycle, sensitivity to selective BRAF inhibitors, and in xenograft models of melanoma progression (n = 12 mice per group). The biomarker role of BPTF in melanoma progression was assessed using fluorescence in situ hybridization and immunohistochemical analyses. All statistical tests were two-sided. Results: shRNA-mediated BPTF silencing suppressed the proliferative capacity (by 65.5%) and metastatic potential (by 66.4%) of melanoma cells. Elevated BPTF copy number (mean ≥ 3) was observed in 28 of 77 (36.4%) melanomas. BPTF overexpression predicted poor survival in a cohort of 311 melanoma patients (distant metastasis-free survival P = .03, and disease-specific survival P = .008), and promoted resistance to BRAF inhibitors in melanoma cell lines. Metastatic melanoma tumors progressing on BRAF inhibitors contained low BPTF-expressing, apoptotic tumor cell subclones, indicating the continued presence of drug-responsive subclones within tumors demonstrating overall resistance to anti-BRAF agents. Conclusions: These studies demonstrate multiple protumorigenic functions for BPTF and identify it as a novel target for anticancer therapy. They also suggest the combination of BPTF targeting with BRAF inhibitors as a novel therapeutic strategy for melanomas with mutant BRAF. PMID:25713167

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

PubMed

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

2014-01-01

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

Overview of Progress on the LANSCE Accelerator and Target Facilities Improvement Program

NASA Astrophysics Data System (ADS)

Macek, R. J.; Brun, T.; Donahue, J. B.; Fitzgerald, D. H.

1997-05-01

Three projects to improve the performance of the accelerator and target facilities for the Los Alamos Neutron Science Center have been initiated since 1994. The LANSCE Reliability Improvement Project was separated into two phases. Phase I, completed in 1995, was targeted at near-term improvements to beam availability that could be completed in a year. Phase II, now underway, consists of two projects: 1) converting the beam injection into the Proton Storage Ring (PSR) from the present two-step process H^- to H^0 to H^+) to direct injection of H^- beam in one step (H^- to H^+), and 2) an upgrade of the spallation neutron production target which will reduce the target change-out time from about a year to about three weeks. The third project, the SPSS Enhancement Project, is aimed at increasing the PSR output beam current from the present 70 μA at 20 Hz to 200 μA at 30 Hz, plus implementing seven new neutron scattering instruments. Objectives, plans, results and progress to date will be summarized.

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.

The soil biota composition along a progressive succession of secondary vegetation in a karst area.

PubMed

Zhao, Jie; Li, Shengping; He, Xunyang; Liu, Lu; Wang, Kelin

2014-01-01

Karst ecosystems are fragile and are in many regions degraded by anthropogenic activities. Current management of degraded karst areas focuses on aboveground vegetation succession or recovery and aims at establishing a forest ecosystem. Whether progressive succession of vegetation in karst areas is accompanied by establishment of soil biota is poorly understood. In the present study, soil microbial and nematode communities, as well as soil physico-chemical properties were studied along a progressive succession of secondary vegetation (from grassland to shrubland to forest) in a karst area in southwest China. Microbial biomass, nematode density, ratio of fungal to bacterial biomass, nematode structure index, and nematode enrichment index decreased with the secondary succession in the plant community. Overall, the results indicated a pattern of declines in soil biota abundance and food web complexity that was associated with a decrease in soil pH and a decrease in soil organic carbon content with the progressive secondary succession of the plant community. Our findings suggest that soil biota amendment is necessary during karst ecosystem restoration and establishment and management of grasslands may be feasible in karst areas.

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

PubMed

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

2018-05-01

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

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.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2011-04-15

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

Progressive alterations of the auditory association areas in young non-psychotic offspring of schizophrenia patients.

PubMed

Bhojraj, Tejas S; Sweeney, John A; Prasad, Konasale M; Eack, Shaun; Rajarethinam, Rajaprabhakaran; Francis, Alan N; Montrose, Debra M; Keshavan, Matcheri S

2011-02-01

Schizophrenia may involve progressive alterations of structure and hemispheric lateralization of auditory association areas (AAA) within the superior temporal gyrus. These alterations may be greater in male patients. It is unclear if these deficits are state-dependent or whether they predate illness onset and reflect familial diathesis. We sought to compare AAA cortical thickness, surface area and lateralization across adolescent and young adult non-psychotic offspring of schizophrenia patients (OS) and healthy controls at baseline and one year follow-up. We also assessed the moderating effect of gender on these measures. Fifty-six OS and thirty-six control subjects were assessed at baseline and at follow-up on AAA surface area and thickness using FreeSurfer to process T1-MRI-images. We used repeated measures ANCOVAs, controlling intra cranial volume and age with assessment-time and side as within-subject factors and gender and study group as between-subject factors. Surface area deficit in OS was greater on the left than on the right, as reflected in a lower surface area laterality-index (left-right/left + right × 100) in OS compared to controls. Left, but not right surface area and surface area laterality-index showed a longitudinal decline in OS compared to controls. Male OS declined more than controls on surface area and thickness. Left AAA surface area may progressively decline in young non-psychotic offspring at familial diathesis for schizophrenia causing a continuing reversal of the leftward AAA lateralization. Progressive surface area reduction and thinning of AAA may be more prominent in young non-psychotic male offspring at risk for schizophrenia. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Soil Biota Composition along a Progressive Succession of Secondary Vegetation in a Karst Area

PubMed Central

He, Xunyang; Liu, Lu; Wang, Kelin

2014-01-01

Karst ecosystems are fragile and are in many regions degraded by anthropogenic activities. Current management of degraded karst areas focuses on aboveground vegetation succession or recovery and aims at establishing a forest ecosystem. Whether progressive succession of vegetation in karst areas is accompanied by establishment of soil biota is poorly understood. In the present study, soil microbial and nematode communities, as well as soil physico-chemical properties were studied along a progressive succession of secondary vegetation (from grassland to shrubland to forest) in a karst area in southwest China. Microbial biomass, nematode density, ratio of fungal to bacterial biomass, nematode structure index, and nematode enrichment index decreased with the secondary succession in the plant community. Overall, the results indicated a pattern of declines in soil biota abundance and food web complexity that was associated with a decrease in soil pH and a decrease in soil organic carbon content with the progressive secondary succession of the plant community. Our findings suggest that soil biota amendment is necessary during karst ecosystem restoration and establishment and management of grasslands may be feasible in karst areas. PMID:25379741

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

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.

Esophageal cancer in high-risk areas of China: research progress and challenges.

PubMed

Lin, Yingsong; Totsuka, Yukari; Shan, Baoen; Wang, Chaochen; Wei, Wenqiang; Qiao, Youlin; Kikuchi, Shogo; Inoue, Manami; Tanaka, Hideo; He, Yutong

2017-03-01

The extremely high incidence of esophageal cancer in certain rural areas of China has prompted significant intellectual curiosity and research efforts both in China and abroad. We summarize the research progress over the past several decades in high-risk areas (Linxian, Cixian, Shexian, and Yanting) based on literature research and our field trip (2012-2013). Considerable progress in clarifying the environmental risk factors and pathogenesis of esophageal cancer in high-risk areas has been achieved over the past several decades. Epidemiologic evidence suggests that carcinogen exposure and nutritional deficiency, rather than smoking and drinking, may be the major risk factors for esophageal cancer in the Taihang Mountains region, where the incidence of esophageal cancer is among the highest in the world. Two genome-wide association studies have identified variants in PLCE1 at 10q23 that are significantly associated with esophageal cancer risk. Recent whole-exome studies have revealed a comprehensive mutation pattern, in which the C>T transition is the predominant mutation type. Despite extensive research, the main causative factors that contribute to esophageal cancer in high-risk areas have not yet been elucidated. Challenges in this research area include determining the causative role of nitrosamine, identifying other potential carcinogens, and conducting fruitful international collaborative studies based on a multidisciplinary approach. Increased international collaboration will contribute to a better understanding of the etiology of esophageal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

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

NASA Technical Reports Server (NTRS)

Dorman, Lane

2015-01-01

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

Targeted Therapies for Advanced Oesophagogastric Cancer: Recent Progress and Future Directions.

PubMed

Young, Kate; Chau, Ian

2016-01-01

The genomic landscape of oesophagogastric (OG) cancer is highly complex. The recent elucidation of some of the pathways involved has suggested a number of novel targets for therapy. This therapy is urgently required as with conventional chemotherapy regimens patients with advanced OG cancer still have a median overall survival of under a year. This review outlines the rationale for the current treatment of OG cancer with chemotherapy and describes both previously conducted and ongoing clinical trials of novel agents in this area. The targets and associated treatments discussed include HER-2, EGFR, VEGF, c-Met, FGFR-2, PI3K, mTOR andIGF-1. To date only two targeted treatments, trastuzumab and ramucirumab, have become part of the treatment paradigm for OG cancer, partly due to difficulties in defining predictive biomarkers in this disease. However, there are a number of promising drugs in the pipeline and this article seeks to describe these and other potential novel approaches including targeting DNA repair deficiencies and the immune system.

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

PubMed Central

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

2014-01-01

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

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.

COX-derived prostanoid pathways in gastrointestinal cancer development and progression: novel targets for prevention and intervention.

PubMed

Cathcart, Mary-Clare; O'Byrne, Kenneth J; Reynolds, John V; O'Sullivan, Jacintha; Pidgeon, Graham P

2012-01-01

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE(2), which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA(2) in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD(2) and its metabolite 15d-PGJ2, PGF(1α) and PGI(2). Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity. A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will

Progress on LMJ targets for ignition

NASA Astrophysics Data System (ADS)

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

2009-12-01

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

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

PubMed Central

2009-01-01

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

Prevention of abdominal aortic aneurysm progression by targeted inhibition of matrix metalloproteinase activity with batimastat-loaded nanoparticles.

PubMed

Nosoudi, Nasim; Nahar-Gohad, Pranjal; Sinha, Aditi; Chowdhury, Aniqa; Gerard, Patrick; Carsten, Christopher G; Gray, Bruce H; Vyavahare, Naren R

2015-11-06

Matrix metalloproteinases (MMPs)-mediated extracellular matrix destruction is the major cause of development and progression of abdominal aortic aneurysms. Systemic treatments of MMP inhibitors have shown effectiveness in animal models, but it did not translate to clinical success either because of low doses used or systemic side effects of MMP inhibitors. We propose a targeted nanoparticle (NP)-based delivery of MMP inhibitor at low doses to the abdominal aortic aneurysms site. Such therapy will be an attractive option for preventing expansion of aneurysms in patients without systemic side effects. Our previous study showed that poly(d,l-lactide) NPs conjugated with an antielastin antibody could be targeted to the site of an aneurysm in a rat model of abdominal aortic aneurysms. In the study reported here, we tested whether such targeted NPs could deliver the MMP inhibitor batimastat (BB-94) to the site of an aneurysm and prevent aneurysmal growth. Poly(d,l-lactide) NPs were loaded with BB-94 and conjugated with an elastin antibody. Intravenous injections of elastin antibody-conjugated BB-94-loaded NPs targeted the site of aneurysms and delivered BB-94 in a calcium chloride injury-induced abdominal aortic aneurysms in rats. Such targeted delivery inhibited MMP activity, elastin degradation, calcification, and aneurysmal development in the aorta (269% expansion in control versus 40% elastin antibody-conjugated BB-94-loaded NPs) at a low dose of BB-94. The systemic administration of BB-94 alone at the same dose was ineffective in producing MMP inhibition. Targeted delivery of MMP inhibitors using NPs may be an attractive strategy to inhibit aneurysmal progression. © 2015 American Heart Association, Inc.

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...

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

PubMed

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

2018-01-01

The Glaucoma Stereo Analysis Study, a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We compared the associations of each parameter between the visual field loss progression group and no-progression group. The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. We divided the mean deviation (MD) slope values of all patients into the progression group (<-0.3 dB/year) and no-progression group (≧-0.3 dB/year). ONH morphological parameters were calculated with prototype analysis software. The correlations between glaucomatous visual field progression and patient characteristics or each ONH parameter were analyzed with Spearman's rank correlation coefficient. The MD slope averages in the progression group and no-progression group were -0.58 ± 0.28 dB/year and 0.05 ± 0.26 dB/year, respectively. Among disc parameters, vertical disc width (diameter), disc area, cup area, and cup volume in the progression group were significantly less than those in the no-progression group. Logistic regression analysis revealed a significant association between the visual field progression and disc area (odds ratio 0.49/mm 2 disc area). A smaller disc area may be associated with more rapid glaucomatous visual field progression.

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...

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.

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

PubMed

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

2016-11-01

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

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

Imaging of oxidation-specific epitopes with targeted nanoparticles to detect high-risk atherosclerotic lesions: Progress and future directions

PubMed Central

Briley-Saebo, Karen; Yeang, Calvin; Witztum, Joseph L.; Tsimikas, Sotirios

2014-01-01

Oxidation-specific epitopes (OSE) within developing atherosclerotic lesions are key antigens that drive innate and adaptive immune responses in atherosclerosis, leading to chronic inflammation. Oxidized phospholipids and malondialdehyde-lysine epitopes are well-characterized OSE present in human atherosclerotic lesions, particularly in pathologically defined vulnerable plaques. Using murine and human OSE-specific antibodies as targeting agents, we have developed radionuclide and magnetic resonance based nanoparticles, containing gadolinium, manganese or lipid-coated ultrasmall superparamagnetic iron oxide, to noninvasively image OSE within experimental atherosclerotic lesions. These methods quantitate plaque burden, allow detection of lesion progression and regression, plaque stabilization, and accumulation of OSE within macrophage-rich areas of the artery wall, suggesting they detect the most active lesions. Future studies will focus on using “natural” antibodies, lipopeptides and mimotopes for imaging applications. These approaches should enhance the clinical translation of this technique to image, monitor, evaluate efficacy of novel therapeutic agents and guide optimal therapy of high-risk atherosclerotic lesions. PMID:25297940

[Target chemotherapy of intestinal nematode infection in area with low endemicity].

PubMed

Zhang, Tao; Shen, Yi-ping; Liu, Ying; Yang, Wei-ping; Shao, Jing-ou; Ju, Shao-you; Dong, Kai; Xu, Ju-ling; Jiang, Ji-min

2002-01-01

To evaluate the control measures for intestinal nematodiasis in endemic area with low prevalence and intensity of infection. Target chemotherapy was carried out in high-risk population based on the epidemiological characteristics such as age and clinical findings. Albendazole and mebendazole were administered each 200 mg once daily every year for 3 or 5 years. Saturated brine floatation and Kato-Katz thick smear techniques were used for stool examination to evaluate the efficacy of treatment. Two hundred residents from each of the three investigation villages were selected for target chemotherapy once a year for three years. The prevalence of intestinal nematodes decreased from 6.2% in 1995 to 5.4% in 1996 and 3.2% in 1997, and remained at 2.3% after three years in 2000. One control village where only primary school students were treated once a year for 5 years, the prevalence of Ascaris and Trichuris infection also decreased from 1.4% and 4.2% in 1995 to 0.9% and 1.4% in 2000, respectively. The target chemotherapy on the predisposed population to hookworm infection showed that the prevalence in the population above 41 years old was declined from 19.4% to 10.9%. The target chemotherapy is an economical and effective approach for the control of intestinal nematode infection in endemic area with low prevalence and intensity of infection.

Progress towards malaria control targets in relation to national malaria programme funding

PubMed Central

2013-01-01

Background Malaria control has been dramatically scaled up the past decade, mainly thanks to increasing international donor financing since 2003. This study assessed progress up to 2010 towards global malaria impact targets, in relation to Global Fund, other donor and domestic malaria programme financing over 2003 to 2009. Methods Assessments used domestic malaria financing reported by national programmes, and Global Fund/OECD data on donor financing for 90 endemic low- and middle-income countries, WHO estimates of households owning one or more insecticide-treated mosquito net (ITN) for countries in sub-Saharan Africa, and WHO-estimated malaria case incidence and deaths in countries outside sub-Saharan Africa. Results Global Fund and other donor funding is concentrated in a subset of the highest endemic African countries. Outside Africa, donor funding is concentrated in those countries with highest malaria mortality and case incidence rates over the years 2000 to 2003. ITN coverage in 2010 in Africa, and declines in case and death rates per person at risk over 2004 to 2010 outside Africa, were greatest in countries with highest donor funding per person at risk, and smallest in countries with lowest donor malaria funding per person at risk. Outside Africa, all-source malaria programme funding over 2003 to 2009 per case averted ($56-5,749) or per death averted ($58,000-3,900,000) over 2004 to 2010 tended to be lower (more favourable) in countries with higher donor malaria funding per person at risk. Conclusions Increases in malaria programme funding are associated with accelerated progress towards malaria control targets. Associations between programme funding per person at risk and ITN coverage increases and declines in case and death rates suggest opportunities to maximize the impact of donor funding, by strategic re-allocation to countries with highest continued need. PMID:23317000

MiR-200c Inhibits the Tumor Progression of Glioma via Targeting Moesin

PubMed Central

Qin, Yuanyuan; Chen, Weilong; Liu, Bingjie; Zhou, Lei; Deng, Lu; Niu, Wanxiang; Bao, Dejun; Cheng, Chuandong; Li, Dongxue; Liu, Suling; Niu, Chaoshi

2017-01-01

We attempt to demonstrate the regulatory role of miR-200c in glioma progression and its mechanisms behind. Here, we show that miR-200c expression was significantly reduced in the glioma tissues compared to paratumor tissues, especially in malignant glioma. Exogenous overexpression of miR-200c inhibited the proliferation and invasion of glioma cells. In addition, the in vivo mouse xenograft model showed that miR-200c inhibited glioma growth and liver metastasis, which is mainly regulated by targeting moesin (MSN). We demonstrated that the expression of MSN in glioma specimens were negatively correlated with miR-200c expression, and MSN overexpression rescued the phenotype about cell proliferation and invasion induced by miR-200c. Moreover, knockdown of MSN was able to mimic the effects induced by miR-200c in glioma cells. These results indicate that miR-200c plays an important role in the regulation of glioma through targeting MSN. PMID:28529643

Coordination of Myeloid Differentiation with Reduced Cell Cycle Progression by PU.1 Induction of MicroRNAs Targeting Cell Cycle Regulators and Lipid Anabolism.

PubMed

Solomon, Lauren A; Podder, Shreya; He, Jessica; Jackson-Chornenki, Nicholas L; Gibson, Kristen; Ziliotto, Rachel G; Rhee, Jess; DeKoter, Rodney P

2017-05-15

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1-inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1 , an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism. Copyright © 2017 American Society for Microbiology.

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...

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

PubMed Central

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

2016-01-01

Purpose We investigated the progression of Stargardt disease (STGD1) over a multiyear follow-up by evaluating the macular lesion area as computed by an automatic algorithm from spectral-domain optical coherence tomography (SD-OCT). Methods We reviewed medical records of STGD1 patients, with a clinical and molecular diagnosis of STGD1 at a single institution, who underwent best-corrected visual acuity (BCVA), fundus photography, SD-OCT, full-field electroretinography, and, when available, fundus autofluorescence (FAF). Regression models were fitted on the selected clinical parameters; in particular, on the macular lesion area computed by SD-OCT, to evaluate the disease progression over a multiyear follow-up. Results The comparison between SD-OCT and FAF, available for 22 patients, showed that macular lesion area, assessed by SD-OCT, significantly correlated with the area of absent FAF (P < 0.001). Moreover, the longitudinal analysis, performed in 98 patients, showed a significant enlargement of macular lesion area at an estimated exponential rate of 4.6% per year (P = 0.046), together with a significant worsening of BCVA (0.06 logMAR per year; P < 0.001) and a significant decrease of macular thickness (1.6% per year; P = 0.005) over the follow-up. Conclusions The current study describes, for the first time in literature, a longitudinal analysis of the macular lesion area assessed by SD-OCT in STGD1 disease, showing a significant progression over the follow-up. Our findings suggest that the evaluation of macular lesion area by en face SD-OCT, together with FAF, could drive the choice of the most amenable candidates and the most suitable area to be treated in gene therapy clinical trials. PMID:27409479

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

PubMed

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

2016-07-01

We investigated the progression of Stargardt disease (STGD1) over a multiyear follow-up by evaluating the macular lesion area as computed by an automatic algorithm from spectral-domain optical coherence tomography (SD-OCT). We reviewed medical records of STGD1 patients, with a clinical and molecular diagnosis of STGD1 at a single institution, who underwent best-corrected visual acuity (BCVA), fundus photography, SD-OCT, full-field electroretinography, and, when available, fundus autofluorescence (FAF). Regression models were fitted on the selected clinical parameters; in particular, on the macular lesion area computed by SD-OCT, to evaluate the disease progression over a multiyear follow-up. The comparison between SD-OCT and FAF, available for 22 patients, showed that macular lesion area, assessed by SD-OCT, significantly correlated with the area of absent FAF (P < 0.001). Moreover, the longitudinal analysis, performed in 98 patients, showed a significant enlargement of macular lesion area at an estimated exponential rate of 4.6% per year (P = 0.046), together with a significant worsening of BCVA (0.06 logMAR per year; P < 0.001) and a significant decrease of macular thickness (1.6% per year; P = 0.005) over the follow-up. The current study describes, for the first time in literature, a longitudinal analysis of the macular lesion area assessed by SD-OCT in STGD1 disease, showing a significant progression over the follow-up. Our findings suggest that the evaluation of macular lesion area by en face SD-OCT, together with FAF, could drive the choice of the most amenable candidates and the most suitable area to be treated in gene therapy clinical trials.

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.

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...

Progress on LMJ targets for ignition

NASA Astrophysics Data System (ADS)

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

2010-08-01

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

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.

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.

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

PubMed

Ma, Xiaopeng; Phi Van, Valerie; Kimm, Melanie A; Prakash, Jaya; Kessler, Horst; Kosanke, Katja; Feuchtinger, Annette; Aichler, Michaela; Gupta, Aayush; Rummeny, Ernst J; Eisenblätter, Michel; Siveke, Jens; Walch, Axel K; Braren, Rickmer; Ntziachristos, Vasilis; Wildgruber, Moritz

2017-01-01

Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT) for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC) model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF) probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib) for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

Fanzo, Jessica C; Pronyk, Paul M

2011-06-01

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

Progress in gene targeting and gene therapy for retinitis pigmentosa

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

Farrar, G.J.; Humphries, M.M.; Erven, A.

1994-09-01

Previously, we localized disease genes involved in retinitis pigmentosa (RP), an inherited retinal degeneration, close to the rhodopsin and peripherin genes on 3q and 6p. Subsequently, we and others identified mutations in these genes in RP patients. Currently animal models for human retinopathies are being generated using gene targeting by homologous recombination in embryonic stem (ES) cells. Genomic clones for retinal genes including rhodopsin and peripherin have been obtained from a phage library carrying mouse DNA isogenic with the ES cell line (CC1.2). The peripherin clone has been sequenced to establish the genomic structure of the mouse gene. Targeting vectorsmore » for rhodopsin and peripherin including a neomycin cassette for positive selection and thymidine kinase genes enabling selection against random intergrants are under construction. Progress in vector construction will be presented. Simultaneously we are developing systems for delivery of gene therapies to retinal tissues utilizing replication-deficient adenovirus (Ad5). Efficacy of infection subsequent to various methods of intraocular injection and with varying viral titers is being assayed using an adenovirus construct containing a CMV promoter LacZ fusion as reporter and the range of tissues infected and the level of duration of LacZ expression monitored. Viral constructs with the LacZ reporter gene under the control of retinal specific promoters such as rhodopsin and IRBP cloned into pXCJL.1 are under construction. An update on developments in photoreceptor cell-directed expression of virally delivered genes will be presented.« less

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...

Taking Targets to Task Revisited: How Indicators of Progress on Access to Education can Mislead. CREATE Pathways to Access. Research Monograph No. 54

ERIC Educational Resources Information Center

Lewin, Keith M.

2011-01-01

"Education for All" (EFA) identifies goals and targets and translates these into indicators which are used to evaluate progress and influence flows of external financing. The search for evidence based policy depends on measures of performance that can link cause and effect and that represent real gains in progress towards desired…

Glucose targets for preventing diabetic kidney disease and its progression.

PubMed

Ruospo, Marinella; Saglimbene, Valeria M; Palmer, Suetonia C; De Cosmo, Salvatore; Pacilli, Antonio; Lamacchia, Olga; Cignarelli, Mauro; Fioretto, Paola; Vecchio, Mariacristina; Craig, Jonathan C; Strippoli, Giovanni Fm

2017-06-08

Diabetes is the leading cause of end-stage kidney disease (ESKD) around the world. Blood pressure lowering and glucose control are used to reduce diabetes-associated disability including kidney failure. However there is a lack of an overall evidence summary of the optimal target range for blood glucose control to prevent kidney failure. To evaluate the benefits and harms of intensive (HbA1c < 7% or fasting glucose levels < 120 mg/dL versus standard glycaemic control (HbA1c ≥ 7% or fasting glucose levels ≥ 120 mg/dL for preventing the onset and progression of kidney disease among adults with diabetes. We searched the Cochrane Kidney and Transplant Specialised Register up to 31 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials evaluating glucose-lowering interventions in which people (aged 14 year or older) with type 1 or 2 diabetes with and without kidney disease were randomly allocated to tight glucose control or less stringent blood glucose targets. Two authors independently assessed studies for eligibility and risks of bias, extracted data and checked the processes for accuracy. Outcomes were mortality, cardiovascular complications, doubling of serum creatinine (SCr), ESKD and proteinuria. Confidence in the evidence was assessing using GRADE. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Fourteen studies involving 29,319 people with diabetes were included and 11 studies involving 29,141 people were

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

Targeting cancer with kinase inhibitors

PubMed Central

Gross, Stefan; Rahal, Rami; Stransky, Nicolas; Lengauer, Christoph; Hoeflich, Klaus P.

