Stem cells as the root of pancreatic ductal adenocarcinoma

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

Balic, Anamaria; Dorado, Jorge; Alonso-Gomez, Mercedes

2012-04-01

Emerging evidence suggests that stem cells play a crucial role not only in the generation and maintenance of different tissues, but also in the development and progression of malignancies. For the many solid cancers, it has now been shown that they harbor a distinct subpopulation of cancer cells that bear stem cell features and therefore, these cells are termed cancer stem cells (CSC) or tumor-propagating cells. CSC are exclusively tumorigenic and essential drivers for tumor progression and metastasis. Moreover, it has been shown that pancreatic ductal adenocarcinoma does not only contain one homogeneous population of CSC rather than diverse subpopulationsmore » that may have evolved during tumor progression. One of these populations is called migrating CSC and can be characterized by CXCR4 co-expression. Only these cells are capable of evading the primary tumor and traveling to distant sites such as the liver as the preferred site of metastatic spread. Clinically even more important, however, is the observation that CSC are highly resistant to chemo- and radiotherapy resulting in their relative enrichment during treatment and rapid relapse of disease. Many laboratories are now working on the further in-depth characterization of these cells, which may eventually allow for the identification of their Achilles heal and lead to novel treatment modalities for fighting this deadly disease.« less

Yucca Mountain site characteriztion project bibliography. Progress Report, 1994--1995

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

NONE

1996-08-01

Following a reorganization of the Office of Civilian Radioactive Waste Management in 1990, the Yucca Mountain Project was renamed Yucca Mountain Site Characterization Project. The title of this bibliography was also changed to Yucca Mountain Site Characterization Project Bibliography. Prior to August 5, 1988, this project was called the Nevada Nuclear Waste Storage Investigations. This bibliography contains information on this ongoing project which was added to the Department of Energy`s Energy Science and Technology Database from January 1, 1994, through December 31, 1995. The bibliography is categorized by principal project participating organization. Participant-sponsored subcontractor reports, papers, and articles are includedmore » in the sponsoring organization`s list. Another section contains information about publications on the Energy Science and Technology database which were not sponsored by the project but have some relevance to it.« less

CD117/c-kit in Cancer Stem Cell-Mediated Progression and Therapeutic Resistance

PubMed Central

Young, Tyler R.; Mobley, Mary E.

2018-01-01

Metastasis is the primary cause of cancer patient morbidity and mortality, but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patient tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven by a cancer stem-like cell or tumor progenitor cell, while recurrence at a secondary site is driven by metastatic cancer stem cells or metastasis-initiating cells. Ongoing efforts are aimed at identifying and characterizing these stem-like cells driving recurrence and metastasis. One potential marker for the cancer stem-like cell subpopulation is CD117/c-kit, a tyrosine kinase receptor associated with cancer progression and normal stem cell maintenance. Further, activation of CD117 by its ligand stem cell factor (SCF; kit ligand) in the progenitor cell niche stimulates several signaling pathways driving proliferation, survival, and migration. This review examines evidence that the SCF/CD117 signaling axis may contribute to the control of cancer progression through the regulation of stemness and resistance to tyrosine kinase inhibitors. PMID:29518044

Kinetics of disease progression and host response in a rat model of bubonic plague.

PubMed

Sebbane, Florent; Gardner, Donald; Long, Daniel; Gowen, Brian B; Hinnebusch, B Joseph

2005-05-01

Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease.

Updates from the AmeriFlux Management Project Tech Team

NASA Astrophysics Data System (ADS)

Biraud, S.; Chan, S.; Dengel, S.; Polonik, P.; Hanson, C. V.; Billesbach, D. P.; Torn, M. S.

2017-12-01

The goal of AmeriFlux is to develop a network of long-term flux sites for quantifying and understanding the role of the terrestrial biosphere in global climate and environmental change. The AmeriFlux Management Program (AMP) Tech Team at LBNL strengthens the AmeriFlux Network by (1) standardizing operational practices, (2) developing calibration and maintenance routines, and (3) setting clear data quality goals. In this poster we will present results and recent progress in three areas: IRGA intercomparison experiment in cooperation with UC Davis, and main manufacturers of sensors used in the AmeriFlux network (LI-COR, Picarro, and Campbell Scientific). Gill sonic anemometers characterization in collaboration with John Frank and Bill Massman (US Forest Service) following the discovery of a significant firmware problem in commonly used Gill Sonic anemometer, Unmanned aerial systems (UAS), and sensors systematically used at AmeriFlux sites to improve site characterization.

High frequency of brain metastases after adjuvant therapy for high-risk melanoma.

PubMed

Samlowski, Wolfram E; Moon, James; Witter, Merle; Atkins, Michael B; Kirkwood, John M; Othus, Megan; Ribas, Antoni; Sondak, Vernon K; Flaherty, Lawrence E

2017-11-01

The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7 years (range: 1 month to 11 years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3 years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT = 25, HDI = 34, P = 0.24). Lymph node macrometastases strongly associated with CNS progression (P = 0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Characterization of sleeping sickness transmission sites in rural and periurban areas of Kinshasa (République Démocratique du Congo).

PubMed

Grébaut, Pascal; Bena, Jean-Marie; Manzambi, Emile Zola; Mansinsa, Philémon; Khande, Victor; Ollivier, Gaelle; Cuny, Gérard; Simo, Gustave

2009-12-01

To characterize the potential transmission sites of sleeping sickness in Kinshasa, two entomologic surveys were carried out during the dry and the rainy seasons in rural and periurban areas of Kinshasa in 2005. About 610 pyramidal traps were set up, and 897 Glossina fuscipes quanzensis were captured. Environmental and biologic factors were reported, and relationships between these factors were evaluated using logistic regression and multiple correspondence analysis. The biologic factors (the presence of tsetse flies, human blood meals, and teneral flies) were progressively accumulated at each capture site to permit the characterization of the sleeping sickness transmission risk. The dry season was found to be a more favorable period for the disease transmission than the rainy season. Moreover, the landscapes characterized by the presence of argillaceous soils, raised ground cover with forest residues and rivers, were identified as types of environments with greater risk of sleeping sickness transmission. Pig breeding appeared as an important factor increasing the disease transmission. If vector control is continuously performed along rivers segments at high risk, the transmission of sleeping sickness in rural and periurban areas of Kinshasa will considerably decrease.

Kinetics of Disease Progression and Host Response in a Rat Model of Bubonic Plague

PubMed Central

Sebbane, Florent; Gardner, Donald; Long, Daniel; Gowen, Brian B.; Hinnebusch, B. Joseph

2005-01-01

Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease. PMID:15855643

Metal–organic and covalent organic frameworks as single-site catalysts

PubMed Central

Rogge, S. M. J.; Bavykina, A.; Hajek, J.; Garcia, H.; Olivos-Suarez, A. I.; Sepúlveda-Escribano, A.; Vimont, A.; Clet, G.; Bazin, P.; Kapteijn, F.

2017-01-01

Heterogeneous single-site catalysts consist of isolated, well-defined, active sites that are spatially separated in a given solid and, ideally, structurally identical. In this review, the potential of metal–organic frameworks (MOFs) and covalent organic frameworks (COFs) as platforms for the development of heterogeneous single-site catalysts is reviewed thoroughly. In the first part of this article, synthetic strategies and progress in the implementation of such sites in these two classes of materials are discussed. Because these solids are excellent playgrounds to allow a better understanding of catalytic functions, we highlight the most important recent advances in the modelling and spectroscopic characterization of single-site catalysts based on these materials. Finally, we discuss the potential of MOFs as materials in which several single-site catalytic functions can be combined within one framework along with their potential as powerful enzyme-mimicking materials. The review is wrapped up with our personal vision on future research directions. PMID:28338128

Site characterization progress report: Yucca Mountain, Nevada. Number 15, April 1--September 30, 1996

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

NONE

1997-04-01

During the second half of fiscal year 1996, activities at the Yucca Mountain Site Characterization Project (Project) supported the objectives of the revised Program Plan released this period by the Office of Civilian Radioactive Waste Management of the US Department of Energy (Department). Outlined in the revised plan is a focused, integrated program of site characterization, design, engineering, environmental, and performance assessment activities that will achieve key Program and statutory objectives. The plan will result in the development of a license application for repository construction at Yucca Mountain, if the site is found suitable. Activities this period focused on twomore » of the three near-term objectives of the revised plan: updating in 1997 the regulatory framework for determining the suitability of the site for the proposed repository concept and providing information for a 1998 viability assessment of continuing toward the licensing of a repository. The Project has also developed a new design approach that uses the advanced conceptual design published during the last reporting period as a base for developing a design that will support the viability assessment. The initial construction phase of the Thermal Testing Facility was completed and the first phase of the in situ heater tests began on schedule. In addition, phase-one construction was completed for the first of two alcoves that will provide access to the Ghost Dance fault.« less

Progressive failure site generation in AlGaN/GaN high electron mobility transistors under OFF-state stress: Weibull statistics and temperature dependence

NASA Astrophysics Data System (ADS)

Sun, Huarui; Bajo, Miguel Montes; Uren, Michael J.; Kuball, Martin

2015-01-01

Gate leakage degradation of AlGaN/GaN high electron mobility transistors under OFF-state stress is investigated using a combination of electrical, optical, and surface morphology characterizations. The generation of leakage "hot spots" at the edge of the gate is found to be strongly temperature accelerated. The time for the formation of each failure site follows a Weibull distribution with a shape parameter in the range of 0.7-0.9 from room temperature up to 120 °C. The average leakage per failure site is only weakly temperature dependent. The stress-induced structural degradation at the leakage sites exhibits a temperature dependence in the surface morphology, which is consistent with a surface defect generation process involving temperature-associated changes in the breakdown sites.

Elucidation of the Hsp90 C-terminal Inhibitor Binding Site

PubMed Central

Matts, Robert L.; Dixit, Anshuman; Peterson, Laura B.; Sun, Liang; Voruganti, Sudhakar; Kalyanaraman, Palgunan; Hartson, Steve D.; Verkhivker, Gennady M.; Blagg, Brian S. J.

2011-01-01

The Hsp90 chaperone machine is required for the folding, activation and/or stabilization of more than 50 proteins directly related to malignant progression. Hsp90 contains small molecule binding sites at both its N- and C-terminal domains, however, limited structural and biochemical data regarding the C-terminal binding site is available. In this report, the small molecule binding site in the Hsp90 C-terminal domain was revealed by protease fingerprinting and photoaffinity labeling utilizing LC-MS/MS. The identified site was characterized by generation of a homology model for hHsp90α using the SAXS open structure of HtpG and docking the bioactive conformation of NB into the generated model. The resulting model for the bioactive conformation of NB bound to Hsp90α is presented herein. PMID:21548602

MDM2 copy numbers in well-differentiated and dedifferentiated liposarcoma: characterizing progression to high-grade tumors.

PubMed

Ware, Patrick L; Snow, Anthony N; Gvalani, Maya; Pettenati, Mark J; Qasem, Shadi A

2014-03-01

MDM2 gene amplification is associated with well-differentiated (WDL) and dedifferentiated liposarcomas (DDL). Using fluorescent in situ hybridization (FISH), we sought to characterize various patterns of MDM2 amplification among the morphologic spectrum of liposarcoma. Forty-six cases of liposarcoma in various sites were examined and included 22 WDLs, 14 DLLs, and 10 negative control subjects. The MDM2 amplification ratio (MDM2/CEP12) was lower in WDL (10.2) compared with DDL (18.3) cases (P = .0000002). An amplification ratio of 16 showed optimal sensitivity (0.86) and specificity (0.96) as a cutoff point for progression to DDL. Borderline areas, defined as tumors with increased cellularity and atypia but with preserved lipomatous differentiation, showed a significantly higher MDM2 ratio (17.5; P = .0007) compared with WDL. Central (retroperitoneal and intra-abdominal) tumors also showed a significantly higher MDM2 ratio than peripheral ones (P = .02). Differences in MDM2 amplification profiles among liposarcomas could help further define and predict progression to high-grade neoplasia.

NRC TLD Direct Radiation Monitoring Network. Progress report, October--December 1996

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

Struckmeyer, R.

This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1996. It provides the ambient radiation levels measured in the vicinity of 74 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program. 3 figs., 4 tabs.

NASA/ESMD Analogue Mission Plans

NASA Technical Reports Server (NTRS)

Hoffman, Stephen J.

2007-01-01

A viewgraph presentation exploring Earth and its analogues is shown. The topics include: 1) ESMD Goals for the Use of Earth Analogues; 2) Stakeholders Summary; 3) Issues with Current Analogue Situation; 4) Current state of Analogues; 5) External Implementation Plan (Second Step); 6) Recent Progress in Utilizing Analogues; 7) Website Layout Example-Home Page; 8) Website Layout Example-Analogue Site; 9) Website Layout Example-Analogue Mission; 10) Objectives of ARDIG Analog Initiatives; 11) Future Plans; 12) Example: Cold-Trap Sample Return; 13) Example: Site Characterization Matrix; 14) Integrated Analogue Studies-Prerequisites for Human Exploration; and 15) Rating Scale Definitions.

Peri-implantitis.

PubMed

Schwarz, Frank; Derks, Jan; Monje, Alberto; Wang, Hom-Lay

2018-06-01

This narrative review provides an evidence-based overview on peri-implantitis for the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. A literature review was conducted addressing the following topics: 1) definition of peri-implantitis; 2) conversion from peri-implant mucositis to peri-implantitis, 3) onset and pattern of disease progression, 4) characteristics of peri-implantitis, 5) risk factors/indicators for peri-implantitis, and 6) progressive crestal bone loss in the absence of soft tissue inflammation. 1)Peri-implantitis is a pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri-implant connective tissue and progressive loss of supporting bone. 2)The histopathologic and clinical conditions leading to the conversion from peri-implant mucositis to peri-implantitis are not completely understood. 3)The onset of peri-implantitis may occur early during follow-up and the disease progresses in a non-linear and accelerating pattern. 4a)Peri-implantitis sites exhibit clinical signs of inflammation and increased probing depths compared to baseline measurements. 4b)At the histologic level, compared to periodontitis sites, peri-implantitis sites often have larger inflammatory lesions. 4c)Surgical entry at peri-implantitis sites often reveals a circumferential pattern of bone loss. 5a)There is strong evidence that there is an increased risk of developing peri-implantitis in patients who have a history of chronic periodontitis, poor plaque control skills, and no regular maintenance care after implant therapy. Data identifying "smoking" and "diabetes" as potential risk factors/indicators for peri-implantitis are inconclusive. 5b)There is some limited evidence linking peri-implantitis to other factors such as: post-restorative presence of submucosal cement, lack of peri-implant keratinized mucosa and positioning of implants that make it difficult to perform oral hygiene and maintenance. 6)Evidence suggests that progressive crestal bone loss around implants in the absence of clinical signs of soft tissue inflammation is a rare event. © 2018 American Academy of Periodontology and European Federation of Periodontology.

Unconventional binding sites and receptors for VIP and related peptides PACAP and PHI/PHM: an update.

PubMed

Muller, Jean-Marc; Debaigt, Colin; Goursaud, Stéphanie; Montoni, Alicia; Pineau, Nicolas; Meunier, Annie-Claire; Janet, Thierry

2007-09-01

The 28-amino-acid neuropeptide VIP and related peptides PACAP and PHI/PHM modulate virtually all of the vital functions in the body. These peptides are also commonly recognized as major regulators of cell growth and differentiation. Through their trophic and cytoprotective functions, they appear to play major roles in embryonic development, neurogenesis and the progression of a number of cancer types. These peptides bind to three well-characterized subtypes of G-protein coupled receptors: VPAC1 and VPAC2 share a common high affinity in the nanomolar range for VIP and PACAP; a third receptor type, PAC1, has been characterized for its high affinity for PACAP but its low affinity for VIP. Complex effects and pharmacological behaviors of these peptides suggest that multiple subtypes of binding sites may cooperate to mediate their function in target cells and tissues. In this complex response, some of these binding sites correspond to the definition of the conventional receptors cited above, while others display unexpected pharmacological and functional properties. Here we present potential clues that may lead investigators to further characterize the molecular nature and functions of these atypical binding species.

Gypsy Field project in reservoir characterization

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

Castagna, John P.; Jr., O'Meara, Daniel J.

The overall objective of this project was to use extensive Gypsy Field Laboratory and data as a focus for developing and testing reservoir characterization methods that are targeted at improved recovery of conventional oil. This report describes progress since project report DOE/BC/14970-7 and covers the period June 1997-September 1998 and represents one year of funding originally allocated for the year 1996. During the course of the work previously performed, high resolution geophysical and outcrop data revealed the importance of fractures at the Gypsy site. In addition, personnel changes and alternative funding (OCAST and oil company support of various kinds) allowedmore » the authors to leverage DOE contributions and focus more on geophysical characterization.« less

The magnetohydrodynamics coal-fired flow facility

NASA Astrophysics Data System (ADS)

1995-01-01

In this quarterly technical progress report, UTSI reports on the status of a multitask contract to develop the technology for the steam bottoming portion of a MHD Steam Combined Cycle Power Plant. The report describes the facility maintenance and environmental work completed, status of completing technical reports and certain key administrative actions occurring during the quarter. With program resources at a minimum to closeout the MHD program, no further testing occurred during the quarter, but the DOE CFFF facility was maintained in a standby status with winterization, preventive maintenance and repairs accomplished as needed. Plans and preparations progressed for environmental actions needed at the site to investigate and characterize the groundwater and for removal/disposal of asbestos in the cooling tower. Work continued to progress on archiving the results of the MHD program.

Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non-Small Cell Lung Cancer.

PubMed

Gettinger, Scott N; Wurtz, Anna; Goldberg, Sarah B; Rimm, David; Schalper, Kurt; Kaech, Susan; Kavathas, Paula; Chiang, Anne; Lilenbaum, Rogerio; Zelterman, Daniel; Politi, Katerina; Herbst, Roy S

2018-06-01

With expanding indications for programmed death 1 (PD-1) axis inhibitors in non-small cell lung cancer (NSCLC), acquired resistance (AR) to these therapies is increasingly being encountered. We sought to characterize clinical patterns of AR to PD-1 axis inhibitors in patients with advanced NSCLC, and evaluate subsequent outcome and management strategies for such patients. Patients with NSCLC who developed AR to PD-1 axis inhibitor therapy initiated between December 2009 and February 2016 at one institution were identified and examined by clinical and radiographic features. AR was defined as progressive disease after initial response by either Response Evaluation Criteria in Solid Tumors v1.1 or immune-related response criteria. Twenty-six patients with AR to PD-1 axis inhibitor therapy were identified and evaluated. Median time to AR was 313 days; the 2-year survival rate from AR was 70% (95% confidence interval: 0.53-0.92). Twenty patients (77%) experienced AR in lymph nodes (LNs), including 11 patients with LN-only progression. Twenty-three (88%) patients had recurrence limited to one (54%) or two (35%) sites of disease. Fourteen patients (54%) continued PD-1 axis inhibitor therapy beyond progression. Three patients were re-challenged with the same PD-1 axis inhibitor after holiday from and progression off therapy, 2 again responded. Fifteen patients (58%) received local therapy to site(s) of AR, 11 continued respective PD-1 axis inhibitor after local therapy. The 2-year survival rate from AR among these 15 patients was 92% (95% confidence interval: 0.77-1). Acquired resistance to PD-1 axis inhibitors is often limited to one or two sites when local therapy and continuation of PD-1 axis inhibitor therapy can result in prolonged benefit. LN metastases appear to be particularly susceptible sites to AR. When progression of disease following response occurs after holiday from PD-1 axis inhibitor, re-challenge can again lead to tumor regression. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Target characterizations for a 14N(p,γ)15O cross section measurement

NASA Astrophysics Data System (ADS)

Gyürky, Gy.; Csik, A.; Mátyus, Zs.; Fülöp, Zs.; Halász, Z.; Kiss, G. G.; Szücs, T.; Wagner, L.

2018-01-01

The 14N(p,γ)15O reaction controls the rate of CNO cycle hydrogen burning in various astrophysical sites and it is therefore one of the most important reactions in nuclear astrophysics. An experimental program is in progress to measure the 14N(p,γ)15O cross section in a wide energy range using a novel approach. A crucial quantity for the cross section determination is the number of N atoms in the target. In this paper the results of different experiments used for N target characterization are presented.

Progressive failure site generation in AlGaN/GaN high electron mobility transistors under OFF-state stress: Weibull statistics and temperature dependence

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

Sun, Huarui, E-mail: huarui.sun@bristol.ac.uk; Bajo, Miguel Montes; Uren, Michael J.

2015-01-26

Gate leakage degradation of AlGaN/GaN high electron mobility transistors under OFF-state stress is investigated using a combination of electrical, optical, and surface morphology characterizations. The generation of leakage “hot spots” at the edge of the gate is found to be strongly temperature accelerated. The time for the formation of each failure site follows a Weibull distribution with a shape parameter in the range of 0.7–0.9 from room temperature up to 120 °C. The average leakage per failure site is only weakly temperature dependent. The stress-induced structural degradation at the leakage sites exhibits a temperature dependence in the surface morphology, which ismore » consistent with a surface defect generation process involving temperature-associated changes in the breakdown sites.« less

The role of organic complexants and microparticulates in the facilitated transport of radionuclides

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

Schilk, A.J.; Robertson, D.E.; Abel, K.H.

1996-12-01

This progress report describes the results of ongoing radiological and geochemical investigations of the mechanisms of radionuclide transport in groundwater at two low-level waste (LLW) disposal sites within the waste management area of the Chalk River Laboratories (CRL), Ontario, Canada. These sites, the Chemical Pit liquid disposal facility and the Waste Management Area C solid LLW disposal site, have provided valuable 30- to 40-year-old field locations for characterizing the migration of radionuclides and evaluating a number of recent site performance objectives for LLW disposal facilities. This information will aid the NRC and other federal, state, and local regulators, as wellmore » as LLW disposal site developers and waste generators, in maximizing the effectiveness of existing or projected LLW disposal facilities for isolating radionuclides from the general public and thereby improving the health and safety aspects of LLW disposal.« less

NRC TLD Direct Radiation Monitoring Network. Volume 15, No. 4: Quarterly progress report, October--December 1995

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

Struckmeyer, R.