2015-01-01

Kinase inhibitors have played an increasingly prominent role in the treatment of cancer and other diseases. Currently, more than 25 oncology drugs that target kinases have been approved, and numerous additional therapeutics are in various stages of clinical evaluation. In this Review, we provide an in-depth analysis of activation mechanisms for kinases in cancer, highlight recent successes in drug discovery, and demonstrate the clinical impact of selective kinase inhibitors. We also describe the substantial progress that has been made in designing next-generation inhibitors to circumvent on-target resistance mechanisms, as well as ongoing strategies for combining kinase inhibitors in the clinic. Last, there are numerous prospects for the discovery of novel kinase targets, and we explore cancer immunotherapy as a new and promising research area for studying kinase biology. PMID:25932675

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

PubMed

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

2016-01-15

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

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

PubMed

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

2018-04-25

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

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

PubMed

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

2014-03-24

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

Hurricane Prediction: Progress and Problem Areas

ERIC Educational Resources Information Center

Simpson, R. H.

1973-01-01

Describes progress made in recent decades in predicting the track and landfall of hurricanes. Examines the problems of detecting, tracking, and describing tropical cyclones, and the difficulties which continue to complicate the matter of warning and evacuating coastal residents. (JR)

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...

Targeting EphA2 impairs cell cycle progression and growth of basal-like/triple-negative breast cancers.

PubMed

Song, W; Hwang, Y; Youngblood, V M; Cook, R S; Balko, J M; Chen, J; Brantley-Sieders, D M

2017-10-05

Basal-like/triple-negative breast cancers (TNBCs) are among the most aggressive forms of breast cancer, and disproportionally affects young premenopausal women and women of African descent. Patients with TNBC suffer a poor prognosis due in part to a lack of molecularly targeted therapies, which represents a critical barrier for effective treatment. Here, we identify EphA2 receptor tyrosine kinase as a clinically relevant target for TNBC. EphA2 expression is enriched in the basal-like molecular subtype in human breast cancers. Loss of EphA2 function in both human and genetically engineered mouse models of TNBC reduced tumor growth in culture and in vivo. Mechanistically, targeting EphA2 impaired cell cycle progression through S-phase via downregulation of c-Myc and stabilization of the cyclin-dependent kinase inhibitor p27/KIP1. A small molecule kinase inhibitor of EphA2 effectively suppressed tumor cell growth in vivo, including TNBC patient-derived xenografts. Thus, our data identify EphA2 as a novel molecular target for TNBC.

Targeting EphA2 impairs cell cycle progression and growth of basal-like/triple-negative breast cancers

PubMed Central

Song, W; Hwang, Y; Youngblood, V M; Cook, R S; Balko, J M; Chen, J; Brantley-Sieders, D M

2017-01-01

Basal-like/triple-negative breast cancers (TNBCs) are among the most aggressive forms of breast cancer, and disproportionally affects young premenopausal women and women of African descent. Patients with TNBC suffer a poor prognosis due in part to a lack of molecularly targeted therapies, which represents a critical barrier for effective treatment. Here, we identify EphA2 receptor tyrosine kinase as a clinically relevant target for TNBC. EphA2 expression is enriched in the basal-like molecular subtype in human breast cancers. Loss of EphA2 function in both human and genetically engineered mouse models of TNBC reduced tumor growth in culture and in vivo. Mechanistically, targeting EphA2 impaired cell cycle progression through S-phase via downregulation of c-Myc and stabilization of the cyclin-dependent kinase inhibitor p27/KIP1. A small molecule kinase inhibitor of EphA2 effectively suppressed tumor cell growth in vivo, including TNBC patient-derived xenografts. Thus, our data identify EphA2 as a novel molecular target for TNBC. PMID:28581527

Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma.

PubMed

Patel, Kruti R; Bai, Yan; Trieu, Kenneth G; Barrios, Juliana; Ai, Xingbin

2017-10-01

Asthma often progresses into adulthood from early-life episodes of adverse environmental exposures. However, how the injury to developing lungs contributes to the pathophysiology of persistent asthma remains poorly understood. In this study, we identified an age-related mechanism along the cholinergic nerve-airway smooth muscle (ASM) axis that underlies prolonged airway hyperreactivity (AHR) in mice. We showed that ASM continued to mature until ∼3 wk after birth. Coinciding with postnatal ASM maturation, there was a critical time window for the development of ASM hypercontractility after cholinergic stimulation. We found that allergen exposure in neonatal mice, but not in adult mice, elevated the level and activity of cholinergic nerves (termed neuroplasticity). We demonstrated that cholinergic neuroplasticity is necessary for the induction of persistent AHR after neonatal exposure during rescue assays in mice deficient in neuroplasticity. In addition, early intervention with cholinergic receptor muscarinic (ChRM)-3 blocker reversed the progression of AHR in the neonatal exposure model, whereas β2-adrenoceptor agonists had no such effect. Together, our findings demonstrate a functional relationship between cholinergic neuroplasticity and ASM contractile phenotypes that operates uniquely in early life to induce persistent AHR after allergen exposure. Targeting ChRM3 may have disease-modifying benefits in childhood asthma.-Patel, K. R., Bai, Y., Trieu, K. G., Barrios, J., Ai, X. Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma. © FASEB.

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.

RNA-Targeted Therapeutics.

PubMed

Crooke, Stanley T; Witztum, Joseph L; Bennett, C Frank; Baker, Brenda F

2018-04-03

RNA-targeted therapies represent a platform for drug discovery involving chemically modified oligonucleotides, a wide range of cellular RNAs, and a novel target-binding motif, Watson-Crick base pairing. Numerous hurdles considered by many to be impassable have been overcome. Today, four RNA-targeted therapies are approved for commercial use for indications as diverse as Spinal Muscular Atrophy (SMA) and reduction of low-density lipoprotein cholesterol (LDL-C) and by routes of administration including subcutaneous, intravitreal, and intrathecal delivery. The technology is efficient and supports approaching "undruggable" targets. Three additional agents are progressing through registration, and more are in clinical development, representing several chemical and structural classes. Moreover, progress in understanding the molecular mechanisms by which these drugs work has led to steadily better clinical performance and a wide range of mechanisms that may be exploited for therapeutic purposes. Here we summarize the progress, future challenges, and opportunities for this drug discovery platform. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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.

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

PubMed Central

2014-01-01

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

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

PubMed Central

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

2017-01-01

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

Progress in Computational Electron-Molecule Collisions

NASA Astrophysics Data System (ADS)

Rescigno, Tn

1997-10-01

The past few years have witnessed tremendous progress in the development of sophisticated ab initio methods for treating collisions of slow electrons with isolated small molecules. Researchers in this area have benefited greatly from advances in computer technology; indeed, the advent of parallel computers has made it possible to carry out calculations at a level of sophistication inconceivable a decade ago. But bigger and faster computers are only part of the picture. Even with today's computers, the practical need to study electron collisions with the kinds of complex molecules and fragments encountered in real-world plasma processing environments is taxing present methods beyond their current capabilities. Since extrapolation of existing methods to handle increasingly larger targets will ultimately fail as it would require computational resources beyond any imagined, continued progress must also be linked to new theoretical developments. Some of the techniques recently introduced to address these problems will be discussed and illustrated with examples of electron-molecule collision calculations we have carried out on some fairly complex target gases encountered in processing plasmas. Electron-molecule scattering continues to pose many formidable theoretical and computational challenges. I will touch on some of the outstanding open questions.

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

Prevention and treatment of cancer targeting chronic inflammation: research progress, potential agents, clinical studies and mechanisms.

PubMed

Zhang, Yong; Kong, Weijia; Jiang, Jiandong

2017-06-01

Numerous experimental and clinical studies indicate that chronic inflammation is closely related to the initiation, progression, and spread of cancer, in which proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α), and transcription factors, such as nuclear factor-κB (NF-κB), and signal transducer and activator of transcription 3 (STAT3), play pivotal roles. Stimulated by proinflammatory cytokines, NF-κB and STAT3 can modulate the expression of target genes, most of which are oncogenic ones, and promote the survival, proliferation, invasion, and metastasis of cancer cells. Now it is generally accepted that inflammation-related molecules and pathways are useful targets for the prevention and treatment of cancer. In this review, we summarize the relationship between chronic inflammation and cancer and describe some potentially useful agents including aspirin, meformin, statins, and some natural products (green tea catechins, andrographolide, curcumin) for their cancer prevention and treatment activities targeting chronic inflammation. The results of typical clinical studies are included, and the influences of these agents on the proinflammatory cytokines and inflammation-related pathways are discussed. Data from the present review support that agents targeting chronic inflammation may have a broad application prospect for the prevention and treatment of cancer in the future.

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

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

PubMed Central

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

2015-01-01

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

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

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.

FGFR-targeted therapeutics for the treatment of breast cancer.

PubMed

De Luca, Antonella; Frezzetti, Daniela; Gallo, Marianna; Normanno, Nicola

2017-03-01

Breast cancer is a complex disease and several molecular drivers regulate its progression. Fibroblast growth factor receptor (FGFR) signaling is frequently deregulated in many cancers, including breast cancer. Due the involvement of the FGFR/FGF axis in the pathogenesis and progression of tumors, FGFR-targeted agents might represent a potential therapeutic option for breast cancer patients. Areas covered: This review offers an overview of targeted agents against FGFRs and their clinical development in breast cancer. The most relevant literature and the latest studies in the Clinicaltrial.com database have been discussed. Expert opinion: FGFR inhibition has been recently considered as a promising therapeutic option for different tumor types. However, preliminary results of clinical trials of FGFR inhibitors in breast cancer have been quite disappointing. In order to increase the clinical benefit of FGFR therapies in breast cancer, future studies should focus on: understanding the role of the various FGFR aberrations in cancer progression; identifying potential biomarkers to select patients that could benefit of FGFR inhibitors and developing therapeutic strategies that improve the efficacy of these agents and minimize toxicities.

St. Louis Area Earthquake Hazards Mapping Project - December 2008-June 2009 Progress Report

USGS Publications Warehouse

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

2009-01-01

This report summarizes the mission, the project background, the participants, and the progress of the St. Louis Area Earthquake Hazards Mapping Project (SLAEHMP) for the period from December 2008 through June 2009. During this period, the SLAEHMP held five conference calls and two face-to-face meetings in St. Louis, participated in several earthquake awareness public meetings, held one outreach field trip for the business and government community, collected and compiled new borehole and digital elevation data from partners, and published a project summary.

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...

Progression of mouse skin carcinogenesis is associated with the orchestrated deregulation of mir-200 family members, mir-205 and their common targets.

PubMed

Skourti, Elena; Logotheti, Stella; Kontos, Christos K; Pavlopoulou, Athanasia; Dimoragka, Paraskevi T; Trougakos, Ioannis P; Gorgoulis, Vassilis; Scorilas, Andreas; Michalopoulos, Ioannis; Zoumpourlis, Vassilis

2016-08-01

MicroRNAs are small, non-coding RNAs which regulate post-transcriptionally hundreds of target mRNAs. Given that their expression is deregulated in several cancer types, they represent potential diagnostic, prognostic, and predictive biomarkers, as well as next-generation therapeutic targets. Nevertheless, the involvement of miRNAs in non-melanoma skin cancer, a cancer type with increasing prevalence, is not extensively studied, and their comprehensive characterization as regard to the initiation, promotion, and progression stages is missing. To this end, we exploited a well-established multistage mouse skin carcinogenesis model in order to identify miRNAs consistently implicated in different stages of skin carcinogenesis. The cell lines comprising this model were subjected to miRNA expression profiling using microarrays, followed by bioinformatics analysis and validation with Q-PCR, as well as treatment with miRNA modulators. We showed that among all deregulated miRNAs in our system, only a functionally coherent group consisting of the miR-200 family members and miR-205-5p displays a pattern of progressive co-downregulation from the early toward the most aggressive stages of carcinogenesis. Their overlapping, co-regulated putative targets are potentially inter-associated and, of these, the EMT-related Rap1a is overexpressed toward aggressive stages. Ectopic expression of miR-205-5p in spindle cancer cells reduces Rap1a, mitigates cell invasiveness, decreases proliferation, and delays tumor onset. We conclude that deregulation of this miRNA group is primarily associated with aggressive phenotypes of skin cancer cells. Restoration of the miR-205-5p member of this group in spindle cells reduces the expression of critical, co-regulated targets that favor cancer progression, thus reversing the EMT characteristics. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Atherosclerosis. Potential targets for stabilization and regression.

PubMed

Schwartz, C J; Valente, A J; Sprague, E A; Kelley, J L; Cayatte, A J; Mowery, J

1992-12-01

Reviewed are various aspects of atherosclerotic plaque stabilization and regression in humans and experimental animals. Plaque regression is a function of the dynamic balance among initiation, progression, stabilization, and removal of plaque constituents. Pseudoregression, the result of the triad thrombolysis, age- or lesion-dependent arterial dilatation, and relaxation of vasospasm, may readily give rise to angiographic misinterpretation. Although lowering of plasma cholesterol and low density lipoprotein-cholesterol has demonstrated significant clinical benefits in a number of clinical trials, the magnitude of angiographic regressive changes is relatively small despite aggressive lipid-lowering regimens. The emerging need for alternative or complementary therapeutic interventions has been emphasized. In particular, they should be targeted to pivotal cellular or molecular mechanisms in initiation, progression, or stabilization. Potentially important therapeutic targets include the use of antioxidants or free radical scavengers such as Probucol or its analogues, butylated hydroxytoluene, tocopherols, and possibly the tocotrienols. Other therapeutic targets include intimal monocyte-macrophage recruitment, macrophage cholesterol acyltransferase inhibition, stimulation of the high density lipoprotein-mediated reverse cholesterol transport system, smooth muscle cell migration to and proliferation in the arterial intima, and intimal connective tissue synthesis. Whether the isoprenylated proteins associated with the cholesterol biosynthetic pathway will give rise to compounds regulating smooth muscle cell growth has yet to be determined. Because of the importance of thrombosis in the pathogenesis and progression of lesions, the need to develop interventional strategies targeted at endothelial cell thromboresistance and thromboregulation must assume a high priority in future research and development. Other areas of therapeutic promise include the calcium channel blockers

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

PubMed

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

2015-01-01

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

Advances in targeted genome editing.

PubMed

Perez-Pinera, Pablo; Ousterout, David G; Gersbach, Charles A

2012-08-01

New technologies have recently emerged that enable targeted editing of genomes in diverse systems. This includes precise manipulation of gene sequences in their natural chromosomal context and addition of transgenes to specific genomic loci. This progress has been facilitated by advances in engineering targeted nucleases with programmable, site-specific DNA-binding domains, including zinc finger proteins and transcription activator-like effectors (TALEs). Recent improvements have enhanced nuclease performance, accelerated nuclease assembly, and lowered the cost of genome editing. These advances are driving new approaches to many areas of biotechnology, including biopharmaceutical production, agriculture, creation of transgenic organisms and cell lines, and studies of genome structure, regulation, and function. Genome editing is also being investigated in preclinical and clinical gene therapies for many diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms

PubMed Central

Burd, Christin E.; Gill, Matthew S.; Niedernhofer, Laura J.; Robbins, Paul D.; Austad, Steven N.; Barzilai, Nir

2016-01-01

Through the progress of basic science research, fundamental mechanisms that contribute to age-related decline are being described with increasing depth and detail. Although these efforts have identified new drug targets and compounds that extend life span in model organisms, clinical trials of therapeutics that target aging processes remain scarce. Progress in aging research is hindered by barriers associated with the translation of basic science discoveries into the clinic. This report summarizes discussions held at a 2014 Geroscience Network retreat focused on identifying hurdles that currently impede the preclinical development of drugs targeting fundamental aging processes. From these discussions, it was evident that aging researchers have varied perceptions of the ideal preclinical pipeline. To forge a clear and cohesive path forward, several areas of controversy must first be resolved and new tools developed. Here, we focus on five key issues in preclinical drug development (drug discovery, lead compound development, translational preclinical biomarkers, funding, and integration between researchers and clinicians), expanding upon discussions held at the Geroscience Retreat and suggesting areas for further research. By bringing these findings to the attention of the aging research community, we hope to lay the foundation for a concerted preclinical drug development pipeline. PMID:27535964

Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms.

PubMed

Burd, Christin E; Gill, Matthew S; Niedernhofer, Laura J; Robbins, Paul D; Austad, Steven N; Barzilai, Nir; Kirkland, James L

2016-11-01

Through the progress of basic science research, fundamental mechanisms that contribute to age-related decline are being described with increasing depth and detail. Although these efforts have identified new drug targets and compounds that extend life span in model organisms, clinical trials of therapeutics that target aging processes remain scarce. Progress in aging research is hindered by barriers associated with the translation of basic science discoveries into the clinic. This report summarizes discussions held at a 2014 Geroscience Network retreat focused on identifying hurdles that currently impede the preclinical development of drugs targeting fundamental aging processes. From these discussions, it was evident that aging researchers have varied perceptions of the ideal preclinical pipeline. To forge a clear and cohesive path forward, several areas of controversy must first be resolved and new tools developed. Here, we focus on five key issues in preclinical drug development (drug discovery, lead compound development, translational preclinical biomarkers, funding, and integration between researchers and clinicians), expanding upon discussions held at the Geroscience Retreat and suggesting areas for further research. By bringing these findings to the attention of the aging research community, we hope to lay the foundation for a concerted preclinical drug development pipeline. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

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...

Targeted DNA Sequencing Reveals Patterns of Local Progression in the Pancreatic Remnant Following Resection of Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

PubMed Central

Pea, Antonio; Yu, Jun; Rezaee, Neda; Luchini, Claudio; He, Jin; Molin, Marco Dal; Griffin, James F.; Fedor, Helen; Fesharakizadeh, Shahriar; Salvia, Roberto; Weiss, Matthew J.; Bassi, Claudio; Cameron, John L.; Zheng, Lei; Scarpa, Aldo; Hruban, Ralph H.; Lennon, Anne Marie; Goggins, Michael

2016-01-01

Objective The aim of this study was to characterize patterns of local progression following resection for pancreatic intraductal papillary mucinous neoplasms (IPMN) using targeted next-generation sequencing (NGS). Background Progression of neoplastic disease in the remnant pancreas following resection of IPMN may include development of a new IPMN or ductal adenocarcinoma (PDAC). However, it is not clear whether this progression represents recurrence of the same neoplasm or an independent second neoplasm. Methods Targeted-NGS on genes commonly mutated in IPMN and PDAC was performed on tumors from (1) 13 patients who developed disease progression in the remnant pancreas following resection of IPMN; and (2) 10 patients who underwent a resection for PDAC and had a concomitant IPMN. Mutations in the tumors were compared in order to determine the relationship between neoplasms. In parallel, clinical and pathological characteristics of 260 patients who underwent resection of noninvasive IPMN were reviewed to identify risk factors associated with local progression. Results We identified 3 mechanisms underlying local progression in the remnant pancreas: (1) residual microscopic disease at the resection margin, (2) intraparenchymal spread of neoplastic cells, leading to an anatomically separate but genetically related recurrence, and (3) multifocal disease with genetically distinct lesions. Analysis of the 260 patients with noninvasive IPMNs showed that family history of pancreatic cancer (P = 0.027) and high-grade dysplasia (HGD) (P = 0.003) were independent risk factors for the development of an IPMN with HGD or an invasive carcinoma in the remnant pancreas. Conclusions Using NGS, we identify distinct mechanisms for development of metachronous or synchronous neoplasms in patients with IPMN. Patients with a primary IPMN with HGD or with positive family history are at an increased risk to develop subsequent high-risk neoplasms in the remnant pancreas. PMID:27433916

Fear of progression.

PubMed

Herschbach, Peter; Dinkel, Andreas

2014-01-01

Fear of progression (or fear of recurrence) is an appropriate, rational response to the real threat of cancer and cancer treatments. However, elevated levels of fear of progression can become dysfunctional, affecting well-being, quality of life, and social functioning. Research has shown that fear of progression is one of the most frequent distress symptoms of patients with cancer and with other chronic diseases. As a clear consensus concerning clinically relevant states of fear of progression is currently lacking, it is difficult to provide a valid estimate of the rate of cancer patients who clearly suffer from fear of progression. However, recent systematic reviews suggest that probably 50 % of cancer patients experience moderate to severe fear of progression. Furthermore, many patients express unmet needs in dealing with the fear of cancer spreading. These results underline the necessity to provide effective psychological treatments for clinical levels of fear of progression. A few psychosocial interventions for treating fear of progression have been developed so far. Our own, targeted intervention study showed that dysfunctional fear of progression can be effectively treated with a brief group therapy.

Target Acquired: Progress and Promise of Targeted Therapeutics in the Treatment of Prostate Cancer.

PubMed

Stuchbery, Ryan; Kurganovs, Natalie J; McCoy, Patrick J; Nelson, Colleen C; Hayes, Vanessa M; Corcoran, Niall M; Hovens, Christopher M

2015-01-01

Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient's disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

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

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

NONE

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

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

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

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

1990-01-01

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

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

Apathy associated with neurocognitive disorders: Recent progress and future directions.

PubMed

Lanctôt, Krista L; Agüera-Ortiz, Luis; Brodaty, Henry; Francis, Paul T; Geda, Yonas E; Ismail, Zahinoor; Marshall, Gad A; Mortby, Moyra E; Onyike, Chiadi U; Padala, Prasad R; Politis, Antonios M; Rosenberg, Paul B; Siegel, Emma; Sultzer, David L; Abraham, Eleenor H

2017-01-01

Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs. Progress has recently been made in three areas relevant to apathy: (1) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches. Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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

USGS Publications Warehouse

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

2016-01-01

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

Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ.

PubMed

Stucki, David M; Ruegsegger, Céline; Steiner, Silvio; Radecke, Julika; Murphy, Michael P; Zuber, Benoît; Saxena, Smita

2016-08-01

Spinocerebellar ataxia type 1 (SCA1), due to an unstable polyglutamine expansion within the ubiquitously expressed Ataxin-1 protein, leads to the premature degeneration of Purkinje cells (PCs), decreasing motor coordination and causing death within 10-15 years of diagnosis. Currently, there are no therapies available to slow down disease progression. As secondary cellular impairments contributing to SCA1 progression are poorly understood, here, we focused on identifying those processes by performing a PC specific proteome profiling of Sca1(154Q/2Q) mice at a symptomatic stage. Mass spectrometry analysis revealed prominent alterations in mitochondrial proteins. Immunohistochemical and serial block-face scanning electron microscopy analyses confirmed that PCs underwent age-dependent alterations in mitochondrial morphology. Moreover, colorimetric assays demonstrated impairment of the electron transport chain complexes (ETC) and decrease in ATPase activity. Subsequently, we examined whether the mitochondria-targeted antioxidant MitoQ could restore mitochondrial dysfunction and prevent SCA1-associated pathology in Sca1(154Q/2Q) mice. MitoQ treatment both presymptomatically and when symptoms were evident ameliorated mitochondrial morphology and restored the activities of the ETC complexes. Notably, MitoQ slowed down the appearance of SCA1-linked neuropathology such as lack of motor coordination as well as prevented oxidative stress-induced DNA damage and PC loss. Our work identifies a central role for mitochondria in PC degeneration in SCA1 and provides evidence for the supportive use of mitochondria-targeted therapeutics in slowing down disease progression. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2018-03-01

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

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

PubMed Central

Liskay, R.Michael

2014-01-01

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

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.

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...

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

PubMed Central

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

2015-01-01

Objective To quantify progress with the initiation of salt reduction strategies around the world in the context of the global target to reduce population salt intake by 30% by 2025. Methods A systematic review of the published and grey literature was supplemented by questionnaires sent to country program leaders. Core characteristics of strategies were extracted and categorised according to a pre-defined framework. Results A total of 75 countries now have a national salt reduction strategy, more than double the number reported in a similar review done in 2010. The majority of programs are multifaceted and include industry engagement to reformulate products (n = 61), establishment of sodium content targets for foods (39), consumer education (71), front-of-pack labelling schemes (31), taxation on high-salt foods (3) and interventions in public institutions (54). Legislative action related to salt reduction such as mandatory targets, front of pack labelling, food procurement policies and taxation have been implemented in 33 countries. 12 countries have reported reductions in population salt intake, 19 reduced salt content in foods and 6 improvements in consumer knowledge, attitudes or behaviours relating to salt. Conclusion The large and increasing number of countries with salt reduction strategies in place is encouraging although activity remains limited in low- and middle-income regions. The absence of a consistent approach to implementation highlights uncertainty about the elements most important to success. Rigorous evaluation of ongoing programs and initiation of salt reduction programs, particularly in low- and middle- income countries, will be vital to achieving the targeted 30% reduction in salt intake. PMID:26201031

Enhanced surveillance program FY97 accomplishments. Progress report

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

Mauzy, A.; Laake, B.

1997-10-01

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

MUC4 mucin- a therapeutic target for pancreatic ductal adenocarcinoma.

PubMed

Gautam, Shailendra K; Kumar, Sushil; Cannon, Andrew; Hall, Bradley; Bhatia, Rakesh; Nasser, Mohd Wasim; Mahapatra, Sidharth; Batra, Surinder K; Jain, Maneesh

2017-07-01

Pancreatic cancer (PC) is characterized by mucin overexpression. MUC4 is the most differentially overexpressed membrane-bound mucin that plays a functional role in disease progression and therapy resistance. Area covered: We describe the clinicopathological significance of MUC4, summarize mechanisms contributing to its deregulated expression, review preclinical studies aimed at inhibiting MUC4, and discuss how MUC4 overexpression provides opportunities for developing targeted therapies. Finally, we discuss the challenges for developing MUC4-based therapeutics, and identify areas where efforts should be directed to effectively exploit MUC4 as a therapeutic target for PC. Expert opinion: Studies demonstrating that abrogation of MUC4 expression reduces proliferation and metastasis of PC cells and enhances sensitivity to therapeutic agents affirm its utility as a therapeutic target. Emerging evidence also supports the suitability of MUC4 as a potential immunotherapy target. However, these studies have been limited to in vitro, ex vivo or in vivo approaches using xenograft tumors in immunodeficient murine models. For translational relevance, MUC4-targeted therapies should be evaluated in murine models with intact immune system and accurate tumor microenvironment. Additionally, future studies evaluating MUC4 as a target for immunotherapy must entail characterization of immune response in PC patients and investigate its association with immunosuppression and survival.

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

PubMed

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

2017-11-15

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

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...

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

PubMed

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

2016-11-01

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

Active Targeted Drug Delivery for Microbes Using Nano-Carriers

PubMed Central

Lin, Yung-Sheng; Lee, Ming-Yuan; Yang, Chih-Hui; Huang, Keng-Shiang

2015-01-01

Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects. Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery. However, it still has some challenges like lack of specificity toward targeting the infectious site. Nano-carriers utilized targeting ligands on their surface called ‘active target’ provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or side-effects. In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes. The four common nano-carriers (e.g. liposomes, nanoparticles, dendrimers and carbon nanotubes) delivering encapsulated drugs are introduced. PMID:25877093

Current progress on aptamer-targeted oligonucleotide therapeutics

PubMed Central

Dassie, Justin P; Giangrande, Paloma H

2014-01-01

Exploiting the power of the RNAi pathway through the use of therapeutic siRNA drugs has remarkable potential for treating a vast array of human disease conditions. However, difficulties in delivery of these and similar nucleic acid-based pharmacological agents to appropriate organs or tissues, remains a major impediment to their broad clinical application. Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery vehicles for therapeutic oligonucleotides, including siRNAs. In this review, we summarize recent attractive developments in creatively employing cell-internalizing aptamers to deliver therapeutic oligonucleotides (e.g., siRNAs, miRNAs, anti-miRs and antisense oligos) to target cells. We also discuss advancements in aptamer-siRNA chimera technology, as well as, aptamer-functionalized nanoparticles for siRNA delivery. In addition, the challenges and future prospects of aptamer-targeted oligonucleotide drugs for clinical translation are further highlighted. PMID:24304250

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

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

Wang, Maomao; Deng, Xiaodong; Ying, Qi

2015-05-01

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

Hormonally up-regulated neu-associated kinase: A novel target for breast cancer progression.

PubMed

Zambrano, Joelle N; Neely, Benjamin A; Yeh, Elizabeth S

2017-05-01

Hormonally up-regulated neu-associated Kinase (Hunk) is a protein kinase that was originally identified in the murine mammary gland and has been shown to be highly expressed in Human Epidermal Growth Factor Receptor 2 positive (HER2 + /ErbB2 + ) breast cancer cell lines as well as MMTV-neu derived mammary tumor cell lines. However, the physiological role of Hunk has been largely elusive since its identification. Though Hunk is predicted to be a Serine/Threonine (Ser/Thr) protein kinase with homology to the SNF1/AMPK family of protein kinases, there are no known Hunk substrates that have been identified to date. Recent work demonstrates a role for Hunk in HER2 + /ErbB2 + breast cancer progression, including drug resistance to HER2/ErbB2 inhibitors, with Hunk potentially acting downstream of HER2/ErbB2 and the PI3K/Akt pathway. These studies have collectively shown that Hunk plays a vital role in promoting mammary tumorigenesis, as Hunk knockdown via shRNA in xenograft tumor models or crossing MMTV-neu or Pten-deficient genetically engineered mouse models into a Hunk knockout (Hunk-/-) background impairs mammary tumor growth in vivo. Because the majority of HER2 + /ErbB2 + breast cancer patients acquire drug resistance to HER2/ErbB2 inhibitors, the characterization of novel drug targets like Hunk that have the potential to simultaneously suppress tumorigenesis and potentially enhance efficacy of current therapeutics is an important facet of drug development. Therefore, work aimed at uncovering specific regulatory functions for Hunk that could contribute to this protein kinase's role in both tumorigenesis and drug resistance will be informative. This review focuses on what is currently known about this under-studied protein kinase, and how targeting Hunk may prove to be a potential therapeutic target for the treatment of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dendritic cell targeted vaccines: Recent progresses and challenges

PubMed Central

Chen, Pengfei; Liu, Xinsheng; Sun, Yuefeng; Zhou, Peng; Wang, Yonglu; Zhang, Yongguang

2016-01-01

ABSTRACT Dendritic cells (DCs) are known to be a set of morphology, structure and function of heterogeneous professional antigen presenting cells (APCs), as well as the strongest functional antigen presenting cells, which can absorb, process and present antigens. As the key regulators of innate and adaptive immune responses, DCs are at the center of the immune system and capable of interacting with both B cells and T cells, thereby manipulating the humoral and cellular immune responses. DCs provide an essential link between the innate and adaptive immunity, and the strong immune activation function of DCs and their properties of natural adjuvants, make them a valuable target for antigen delivery. Targeting antigens to DC-specific endocytic receptors in combination with the relevant antibodies or ligands along with immunostimulatory adjuvants has been recently recognized as a promising strategy for designing an effective vaccine that elicits a strong and durable T cell response against intracellular pathogens and cancer. This opinion article provides a brief summary of the rationales, superiorities and challenges of existing DC-targeting approaches. PMID:26513200

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.

Pathways and therapeutic targets in melanoma

PubMed Central

Shtivelman, Emma; Davies, Michael A.; Hwu, Patrick; Yang, James; Lotem, Michal; Oren, Moshe; Flaherty, Keith T.; Fisher, David E.

2014-01-01

This review aims to summarize the current knowledge of molecular pathways and their clinical relevance in melanoma. Metastatic melanoma was a grim diagnosis, but in recent years tremendous advances have been made in treatments. Chemotherapy provided little benefit in these patients, but development of targeted and new immune approaches made radical changes in prognosis. This would not have happened without remarkable advances in understanding the biology of disease and tremendous progress in the genomic (and other “omics”) scale analyses of tumors. The big problems facing the field are no longer focused exclusively on the development of new treatment modalities, though this is a very busy area of clinical research. The focus shifted now to understanding and overcoming resistance to targeted therapies, and understanding the underlying causes of the heterogeneous responses to immune therapy. PMID:24743024

Adaptive block online learning target tracking based on super pixel segmentation

NASA Astrophysics Data System (ADS)

Cheng, Yue; Li, Jianzeng

2018-04-01

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

Evansville Area Earthquake Hazards Mapping Project (EAEHMP) - Progress Report, 2008

USGS Publications Warehouse

Boyd, Oliver S.; Haase, Jennifer L.; Moore, David W.

2009-01-01

Maps of surficial geology, deterministic and probabilistic seismic hazard, and liquefaction potential index have been prepared by various members of the Evansville Area Earthquake Hazard Mapping Project for seven quadrangles in the Evansville, Indiana, and Henderson, Kentucky, metropolitan areas. The surficial geologic maps feature 23 types of surficial geologic deposits, artificial fill, and undifferentiated bedrock outcrop and include alluvial and lake deposits of the Ohio River valley. Probabilistic and deterministic seismic hazard and liquefaction hazard mapping is made possible by drawing on a wealth of information including surficial geologic maps, water well logs, and in-situ testing profiles using the cone penetration test, standard penetration test, down-hole shear wave velocity tests, and seismic refraction tests. These data were compiled and collected with contributions from the Indiana Geological Survey, Kentucky Geological Survey, Illinois State Geological Survey, United States Geological Survey, and Purdue University. Hazard map products are in progress and are expected to be completed by the end of 2009, with a public roll out in early 2010. Preliminary results suggest that there is a 2 percent probability that peak ground accelerations of about 0.3 g will be exceeded in much of the study area within 50 years, which is similar to the 2002 USGS National Seismic Hazard Maps for a firm rock site value. Accelerations as high as 0.4-0.5 g may be exceeded along the edge of the Ohio River basin. Most of the region outside of the river basin has a low liquefaction potential index (LPI), where the probability that LPI is greater than 5 (that is, there is a high potential for liquefaction) for a M7.7 New Madrid type event is only 20-30 percent. Within the river basin, most of the region has high LPI, where the probability that LPI is greater than 5 for a New Madrid type event is 80-100 percent.

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

PubMed

Bojadzic, Damir; Buchwald, Peter

2018-05-30

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

Progress in Organization Development Research.

ERIC Educational Resources Information Center

Roberts, Nancy C.; Porras, Jerry I.

1982-01-01

Describes major areas of progress in organization development (OD): progress in operationalizing the concept of change; progress in improving measurement; and progress in designing statistical procedures used to analyze OD intervention data. Suggests recent research developments point to a more solid base on which to build OD practice and theory.…

Targeting pH regulating proteins for cancer therapy-Progress and limitations.

PubMed

Parks, Scott K; Pouysségur, Jacques

2017-04-01

Tumour acidity induced by metabolic alterations and incomplete vascularisation sets cancer cells apart from normal cellular physiology. This distinguishing tumour characteristic has been an area of intense study, as cellular pH (pH i ) disturbances disrupt protein function and therefore multiple cellular processes. Tumour cells effectively utilise pH i regulating machinery present in normal cells with enhancements provided by additional oncogenic or hypoxia induced protein modifications. This overall improvement of pH regulation enables maintenance of an alkaline pH i in the continued presence of external acidification (pH e ). Considerable experimentation has revealed targets that successfully disrupt tumour pH i regulation in efforts to develop novel means to weaken or kill tumour cells. However, redundancy in these pH-regulating proteins, which include Na + /H + exchangers (NHEs), carbonic anhydrases (CAs), Na + /HCO 3 - co-transporters (NBCs) and monocarboxylate transporters (MCTs) has prevented effective disruption of tumour pH i when individual protein targeting is performed. Here we synthesise recent advances in understanding both normoxic and hypoxic pH regulating mechanisms in tumour cells with an ultimate focus on the disruption of tumour growth, survival and metastasis. Interactions between tumour acidity and other cell types are also proving to be important in understanding therapeutic applications such as immune therapy. Promising therapeutic developments regarding pH manipulation along with current limitations are highlighted to provide a framework for future research directives. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

Summer temperature extremes over the global land area were investigated by comparing 26 models of the fifth phase of the Coupled Model Intercomparison Project (CMIP5) with observations from the Goddard Institute for Space Studies (GISS) and the Climate Research Unit (CRU). Monthly data of the observations and models were averaged for each season, and statistics were calculated for individual models before averaging them to obtain ensemble means. The summers with temperature anomalies (relative to 1951–1980) exceeding 3σ (σ is based on the local internal variability) are defined as “extremely hot”. The models well reproduced the statistical characteristics evolution, and partly captured the spatial distributions of historical summer temperature extremes. If the global mean temperature increases 2°C relative to the pre-industrial level, “extremely hot” summers are projected to occur over nearly 40% of the land area (multi-model ensemble mean projection). Summers that exceed 5σ warming are projected to occur over approximately 10% of the global land area, which were rarely observed during the reference period. Scenarios reaching warming levels of 3°C to 5°C were also analyzed. After exceeding the 5°C warming target, “extremely hot” summers are projected to occur throughout the entire global land area, and summers that exceed 5σ warming would become common over 70% of the land area. In addition, the areas affected by “extremely hot” summers are expected to rapidly expand by more than 25%/°C as the global mean temperature increases by up to 3°C before slowing to less than 16%/°C as the temperature continues to increase by more than 3°C. The area that experiences summers with warming of 5σ or more above the warming target of 2°C is likely to maintain rapid expansion of greater than 17%/°C. To reduce the impacts and damage from severely hot summers, the global mean temperature increase should remain low. PMID:26090931

Processes of energy deposition by heavy-particle and electron impact. Final progress report

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

Salop, A.; Smith, F.T.

1978-04-18

Progress is reported in three areas of reasearch during the present period: K-shell ionization in high energy collisions of heavy ions with light target atoms using the sudden (Magnus) approximation, K-L level matching phenomena associated with K-shell vacancy production in heavy-ion collisions, and studies of low energy collisions of electrons with molecules using semi-classical perturbation theory. A brief discussion of each of these activities is given.

Strategies to target non-T-cell HIV reservoirs.

PubMed

Sacha, Jonah B; Ndhlovu, Lishomwa C

2016-07-01

A central question for the HIV cure field is to determine new ways to target clinically relevant, latently and actively replicating HIV-infected cells beyond resting memory CD4 T cells, particularly in anatomical areas of low drug penetrability. HIV eradication strategies being positioned for targeting HIV for extinction in the CD4 T-cell compartment may also show promise in non-CD4 T-cells reservoirs. Furthermore, several exciting novel therapeutic approaches specifically focused on HIV clearance from non-CD4 T-cell populations are being developed. Although reservoir validity in these non-CD4 T cells continues to remain debated, this review will highlight recent advances and make an argument as to their clinical relevancy as we progress towards an HIV cure.

Targeted therapies in the treatment of urothelial cancers.

PubMed

Aragon-Ching, Jeanny B; Trump, Donald L

2017-07-01

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

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

PubMed

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

2012-03-01

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

Second progress report on the cooperative investigation of springs and stream flow in the Tecolote Tunnel area of Santa Barbara County, California

USGS Publications Warehouse

Troxell, Harold C.; Burgess, C.E.

1950-01-01

This report represents the second of a series of progress reports giving the results of discharge measurements made at more than 100 locations in the Santa Ynez Mountains from the Refugio Canyon on the west to the San Marcos Pass and Painted Cave area on the east. The flow in all the developed springs and headwater streams within this area, here designated as the Tecolote Tunnel Area of the purpose of this report, is generally measured monthly. The primary purpose of this second progress report is to make available to the public all factual data regarding the flow at these locations obtained since the preparation of the first progress report, issued in May 1949. Near the mid-point of this area the Bureau of Reclamation and the Santa Barbara County Water Agency proposed a tunnel, known as Tecolote Tunnel, for the purpose of diverting a portion of the runoff of the Santa Ynez River drainage area into water-deficient Santa Barbara and the coastal areas to the east and west, Because the water users of the mountain springs in the Tecolote Tunnel Area are somewhat apprehensive as to the influence this tunnel may have on their present water supply, the Santa Barbara Water Agency has requested the Geological Survey to obtain records of flow in their springs at frequent and regular intervals. During the current fiscal year these observations have been made as a result of a cooperative agreement between the Geological Survey and the Santa Barbara County Water Agency whereby each paid half the cost of the investigation. During the previous fiscal year all the costs to the Geological Survey in obtaining these observations were completely reimbursed by the Bureau of Reclamation.

Webinar May 17: Fuel Cell Electric Bus Progress Toward Meeting Technical

Science.gov Websites

Targets | News | NREL Webinar May 17: Fuel Cell Electric Bus Progress toward Meeting Technical Targets Webinar May 17: Fuel Cell Electric Bus Progress toward Meeting Technical Targets May 14, 2018 The U.S. Department of Energy's (DOE's) Fuel Cell Technologies Office will present a live webinar titled

Leukocytes as carriers for targeted cancer drug delivery

PubMed Central

Mitchell, Michael J

2017-01-01

Introduction Metastasis contributes to over 90% of cancer-related deaths. Numerous nanoparticle platforms have been developed to target and treat cancer, yet efficient delivery of these systems to the appropriate site remains challenging. Leukocytes, which share similarities to tumor cells in terms of their transport and migration through the body, are well suited to serve as carriers of drug delivery systems to target cancer sites. Areas covered This review focuses on the use and functionalization of leukocytes for therapeutic targeting of metastatic cancer. Tumor cell and leukocyte extravasation, margination in the bloodstream, and migration into soft tissue are discussed, along with the potential to exploit these functional similarities to effectively deliver drugs. Current nanoparticle-based drug formulations for the treatment of cancer are reviewed, along with methods to functionalize delivery vehicles to leukocytes, either on the surface and/or within the cell. Recent progress in this area, both in vitro and in vivo, is also discussed, with a particular emphasis on targeting cancer cells in the bloodstream as a means to interrupt the metastatic process. Expert opinion Leukocytes interact with cancer cells both in the bloodstream and at the site of solid tumors. These interactions can be utilized to effectively deliver drugs to targeted areas, which can reduce both the amount of drug required and various nonspecific cytotoxic effects within the body. If drug delivery vehicle functionalization does not interfere with leukocyte function, this approach may be utilized to neutralize tumor cells in the bloodstream to prevent the formation of new metastases, and also to deliver drugs to metastatic sites within tissues. PMID:25270379

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 ...

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

PubMed

2011-04-15

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

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

USGS Publications Warehouse

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

2009-01-01

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

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

PubMed

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

2014-05-01

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

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.

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

PubMed

Wilkinson, Trevor C I

2016-06-15

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

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.

Scrutinizing data helps team target high-cost DRGs, improve costly tracheostomy care.

PubMed

1997-10-01

Targeting high-cost DRGs using data collection, analysis: A hospital team analyzed DRGs with the highest excess charges and found DRG 483 (tracheostomy) had astronomical charges. Here's the step-by-step story of how they analyzed individual physician resource utilization, care progression through the hospital, and admission source to identify areas for clinical improvement, plus their findings and how they're putting them to use to improve care and reduce costs.

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

PubMed

Asi, Yara M; Williams, Cynthia

2018-06-01

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

Multiple Target Laser Designator (MTLD)

DTIC Science & Technology

2007-03-01

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

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

PubMed

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

2017-03-01

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

[Necrotizing fasciitis in head and neck area].

PubMed

Sántha, Beáta; Sári, Katalin; Fülep, Zoltán; Patyi, Márta; Oberna, Ferenc

2017-03-01

Necrotizing fasciitis is a fulminant infection of the deeper layers of skin and subcutaneous tissues characterized by progressive soft tissue necrosis and high mortality. It rarely occurs in the head and neck area. The clinical picture includes non-specific but typical local and systemic symptoms. The treatment is a complex, multidisciplinary task which includes radical surgical exploration, debridement and drainage, empirically started and then targeted intravenous antibiotics and supportive therapy. Authors report a case of necrotizing fasciitis localized on the right side of the face which caused multi-organ failure and phlegmone of the neck.

Targeting RhoA/Rho kinase and p21-activated kinase signaling to prevent cancer development and progression.

PubMed

Chang, Yu-Wen E; Bean, Ronald R; Jakobi, Rolf

2009-06-01

Elevated RhoA/Rho kinase and p21-activated kinase signaling have been shown to promote cancer development and metastasis and have drawn much attention as potential targets of anti-cancer therapy. Elevated RhoA and Rho kinase activity promote cancer cell invasion and eventually lead to metastasis by disrupting E-cadherin-mediated adherens junctions and degradation of the extracellular matrix. Elevated p21-activated kinase activity promotes invasion by stimulating cell motility but also promotes cancer cell survival and growth. In this review we describe normal functions of RhoA/Rho kinase and p21-activated kinase signaling, mechanisms that lead to constitutive activation of RhoA/Rho kinase and p21-activated kinase pathways, and processes by which constitutive RhoA/Rho kinase and p21-activated kinase activity promote cancer development and progression to more aggressive and metastatic phenotypes. In addition, we summarize relevant patents on RhoA/Rho kinase and p21-activated kinase as targets of anti-cancer therapy and discuss the clinical potential of different approaches to modulate RhoA/Rho kinase and p21-activated kinase signaling.

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

Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

PubMed

Castellanos, Emily H; Horn, Leora

2016-06-01

: The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease. ©AlphaMed Press.

Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

PubMed Central

Castellanos, Emily H.

2016-01-01

The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. Implications for Practice: The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease. PMID:27053502

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.

Progress of targeted genome modification approaches in higher plants.

PubMed

Cardi, Teodoro; Neal Stewart, C

2016-07-01

Transgene integration in plants is based on illegitimate recombination between non-homologous sequences. The low control of integration site and number of (trans/cis)gene copies might have negative consequences on the expression of transferred genes and their insertion within endogenous coding sequences. The first experiments conducted to use precise homologous recombination for gene integration commenced soon after the first demonstration that transgenic plants could be produced. Modern transgene targeting categories used in plant biology are: (a) homologous recombination-dependent gene targeting; (b) recombinase-mediated site-specific gene integration; (c) oligonucleotide-directed mutagenesis; (d) nuclease-mediated site-specific genome modifications. New tools enable precise gene replacement or stacking with exogenous sequences and targeted mutagenesis of endogeneous sequences. The possibility to engineer chimeric designer nucleases, which are able to target virtually any genomic site, and use them for inducing double-strand breaks in host DNA create new opportunities for both applied plant breeding and functional genomics. CRISPR is the most recent technology available for precise genome editing. Its rapid adoption in biological research is based on its inherent simplicity and efficacy. Its utilization, however, depends on available sequence information, especially for genome-wide analysis. We will review the approaches used for genome modification, specifically those for affecting gene integration and modification in higher plants. For each approach, the advantages and limitations will be noted. We also will speculate on how their actual commercial development and implementation in plant breeding will be affected by governmental regulations.

Leukocytes as carriers for targeted cancer drug delivery.

PubMed

Mitchell, Michael J; King, Michael R

2015-03-01

Metastasis contributes to over 90% of cancer-related deaths. Numerous nanoparticle platforms have been developed to target and treat cancer, yet efficient delivery of these systems to the appropriate site remains challenging. Leukocytes, which share similarities to tumor cells in terms of their transport and migration through the body, are well suited to serve as carriers of drug delivery systems to target cancer sites. This review focuses on the use and functionalization of leukocytes for therapeutic targeting of metastatic cancer. Tumor cell and leukocyte extravasation, margination in the bloodstream, and migration into soft tissue are discussed, along with the potential to exploit these functional similarities to effectively deliver drugs. Current nanoparticle-based drug formulations for the treatment of cancer are reviewed, along with methods to functionalize delivery vehicles to leukocytes, either on the surface and/or within the cell. Recent progress in this area, both in vitro and in vivo, is also discussed, with a particular emphasis on targeting cancer cells in the bloodstream as a means to interrupt the metastatic process. Leukocytes interact with cancer cells both in the bloodstream and at the site of solid tumors. These interactions can be utilized to effectively deliver drugs to targeted areas, which can reduce both the amount of drug required and various nonspecific cytotoxic effects within the body. If drug delivery vehicle functionalization does not interfere with leukocyte function, this approach may be utilized to neutralize tumor cells in the bloodstream to prevent the formation of new metastases, and also to deliver drugs to metastatic sites within tissues.

Benzene | Cancer Trends Progress Report

Cancer.gov

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

Nitrate | Cancer Trends Progress Report

Cancer.gov

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

Radon | Cancer Trends Progress Report

Cancer.gov

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

Prevention | Cancer Trends Progress Report

Cancer.gov

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

Arsenic | Cancer Trends Progress Report

Cancer.gov

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

Cadmium | Cancer Trends Progress Report

Cancer.gov

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

Sunburn | Cancer Trends Progress Report

Cancer.gov

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

Highlights | Cancer Trends Progress Report

Cancer.gov

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

Diagnosis | Cancer Trends Progress Report

Cancer.gov

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

Acknowledgments | Cancer Trends Progress Report

Cancer.gov

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

Introduction | Cancer Trends Progress Report

Cancer.gov

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

Mortality | Cancer Trends Progress Report

Cancer.gov

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

Survival | Cancer Trends Progress Report

Cancer.gov

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

Incidence | Cancer Trends Progress Report

Cancer.gov

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

Treatment | Cancer Trends Progress Report

Cancer.gov

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

Home | Cancer Trends Progress Report

Cancer.gov

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

Weight | Cancer Trends Progress Report

Cancer.gov

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

Sixth progress report on the cooperative investigation of springs and streamflow in the Tecolote Tunnel area of Santa Barbara County, California

USGS Publications Warehouse

Hofmann, Walter

1955-01-01

This report is the sixth in a continuing series of progress reports giving the results of discharge measurements obtained at more than 120 selected sites in the "Tecolote Tunnel Area" of the Santa Ynez Mountains.  The area derives its name from the tunnel now being completed by the Bureau of Reclamation for the purpose of diverting the flood waters of the Santa Ynez River stored in Cachuma Reservoir into urban and agricultural areas in and near the city of Santa barbara.  The observational area for purposes of this investigation extends from Refugio Pass on the west to San Marcos Pass and the Painted Cave area on the east.  The tunnel alignment is rouhly north and south through the center of this area.

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.

Doxycycline directly targets PAR1 to suppress tumor progression.

PubMed

Zhong, Weilong; Chen, Shuang; Zhang, Qiang; Xiao, Ting; Qin, Yuan; Gu, Ju; Sun, Bo; Liu, Yanrong; Jing, Xiangyan; Hu, Xuejiao; Zhang, Peng; Zhou, Honggang; Sun, Tao; Yang, Cheng

2017-03-07

Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials.

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

PubMed Central

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

2017-01-01

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

ISS Progress 24 Rollout

NASA Image and Video Library

2007-01-16

JSC2007-E-03082 (16 Jan. 2007) --- Roll-out of the Progress 24 vehicle occurred on schedule at 7:00 a.m., Jan. 16, 2007 at the Baikonur Cosmodrome, Kazakhstan. The vehicle was in the vertical and hard-down at the pad by 9:30 a.m. The gantry towers were placed around the vehicle shortly thereafter. Progress is targeted for launch on Jan. 18, 2007 for a two-day trip to the International Space Station carrying 2 1/2 tons of food, fuel and supplies for the Expedition 14 crew. Photo Credit: NASA

Tracking progress toward global polio eradication, 2010-2011.

PubMed

2012-04-20

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

Doxycycline directly targets PAR1 to suppress tumor progression

PubMed Central

Qin, Yuan; Gu, Ju; Sun, Bo; Liu, Yanrong; Jing, Xiangyan; Hu, Xuejiao; Zhang, Peng; Zhou, Honggang; Sun, Tao; Yang, Cheng

2017-01-01

Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials. PMID:28187433

Progress and Challenges in Selected Areas of Tobacco Carcinogenesis

PubMed Central

Hecht, Stephen S.

2008-01-01

Tobacco use continues to be a major cause of cancer in the developed world and, despite significant progress in this country in tobacco control which is driving a decrease in cancer mortality, there are still over one billion smokers in the world. This perspective discusses some selected issues in tobacco carcinogenesis focusing on progress during the 20 years of publication of Chemical Research in Toxicology. The topics covered include metabolism and DNA modification by tobacco-specific nitrosamines, tobacco carcinogen biomarkers, an unidentified DNA ethylating agent in cigarette smoke, mutations in the K-RAS and p53 gene in tobacco-induced lung cancer and their possible relationship to specific carcinogens, secondhand smoke and lung cancer, emerging issues in smokeless tobacco use, and a conceptual model for understanding tobacco carcinogenesis. It is hoped that a better understanding of mechanisms of tobacco-induced cancer will lead to new and useful approaches for prevention of lung cancer and other cancers caused by tobacco use. PMID:18052103

Approaches to the implementation of the Water Framework Directive: targeting mitigation measures at critical source areas of diffuse phosphorus in Irish catchments.