This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1995. It provides the ambient radiation levels measured in the vicinity of 75 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program.

TTP AL921102: An integrated geophysics program for non-intrusive characterization of mixed-waste landfill sites

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

Hasbrouck, J.C.

1992-11-01

Chem-Nuclear Geotech, Inc. (Geotech), operating contractor for the US Department of Energy Grand Junction Projects Office, is conducting the Integrated Geophysics Program for Non-Intrusive Characterization of Mixed-Waste Landfill Sites (Technical Task Plan [TTP] AL921102). The TTP is part of the Mixed-Waste Landfill Integrated Demonstration (MWLID). The objective of this task was to demonstrate that an integrated program of surface geophysics can be used to effectively and nonintrusively characterize n-mixed-waste landfill sites. To accomplish this objective, integrated field demonstrations were conducted over two previously identified areas of interest (designated Areas A and B) within the MWLID test site at the Chemicalmore » Waste Landfill (CWL), Technical Area 3, at the Sandia National Laboratories, Albuquerque, New Mexico (Figures 1 and 2). Area A was centered roughly around the Chromic Acid and Organics Pits in the southeast-central portion of the landfill and Area B was centered around the 60's Pits'' area in the northeast-central portion of the landfill. Pit locations were known in Area A and suspected in Area B. This progress report describes the geophysical surveys conducted by Geotech and presents preliminary displays and analyses. Volume 2 of this report contains the raw data for all the surveys conducted by Geotech for this TTP.« less

A stochastic Markov chain model to describe lung cancer growth and metastasis.

PubMed

Newton, Paul K; Mason, Jeremy; Bethel, Kelly; Bazhenova, Lyudmila A; Nieva, Jorge; Kuhn, Peter

2012-01-01

A stochastic Markov chain model for metastatic progression is developed for primary lung cancer based on a network construction of metastatic sites with dynamics modeled as an ensemble of random walkers on the network. We calculate a transition matrix, with entries (transition probabilities) interpreted as random variables, and use it to construct a circular bi-directional network of primary and metastatic locations based on postmortem tissue analysis of 3827 autopsies on untreated patients documenting all primary tumor locations and metastatic sites from this population. The resulting 50 potential metastatic sites are connected by directed edges with distributed weightings, where the site connections and weightings are obtained by calculating the entries of an ensemble of transition matrices so that the steady-state distribution obtained from the long-time limit of the Markov chain dynamical system corresponds to the ensemble metastatic distribution obtained from the autopsy data set. We condition our search for a transition matrix on an initial distribution of metastatic tumors obtained from the data set. Through an iterative numerical search procedure, we adjust the entries of a sequence of approximations until a transition matrix with the correct steady-state is found (up to a numerical threshold). Since this constrained linear optimization problem is underdetermined, we characterize the statistical variance of the ensemble of transition matrices calculated using the means and variances of their singular value distributions as a diagnostic tool. We interpret the ensemble averaged transition probabilities as (approximately) normally distributed random variables. The model allows us to simulate and quantify disease progression pathways and timescales of progression from the lung position to other sites and we highlight several key findings based on the model.

Analysis of Vlbi, Slr and GPS Site Position Time Series

NASA Astrophysics Data System (ADS)

Angermann, D.; Krügel, M.; Meisel, B.; Müller, H.; Tesmer, V.

Conventionally the IERS terrestrial reference frame (ITRF) is realized by the adoption of a set of epoch coordinates and linear velocities for a set of global tracking stations. Due to the remarkable progress of the space geodetic observation techniques (e.g. VLBI, SLR, GPS) the accuracy and consistency of the ITRF increased continuously. The accuracy achieved today is mainly limited by technique-related systematic errors, which are often poorly characterized or quantified. Therefore it is essential to analyze the individual techniques' solutions with respect to systematic differences, models, parameters, datum definition, etc. Main subject of this presentation is the analysis of GPS, SLR and VLBI time series of site positions. The investigations are based on SLR and VLBI solutions computed at DGFI with the software systems DOGS (SLR) and OCCAM (VLBI). The GPS time series are based on weekly IGS station coordinates solutions. We analyze the time series with respect to the issues mentioned above. In particular we characterize the noise in the time series, identify periodic signals, and investigate non-linear effects that complicate the assignment of linear velocities for global tracking sites. One important aspect is the comparison of results obtained by different techniques at colocation sites.

A progress report on the ARRA-funded geotechnical site characterization project

NASA Astrophysics Data System (ADS)

Martin, A. J.; Yong, A.; Stokoe, K.; Di Matteo, A.; Diehl, J.; Jack, S.

2011-12-01

For the past 18 months, the 2009 American Recovery and Reinvestment Act (ARRA) has funded geotechnical site characterizations at 189 seismographic station sites in California and the central U.S. This ongoing effort applies methods involving surface-wave techniques, which include the horizontal-to-vertical spectral ratio (HVSR) technique and one or more of the following: spectral analysis of surface wave (SASW), active and passive multi-channel analysis of surface wave (MASW) and passive array microtremor techniques. From this multi-method approach, shear-wave velocity profiles (VS) and the time-averaged shear-wave velocity of the upper 30 meters (VS30) are estimated for each site. To accommodate the variability in local conditions (e.g., rural and urban soil locales, as well as weathered and competent rock sites), conventional field procedures are often modified ad-hoc to fit the unanticipated complexity at each location. For the majority of sites (>80%), fundamental-mode Rayleigh wave dispersion-based techniques are deployed and where complex geology is encountered, multiple test locations are made. Due to the presence of high velocity layers, about five percent of the locations require multi-mode inversion of Rayleigh wave (MASW-based) data or 3-D array-based inversion of SASW dispersion data, in combination with shallow P-wave seismic refraction and/or HVSR results. Where a strong impedance contrast (i.e. soil over rock) exists at shallow depth (about 10% of sites), dominant higher modes limit the use of Rayleigh wave dispersion techniques. Here, use of the Love wave dispersion technique, along with seismic refraction and/or HVSR data, is required to model the presence of shallow bedrock. At a small percentage of the sites, surface wave techniques are found not suitable for stand-alone deployment and site characterization is limited to the use of the seismic refraction technique. A USGS Open File Report-describing the surface geology, VS profile and the calculated VS30 for each site-will be prepared after the completion of the project in November 2011.

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

PubMed

Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R; Andrews, Leslie; Rabkin, Judith G; McElhiney, Martin; Nieves, Jeri; Santella, Regina M; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S; Miller, Robert G; Katz, Jonathan S; Forshew, Dallas; Barohn, Richard J; Sorenson, Eric J; Oskarsson, Bjorn; Fernandes Filho, J Americo M; Kasarskis, Edward J; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D; Nations, Sharon P; Swenson, Andrea J; Shefner, Jeremy M; Andrews, Jinsy A; Koczon-Jaremko, Boguslawa A

2014-06-01

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

Identification and characterization of regulatory elements in the promoter of ACVR1, the gene mutated in Fibrodysplasia Ossificans Progressiva

PubMed Central

2013-01-01

Background The ACVR1 gene encodes a type I receptor for bone morphogenetic proteins (BMPs). Mutations in the ACVR1 gene are associated with Fibrodysplasia Ossificans Progressiva (FOP), a rare and extremely disabling disorder characterized by congenital malformation of the great toes and progressive heterotopic endochondral ossification in muscles and other non-skeletal tissues. Several aspects of FOP pathophysiology are still poorly understood, including mechanisms regulating ACVR1 expression. This work aimed to identify regulatory elements that control ACVR1 gene transcription. Methods and results We first characterized the structure and composition of human ACVR1 gene transcripts by identifying the transcription start site, and then characterized a 2.9 kb upstream region. This region showed strong activating activity when tested by reporter gene assays in transfected cells. We identified specific elements within the 2.9 kb region that are important for transcription factor binding using deletion constructs, co-transfection experiments with plasmids expressing selected transcription factors, site-directed mutagenesis of consensus binding-site sequences, and by protein/DNA binding assays. We also characterized a GC-rich minimal promoter region containing binding sites for the Sp1 transcription factor. Conclusions Our results showed that several transcription factors such as Egr-1, Egr-2, ZBTB7A/LRF, and Hey1, regulate the ACVR1 promoter by binding to the -762/-308 region, which is essential to confer maximal transcriptional activity. The Sp1 transcription factor acts at the most proximal promoter segment upstream of the transcription start site. We observed significant differences in different cell types suggesting tissue specificity of transcriptional regulation. These findings provide novel insights into the molecular mechanisms that regulate expression of the ACVR1 gene and that could be targets of new strategies for future therapeutic treatments. PMID:24047559

Alcoholic Liver Disease: Pathogenesis and Current Management

PubMed Central

Osna, Natalia A.; Donohue, Terrence M.; Kharbanda, Kusum K.

2017-01-01

Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID:28988570

Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia.

PubMed

Rogalski, E; Cobia, D; Harrison, T M; Wieneke, C; Weintraub, S; Mesulam, M-M

2011-05-24

To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials. Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S). There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere. The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects.

Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia

PubMed Central

Cobia, D.; Harrison, T.M.; Wieneke, C.; Weintraub, S.; Mesulam, M.-M.

2011-01-01

Objectives: To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials. Methods: Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S). Results: There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere. Conclusions: The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects. PMID:21606451

Comprehensive analysis of MGMT promoter methylation: correlation with MGMT expression and clinical response in GBM.

PubMed

Shah, Nameeta; Lin, Biaoyang; Sibenaller, Zita; Ryken, Timothy; Lee, Hwahyung; Yoon, Jae-Geun; Rostad, Steven; Foltz, Greg

2011-01-07

O⁶-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089-13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301-7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting.

Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM

PubMed Central

Shah, Nameeta; Lin, Biaoyang; Sibenaller, Zita; Ryken, Timothy; Lee, Hwahyung; Yoon, Jae-Geun; Rostad, Steven; Foltz, Greg

2011-01-01

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089–13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301–7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting. PMID:21249131

Longitudinal evaluation of patients with oral potentially malignant disorders using optical imaging and spectroscopy

NASA Astrophysics Data System (ADS)

Schwarz, Richard A.; Pierce, Mark C.; Mondrik, Sharon; Gao, Wen; Quinn, Mary K.; Bhattar, Vijayashree; Williams, Michelle D.; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Richards-Kortum, Rebecca

2012-02-01

Dysplastic and cancerous alterations in oral tissue can be detected noninvasively in vivo using optical techniques including autofluorescence imaging, high-resolution imaging, and spectroscopy. Interim results are presented from a longitudinal study in which optical imaging and spectroscopy were used to evaluate the progression of lesions over time in patients at high risk for development of oral cancer. Over 100 patients with oral potentially malignant disorders have been enrolled in the study to date. Areas of concern in the oral cavity are measured using widefield autofluorescence imaging and depth-sensitive optical spectroscopy during successive clinical visits. Autofluorescence intensity patterns and autofluorescence spectra are tracked over time and correlated with clinical observations. Patients whose lesions progress and who undergo surgery are also measured in the operating room immediately prior to surgery using autofluorescence imaging and spectroscopy, with the addition of intraoperative high-resolution imaging to characterize nuclear size, nuclear crowding, and tissue architecture at selected sites. Optical measurements are compared to histopathology results from biopsies and surgical specimens collected from the measured sites. Autofluorescence imaging and spectroscopy measurements are continued during post-surgery followup visits. We examined correlations between clinical impression and optical classification over time with an average followup period of 4 months. The data collected to date suggest that multimodal optical techniques may aid in noninvasive monitoring of the progression of oral premalignant lesions, biopsy site selection, and accurate delineation of lesion extent during surgery.

Site-level progression of periodontal disease during a follow-up period

PubMed Central

Morozumi, Toshiya; Nakagawa, Taneaki; Sugaya, Tsutomu; Kawanami, Masamitsu; Suzuki, Fumihiko; Takahashi, Keiso; Abe, Yuzo; Sato, Soh; Makino-Oi, Asako; Saito, Atsushi; Takano, Satomi; Minabe, Masato; Nakayama, Yohei; Ogata, Yorimasa; Kobayashi, Hiroaki; Izumi, Yuichi; Sugano, Naoyuki; Ito, Koichi; Sekino, Satoshi; Numabe, Yukihiro; Fukaya, Chie; Yoshinari, Nobuo; Fukuda, Mitsuo; Noguchi, Toshihide; Kono, Tomoo; Umeda, Makoto; Fujise, Osamu; Nishimura, Fusanori; Yoshimura, Atsutoshi; Hara, Yoshitaka; Nakamura, Toshiaki; Noguchi, Kazuyuki; Kakuta, Erika; Hanada, Nobuhiro; Takashiba, Shogo; Amitani, Yasuharu; Yoshie, Hiromasa

2017-01-01

Periodontal disease is assessed and its progression is determined via observations on a site-by-site basis. Periodontal data are complex and structured in multiple levels; thus, applying a summary statistical approach (i.e., the mean) for site-level evaluations results in loss of information. Previous studies have shown the availability of mixed effects modeling. However, clinically beneficial information on the progression of periodontal disease during the follow-up period is not available. We conducted a multicenter prospective cohort study. Using mixed effects modeling, we analyzed 18,834 sites distributed on 3,139 teeth in 124 patients, and data were collected 5 times over a 24-month follow-up period. The change in the clinical attachment level (CAL) was used as the outcome variable. The CAL at baseline was an important determinant of the CAL changes, which varied widely according to the tooth surface. The salivary levels of periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were affected by CAL progression. “Linear”- and “burst”-type patterns of CAL progression occurred simultaneously within the same patient. More than half of the teeth that presented burst-type progression sites also presented linear-type progression sites, and most of the progressions were of the linear type. Maxillary premolars and anterior teeth tended to show burst-type progression. The parameters identified in this study may guide practitioners in determining the type and extent of treatment needed at the site and patient levels. In addition, these results show that prior hypotheses concerning "burst" and "linear" theories are not valid. PMID:29206238

A retrospective study of correlation of morphologic patterns, MIB1 proliferation index, and survival analysis in 134 cases of plasmacytoma.

PubMed

Ghodke, Kiran; Shet, Tanuja; Epari, Sridhar; Sengar, Manju; Menon, Hari; Gujral, Sumeet

2015-06-01

Plasmacytoma classified into solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) is characterized by infiltrate of plasma cells of diverse maturity and by their monoclonal immunoglobulin products. Both SPB and EMP represent different groups of neoplasm in terms of location, tumor progression, and overall survival rate. There is a need for features that indicate likelihood of myeloma in patients with plasmacytoma without other manifestations. This study was an attempt to study the morphologic patterns of plasmacytoma (SPB and EMP), MIB1 proliferation index, and correlation of these with clinicopathologic features and survival of the patients. The study group comprised of 134 cases of plasmacytoma (88 SPB and 46 EMP) over duration of 8 years and were graded as per Bartl's histologic grading system. Commonest site was vertebral body in SPB (36%) and upper aerodigestive tract in EMP (48%). On serum electrophoresis, overall M band was detected in 41% cases. Both SPB and EMP on histology revealed similar morphologic features. MIB1 proliferation index ranged from less than 1% to 80%. It was slightly higher in EMP in comparison with SPB (P value = .002). Seventy percent of cases, which progressed to multiple myeloma (MM) showed MIB1 labeling index more than 10%; however, it was not statistically significant in predicting the disease progression. With the median follow-up of 19 months (range, 1-99 months), 10 SPB had disease progression of which 7 converted to MM, and 3 developed EMP, with a median interval of 21 months (range, 8-75 months) for the development of MM and 3 months (range, 3-9 months) for the progression to EMP. Five-year survival for EMP varied by site, with poorest survival in brain/central nervous system EMP as compared with EMP at other sites. To conclude, grade and MIB1 proliferation index help in predicting aggressive course in plasmacytoma. Copyright © 2015 Elsevier Inc. All rights reserved.

Integrated risk and recovery monitoring of ecosystem restorations on contaminated sites

USGS Publications Warehouse

Hooper, Michael J.; Glomb, Stephen J.; Harper, David; Hoelzle, Timothy B.; McIntosh, Lisa M.; Mulligan, David R.

2016-01-01

Ecological restorations of contaminated sites balance the human and ecological risks of residual contamination with the benefits of ecological recovery and the return of lost ecological function and ecosystem services. Risk and recovery are interrelated dynamic conditions, changing as remediation and restoration activities progress through implementation into long-term management and ecosystem maturation. Monitoring restoration progress provides data critical to minimizing residual contaminant risk and uncertainty, while measuring ecological advancement toward recovery goals. Effective monitoring plans are designed concurrently with restoration plan development and implementation and are focused on assessing the effectiveness of activities performed in support of restoration goals for the site. Physical, chemical, and biotic measures characterize progress toward desired structural and functional ecosystem components of the goals. Structural metrics, linked to ecosystem functions and services, inform restoration practitioners of work plan modifications or more substantial adaptive management actions necessary to maintain desired recovery. Monitoring frequency, duration, and scale depend on specific attributes and goals of the restoration project. Often tied to restoration milestones, critical assessment of monitoring metrics ensures attainment of risk minimization and ecosystem recovery. Finally, interpretation and communication of monitoring findings inform and engage regulators, other stakeholders, the scientific community, and the public. Because restoration activities will likely cease before full ecosystem recovery, monitoring endpoints should demonstrate risk reduction and a successional trajectory toward the condition established in the restoration goals. A detailed assessment of the completed project's achievements, as well as unrealized objectives, attained through project monitoring, will determine if contaminant risk has been minimized, if injured resources have recovered, and if ecosystem services have been returned. Such retrospective analysis will allow better planning for future restoration goals and strengthen the evidence base for quantifying injuries and damages at other sites in the future.

Geochemical and radiological characterization of soils from former radium processing sites

USGS Publications Warehouse

Landa, E.R.

1984-01-01

Soil samples were collected from former radium processing sites in Denver, CO, and East Orange, NJ. Particle-size separations and radiochemical analyses of selected samples showed that while the greatest contents of both 226Ra and U were generally found in the finest (< 45 ??m) fraction, the pattern was not always of progressive increase in radionuclide content with decreasing particle size. Leaching tests on these samples showed a large portion of the 225Ra and U to be soluble in dilute hydrochloric acid. Radon-emanation coefficients measured for bulk samples of contaminated soil were about 20%. Recovery of residual uranium and vanadium, as an adjunct to any remedial action program, appears unlikely due to economic considerations.

Pretest characterization of WIPP experimental waste

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

Johnson, J.; Davis, H.; Drez, P.E.

The Waste Isolation Pilot Plant (WIPP) near Carlsbad, New Mexico, is an underground repository designed for the storage and disposal of transuranic (TRU) wastes from US Department of Energy (DOE) facilities across the country. The Performance Assessment (PA) studies for WIPP address compliance of the repository with applicable regulations, and include full-scale experiments to be performed at the WIPP site. These experiments are the bin-scale and alcove tests to be conducted by Sandia National Laboratories (SNL). Prior to conducting these experiments, the waste to be used in these tests needs to be characterized to provide data on the initial conditionsmore » for these experiments. This characterization is referred to as the Pretest Characterization of WIPP Experimental Waste, and is also expected to provide input to other programmatic efforts related to waste characterization. The purpose of this paper is to describe the pretest waste characterization activities currently in progress for the WIPP bin-scale waste, and to discuss the program plan and specific analytical protocols being developed for this characterization. The relationship between different programs and documents related to waste characterization efforts is also highlighted in this paper.« less

Recombinant Human Lysyl Oxidase-like 2 Secreted from Human Embryonic Kidney Cells Displays Complex and Acidic Glycans at All Three N-Linked Glycosylation Sites.

PubMed

Go, Eden P; Moon, Hee-Jung; Mure, Minae; Desaire, Heather

2018-05-04

Human lysyl oxidase-like 2 (hLOXL2), a glycoprotein implicated in tumor progression and organ fibrosis, is a molecular target for anticancer and antifibrosis treatment. This glycoprotein contains three predicted N-linked glycosylation sites; one is near the protein's active site, and at least one more is known to facilitate the protein's secretion. Because the glycosylation impacts the protein's biology, we sought to characterize the native, mammalian glycosylation profile and to determine how closely this profile is recapitulated when the protein is expressed in insect cells. All three glycosylation sites on the protein, expressed in human embryonic kidney (HEK) cells, were characterized individually using a mass spectrometry-based glycopeptide analysis workflow. These data were compared to the glycosylation profile of the same protein expressed in insect cells. We found that the producer cell type imparts a substantial influence on the glycosylation of this important protein. The more-relevant version, expressed in HEK cells, contains large, acidic glycoforms; these glycans are not generated in insect cells. The glycosylation differences likely have structural and functional consequences, and these data should be considered when generating protein for functional studies or for high-throughput screening campaigns.

Systematic characterization of the specificity of the SH2 domains of cytoplasmic tyrosine kinases.

PubMed

Zhao, Bing; Tan, Pauline H; Li, Shawn S C; Pei, Dehua

2013-04-09

Cytoplasmic tyrosine kinases (CTK) generally contain a Src-homology 2 (SH2) domain, whose role in the CTK family is not fully understood. Here we report the determination of the specificity of 25 CTK SH2 domains by screening one-bead-one-compound (OBOC) peptide libraries. Based on the peptide sequences selected by the SH2 domains, we built Support Vector Machine (SVM) models for the prediction of binding ligands for the SH2 domains. These models yielded support for the progressive phosphorylation model for CTKs in which the overlapping specificity of the CTK SH2 and kinase domains has been proposed to facilitate targeting of the CTK substrates with at least two potential phosphotyrosine (pTyr) sites. We curated 93 CTK substrates with at least two pTyr sites catalyzed by the same CTK, and showed that 71% of these substrates had at least two pTyr sites predicted to bind a common CTK SH2 domain. More importantly, we found 34 instances where there was at least one pTyr site predicted to be recognized by the SH2 domain of the same CTK, suggesting that the SH2 and kinase domains of the CTKs may cooperate to achieve progressive phosphorylation of a protein substrate. This article is part of a Special Issue entitled: From protein structures to clinical applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Explosively produced fracture of oil shale

NASA Astrophysics Data System (ADS)

Morris, W. A.