PubMed

Doody, D G; Archbold, M; Foy, R H; Flynn, R

2012-01-01

The Water Framework Directive (WFD) has initiated a shift towards a targeted approach to implementation through its focus on river basin districts as management units and the natural ecological characteristics of waterbodies. Due to its role in eutrophication, phosphorus (P) has received considerable attention, resulting in a significant body of research, which now forms the evidence base for the programme of measures (POMs) adopted in WFD River Basin Management Plans (RBMP). Targeting POMs at critical sources areas (CSAs) of P could significantly improve environmental efficiency and cost effectiveness of proposed mitigation strategies. This paper summarises the progress made towards targeting mitigation measures at CSAs in Irish catchments. A review of current research highlights that knowledge related to P export at field scale is relatively comprehensive however; the availability of site-specific data and tools limits widespread identification of CSA at this scale. Increasing complexity of hydrological processes at larger scales limits accurate identification of CSA at catchment scale. Implementation of a tiered approach, using catchment scale tools in conjunction with field-by-field surveys could decrease uncertainty and provide a more practical and cost effective method of delineating CSA in a range of catchments. Despite scientific and practical uncertainties, development of a tiered CSA-based approach to assist in the development of supplementary measures would provide a means of developing catchment-specific and cost-effective programmes of measures for diffuse P. The paper presents a conceptual framework for such an approach, which would have particular relevance for the development of supplementary measures in High Status Waterbodies (HSW). The cost and resources necessary for implementation are justified based on HSWs' value as undisturbed reference condition ecosystems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Socio-economic and ecological impacts of global protected area expansion plans

PubMed Central

Visconti, Piero; Bakkenes, Michel; Smith, Robert J.; Joppa, Lucas; Sykes, Rachel E.

2015-01-01

Several global strategies for protected area (PA) expansion have been proposed to achieve the Convention on Biological Diversity's Aichi target 11 as a means to stem biodiversity loss, as required by the Aichi target 12. However, habitat loss outside PAs will continue to affect habitats and species, and PAs may displace human activities into areas that might be even more important for species persistence. Here we measure the expected contribution of PA expansion strategies to Aichi target 12 by estimating the extent of suitable habitat available for all terrestrial mammals, with and without additional protection (the latter giving the counterfactual outcome), under different socio-economic scenarios and consequent land-use change to 2020. We found that expanding PAs to achieve representation targets for ecoregions under a Business-as-usual socio-economic scenario will result in a worse prognosis than doing nothing for more than 50% of the world's terrestrial mammals. By contrast, targeting protection towards threatened species can increase the suitable habitat available to over 60% of terrestrial mammals. Even in the absence of additional protection, an alternative socio-economic scenario, adopting progressive changes in human consumption, leads to positive outcomes for mammals globally and to the largest improvements for wide-ranging species. PMID:26460136

Socio-economic and ecological impacts of global protected area expansion plans.

PubMed

Visconti, Piero; Bakkenes, Michel; Smith, Robert J; Joppa, Lucas; Sykes, Rachel E

2015-11-05

Several global strategies for protected area (PA) expansion have been proposed to achieve the Convention on Biological Diversity's Aichi target 11 as a means to stem biodiversity loss, as required by the Aichi target 12. However, habitat loss outside PAs will continue to affect habitats and species, and PAs may displace human activities into areas that might be even more important for species persistence. Here we measure the expected contribution of PA expansion strategies to Aichi target 12 by estimating the extent of suitable habitat available for all terrestrial mammals, with and without additional protection (the latter giving the counterfactual outcome), under different socio-economic scenarios and consequent land-use change to 2020. We found that expanding PAs to achieve representation targets for ecoregions under a Business-as-usual socio-economic scenario will result in a worse prognosis than doing nothing for more than 50% of the world's terrestrial mammals. By contrast, targeting protection towards threatened species can increase the suitable habitat available to over 60% of terrestrial mammals. Even in the absence of additional protection, an alternative socio-economic scenario, adopting progressive changes in human consumption, leads to positive outcomes for mammals globally and to the largest improvements for wide-ranging species. © 2015 The Author(s).

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 U.S. RERTR program status and progress.

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

Travelli, A.

1998-01-21

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

Loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CDC28 protein kinase regulatory subunit 1B.

PubMed

Hu, Minghua; Wang, Mingwei; Lu, Huihong; Wang, Xiaoming; Fang, Xiaoshan; Wang, Jinguo; Ma, Chenyang; Chen, Xiaobing; Xia, Hongping

2016-07-12

Hepatocellular carcinoma (HCC) is the leading cause of cancer related death worldwide. The number of deaths is proportional to the global incidence, which highlights the aggressive tumor biology and lack of effective therapies. Dysregulation of microRNAs has been implicated in carcinogenesis and progression of liver cancer. Here, we identified that miR-1258 was significantly downregulated in HCC and associated with poor patients' survival. Overexpression of miR-1258 significantly inhibits liver cancer cell growth, proliferation and tumorigenicity through increasing cell cycle arrest in G0/G1 phase and promotes cell apoptosis. Interestingly, stable overexpression of miR-1258 suppresses cell migration, stemness and increases sensitivity of HCC cells to chemotherapy drug like doxorubicin. The CDC28 protein kinase regulatory subunit 1B (CKS1B) was identified as a functional downstream target of miR-1258. Re-expression of CKS1B overcomes miR-1258 induced apoptosis and increases stemness of HCC cells, suggesting that loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CKS1B . Therefore, loss of miR-1258 may be a potential diagnostic and prognostic biomarker and blocking miR-1258-CKS1B axis is a potential therapeutic strategy in HCC.

Targeting gene expression selectively in cancer cells by using the progression-elevated gene-3 promoter.

PubMed

Su, Zhao-Zhong; Sarkar, Devanand; Emdad, Luni; Duigou, Gregory J; Young, Charles S H; Ware, Joy; Randolph, Aaron; Valerie, Kristoffer; Fisher, Paul B

2005-01-25

One impediment to effective cancer-specific gene therapy is the rarity of regulatory sequences targeting gene expression selectively in tumor cells. Although many tissue-specific promoters are recognized, few cancer-selective gene promoters are available. Progression-elevated gene-3 (PEG-3) is a rodent gene identified by subtraction hybridization that displays elevated expression as a function of transformation by diversely acting oncogenes, DNA damage, and cancer cell progression. The promoter of PEG-3, PEG-Prom, displays robust expression in a broad spectrum of human cancer cell lines with marginal expression in normal cellular counterparts. Whereas GFP expression, when under the control of a CMV promoter, is detected in both normal and cancer cells, when GFP is expressed under the control of the PEG-Prom, cancer-selective expression is evident. Mutational analysis identifies the AP-1 and PEA-3 transcription factors as primary mediators of selective, cancer-specific expression of the PEG-Prom. Synthesis of apoptosis-inducing genes, under the control of the CMV promoter, inhibits the growth of both normal and cancer cells, whereas PEG-Prom-mediated expression of these genes kills only cancer cells and spares normal cells. The efficacy of the PEG-Prom as part of a cancer gene therapeutic regimen is further documented by in vivo experiments in which PEG-Prom-controlled expression of an apoptosis-inducing gene completely inhibited prostate cancer xenograft growth in nude mice. These compelling observations indicate that the PEG-Prom, with its cancer-specific expression, provides a means of selectively delivering genes to cancer cells, thereby providing a crucial component in developing effective cancer gene therapies.

Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer

PubMed Central

Chavez-Gonzalez, Antonieta; Bakhshinejad, Babak; Pakravan, Katayoon

2018-01-01

Background Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are characterized by high self-renewal and multi-lineage differentiation capacities. CSCs are thought to play indispensable roles in the initiation, progression and metastasis of many types of cancer. Leukemias are thought to be initiated and maintained by a specific sub-type of CSC, the leukemia stem cell (LSC). An important feature of LSCs is their resistance to standard therapy, which may lead to relapse. Increasing efforts are aimed at developing novel therapeutic strategies that selectively target LSCs, while sparing their normal counterparts and, thus, minimizing adverse treatment-associated side-effects. These LSC targeting therapies aim to eradicate LSCs through affecting mechanisms that control their survival, self-renewal, differentiation, proliferation and cell cycle progression. Some LSC targeting therapies have already been proven successful in pre-clinical studies and they are now being tested in clinical studies, mainly in combination with conventional treatment regimens. Conclusions A growing body of evidence indicates that the selective targeting of LSCs represents a promising approach to improve disease outcome. Beyond doubt, the CSC hypothesis has added a new dimension to the area of anticancer research, thereby paving the way for shaping a new trend in cancer therapy. PMID:27678246

Progress In Magnetized Target Fusion Driven by Plasma Liners

NASA Technical Reports Server (NTRS)

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

The 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.

Upregulation of mucin glycoprotein MUC1 in the progression to esophageal adenocarcinoma and therapeutic potential with a targeted photoactive antibody-drug conjugate

PubMed Central

Haidry, Rehan J.; Oukrif, Dahmane; Khan, Saif-U-Rehman; Puccio, Ignazio; Gandy, Michael; Reinert, Halla W.; Bloom, Ellie; Rashid, Mohammed; Yahioglu, Gokhan; Deonarain, Mahendra P.; Hamoudi, Rifat; Rodriguez-Justo, Manuel; Novelli, Marco R.; Lovat, Laurence B.

2017-01-01

Background Mucin glycoprotein 1 (MUC1) is a glycosylated transmembrane protein on epithelial cells. We investigate MUC1 as a therapeutic target in Barrett’s epithelium (BE) and esophageal adenocarcinoma (EA) and provide proof of concept for a light based therapy targeting MUC1. RESULTS MUC1 was present in 21% and 30% of significantly enriched pathways comparing BE and EA to squamous epithelium respectively. MUC1 gene expression was x2.3 and x2.2 higher in BE (p=<0.001) and EA (p=0.03). MUC1 immunohistochemical expression increased during progression to EA and followed tumor invasion. HuHMFG1 based photosensitive antibody drug conjugates (ADC) showed cell internalization, MUC1 selective and light-dependent cytotoxicity (p=0.0006) and superior toxicity over photosensitizer alone (p=0.0022). Methods Gene set enrichment analysis (GSEA) evaluated pathways during BE and EA development and quantified MUC1 gene expression. Immunohistochemistry and flow cytometry evaluated the anti-MUC1 antibody HuHMFG1 in esophageal cells of varying pathological grade. Confocal microscopy examined HuHMFG1 internalization and HuHMFG1 ADCs were created to deliver a MUC1 targeted phototoxic payload. Conclusions MUC1 is a promising target in EA. Molecular and light based targeting of MUC1 with a photosensitive ADC is effective in vitro and after development may enable treatment of locoregional tumors endoscopically. PMID:28212575

miRNA-27b Targets Vascular Endothelial Growth Factor C to Inhibit Tumor Progression and Angiogenesis in Colorectal Cancer

PubMed Central

Wu, Dang; Wu, Pin; Ni, Chao; Zhang, Zhigang; Chen, Zhigang; Qiu, Fuming; Xu, Jinghong; Huang, Jian

2013-01-01

Colorectal cancer (CRC) is one of the most prevalent cancers globally and is one of the leading causes of cancer-related deaths due to therapy resistance and metastasis. Understanding the mechanism underlying colorectal carcinogenesis is essential for the diagnosis and treatment of CRC. microRNAs (miRNAs) can act as either oncogenes or tumor suppressors in many cancers. A tumor suppressor role for miR-27b has recently been reported in neuroblastoma, while no information about miR-27b in CRC is available. In this study, we demonstrated that miR-27b expression is decreased in most CRC tissues and determined that overexpression of miR-27b represses CRC cell proliferation, colony formation and tumor growth in vitro and in vivo. We identified vascular endothelial growth factor C (VEGFC) as a novel target gene of miR-27b and determined that miR-27b functioned as an inhibitor of tumor progression and angiogenesis through targeting VEGFC in CRC. We further determined that DNA hypermethylation of miR-27b CpG islands decreases miR-27b expression. In summary, an anti-tumor role for miR-27b and its novel target VEGFC in vivo could lead to tumor necrosis and provide a rationale for developing miR-27b as a therapeutic agent. PMID:23593282

Castration-resistant prostate cancer: targeted therapies.

PubMed

Leo, S; Accettura, C; Lorusso, V

2011-01-01

Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited. To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC. Novel targeted therapies in clinical trials were identified from registries. The Medline database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies. Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression have translated into a variety of treatment approaches. Agents targeting androgen receptor activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase III trials for patients with CRPC. There has been an increase in the understanding of the mechanisms of progression of CRPC. A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future. Copyright © 2011 S. Karger AG, Basel.

The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low-density media.

PubMed

Kan, Monica W K; Leung, Lucullus H T; Yu, Peter K N

2013-11-04

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric-modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no-air) for RapidArc planning in targets with low-density media of different sizes and complexities. The performance of PRO10_no-air and PRO10_air was initially compared using single-arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple-arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non-small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no-air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low-density media were present in or adjacent to the target volume, the use of the air cavity correction option in PRO10 was shown to be beneficial. For NPC cases or cases for which small volumes of both low- and high-density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between

The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low‐density media

PubMed Central

Leung, Lucullus H.T.; Yu, Peter K.N.

2013-01-01

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric‐modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no‐air) for RapidArc planning in targets with low‐density media of different sizes and complexities. The performance of PRO10_no‐air and PRO10_air was initially compared using single‐arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple‐arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non‐small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no‐air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low‐density media were present in or adjacent to the target volume, the use of the air cavity correction option in PROIO was shown to be beneficial. For NPC cases or cases for which small volumes of both low‐ and high‐density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan

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

PubMed

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

2017-01-01

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

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

PubMed Central

Qin, Yaochen; Lee, Jay

2017-01-01

This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention. PMID:28950027

Global progress in prevention of cardiovascular disease

PubMed Central

2017-01-01

Although there is measurable global progress in prevention of cardiovascular disease (CVD), it has been highly uneven and inadequate, particularly in low- and middle-income countries. Voluntary global targets have helped to galvanize attention, resources and accountability on tobacco use, harmful use of alcohol, unhealthy diet and physical inactivity which are the major behavioural drivers of CVD. Many obstacles and challenges continue to impede the progress of cardiovascular prevention. The inclusion of noncommunicable diseases (NCDs) in the sustainable development agenda as a specific target, offers an unprecedented opportunity to further advance the global progress of cardiovascular prevention. In order to seize this opportunity, a paradigm shift is required in the way key challenges to cardiovascular prevention are addressed. Such an approach must provide leadership for intersectoral policy coherence, identify effective means of tackling commercial determinants of behavioural risk factors, use rights based arguments, enhance public engagement and ensure accountability. PMID:28529920

Scales of Progress

ERIC Educational Resources Information Center

Jung, Lee Ann

2018-01-01

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

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

PubMed

Neelsen, Sven; O'Donnell, Owen

2017-12-01

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

Progress in myeloma stem cells

PubMed Central

Cruz, Richard Dela; Tricot, Guido; Zangari, Maurizio; Zhan, Fenghuang

2011-01-01

Multiple myeloma (MM) is the second most common hematologic malignancy in the United States and affects about 4 in 100,000 Americans. Even though much progress has been made in MM therapy, MM remains an incurable disease for the vast majority of patients. The existence of MM stem cell is considered one of the major causes of MM drug-resistance, leading to relapse. This highlights the importance and urgency of developing approaches to target MM stem cells. However, very little is known about the molecular characteristics of the MM stem cells, which makes it difficult to target MM stem cells therapeutically. Evidence of the existence of a myeloma stem cell has been provided by Matsui et al. showing that the CD138- and CD20+ fraction, which is a minor population of the MM cells, has a greater clonogenic potential and has the phenotype of a memory B-cell (CD19+, CD27+). In this review, we report recent progress of cell surface markers in cancer stem cells, especially in myeloma and the molecular mechanisms related to drug resistance and myeloma disease progression. PMID:22432075

Substantial heterogeneity in progress towards reaching the 90-90-90 HIV target in the WHO European Region.

PubMed

Porter, Kholoud; Gourlay, Annabelle; Attawell, Kathy; Hales, David; Supervie, Virginie; Touloumi, Giota; Rosinska, Magda; Vourli, Georgia; van Sighem, Ard; Pharris, Anastasia; Noori, Teymur

2018-05-25

Achieving the UNAIDS 90-90-90 target by 2020 is expected to end the HIV epidemic by 2030. We report on progress in the WHO European Region in meeting this target. The European Centre for Disease Prevention and Control (ECDC) sent questionnaires to 55 countries in 2016. We report estimates for four stages of the continuum of HIV care (living with HIV; diagnosed; treated; virally-suppressed), corresponding to UNAIDS' target, explore differences by sub-region, and challenges with reporting data. Forty-four countries provided data for ≥ one stage, and 29 for all four stages. Estimated HIV prevalence was 0.19% (range 0.02-0.84%, n=37 countries providing stage one data). The proportion diagnosed of people living with HIV (PLHIV) ranged from 38-98% (n=37 reporting number of PLHIV and diagnosed). The proportion on ART of those diagnosed ranged from 27-96% (n=40 reporting numbers diagnosed and treated), and viral suppression rates ranged from 32-97% (n=31 providing numbers treated and virally-suppressed). The overall continuum of care estimate for 29 countries with complete data was 81-84-88, which differed by sub-region: 84-88-90, 84-69-62, and 57-45-57 for western, central and eastern sub-regions, respectively. Challenges in reporting data included absence of a single data source for all stages, shortage of expertise, and lack of financial and human resources. There is an urgent need to strengthen HIV testing programmes throughout Europe, particularly in the eastern sub-region, and to remove constraints hampering access to testing and care. Recent changes to treatment guidelines should help reduce the numbers diagnosed not treated.

Director's Message | Cancer Trends Progress Report

Cancer.gov

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

Contact Us | Cancer Trends Progress Report

Cancer.gov

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

Summary Tables | Cancer Trends Progress Report

Cancer.gov

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

Indoor Tanning | Cancer Trends Progress Report

Cancer.gov

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

Early Detection | Cancer Trends Progress Report

Cancer.gov

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

Data Sources | Cancer Trends Progress Report

Cancer.gov

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

Fat Consumption | Cancer Trends Progress Report

Cancer.gov

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

Secondhand Smoke | Cancer Trends Progress Report

Cancer.gov

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

HPV Immunization | Cancer Trends Progress Report

Cancer.gov

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

Smoking Cessation | Cancer Trends Progress Report

Cancer.gov

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

Tobacco Use | Cancer Trends Progress Report

Cancer.gov

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

Data Resources | Cancer Trends Progress Report

Cancer.gov

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

Alcohol Consumption | Cancer Trends Progress Report

Cancer.gov

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

Custom Report | Cancer Trends Progress Report

Cancer.gov

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

Physical Activity | Cancer Trends Progress Report

Cancer.gov

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

Quitting Smoking | Cancer Trends Progress Report

Cancer.gov

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

NCI Dictionary | Cancer Trends Progress Report

Cancer.gov

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

Emerging therapeutic targets in metastatic progression: a focus on breast cancer

PubMed Central

Li, Zhuo; Kang, Yibin

2016-01-01

Metastasis is the underlying cause of death for the majority of breast cancer patients. Despite significant advances in recent years in basic research and clinical development, therapies that specifically target metastatic breast cancer remain inadequate, and represents the single greatest obstacle to reducing mortality of late-stage breast cancer. Recent efforts have leveraged genomic analysis of breast cancer and molecular dissection of tumor-stromal cross-talk to uncover a number of promising candidates for targeted treatment of metastatic breast cancer. Rational combinations of therapeutic agents targeting tumor-intrinsic properties and microenvironmental components provide a promising strategy to develop precision treatments with higher specificity and less toxicity. In this review, we discuss the emerging therapeutic targets in breast cancer metastasis, from tumor-intrinsic pathways to those that involve the host tissue components, including the immune system. PMID:27000769

TARGET Research Goals

Cancer.gov

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

Mutation testing for directing upfront targeted therapy and post-progression combination therapy strategies in lung adenocarcinoma

PubMed Central

Salgia, Ravi

2016-01-01

ABSTRACT Introduction: Advances in the biology of non-small-cell lung cancer, especially adenocarcinoma, reveal multiple molecular subtypes driving oncogenesis. Accordingly, individualized targeted therapeutics are based on mutational diagnostics. Areas covered: Advances in strategies and techniques for individualized treatment, particularly of adenocarcinoma, are described through literature review. Approved therapies are established for some molecular subsets, with new driver mutations emerging that represent increasing proportions of patients. Actionable mutations are de novo oncogenic drivers or acquired resistance mediators, and mutational profiling is important for directing therapy. Patients should be monitored for emerging actionable resistance mutations. Liquid biopsy and associated multiplex diagnostics will be important means to monitor patients during treatment. Expert commentary: Outcomes with targeted agents may be improved by integrating mutation screens during treatment to optimize subsequent therapy. In order for this to be translated into impactful patient benefit, appropriate platforms and strategies need to be optimized and then implemented universally. PMID:27139190

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

PubMed

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

2013-11-07

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

Progress and challenges in consolidating the management of Amazonian protected areas and indigenous territories.

PubMed

Gullison, Raymond E; Hardner, Jared

2018-05-18

Achieving the effective management of all existing protected areas and indigenous territories in the Amazon Biome may be needed to avoid a deforestation "tipping point" beyond which regional climatic feedbacks and global climate change interact to catalyze irreversible drying and savannization of large portions of the biome. However, the time and money required to consolidate the effective management of all types of protected sites in the Amazon is still poorly understood. At present, protected areas and indigenous territories cover 45.5% of the biome (3.55 million km 2 ), the lion's share of the 60-70% forest cover required to maintain hydrologic and climatic function. Three independent evaluations of the 1.68 million km 2 of protected areas and indigenous territories supported by one philanthropic foundation yield insights into the challenges and advances towards achieving effective management of these sites. Considerable progress has been made in improving the management of protected areas and indigenous territories. Despite this, few sites can be considered effectively managed and many continue to lack sufficient long-term finance, adequate capacity in governments or NGOs, and the ability to withstand economic pressures. External funding will continue to be critical as long as core-funding needs are not met by governments or other sources such as payments for environmental services. The duration of external funding required could easily be on the scale of decades, with strict protected areas achieving effective management status the soonest, and indigenous territories taking the longest. Despite these challenges, the fact that legal protection has expanded so greatly in recent years is encouraging, and that management of sites is improving steadily over time. These lessons are relevant for the consolidation of sites in other developing countries that are trying to increase their management effectiveness under the constraint of limited resources. This article is

Dissecting and Targeting Latent Metastasis

DTIC Science & Technology

2013-09-01

particular. Developing and using experimental models of LMBC to elucidate these survival mechanisms will provide a basis for therapeutically targeting...stochastic, low frequency generation of lethal macrometastatic lesion. Progress Item 1.1. Using this approach, we have successfully isolated latent...cells lines are being used to illuminate the molecular basis for the latent metastasis state. Progress Item 1.2. In parallel with the isolation of

Perspective of Muon Production Target at J-PARC MLF MUSE

NASA Astrophysics Data System (ADS)

Makimura, Shunsuke; Matoba, Shiro; Kawamura, Naritoshi; Matsuzawa, Yukihiro; Tabe, Masato; Aoyagi, Hiroyuki; Kondo, Hiroto; Kobayashi, Yasuo; Fujimori, Hiroshi; Ikedo, Yutaka; Kadono, Ryosuke; Koda, Akihiro; Kojima, Kenji M.; Miyake, Yasuhiro; Nakamura, Jumpei G.; Oishi, Yu; Okabe, Hirotaka; Shimomura, Koichiro; Strasser, Patrick

A pulsed muon beam with unprecedented intensity will be generated by a 3-GeV 333-microA proton beam on a muon target made of 20-mm thick isotropic graphite at J-PARC MLF MUSE (Muon Science Establishment). The first muon beam was successfully generated on September 26th, 2008. Gradually upgrading the beam intensity, continuous 300-kW proton beam has been operated by a fixed target method without replacements till June of 2014. However, the lifetime of the fixed target was anticipated to be less than 1 year by the proton-irradiation damage of the graphite through 1-MW beam operation. To extend the lifetime, a muon rotating target, in which the radiation damage is distributed to a wider area, was installed in September of 2014, and continuous and stable operation has been successfully performed. Because the muon target becomes highly radioactive by the proton irradiation, the maintenance is conducted by remote handling in the Hot cell. In September of 2015, a scraper No. 1 to collimate the proton beam scattered by the target was replaced for further high-power beam operation. Recently, new developments on monitoring and maintenance of the muon target for higher power operation are in progress. In this article, perspective of muon production target at J-PARC MLF MUSE will be described.

The neural basis of monitoring goal progress

PubMed Central

Benn, Yael; Webb, Thomas L.; Chang, Betty P. I.; Sun, Yu-Hsuan; Wilkinson, Iain D.; Farrow, Tom F. D.

2014-01-01

The neural basis of progress monitoring has received relatively little attention compared to other sub-processes that are involved in goal directed behavior such as motor control and response inhibition. Studies of error-monitoring have identified the dorsal anterior cingulate cortex (dACC) as a structure that is sensitive to conflict detection, and triggers corrective action. However, monitoring goal progress involves monitoring correct as well as erroneous events over a period of time. In the present research, 20 healthy participants underwent functional magnetic resonance imagining (fMRI) while playing a game that involved monitoring progress toward either a numerical or a visuo-spatial target. The findings confirmed the role of the dACC in detecting situations in which the current state may conflict with the desired state, but also revealed activations in the frontal and parietal regions, pointing to the involvement of processes such as attention and working memory (WM) in monitoring progress over time. In addition, activation of the cuneus was associated with monitoring progress toward a specific target presented in the visual modality. This is the first time that activation in this region has been linked to higher-order processing of goal-relevant information, rather than low-level anticipation of visual stimuli. Taken together, these findings identify the neural substrates involved in monitoring progress over time, and how these extend beyond activations observed in conflict and error monitoring. PMID:25309380

The Progress of Nations, 2000.

ERIC Educational Resources Information Center

United Nations Children's Fund, New York, NY.

This report summarizes the latest available statistics on international progress on children's well-being. Each section of the report contains a commentary, related statistics, and a discussion on progress and disparity in the section's particular area. Following a foreword by United Nations Secretary-General Kofi A. Annan, the sections of the…

The Progress of Nations, 1999.

ERIC Educational Resources Information Center

United Nations Children's Fund, New York, NY.

This report summarizes the latest available statistics on international progress on children's well-being. Each of the report's sections contains a commentary, related statistics, and a discussion on progress and disparity in the section's particular area. Following a foreword by United Nations Secretary-General Kofi A. Annan, the sections of the…

Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer.

PubMed

Singh, Prabhsimranjot; Toom, Sudhamshi; Huang, Yiwu

2017-05-12

Targeted therapy and immunotherapy have revolutionized treatment of various cancers in the past decade. Despite targeted therapy with trastuzumab in Her2-positive gastric cancer patients, survival has been dismal, mostly due to disease progression and toxicity related to the treatments. One area of active development is looking for ideal monoclonal antibodies (IMAB) specific to the proteins only on the tumor and hence avoiding unnecessary side effects. Claudin proteins with isoform 2 are one such protein, specific for several cancers, particularly gastric cancer and its metastases, leading to the development of anti-claudin 18.2 specific antibody, claudiximab. This review will highlight the latest development of claudiximab as first in class IMAB for the treatment of gastric cancer.

Antihelminthics in helminth-endemic areas: effects on Hiv disease progression

PubMed Central

Means, Arianna Rubin; Burns, Paul; Sinclair, David; Walson, Judd L

2016-01-01

confirmed helminth infections (difference in mean change 37.86 CD4+ cells/µL, 95% CI 7.36 to 68.35; P = 0.01; three trials, 358 participants, low quality evidence). Adverse events and mortality There is no indication that antihelminthic drugs impart additional risks in HIV-positive populations. However, adverse events were not well reported (very low quality evidence) and trials were underpowered to evaluate effects on mortality (low quality evidence). Authors' conclusions There is low quality evidence that treating confirmed helminth infections in HIV-positive adults may have small, short-term favourable effects on markers of HIV disease progression. Further studies are required to confirm this finding. Current evidence suggests that deworming with antihelminthics is not harmful, and this is reassuring for the routine treatment of confirmed or suspected helminth infections in people living with HIV in co-endemic areas. Further long-term studies are required to make confident conclusions regarding the impact of presumptively deworming all HIV-positive individuals irrespective of helminth infection status, as the only long-term trial to date did not demonstrate an effect. Antihelminthics in helminth endemic areas: effects on HIV infection This Cochrane Review summarizes trials that evaluated the benefits and potential risks of providing deworming drugs (antihelminthics) to people infected with human immunodeficiency virus (HIV). After we searched for relevant trials up to 29 September 2015 we included eight trials that enrolled 1612 participants. What are deworming drugs and why might they delay HIV disease progression Deworming drugs are used to treat a variety of human helminth infections, such as soil-transmitted helminths, schistosomiasis, onchocerciasis, and lymphatic filariasis. In areas where these infections are common, the World Health Organization currently recommends that targeted populations are routinely treated every six to 12 months without prior confirmation

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

Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma

PubMed Central

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

2017-01-01

While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors. PMID:26202204

Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma.

PubMed

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

2016-01-01

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

Measuring progress toward the Millennium Development Goals and the missing millions.

PubMed

Carr-Hill, Roy A

2013-01-01

The 2015 target date for achieving the Millennium Development Goals (MDGs) is fast approaching, but there is very little discussion of the validity of the indicators used to measure progress. In particular, there has been little attention given to the problems that arise when assessments of progress are based on household surveys. These are inappropriate for obtaining information about the poorest of the poor. Typically, they omit by design those not in households because they are homeless; those who are in institutions; and mobile, nomadic or pastoralist populations; and, in practice, household surveys will typically under-represent those in fragile, disjointed or multiple occupancy households; and those in urban slums and insecure areas of a country. Those six subgroups constitute a pretty comprehensive ostensive definition of the "poorest of the poor." Between 300 and 500 million people--mainly in developing countries--will be missed worldwide from the sampling frames of household surveys.

Understanding Your Adequate Yearly Progress (AYP), 2011-2012

ERIC Educational Resources Information Center

Missouri Department of Elementary and Secondary Education, 2011

2011-01-01

The "No Child Left Behind Act (NCLB) of 2001" requires all schools, districts/local education agencies (LEAs) and states to show that students are making Adequate Yearly Progress (AYP). NCLB requires states to establish targets in the following ways: (1) Annual Proficiency Target; (2) Attendance/Graduation Rates; and (3) Participation…

[Current Status of Targeted Treatment in Breast Cancer].

PubMed

Seiffert, Katharina; Schmalfeldt, Barbara; Müller, Volkmar

2017-11-01

Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has been a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer. Evidence-based further line therapy options in the metastatic setting include T-DM1 and in later lines Lapatinib. For triple negative disease the angiogenesis inhibitor Bevacizumab is approved, which increases progression free survival. Immune checkpoint inhibitors, PARP-inhibitors or anti-androgens represent promising strategies, all of which are currently being evaluated in clinical trials. The development of predictive biomarkers to guide targeted therapies is still the subject of research. © Georg Thieme Verlag KG Stuttgart · New York.

EM connectomics reveals axonal target variation in a sequence-generating network

PubMed Central

Narayanan, Rajeevan T; Svara, Fabian; Egger, Robert; Oberlaender, Marcel; Denk, Winfried; Long, Michael A

2017-01-01

The sequential activation of neurons has been observed in various areas of the brain, but in no case is the underlying network structure well understood. Here we examined the circuit anatomy of zebra finch HVC, a cortical region that generates sequences underlying the temporal progression of the song. We combined serial block-face electron microscopy with light microscopy to determine the cell types targeted by HVC(RA) neurons, which control song timing. Close to their soma, axons almost exclusively targeted inhibitory interneurons, consistent with what had been found with electrical recordings from pairs of cells. Conversely, far from the soma the targets were mostly other excitatory neurons, about half of these being other HVC(RA) cells. Both observations are consistent with the notion that the neural sequences that pace the song are generated by global synaptic chains in HVC embedded within local inhibitory networks. DOI: http://dx.doi.org/10.7554/eLife.24364.001 PMID:28346140

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

PubMed

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

2017-12-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2018-06-01

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

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

PubMed

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

2014-12-01

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

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.

ALK-targeted therapy for lung cancer: ready for prime time.

PubMed

Husain, Hatim; Rudin, Charles M

2011-06-01

Lung cancer remains the leading cause of cancer-related death in the United States. Ongoing research into the molecular basis of lung cancer has yielded insight into various critical pathways that are deregulated in lung tumorigenesis, and in particular key driver mutations integral to cancer cell survival and proliferation. One of the most recent examples of this has been definition of translocations and functional dysregulation of the anaplastic lymphoma kinase (ALK) gene in a subset of patients with non-small-cell lung cancer. The pace of research progress in this area has been remarkable: chromosomal rearrangements involving this gene in lung cancer were first reported in 2007 by a team of investigators in Japan. Less than 3 years later, an early-phase clinical trial of a targeted ALK inhibitor has yielded impressive responses in patients with advanced lung cancer containing ALK rearrangements, and mechanisms of acquired resistance to ALK-targeted therapy are being reported. A definitive study randomizing patients with ALK-mutant lung cancer to crizotinib (also known as PF-02341066 or 1066) versus standard therapy has recently completed enrollment.Taken together, these data describe a trajectory of research progress from basic discovery science to real-world implementation that should serve as a model for future integration of preclinical and clinical therapeutic research.

Genetic progression of malignant melanoma.

PubMed

Tímár, J; Vizkeleti, L; Doma, V; Barbai, T; Rásó, E

2016-03-01

Malignant melanoma of the skin is the most aggressive human cancer given that a primary tumor a few millimeters in diameter frequently has full metastatic competence. In view of that, revealing the genetic background of this potential may also help to better understand tumor dissemination in general. Genomic analyses have established the molecular classification of melanoma based on the most frequent driver oncogenic mutations (BRAF, NRAS, KIT) and have also revealed a long list of rare events, including mutations and amplifications as well as genetic microheterogeneity. At the moment, it is unclear whether any of these rare events have role in the metastasis initiation process since the major drivers do not have such a role. During lymphatic and hematogenous dissemination, the clonal selection process is evidently reflected by differences in oncogenic drivers in the metastases versus the primary tumor. Clonal selection is also evident during lymphatic progression, though the genetic background of this immunoselection is less clear. Genomic analyses of metastases identified further genetic alterations, some of which may correspond to metastasis maintenance genes. The natural genetic progression of melanoma can be modified by targeted (BRAF or MEK inhibitor) or immunotherapies. Some of the rare events in primary tumors may result in primary resistance, while further new genetic lesions develop during the acquired resistance to both targeted and immunotherapies. Only a few genetic lesions of the primary tumor are constant during natural or therapy-modulated progression. EGFR4 and NMDAR2 mutations, MITF and MET amplifications and PTEN loss can be considered as metastasis drivers. Furthermore, BRAF and MITF amplifications as well as PTEN loss are also responsible for resistance to targeted therapies, whereas NRAS mutation is the only founder genetic lesion showing any association with sensitivity to immunotherapies. Unfortunately, there are hardly any data on the

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.

Ovarian Cancer Treatment | Cancer Trends Progress Report

Cancer.gov

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

End of Life | Cancer Trends Progress Report

Cancer.gov

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

Life After Cancer | Cancer Trends Progress Report

Cancer.gov

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

Stage at Diagnosis | Cancer Trends Progress Report

Cancer.gov

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

Kidney Cancer Treatment | Cancer Trends Progress Report

Cancer.gov

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

Lung Cancer Treatment | Cancer Trends Progress Report

Cancer.gov

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

Colorectal Cancer Treatment | Cancer Trends Progress Report

Cancer.gov

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

Cervical Cancer Screening | Cancer Trends Progress Report

Cancer.gov

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

Prostate Cancer Treatment | Cancer Trends Progress Report

Cancer.gov

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

Bladder Cancer Treatment | Cancer Trends Progress Report

Cancer.gov

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

Tobacco Use Initiation | Cancer Trends Progress Report

Cancer.gov

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

Youth Tobacco Use | Cancer Trends Progress Report

Cancer.gov

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

Lung Cancer Screening | Cancer Trends Progress Report

Cancer.gov

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

Secondhand Smoke Exposure | Cancer Trends Progress Report

Cancer.gov

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

Breast Cancer Treatment | Cancer Trends Progress Report

Cancer.gov

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

Frequently Asked Questions | Cancer Trends Progress Report

Cancer.gov

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

Prevention Summary Tables | Cancer Trends Progress Report

Cancer.gov

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

Treatment Summary Tables | Cancer Trends Progress Report

Cancer.gov

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

Red Meat Consumption | Cancer Trends Progress Report

Cancer.gov

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

About the Report | Cancer Trends Progress Report

Cancer.gov

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

Adult Tobacco Use | Cancer Trends Progress Report

Cancer.gov

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

Prostate Cancer Screening | Cancer Trends Progress Report

Cancer.gov

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

Colorectal Cancer Screening | Cancer Trends Progress Report

Cancer.gov

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

Breast Cancer Screening | Cancer Trends Progress Report

Cancer.gov

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

Sun-Protective Behavior | Cancer Trends Progress Report

Cancer.gov

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

Evolving targets for lipid-modifying therapy

PubMed Central

Do, Rose Q; Nicholls, Stephen J; Schwartz, Gregory G

2014-01-01

The pathogenesis and progression of atherosclerosis are integrally connected to the concentration and function of lipoproteins in various classes. This review examines existing and emerging approaches to modify low-density lipoprotein and lipoprotein (a), triglyceride-rich lipoproteins, and high-density lipoproteins, emphasizing approaches that have progressed to clinical evaluation. Targeting of nuclear receptors and phospholipases is also discussed. PMID:25172365

Androgen receptor (AR) cistrome in prostate differentiation and cancer progression.

PubMed

Wang, Fengtian; Koul, Hari K

2017-01-01

Despite the progress in development of better AR-targeted therapies for prostate cancer (PCa), there is no curative therapy for castration-resistant prostate cancer (CRPC). Therapeutic resistance in PCa can be characterized in two broad categories of AR therapy resistance: the first and most prevalent one involves restoration of AR activity despite AR targeted therapy, and the second one involves tumor progression despite blockade of AR activity. As such AR remains the most attractive drug target for CRPC. Despite its oncogenic role, AR signaling also contributes to the maturation and differentiation of prostate luminal cells during development. Recent evidence suggests that AR cistrome is altered in advanced PCa. Alteration in AR may result from AR amplification, alternative splicing, mutations, post-translational modification of AR, and altered expression of AR co-factors. We reasoned that such alterations would result in the transcription of disparate AR target genes and as such may contribute to the emergence of castration-resistance. In the present study, we evaluated the expression of genes associated with canonical or non-canonical AR cistrome in relationship with PCa progression and prostate development by analyzing publicly available datasets. We discovered a transcription switch from canonical AR cistrome target genes to the non-canonical AR cistrome target genes during PCa progression. Using Gene Set Enrichment Analysis (GSEA), we discovered that canonical AR cistrome target genes are enriched in indolent PCa patients and the loss of canonical AR cistrome is associated with tumor metastasis and poor clinical outcome. Analysis of the datasets involving prostate development, revealed that canonical AR cistrome target genes are significantly enriched in prostate luminal cells and can distinguish luminal cells from basal cells, suggesting a pivotal role for canonical AR cistrome driven genes in prostate development. These data suggest that the expression of

Quantifying Disease Progression in Amyotrophic Lateral Sclerosis

PubMed Central

Simon, Neil G; Turner, Martin R; Vucic, Steve; Al-Chalabi, Ammar; Shefner, Jeremy; Lomen-Hoerth, Catherine; Kiernan, Matthew C

2014-01-01

Amyotrophic lateral sclerosis (ALS) exhibits characteristic variability of onset and rate of disease progression, with inherent clinical heterogeneity making disease quantitation difficult. Recent advances in understanding pathogenic mechanisms linked to the development of ALS impose an increasing need to develop strategies to predict and more objectively measure disease progression. This review explores phenotypic and genetic determinants of disease progression in ALS, and examines established and evolving biomarkers that may contribute to robust measurement in longitudinal clinical studies. With targeted neuroprotective strategies on the horizon, developing efficiencies in clinical trial design may facilitate timely entry of novel treatments into the clinic. PMID:25223628

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

In Vivo Biomarkers for Targeting Colorectal Neoplasms

PubMed Central

Hsiung, Pei-Lin; Wang, Thomas

2011-01-01

Summary Colorectal carcinoma continues to be a leading cause of cancer morbidity and mortality despite widespread adoption of screening methods. Targeted detection and therapy using recent advances in our knowledge of in vivo cancer biomarkers promise to significantly improve methods for early detection, risk stratification, and therapeutic intervention. The behavior of molecular targets in transformed tissues is being comprehensively assessed using new techniques of gene expression profiling and high throughput analyses. The identification of promising targets is stimulating the development of novel molecular probes, including significant progress in the field of activatable and peptide probes. These probes are being evaluated in small animal models of colorectal neoplasia and recently in the clinic. Furthermore, innovations in optical imaging instrumentation are resulting in the scaling down of size for endoscope compatibility. Advances in target identification, probe development, and novel instruments are progressing rapidly, and the integration of these technologies has a promising future in molecular medicine. PMID:19126961

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

PubMed

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

2014-11-21

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

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

DTIC Science & Technology

2007-01-31

progress on the reserach grant "Low-Cost Radar Sensors for Personnel Detection and Tracking in Urban Areas" during the period 1 May 2005 - 31 December...the DOA of target i with respect to the array boresight is given by: O 1sin-1 -/- fD)--F2(. )(1) where d is the spacing between the elements and A, is...wall. A large database was collected for different parameter spaces including number of humans, types of movements, wall types and radar polarization

Novel targets for prostate cancer chemoprevention

PubMed Central

Sarkar, Fazlul H; Li, Yiwei; Wang, Zhiwei; Kong, Dejuan

2010-01-01

Among many endocrine-related cancers, prostate cancer (PCa) is the most frequent male malignancy, and it is the second most common cause of cancer-related death in men in the United States. Therefore, this review focuses on summarizing the knowledge of molecular signaling pathways in PCa because, in order to better design new preventive strategies for the fight against PCa, documentation of the knowledge on the pathogenesis of PCa at the molecular level is very important. Cancer cells are known to have alterations in multiple cellular signaling pathways; indeed, the development and the progression of PCa are known to be caused by the deregulation of several selective signaling pathways such as the androgen receptor, Akt, nuclear factor-κB, Wnt, Hedgehog, and Notch. Therefore, strategies targeting these important pathways and their upstream and downstream signaling could be promising for the prevention of PCa progression. In this review, we summarize the current knowledge regarding the alterations in cell signaling pathways during the development and progression of PCa, and document compelling evidence showing that these are the targets of several natural agents against PCa progression and its metastases. PMID:20576802

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

PubMed

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

2014-01-01

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

The Crosstalk of RAS with the TGF-β Family During Carcinoma Progression and its Implications for Targeted Cancer Therapy

PubMed Central

Grusch, M.; Petz, M.; Metzner, T.; Öztürk, D.; Schneller, D.; Mikulits, W.

2010-01-01

Both RAS and transforming growth factor (TGF)-β signaling cascades are central in tumorigenesis and show synergisms depending on tumor stage and tissue context. In this review we focus on the interaction of RAS subeffector proteins with signaling components of the TGF-β family including those of TGF-βs, activins and bone morphogenic proteins. Compelling evidence indicates that RAS signaling is essentially involved in the switch from tumor-suppressive to tumor-promoting functions of the TGF-β family leading to enhanced cancer growth and metastatic dissemination of primary tumors. Thus, the interface of these signaling cascades is considered as a promising target for the development of novel cancer therapeutics. The current pharmacological anti-cancer concepts combating the molecular cooperation between RAS and TGF-β family signaling during carcinoma progression are critically discussed. PMID:20718708

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

PubMed

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

2010-12-01

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

Developing Medications Targeting Glutamatergic Dysfunction in Autism: Progress to Date

PubMed Central

Fung, Lawrence K.; Hardan, Antonio Y.

2015-01-01

Pharmacologic treatments targeting specific molecular mechanisms relevant for autism spectrum disorder (ASD) are beginning to emerge in early drug development. This article reviews the evidence for the disruption of glutamatergic neurotransmission in animal models of social deficits and summarizes key pre-clinical and clinical efforts in developing pharmacologic interventions based on modulation of glutamatergic systems in individuals with ASD. Understanding the pathobiology of the glutamatergic system has led to the development of new investigational treatments for individuals with ASD. Specific examples of medications that modulate the glutamatergic system in preclinical and clinical studies are described. Finally, we will discuss the limitations of current strategies and future opportunities in developing medications targeting the glutamatergic system for treating individuals with ASD. PMID:26104862

Target identification of small molecules based on chemical biology approaches.

PubMed

Futamura, Yushi; Muroi, Makoto; Osada, Hiroyuki

2013-05-01

Recently, a phenotypic approach-screens that assess the effects of compounds on cells, tissues, or whole organisms-has been reconsidered and reintroduced as a complementary strategy of a target-based approach for drug discovery. Although the finding of novel bioactive compounds from large chemical libraries has become routine, the identification of their molecular targets is still a time-consuming and difficult process, making this step rate-limiting in drug development. In the last decade, we and other researchers have amassed a large amount of phenotypic data through progress in omics research and advances in instrumentation. Accordingly, the profiling methodologies using these datasets expertly have emerged to identify and validate specific molecular targets of drug candidates, attaining some progress in current drug discovery (e.g., eribulin). In the case of a compound that shows an unprecedented phenotype likely by inhibiting a first-in-class target, however, such phenotypic profiling is invalid. Under the circumstances, a photo-crosslinking affinity approach should be beneficial. In this review, we describe and summarize recent progress in both affinity-based (direct) and phenotypic profiling (indirect) approaches for chemical biology target identification.

Paradigm shift in bacteriophage-mediated delivery of anticancer drugs: from targeted 'magic bullets' to self-navigated 'magic missiles'.

PubMed

Petrenko, Valery A; Gillespie, James W

2017-03-01

New phage-directed nanomedicines have emerged recently as a result of the in-depth study of the genetics and structure of filamentous phage and evolution of phage display and phage nanobiotechnology. This review focuses on the progress made in the development of the cancer-targeted nanomaterials and discusses the trends in using phage as a bioselectable molecular navigation system. Areas covered: The merging of phage display technologies with nanotechnology in recent years has proved promising in different areas of medicine and technology, such as medical diagnostics, molecular imaging, vaccine development and targeted drug/gene delivery, which is the focus of this review. The authors used data obtained from their research group and sourced using Science Citation Index (Web of Science) and NCBI PubMed search resources. Expert opinion: First attempts of adapting traditional concepts of direct targeting of tumor using phage-targeted nanomedicines has shown minimal improvements. With discovery and study of biological and technical barriers that prevent anti-tumor drug delivery, a paradigm shift from traditional drug targeting to nanomedicine navigation systems is required. The advanced bacteriophage-driven self-navigation systems are thought to overcome those barriers using more precise, localized phage selection methods, multi-targeting 'promiscuous' ligands and advanced multifunctional nanomedicine platforms.

Tier-scalable reconnaissance: the future in autonomous C4ISR systems has arrived: progress towards an outdoor testbed

NASA Astrophysics Data System (ADS)

Fink, Wolfgang; Brooks, Alexander J.-W.; Tarbell, Mark A.; Dohm, James M.

2017-05-01

Autonomous reconnaissance missions are called for in extreme environments, as well as in potentially hazardous (e.g., the theatre, disaster-stricken areas, etc.) or inaccessible operational areas (e.g., planetary surfaces, space). Such future missions will require increasing degrees of operational autonomy, especially when following up on transient events. Operational autonomy encompasses: (1) Automatic characterization of operational areas from different vantages (i.e., spaceborne, airborne, surface, subsurface); (2) automatic sensor deployment and data gathering; (3) automatic feature extraction including anomaly detection and region-of-interest identification; (4) automatic target prediction and prioritization; (5) and subsequent automatic (re-)deployment and navigation of robotic agents. This paper reports on progress towards several aspects of autonomous C4ISR systems, including: Caltech-patented and NASA award-winning multi-tiered mission paradigm, robotic platform development (air, ground, water-based), robotic behavior motifs as the building blocks for autonomous tele-commanding, and autonomous decision making based on a Caltech-patented framework comprising sensor-data-fusion (feature-vectors), anomaly detection (clustering and principal component analysis), and target prioritization (hypothetical probing).

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

PubMed

Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

2010-09-01

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

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

PubMed

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

2017-10-27

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan, † with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive

Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors

PubMed Central

Linger, Rachel M.A.; Keating, Amy K.; Earp, H. Shelton

2010-01-01

Importance of the field Axl and/or Mer expression correlates with poor prognosis in several cancers. Until recently, the specific role of these receptor tyrosine kinases (RTKs) in the development and progression of cancer remained unexplained. Studies demonstrating that Axl and Mer contribute to mechanisms of cell survival, migration, invasion, metastasis, and chemosensitivity justify further investigation of Axl and Mer as novel therapeutic targets in cancer. Areas covered in this review Axl and Mer signaling pathways in cancer cells are summarized and evidence validating these RTKs as therapeutic targets in glioblastoma multiforme, non-small cell lung cancer, and breast cancer is examined. A comprehensive discussion of Axl and/or Mer inhibitors in development is also provided. What the reader will gain Potential toxicities associated with Axl or Mer inhibition are addressed. We hypothesize that the probable action of Mer and Axl inhibitors on cells within the tumor microenvironment will provide a unique therapeutic opportunity to target both tumor cells and the stromal components which facilitate disease progression. Take home message Axl and Mer mediate multiple oncogenic phenotypes and activation of these RTKs constitutes a mechanism of chemoresistance in a variety of solid tumors. Targeted inhibition of these RTKs may be effective as anti-tumor and/or anti-metastatic therapy, particularly if combined with standard cytotoxic therapies. PMID:20809868

Toward intracellular targeted delivery of cancer therapeutics: progress and clinical outlook for brain tumor therapy.

PubMed

Pandya, Hetal; Debinski, Waldemar

2012-08-01

A number of anti-cancer drugs have their targets localized to particular intracellular compartments. These drugs reach the targets mainly through diffusion, dependent on biophysical and biochemical forces that allow cell penetration. This means that both cancer cells and normal cells will be subjected to such diffusion; hence many of these drugs, like chemotherapeutics, are potentially toxic and the concentration achieved at the site of their action is often suboptimal. The same relates to radiation that indiscriminately affects normal and diseased cells. However, nature-designed systems enable compounds present in the extracellular environment to end up inside the cell and even travel to more specific intracellular compartments. For example, viruses and bacterial toxins can more or less specifically recognize eukaryotic cells, enter these cells, and direct some protein portions to designated intracellular areas. These phenomena have led to creative thinking, such as employing viruses or bacterial toxins for cargo delivery to cells and, more specifically, to cancer cells. Proteins can be genetically engineered in order to not only mimic what viruses and bacterial toxins can do, but also to add new functions, extending or changing the intracellular routes. It is possible to make conjugates or, more preferably, single-chain proteins that recognize cancer cells and deliver cargo inside the cells, even to the desired subcellular compartment. These findings offer new opportunities to deliver drugs/labels only to cancer cells and only to their site of action within the cells. The development of such dual-specificity vectors for targeting cancer cells is an attractive and potentially safer and more efficacious way of delivering drugs. We provide examples of this approach for delivering brain cancer therapeutics, using a specific biomarker on glioblastoma tumor cells.

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

Opportunities and progress.

PubMed

Litchfield, John H

2014-01-01

In this review, I cover my professional experiences in food science and technology and related areas of applied and industrial microbiology over the span of my career. It emphasizes opportunities and technological problems that I encountered together with my progress in follow-up development of products and processes.

Research progress on osteoarthritis treatment mechanisms.