1982-05-01

Rock fragmentation research in oil shale to develop the blasting technologies and designs required to prepare a rubble bed for a modified in situ retort is reported. Experimental work is outlined, proposed studies in explosive characterization are detailed and progress in numerical calculation techniques to predict fracture of the shale is described. A detailed geologic characterization of two Anvil Points experiment sites is related to previous work at Colony Mine. The second section focuses on computer modeling and theory. The latest generation of the stress wave code SHALE, its three dimensional potential, and the slide line package for it are described. A general stress rate equation that takes energy dependence into account is discussed.

Development of the INEEL Site Wide Vadose Zone Roadmap

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

Yonk, Alan Keith

2001-09-01

The INEEL Vadose Zone Roadmap was developed to identify inadquacies in current knowledge, to assist in contaminant management capabilities relative to the INEEL vadose zone, and to ensure that ongoing and planned Science and Technology developments will meet the risk management challenges facing the INEEL in coming years. The primary objective of the Roadmap is to determine the S&T needs that will facilitate monitoring, characterization, prediction, and assessment activities necessary to support INEEL risk management decisions and to ensure that long-term stewardship of contaminated sites at the INEEL is achieved. The mission of the Roadmap is to insure that themore » long-term S&T strategy is aligned with site programs, that it takes advantage of progress made to date, and that it can assist in meeting the milestones and budgets of operations.« less

BAF57 Modulation of Androgen Receptor Action and Prostate Cancer Progression

DTIC Science & Technology

2007-12-01

mapped the AR binding site on BAF57 to the N-terminus (proline-rich region). Furthermore, the DBD and hinge region of AR also appear to play a...Accomplishments of Task 1: BAF57 binds to DNA binding domain ( DBD ) and hinge region of AR As outlined in the initial proposal, the first task...the above construct are the well-characterized zinc finger DNA binding domain ( DBD ) and the hinge region. Given the significant role of these two

BAF57 Modulation of Androgen Receptor Action and Prostate Cancer Progression

DTIC Science & Technology

2006-12-01

has fine mapped the AR binding site on BAF57 to the N-terminus (proline-rich region). Furthermore, the DBD and hinge region of AR also appear to...Accomplishments of Task 1: BAF57 binds to DNA binding domain ( DBD ) and hinge region of AR As outlined in the initial proposal, the first task was to...construct are the well-characterized zinc finger DNA binding domain ( DBD ) and the hinge region. Given the significant role of these two domains in AR

Granulomatous slack skin syndrome: Report of a unique case.

PubMed

Maheswari, S Uma; Sampath, V; Ramesh, A

2018-01-01

Granulomatous slack skin syndrome is a rare variant of cutaneous T-cell lymphoma (mycosis fungoides). It is characterized clinically by redundant skin folds, which show a predilection towards flexural areas such as the axilla and the groin. Histologically, it shows a granulomatous T-cell infiltrate and loss of elastic tissue. It has an indolent but progressive course; and is usually refractory to treatment. We report a unique case of slack skin syndrome, sparing the classical sites with rapid and unusual involvement of non-intertriginous areas.

Biophysics of cancer progression and high-throughput mechanical characterization of biomaterials

NASA Astrophysics Data System (ADS)

Osborne, Lukas Dylan

Cancer metastasis involves a series of events known as the metastatic cascade. In this complex progression, cancer cells detach from the primary tumor, invade the surrounding stromal space, transmigrate the vascular system, and establish secondary tumors at distal sites. Specific mechanical phenotypes are likely adopted to enable cells to successfully navigate the mechanical environments encountered during metastasis. To examine the role of cell mechanics in cancer progression, I employed force-consistent biophysical and biochemical assays to characterize the mechanistic links between stiffness, stiffness response and cell invasion during the epithelial to mesenchymal transition (EMT). EMT is an essential physiological process, whose abnormal reactivation has been implicated in the detachment of cancer cells from epithelial tissue and their subsequent invasion into stromal tissue. I demonstrate that epithelial-state cells respond to force by evoking a stiffening response, and that after EMT, mesenchymal-state cells have reduced stiffness but also lose the ability to increase their stiffness in response to force. Using loss and gain of function studies, two proteins are established as functional connections between attenuated stiffness and stiffness response and the increased invasion capacity acquired after EMT. To enable larger scale assays to more fully explore the connection between biomechanics and cancer, I discuss the development of an automated array high throughput (AHT) microscope. The AHT system is shown to implement passive microbead rheology to accurately characterize the mechanical properties of biomaterials. Compared to manually performed mechanical characterizations, the AHT system executes experiments in two orders of magnitude less time. Finally, I use the AHT microscope to study the effect of gain of function oncogenic molecules on cell stiffness. I find evidence that our assay can identify alterations in cell stiffness due to constitutive activation of cancer pathways.

Survey of the enthesopathy of X-linked hypophosphatemia and its characterization in Hyp mice.

PubMed

Liang, Guoying; Katz, Lee D; Insogna, Karl L; Carpenter, Thomas O; Macica, Carolyn M

2009-09-01

X-linked hypophosphatemia (XLH) is characterized by rickets and osteomalacia as a result of an inactivating mutation of the PHEX (phosphate-regulating gene with homology to endopeptidases on the X chromosome) gene. PHEX encodes an endopeptidase that, when inactivated, results in elevated circulating levels of FGF-23, a novel phosphate-regulating hormone (a phosphatonin), thereby resulting in increased phosphate excretion and impaired bone mineralization. A generalized and severe mineralizing enthesopathy in patients with XLH was first reported in 1985; we likewise report a survey in which we found evidence of enthesopathy in fibrocartilaginous insertion sites, as well as osteophyte formation, in the majority of patients. Nonetheless, there has been very little focus on the progression and pathogenesis underlying the paradoxical heterotopic calcification of tendon and ligament insertion sites. Such studies have been hampered by lack of a model of mineralizing enthesopathy. We therefore characterized the involvement of the most frequently targeted fibrocartilaginous tendon insertion sites in Hyp mice, a murine model of the XLH mutation that phenocopies the human syndrome in every detail including hypophosphatemia and elevated FGF-23. Histological examination of the affected entheses revealed that mineralizing insertion sites, while thought to involve bone spur formation, were not due to bone-forming osteoblasts but instead to a significant expansion of mineralizing fibrocartilage. Our finding that enthesis fibrocartilage cells specifically express fibroblast growth factor receptor 3 (FGFR3)/Klotho suggests that the high circulating levels of FGF-23, characteristic of XLH and Hyp mice, may be part of the biochemical milieu that underlies the expansion of mineralizing enthesis fibrocartilage.

Geochemical and radiological characterization of soils from former radium processing sites.

PubMed

Landa, E R

1984-02-01

Soil samples were collected from former radium processing sites in Denver, CO, and East Orange, NJ. Particle-size separations and radiochemical analyses of selected samples showed that while the greatest contents of both 226Ra and U were generally found in the finest (less than 45 micron) fraction, the pattern was not always of progressive increase in radionuclide content with decreasing particle size. Leaching tests on these samples showed a large portion of the 226Ra and U to be soluble in dilute hydrochloric acid. Radon-emanation coefficients measured for bulk samples of contaminated soil were about 20%. Recovery of residual uranium and vanadium, as an adjunct to any remedial action program, appears unlikely due to economic considerations.

Viral Carcinogenesis Beyond Malignant Transformation: EBV in the Progression of Human Cancers

PubMed Central

Müller-Coan, Bárbara G.; Pagano, Joseph S.

2017-01-01

Cancer progression begins when malignant cells colonize adjacent sites, and it is characterized by increasing tumor heterogeneity, invasion and dissemination of cancer cells. Clinically, progression is the most relevant stage in the natural history of cancers. A given virus is usually regarded as oncogenic because of its ability to induce malignant transformation of cells. Nonetheless, oncogenic viruses may also be important for the progression of infection-associated cancers. Recently this hypothesis has been addressed because of studies on the contribution of the Epstein–Barr virus (EBV) to the aggressiveness of nasopharyngeal carcinoma (NPC). Several EBV products modulate cancer progression phenomena, such as the epithelial–mesenchymal transition, cell motility, invasiveness, angiogenesis, and metastasis. In this regard, there are compelling data about the effects of EBV latent membrane proteins (LMPs) and EBV nuclear antigens (EBNAs), as well as nontranslated viral RNAs, such as the EBV-encoded small nonpolyadenylated RNAs (EBERs) and viral microRNAs, notably EBV miR-BARTs. The available data on the mechanisms and players involved in the contribution of EBV infection to the aggressiveness of NPC are discussed in this review. Overall, this conceptual framework may be valuable for the understanding of the contribution of some infectious agents in the progression of cancers. PMID:27068530

Local-order metric for condensed-phase environments

NASA Astrophysics Data System (ADS)

Martelli, Fausto; Ko, Hsin-Yu; Oǧuz, Erdal C.; Car, Roberto

2018-02-01

We introduce a local order metric (LOM) that measures the degree of order in the neighborhood of an atomic or molecular site in a condensed medium. The LOM maximizes the overlap between the spatial distribution of sites belonging to that neighborhood and the corresponding distribution in a suitable reference system. The LOM takes a value tending to zero for completely disordered environments and tending to one for environments that perfectly match the reference. The site-averaged LOM and its standard deviation define two scalar order parameters, S and δ S , that characterize with excellent resolution crystals, liquids, and amorphous materials. We show with molecular dynamics simulations that S , δ S , and the LOM provide very insightful information in the study of structural transformations, such as those occurring when ice spontaneously nucleates from supercooled water or when a supercooled water sample becomes amorphous upon progressive cooling.

Uranium speciation in Fernald soils. Progress report, January 1--May 31, 1992

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

Morris, D.E.; Conradson, S.D.; Tait, C.D.

1992-05-31

This report details progress made from January 1 to May 31, 1992 in this analytical support task to determine the speciation of uranium in contaminated soil samples from the Fernald Environmental Management Project site under the auspices of the Uranium in Soils Integrated Demonstration funded through the US DOE`s Office of Technology Development. The authors` efforts have focused on characterization of soil samples collected by S.Y. Lee (Oak Ridge National Laboratory) from five locales at the Fernald site. These were chosen to sample a broad range of uranium source terms. On the basis of x-ray absorption spectroscopy data, they havemore » determined that the majority of uranium (> 80--90%) exists in the hexavalent oxidation state for all samples examined. This is a beneficial finding from the perspective of remediation, because U(VI) species are more soluble in general than uranium species in other oxidation states. Optical luminescence data from many of the samples show the characteristic structured yellow-green emission from the uranyl (UO{sub 2}{sup 2+}) moiety. The luminescence data also suggest that much of the uranium in these soils is present as well-crystallized UO{sub 2}{sup 2+} species. Some clear spectroscopic distinctions have been noted for several samples that illustrate significant differences in the speciation (1) from site to site, (2) within different horizons at the same site, and (3) within different size fractions of the soils in the same horizon at the same site. This marked heterogeneity in uranyl speciation suggests that several soil washing strategies may be necessary to reduce the total uranium concentrations within these soils to regulatory limits.« less

Elemental, stable isotopic and biochemical characterization of soil organic matter alteration across a natural peatland gradient

NASA Astrophysics Data System (ADS)

Cowie, G.; Mowbray, S.; Belyea, L.; Laing, C.; Allton, K.; Abbott, G.; Muhammad, A.

2010-12-01

Northern peatlands store around one third of global soil C and thus represent a key reservoir. To elucidate how these systems might respond to climate change, field- and laboratory-based experimental incubation studies are being conducted at sites across a natural peatland gradient in the boreonemoral zone of central Sweden (Ryggmossen). The site comprises four successional stages, from edge to centre; Swamp Forest (SF), Lagg Fen (LF), Bog Margin (BM) and Bog Plateau (BP). The well-preserved succession shows strong decreases in mineral cations and pH, and distinct changes in vegetation and water-table depth. As an underpinning to these experiments, comprehensive characterization of natural soil organic matter (SOM) alteration has been carried out through detailed analyses of vegetation and downcore profiles at contrasting topographic sites (hummock vs hollow) in each of the four locations. As illustrated in Figure 1, while some similarities occur in downcore trends, contrasts are observed in C and N elemental and stable isotopic compositions, between stages and, in some cases, between microtopographic settings. Downcore trends and intersite differences are also observed in biochemical yields and molecular composition (carbohydrates, amino acids, phenols, lipids and D/L amino acid ratios). These reflect SOM decay and alteration combined with the effects of contrasting hydrologic, redox and nutrient regimes and differing vegetation and microbial inputs at each of the study sites. Multivariate analysis is used to to elucidate compositional patterns that characterize and delineate progressive SOM decay, specific vegetation types, and the effects of contrasting environmental conditions at the different sites. Figure 1. A. Organic carbon content (wt %), B. Atomic ratio of organic C to total N, C. Stable C isotopic composition of organic C (d13Corg), and D. Stable N isotopic composition of total nitrogen (d15N), all for core profiles from contrasting settings (hummock and hollow) at locations spanning a peatland gradient. Site locations are defined in the text.

The Human RNA Polymerase I Transcription Terminator Complex Acts as a Replication Fork Barrier That Coordinates the Progress of Replication with rRNA Transcription Activity.

PubMed

Akamatsu, Yufuko; Kobayashi, Takehiko

2015-05-01

In S phase, the replication and transcription of genomic DNA need to accommodate each other, otherwise their machineries collide, with chromosomal instability as a possible consequence. Here, we characterized the human replication fork barrier (RFB) that is present downstream from the 47S pre-rRNA gene (ribosomal DNA [rDNA]). We found that the most proximal transcription terminator, Sal box T1, acts as a polar RFB, while the other, Sal box T4/T5, arrests replication forks bidirectionally. The fork-arresting activity at these sites depends on polymerase I (Pol I) transcription termination factor 1 (TTF-1) and a replisome component, TIMELESS (TIM). We also found that the RFB activity was linked to rDNA copies with hypomethylated CpG and coincided with the time that actively transcribed rRNA genes are replicated. Failed fork arrest at RFB sites led to a slowdown of fork progression moving in the opposite direction to rRNA transcription. Chemical inhibition of transcription counteracted this deceleration of forks, indicating that rRNA transcription impedes replication in the absence of RFB activity. Thus, our results reveal a role of RFB for coordinating the progression of replication and transcription activity in highly transcribed rRNA genes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Spreaders and Sponges define metastasis in lung cancer: A Markov chain Monte Carlo Mathematical Model

PubMed Central

Newton, Paul K.; Mason, Jeremy; Bethel, Kelly; Bazhenova, Lyudmila; Nieva, Jorge; Norton, Larry; Kuhn, Peter

2013-01-01

The classic view of metastatic cancer progression is that it is a unidirectional process initiated at the primary tumor site, progressing to variably distant metastatic sites in a fairly predictable, though not perfectly understood, fashion. A Markov chain Monte Carlo mathematical approach can determine a pathway diagram that classifies metastatic tumors as ‘spreaders’ or ‘sponges’ and orders the timescales of progression from site to site. In light of recent experimental evidence highlighting the potential significance of self-seeding of primary tumors, we use a Markov chain Monte Carlo (MCMC) approach, based on large autopsy data sets, to quantify the stochastic, systemic, and often multi-directional aspects of cancer progression. We quantify three types of multi-directional mechanisms of progression: (i) self-seeding of the primary tumor; (ii) re-seeding of the primary tumor from a metastatic site (primary re-seeding); and (iii) re-seeding of metastatic tumors (metastasis re-seeding). The model shows that the combined characteristics of the primary and the first metastatic site to which it spreads largely determine the future pathways and timescales of systemic disease. For lung cancer, the main ‘spreaders’ of systemic disease are the adrenal gland and kidney, whereas the main ‘sponges’ are regional lymph nodes, liver, and bone. Lung is a significant self-seeder, although it is a ‘sponge’ site with respect to progression characteristics. PMID:23447576

Status of Environmental Management Initiatives to Accelerate the Reduction of Environmental Risks and Challenges Posed by the Legacy of the Cold War

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

None

2009-01-01

Fifty years of nuclear weapons production and energy research in the United States during the Cold War generated large amounts of radioactive wastes, spent nuclear fuel (SNF), excess plutonium and uranium, thousands of contaminated facilities, and contaminated soil and groundwater. During most of that half century, the Nation did not have the environmental regulatory structure or nuclear waste cleanup technologies that exist today. The result was a legacy of nuclear waste that was stored and disposed of in ways now considered unacceptable. Cleaning up and ultimately disposing of these wastes is the responsibility of the U.S. Department of Energy (DOE).more » In 1989, DOE established the Office of Environmental Management (EM) to solve the large scale and technically challenging risks posed by the world's largest nuclear cleanup. This required EM to build a new nuclear cleanup infrastructure, assemble and train a technically specialized workforce, and develop the technologies and tools required to safely decontaminate, disassemble, stabilize, disposition, and remediate unique radiation hazards. The sites where nuclear activities produced legacy waste and contamination include the original Manhattan Project sites--Los Alamos, New Mexico; Hanford, Washington; and Oak Ridge, Tennessee--as well as major Cold War sites, such as Savannah River Site, South Carolina; the Idaho National Laboratory, Idaho; Rocky Flats Plant, Colorado; and Fernald, Ohio. Today EM has responsibility for nuclear cleanup activities at 21 sites covering more than two million acres in 13 states, and employs more than 30,000 Federal and contractor employees, including scientists, engineers and hazardous waste technicians. This cleanup poses unique, technically complex problems, which must be solved under the most hazardous of conditions, and which will require billions of dollars a year for several more decades. The EM program focus during its first 10 years was on managing the most urgent risks and maintaining safety at each site while negotiating state and Federal environmental compliance agreements. The program also concentrated on characterizing waste and nuclear materials and assessing the magnitude and extent of environmental contamination. By the late 1990s, EM had made significant progress in identifying and characterizing the extent of contamination and cleanup required and began transitioning from primarily a characterization and stabilization program to an active cleanup and closure program. During that time, EM formulated multi-year cleanup and closure plans, which contributed to cleanup progress; however, reducing the overall environmental risk associated with the cleanup program remained a challenge. In response, the Secretary of Energy directed a review of the EM program be undertaken. The resulting 'Top-to Bottom Review' re-directed the program focus from managing risks to accelerating the reduction of these risks.« less

Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs

PubMed Central

Ezzati Nazhad Dolatabadi, Jafar; Valizadeh, Hadi; Hamishehkar, Hamed

2015-01-01

In recent years, nanomaterials have been widely applied as advanced drug and gene delivery nanosystems. Among them, solid lipid nanoparticles (SLNs) have attracted great attention as colloidal drug delivery systems for incorporating hydrophilic or lipophilic drugs and various macromolecules as well as proteins and nucleic acids. Therefore, SLNs offer great promise for controlled and site specific drug and gene delivery. This article includes general information about SLN structures and properties, production procedures, characterization. In addition, recent progress on development of drug and gene delivery systems using SLNs was reviewed. PMID:26236652

Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

PubMed

Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

2007-04-01

Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

Performance-assessment progress for the Rozan low-level waste disposal facility

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

Smietanski, L.; Mitrega, J.; Frankowski, Z.

1995-12-31

The paper presents a condensed progress report on the performance assessment of Poland`s low-level waste disposal facility which is operating since 1961. The Rozan repository is of near-surface type with facilities which are the concrete fortifications built about 1910. Site characterization activities supplied information on regional geology, geohydrology, climatic and hydrologic conditions and terrain surface evolution due to geodynamic processes. Field surveys enabled to decode lithological, hydrogeological and geochemical site specific conditions. From the laboratory tests the data on groundwater chemistry and soil geochemical and hydraulic characteristics were obtained. The site geohydrologic main vulnerable element is the upmost directly endangeredmore » unconfined aquifer which is perched in relation to the region-wide hydraulic system. Heterogeneity of this system reflects in a wide range of hydraulic conductivity and thickness variations. It strongly affects velocity and flow directions. The chemistry of groundwater is unstable due to large sensitivity to external impacts. Modeling of the migration of the critical long-lived radionuclides Tc-99, U-238 and Pu-239 showed that the nearly 20 m thick unsaturated zone plays crucial role as an effective protective barrier. These radionuclides constitute minor part of the total inventory. Modeling of the development of the H-3 plume pointed out the role the macrodispersion plays in the unsaturated zone beneath the repository.« less

The application of micro UAV in construction project

NASA Astrophysics Data System (ADS)

Kaamin, Masiri; Razali, Siti Nooraiin Mohd; Ahmad, Nor Farah Atiqah; Bukari, Saifullizan Mohd; Ngadiman, Norhayati; Kadir, Aslila Abd; Hamid, Nor Baizura

2017-10-01

In every outstanding construction project, there is definitely have an effective construction management. Construction management allows a construction project to be implemented according to plan. Every construction project must have a progress development works that is usually created by the site engineer. Documenting the progress of works is one of the requirements in construction management. In a progress report it is necessarily have a visual image as an evidence. The conventional method used for photographing on the construction site is by using common digital camera which is has few setback comparing to Micro Unmanned Aerial Vehicles (UAV). Besides, site engineer always have a current issues involving limitation of monitoring on high reach point and entire view of the construction site. The purpose of this paper is to provide a concise review of Micro UAV technology in monitoring the progress on construction site through visualization approach. The aims of this study are to replace the conventional method of photographing on construction site using Micro UAV which can portray the whole view of the building, especially on high reach point and allows to produce better images, videos and 3D model and also facilitating site engineer to monitor works in progress. The Micro UAV was flown around the building construction according to the Ground Control Points (GCPs) to capture images and record videos. The images taken from Micro UAV have been processed generate 3D model and were analysed to visualize the building construction as well as monitoring the construction progress work and provides immediate reliable data for project estimation. It has been proven that by using Micro UAV, a better images and videos can give a better overview of the construction site and monitor any defects on high reach point building structures. Not to be forgotten, with Micro UAV the construction site progress is more efficiently tracked and kept on the schedule.