PubMed

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

2017-09-01

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

Chemical and Environmental Exposures | Cancer Trends Progress Report

Cancer.gov

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

Methodology for Characterizing Trends | Cancer Trends Progress Report

Cancer.gov

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

Cancer Survivors and Smoking | Cancer Trends Progress Report

Cancer.gov

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

Smoke-free Home Rules | Cancer Trends Progress Report

Cancer.gov

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

Tobacco Company Marketing Expenditures | Cancer Trends Progress Report

Cancer.gov

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

Recent Updates and Archive | Cancer Trends Progress Report

Cancer.gov

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

Trends at a Glance | Cancer Trends Progress Report

Cancer.gov

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

Cancer Survivors and Obesity | Cancer Trends Progress Report

Cancer.gov

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

Diet - Prevention Summary Table | Cancer Trends Progress Report

Cancer.gov

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

Tobacco Policy/Regulatory Factors | Cancer Trends Progress Report

Cancer.gov

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

Fruit and Vegetable Consumption | Cancer Trends Progress Report

Cancer.gov

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

S100-alarmins: potential therapeutic targets for arthritis.

PubMed

Austermann, Judith; Zenker, Stefanie; Roth, Johannes

2017-07-01

In arthritis, inflammatory processes are triggered by numerous factors that are released from joint tissues, promoting joint destruction and pathological progression. During inflammation, a novel family of pro-inflammatory molecules called alarmins is released, amplifying inflammation and joint damage. Areas covered: With regard to the role of the alarmins S100A8 and S100A9 in the pathogenesis of arthritis, recent advances and the future prospects in terms of therapeutic implications are considered. Expert opinion: There is still an urgent need for novel treatment strategies addressing the local mechanisms of joint inflammation and tissue destruction, offering promising therapeutic alternatives. S100A8 and S100A9, which are the most up-regulated alarmins during arthritis, are endogenous triggers of inflammation, defining these proteins as promising targets for local suppression of arthritis. In murine models, the blockade of S100A8/S100A9 ameliorates inflammatory processes, including arthritis, and there are several lines of evidence that S100-alarmins may already be targeted in therapeutic approaches in man.

Immunotherapy Targets in Pediatric Cancer

PubMed Central

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

2011-01-01

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer. PMID:22645714

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

Treesearch

Daniel C. Dey; Callie Jo. Schweitzer

2014-01-01

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

Therapeutic targeting of the p53 pathway in cancer stem cells

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2014-01-01

Background Multifocal glasses (bifocals, trifocals, and progressives) increase the risk of falling in elderly people, but how they do so is unclear. To explain why glasses with progressive addition lenses increase the risk of falls and whether this can be attributed to false projection, this study aimed to 1) map the prismatic displacement of a progressive lens, and 2) test whether this displacement impaired reaction time and accuracy. Methods The reaction times of healthy ≥75-year-olds (31 participants) were measured when grasping for a bar and touching a black line. Participants performed each test twice, wearing their progressives and new, matched single vision (distance) glasses in random order. The line and bar targets were positioned according to the maximum and minimum prismatic displacement effect through the progressive lens, mapped using a focimeter. Results Progressive spectacle lenses have large areas of prismatic displacement in the central visual axis and edges. Reaction time was faster for progressives compared with single vision glasses with a centrally-placed horizontal grab bar (mean difference 101 ms, P=0.011 [repeated measures analysis]) and a horizontal black line placed 300 mm below center (mean difference 80 ms, P=0.007). There was no difference in accuracy between the two types of glasses. Conclusion Older people appear to adapt to the false projection of progressives in the central visual axis. This adaptation means that swapping to new glasses or a large change in prescription may lead to a fall. Frequently updating glasses may be more beneficial. PMID:24872674

Interleukin-22 promotes aerobic glycolysis associated with tumor progression via targeting hexokinase-2 in human colon cancer cells.

PubMed

Liu, Yulin; Xiang, Fan; Huang, Yongming; Shi, Liang; Hu, Chaojie; Yang, Yiming; Wang, Di; He, Nan; Tao, Kaixiong; Wu, Ke; Wang, Guobin

2017-04-11

Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2. We further demonstrated that hexokinase-2 partly accounted for interleukin-22-mediated cellular proliferation in DLD-1 cells. In vivo, our data demonstrated that interleukin-22 significantly promoted tumor growth along with elevated expression of c-Myc and hexokinase-2 in mice. In summary, our findings provide a new perspective on the pro-inflammatory cytokine interleukin-22 in promoting aerobic glycolysis associated with tumor progression in human colon cancer cells.

Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk.

PubMed

Orozco, Carlos A; Martinez-Bosch, Neus; Guerrero, Pedro E; Vinaixa, Judith; Dalotto-Moreno, Tomás; Iglesias, Mar; Moreno, Mireia; Djurec, Magdolna; Poirier, Françoise; Gabius, Hans-Joachim; Fernandez-Zapico, Martin E; Hwang, Rosa F; Guerra, Carmen; Rabinovich, Gabriel A; Navarro, Pilar

2018-04-17

Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras -driven mouse model of PDA ( Ela-Kras G12V p53 -/- ) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.

Preclinical Trials for Prevention of Tumor Progression of Hepatocellular Carcinoma by LZ-8 Targeting c-Met Dependent and Independent Pathways

PubMed Central

Wu, Jia-Ru; Hu, Chi-Tan; You, Ren-In; Ma, Pei-Ling; Pan, Siou-Mei; Lee, Ming-Che; Wu, Wen-Sheng

2015-01-01

Hepatocellular carcinoma (HCC) is among the most lethal cancers. Mounting studies highlighted the essential role of the HGF/c-MET axis in driving HCC tumor progression. Therefore, c-Met is a potential therapeutic target for HCC. However, several concerns remain unresolved in c-Met targeting. First, the status of active c-Met in HCC must be screened to determine patients suitable for therapy. Second, resistance and side effects have been observed frequently when using conventional c-Met inhibitors. Thus, a preclinical system for screening the status of c-Met signaling and identifying efficient and safe anti-HCC agents is urgently required. In this study, immunohistochemical staining of phosphorylated c-Met (Tyr1234) on tissue sections indicated that HCCs with positive c-Met signaling accounted for approximately 46% in 26 cases. Second, many patient-derived HCC cell lines were established and characterized according to motility and c-Met signaling status. Moreover, LZ8, a medicinal peptide purified from the herb Lingzhi, featuring immunomodulatory and anticancer properties, was capable of suppressing cell migration and slightly reducing the survival rate of both c-Met positive and negative HCCs, HCC372, and HCC329, respectively. LZ8 also suppressed the intrahepatic metastasis of HCC329 in SCID mice. On the molecular level, LZ8 suppressed the expression of c-Met and phosphorylation of c-Met, ERK and AKT in HCC372, and suppressed the phosphorylation of JNK, ERK, and AKT in HCC329. According to receptor array screening, the major receptor tyrosine kinase activated in HCC329 was found to be the epidermal growth factor receptor (EGFR). Moreover, tyrosine-phosphorylated EGFR (the active EGFR) was greatly suppressed in HCC329 by LZ8 treatment. In addition, LZ8 blocked HGF-induced cell migration and c-Met-dependent signaling in HepG2. In summary, we designed a preclinical trial using LZ8 to prevent the tumor progression of patient-derived HCCs with c-Met-positive or

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.

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

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.

Targeting ubiquitination for cancer therapies.

PubMed

Morrow, John Kenneth; Lin, Hui-Kuan; Sun, Shao-Cong; Zhang, Shuxing

2015-01-01

Ubiquitination, the structured degradation and turnover of cellular proteins, is regulated by the ubiquitin-proteasome system (UPS). Most proteins that are critical for cellular regulations and functions are targets of the process. Ubiquitination is comprised of a sequence of three enzymatic steps, and aberrations in the pathway can lead to tumor development and progression as observed in many cancer types. Recent evidence indicates that targeting the UPS is effective for certain cancer treatment, but many more potential targets might have been previously overlooked. In this review, we will discuss the current state of small molecules that target various elements of ubiquitination. Special attention will be given to novel inhibitors of E3 ubiquitin ligases, especially those in the SCF family.

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

PubMed

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

2016-07-05

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

Chemoprevention in gastrointestinal physiology and disease. Targeting the progression of cancer with natural products: a focus on gastrointestinal cancer.

PubMed

Khoogar, Roxane; Kim, Byung-Chang; Morris, Jay; Wargovich, Michael J

2016-05-01

The last decade has witnessed remarkable progress in the utilization of natural products for the prevention and treatment of human cancer. Many agents now in the pipeline for clinical trial testing have evolved from our understanding of how human nutritional patterns account for widespread differences in cancer risk. In this review, we have focused on many of these promising agents arguing that they may provide a new strategy for cancer control: natural products once thought to be only preventive in their mode of action now are being explored for efficacy in tandem with cancer therapeutics. Natural products may reduce off-target toxicity of therapeutics while making cancers more amenable to therapy. On the horizon is the use of certain natural products, in their own right, as mitigants of late-stage cancer, a new frontier for small-molecule natural product drug discovery. Copyright © 2016 the American Physiological Society.

40 CFR 52.2038 - Rate of Progress Plans: Ozone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Rate of Progress Plans: Ozone. 52.2038... Progress Plans: Ozone. (a) EPA grants full approval to Pennsylvania's 15 Percent Rate of Progress Plan for the Pittsburgh-Beaver Valley ozone nonattainment area, submitted by the Secretary of the Pennsylvania...

40 CFR 52.2038 - Rate of Progress Plans: Ozone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Rate of Progress Plans: Ozone. 52.2038... Progress Plans: Ozone. (a) EPA grants full approval to Pennsylvania's 15 Percent Rate of Progress Plan for the Pittsburgh-Beaver Valley ozone nonattainment area, submitted by the Secretary of the Pennsylvania...

40 CFR 52.2038 - Rate of Progress Plans: Ozone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Rate of Progress Plans: Ozone. 52.2038... Progress Plans: Ozone. (a) EPA grants full approval to Pennsylvania's 15 Percent Rate of Progress Plan for the Pittsburgh-Beaver Valley ozone nonattainment area, submitted by the Secretary of the Pennsylvania...

40 CFR 52.2038 - Rate of Progress Plans: Ozone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Rate of Progress Plans: Ozone. 52.2038... Progress Plans: Ozone. (a) EPA grants full approval to Pennsylvania's 15 Percent Rate of Progress Plan for the Pittsburgh-Beaver Valley ozone nonattainment area, submitted by the Secretary of the Pennsylvania...

40 CFR 52.2038 - Rate of Progress Plans: Ozone.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Rate of Progress Plans: Ozone. 52.2038... Progress Plans: Ozone. (a) EPA grants full approval to Pennsylvania's 15 Percent Rate of Progress Plan for the Pittsburgh-Beaver Valley ozone nonattainment area, submitted by the Secretary of the Pennsylvania...

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

PubMed Central

Unger, Sofia; Corte, Tamera J.; Keller, Michael; Wolters, Paul J.; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M.; Hansbro, Philip M.; Argraves, William Scott; Oliver, Rema A.; Oliver, Brian G.; Black, Judith L.; Burgess, Janette K.

2014-01-01

BACKGROUND: The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF. METHODS: Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry. RESULTS: Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = −0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012). CONCLUSIONS: Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments. PMID:24832167

Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.

PubMed

Jaffar, Jade; Unger, Sofia; Corte, Tamera J; Keller, Michael; Wolters, Paul J; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M; Hansbro, Philip M; Argraves, William Scott; Oliver, Rema A; Oliver, Brian G; Black, Judith L; Burgess, Janette K

2014-10-01

The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF. Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry. Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = -0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012). Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments.

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

PubMed

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

2016-10-01

To assess the US packaged food industry's progress from 2009 to 2014, when the National Salt Reduction Initiative had voluntary, category-specific sodium targets with the goal of reducing sodium in packaged and restaurant foods by 25% over 5 years. Using the National Salt Reduction Initiative Packaged Food Database, we assessed target achievement and change in sales-weighted mean sodium density in top-selling products in 61 food categories in 2009 (n = 6336), 2012 (n = 6898), and 2014 (n = 7396). In 2009, when the targets were established, no categories met National Salt Reduction Initiative 2012 or 2014 targets. By 2014, 26% of categories met 2012 targets and 3% met 2014 targets. From 2009 to 2014, the sales-weighted mean sodium density declined significantly in almost half of all food categories (43%; 26/61 categories). Overall, sales-weighted mean sodium density declined significantly (by 6.8%; P < .001). National target setting with monitoring through a partnership of local, state, and national health organizations proved feasible, but industry progress was modest. The US Food and Drug Administration's proposed voluntary targets will be an important step in achieving more substantial sodium reductions.

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

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

Yao, Jingjing; Xu, Chen; Department of Orthopedics, Changzheng Hospital Affiliated to Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003

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

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

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

Li, Butian; Zhang, Shengping; Shen, Hao

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

Progress towards the development of SH2 domain inhibitors.

PubMed

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

2013-04-21

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

Target Salt 2025: A Global Overview of National Programs to Encourage the Food Industry to Reduce Salt in Foods

PubMed Central

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

2014-01-01

Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce salt. A systematic review of the literature was supplemented by key informant questionnaires to inform categorization of the initiatives. Fifty nine food industry salt reduction programs were identified. Thirty eight countries had targets for salt levels in foods and nine countries had introduced legislation for some products. South Africa and Argentina have both introduced legislation limiting salt levels across a broad range of foods. Seventeen countries reported reductions in salt levels in foods—the majority in bread. While these trends represent progress, many countries have yet to initiate work in this area, others are at early stages of implementation and further monitoring is required to assess progress towards achieving the global target. PMID:25195640

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

PubMed

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

2014-08-21

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

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…

Design and fabrication of the progressive addition lenses

NASA Astrophysics Data System (ADS)

Qin, Linling; Qian, Lin; Yu, Jingchi

2011-11-01

The use of progressive addition lenses (PALs) for the correction of presbyopia has increased dramatically in recent years. These lenses are now being used as the preferred alternative to bifocal and trifocal lenses in many parts of the world. Progressive addition lenses are a kind of opthalmic lenses with freeform surface. The surface curvature of the Progressive addition lenses varies gradually from a minimum value in the upper area, to a maximum value in the lower area. Thus a PAL has a surface with three zones which have very small astigmatism: far-view zone, near-view zone, and intermediate zone. The far view zone and near view zone have relatively constant powers and connected by the intermediate zone with power varies progressively. The design and fabrication technologies of progressive addition lenses have fast progresses because of the massive development of the optical simulation software, multi-axis ultraprecision machining technologies and CNC machining technologies. The design principles of progressive addition lenses are discussed in a historic review. Several kinds of design methods are illustrated, and their advantages and disadvantages are also represented. In the current study, it is shown that the optical characteristics of the different progressive addition lenses designs are significantly different from one another. The different fabrication technologies of Progressive addition lenses are also discussed in the paper. Plastic injection molding and precision-machine turning are the common fabrication technologies for exterior PALs and Interior PALs respectively.

HER-2 as a Progression Factor and Therapeutic Target in Breast Cancer.

DTIC Science & Technology

1999-06-01

used gene specific targeting of HER-2 with hammerhead - ribozyme expression constructs, a technology which we have applied successfully in the...2 in MCF-7 cells by ribozyme -targeting estradiol lost its ability to induce anchorage- independent colony formation in soft agar of the tumor cells...between estrogen and HER-2 signal transduction is ongoing. 14. SUBJECT TERMS Breast Cancer HER-2, estradiol, ribozymes , apoptosis, cell cycle, cDNA

Targeting BET bromodomain proteins in solid tumors

PubMed Central

Sahai, Vaibhav; Redig, Amanda J.; Collier, Katharine A.; Eckerdt, Frank D.; Munshi, Hidayatullah G.

2016-01-01

There is increasing interest in inhibitors targeting BET (bromodomain and extra-terminal) proteins because of the association between this family of proteins and cancer progression. BET inhibitors were initially shown to have efficacy in hematologic malignancies; however, a number of studies have now shown that BET inhibitors can also block progression of non-hematologic malignancies. In this Review, we summarize the efficacy of BET inhibitors in select solid tumors; evaluate the role of BET proteins in mediating resistance to current targeted therapies; and consider potential toxicities of BET inhibitors. We also evaluate recently characterized mechanisms of resistance to BET inhibitors; summarize ongoing clinical trials with these inhibitors; and discuss potential future roles of BET inhibitors in patients with solid tumors. PMID:27283767

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

PubMed

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

2010-05-01

Beta-Zone parapapillary atrophy (PPA) occurs more commonly in eyes with glaucoma. Rates of glaucomatous visual field (VF) progression in eyes with and without beta-zone PPA at the time of baseline assessment were compared. Retrospective, comparative study. Two hundred forty-five patients from the New York Glaucoma Progression Study. Subjects with glaucomatous optic neuropathy and repeatable VF loss were assessed for eligibility. Eyes with a Heidelberg Retina Tomograph II (HRT) examination, at least 5 visual field tests after the HRT in either eye, optic disc photographs, and <6 diopters of myopia were enrolled. beta-Zone PPA was defined as a region of chorioretinal atrophy with visible sclera and choroidal vessels adjacent to the optic disc. Global rates of VF progression were determined by automated pointwise linear regression analysis. Univariate analysis included age, gender, ethnicity, central corneal thickness (CCT), refractive error, baseline mean deviation, baseline intraocular pressure (IOP), mean IOP, IOP fluctuation, disc area, rim area, rim area-to-disc area ratio, beta-zone PPA area, beta-zone PPA area-to-disc area ratio, and presence or absence of beta-zone PPA. The relationship between beta-zone PPA and the rate and risk of glaucoma progression. Two hundred forty-five eyes of 245 patients (mean age, 69.6+/-12.3 years) were enrolled. The mean follow-up was 4.9+/-1.4 years and the mean number of VFs after HRT was 9.3+/-2.7. beta-Zone PPA was present in 146 eyes (65%). Eyes with beta-zone PPA progressed more rapidly (-0.84+/-0.8 dB/year) than eyes without it (-0.51+/-0.6 dB/year; P<0.01). Multivariate regression showed significant influence of mean IOP (hazard ratio [HR], 1.11; P<0.01), IOP fluctuation (HR, 1.17; P = 0.02), and presence of beta-zone PPA (HR, 2.59; P<0.01) on VF progression. Moderate (0.5-1.5 dB/year; P = 0.01) and fast (>1.5 dB/year; P = 0.08) global rates of progression occurred more commonly in eyes with beta-zone PPA than in eyes

Progression to established smoking among US youths.

PubMed

Mowery, Paul D; Farrelly, Matthew C; Haviland, M Lyndon; Gable, Julia M; Wells, Henry E

2004-02-01

Our study presents national estimates of the proportion of youths in each of 7 stages of smoking and investigates the associations between risk/protective factors and progression to established smoking. We analyzed data from the 1999 and 2000 National Youth Tobacco Surveys. In 1999 and 2000, 48.6% of US adolescents had at least experimented with tobacco, and 7.8% were established smokers. Important correlates of progression to established smoking included parental advice not to smoke, antismoking lessons in school, susceptibility to tobacco industry advertising and promotion, peer smoking, and exposure to smoking at home. Interventions to stop adolescent progression to established smoking should target susceptible never smokers and early experimenters as well as those in later stages of smoking.

Hydrologic Resources Management Program and Underground Test Area Project FY 2006 Progress Report

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

Culham, H W; Eaton, G F; Genetti, V

2008-04-08

and USGS HGH No.2 WW2 located in Yucca Flat. In addition, three springs were sampled White Rock Spring and Captain Jack Spring in Area 12 on Rainier Mesa and Topopah Spring in Area 29. Chapter 3 is a compilation of existing noble gas data that has been reviewed and edited to remove inconsistencies in presentation of total vs. single isotope noble gas values reported in the previous HRMP and UGTA progress reports. Chapter 4 is a summary of the results of batch sorption and desorption experiments performed to determine the distribution coefficients (Kd) of Pu(IV), Np(V), U(VI), Cs and Sr to zeolitized tuff (tuff confining unit, TCU) and carbonate (lower carbonate aquifer, LCA) rocks in synthetic NTS groundwater Chapter 5 is a summary of the results of a series of flow-cell experiments performed to examine Np(V) and Pu(V) sorption to and desorption from goethite. Np and Pu desorption occur at a faster rate and to a greater extent than previously reported. In addition, oxidation changes occurred with the Pu whereby the surface-sorbed Pu(IV) was reoxidized to aqueous Pu(V) during desorption.« less

Targeted cancer drug delivery with aptamer-functionalized polymeric nanoparticles.

PubMed

Zununi Vahed, Sepideh; Fathi, Nazanin; Samiei, Mohammad; Maleki Dizaj, Solmaz; Sharifi, Simin

2018-06-21

Based on exceptional advantages of aptamers, increasing attention has been presented in the utilize of them as targeted ligands for cancer drug delivery. Recently, the progress of aptamer- targeted nanoparticles has presented new therapeutic systems for several types of cancer with decreased toxicity and improved efficacy. We highlight some of the promising formulations of aptamer-conjugated polymeric nanoparticles for specific targeted drug delivery to cancer cells. This review paper focuses on the current progresses in the use of the novel strategies to aptamer-targeted drug delivery for chemotherapy. An extensive literature review was performed using internet database, mainly PubMed based on MeSH keywords. The searches included full-text publications written in English without any limitation in date. The abstracts, reviews, books as well as studies without obvious relating of aptamers as targeted ligands for cancer drug delivery were excluded from the study. The reviewed literature revealed that aptamers with ability to modify and conjugate to various molecules can be used as targeted cancer therapy agents. However, development of aptamers unique to each individual's tumor to the development of personalized medicine seems to be needed.

Specific c-Jun target genes in malignant melanoma.

PubMed

Schummer, Patrick; Kuphal, Silke; Vardimon, Lily; Bosserhoff, Anja K; Kappelmann, Melanie

2016-05-03

A fundamental event in the development and progression of malignant melanoma is the de-regulation of cancer-relevant transcription factors. We recently showed that c-Jun is a main regulator of melanoma progression and, thus, is the most important member of the AP-1 transcription factor family in this disease. Surprisingly, no cancer-related specific c-Jun target genes in melanoma were described in the literature, so far. Therefore, we focused on pre-existing ChIP-Seq data (Encyclopedia of DNA Elements) of 3 different non-melanoma cell lines to screen direct c-Jun target genes. Here, a specific c-Jun antibody to immunoprecipitate the associated promoter DNA was used. Consequently, we identified 44 direct c-Jun targets and a detailed analysis of 6 selected genes confirmed their deregulation in malignant melanoma. The identified genes were differentially regulated comparing 4 melanoma cell lines and normal human melanocytes and we confirmed their c-Jun dependency. Direct interaction between c-Jun and the promoter/enhancer regions of the identified genes was confirmed by us via ChIP experiments. Interestingly, we revealed that the direct regulation of target gene expression via c-Jun can be independent of the existence of the classical AP-1 (5´-TGA(C/G)TCA-3´) consensus sequence allowing for the subsequent down- or up-regulation of the expression of these cancer-relevant genes. In summary, the results of this study indicate that c-Jun plays a crucial role in the development and progression of malignant melanoma via direct regulation of cancer-relevant target genes and that inhibition of direct c-Jun targets through inhibition of c-Jun is a potential novel therapeutic option for treatment of malignant melanoma.

Tobacco Use - Prevention Summary Table | Cancer Trends Progress Report

Cancer.gov

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

Chemical Exposures - Prevention Summary Table | Cancer Trends Progress Report

Cancer.gov

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

Financial Burden of Cancer Care | Cancer Trends Progress Report

Cancer.gov

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

Person-Years of Life Lost | Cancer Trends Progress Report

Cancer.gov

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

Secondhand Smoke - Prevention Summary Table | Cancer Trends Progress Report

Cancer.gov

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

HPV Immunization - Prevention Summary Table | Cancer Trends Progress Report

Cancer.gov

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

Life After Cancer Summary Tables | Cancer Trends Progress Report

Cancer.gov

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

Smoking Cessation - Prevention Summary Table | Cancer Trends Progress Report

Cancer.gov

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

Cancer Survivors and Physical Activity | Cancer Trends Progress Report

Cancer.gov

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

Clinicians' Advice to Quit Smoking | Cancer Trends Progress Report

Cancer.gov

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

Diet, Physical Activity, and Weight | Cancer Trends Progress Report

Cancer.gov

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

Genetic risk variants as therapeutic targets for Crohn's disease.

PubMed

Gabbani, Tommaso; Deiana, Simona; Marocchi, Margherita; Annese, Vito

2017-04-01

The pathogenesis of Inflammatory bowel diseases (IBD) is multifactorial, with interactions between genetic and environmental factors. Despite the existence of genetic factors being largely demonstrated by epidemiological data and several genetic studies, only a few findings have been useful in term of disease prediction, disease progression and targeting therapy. Areas covered: This review summarizes the results of genome-wide association studies in Crohn's disease, the role of epigenetics and the recent discovery by genetic studies of new pathogenetic pathways. Furthermore, it focuses on the importance of applying genetic data to clinical practice, and more specifically how to better target therapy and predict potential drug-related toxicity. Expert opinion: Some genetic markers identified in Crohn`s disease have allowed investigators to hypothesize about, and in some cases, prove the usefulness of new specific therapeutic agents. However, the heterogeneity and complexity of this disease has so far limited the daily clinical use of genetic information. Finally, the study of the implications of genetics on therapy, either to predict efficacy or avoid toxicity, is considered still to be in its infancy.

Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs

PubMed Central

Pierce, Christopher G.; Lopez-Ribot, Jose L.

2014-01-01

Introduction Targeting pathogenetic mechanisms rather than essential processes represents a very attractive alternative for the development of new antibiotics. This may be particularly important in the case of antimycotics, due to the urgent need for novel antifungal drugs and the paucity of selective fungal targets. The opportunistic pathogenic fungus Candida albicans is the main etiological agent of candidiasis, the most common human fungal infection. These infections carry unacceptably high mortality rates, a clear reflection of the many shortcomings of current antifungal therapy, including the limited armamentarium of antifungal agents, their toxicity, and the emergence of resistance. Moreover the antifungal pipeline is mostly dry. Areas covered This review covers some of the most recent progress towards understanding C. albicans pathogenetic processes and how to harness this information for the development of anti-virulence agents. The two principal areas covered are filamentation and biofilm formation, as C. albicans pathogenicity is intimately linked to its ability to undergo morphogenetic conversions between yeast and filamentous morphologies and to its ability to form biofilms. Expert opinion We argue that filamentation and biofilm formation represent high value targets, yet clinically unexploited, for the development of novel anti-virulence approaches against candidiasis. Although this has proved a difficult task despite increasing understanding at the molecular level of C. albicans virulence, we highlight new opportunities and prospects for antifungal drug development targeting these two important biological processes. PMID:23738751

Progress toward poliomyelitis eradication - Pakistan, January 2012-September 2013.