A 4-year prospective study of the progression of periodontal disease in a rural Chinese population.

PubMed

Pei, Xiyan; Ouyang, Xiangying; He, Lu; Cao, Caifang; Luan, Qingxian; Suda, Reiko

2015-02-01

The natural progression of periodontitis in the Chinese population is not well researched. We investigated the progression of periodontal disease over 4 years in 15-44-year-old Chinese villagers with no access to regular dental care. In 1992, 486 villagers were enrolled, and in 1996, 413 villagers were re-examined. Probing depth (PD) and clinical attachment level (CAL) were examined at six sites per tooth. Sites with ΔCAL ≥3 mm were defined as active sites. Cross-sectional and longitudinal analyses were performed using means and percentile plots. The mean CAL increased by 0.26 mm over 4 years. The incidence of periodontitis (at least one site with CAL ≥3 mm) was 8%. The incidence of periodontitis among those with no periodontal disease at baseline was 44.9%. Seventy-eight percent of the subjects had at least one active site. In the 15-24-year group, 244 of 401 active sites had gingival recession, while only 51 active sites had both gingival recession and deeper pockets. In the 25-34-year and 35-44-year groups, almost one-third of the active sites (329/1087) and more than one-third of the active sites (580/1312) respectively had a combination of gingival recession and deeper pockets. In this study, we demonstrated that in Chinese population without regular dental care, both the initiation of periodontitis and progression of previously existed periodontitis contributed to the natural progression of periodontitis and periodontal pocketing played a greater role with age increasing. This rare study reports the natural progression of periodontal disease in a group of Chinese villagers (15-44 years) with virtually no access to regular dental care. Copyright © 2014 Elsevier Ltd. All rights reserved.

Generic protease detection technology for monitoring periodontal disease.

PubMed

Zheng, Xinwei; Cook, Joseph P; Watkinson, Michael; Yang, Shoufeng; Douglas, Ian; Rawlinson, Andrew; Krause, Steffi

2011-01-01

Periodontal diseases are inflammatory conditions that affect the supporting tissues of teeth and can lead to destruction of the bone support and ultimately tooth loss if untreated. Progression of periodontitis is usually site specific but not uniform, and currently there are no accurate clinical methods for distinguishing sites where there is active disease progression from sites that are quiescent. Consequently, unnecessary and costly treatment of periodontal sites that are not progressing may occur. Three proteases have been identified as suitable markers for distinguishing sites with active disease progression and quiescent sites: human neutrophil elastase, cathepsin G and MMP8. Generic sensor materials for the detection of these three proteases have been developed based on thin dextran hydrogel films cross-linked with peptides. Degradation of the hydrogel films was monitored using impedance measurements. The target proteases were detected in the clinically relevant range within a time frame of 3 min. Good specificity for different proteases was achieved by choosing appropriate peptide cross-linkers.

Characterizing lamina propria of human gastric mucosa by multiphoton microscopy

NASA Astrophysics Data System (ADS)

Liu, Y. C.; Yang, H. Q.; Chen, G.; Zhuo, S. M.; Chen, J. X.; Yan, J.

2011-01-01

Lamina propria (LP) of gastric mucosa plays an important role in progression of gastric cancer because of the site at where inflammatory reactions occur. Multiphoton imaging has been recently employed for microscopic examination of intact tissue. In this paper, using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), high resolution multiphoton microscopic images of lamina propria (LP) are obtained in normal human gastric mucosa at excitation wavelength λex = 800 nm. The main source of tissue TPEF originated from the cells of gastric glands, and loose connective tissue, collagen, produced SHG signals. Our results demonstrated that MPM can be effective for characterizing the microstructure of LP in human gastric mucosa. The findings will be helpful for diagnosing and staging early gastric cancer in the clinics.

Identification and functional validation of novel autoantigens in equine uveitis.

PubMed

Deeg, Cornelia A; Pompetzki, Dirk; Raith, Albert J; Hauck, Stefanie M; Amann, Barbara; Suppmann, Sabine; Goebel, Thomas W F; Olazabal, Ursula; Gerhards, Hartmut; Reese, Sven; Stangassinger, Manfred; Kaspers, Bernd; Ueffing, Marius

2006-08-01

The development, progression, and recurrence of autoimmune diseases are frequently driven by a group of participatory autoantigens. We identified and characterized novel autoantigens by analyzing the autoantibody binding pattern from horses affected by spontaneous equine recurrent uveitis to the retinal proteome. Cellular retinaldehyde-binding protein (cRALBP) had not been described previously as autoantigen, but subsequent characterization in equine recurrent uveitis horses revealed B and T cell autoreactivity to this protein and established a link to epitope spreading. We further immunized healthy rats and horses with cRALBP and observed uveitis in both species with typical tissue lesions at cRALBP expression sites. The autoantibody profiling outlined here could be used in various autoimmune diseases to detect autoantigens involved in the dynamic spreading cascade or serve as predictive markers.

Entropy, complexity, and Markov diagrams for random walk cancer models.

PubMed

Newton, Paul K; Mason, Jeremy; Hurt, Brian; Bethel, Kelly; Bazhenova, Lyudmila; Nieva, Jorge; Kuhn, Peter

2014-12-19

The notion of entropy is used to compare the complexity associated with 12 common cancers based on metastatic tumor distribution autopsy data. We characterize power-law distributions, entropy, and Kullback-Liebler divergence associated with each primary cancer as compared with data for all cancer types aggregated. We then correlate entropy values with other measures of complexity associated with Markov chain dynamical systems models of progression. The Markov transition matrix associated with each cancer is associated with a directed graph model where nodes are anatomical locations where a metastatic tumor could develop, and edge weightings are transition probabilities of progression from site to site. The steady-state distribution corresponds to the autopsy data distribution. Entropy correlates well with the overall complexity of the reduced directed graph structure for each cancer and with a measure of systemic interconnectedness of the graph, called graph conductance. The models suggest that grouping cancers according to their entropy values, with skin, breast, kidney, and lung cancers being prototypical high entropy cancers, stomach, uterine, pancreatic and ovarian being mid-level entropy cancers, and colorectal, cervical, bladder, and prostate cancers being prototypical low entropy cancers, provides a potentially useful framework for viewing metastatic cancer in terms of predictability, complexity, and metastatic potential.

Entropy, complexity, and Markov diagrams for random walk cancer models

NASA Astrophysics Data System (ADS)

Newton, Paul K.; Mason, Jeremy; Hurt, Brian; Bethel, Kelly; Bazhenova, Lyudmila; Nieva, Jorge; Kuhn, Peter

2014-12-01

The notion of entropy is used to compare the complexity associated with 12 common cancers based on metastatic tumor distribution autopsy data. We characterize power-law distributions, entropy, and Kullback-Liebler divergence associated with each primary cancer as compared with data for all cancer types aggregated. We then correlate entropy values with other measures of complexity associated with Markov chain dynamical systems models of progression. The Markov transition matrix associated with each cancer is associated with a directed graph model where nodes are anatomical locations where a metastatic tumor could develop, and edge weightings are transition probabilities of progression from site to site. The steady-state distribution corresponds to the autopsy data distribution. Entropy correlates well with the overall complexity of the reduced directed graph structure for each cancer and with a measure of systemic interconnectedness of the graph, called graph conductance. The models suggest that grouping cancers according to their entropy values, with skin, breast, kidney, and lung cancers being prototypical high entropy cancers, stomach, uterine, pancreatic and ovarian being mid-level entropy cancers, and colorectal, cervical, bladder, and prostate cancers being prototypical low entropy cancers, provides a potentially useful framework for viewing metastatic cancer in terms of predictability, complexity, and metastatic potential.

Extensive Loss of Islet Mass Beyond the First Day After Intraportal Human Islet Transplantation in a Mouse Model.

PubMed

Liljebäck, Hanna; Grapensparr, Liza; Olerud, Johan; Carlsson, Per-Ola

2016-01-01

Clinical islet transplantation is characterized by a progressive deterioration of islet graft function, which renders many patients once again dependent on exogenous insulin administration within a couple of years. In this study, we aimed to investigate possible engraftment factors limiting the survival and viability of experimentally transplanted human islets beyond the first day after their transplantation to the liver. Human islets were transplanted into the liver of nude mice and characterized 1 or 30 days after transplantation by immunohistochemistry. The factors assessed were endocrine mass, cellular death, hypoxia, vascular density and amyloid formation in the transplanted islets. One day posttransplantation, necrotic cells, as well as apoptotic cells, were commonly observed. In contrast to necrotic death, apoptosis rates remained high 1 month posttransplantation, and the total islet mass was reduced by more than 50% between 1 and 30 days posttransplantation. Islet mass at 30 days posttransplantation correlated negatively to apoptotic death. Vascular density within the transplanted islets remained less than 30% of that in native human islets up to 30 days posttransplantation and was associated with prevailing hypoxia. Amyloid formation was rarely observed in the 1-day-old transplants, but was commonly observed in the 30-day-old islet transplants. We conclude that substantial islet cell death occurs beyond the immediate posttransplantation phase, particularly through apoptotic events. Concomitant low vascularization with prevailing hypoxia and progressive amyloid development was observed in the human islet grafts. Strategies to improve engraftment at the intraportal site or change of implantation site in the clinical setting are needed.

Yucca Mountain Project Subsurface Facilities Design

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

A. Linden; R.S. Saunders; R.J. Boutin

2002-11-19

Four units of the Topopah Springs formation (volcanic tuff) are considered for the proposed repository: the upper lithophysal, the middle non-lithophysal, the lower lithophysal, and the lower non-lithophysal. Yucca Mountain was recently designated the site for a proposed repository to dispose of spent nuclear fuel and high-level radioactive waste. Work is proceeding to advance the design of subsurface facilities to accommodate emplacing waste packages in the proposed repository. This paper summarized recent progress in the design of subsurface layout of the proposed repository. The original Site Recommendation (SR) concept for the subsurface design located the repository largely within the lowermore » lithophysal zone (approximately 73%) of the Topopah The Site Recommendation characterized area suitable for emplacement consisted of the primary upper block, the lower block and the southern upper block extension. The primary upper block accommodated the mandated 70,000 metric tons of heavy metal (MTHM) at a 1.45 kW/m hear heat load. Based on further study of the Site Recommendation concept, the proposed repository siting area footprint was modified to make maximum use of available site characterization data, and thus, reduce uncertainties associated with performance assessment. As a result of this study, a modified repository footprint has been proposed and is presently being review for acceptance by the DOE. A panel design concept was developed to reduce overall costs and reduce the overall emplacement schedule. This concept provides flexibility to adjust the proposed repository subsurface layout with time, as it makes it unnecessary to ''commit'' to development of a large single panel at the earliest stages of construction. A description of the underground layout configuration and influencing factors that affect the layout configuration are discussed in the report.« less

Impact of bottom trawling on deep-sea sediment properties along the flanks of a submarine canyon.

PubMed

Martín, Jacobo; Puig, Pere; Masqué, Pere; Palanques, Albert; Sánchez-Gómez, Anabel

2014-01-01

The offshore displacement of commercial bottom trawling has raised concerns about the impact of this destructive fishing practice on the deep seafloor, which is in general characterized by lower resilience than shallow water regions. This study focuses on the flanks of La Fonera (or Palamós) submarine canyon in the Northwestern Mediterranean, where an intensive bottom trawl fishery has been active during several decades in the 400-800 m depth range. To explore the degree of alteration of surface sediments (0-50 cm depth) caused by this industrial activity, fishing grounds and control (untrawled) sites were sampled along the canyon flanks with an interface multicorer. Sediment cores were analyzed to obtain vertical profiles of sediment grain-size, dry bulk density, organic carbon content and concentration of the radionuclide 210Pb. At control sites, surface sediments presented sedimentological characteristics typical of slope depositional systems, including a topmost unit of unconsolidated and bioturbated material overlying sediments progressively compacted with depth, with consistently high 210Pb inventories and exponential decaying profiles of 210Pb concentrations. Sediment accumulation rates at these untrawled sites ranged from 0.3 to 1.0 cm y-1. Sediment properties at most trawled sites departed from control sites and the sampled cores were characterized by denser sediments with lower 210Pb surface concentrations and inventories that indicate widespread erosion of recent sediments caused by trawling gears. Other alterations of the physical sediment properties, including thorough mixing or grain-size sorting, as well as organic carbon impoverishment, were also visible at trawled sites. This work contributes to the growing realization of the capacity of bottom trawling to alter the physical properties of surface sediments and affect the seafloor integrity over large spatial scales of the deep-sea.

Impact of Bottom Trawling on Deep-Sea Sediment Properties along the Flanks of a Submarine Canyon

PubMed Central

Martín, Jacobo; Puig, Pere; Masqué, Pere; Palanques, Albert; Sánchez-Gómez, Anabel

2014-01-01

The offshore displacement of commercial bottom trawling has raised concerns about the impact of this destructive fishing practice on the deep seafloor, which is in general characterized by lower resilience than shallow water regions. This study focuses on the flanks of La Fonera (or Palamós) submarine canyon in the Northwestern Mediterranean, where an intensive bottom trawl fishery has been active during several decades in the 400–800 m depth range. To explore the degree of alteration of surface sediments (0–50 cm depth) caused by this industrial activity, fishing grounds and control (untrawled) sites were sampled along the canyon flanks with an interface multicorer. Sediment cores were analyzed to obtain vertical profiles of sediment grain-size, dry bulk density, organic carbon content and concentration of the radionuclide 210Pb. At control sites, surface sediments presented sedimentological characteristics typical of slope depositional systems, including a topmost unit of unconsolidated and bioturbated material overlying sediments progressively compacted with depth, with consistently high 210Pb inventories and exponential decaying profiles of 210Pb concentrations. Sediment accumulation rates at these untrawled sites ranged from 0.3 to 1.0 cm y−1. Sediment properties at most trawled sites departed from control sites and the sampled cores were characterized by denser sediments with lower 210Pb surface concentrations and inventories that indicate widespread erosion of recent sediments caused by trawling gears. Other alterations of the physical sediment properties, including thorough mixing or grain-size sorting, as well as organic carbon impoverishment, were also visible at trawled sites. This work contributes to the growing realization of the capacity of bottom trawling to alter the physical properties of surface sediments and affect the seafloor integrity over large spatial scales of the deep-sea. PMID:25111298

Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)-Enabled Intact Glycopeptide/Glycoproteome Characterization

NASA Astrophysics Data System (ADS)

Yu, Qing; Wang, Bowen; Chen, Zhengwei; Urabe, Go; Glover, Matthew S.; Shi, Xudong; Guo, Lian-Wang; Kent, K. Craig; Li, Lingjun

2017-09-01

Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding five glycosylation sites identified. Subsequent experiments tested its utility for human plasma N-glycoproteins. Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. We also anticipate this approach can be readily applied to large-scale O-glycoproteome characterization. [Figure not available: see fulltext.

Recent Seismicity in Texas and Research Design and Progress of the TexNet-CISR Collaboration

NASA Astrophysics Data System (ADS)

Hennings, P.; Savvaidis, A.; Rathje, E.; Olson, J. E.; DeShon, H. R.; Datta-Gupta, A.; Eichhubl, P.; Nicot, J. P.; Kahlor, L. A.

2017-12-01

The recent increase in the rate of seismicity in Texas has prompted the establishment of an interdisciplinary, interinstitutional collaboration led by the Texas Bureau of Economic Geology which includes the TexNet Seismic Monitoring and Research project as funded by The State of Texas (roughly 2/3rds of our funding) and the industry-funded Center for Integrated Seismicity Research (CISR) (1/3 of funding). TexNet is monitoring and cataloging seismicity across Texas using a new backbone seismic network, investigating site-specific earthquake sequences by deploying temporary seismic monitoring stations, and conducting reservoir modeling studies. CISR expands TexNet research into the interdisciplinary realm to more thoroughly study the factors that contribute to seismicity, characterize the associated hazard and risk, develop strategies for mitigation and management, and develop methods of effective communication for all stakeholders. The TexNet-CISR research portfolio has 6 themes: seismicity monitoring, seismology, geologic and hydrologic description, geomechanics and reservoir modeling, seismic hazard and risk assessment, and seismic risk social science. Twenty+ specific research projects span and connect these themes. We will provide a synopsis of research progress including recent seismicity trends in Texas; Fort Worth Basin integrated studies including geological modeling and fault characterization, fluid injection data syntheses, and reservoir and geomechanical modeling; regional ground shaking characterization and mapping, infrastructure vulnerability assessment; and social science topics of public perception and information seeking behavior.

Initial insights into bacterial succession during human decomposition.

PubMed

Hyde, Embriette R; Haarmann, Daniel P; Petrosino, Joseph F; Lynne, Aaron M; Bucheli, Sibyl R

2015-05-01

Decomposition is a dynamic ecological process dependent upon many factors such as environment, climate, and bacterial, insect, and vertebrate activity in addition to intrinsic properties inherent to individual cadavers. Although largely attributed to microbial metabolism, very little is known about the bacterial basis of human decomposition. To assess the change in bacterial community structure through time, bacterial samples were collected from several sites across two cadavers placed outdoors to decompose and analyzed through 454 pyrosequencing and analysis of variable regions 3-5 of the bacterial 16S ribosomal RNA (16S rRNA) gene. Each cadaver was characterized by a change in bacterial community structure for all sites sampled as time, and decomposition, progressed. Bacteria community structure is variable at placement and before purge for all body sites. At bloat and purge and until tissues began to dehydrate or were removed, bacteria associated with flies, such as Ignatzschineria and Wohlfahrtimonas, were common. After dehydration and skeletonization, bacteria associated with soil, such as Acinetobacter, were common at most body sites sampled. However, more cadavers sampled through multiple seasons are necessary to assess major trends in bacterial succession.

Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site

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

Lanekoff, Ingela; Cha, Jeeyeon; Kyle, Jennifer E.

Here we demonstrate that conditional deletion of mouse uterine Trp53 (p53d/d), molecularly linked to mTORC1 activation and causally linked to premature uterine senescence and preterm birth, results in aberrant lipid signatures within the heterogeneous cell types of embryo implantation sites on day 8 of pregnancy. In situ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) was used to characterize the molecular speciation of free fatty acids, monoacylglycerols, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53d/d mice and floxed littermates. Implantation sites from p53d/d mice exhibited distinct spatially resolved changes demonstrating accumulation of DGmore » species, depletion of Ox-PC species, and increase in species with more unsaturated acyl chains, including arachidonic and docosahexaenoic acid. Understanding abnormal changes in the abundance and localization of individual lipid species early in the progression to premature birth is important for discovering novel targets for treatments and diagnosis.« less

Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site

NASA Astrophysics Data System (ADS)

Lanekoff, Ingela; Cha, Jeeyeon; Kyle, Jennifer E.; Dey, Sudhansu K.; Laskin, Julia; Burnum-Johnson, Kristin E.

2016-09-01

Here we demonstrate that conditional deletion of mouse uterine Trp53 (p53d/d), molecularly linked to mTORC1 activation and causally linked to premature uterine senescence and preterm birth, results in aberrant lipid signatures within the heterogeneous cell types of embryo implantation sites on day 8 of pregnancy. In situ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) was used to characterize the molecular speciation of free fatty acids, monoacylglycerol species, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53d/d mice and floxed littermates. Implantation sites from p53d/d mice exhibited distinct spatially resolved changes demonstrating accumulation of DG species, depletion of Ox-PC species, and increase in species with more unsaturated acyl chains, including arachidonic and docosahexaenoic acid. Understanding abnormal changes in the abundance and localization of individual lipid species early in the progression to premature birth is an important step toward discovering novel targets for treatments and diagnosis.

Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models

PubMed Central

Mdala, Ibrahimu; Olsen, Ingar; Haffajee, Anne D; Socransky, Sigmund S; Thoresen, Magne; de Blasio, Birgitte Freiesleben

2014-01-01

Aim To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Material and Methods Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. Results In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87–97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4–5 months and sites recovered with a high probability (96–98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Conclusion Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. PMID:24888705

40 CFR Table 6 to Subpart Fff of... - Site-Specific Compliance Schedules and Increments of Progress a

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 8 2011-07-01 2011-07-01 false Site-Specific Compliance Schedules and... Constructed on or Before September 20, 1994 Pt. 62, Subpt. FFF, Table 6 Table 6 to Subpart FFF of Part 62—Site-Specific Compliance Schedules and Increments of Progress a Affected facilities at the following MWC sites...

40 CFR Table 6 to Subpart Fff of... - Site-Specific Compliance Schedules and Increments of Progress a

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Site-Specific Compliance Schedules and... Constructed on or Before September 20, 1994 Pt. 62, Subpt. FFF, Table 6 Table 6 to Subpart FFF of Part 62—Site-Specific Compliance Schedules and Increments of Progress a Affected facilities at the following MWC sites...

2005 AG20/20 Annual Review

NASA Technical Reports Server (NTRS)

Ross, Kenton W.; McKellip, Rodney D.