PubMed

2013-11-22

Pakistan is one of three countries where transmission of indigenous wild poliovirus (WPV) has never been interrupted. This report describes polio eradication activities and progress in Pakistan during January 2012-September 2013 and updates previous reports. During 2012, 58 WPV cases were reported in selected areas, compared with 198 cases throughout the country in 2011; 52 WPV cases were reported during January-September 2013, compared with 54 cases during the same period in 2012. Of the 110 WPV cases reported since January 2012, 92 cases (84%) occurred in the conflict-affected Federally Administered Tribal Areas (FATA) and in security-compromised Khyber Pakhtunkhwa (KP) Province. WPV type 3 (WPV3) was isolated from only three persons with polio in a single district in 2012; the most recent case occurred in April 2012. During August 2012-September 2013, 52 circulating vaccine-derived poliovirus type 2 (cVDPV2) cases were detected, including 30 cases (58%) identified in FATA during January-September 2013. Approximately 350,000 children in certain districts of FATA have not received polio vaccine during supplementary immunization activities (SIAs) conducted since mid-2012 because local authorities have banned polio vaccination. In some other areas of Pakistan, SIAs have been compromised by attacks targeting polio workers that started in mid-2012. Further efforts to reach children in conflict-affected and security-compromised areas, including vaccinating at transit points and conducting additional short-interval-additional-dose (SIAD) SIAs as areas become accessible, will be necessary to prevent reintroduction of WPV into other areas of Pakistan and other parts of the world.

Evaluation of the healthy schools program: Part I. Interim progress.

PubMed

Beam, Margaret; Ehrlich, Ginny; Donze Black, Jessica; Block, Audrey; Leviton, Laura C

2012-01-01

Federal and state policies identify schools as a setting to prevent childhood obesity, but schools need better health-promoting strategies. The objective of this study was to evaluate interim progress in schools receiving hands-on training from the Healthy Schools Program, the nation's largest school-based program aimed at preventing childhood obesity. The 4-year program targets schools with predominantly low-income, African American, or Hispanic students. In 2010 we assessed schools that enrolled in the 2007-2008 and 2008-2009 school years. School representatives completed an inventory of 8 content areas: policy and systems, school meals, competitive foods and beverages, health education, physical education, physical activity outside of physical education, before- and after-school programs, and school employee wellness. Schools' baseline inventory was compared by t test with the most recent inventory available. Schools made significant changes in all content areas, and effect sizes were moderate to large. Participating schools improved environmental policies and practices to prevent childhood obesity. The program is a resource to implement recent federal and state policies.

Targeting EGFRvIII for glioblastoma multiforme.

PubMed

Yang, Ju; Yan, Jing; Liu, Baorui

2017-09-10

Glioblastoma multiforme (GBM) is the most progressive primary brain tumor. Targeting a novel and highly specific tumor antigen is one of the strategies to overcome tumors. EGFR variant III (EGFRvIII) is present in 25%-33% of all patients with GBM and is exclusively expressed on tumor tissue cells. Currently, there are various approaches to target EGFRvIII, including CAR T-cell therapy, therapeutic vaccines, antibodies, and Bi-specific T Cell Engager. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-11-01

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

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises.

PubMed

Garmpis, Nikolaos; Damaskos, Christos; Garmpi, Anna; Kalampokas, Emmanouil; Kalampokas, Theodoros; Spartalis, Eleftherios; Daskalopoulou, Afrodite; Valsami, Serena; Kontos, Michael; Nonni, Afroditi; Kontzoglou, Konstantinos; Perrea, Despina; Nikiteas, Nikolaos; Dimitroulis, Dimitrios

2017-01-01

Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 gene. It comprises approximately 15-20% of breast cancers (BCs). Unfortunately, TNBC's treatment continues to be a clinical problem because of its relatively poor prognosis, its aggressiveness and the lack of targeted therapies, leaving chemotherapy as the mainstay of treatment. It is essential to find new therapies against TNBC, in order to surpass the resistance and the invasiveness of already existing therapies. Given the fact that epigenetic processes control both the initiation and progression of TNBC, there is an increasing interest in the mechanisms, molecules and signaling pathways that participate at the epigenetic modulation of genes expressed in carcinogenesis. The acetylation of histone proteins provokes the transcription of genes involved in cell growth, and the expression of histone deacetylases (HDACs) is frequently up-regulated in many malignancies. Unfortunately, in the field of BC, HDAC inhibitors have shown limited effect as single agents. Nevertheless, their use in combination with kinase inhibitors, autophagy inhibitors, ionizing radiation, or two HDAC inhibitors together is currently being evaluated. HDAC inhibitors such as suberoylanilidehydroxamic acid (SAHA), sodium butyrate, mocetinostat, panobinostat, entinostat, YCW1 and N-(2-hydroxyphenyl)-2-propylpentanamide have shown promising therapeutic outcomes against TNBC, especially when they are used in combination with other anticancer agents. More studies concerning HDAC inhibitors in breast carcinomas along with a more accurate understanding of the TNBC's pathobiology are required for the possible identification of new therapeutic strategies. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

Treesearch

Kurt F. Anschuetz; Carol B. Raish

2010-01-01

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

Progressive video coding for noisy channels

NASA Astrophysics Data System (ADS)

Kim, Beong-Jo; Xiong, Zixiang; Pearlman, William A.

1998-10-01

We extend the work of Sherwood and Zeger to progressive video coding for noisy channels. By utilizing a 3D extension of the set partitioning in hierarchical trees (SPIHT) algorithm, we cascade the resulting 3D SPIHT video coder with a rate-compatible punctured convolutional channel coder for transmission of video over a binary symmetric channel. Progressive coding is achieved by increasing the target rate of the 3D embedded SPIHT video coder as the channel condition improves. The performance of our proposed coding system is acceptable at low transmission rate and bad channel conditions. Its low complexity makes it suitable for emerging applications such as video over wireless channels.

[Research progress on ebola virus glycoprotein].

PubMed

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

2013-03-01

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

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

PubMed

Shields, Judith A; Jennings, Jerry L

2013-01-01

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

Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

PubMed

Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

2016-05-01

Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Epigenetic pathway targets for the treatment of disease: accelerating progress in the development of pharmacological tools: IUPHAR Review 11

PubMed Central

Tough, David F; Lewis, Huw D; Rioja, Inmaculada; Lindon, Matthew J; Prinjha, Rab K

2014-01-01

The properties of a cell are determined both genetically by the DNA sequence of its genes and epigenetically through processes that regulate the pattern, timing and magnitude of expression of its genes. While the genetic basis of disease has been a topic of intense study for decades, recent years have seen a dramatic increase in the understanding of epigenetic regulatory mechanisms and a growing appreciation that epigenetic misregulation makes a significant contribution to human disease. Several large protein families have been identified that act in different ways to control the expression of genes through epigenetic mechanisms. Many of these protein families are finally proving tractable for the development of small molecules that modulate their function and represent new target classes for drug discovery. Here, we provide an overview of some of the key epigenetic regulatory proteins and discuss progress towards the development of pharmacological tools for use in research and therapy. PMID:25060293

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

PubMed

Willis, Rudolph E

2016-09-14

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

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

PubMed

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

2013-09-11

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

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

PubMed

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

2018-04-01

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

Improved discriminability of spatiotemporal neural patterns in rat motor cortical areas as directional choice learning progresses

PubMed Central

Mao, Hongwei; Yuan, Yuan; Si, Jennie

2015-01-01

Animals learn to choose a proper action among alternatives to improve their odds of success in food foraging and other activities critical for survival. Through trial-and-error, they learn correct associations between their choices and external stimuli. While a neural network that underlies such learning process has been identified at a high level, it is still unclear how individual neurons and a neural ensemble adapt as learning progresses. In this study, we monitored the activity of single units in the rat medial and lateral agranular (AGm and AGl, respectively) areas as rats learned to make a left or right side lever press in response to a left or right side light cue. We noticed that rat movement parameters during the performance of the directional choice task quickly became stereotyped during the first 2–3 days or sessions. But learning the directional choice problem took weeks to occur. Accompanying rats' behavioral performance adaptation, we observed neural modulation by directional choice in recorded single units. Our analysis shows that ensemble mean firing rates in the cue-on period did not change significantly as learning progressed, and the ensemble mean rate difference between left and right side choices did not show a clear trend of change either. However, the spatiotemporal firing patterns of the neural ensemble exhibited improved discriminability between the two directional choices through learning. These results suggest a spatiotemporal neural coding scheme in a motor cortical neural ensemble that may be responsible for and contributing to learning the directional choice task. PMID:25798093

Progress in health-related millennium development goals in the WHO South-East Asia Region.

PubMed

Singh, Poonam Khetrapal

2012-01-01

Home to 25% of the world's population and bearing 30% of the Global disease burden, the South-East Asia Region [1] of the World Health Organization has an important role in the progress of global health. Three of the eight million development goal (MDG) goals that relate to health are MDG 4, 5, and 6. There is progress in all three goals within the countries of the region, although the progress varies across countries and even within countries. With concerted and accelerated efforts in some countries and certain specific areas, the region will achieve the targets of the three health MDGs. The key challenges are in sustainable scaling up of evidence-based interventions to improve maternal and child health and controlling communicable diseases. This will require continued focus and investments in strengthening health systems that provide individual and family centered comprehensive package of interventions with equitable reach and that which is provided free at the point of service delivery. Important lessons that have been learnt in implementing the MDG agenda in the past two decades will inform setting up of the post MDG global health agenda. This article provides a snap shot of progress thus far, key challenges and opportunities in WHO South-East Asia Region and lays down the way forward for the global health agenda post 2015.

Developments in Neuropsychological and Neurophysiological Assessment: An Overview of Progress and Products of the JWGD3 (Joint Working Group on Drug Dependent Degradation) Level I Neuropsychology Task Area Group

DTIC Science & Technology

1986-01-01

995AB.081 IDA303502 11. TITLE (Indclude Security Classafication) Developments in Neuropsychological and Neurophysiological Assessment: An overview of...progress and products of the JWGD3 Level I Neuropsychology Task Area Group 12. PERSONAL AU1TOR(S) Reeves, D.L.; Taube, S.L. 13a. TYPE OF REPORT I13b...Phone: (301) 588-0058 7 Developments in Neuropsychological and Neurophysiological Assessment An Overview of Progress and Products of the JWGD3 Level I

Emerging preclinical pharmacological targets for Parkinson's disease

PubMed Central

More, Sandeep Vasant; Choi, Dong-Kug

2016-01-01

Parkinson's disease (PD) is a progressive neurological condition caused by the degeneration of dopaminergic neurons in the basal ganglia. It is the most prevalent form of Parkinsonism, categorized by cardinal features such as bradykinesia, rigidity, tremors, and postural instability. Due to the multicentric pathology of PD involving inflammation, oxidative stress, excitotoxicity, apoptosis, and protein aggregation, it has become difficult to pin-point a single therapeutic target and evaluate its potential application. Currently available drugs for treating PD provide only symptomatic relief and do not decrease or avert disease progression resulting in poor patient satisfaction and compliance. Significant amount of understanding concerning the pathophysiology of PD has offered a range of potential targets for PD. Several emerging targets including AAV-hAADC gene therapy, phosphodiesterase-4, potassium channels, myeloperoxidase, acetylcholinesterase, MAO-B, dopamine, A2A, mGlu5, and 5-HT-1A/1B receptors are in different stages of clinical development. Additionally, alternative interventions such as deep brain stimulation, thalamotomy, transcranial magnetic stimulation, and gamma knife surgery, are also being developed for patients with advanced PD. As much as these therapeutic targets hold potential to delay the onset and reverse the disease, more targets and alternative interventions need to be examined in different stages of PD. In this review, we discuss various emerging preclinical pharmacological targets that may serve as a new promising neuroprotective strategy that could actually help alleviate PD and its symptoms. PMID:26988916

MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression

PubMed Central

Zhang, Ying; Li, Tao; Guo, Pengbo; Kang, Jia; Wei, Qing; Jia, Xiaoqing; Zhao, Wei; Huai, Wanwan; Qiu, Yumin; Sun, Lei; Han, Lihui

2014-01-01

Resistance to anoikis and Epithelial-mesenchymal transition (EMT) are two processes critically involved in cancer metastasis. In this study, we demonstrated that after anchorage deprival, hepatocellular carcinoma (HCC) cells not only resisted anoikis, but also exhibited EMT process. Microarray expression profiling revealed that expression of miR-424-5p was significantly decreased in anoikis-resistant HCC cells. Ectopic overexpression of miR-424-5p was sufficient to reverse resistance to anoikis, block EMT process and inhibit malignant behaviors of HCC cells. Target analysis showed that a potent β-catenin inhibitor, ICAT/CTNNBIP1 was a direct target of miR-424-5p. Further study demonstrated that miR-424-5p reversed resistance to anoikis and EMT of HCCs by directly targeting ICAT and further maintaining the E-cadherin/β-catanin complex on the cellular membrance. In vivo study further demonstrated that miR-424-5p significantly inhibited the tumorigenicity of HCC cells in nude mice. Clinical investigation demonstrated that miR-424-5p was significantly downregulated in HCC tissues compared with that of the non-cancerous liver tissues, and this decreased expression of miR-424-5p was significantly correlated with higher pathological grades and more advanced TNM stages. Therefore, aberrant expression of miR-424-5p is critically involved in resistance to anoikis and EMT during the metastatic process of HCC, and its downregulation significantly contributes to liver cancer progression. PMID:25175916

Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

PubMed Central

Ontaneda, Daniel; Fox, Robert J.; Chataway, Jeremy

2015-01-01

Progressive multiple sclerosis is characterized by the gradual accrual of disability independent of relapses and can occur with disease onset (primary progressive) or preceded by a relapsing disease course (secondary progressive). An effective disease modifying treatment for progressive multiple sclerosis has not been identified, and the results of clinical trials to date have been generally disappointing. Ongoing advances in our understanding of pathogenesis, identification of novel targets for neuro-protection, and improved outcome measures have the potential to lead to effective treatments for progressive multiple sclerosis. In this review lessons learned from previous clinical trials and perspectives from current trials in progressive multiple sclerosis are summarized. Promising clinical, imaging, and biological markers will also be reviewed, along with novel clinical trial designs. PMID:25772899

PDE4 as a target for cognition enhancement

PubMed Central

Richter, Wito; Menniti, Frank S.; Zhang, Han-Ting; Conti, Marco

2014-01-01

Introduction The second messengers cAMP and cGMP mediate fundamental aspects of brain function relevant to memory, learning and cognitive functions. Consequently, cyclic nucleotide phosphodiesterases (PDEs), the enzymes that inactivate the cyclic nucleotides, are promising targets for the development of cognition-enhancing drugs. Areas covered PDE4 is the largest of the eleven mammalian PDE families. This review covers the properties and functions of the PDE4 family, highlighting procognitive and memory-enhancing effects associated with their inactivation. Expert opinion PAN-selective PDE4 inhibitors exert a number of memory- and cognition-enhancing effects and have neuroprotective and neuroregenerative properties in preclinical models. The major hurdle for their clinical application is to target inhibitors to specific PDE4 isoforms relevant to particular cognitive disorders to realize the therapeutic potential while avoiding side effects, in particular emesis and nausea. The PDE4 family comprises four genes, PDE4A-D, each expressed as multiple variants. Progress to date stems from characterization of rodent models with selective ablation of individual PDE4 subtypes, revealing that individual subtypes exert unique and non-redundant functions in the brain. Thus, targeting specific PDE4 subtypes, as well as splicing variants or conformational states, represents a promising strategy to separate the therapeutic benefits from the side effects of PAN-PDE4 inhibitors. PMID:23883342

LDHA is a direct target of miR-30d-5p and contributes to aggressive progression of gallbladder carcinoma.

PubMed

He, Yuting; Chen, Xiaolong; Yu, Yan; Li, Juan; Hu, Qiuyue; Xue, Chen; Chen, Jianan; Shen, Shen; Luo, Yonggang; Ren, Fang; Li, Chao; Bao, Jie; Yan, Jingya; Qian, Guowu; Ren, Zhigang; Sun, Ranran; Cui, Guangying

2018-06-01

Gallbladder cancer (GBC) is the most general biliary tract malignancy, with poor prognosis due to rapid tumor progression and lack of specific symptoms. Lactate dehydrogenase-A (LDHA) can promote Warburg effect to produce lactate and Adenosine Triphosphate (ATP) in aerobic condition, which contributes to oncogenesis metastasis and drug resistance in various cancers. However, the expression and functional role of LDHA in GBC are largely unknown. We determined that LDHA was over-expressed in GBC tumor tissues compared with normal tissues, which was also an independent prognostic factor for the overall survival of GBC patients by tissue microarrays analysis. In addition, RNAi-mediated LDHA silencing could suppress the GBC cell proliferation, invasion, colony formation and glycolysis while promoting cell apoptosis in vitro. Similar results were observed in GBC cells treated with LDHA specific inhibitor FX11. Moreover, we confirmed that knockdown of LDHA could inhibit tumor growth in vivo. Additionally, we found that the 3'-untranslated region (3'-UTR) of LDHA mRNA was the direct target of microRNA-30d-5p (miR-30d-5p), which was low expressed in GBC tissues and associated with poor prognosis of GBC patients. Our findings disclose a novel role for miR-30d-5p/LDHA axis contribute to aggressive progression by reprogramming the metabolic process in GBC cells, and suggest a potential application of miR-30d-5p/LDHA axis in prognosis prediction and GBC treatment. © 2018 Wiley Periodicals, Inc.

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.

ALK and ROS1 as targeted therapy paradigms and clinical implications to overcome crizotinib resistance

PubMed Central

Li, Nan; Zhang, Yong; Jing, Pengyu; Chang, Ning; Wu, Jianxiong; Ren, Xinling; Zhang, Jian

2016-01-01

During the past decade, more than 10 targetable oncogenic driver genes have been validated in non-small cell lung cancer (NSCLC). Anaplastic lymphoma kinase (ALK) and ROS1 kinase are two new driver genes implicated in ALK- and ROS1-rearranged NSCLC. Inhibition of ALK and ROS1 by crizotinib has been reported to be highly effective and well tolerated in these patients. However, resistance to crizotinib emerges years after treatment, and increasing efforts have been made to overcome this issue. Here, we review the biology of ALK and ROS1 and their roles in cancer progression. We also summarize the ongoing and completed clinical trials validating ALK and ROS1 as targets for cancer treatment. In the last section of the review, we will discuss the molecular mechanisms of crizotinib resistance and focus approaches to overcome it. This review describes an exciting new area of research and may provide new insights for targeted cancer therapies. PMID:26802023

Hidden targets of ubiquitin proteasome system: To prevent diabetic nephropathy.

PubMed

Goru, Santosh Kumar; Kadakol, Almesh; Gaikwad, Anil Bhanudas

2017-06-01

Diabetic nephropathy (DN) is the major cause of end stage renal failure. Although, several therapeutic targets have emerged to prevent the progression of DN, the number of people with DN still continues to rise worldwide, suggesting an urgent need of novel targets to prevent DN completely. Currently, the role of ubiquitin proteasome system (UPS) has been highlighted in the pathogenesis and progression of various diseases like obesity, insulin resistance, atherosclerosis, cancers, neurodegerative disorders and including secondary complications of diabetes. UPS mainly involves in protein homeostatis through ubiquitination (post translational modification) and proteasomal degradation of various proteins. Ubiquitination, not only involves in proteasomal degradation, but also directs the substrate proteins to participate in multitude of cell signalling pathways. However, very little is known about ubiquitination and UPS in the progression of DN. This review mainly focuses on UPS and its components including E2 conjugating enzymes, E3 ligases and deubiquitinases (DUBs) in the development of DN and thus may help us to find novel therapeutic targets with in UPS to prevent DN completely in future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neonatal tetanus elimination in Pakistan: progress and challenges.

PubMed

Lambo, Jonathan A; Nagulesapillai, Tharsiya

2012-12-01

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

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

PubMed Central

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

2015-01-01

Protected areas (PAs) are at the forefront of conservation efforts, and yet despite considerable progress towards the global target of having 17% of the world's land area within protected areas by 2020, biodiversity continues to decline. The discrepancy between increasing PA coverage and negative biodiversity trends has resulted in renewed efforts to enhance PA effectiveness. The global conservation community has conducted thousands of assessments of protected area management effectiveness (PAME), and interest in the use of these data to help measure the conservation impact of PA management interventions is high. Here, we summarize the status of PAME assessment, review the published evidence for a link between PAME assessment results and the conservation impacts of PAs, and discuss the limitations and future use of PAME data in measuring the impact of PA management interventions on conservation outcomes. We conclude that PAME data, while designed as a tool for local adaptive management, may also help to provide insights into the impact of PA management interventions from the local-to-global scale. However, the subjective and ordinal characteristics of the data present significant limitations for their application in rigorous scientific impact evaluations, a problem that should be recognized and mitigated where possible. PMID:26460133

Development of target ion source systems for radioactive beams at GANIL

NASA Astrophysics Data System (ADS)

Bajeat, O.; Delahaye, P.; Couratin, C.; Dubois, M.; Franberg-Delahaye, H.; Henares, J. L.; Huguet, Y.; Jardin, P.; Lecesne, N.; Lecomte, P.; Leroy, R.; Maunoury, L.; Osmond, B.; Sjodin, M.

2013-12-01

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

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

PubMed

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

2017-12-16

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

Exploration of the medical periodic table: towards new targets.

PubMed

Barry, Nicolas P E; Sadler, Peter J

2013-06-07

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

miR-155 modulates the progression of neuropathic pain through targeting SGK3

PubMed Central

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

2015-01-01

This study aimed to illustrate the potential effects of miR-155 in neuropathic pain and its potential mechanism. Spragure-Dawley (SD) rats were used for neuropathic pain model of bilateral chronic constriction injury (bCCI) construction. Effects of miR-155 expression on pain threshold of mechanical stimuli (MWT), paw withdrawal threshold latency (PMTL) and cold threshold were analyzed. Target for miR-155 was analyzed using bioinformatics methods. Moreover, effects of miR-155 target gene expression on pain thresholds were also assessed. Compared with the controls and sham group, miR-155 was overexpressed in neuropathic pain rats (P<0.05), but miR-155 slicing could significantly decreased the pain thresholds (P<0.05). Serum and glucocorticoid regulated protein kinase 3 (SGK3) was predicted as the target gene for miR-155, and miR-155 expression was negatively correlated to SGK3 expression. Furthermore, SGK3 overexpression could significantly decreased the pain thresholds which was the same as miR-155 (P<0.05). Moreover, miR-155 slicing and SGK3 overexpression could significantly decrease the painthreshold. The data presented in this study suggested that miR-155 slicing could excellently alleviate neuropathic pain in rats through targeting SGK3 expression. miR-155 may be a potential therapeutic target for neuropathic pain treatment. PMID:26823753

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

PubMed

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

2015-01-01

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

Glycogen Synthase Kinase-3 and Mammalian Target of Rapamycin Pathways Contribute to DNA Synthesis, Cell Cycle Progression, and Proliferation in Human Islets

PubMed Central

Liu, Hui; Remedi, Maria S.; Pappan, Kirk L.; Kwon, Guim; Rohatgi, Nidhi; Marshall, Connie A.; McDaniel, Michael L.

2009-01-01

OBJECTIVE—Our previous studies demonstrated that nutrient regulation of mammalian target of rapamycin (mTOR) signaling promotes regenerative processes in rodent islets but rarely in human islets. Our objective was to extend these findings by using therapeutic agents to determine whether the regulation of glycogen synthase kinase-3 (GSK-3)/β-catenin and mTOR signaling represent key components necessary for effecting a positive impact on human β-cell mass relevant to type 1 and 2 diabetes. RESEARCH DESIGN AND METHODS—Primary adult human and rat islets were treated with the GSK-3 inhibitors, LiCl and the highly potent 1-azakenpaullone (1-Akp), and with nutrients. DNA synthesis, cell cycle progression, and proliferation of β-cells were assessed. Measurement of insulin secretion and content and Western blot analysis of GSK-3 and mTOR signaling components were performed. RESULTS—Human islets treated for 4 days with LiCl or 1-Akp exhibited significant increases in DNA synthesis, cell cycle progression, and proliferation of β-cells that displayed varying degrees of sensitivity to rapamycin. Intermediate glucose (8 mmol/l) produced a striking degree of synergism in combination with GSK-3 inhibition to enhance bromodeoxyuridine (BrdU) incorporation and Ki-67 expression in human β-cells. Nuclear translocation of β-catenin responsible for cell proliferation was found to be particularly sensitive to rapamycin. CONCLUSIONS—A combination of GSK-3 inhibition and nutrient activation of mTOR contributes to enhanced DNA synthesis, cell cycle progression, and proliferation of human β-cells. Identification of therapeutic agents that appropriately regulate GSK-3 and mTOR signaling may provide a feasible and available approach to enhance human islet growth and proliferation. PMID:19073772

Stem cell signaling as a target for novel drug discovery: recent progress in the WNT and Hedgehog pathways.

PubMed

An, Songzhu Michael; Ding, Qiang Peter; Li, Ling-song

2013-06-01

One of the most exciting fields in biomedical research over the past few years is stem cell biology, and therapeutic application of stem cells to replace the diseased or damaged tissues is also an active area in development. Although stem cell therapy has a number of technical challenges and regulatory hurdles to overcome, the use of stem cells as tools in drug discovery supported by mature technologies and established regulatory paths is expected to generate more immediate returns. In particular, the targeting of stem cell signaling pathways is opening up a new avenue for drug discovery. Aberrations in these pathways result in various diseases, including cancer, fibrosis and degenerative diseases. A number of drug targets in stem cell signaling pathways have been identified. Among them, WNT and Hedgehog are two most important signaling pathways, which are the focus of this review. A hedgehog pathway inhibitor, vismodegib (Erivedge), has recently been approved by the US FDA for the treatment of skin cancer, while several drug candidates for the WNT pathway are entering clinical trials. We have discovered that the stem cell signaling pathways respond to traditional Chinese medicines. Substances isolated from herbal medicine may act specifically on components of stem cell signaling pathways with high affinities. As many of these events can be explained through molecular interactions, these phenomena suggest that discovery of stem cell-targeting drugs from natural products may prove to be highly successful.