2005-01-01

Topics covered include: Implementation and Validation of Sensor-Based Site-Specific Crop Management; Enhanced Management of Agricultural Perennial Systems (EMAPS) Using GIS and Remote Sensing; Validation and Application of Geospatial Information for Early Identification of Stress in Wheat; Adapting and Validating Precision Technologies for Cotton Production in the Mid-Southern United States - 2004 Progress Report; Development of a System to Automatically Geo-Rectify Images; Economics of Precision Agriculture Technologies in Cotton Production-AG 2020 Prescription Farming Automation Algorithms; Field Testing a Sensor-Based Applicator for Nitrogen and Phosphorus Application; Early Detection of Citrus Diseases Using Machine Vision and DGPS; Remote Sensing of Citrus Tree Stress Levels and Factors; Spectral-based Nitrogen Sensing for Citrus; Characterization of Tree Canopies; In-field Sensing of Shallow Water Tables and Hydromorphic Soils with an Electromagnetic Induction Profiler; Maintaining the Competitiveness of Tree Fruit Production Through Precision Agriculture; Modeling and Visualizing Terrain and Remote Sensing Data for Research and Education in Precision Agriculture; Thematic Soil Mapping and Crop-Based Strategies for Site-Specific Management; and Crop-Based Strategies for Site-Specific Management.

Functional Characterization of HFR1, a High-Mannose N-Glycan-Specific Wheat Lectin Induced by Hessian Fly Larvae1[C][W

PubMed Central

Subramanyam, Subhashree; Smith, David F.; Clemens, James C.; Webb, Mary A.; Sardesai, Nagesh; Williams, Christie E.

2008-01-01

We previously cloned and characterized a novel jacalin-like lectin gene from wheat (Triticum aestivum) plants that responds to infestation by Hessian fly (Mayetiola destructor) larvae, a major dipteran pest of this crop. The infested resistant plants accumulated higher levels of Hfr-1 (for Hessian fly-responsive gene 1) transcripts compared with uninfested or susceptible plants. Here, we characterize the soluble and active recombinant His6-HFR1 protein isolated from Escherichia coli. Functional characterization of the protein using hemagglutination assays revealed lectin activity. Glycan microarray-binding assays indicated strong affinity of His6-HFR1 to Manα1-6(Manα1-3)Man trisaccharide structures. Resistant wheat plants accumulated high levels of HFR1 at the larval feeding sites, as revealed by immunodetection, but the avirulent larvae were deterred from feeding and consumed only small amounts of the lectin. Behavioral studies revealed that avirulent Hessian fly larvae on resistant plants exhibited prolonged searching and writhing behaviors as they unsuccessfully attempted to establish feeding sites. During His6-HFR1 feeding bioassays, Drosophila melanogaster larvae experienced significant delays in growth and pupation, while percentage mortality increased with progressively higher concentrations of His6-HFR1 in the diet. Thus, HFR1 is an antinutrient to dipteran larvae and may play a significant role in deterring Hessian fly larvae from feeding on resistant wheat plants. PMID:18467454

HAZBOT - A hazardous materials emergency response mobile robot

NASA Technical Reports Server (NTRS)

Stone, H. W.; Edmonds, G.

1992-01-01

The authors describe the progress that has been made towards the development of a mobile robot that can be used by hazardous materials emergency response teams to perform a variety of tasks including incident localization and characterization, hazardous material identification/classification, site surveillance and monitoring, and ultimately incident mitigation. In September of 1991, the HAZBOT II vehicle performed its first end-to-end demonstration involving a scenario in which the vehicle: navigated to the incident location from a distant (150-200 ft.) deployment site; entered a building through a door with thumb latch style handle and door closer; located and navigated to the suspected incident location (a chemical storeroom); unlocked and opened the storeroom's door; climbed over the storeroom's 12 in. high threshold to enter the storeroom; and located and identified a broken container of benzene.

HAZBOT - A hazardous materials emergency response mobile robot

NASA Astrophysics Data System (ADS)

Stone, H. W.; Edmonds, G.

The authors describe the progress that has been made towards the development of a mobile robot that can be used by hazardous materials emergency response teams to perform a variety of tasks including incident localization and characterization, hazardous material identification/classification, site surveillance and monitoring, and ultimately incident mitigation. In September of 1991, the HAZBOT II vehicle performed its first end-to-end demonstration involving a scenario in which the vehicle: navigated to the incident location from a distant (150-200 ft.) deployment site; entered a building through a door with thumb latch style handle and door closer; located and navigated to the suspected incident location (a chemical storeroom); unlocked and opened the storeroom's door; climbed over the storeroom's 12 in. high threshold to enter the storeroom; and located and identified a broken container of benzene.

RNAi therapeutics for brain cancer: current advancements in RNAi delivery strategies.

PubMed

Malhotra, Meenakshi; Toulouse, André; Godinho, Bruno M D C; Mc Carthy, David John; Cryan, John F; O'Driscoll, Caitriona M

2015-10-01

Malignant primary brain tumors are aggressive cancerous cells that invade the surrounding tissues of the central nervous system. The current treatment options for malignant brain tumors are limited due to the inability to cross the blood-brain barrier. The advancements in current research has identified and characterized certain molecular markers that are essential for tumor survival, progression, metastasis and angiogenesis. These molecular markers have served as therapeutic targets for the RNAi based therapies, which enable site-specific silencing of the gene responsible for tumor proliferation. However, to bring about therapeutic success, an efficient delivery carrier that can cross the blood-brain barrier and reach the targeted site is essential. The current review focuses on the potential of targeted, non-viral and viral particles containing RNAi therapeutic molecules as delivery strategies specifically for brain tumors.

Diffusion magnetic resonance imaging: A molecular imaging tool caught between hope, hype and the real world of “personalized oncology”

PubMed Central

Mahajan, Abhishek; Deshpande, Sneha S; Thakur, Meenakshi H

2017-01-01

“Personalized oncology” is a multi-disciplinary science, which requires inputs from various streams for optimal patient management. Humongous progress in the treatment modalities available and the increasing need to provide functional information in addition to the morphological data; has led to leaping progress in the field of imaging. Magnetic resonance imaging has undergone tremendous progress with various newer MR techniques providing vital functional information and is becoming the cornerstone of “radiomics/radiogenomics”. Diffusion-weighted imaging is one such technique which capitalizes on the tendency of water protons to diffuse randomly in a given system. This technique has revolutionized oncological imaging, by giving vital qualitative and quantitative information regarding tumor biology which helps in detection, characterization and post treatment surveillance of the lesions and challenging the notion that “one size fits all”. It has been applied at various sites with different clinical experience. We hereby present a brief review of this novel functional imaging tool, with its application in “personalized oncology”. PMID:28717412

Distribution of Epiphytic Diatoms in a Sub-Tropical Estuary

NASA Astrophysics Data System (ADS)

Frankovich, T. A.; Gaiser, E. E.; Wachnicka, A.; Zieman, J. C.

2005-05-01

Within estuaries, seagrasses may represent an order of magnitude greater surface area relative to sediments for the colonization and growth of diatoms. Fossil diatom distributions have proven useful in inferring paleoenvironmental conditions. The strength of these inferences is dependent upon defining the environmental relationships of contempory diatom compositions. The present investigation characterized the modern epiphytic diatom flora on the seagrass Thalassia testudinum at seven sites in the sub-tropical Florida Bay estuary and at one Atlantic Ocean site east of the upper Florida Keys. These sites were sampled six times between March 2000 and April 2001. Diatom species composition was related to water quality parameters using multivariate statistics. 338 diatom species were identified. The seven most abundant species from pooled samples were Cocconeis placentula, Brachysira aponina, Nitzschia liebetruthii, Hyalosynedra laevigata, Amphora cf. tenerrima, Mastogloia crucicula, and M. pusilla. These seven species collectively accounted for 51.7 percent of all valves counted and occurred in at least 85 percent of all samples. Analysis of similiarity and NMDS ordination of species relative abundances revealed four distinct diatom communities across the study region. The spatial variability of these communities was correlated with salinity and water-column nutrient availability. Summertime communities were significantly different from winter-spring communities, but these communities showed a gradual temporal progression with much overlap. The temporal variability was correlated with temperature. Indicator species analysis identified many species significantly influencing the four spatial groups. The Atlantic marine site was characterized by many different Mastogloia species and some epipsammic (sand-grain associated) diatoms (i.e., Cymatosira lorenziana, Dimerogramma dubium, and Neofragilaria nicobarica). Mastogloia pusilla, Rhopalodia pacifica, and Cocconeis woodii were strong indicators of the Gulf of Mexico marine site. Reimerothrix floridensis was particularly abundant in the western interior of Florida Bay (i.e., sites 2, 3, and 4) during summer months. The eastern interior of Florida Bay was characterized by high relative abundances of Brachysira aponina and Nitzschia liebetruthii. The optima and tolerance of these indicator species relative to individual water quality parameters were also determined.

Conventional wastewater treatment and reuse site practices modify bacterial community structure but do not eliminate some opportunistic pathogens in reclaimed water.

PubMed

Kulkarni, Prachi; Olson, Nathan D; Paulson, Joseph N; Pop, Mihai; Maddox, Cynthia; Claye, Emma; Rosenberg Goldstein, Rachel E; Sharma, Manan; Gibbs, Shawn G; Mongodin, Emmanuel F; Sapkota, Amy R

2018-10-15

Water recycling continues to expand across the United States, from areas that have access to advanced, potable-level treated reclaimed water, to those having access only to reclaimed water treated at conventional municipal wastewater treatment plants. This expansion makes it important to further characterize the microbial quality of these conventionally-treated water sources. Therefore, we used 16S rRNA gene sequencing to characterize total bacterial communities present in differentially-treated wastewater and reclaimed water (n = 67 samples) from four U.S. wastewater treatment plants and one associated spray irrigation site conducting on-site ultraviolet treatment and open-air storage. The number of observed operational taxonomic units was significantly lower (p < 0.01) in effluent, compared to influent, after conventional treatment. Effluent community structure was influenced more by treatment method than by influent community structure. The abundance of Legionella spp. increased as treatment progressed in one treatment plant that performed chlorination and in another that seasonally chlorinated. Overall, the alpha-diversity of bacterial communities in reclaimed water decreased (p < 0.01) during wastewater treatment and spray irrigation site ultraviolet treatment (p < 0.01), but increased (p < 0.01) after open-air storage at the spray irrigation site. The abundance of Legionella spp. was higher at the sprinkler system pumphouse at the spray irrigation site than in the influent from the treatment plant supplying the site. Legionella pneumophila was detected in conventionally treated effluent samples and in samples collected after ultraviolet treatment at the spray irrigation site, while Legionella feeleii persisted throughout on-site treatment at the spray irrigation site, and, along with Mycobacterium gordonae, was also detected at the sprinkler system pumphouse at the spray irrigation site. These data could inform the development of future treatment technologies and reuse guidelines that address a broader assemblage of the bacterial community of reclaimed water, resulting in reuse practices that may be more protective of public health. Copyright © 2018 Elsevier B.V. All rights reserved.

Phenological Indicators of Vegetation Recovery in Wetland Ecosystems

NASA Astrophysics Data System (ADS)

Taddeo, S.; Dronova, I.

2017-12-01

Landscape phenology is increasingly used to measure the impacts of climatic and environmental disturbances on plant communities. As plants show rapid phenological responses to environmental changes, variation in site phenology can help characterize vegetation recovery following restoration treatments and qualify their resistance to environmental fluctuations. By leveraging free remote sensing datasets, a phenology-based analysis of vegetation dynamics could offer a cost-effective assessment of restoration progress in wetland ecosystems. To fulfill this objective, we analyze 20 years of free remote sensing data from NASA's Landsat archive to offer a landscape-scale synthesis of wetland restoration efforts in the Sacramento-San Joaquin Delta of California, USA. Through an analysis of spatio-temporal changes in plant phenology and greenness, we assess how 25 restored wetlands across the Delta have responded to restoration treatments, time, and landscape context. We use a spline smoothing approach to generate both site-wide and pixel-specific phenological curves and identify key phenological events. Preliminary results reveal a greater variability in greenness and growing season length during the initial post-restoration years and a significant impact of landscape context in the time needed to reach phenological stability. Well-connected sites seem to benefit from an increased availability of propagules enabling them to reach peak greenness and maximum growing season length more rapidly. These results demonstrate the potential of phenological analyses to measure restoration progress and detect factors promoting wetland recovery. A thorough understanding of wetland phenology is key to the quantification of ecosystem processes including carbon sequestration and habitat provisioning.

Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models.

PubMed

Mdala, Ibrahimu; Olsen, Ingar; Haffajee, Anne D; Socransky, Sigmund S; Thoresen, Magne; de Blasio, Birgitte Freiesleben

2014-09-01

To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87-97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4-5 months and sites recovered with a high probability (96-98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. © 2014 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

SITE CHARACTERIZATION LIBRARY VERSION 3.0

EPA Science Inventory

The Site Characterization Library is a CD that provides a centralized, field-portable source for site characterization information. Version 3 of the Site Characterization Library contains additional (from earlier versions) electronic documents and computer programs related to th...

Substrate and Substrate-Mimetic Chaperone Binding Sites in Human α-Galactosidase A Revealed by Affinity-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Moise, Adrian; Maeser, Stefan; Rawer, Stephan; Eggers, Frederike; Murphy, Mary; Bornheim, Jeff; Przybylski, Michael

2016-06-01

Fabry disease (FD) is a rare metabolic disorder of a group of lysosomal storage diseases, caused by deficiency or reduced activity of the enzyme α-galactosidase. Human α-galactosidase A (hαGAL) hydrolyses the terminal α-galactosyl moiety from glycosphingolipids, predominantly globotriaosylceramide (Gb3). Enzyme deficiency leads to incomplete or blocked breakdown and progressive accumulation of Gb3, with detrimental effects on normal organ functions. FD is successfully treated by enzyme replacement therapy (ERT) with purified recombinant hαGAL. An emerging treatment strategy, pharmacologic chaperone therapy (PCT), employs small molecules that can increase and/or reconstitute the activity of lysosomal enzyme trafficking by stabilizing misfolded isoforms. One such chaperone, 1-deoxygalactonojirimycin (DGJ), is a structural galactose analogue currently validated in clinical trials. DGJ is an active-site-chaperone that binds at the same or similar location as galactose; however, the molecular determination of chaperone binding sites in lysosomal enzymes represents a considerable challenge. Here we report the identification of the galactose and DGJ binding sites in recombinant α-galactosidase through a new affinity-mass spectrometry-based approach that employs selective proteolytic digestion of the enzyme-galactose or -inhibitor complex. Binding site peptides identified by mass spectrometry, [39-49], [83-100], and [141-168], contain the essential ligand-contacting amino acids, in agreement with the known X-ray crystal structures. The inhibitory effect of DGJ on galactose recognition was directly characterized through competitive binding experiments and mass spectrometry. The methods successfully employed in this study should have high potential for the characterization of (mutated) enzyme-substrate and -chaperone interactions, and for identifying chaperones without inhibitory effects.

[Odor pollution from landfill sites and its control: a review].

PubMed

Hu, Bin; Ding, Ying; Wu, Wei-Xiang; Hu, Bei-Gang; Chen, Ying-Xu

2010-03-01

Landfill sites are the major sources of offensive odor in urban public facilities. With the progress of urbanization and the residents' demands for a higher living environment quality, the odor emission from landfill sites has become a severe pollution problem, and the odor control at landfill sites has been one of the research hotspots. This paper summarized the main components and their concentrations of the odor from landfill sites, and expatiated on the research progress in the in-situ control of the odor. The further research directions in in-situ control of the odor from landfill sites were prospected.

Progress on Cleaning Up the Only Commercial Nuclear Fuel Reprocessing Facility to Operate in the United States

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

Jackson, T. J.; MacVean, S. A.; Szlis, K. A.

2002-02-26

This paper describes the progress on cleanup of the West Valley Demonstration Project (WVDP), an environmental management project located south of Buffalo, NY. The WVDP was the site of the only commercial nuclear fuel reprocessing facility to have operated in the United States (1966 to 1972). Former fuel reprocessing operations generated approximately 600,000 gallons of liquid high-level radioactive waste stored in underground tanks. The U.S. Congress passed the WVDP Act in 1980 (WVDP Act) to authorize cleanup of the 220-acre facility. The facility is unique in that it sits on the 3,345-acre Western New York Nuclear Service Center (WNYNSC), whichmore » is owned by New York State through the New York State Energy Research and Development Authority (NYSERDA). The U.S. Department of Energy (DOE) has overall responsibility for the cleanup that is authorized by the WVDP Act, paying 90 percent of the WVDP costs; NYSERDA pays 10 percent. West Valley Nuclear Services Company (WVNSCO) is the management contractor at the WVDP. This paper will provide a description of the many accomplishments at the WVDP, including the pretreatment and near completion of vitrification of all the site's liquid high-level radioactive waste, a demonstration of technologies to characterize the remaining material in the high-level waste tanks, the commencement of decontamination and decommissioning (D&D) activities to place the site in a safe configuration for long-term site management options, and achievement of several technological firsts. It will also include a discussion of the complexities involved in completing the WVDP due to the various agency interests that require integration for future cleanup decisions.« less

Progression of chronic periodontitis can be predicted by the levels of Porphyromonas gingivalis and Treponema denticola in subgingival plaque.

PubMed

Byrne, S J; Dashper, S G; Darby, I B; Adams, G G; Hoffmann, B; Reynolds, E C

2009-12-01

Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth associated with bacteria. Diagnosis is achieved retrospectively by clinical observation of attachment loss. Predicting disease progression would allow for targeted preventive therapy. The aim of this study was to monitor disease progression in patients on a maintenance program and determine the levels of specific bacteria in subgingival plaque samples and then examine the ability of the clinical parameters of disease and levels of specific bacteria in the plaque samples to predict disease progression. During a 12-month longitudinal study of 41 subjects, 25 sites in 21 subjects experienced disease progression indicated by at least 2 mm of clinical attachment loss. Real-time polymerase chain reaction was used to determine the levels of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in subgingival plaque samples. No clinical parameters were able to predict periodontal disease progression. In sites undergoing imminent periodontal disease progression within the next 3 months, significant partial correlations were found between P. gingivalis and T. forsythia (r = 0.55, P < 0.001) and T. denticola and T. forsythia (r = 0.43, P = 0.04). The odds of a site undergoing imminent periodontal disease progression increased with increasing levels of P. gingivalis and T. denticola. Monitoring the proportions of P. gingivalis and T. denticola in subgingival plaque has the potential to help identify sites at significant risk for progression of periodontitis, which would assist in the targeted treatment of disease.

Entropy, complexity, and Markov diagrams for random walk cancer models

PubMed Central

Newton, Paul K.; Mason, Jeremy; Hurt, Brian; Bethel, Kelly; Bazhenova, Lyudmila; Nieva, Jorge; Kuhn, Peter

2014-01-01

The notion of entropy is used to compare the complexity associated with 12 common cancers based on metastatic tumor distribution autopsy data. We characterize power-law distributions, entropy, and Kullback-Liebler divergence associated with each primary cancer as compared with data for all cancer types aggregated. We then correlate entropy values with other measures of complexity associated with Markov chain dynamical systems models of progression. The Markov transition matrix associated with each cancer is associated with a directed graph model where nodes are anatomical locations where a metastatic tumor could develop, and edge weightings are transition probabilities of progression from site to site. The steady-state distribution corresponds to the autopsy data distribution. Entropy correlates well with the overall complexity of the reduced directed graph structure for each cancer and with a measure of systemic interconnectedness of the graph, called graph conductance. The models suggest that grouping cancers according to their entropy values, with skin, breast, kidney, and lung cancers being prototypical high entropy cancers, stomach, uterine, pancreatic and ovarian being mid-level entropy cancers, and colorectal, cervical, bladder, and prostate cancers being prototypical low entropy cancers, provides a potentially useful framework for viewing metastatic cancer in terms of predictability, complexity, and metastatic potential. PMID:25523357

Frontal fibrosing alopecia: clinical presentations and prognosis.

PubMed

Tan, K T; Messenger, A G

2009-01-01

Frontal fibrosing alopecia is an uncommon condition characterized by progressive frontotemporal recession due to inflammatory destruction of hair follicles. Little is known about the natural history of this disease. To determine the clinical features and natural history of frontal fibrosing alopecia. We studied the cases notes of patients diagnosed with frontal fibrosing alopecia from 1993 to 2008 at the Royal Hallamshire Hospital, Sheffield. There were 18 patients aged between 34 and 71 years. Three were premenopausal. All had frontotemporal recession with scarring. This was associated with partial or complete loss of eyebrows in 15 patients while four had hair loss at other sites. One had keratosis pilaris-like papules on the face, and one had follicular erythema on the cheeks. Three patients had oral lichen planus, of whom two also had cutaneous lichen planus affecting other sites of the body. Treatments given included intralesional triamcinolone acetonide, 0.1% tacrolimus ointment and oral hydroxychloroquine. Progression of frontotemporal recession was seen in some patients, but not all. In one patient the hair line receded by 30 mm over 72 months, whereas in another patient there was no positional change in the hair line after 15 years. Frontal fibrosing alopecia is more common in postmenopausal women, but it can occur in younger women. It may be associated with mucocutaneous lichen planus. Recession of the hair line may progress inexorably over many years but this is not inevitable. It is not clear whether or not treatment alters the natural history of the disease - the disease stabilized with time in most of the patients with or without continuing treatment.

Persistent, Biologically Meaningful Prostate Cancer After 1 Year of Androgen Ablation and Docetaxel Treatment

PubMed Central

Tzelepi, Vassiliki; Efstathiou, Eleni; Wen, Sijin; Troncoso, Patricia; Karlou, Maria; Pettaway, Curtis A.; Pisters, Louis L.; Hoang, Anh; Logothetis, Christopher J.; Pagliaro, Lance C.