Using BCG as a framework for setting goals and communicating progress toward those goals

EPA Science Inventory

This 5 minute Lightning Talk will discuss the benefits of stakeholder-supported quantitative targets in measuring progress, and will describe the Biological Condition Gradient (BCG) as one way to develop these quantitative targets.

Molecular targeted therapy for advanced gastric cancer.

PubMed

Kim, Jong Gwang

2013-03-01

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

Targeting inflammation in pancreatic cancer: Clinical translation

PubMed Central

Steele, Colin William; Kaur Gill, Nina Angharad; Jamieson, Nigel Balfour; Carter, Christopher Ross

2016-01-01

Preclinical modelling studies are beginning to aid development of therapies targeted against key regulators of pancreatic cancer progression. Pancreatic cancer is an aggressive, stromally-rich tumor, from which few people survive. Within the tumor microenvironment cellular and extracellular components exist, shielding tumor cells from immune cell clearance, and chemotherapy, enhancing progression of the disease. The cellular component of this microenvironment consists mainly of stellate cells and inflammatory cells. New findings suggest that manipulation of the cellular component of the tumor microenvironment is possible to promote immune cell killing of tumor cells. Here we explore possible immunogenic therapeutic strategies. Additionally extracellular stromal elements play a key role in protecting tumor cells from chemotherapies targeted at the pancreas. We describe the experimental findings and the pitfalls associated with translation of stromally targeted therapies to clinical trial. Finally, we discuss the key inflammatory signal transducers activated subsequent to driver mutations in oncogenic Kras in pancreatic cancer. We present the preclinical findings that have led to successful early trials of STAT3 inhibitors in pancreatic adenocarcinoma. PMID:27096033

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.

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

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.

Progress in HTS Trapped Field Magnets: J(sub c), Area, and Applications

NASA Technical Reports Server (NTRS)

Weinstein, Roy; Ren, Yanru; Liu, Jian-Xiong; Sawh, Ravi; Parks, Drew; Foster, Charles; Obot, Victor; Arndt, G. Dickey; Crapo, Alan

1995-01-01

Progress in trapped field magnets is reported. Single YBCO grains with diameters of 2 cm are made in production quantities, while 3 cm, 4 1/2 cm and 6 cm diameters are being explored. For single grain tiles: J(sub c) - 10,000 A/sq cm for melt textured grains; J(sub c) - 40,000 A/sq cm for light ion irradiation; and J(sub c) - 85,000 A/J(sub c) for heavy ion irradiation. Using 2 cm diameter tiles bombarded by light ions, we have fabricated a mini-magnet which trapped 2.25 Tesla at 77K, and 5.3 Tesla at 65K. A previous generation of tiles, 1 cm x 1 cm, was used to trap 7.0 Tesla at 55K. Unirradiated 2.0 cm tiles were used to provide 8 magnets for an axial gap generator, in a collaborative experiment with Emerson Electric Co. This generator delivered 100 Watts to a resistive load, at 2265 rpm. In this experiment, activation of the TFMs was accomplished by a current pulse of 15 ms duration. Tiles have also been studied for application as a bumper-tether system for the soft docking of spacecraft. A method for optimizing tether forces, and mechanisms of energy dissipation are discussed. A bus bar was constructed by welding three crystals while melt-texturing, such that their a,b planes were parallel and interleaved. The bus bar, of area approx. 2 sq cm, carried a transport current of 1000 amps, the limit of the testing equipment available.

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

PubMed

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

2017-01-01

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

Neuroretinal Rim Area Change in Glaucoma Patients With Visual Field Progression Endpoints and Intraocular Pressure Reduction. The Canadian Glaucoma Study: 4.

PubMed

Malik, Rizwan; O'Leary, Neil; Mikelberg, Frederick S; Balazsi, A Gordon; LeBlanc, Raymond P; Lesk, Mark R; Nicolela, Marcelo T; Trope, Graham E; Chauhan, Balwantray C

2016-03-01

To compare rim area rates in patients with and without the visual field (VF) progression endpoint in the Canadian Glaucoma Study and determine whether intraocular pressure (IOP) reduction following the endpoint altered rim area rate. Prospective multicenter cohort study. setting: University hospitals. Two hundred and six patients with open-angle glaucoma were examined at 4-month intervals with standard automated perimetry and confocal scanning laser tomography. After the endpoint, IOP was reduced by ≥20%. Univariate analysis for change in rim area rate and multivariable analysis to adjust for independent covariates (eg, age, sex, and IOP). Patients with an endpoint (n = 59) had a worse rim area rate prior to the endpoint compared to those without (n = 147; median [interquartile range]: -14 [-32, 11] × 10(-3) mm(2)/y and -5 [-14, 5] × 10(-3) mm(2)/y, respectively, P = .02). In univariate analysis, there was no difference in rim area rate before and after the endpoint (median difference [95% CI], 8 (-10, 24) × 10(-3) mm(2)/y), but the muItivariate analysis showed that IOP reduction >2 mm Hg after the endpoint was strongly linked to a reduction in rim area rate decline (8 × 10(-3) mm(2)/y for each additional 1 mm Hg reduction). Patients with a VF endpoint had a median rim area rate that was nearly 3 times worse than those without an endpoint. Lower mean follow-up IOP was independently associated with a slower decline in rim area. Copyright © 2016 Elsevier Inc. All rights reserved.

Toward surface quantification of liver fibrosis progression

NASA Astrophysics Data System (ADS)

He, Yuting; Kang, Chiang Huen; Xu, Shuoyu; Tuo, Xiaoye; Trasti, Scott; Tai, Dean C. S.; Raja, Anju Mythreyi; Peng, Qiwen; So, Peter T. C.; Rajapakse, Jagath C.; Welsch, Roy; Yu, Hanry

2010-09-01

Monitoring liver fibrosis progression by liver biopsy is important for certain treatment decisions, but repeated biopsy is invasive. We envision redefinition or elimination of liver biopsy with surface scanning of the liver with minimally invasive optical methods. This would be possible only if the information contained on or near liver surfaces accurately reflects the liver fibrosis progression in the liver interior. In our study, we acquired the second-harmonic generation and two-photon excitation fluorescence microscopy images of liver tissues from bile duct-ligated rat model of liver fibrosis. We extracted morphology-based features, such as total collagen, collagen in bile duct areas, bile duct proliferation, and areas occupied by remnant hepatocytes, and defined the capsule and subcapsular regions on the liver surface based on image analysis of features. We discovered a strong correlation between the liver fibrosis progression on the anterior surface and interior in both liver lobes, where biopsy is typically obtained. The posterior surface exhibits less correlation with the rest of the liver. Therefore, scanning the anterior liver surface would obtain similar information to that obtained from biopsy for monitoring liver fibrosis progression.

How may targeted proteomics complement genomic data in breast cancer?

PubMed

Guerin, Mathilde; Gonçalves, Anthony; Toiron, Yves; Baudelet, Emilie; Audebert, Stéphane; Boyer, Jean-Baptiste; Borg, Jean-Paul; Camoin, Luc

2017-01-01

Breast cancer (BC) is the most common female cancer in the world and was recently deconstructed in different molecular entities. Although most of the recent assays to characterize tumors at the molecular level are genomic-based, proteins are the actual executors of cellular functions and represent the vast majority of targets for anticancer drugs. Accumulated data has demonstrated an important level of quantitative and qualitative discrepancies between genomic/transcriptomic alterations and their protein counterparts, mostly related to the large number of post-translational modifications. Areas covered: This review will present novel proteomics technologies such as Reverse Phase Protein Array (RPPA) or mass-spectrometry (MS) based approaches that have emerged and that could progressively replace old-fashioned methods (e.g. immunohistochemistry, ELISA, etc.) to validate proteins as diagnostic, prognostic or predictive biomarkers, and eventually monitor them in the routine practice. Expert commentary: These different targeted proteomic approaches, able to complement genomic data in BC and characterize tumors more precisely, will permit to go through a more personalized treatment for each patient and tumor.

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.

Spelling Strategies: Take Stock of Students' Spelling Progress.

ERIC Educational Resources Information Center

Gentry, J. Richard

1998-01-01

Presents four informal assessments that elementary teachers can use to compare students' spelling progress to typical midyear benchmarks. The assessments, which target K-6 students, emphasize alphabet recognition, phonemic awareness, attitude and consciousness about spelling, and spelling growth through writing samples. The paper includes a…

[Treatment progress of gastrointestinal stromal tumor].

PubMed

Ji, Xin; Ji, Jia-fu

2013-03-01

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Its pathogenesis is defined by mutations within the KIT and PDGFRα gene. Surgical resection is the only radical treatment at present, but recurrence is common. In recent years, targeted therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. For resectable GIST, operation combined with neoadjuvant and adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors can improve the prognosis of high-risk patients before or after complete resection. For unresectable GIST, targeted therapy with imatinib mesylate can effectively inhibit and ameliorate the progression of GIST.

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

PubMed

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

2017-10-01

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

Medicaid Coverage of Tobacco Dependency Treatments | Cancer Trends Progress Report

Cancer.gov

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

UV Exposure and Sun Protective Practices | Cancer Trends Progress Report

Cancer.gov

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

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

Cancer.gov

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

Targeting protein kinase-b3 (akt3) signaling in melanoma.

PubMed

Madhunapantula, SubbaRao V; Robertson, Gavin P

2017-03-01

Deregulated Akt activity leading to apoptosis inhibition, enhanced proliferation and drug resistance has been shown to be responsible for 35-70% of advanced metastatic melanomas. Of the three isoforms, the majority of melanomas have elevated Akt3 expression and activity. Hence, potent inhibitors targeting Akt are urgently required, which is possible only if (a) the factors responsible for the failure of Akt inhibitors in clinical trials is known; and (b) the information pertaining to synergistically acting targeted therapeutics is available. Areas covered: This review provides a brief introduction of the PI3K-Akt signaling pathway and its role in melanoma development. In addition, the functional role of key Akt pathway members such as PRAS40, GSK3 kinases, WEE1 kinase in melanoma development are discussed together with strategies to modulate these targets. Efficacy and safety of Akt inhibitors is also discussed. Finally, the mechanism(s) through which Akt leads to drug resistance is discussed in this expert opinion review. Expert opinion: Even though Akt play key roles in melanoma tumor progression, cell survival and drug resistance, many gaps still exist that require further understanding of Akt functions, especially in the (a) metastatic spread; (b) circulating melanoma cells survival; and (c) melanoma stem cells growth.

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

PubMed

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

2017-08-18

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

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2013-08-01

This project is to use cutting-edge technologies to characterize novel RSR genes and their functions in tumor suppression; identify gene signature...and membrane proteins associated with defective RSR; identify drugs that target these defects; and develop RSR-defect-targeting nanoparticles for...screening and validation of drugs that target RSR-defect cells. The progress of our third year research is described below. BODY The tasks

Progress report No. 2, design of new pile area {open_quotes}G,{close_quotes} Project C-300, Atomic Energy Commission Directive HW-104

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

Lowe, P.E.

1950-01-16

This document is the progress report for the design and development of Pile Area {open_quotes}G{close_quotes}, to cover the period June 1, 1949 to December 31, 1949. This project represents the major effort of the Reactor Division of the Design and Construction Divisions. It is being pursued with the aim of being able to incorporate the major project objectives in a finished pile design if that design is begun about January, 1951.

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

ERIC Educational Resources Information Center

Gorard, Stephen; Selwyn, Neil; Rees, Gareth

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

An iterative and targeted sampling design informed by habitat suitability models for detecting focal plant species over extensive areas.

PubMed

Wang, Ophelia; Zachmann, Luke J; Sesnie, Steven E; Olsson, Aaryn D; Dickson, Brett G

2014-01-01

Prioritizing areas for management of non-native invasive plants is critical, as invasive plants can negatively impact plant community structure. Extensive and multi-jurisdictional inventories are essential to prioritize actions aimed at mitigating the impact of invasions and changes in disturbance regimes. However, previous work devoted little effort to devising sampling methods sufficient to assess the scope of multi-jurisdictional invasion over extensive areas. Here we describe a large-scale sampling design that used species occurrence data, habitat suitability models, and iterative and targeted sampling efforts to sample five species and satisfy two key management objectives: 1) detecting non-native invasive plants across previously unsampled gradients, and 2) characterizing the distribution of non-native invasive plants at landscape to regional scales. Habitat suitability models of five species were based on occurrence records and predictor variables derived from topography, precipitation, and remotely sensed data. We stratified and established field sampling locations according to predicted habitat suitability and phenological, substrate, and logistical constraints. Across previously unvisited areas, we detected at least one of our focal species on 77% of plots. In turn, we used detections from 2011 to improve habitat suitability models and sampling efforts in 2012, as well as additional spatial constraints to increase detections. These modifications resulted in a 96% detection rate at plots. The range of habitat suitability values that identified highly and less suitable habitats and their environmental conditions corresponded to field detections with mixed levels of agreement. Our study demonstrated that an iterative and targeted sampling framework can address sampling bias, reduce time costs, and increase detections. Other studies can extend the sampling framework to develop methods in other ecosystems to provide detection data. The sampling methods

An Iterative and Targeted Sampling Design Informed by Habitat Suitability Models for Detecting Focal Plant Species over Extensive Areas

PubMed Central

Wang, Ophelia; Zachmann, Luke J.; Sesnie, Steven E.; Olsson, Aaryn D.; Dickson, Brett G.

2014-01-01

Prioritizing areas for management of non-native invasive plants is critical, as invasive plants can negatively impact plant community structure. Extensive and multi-jurisdictional inventories are essential to prioritize actions aimed at mitigating the impact of invasions and changes in disturbance regimes. However, previous work devoted little effort to devising sampling methods sufficient to assess the scope of multi-jurisdictional invasion over extensive areas. Here we describe a large-scale sampling design that used species occurrence data, habitat suitability models, and iterative and targeted sampling efforts to sample five species and satisfy two key management objectives: 1) detecting non-native invasive plants across previously unsampled gradients, and 2) characterizing the distribution of non-native invasive plants at landscape to regional scales. Habitat suitability models of five species were based on occurrence records and predictor variables derived from topography, precipitation, and remotely sensed data. We stratified and established field sampling locations according to predicted habitat suitability and phenological, substrate, and logistical constraints. Across previously unvisited areas, we detected at least one of our focal species on 77% of plots. In turn, we used detections from 2011 to improve habitat suitability models and sampling efforts in 2012, as well as additional spatial constraints to increase detections. These modifications resulted in a 96% detection rate at plots. The range of habitat suitability values that identified highly and less suitable habitats and their environmental conditions corresponded to field detections with mixed levels of agreement. Our study demonstrated that an iterative and targeted sampling framework can address sampling bias, reduce time costs, and increase detections. Other studies can extend the sampling framework to develop methods in other ecosystems to provide detection data. The sampling methods

Socioeconomic research in agroforestry: progress, prospects, priorities

Treesearch

D. Evan Mercer; R.P. Miller

1998-01-01

Fourteen years after the birth of the journal Agroforestry Systems, biophysical studies continue to dominate agroforestry research while other important areas have not received the attention they deserve. This paper reviews the progress in one of these under-researched areas, socioeconomics. A quantitative and qualitative analysis of published socioeconomic research...

Target attribute-based false alarm rejection in small infrared target detection

NASA Astrophysics Data System (ADS)

Kim, Sungho

2012-11-01

Infrared search and track is an important research area in military applications. Although there are a lot of works on small infrared target detection methods, we cannot apply them in real field due to high false alarm rate caused by clutters. This paper presents a novel target attribute extraction and machine learning-based target discrimination method. Eight kinds of target features are extracted and analyzed statistically. Learning-based classifiers such as SVM and Adaboost are developed and compared with conventional classifiers for real infrared images. In addition, the generalization capability is also inspected for various infrared clutters.

In Vitro and In Vivo Tumor Targeted Photothermal Cancer Therapy Using Functionalized Graphene Nanoparticles.

PubMed

Kim, Sung Han; Lee, Jung Eun; Sharker, Shazid Md; Jeong, Ji Hoon; In, Insik; Park, Sung Young

2015-11-09

Despite the tremendous progress that photothermal therapy (PTT) has recently achieved, it still has a long way to go to gain the effective targeted photothermal ablation of tumor cells. Driven by this need, we describe a new class of targeted photothermal therapeutic agents for cancer cells with pH responsive bioimaging using near-infrared dye (NIR) IR825, conjugated poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) (PEG-g-PDMA, PgP), and hyaluronic acid (HA) anchored reduced graphene oxide (rGO) hybrid nanoparticles. The obtained rGO nanoparticles (PgP/HA-rGO) showed pH-dependent fluorescence emission and excellent near-infrared (NIR) irradiation of cancer cells targeted in vitro to provide cytotoxicity. Using intravenously administered PTT agents, the time-dependent in vivo tumor target accumulation was exactly defined, presenting eminent photothermal conversion at 4 and 8 h post-injection, which was demonstrated from the ex vivo biodistribution of tumors. These tumor environment responsive hybrid nanoparticles generated photothermal heat, which caused dominant suppression of tumor growth. The histopathological studies obtained by H&E staining demonstrated complete healing from malignant tumor. In an area of limited successes in cancer therapy, our translation will pave the road to design stimulus environment responsive targeted PTT agents for the safe eradication of devastating cancer.

How to reach haze control targets by air pollutants emission reduction in the Beijing-Tianjin-Hebei region of China?

PubMed

Xu, Feng; Xiang, Nan; Higano, Yoshiro

2017-01-01

Currently, Haze is one of the greatest environmental problems with serious impacts on human health in China, especially in capital region (Beijing-Tianjin-Hebei region). To alleviate this problem, the Chinese government introduced a National Air Pollution Control Action Plan (NAPCAP) with air pollutants reduction targets by 2017. However, there is doubt whether these targets can be achieved once the plan is implemented. In this work, the effectiveness of NAPCAP is analyzed by developing models of the statistical relationship between PM2.5 concentrations and air pollutant emissions (SO2, NOx, smoke and dust), while taking into account wind and neighboring transfer impacts. The model can also identify ways of calculating the intended emission levels in the Beijing-Tianjin-Hebei area. The results indicate that haze concentration control targets will not be attained by following the NAPCAP, and that the amount of progress needed to meet the targets is unrealistic. A more appropriate approach to reducing air emissions is proposed, which addresses joint regional efforts.

Curcumin inhibits cancer progression through regulating expression of microRNAs.

PubMed

Zhou, Siying; Zhang, Sijie; Shen, Hongyu; Chen, Wei; Xu, Hanzi; Chen, Xiu; Sun, Dawei; Zhong, Shanliang; Zhao, Jianhua; Tang, Jinhai

2017-02-01

Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

The therapeutic potential of cell cycle targeting in multiple myeloma.

PubMed

Maes, Anke; Menu, Eline; Veirman, Kim De; Maes, Ken; Vand Erkerken, Karin; De Bruyne, Elke

2017-10-27

Proper cell cycle progression through the interphase and mitosis is regulated by coordinated activation of important cell cycle proteins (including cyclin-dependent kinases and mitotic kinases) and several checkpoint pathways. Aberrant activity of these cell cycle proteins and checkpoint pathways results in deregulation of cell cycle progression, which is one of the key hallmarks of cancer. Consequently, intensive research on targeting these cell cycle regulatory proteins identified several candidate small molecule inhibitors that are able to induce cell cycle arrest and even apoptosis in cancer cells. Importantly, several of these cell cycle regulatory proteins have also been proposed as therapeutic targets in the plasma cell malignancy multiple myeloma (MM). Despite the enormous progress in the treatment of MM the past 5 years, MM still remains most often incurable due to the development of drug resistance. Deregulated expression of the cyclins D is observed in virtually all myeloma patients, emphasizing the potential therapeutic interest of cyclin-dependent kinase inhibitors in MM. Furthermore, other targets have also been identified in MM, such as microtubules, kinesin motor proteins, aurora kinases, polo-like kinases and the anaphase promoting complex/cyclosome. This review will provide an overview of the cell cycle proteins and checkpoint pathways deregulated in MM and discuss the therapeutic potential of targeting proteins or protein complexes involved in cell cycle control in MM.

Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

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

Bajenova, Olga, E-mail: o.bazhenova@spbu.ru; Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034; Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178

2014-06-10

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

Learning Progressions, Vertical Scales, and Testable Hypotheses: Promising Intuitions and Points for Clarification

ERIC Educational Resources Information Center

Maul, Andrew

2015-01-01

Briggs and Peck [in "Using Learning Progressions to Design Vertical Scales That Support Coherent Inferences about Student Growth"] call for greater care in the conceptualization of the target attributes of students, or "what it is that is growing from grade to grade." In particular, they argue that learning progressions can…

Progress toward a practical laser driven ion source using variable thickness liquid crystal targets

NASA Astrophysics Data System (ADS)

Poole, Patrick; Cochran, Ginevra; Zeil, Karl; Metzkes, Josephine; Obst, Lieselotte; Kluge, Thomas; Schlenvoigt, Hans-Peter; Prencipe, Irene; Cowan, Tom; Schramm, Uli; Schumacher, Douglass

2016-10-01

Ion acceleration from ultra-intense laser interaction has been long investigated in pursuit of requisite energies and spectral distributions for applications like proton cancer therapy. However, the details of ion acceleration mechanisms and their laser intensity scaling are not fully understood, especially the complete role of pulse contrast and target thickness. Additionally, target delivery and alignment at appropriate rates for study and subsequent treatment pose significant challenges. We present results from a campaign on the Draco laser using liquid crystal targets that have on-demand, in-situ thickness tunability over more than three orders of magnitude, enabling rapid data collection due to <1 minute, automatically aligned target formation. Diagnostics include spectral and spatial measurement of ions, electrons, and reflected and transmitted light, all with thickness, laser focus, and pulse contrast variations. In particular we discuss optimal thickness vs. contrast and details of ultra-thin target normal ion acceleration, along with supporting particle-in-cell studies. This work was supported by the DARPA PULSE program through AMRDEC, by the NNSA (DE-NA0001976), by EC Horizon 2020 LASERLAB-EUROPE/LEPP (654148), and by the German Federal Ministry of Education and Research (BMBF, 03Z1O511).

Cancer-associated fibroblasts drive glycolysis in a targetable signaling loop implicated in head and neck squamous cell carcinoma progression.

PubMed

Kumar, Dhruv; New, Jacob; Vishwakarma, Vikalp; Joshi, Radhika; Enders, Jonathan; Lin, Fangchen; Dasari, Sumana; Gutierrez, Wade R; Leef, George; Ponnurangam, Sivapriya; Chavan, Hemantkumar; Ganaden, Lydia; Thornton, Mackenzie M; Dai, Hongying; Tawfik, Ossama; Straub, Jeffrey; Shnayder, Yelizaveta; Kakarala, Kiran; Tsue, Terance Ted; Girod, Douglas A; Van Houten, Bennett; Anant, Shrikant; Krishnamurthy, Partha; Thomas, Sufi Mary

2018-05-16

Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted hepatocyte growth factor (HGF) facilitates HNSCC progression, however very little is known about the role of CAFs in HNSCC metabolism. Here we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis. CAF-secreted HGF induced basic fibroblast growth factor (bFGF) secretion from HNSCC. CAFs were more efficient than HNSCC in using lactate as a carbon source. HNSCC-secreted bFGF increased mitochondrial oxidative phosphorylation (OXPHOS) and HGF secretion from CAFs. Combined inhibition of c-Met and FGFR significantly inhibited CAF-induced HNSCC growth in vitro and in vivo (p<0.001). Our cumulative findings underscore reciprocal signaling between CAF and HNSCC involving bFGF and HGF. This contributes to metabolic symbiosis and a targetable therapeutic axis involving c-Met and FGFR. Copyright ©2018, American Association for Cancer Research.

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

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

PubMed Central

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

2018-01-01

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

Tumor glycolysis as a target for cancer therapy: progress and prospects

PubMed Central

2013-01-01

Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the “hallmarks of cancer”. This metabolic phenotype is characterized by preferential dependence on glycolysis (the process of conversion of glucose into pyruvate followed by lactate production) for energy production in an oxygen-independent manner. Although glycolysis is less efficient than oxidative phosphorylation in the net yield of adenosine triphosphate (ATP), cancer cells adapt to this mathematical disadvantage by increased glucose up-take, which in turn facilitates a higher rate of glycolysis. Apart from providing cellular energy, the metabolic intermediates of glycolysis also play a pivotal role in macromolecular biosynthesis, thus conferring selective advantage to cancer cells under diminished nutrient supply. Accumulating data also indicate that intracellular ATP is a critical determinant of chemoresistance. Under hypoxic conditions where glycolysis remains the predominant energy producing pathway sensitizing cancer cells would require intracellular depletion of ATP by inhibition of glycolysis. Together, the oncogenic regulation of glycolysis and multifaceted roles of glycolytic components underscore the biological significance of tumor glycolysis. Thus targeting glycolysis remains attractive for therapeutic intervention. Several preclinical investigations have indeed demonstrated the effectiveness of this therapeutic approach thereby supporting its scientific rationale. Recent reviews have provided a wealth of information on the biochemical targets of glycolysis and their inhibitors. The objective of this review is to present the most recent research on the cancer-specific role of glycolytic enzymes including their non-glycolytic functions in order to explore the potential for therapeutic opportunities. Further, we discuss the translational potential of emerging drug candidates in light of technical advances in treatment modalities such as image

Bacteriophage-Derived Vectors for Targeted Cancer Gene Therapy

PubMed Central

Pranjol, Md Zahidul Islam; Hajitou, Amin

2015-01-01

Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration. PMID:25606974

Bacteriophage-derived vectors for targeted cancer gene therapy.

PubMed

Pranjol, Md Zahidul Islam; Hajitou, Amin

2015-01-19

Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration.

Liver as a target for oligonucleotide therapeutics.

PubMed