2011-01-01

Purpose Clinicians are increasingly willing to treat prostate cancer within the primary site in the presence of regional lymph node or even limited distant metastases. However, no formal study on the merits of this approach has been reported. We used a preoperative clinical discovery platform to prioritize pathways for assessment as therapeutic targets and to test the hypothesis that the primary site harbors potentially lethal tumors after aggressive treatment. Patients and Methods Patients with locally advanced or lymph node–metastatic prostate cancer underwent 1 year of androgen ablation and three cycles of docetaxel therapy, followed by prostatectomy. All specimens were characterized for stage by accepted criteria. Expression of select molecular markers implicated in disease progression and therapy resistance was determined immunohistochemically and compared with that in 30 archived specimens from untreated patients with high-grade prostate cancer. Marker expression was divided into three groups: intracellular signaling pathways, stromal-epithelial interaction pathways, and angiogenesis. Results Forty patients were enrolled, 30 (75%) of whom underwent prostatectomy and two (5%) who underwent cystoprostatectomy. Twenty-nine specimens contained sufficient residual tumor for inclusion in a tissue microarray. Immunohistochemical analysis showed increased epithelial and stromal expression of CYP17, SRD5A1, and Hedgehog pathway components, and modulations of the insulin-like growth factor I pathway. Conclusion A network of molecular pathways reportedly linked to prostate cancer progression is activated after 1 year of therapy; biomarker expression suggests that potentially lethal cancers persist in the primary tumor and may contribute to progression. PMID:21606419

SMARTe Site Characterization Tool. In: SMARTe20ll, EPA/600/C-10/007

EPA Science Inventory

The purpose of the Site Characterization Tool is to: (1) develop a sample design for collecting site characterization data and (2) perform data analysis on uploaded data. The sample design part helps to determine how many samples should be collected to characterize a site with ...

The multifaceted biology of plasmacytoid dendritic cells

PubMed Central

Swiecki, Melissa; Colonna, Marco

2015-01-01

Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the pathogenesis of autoimmune diseases characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. Here, we review recent progress from the field of pDC biology, focusing on: the molecular mechanisms that regulate pDC development and functions; the pathways involved in their sensing of pathogens and endogenous nucleic acids; the function of pDCs at mucosal sites; and their roles in infections, autoimmunity and cancer. PMID:26160613

Convergent pathogenic pathways in Alzheimer’s and Huntington disease: Shared targets for drug development

PubMed Central

Ehrnhoefer, Dagmar E.; Wong, Bibiana K.Y.; Hayden, Michael R.

2011-01-01

Neurodegenerative diseases exemplified by Alzheimer’s and Huntington disease are characterized by the progressive neuropsychiatric dysfunction and loss of specific neuronal subtypes. Even though there are differences in the exact sites of pathology and clinical profiles only partially overlap, considerable similarities in disease mechanisms and pathogenic pathways can be observed. These shared mechanisms raise the possibility of common therapeutic targets for drug development. Huntington disease with a monogenic cause and the possibility to accurately identify pre-manifest mutation carriers could be exploited as a ‘model’ for Alzheimer’s disease to test the efficacy of therapeutic interventions targeting shared pathogenic pathways. PMID:22015920

International Approaches for Nuclear Waste Disposal in Geological Formations: Geological Challenges in Radioactive Waste Isolation—Fifth Worldwide Review

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

Faybishenko, Boris; Birkholzer, Jens; Sassani, David

The overall objective of the Fifth Worldwide Review (WWR-5) is to document the current state-of-the-art of major developments in a number of nations throughout the World pursuing geological disposal programs, and to summarize challenging problems and experience that have been obtained in siting, preparing and reviewing cases for the operational and long-term safety of proposed and operating nuclear waste repositories. The scope of the Review is to address current specific technical issues and challenges in safety case development along with the interplay of technical feasibility, siting, engineering design issues, and operational and post-closure safety. In particular, the chapters included inmore » the report present the following types of information: the current status of the deep geological repository programs for high level nuclear waste and low- and intermediate level nuclear waste in each country, concepts of siting and radioactive waste and spent nuclear fuel management in different countries (with the emphasis of nuclear waste disposal under different climatic conditions and different geological formations), progress in repository site selection and site characterization, technology development, buffer/backfill materials studies and testing, support activities, programs, and projects, international cooperation, and future plans, as well as regulatory issues and transboundary problems.« less

Thinking about Bacillus subtilis as a multicellular organism.

PubMed

Aguilar, Claudio; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

2007-12-01

Initial attempts to use colony morphogenesis as a tool to investigate bacterial multicellularity were limited by the fact that laboratory strains often have lost many of their developmental properties. Recent advances in elucidating the molecular mechanisms underlying colony morphogenesis have been made possible through the use of undomesticated strains. In particular, Bacillus subtilis has proven to be a remarkable model system to study colony morphogenesis because of its well-characterized developmental features. Genetic screens that analyze mutants defective in colony morphology have led to the discovery of an intricate regulatory network that controls the production of an extracellular matrix. This matrix is essential for the development of complex colony architecture characterized by aerial projections that serve as preferential sites for sporulation. While much progress has been made, the challenge for future studies will be to determine the underlying mechanisms that regulate development such that differentiation occurs in a spatially and temporally organized manner.

Live births from artificial insemination of microfluidic-sorted bovine spermatozoa characterized by trajectories correlated with fertility

PubMed Central

Nagata, Maria Portia B.; Endo, Kenji; Ogata, Kazuko; Yamanaka, Kenichi; Egashira, Junki; Katafuchi, Naoto; Yamanouchi, Tadayuki; Matsuda, Hideo; Goto, Yuki; Sakatani, Miki; Hojo, Takuo; Nishizono, Hirofumi; Yotsushima, Kenji; Takenouchi, Naoki; Hashiyada, Yutaka; Yamashita, Kenichi

2018-01-01

Selection of functional spermatozoa plays a crucial role in assisted reproduction. Passage of spermatozoa through the female reproductive tract requires progressive motility to locate the oocyte. This preferential ability to reach the fertilization site confers fertility advantage to spermatozoa. Current routine sperm selection techniques are inadequate and fail to provide conclusive evidence on the sperm characteristics that may affect fertilization. We therefore developed a selection strategy for functional and progressively motile bovine spermatozoa with high DNA integrity based on the ability to cross laminar flow streamlines in a diffuser-type microfluidic sperm sorter (DMSS). The fluid dynamics, with respect to microchannel geometry and design, are relevant in the propulsion of spermatozoa and, consequently, ultrahigh-throughput sorting. Sorted spermatozoa were assessed for kinematic parameters, acrosome reaction, mitochondrial membrane potential, and DNA integrity. Kinematic and trajectory patterns were used to identify fertility-related subpopulations: the rapid, straighter, progressive, nonsinuous pattern (PN) and the transitional, sinuous pattern (TS). In contrast to the conventional notion that the fertilizing spermatozoon is always vigorously motile and more linear, our results demonstrate that sinuous patterns are associated with fertility and correspond to truly functional spermatozoa as supported by more live births produced from predominant TS than PN subpopulation in the inseminate. Our findings ascertain the true practical application significance of microfluidic sorting of functional sperm characterized by sinuous trajectories that can serve as a behavioral sperm phenotype marker for fertility potential. More broadly, we foresee the clinical application of this sorting technology to assisted reproduction in humans. PMID:29555773

Use of Magnetic Parameters to Asses Soil Erosion Rates on Agricultural Site

NASA Astrophysics Data System (ADS)

Petrovsky, E.; Kapicka, A.; Dlouha, S.; Jaksik, O.; Grison, H.; Kodesova, R.

2014-12-01

A detailed field study on a small test site of agricultural land situated in loess region in Southern Moravia (Czech Republic) and laboratory analyses were carried out in order to test the applicability of magnetic methods in assessing soil erosion. Haplic Chernozem, the original dominant soil unit in the area, is nowadays progressively transformed into different soil units along with intense soil erosion. As a result, an extremely diversified soil cover structure has developed due to the erosion. The site was characterized by a flat upper part while the middle part, formed by a substantive side valley, is steeper. We carried out field measurements of magnetic susceptibility on a regular grid, resulting in 101 data points. The bulk soil material for laboratory investigation was gathered from all the grid points. Values of the magnetic susceptibility are spatially distributed depending on the terrain. Higher values were measured in the flat upper part (where the original top horizon remained). The lowest values of were obtained on the steep valley sides. Here the original topsoil was eroded and mixed by tillage with the soil substrate (loess). A soil profile unaffected by erosion was investigated in detail. The vertical distribution of magnetic susceptibility along this "virgin" profile was measured in laboratory on the samples collected with 2-cm spacing. The undisturbed profile shows several soil horizons. Horizons Ac and A show a slight increase in magnetic susceptibility up to a depth of about 70 cm. Horizon A/Ck is characterized by a decrease in susceptibility, and the underlying C horizon (h > 103 cm) has a very low value of magnetic susceptibility. The differences between the values of susceptibility in the undisturbed soil profile and the magnetic signal after uniform mixing the soil material as a result of tillage and erosion are fundamental for the estimation of soil loss in the studied test field. Using the uneroded profile from the studied locality as a basis for examining the changes in cultivated soils, tillage homogenization model can be applied to predict changes in the surface soil magnetism with progressive soil erosion. The model is very well applicable at the studied site. Acknowledgement: This study was supported by NAZV Agency of the Ministry of Agriculture of the Czech Republic through grant No QJ1230319.

Study site characterization. Chapter 2

Treesearch

Chris Potter; Richard Birdsey

2008-01-01

This chapter is an overview of the main site characterization requirements at landscape-scale sampling locations. The overview is organized according to multiple "Site Attribute" headings that require descriptions throughout a given study site area, leading ultimately to a sufficient overall site characterization. Guidance is provided to describe the major...

SHARAD soundings and surface roughness at past, present, and proposed landing sites on Mars: Reflections at Phoenix may be attributable to deep ground ice

NASA Astrophysics Data System (ADS)

Putzig, Nathaniel E.; Phillips, Roger J.; Campbell, Bruce A.; Mellon, Michael T.; Holt, John W.; Brothers, T. Charles

2014-08-01

We use the Shallow Radar (SHARAD) on the Mars Reconnaissance Orbiter to search for subsurface interfaces and characterize surface roughness at the landing sites of Viking Landers 1 and 2, Mars Pathfinder, the Mars Exploration Rovers Spirit and Opportunity, the Phoenix Mars lander, the Mars Science Laboratory Curiosity rover, and three other sites proposed for Curiosity. Only at the Phoenix site do we find clear evidence of subsurface radar returns, mapping out an interface that may be the base of ground ice at depths of ~15-66 m across 2900 km2 in the depression where the lander resides. At the Opportunity, Spirit, and candidate Curiosity sites, images and altimetry show layered materials tens to hundreds of meters thick extending tens to hundreds of kilometers laterally. These scales are well within SHARAD's resolution limits, so the lack of detections is attributable either to low density contrasts in layers of similar composition and internal structure or to signal attenuation within the shallowest layers. At each site, we use the radar return power to estimate surface roughness at scales of 10-100 m, a measure that is important for assessing physical properties, landing safety, and site trafficability. The strongest returns are found at the Opportunity site, indicating that Meridiani Planum is exceptionally smooth. Returns of moderate strength at the Spirit site reflect roughness more typical of Mars. Gale crater, Curiosity's ultimate destination, is the smoothest of the four proposed sites we examined, with Holden crater, Eberswalde crater, and Mawrth Vallis exhibiting progressively greater roughness.

Annual Reports Regarding Progress in Developing a Dredged Material Management Plan for the Long Island Sound Region

EPA Pesticide Factsheets

The site designation for the Western and Central Long Island Sound disposal sites requires the completion of a Dredged Material Management Plan (DMMP) and EPA to conduct an annual review of progress toward completion of the DMMP.

A comparison of near-surface potential temperature variance budgets for unstable atmospheric flows over vegetated and non-vegetated flat surfaces and a gentle slope

NASA Astrophysics Data System (ADS)

Hang, C.; Nadeau, D.; Pardyjak, E.; Parlange, M. B.

2017-12-01

Over the past decades, researchers have made much progress toward a fundamental understanding of the budgets of turbulence variables over flat and homogeneous terrain, and only more recently over complex terrain. However, temperature variance budgets, which are parameterized in most meteorological models, are still poorly understood even under relatively idealized conditions. In this work, we rely on near-surface turbulence observations collected as part of the Mountain Terrain Atmospheric Modeling and Observations (MATERHORN) program. Data collected in May 2013 in western Utah at three field sites subjected to similar large-scale forcing are analyzed: a desert playa (dry lakebed), characterized by a at surface devoid of vegetation; a vegetated site, characterized by at valley oor covered with greasewood vegetation, and a mountain terrain site with a slope angle of 2 -4° and covered by high-elevation vegetation. The analysis reveals the presence of a 5-m layer where the production and dissipation terms of potential temperature variance (θ2) drop rapidly below this level. During convective periods, vertical advection and turbulent transport of θ2 can often be non-negligible, in particular at Playa and Slope sites. In addition, within the 5-m layer, turbulent transport of θ2 acts as a sink term at all sites of interest. Neither the ratio of turbulent transport to production nor the ratio of production to dissipation show a stability dependence during the unstable periods studied. A short-period comparison of dissipation rates calculated using dissipation-scale resolving hot-wire/cold-wire anemometry and several common indirect methods using sonic anemometry is presented for data acquired at Playa site. The results indicates that the dissipation rates from all methods follow similar trends, however the magnitudes can differ by a factor of 2 - 3.

ChimericSeq: An open-source, user-friendly interface for analyzing NGS data to identify and characterize viral-host chimeric sequences.

PubMed

Shieh, Fwu-Shan; Jongeneel, Patrick; Steffen, Jamin D; Lin, Selena; Jain, Surbhi; Song, Wei; Su, Ying-Hsiu

2017-01-01

Identification of viral integration sites has been important in understanding the pathogenesis and progression of diseases associated with particular viral infections. The advent of next-generation sequencing (NGS) has enabled researchers to understand the impact that viral integration has on the host, such as tumorigenesis. Current computational methods to analyze NGS data of virus-host junction sites have been limited in terms of their accessibility to a broad user base. In this study, we developed a software application (named ChimericSeq), that is the first program of its kind to offer a graphical user interface, compatibility with both Windows and Mac operating systems, and optimized for effectively identifying and annotating virus-host chimeric reads within NGS data. In addition, ChimericSeq's pipeline implements custom filtering to remove artifacts and detect reads with quantitative analytical reporting to provide functional significance to discovered integration sites. The improved accessibility of ChimericSeq through a GUI interface in both Windows and Mac has potential to expand NGS analytical support to a broader spectrum of the scientific community.

Some Structural Properties of the Mixed Lead-Magnesium Hydroxyapatites

NASA Astrophysics Data System (ADS)

Kaaroud, K.; Ben Moussa, S.; Brigui, N.; Badraoui, B.

2018-02-01

Lead-magnesium hydroxyapatite solid solutions Pb(10- x)Mg x (PO4)6(OH)2 have been prepared via a hydrothermal process. They were characterized by X-ray powder diffraction, Transmission Electron Microscopy (TEM), chemical and IR spectroscopic analyses. The results of the structural refinement indicated that the limits of lead-magnesium solid solutions ( x ≤ 1.5), a regular decrease of the lattice constant a and a preferential magnesium distribution in site S(I). Through the progressive replacement of Pb2+ ( r = 0.133 nm) by the smaller cation Mg2+ ( r = 0.072 nm), all interatomic distances decrease in accordance with the decrease of the cell parameters. According to what could be expected from the coordinance of the metallic sites S(I) (hexacoordination) and S(II) (heptacoordination), the small magnesium cation preferentially occupies the four sites S(I). The results of the TEM analysis confirm the presence of magnesium in the starting solution and reveals the decrease in the average size of crystals. The IR spectra show the presence of the absorption bands characteristic for the apatite structure.

AMF 1 Site Science

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

Miller, Mark Alan

This report documents progress on DOE Grant# DE-FG02-08ER64531 funded by the Department of Energy’s Atmospheric Systems Research (ASR) program covering the period between its inception in 2008 and its conclusion in 2014. The Atmospheric Radiation Measurement (ARM) Program’s Mobile Facility #1 (AMF#1) is a collection of state-of-the art atmospheric sensing systems including remote and in situ instrumentation designed to characterize the atmospheric column above and in the immediate vicinity of the deployment location. The grant discussed in this report funded the activities of the AMF#1 Site Scientist Team. Broad responsibilities of this team included examining new deployment sites and recommendingmore » instrument deployment configurations; data quality control during the early stages of deployments and for certain instruments through the course of the deployment; scientific outreach in the host country or location (particularly international deployments); scientific research oriented toward basic questions about cloud physics and radiation transfer in the deployment region; and training of Ph.D. students to conduct future research relevant to the Atmospheric Systems Research (ASR) program.« less

ChimericSeq: An open-source, user-friendly interface for analyzing NGS data to identify and characterize viral-host chimeric sequences

PubMed Central

Shieh, Fwu-Shan; Jongeneel, Patrick; Steffen, Jamin D.; Lin, Selena; Jain, Surbhi; Song, Wei

2017-01-01

Identification of viral integration sites has been important in understanding the pathogenesis and progression of diseases associated with particular viral infections. The advent of next-generation sequencing (NGS) has enabled researchers to understand the impact that viral integration has on the host, such as tumorigenesis. Current computational methods to analyze NGS data of virus-host junction sites have been limited in terms of their accessibility to a broad user base. In this study, we developed a software application (named ChimericSeq), that is the first program of its kind to offer a graphical user interface, compatibility with both Windows and Mac operating systems, and optimized for effectively identifying and annotating virus-host chimeric reads within NGS data. In addition, ChimericSeq’s pipeline implements custom filtering to remove artifacts and detect reads with quantitative analytical reporting to provide functional significance to discovered integration sites. The improved accessibility of ChimericSeq through a GUI interface in both Windows and Mac has potential to expand NGS analytical support to a broader spectrum of the scientific community. PMID:28829778

Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys▿

PubMed Central

Durudas, Andre; Milush, Jeffrey M.; Chen, Hui-Ling; Engram, Jessica C.; Silvestri, Guido; Sodora, Donald L.

2009-01-01

Cytokines and chemokines are critical for establishing tissue-specific immune responses and play key roles in modulating disease progression in simian immunodeficiency virus (SIV)-infected macaques and human immunodeficiency virus (HIV)-infected humans. The goal here was to characterize the innate immune response at different tissue sites and to correlate these responses to clinical outcome, initially focusing on rhesus macaques orally inoculated with SIV and monitored until onset of simian AIDS. Cytokine and chemokine mRNA transcripts were assessed at lymph nodes (LN) and peripheral blood cells utilizing quantitative real-time PCR at different time points postinfection. The mRNA expression of four immune modulators—alpha interferon (IFN-α), oligoadenylate synthetase (OAS), CXCL9, and CXCL10—was positively associated with disease progression within LN tissue. Elevated cytokine/chemokine expression in LN did not result in any observed beneficial outcome since the numbers of CXCR3+ cells were not increased, nor were the SIV RNA levels decreased. In peripheral blood, increased OAS and CXCL10 expression were elevated in SIV+ monkeys that progress the fastest to simian AIDS. Our results indicate that higher IFN-α, OAS, CXCL9, and CXCL10 mRNA expression in LN was associated with rapid disease progression and a LN environment that may favor SIV replication. Furthermore, higher expression of CXCL10 and OAS in peripheral blood could potentially serve as a diagnostic marker for hosts that are likely to progress to AIDS. Understanding the expression patterns of key innate immune modulators will be useful in assessing the disease state and potential rates of disease progression in HIV+ patients, which could lead to novel therapy and vaccine approaches. PMID:19759147

Elevated levels of innate immune modulators in lymph nodes and blood are associated with more-rapid disease progression in simian immunodeficiency virus-infected monkeys.

PubMed

Durudas, Andre; Milush, Jeffrey M; Chen, Hui-Ling; Engram, Jessica C; Silvestri, Guido; Sodora, Donald L

2009-12-01

Cytokines and chemokines are critical for establishing tissue-specific immune responses and play key roles in modulating disease progression in simian immunodeficiency virus (SIV)-infected macaques and human immunodeficiency virus (HIV)-infected humans. The goal here was to characterize the innate immune response at different tissue sites and to correlate these responses to clinical outcome, initially focusing on rhesus macaques orally inoculated with SIV and monitored until onset of simian AIDS. Cytokine and chemokine mRNA transcripts were assessed at lymph nodes (LN) and peripheral blood cells utilizing quantitative real-time PCR at different time points postinfection. The mRNA expression of four immune modulators-alpha interferon (IFN-alpha), oligoadenylate synthetase (OAS), CXCL9, and CXCL10-was positively associated with disease progression within LN tissue. Elevated cytokine/chemokine expression in LN did not result in any observed beneficial outcome since the numbers of CXCR3(+) cells were not increased, nor were the SIV RNA levels decreased. In peripheral blood, increased OAS and CXCL10 expression were elevated in SIV(+) monkeys that progress the fastest to simian AIDS. Our results indicate that higher IFN-alpha, OAS, CXCL9, and CXCL10 mRNA expression in LN was associated with rapid disease progression and a LN environment that may favor SIV replication. Furthermore, higher expression of CXCL10 and OAS in peripheral blood could potentially serve as a diagnostic marker for hosts that are likely to progress to AIDS. Understanding the expression patterns of key innate immune modulators will be useful in assessing the disease state and potential rates of disease progression in HIV(+) patients, which could lead to novel therapy and vaccine approaches.

Health and Safety Research Division progress report, October 1, 1988--March 31, 1990

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

Not Available

1990-09-01

The Health and Safety Research Division (HASRD) of the Oak Ridge National Laboratory (ORNL) continues to maintain an outstanding program of basic and applied research displaying a high level of creativity and achievement as documented by awards, publications, professional service, and successful completion of variety of projects. Our focus is on human health and the scientific basis for measurement and assessment of health-related impacts of energy technologies. It is our custom to publish a division progress report every 18 months that summarizes our programmatic progress and other measures of achievement over the reporting period. Since it is not feasible tomore » summarize in detail all of our work over the period covered by this report (October 1, 1988, to March 30, 1990), we intend this document to point the way to the expensive open literature that documents our findings. During the reporting period the Division continued to maintain strong programs in its traditional areas of R D, but also achieved noteworthy progress in other areas. Much of the Division's work on site characterization, development of new field instruments, compilation of data bases, and methodology development fits into this initiative. Other new work in tunneling microscopy in support of DOE's Human Genome Program and the comprehensive R D work related to surface-enhanced Raman spectroscopy have attained new and exciting results. These examples of our progress and numerous other activities are highlighted in this report.« less

Functional Nanomaterial’s Synthesis and Characterization

DTIC Science & Technology

2015-04-28

synthesis and characterization of nanoparticles and polymers. Current progress is being made at Argonne National Labs (ANL) and at AFRL in characterization... currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. Florida A&M University 1700 Lee Hall Drive 400 Foote-Hilyer Admin...at Florida A&M University (FAMU) which will play a key role in synthesis and characterization of nanoparticles and polymers. Current progress is

Searching for protein binding sites from Molecular Dynamics simulations and paramagnetic fragment-based NMR studies.

PubMed

Bernini, Andrea; Henrici De Angelis, Lucia; Morandi, Edoardo; Spiga, Ottavia; Santucci, Annalisa; Assfalg, Michael; Molinari, Henriette; Pillozzi, Serena; Arcangeli, Annarosa; Niccolai, Neri

2014-03-01

Hotspot delineation on protein surfaces represents a fundamental step for targeting protein-protein interfaces. Disruptors of protein-protein interactions can be designed provided that the sterical features of binding pockets, including the transient ones, can be defined. Molecular Dynamics, MD, simulations have been used as a reliable framework for identifying transient pocket openings on the protein surface. Accessible surface area and intramolecular H-bond involvement of protein backbone amides are proposed as descriptors for characterizing binding pocket occurrence and evolution along MD trajectories. TEMPOL induced paramagnetic perturbations on (1)H-(15)N HSQC signals of protein backbone amides have been analyzed as a fragment-based search for surface hotspots, in order to validate MD predicted pockets. This procedure has been applied to CXCL12, a small chemokine responsible for tumor progression and proliferation. From combined analysis of MD data and paramagnetic profiles, two CXCL12 sites suitable for the binding of small molecules were identified. One of these sites is the already well characterized CXCL12 region involved in the binding to CXCR4 receptor. The other one is a transient pocket predicted by Molecular Dynamics simulations, which could not be observed from static analysis of CXCL12 PDB structures. The present results indicate how TEMPOL, instrumental in identifying this transient pocket, can be a powerful tool to delineate minor conformations which can be highly relevant in dynamic discovery of antitumoral drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

SU-E-J-115: Using Markov Chain Modeling to Elucidate Patterns in Breast Cancer Metastasis Over Time and Space

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

Comen, E; Mason, J; Kuhn, P

2014-06-01

Purpose: Traditionally, breast cancer metastasis is described as a process wherein cancer cells spread from the breast to multiple organ systems via hematogenous and lymphatic routes. Mapping organ specific patterns of cancer spread over time is essential to understanding metastatic progression. In order to better predict sites of metastases, here we demonstrate modeling of the patterned migration of metastasis. Methods: We reviewed the clinical history of 453 breast cancer patients from Memorial Sloan Kettering Cancer Center who were non-metastatic at diagnosis but developed metastasis over time. We used the variables of organ site of metastases as well as time tomore » create a Markov chain model of metastasis. We illustrate the probabilities of metastasis occurring at a given anatomic site together with the probability of spread to additional sites. Results: Based on the clinical histories of 453 breast cancer patients who developed metastasis, we have learned (i) how to create the Markov transition matrix governing the probabilities of cancer progression from site to site; (ii) how to create a systemic network diagram governing disease progression modeled as a random walk on a directed graph; (iii) how to classify metastatic sites as ‘sponges’ that tend to only receive cancer cells or ‘spreaders’ that receive and release them; (iv) how to model the time-scales of disease progression as a Weibull probability distribution function; (v) how to perform Monte Carlo simulations of disease progression; and (vi) how to interpret disease progression as an entropy-increasing stochastic process. Conclusion: Based on our modeling, metastatic spread may follow predictable pathways. Mapping metastasis not simply by organ site, but by function as either a ‘spreader’ or ‘sponge’ fundamentally reframes our understanding of metastatic processes. This model serves as a novel platform from which we may integrate the evolving genomic landscape that drives cancer metastasis. PS-OC Trans-Network Project Grant Award for “Data Assimilation and ensemble statistical forecasting methods applied to the MSKCC longitudinal metastatic breast cancer cohort.”.« less

National Assessment of Educational Progress.

ERIC Educational Resources Information Center

National Center for Education Statistics (ED), Washington, DC.

The National Center for Education Statistics (NCES) recently unveiled a new Web site about the National Assessment of Educational Progress (NAEP), the "Nation's Report Card." This site (http://nces.ed.gov/nationsreportcard) provides easy access to a wealth of assessment information about the condition of education in the United States,…

Review on physical and chemical characterizations of contaminated sediments from urban stormwater infiltration basins within the framework of the French observatory for urban hydrology (SOERE URBIS).

PubMed

El-Mufleh, Amelène; Béchet, Béatrice; Ruban, Véronique; Legret, Michel; Clozel, Blandine; Barraud, Sylvie; Gonzalez-Merchan, Carolina; Bedell, Jean-Philippe; Delolme, Cécile

2014-04-01

Urban stormwater infiltration basins are designed to hold runoff from impervious surfaces and allow the settling of sediments and associated pollutants. However concerns have been expressed about the environmental impacts that may be exerted by the trapped pollutants on groundwater, soils and ecosystems. In this context, sediment characterization represents a key issue for local authorities in terms of management strategies. During the last two decades, several studies were launched including either physical or chemical characterization of stormwater sediments but without real synthesis of data and methods used. Consequently, there is an important need for reviewing the current experimental techniques devoted to the physico-chemical characterization of sediment. The review is based on the outcomes of two experimental sites for which long term monitoring and data collection have been done: the Cheviré basin (near Nantes) and the Django Reinhardt basin (near Lyon). The authors summarize the studies dealing with bulk properties, pollutant contents, their potential mobility and speciation. This paper aims at promoting the significant progresses that were made through a multidisciplinary approach involving multi-scaled and combined experimental techniques.

Lipid Droplets and Mycobacterium leprae Infection

PubMed Central

Elamin, Ayssar A.; Stehr, Matthias; Singh, Mahavir

2012-01-01

Leprosy is a chronic infectious disease and is a major source of morbidity in developing countries. Leprosy is caused by the obligate intracellular bacterium Mycobacterium leprae, which infects as primary target Schwann cells. Lepromatous leprosy exhibits multiple lesions of the skin, eyes, nerves, and lymph nodes. The sites of infection are characterized by the presence of foamy macrophages, fully packed with lipid droplets (LDs), which are induced by M. leprae. In the last years, it has become evident that M. tuberculosis imports lipids from foamy macrophages and is dependent on fatty acids for growth in infected macrophages. M. leprae seems to have similar mechanisms for scavenging lipids from the host. But due to the inability to culture M. leprae on laboratory media, research progresses only slowly. However, in the last years, substantial progress has been made in the field of lipid metabolism in M. leprae. Herein, we will present and summarize the lipid droplets formation and the metabolism of lipids during M. leprae infection. PMID:23209912

10 CFR 960.3-2-3 - Recommendation of sites for characterization.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Recommendation of sites for characterization. 960.3-2-3... POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-2-3 Recommendation of sites... President not less than three candidate sites for such characterization. The recommendation decision shall...

10 CFR 960.3-1-4-3 - Site recommendation for characterization.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Site recommendation for characterization. 960.3-1-4-3... POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site recommendation for characterization. The evidence required to support the recommendation of a site as a candidate...

Characterization and mapping of the mouse NDP (Norrie disease) locus (Ndp).

PubMed

Battinelli, E M; Boyd, Y; Craig, I W; Breakefield, X O; Chen, Z Y

1996-02-01

Norrie disease is a severe X-linked recessive neurological disorder characterized by congenital blindness with progressive loss of hearing. Over half of Norrie patients also manifest different degrees of mental retardation. The gene for Norrie disease (NDP) has recently been cloned and characterized. With the human NDP cDNA, mouse genomic phage libraries were screened for the homolog of the gene. Comparison between mouse and human genomic DNA blots hybridized with the NDP cDNA, as well as analysis of phage clones, shows that the mouse NDP gene is 29 kb in size (28 kb for the human gene). The organization in the two species is very similar. Both have three exons with similar-sized introns and identical exon-intron boundaries between exon 2 and 3. The mouse open reading frame is 393 bp and, like the human coding sequence, is encoded in exons 2 and 3. The absence of six nucleotides in the second mouse exon results in the encoded protein being two amino acids smaller than its human counterpart. The overall homology between the human and mouse NDP protein is 95% and is particularly high (99%) in exon 3, consistent with the apparent functional importance of this region. Analysis of transcription initiation sites suggests the presence of multiple start sites associated with expression of the mouse NDP gene. Pedigree analysis of an interspecific mouse backcross localizes the mouse NDP gene close to Maoa in the conserved segment, which runs from CYBB to PFC in both human and mouse.

Strategies for Isolation and Molecular Profiling of Circulating Tumor Cells.

PubMed

Chen, Jia-Yang; Chang, Ying-Chih

2017-01-01

Cancer is the leading cause of death by disease worldwide, and metastasis is responsible for more than 90% of the mortality of cancer patients. Metastasis occurs when tumor cells leave the primary tumor, travel through the blood stream as circulating tumor cells (CTCs), and then colonize secondary tumors at sites distant from the primary tumor. The capture, identification, and analysis of CTCs offer both scientific and clinical benefits. On the scientific side, the analysis of CTCs could help elucidate possible genetic alterations and signaling pathway aberrations during cancer progression, which could then be used to find new methods to stop cancer progression. On the clinical side, non-invasive testing of a patient's blood for CTCs can be used for patient diagnosis and prognosis, as well as subsequent monitoring of treatment efficacy in routine clinical practice. Additionally, investigation of CTCs early in the progression of cancer may reveal targets for initial cancer detection and for anti-cancer treatment. This chapter will evaluate strategies and devices used for the isolation and identification of CTCs directly from clinical samples of blood. Recent progress in the understanding of the significance of both single CTCs and circulating tumor microemboli will be discussed. Also, advancements in the use of CTC-based liquid biopsy in clinical diagnosis and the potential of CTC-based molecular characterization for use in clinical applications will be summarized.

Upper Animas Mining District

EPA Pesticide Factsheets

Web page provides narrative of What's New?, Site Description, Site Risk, Cleanup Progress, Community Involvement, Next Steps, Site Documents, FAQ, Contacts and LInks for the Upper Animas Mining District site in San Juan County, Colorado.

Geochemistry of the Bonin Fore-arc Volcanic Sequence: Results from IODP Expedition 352

NASA Astrophysics Data System (ADS)

Godard, M.; Ryan, J. G.; Shervais, J. W.; Whattam, S. A.; Sakuyama, T.; Kirchenbaur, M.; Li, H.; Nelson, W. R.; Prytulak, J.; Pearce, J. A.; Reagan, M. K.

2015-12-01

The Izu-Bonin-Mariana intraoceanic arc system, in the western Pacific, results from ~52 My of subduction of the Pacific plate beneath the eastern margin of the Philippine Sea plate. Four sites were drilled south of the Bonin Islands during IODP Expedition 352 and 1.22 km of igneous basement was cored upslope to the west of the trough. These stratigraphically controlled igneous suites allow study of the earliest stages of arc development from seafloor spreading to convergence. We present the preliminary results of a detailed major and trace element (ICPMS) study on 128 igneous rocks drilled during Expedition 352. Mainly basalts and basaltic andesites were recovered at the two deeper water sites (U1440 and U1441) and boninites at the two westernmost sites (U1439 and U1442). Sites U1440 and U1441 basaltic suites are trace element depleted (e.g. Yb 4-6 x PM); they have fractionated REE patterns (LREE/HREE = 0.2-0.4 x C1-chondrites) compared to mid-ocean ridge basalts. They have compositions overlapping that of previously sampled Fore-Arc Basalts (FAB) series. They are characterized also by an increase in LILE contents relative to neighboring elements up-section (e.g. Rb/La ranging from <1 to 3-7 x PM at Site U1440) suggesting a progressive contamination of their source by fluids. This process in turn may have favored melting and efficient melt extraction from the source and thus its extreme depletion. Boninites are depleted in moderately incompatible elements with a decrease in their contents up-section (e.g. Yb = ~6.2 to 2.8 x C1-chondrite at Site U1439). These changes in trace element contents are associated with the development of a positive Zr-Hf anomaly relative to neighboring elements and a strong increase in LILE (e.g., Zr/Sm=~1 to 2.6 x PM and Rb/La=1-2 to 10-18). The progressive upward depletion of boninitic lavas could reveal the incorporation of harzburgitic residues from FAB generation into their mantle source.

Biomass power for rural development. Technical progress report, January 1--March 31, 1998

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

Neuhauser, E.

Brief progress reports are presented on the following tasks: design packages for retrofits at the Dunkirk Station; fuel supply and site development plans; major equipment guarantees and project risk sharing; power production commitment; power plant site plan, construction and environmental permits; and experimental strategies for system evaluation. The paper then discusses in more detail the following: feedstock development efforts; clone-site testing and genetic studies; and efforts at outreach, extension and technology transfer.

Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia

PubMed Central

Heller, G; Topakian, T; Altenberger, C; Cerny-Reiterer, S; Herndlhofer, S; Ziegler, B; Datlinger, P; Byrgazov, K; Bock, C; Mannhalter, C; Hörmann, G; Sperr, W R; Lion, T; Zielinski, C C; Valent, P; Zöchbauer-Müller, S

2016-01-01

Little is known about the impact of DNA methylation on the evolution/progression of Ph+ chronic myeloid leukemia (CML). We investigated the methylome of CML patients in chronic phase (CP-CML), accelerated phase (AP-CML) and blast crisis (BC-CML) as well as in controls by reduced representation bisulfite sequencing. Although only ~600 differentially methylated CpG sites were identified in samples obtained from CP-CML patients compared with controls, ~6500 differentially methylated CpG sites were found in samples from BC-CML patients. In the majority of affected CpG sites, methylation was increased. In CP-CML patients who progressed to AP-CML/BC-CML, we identified up to 897 genes that were methylated at the time of progression but not at the time of diagnosis. Using RNA-sequencing, we observed downregulated expression of many of these genes in BC-CML compared with CP-CML samples. Several of them are well-known tumor-suppressor genes or regulators of cell proliferation, and gene re-expression was observed by the use of epigenetic active drugs. Together, our results demonstrate that CpG site methylation clearly increases during CML progression and that it may provide a useful basis for revealing new targets of therapy in advanced CML. PMID:27211271

Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.

PubMed

Stephen, Joshi; Nampoothiri, Sheela; Banerjee, Aditi; Tolman, Nathanial J; Penninger, Josef Martin; Elling, Ullrich; Agu, Chukwuma A; Burke, John D; Devadathan, Kalpana; Kannan, Rajesh; Huang, Yan; Steinbach, Peter J; Martinis, Susan A; Gahl, William A; Malicdan, May Christine V

2018-04-01

Progressive microcephaly and neurodegeneration are genetically heterogenous conditions, largely associated with genes that are essential for the survival of neurons. In this study, we interrogate the genetic etiology of two siblings from a non-consanguineous family with severe early onset of neurological manifestations. Whole exome sequencing identified novel compound heterozygous mutations in VARS that segregated with the proband: a missense (c.3192G>A; p.Met1064Ile) and a splice site mutation (c.1577-2A>G). The VARS gene encodes cytoplasmic valyl-tRNA synthetase (ValRS), an enzyme that is essential during eukaryotic translation. cDNA analysis on patient derived fibroblasts revealed that the splice site acceptor variant allele led to nonsense mediated decay, thus resulting in a null allele. Three-dimensional modeling of ValRS predicts that the missense mutation lies in a highly conserved region and could alter side chain packing, thus affecting tRNA binding or destabilizing the interface between the catalytic and tRNA binding domains. Further quantitation of the expression of VARS showed remarkably reduced levels of mRNA and protein in skin derived fibroblasts. Aminoacylation experiments on patient derived cells showed markedly reduced enzyme activity of ValRS suggesting the mutations to be loss of function. Bi-allelic mutations in cytoplasmic amino acyl tRNA synthetases are well-known for their role in neurodegenerative disorders, yet human disorders associated with VARS mutations have not yet been clinically well characterized. Our study describes the phenotype associated with recessive VARS mutations and further functional delineation of the pathogenicity of novel variants identified, which widens the clinical and genetic spectrum of patients with progressive microcephaly.

SMARTE'S SITE CHARACTERIZATION TOOL

EPA Science Inventory

Site Characterization involves collecting environmental data to evaluate the nature and extent of contamination. Environmental data could consist of chemical analyses of soil, sediment, water or air samples. Typically site characterization data are statistically evaluated for thr...

40 CFR 280.63 - Initial site characterization.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Initial site characterization. 280.63... Hazardous Substances § 280.63 Initial site characterization. (a) Unless directed to do otherwise by the implementing agency, owners and operators must assemble information about the site and the nature of the...

Systems pharmacology - Towards the modeling of network interactions.

PubMed

Danhof, Meindert

2016-10-30

Mechanism-based pharmacokinetic and pharmacodynamics (PKPD) and disease system (DS) models have been introduced in drug discovery and development research, to predict in a quantitative manner the effect of drug treatment in vivo in health and disease. This requires consideration of several fundamental properties of biological systems behavior including: hysteresis, non-linearity, variability, interdependency, convergence, resilience, and multi-stationarity. Classical physiology-based PKPD models consider linear transduction pathways, connecting processes on the causal path between drug administration and effect, as the basis of drug action. Depending on the drug and its biological target, such models may contain expressions to characterize i) the disposition and the target site distribution kinetics of the drug under investigation, ii) the kinetics of target binding and activation and iii) the kinetics of transduction. When connected to physiology-based DS models, PKPD models can characterize the effect on disease progression in a mechanistic manner. These models have been found useful to characterize hysteresis and non-linearity, yet they fail to explain the effects of the other fundamental properties of biological systems behavior. Recently systems pharmacology has been introduced as novel approach to predict in vivo drug effects, in which biological networks rather than single transduction pathways are considered as the basis of drug action and disease progression. These models contain expressions to characterize the functional interactions within a biological network. Such interactions are relevant when drugs act at multiple targets in the network or when homeostatic feedback mechanisms are operative. As a result systems pharmacology models are particularly useful to describe complex patterns of drug action (i.e. synergy, oscillatory behavior) and disease progression (i.e. episodic disorders). In this contribution it is shown how physiology-based PKPD and disease models can be extended to account for internal systems interactions. It is demonstrated how SP models can be used to predict the effects of multi-target interactions and of homeostatic feedback on the pharmacological response. In addition it is shown how DS models may be used to distinguish symptomatic from disease modifying effects and to predict the long term effects on disease progression, from short term biomarker responses. It is concluded that incorporation of expressions to describe the interactions in biological network analysis opens new avenues to the understanding of the effects of drug treatment on the fundamental aspects of biological systems behavior. Copyright © 2016 The Author. Published by Elsevier B.V. All rights reserved.

Global Impact of Oncogenic Src on a Phosphotyrosine Proteome

PubMed Central

Luo, Weifeng; Slebos, Robbert J.; Hill, Salisha; Li, Ming; Brábek, Jan; Amanchy, Ramars; Chaerkady, Raghothama; Pandey, Akhilesh; Ham, Amy-Joan L.; Hanks, Steven K.

2008-01-01

Elevated activity of Src, the first characterized protein-tyrosine kinase, is associated with progression of many human cancers, and Src has attracted interest as a therapeutic target. Src is known to act in various receptor signaling systems to impact cell behavior, yet it remains likely that the spectrum of Src protein substrates relevant to cancer is incompletely understood. To better understand the cellular impact of deregulated Src kinase activity, we extensively applied a mass spectrometry shotgun phosphotyrosine (pTyr) proteomics strategy to obtain global pTyr profiles of Src-transformed mouse fibroblasts as well as their nontransformed counterparts. A total of 867 peptides representing 563 distinct pTyr sites on 374 different proteins were identified from the Src-transformed cells, while 514 peptides representing 275 pTyr sites on 167 proteins were identified from nontransformed cells. Distinct characteristics of the two profiles were revealed by spectral counting, indicative of pTyr site relative abundance, and by complementary quantitative analysis using stable isotope labeling with amino acids in cell culture (SILAC). While both pTyr profiles are replete with sites on signaling and adhesion/cytoskeletal regulatory proteins, the Src-transformed profile is more diverse with enrichment in sites on metabolic enzymes and RNA and protein synthesis and processing machinery. Forty-three pTyr sites (32 proteins) are predicted as major biologically relevant Src targets on the basis of frequent identification in both cell populations. This select group, of particular interest as diagnostic biomarkers, includes well-established Src sites on signaling/adhesion/cytoskeletal proteins, but also uncharacterized sites of potential relevance to the transformed cell phenotype. PMID:18563927

Site-specific O-Glycosylation Analysis of Human Blood Plasma Proteins*

PubMed Central

Hoffmann, Marcus; Marx, Kristina; Reichl, Udo; Wuhrer, Manfred; Rapp, Erdmann

2016-01-01

Site-specific glycosylation analysis is key to investigate structure-function relationships of glycoproteins, e.g. in the context of antigenicity and disease progression. The analysis, though, is quite challenging and time consuming, in particular for O-glycosylated proteins. In consequence, despite their clinical and biopharmaceutical importance, many human blood plasma glycoproteins have not been characterized comprehensively with respect to their O-glycosylation. Here, we report on the site-specific O-glycosylation analysis of human blood plasma glycoproteins. To this end pooled human blood plasma of healthy donors was proteolytically digested using a broad-specific enzyme (Proteinase K), followed by a precipitation step, as well as a glycopeptide enrichment and fractionation step via hydrophilic interaction liquid chromatography, the latter being optimized for intact O-glycopeptides carrying short mucin-type core-1 and -2 O-glycans, which represent the vast majority of O-glycans on human blood plasma proteins. Enriched O-glycopeptide fractions were subjected to mass spectrometric analysis using reversed-phase liquid chromatography coupled online to an ion trap mass spectrometer operated in positive-ion mode. Peptide identity and glycan composition were derived from low-energy collision-induced dissociation fragment spectra acquired in multistage mode. To pinpoint the O-glycosylation sites glycopeptides were fragmented using electron transfer dissociation. Spectra were annotated by database searches as well as manually. Overall, 31 O-glycosylation sites and regions belonging to 22 proteins were identified, the majority being acute-phase proteins. Strikingly, also 11 novel O-glycosylation sites and regions were identified. In total 23 O-glycosylation sites could be pinpointed. Interestingly, the use of Proteinase K proved to be particularly beneficial in this context. The identified O-glycan compositions most probably correspond to mono- and disialylated core-1 mucin-type O-glycans (T-antigen). The developed workflow allows the identification and characterization of the major population of the human blood plasma O-glycoproteome and our results provide new insights, which can help to unravel structure-function relationships. The data were deposited to ProteomeXchange PXD003270. PMID:26598643

10. Freiburger Symposium 2011 der SCG-Division Industrielle Chemie Technology Progress, Success Key for our Production Sites.

PubMed

Naef, Olivier

2012-01-01

This short paper presents the abstracts of the different presentations during 10. Freiburger Symposium 2011 der SCG-Division Industrielle Chemie: Technology Progress, Success key for our production sites held Thursday and Friday, September 29 and 30, 2011 at the Ecole d'ingénieurs et d'architectes de Fribourg (Switzerland).

SEMINAR PUBLICATION: SITE CHARACTERIZATION FOR SUBSURFACE REMEDIATION

EPA Science Inventory

This seminar publication provides a comprehensive approach to site characterization for subsurface remediation. Chapter 1 describes a methodology for integrating site characterization with subsurface remediation. The rest of the handbook is divided into three parts. Part I covers...

Demonstration of innovative monitoring technologies at the Savannah River Integrated Demonstration Site

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

Rossabi, J.; Jenkins, R.A.; Wise, M.B.

1993-12-31

The Department of Energy`s Office of Technology Development initiated an Integrated Demonstration Program at the Savannah River Site in 1989. The objective of this program is to develop, demonstrate, and evaluate innovative technologies that can improve present-day environmental restoration methods. The Integrated Demonstration Program at SRS is entitled ``Cleanup of Organics in Soils and Groundwater at Non-Arid Sites.`` New technologies in the areas of drilling, characterization, monitoring, and remediation are being demonstrated and evaluated for their technical performance and cost effectiveness in comparison with baseline technologies. Present site characterization and monitoring methods are costly, time-consuming, overly invasive, and often imprecise.more » Better technologies are required to accurately describe the subsurface geophysical and geochemical features of a site and the nature and extent of contamination. More efficient, nonintrusive characterization and monitoring techniques are necessary for understanding and predicting subsurface transport. More reliable procedures are also needed for interpreting monitoring and characterization data. Site characterization and monitoring are key elements in preventing, identifying, and restoring contaminated sites. The remediation of a site cannot be determined without characterization data, and monitoring may be required for 30 years after site closure.« less

Afraid to Start Because the Outcome is Uncertain?: Social Site Characterization as a Tool for Informing Public Engagement Efforts

USGS Publications Warehouse

Wade, S.; Greenberg, S.

2009-01-01

This paper introduces the concept of social site characterization as a parallel effort to technical site characterization to be used in evaluating and planning carbon dioxides capture and storage (CCS) projects. Social site characterization, much like technical site characterization, relies on a series of iterative investigations into public attitudes towards a CCS project and the factors that will shape those views. This paper also suggests ways it can be used to design approaches for actively engaging stakeholders and communities in the deployment of CCS projects. This work is informed by observing the site selection process for FutureGen and the implementation of research projects under the Regional Carbon Sequestration Partnership Program. ?? 2009 Elsevier Ltd. All rights reserved.

Multi-Scale Mass Transfer Processes Controlling Natural Attenuation and Engineered Remediation: An IFRC Focused on Hanford’s 300 Area Uranium Plume

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

Zachara, John M.; Bjornstad, Bruce N.; Christensen, John N.

2010-02-01

The Integrated Field-Scale Subsurface Research Challenge (IFRC) at the Hanford Site 300 Area uranium (U) plume addresses multi-scale mass transfer processes in a complex hydrogeologic setting where groundwater and riverwater interact. A series of forefront science questions on mass transfer are posed for research which relate to the effect of spatial heterogeneities; the importance of scale; coupled interactions between biogeochemical, hydrologic, and mass transfer processes; and measurements and approaches needed to characterize and model a mass-transfer dominated system. The project was initiated in February 2007, with CY 2007 and CY 2008 progress summarized in preceding reports. The site has 35more » instrumented wells, and an extensive monitoring system. It includes a deep borehole for microbiologic and biogeochemical research that sampled the entire thickness of the unconfined 300 A aquifer. Significant, impactful progress has been made in CY 2009 with completion of extensive laboratory measurements on field sediments, field hydrologic and geophysical characterization, four field experiments, and modeling. The laboratory characterization results are being subjected to geostatistical analyses to develop spatial heterogeneity models of U concentration and chemical, physical, and hydrologic properties needed for reactive transport modeling. The field experiments focused on: (1) physical characterization of the groundwater flow field during a period of stable hydrologic conditions in early spring, (2) comprehensive groundwater monitoring during spring to characterize the release of U(VI) from the lower vadose zone to the aquifer during water table rise and fall, (3) dynamic geophysical monitoring of salt-plume migration during summer, and (4) a U reactive tracer experiment (desorption) during the fall. Geophysical characterization of the well field was completed using the down-well Electrical Resistance Tomography (ERT) array, with results subjected to robust, geostatistically constrained inversion analyses. These measurements along with hydrologic characterization have yielded 3D distributions of hydraulic properties that have been incorporated into an updated and increasingly robust hydrologic model. Based on significant findings from the microbiologic characterization of deep borehole sediments in CY 2008, down-hole biogeochemistry studies were initiated where colonization substrates and spatially discrete water and gas samplers were deployed to select wells. The increasingly comprehensive field experimental results, along with the field and laboratory characterization, are leading to a new conceptual model of U(VI) flow and transport in the IFRC footprint and the 300 Area in general, and insights on the microbiological community and associated biogeochemical processes. A significant issue related to vertical flow in the IFRC wells was identified and evaluated during the spring and fall field experimental campaigns. Both upward and downward flows were observed in response to dynamic Columbia River stage. The vertical flows are caused by the interaction of pressure gradients with our heterogeneous hydraulic conductivity field. These impacts are being evaluated with additional modeling and field activities to facilitate interpretation and mitigation. The project moves into CY 2010 with ambitious plans for a drilling additional wells for the IFRC well field, additional experiments, and modeling. This research is part of the ERSP Hanford IFRC at Pacific Northwest National Laboratory.« less

The Wernicke conundrum and the anatomy of language comprehension in primary progressive aphasia

PubMed Central

Thompson, Cynthia K.; Weintraub, Sandra; Rogalski, Emily J.

2015-01-01

Wernicke’s aphasia is characterized by severe word and sentence comprehension impairments. The location of the underlying lesion site, known as Wernicke’s area, remains controversial. Questions related to this controversy were addressed in 72 patients with primary progressive aphasia who collectively displayed a wide spectrum of cortical atrophy sites and language impairment patterns. Clinico-anatomical correlations were explored at the individual and group levels. These analyses showed that neuronal loss in temporoparietal areas, traditionally included within Wernicke’s area, leave single word comprehension intact and cause inconsistent impairments of sentence comprehension. The most severe sentence comprehension impairments were associated with a heterogeneous set of cortical atrophy sites variably encompassing temporoparietal components of Wernicke’s area, Broca’s area, and dorsal premotor cortex. Severe comprehension impairments for single words, on the other hand, were invariably associated with peak atrophy sites in the left temporal pole and adjacent anterior temporal cortex, a pattern of atrophy that left sentence comprehension intact. These results show that the neural substrates of word and sentence comprehension are dissociable and that a circumscribed cortical area equally critical for word and sentence comprehension is unlikely to exist anywhere in the cerebral cortex. Reports of combined word and sentence comprehension impairments in Wernicke’s aphasia come almost exclusively from patients with cerebrovascular accidents where brain damage extends into subcortical white matter. The syndrome of Wernicke’s aphasia is thus likely to reflect damage not only to the cerebral cortex but also to underlying axonal pathways, leading to strategic cortico-cortical disconnections within the language network. The results of this investigation further reinforce the conclusion that the left anterior temporal lobe, a region ignored by classic aphasiology, needs to be inserted into the language network with a critical role in the multisynaptic hierarchy underlying word comprehension and object naming. PMID:26112340

The Wernicke conundrum and the anatomy of language comprehension in primary progressive aphasia.

PubMed

Mesulam, M-Marsel; Thompson, Cynthia K; Weintraub, Sandra; Rogalski, Emily J

2015-08-01

Wernicke's aphasia is characterized by severe word and sentence comprehension impairments. The location of the underlying lesion site, known as Wernicke's area, remains controversial. Questions related to this controversy were addressed in 72 patients with primary progressive aphasia who collectively displayed a wide spectrum of cortical atrophy sites and language impairment patterns. Clinico-anatomical correlations were explored at the individual and group levels. These analyses showed that neuronal loss in temporoparietal areas, traditionally included within Wernicke's area, leave single word comprehension intact and cause inconsistent impairments of sentence comprehension. The most severe sentence comprehension impairments were associated with a heterogeneous set of cortical atrophy sites variably encompassing temporoparietal components of Wernicke's area, Broca's area, and dorsal premotor cortex. Severe comprehension impairments for single words, on the other hand, were invariably associated with peak atrophy sites in the left temporal pole and adjacent anterior temporal cortex, a pattern of atrophy that left sentence comprehension intact. These results show that the neural substrates of word and sentence comprehension are dissociable and that a circumscribed cortical area equally critical for word and sentence comprehension is unlikely to exist anywhere in the cerebral cortex. Reports of combined word and sentence comprehension impairments in Wernicke's aphasia come almost exclusively from patients with cerebrovascular accidents where brain damage extends into subcortical white matter. The syndrome of Wernicke's aphasia is thus likely to reflect damage not only to the cerebral cortex but also to underlying axonal pathways, leading to strategic cortico-cortical disconnections within the language network. The results of this investigation further reinforce the conclusion that the left anterior temporal lobe, a region ignored by classic aphasiology, needs to be inserted into the language network with a critical role in the multisynaptic hierarchy underlying word comprehension and object naming. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

SITE CHARACTERIZATION LIBRARY: VOLUMN 1 (RELEASE 2.5)

EPA Science Inventory

This CD-ROM, Volume 1, Release 2.5, of EPA's National Exposure Research Laboratory (NERL - Las Vegas) Site Characterization Library, contains additional electronic documents and computer programs related to the characterization of hazardous waste sites. EPA has produced this libr...

Seasonal dynamics of light absorption by chromophoric dissolved organic matter (CDOM) in the NW Mediterranean Sea (BOUSSOLE site)

NASA Astrophysics Data System (ADS)

Organelli, Emanuele; Bricaud, Annick; Antoine, David; Matsuoka, Atsushi

2014-09-01

We analyze a two-year time-series of chromophoric dissolved organic matter (CDOM) light absorption measurements in the upper 400 m of the water column at the BOUSSOLE site in the NW Mediterranean Sea. The seasonal dynamics of the CDOM light absorption coefficients at 440 nm (acdom(440)) is essentially characterized by (i) subsurface maxima forming in spring and progressively reinforcing throughout summer, (ii) impoverishment in the surface layer throughout summer and (iii) vertical homogeneity in winter. Seasonal variations of the spectral dependence of CDOM absorption, as described by the exponential slope value (Scdom), are characterized by highest values in summer and autumn at the surface and low values at the depths of acdom(440) subsurface maxima or just below them. Variations of acdom(440) are likely controlled by microbial digestion of phytoplankton cells, which leads to CDOM production, and by photochemical destruction (photobleaching), which leads to CDOM degradation. Photobleaching is also the main driver of Scdom variations. Consistently with previous observations, acdom(440) for a given chlorophyll a concentration is higher than expected from Case I waters bio-optical models. The total non-water light absorption budget shows that surface waters at the BOUSSOLE site are largely dominated by CDOM during all seasons but the algal bloom in March and April. These results improve the knowledge of CDOM absorption dynamics in the Mediterranean Sea, which is scarcely documented. In addition, they open the way to improved algorithms for the retrieval of CDOM absorption from field or satellite radiometric measurements.

Multiscale characterization of the mineral phase at skeletal sites of breast cancer metastasis.

PubMed

He, Frank; Chiou, Aaron E; Loh, Hyun Chae; Lynch, Maureen; Seo, Bo Ri; Song, Young Hye; Lee, Min Joon; Hoerth, Rebecca; Bortel, Emely L; Willie, Bettina M; Duda, Georg N; Estroff, Lara A; Masic, Admir; Wagermaier, Wolfgang; Fratzl, Peter; Fischbach, Claudia

2017-10-03

Skeletal metastases, the leading cause of death in advanced breast cancer patients, depend on tumor cell interactions with the mineralized bone extracellular matrix. Bone mineral is largely composed of hydroxyapatite (HA) nanocrystals with physicochemical properties that vary significantly by anatomical location, age, and pathology. However, it remains unclear whether bone regions typically targeted by metastatic breast cancer feature distinct HA materials properties. Here we combined high-resolution X-ray scattering analysis with large-area Raman imaging, backscattered electron microscopy, histopathology, and microcomputed tomography to characterize HA in mouse models of advanced breast cancer in relevant skeletal locations. The proximal tibial metaphysis served as a common metastatic site in our studies; we identified that in disease-free bones this skeletal region contained smaller and less-oriented HA nanocrystals relative to ones that constitute the diaphysis. We further observed that osteolytic bone metastasis led to a decrease in HA nanocrystal size and perfection in remnant metaphyseal trabecular bone. Interestingly, in a model of localized breast cancer, metaphyseal HA nanocrystals were also smaller and less perfect than in corresponding bone in disease-free controls. Collectively, these results suggest that skeletal sites prone to tumor cell dissemination contain less-mature HA (i.e., smaller, less-perfect, and less-oriented crystals) and that primary tumors can further increase HA immaturity even before secondary tumor formation, mimicking alterations present during tibial metastasis. Engineered tumor models recapitulating these spatiotemporal dynamics will permit assessing the functional relevance of the detected changes to the progression and treatment of breast cancer bone metastasis.

Multiscale characterization of the mineral phase at skeletal sites of breast cancer metastasis

PubMed Central

Chiou, Aaron E.; Loh, Hyun Chae; Lynch, Maureen; Seo, Bo Ri; Song, Young Hye; Hoerth, Rebecca; Bortel, Emely L.; Willie, Bettina M.; Duda, Georg N.; Masic, Admir; Wagermaier, Wolfgang; Fratzl, Peter; Fischbach, Claudia

2017-01-01

Skeletal metastases, the leading cause of death in advanced breast cancer patients, depend on tumor cell interactions with the mineralized bone extracellular matrix. Bone mineral is largely composed of hydroxyapatite (HA) nanocrystals with physicochemical properties that vary significantly by anatomical location, age, and pathology. However, it remains unclear whether bone regions typically targeted by metastatic breast cancer feature distinct HA materials properties. Here we combined high-resolution X-ray scattering analysis with large-area Raman imaging, backscattered electron microscopy, histopathology, and microcomputed tomography to characterize HA in mouse models of advanced breast cancer in relevant skeletal locations. The proximal tibial metaphysis served as a common metastatic site in our studies; we identified that in disease-free bones this skeletal region contained smaller and less-oriented HA nanocrystals relative to ones that constitute the diaphysis. We further observed that osteolytic bone metastasis led to a decrease in HA nanocrystal size and perfection in remnant metaphyseal trabecular bone. Interestingly, in a model of localized breast cancer, metaphyseal HA nanocrystals were also smaller and less perfect than in corresponding bone in disease-free controls. Collectively, these results suggest that skeletal sites prone to tumor cell dissemination contain less-mature HA (i.e., smaller, less-perfect, and less-oriented crystals) and that primary tumors can further increase HA immaturity even before secondary tumor formation, mimicking alterations present during tibial metastasis. Engineered tumor models recapitulating these spatiotemporal dynamics will permit assessing the functional relevance of the detected changes to the progression and treatment of breast cancer bone metastasis. PMID:28923958

71. ARAII. Construction progress at SL1 site near end of ...

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

71. ARA-II. Construction progress at SL-1 site near end of 1957. Buildings from right to left are guard house, support building, reactor building, water tank and pump house. Construction was 23 percent complete. December 20, 1957. Ineel photo no. 57-6224. Photographer: Jack L. Anderson. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

75 FR 3483 - Notice of Availability of the Draft Site Progress Report to the World Heritage Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-21

... Report to the World Heritage Committee, Yellowstone National Park AGENCY: National Park Service, Interior. ACTION: Notice of Availability of the Draft Site Progress Report to the World Heritage Committee... World Heritage Committee (Documents WHC-03/72.COM/ 7A.12, WHC 32.COM.7B.39) accepted by the [[Page 3484...

Changes in lead and zinc lability during weathering-induced acidification of desert mine tailings: Coupling chemical and micro-scale analyses.

PubMed

Hayes, Sarah M; White, Scott A; Thompson, Thomas L; Maier, Raina M; Chorover, Jon

2009-12-01

Desert mine tailings may accumulate toxic metals in the near surface centimeters because of low water through-flux rates. Along with other constraints, metal toxicity precludes natural plant colonization even over decadal time scales. Since unconsolidated particles can be subjected to transport by wind and water erosion, potentially resulting in direct human and ecosystem exposure, there is a need to know how the lability and form of metals change in the tailings weathering environment. A combination of chemical extractions, X-ray diffraction, micro-X-ray fluorescence spectroscopy, and micro-Raman spectroscopy were employed to study Pb and Zn contamination in surficial arid mine tailings from the Arizona Klondyke State Superfund Site. Initial site characterization indicated a wide range in pH (2.5 to 8.0) in the surficial tailings pile. Ligand-promoted (DTPA) extractions, used to assess plant-available metal pools, showed decreasing available Zn and Mn with progressive tailings acidification. Aluminum shows the inverse trend, and Pb and Fe show more complex pH dependence. Since the tailings derive from a common source and parent mineralogy, it is presumed that variations in pH and "bioavailable" metal concentrations result from associated variation in particle-scale geochemistry. Four sub-samples, ranging in pH from 2.6 to 5.4, were subjected to further characterization to elucidate micro-scale controls on metal mobility. With acidification, total Pb (ranging from 5 - 13 g kg(-1)) was increasingly associated with Fe and S in plumbojarosite aggregates. For Zn, both total (0.4 - 6 g kg(-1)) and labile fractions decreased with decreasing pH. Zinc was found to be primarily associated with the secondary Mn phases manjiroite and chalcophanite. The results suggest that progressive tailings acidification diminishes the overall lability of the total Pb and Zn pools.

Changes in lead and zinc lability during weathering-induced acidification of desert mine tailings: Coupling chemical and micro-scale analyses

PubMed Central

Hayes, Sarah M.; White, Scott A.; Thompson, Thomas L.; Maier, Raina M.; Chorover, Jon

2009-01-01

Desert mine tailings may accumulate toxic metals in the near surface centimeters because of low water through-flux rates. Along with other constraints, metal toxicity precludes natural plant colonization even over decadal time scales. Since unconsolidated particles can be subjected to transport by wind and water erosion, potentially resulting in direct human and ecosystem exposure, there is a need to know how the lability and form of metals change in the tailings weathering environment. A combination of chemical extractions, X-ray diffraction, micro-X-ray fluorescence spectroscopy, and micro-Raman spectroscopy were employed to study Pb and Zn contamination in surficial arid mine tailings from the Arizona Klondyke State Superfund Site. Initial site characterization indicated a wide range in pH (2.5 to 8.0) in the surficial tailings pile. Ligand-promoted (DTPA) extractions, used to assess plant-available metal pools, showed decreasing available Zn and Mn with progressive tailings acidification. Aluminum shows the inverse trend, and Pb and Fe show more complex pH dependence. Since the tailings derive from a common source and parent mineralogy, it is presumed that variations in pH and “bioavailable” metal concentrations result from associated variation in particle-scale geochemistry. Four sub-samples, ranging in pH from 2.6 to 5.4, were subjected to further characterization to elucidate micro-scale controls on metal mobility. With acidification, total Pb (ranging from 5 – 13 g kg−1) was increasingly associated with Fe and S in plumbojarosite aggregates. For Zn, both total (0.4 – 6 g kg−1) and labile fractions decreased with decreasing pH. Zinc was found to be primarily associated with the secondary Mn phases manjiroite and chalcophanite. The results suggest that progressive tailings acidification diminishes the overall lability of the total Pb and Zn pools. PMID:20161492

Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses.

PubMed

Kim, S B; Bozeman, R G; Kaisani, A; Kim, W; Zhang, L; Richardson, J A; Wright, W E; Shay, J W

2016-06-30

Proton radiotherapy is becoming more common as protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared with conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole-body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIRs), which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence-associated gene (P19Arf), are markedly increased. Following these changes, loss of Casein kinase Iα and induction of chronic DNA damage and TP53 mutations are increased compared with X-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-ethyl amide (CDDO-EA), reduces proton irradiation-associated SIR and tumorigenesis. Thus exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA.

Novel Immunotherapies for Autoimmune Hepatitis

PubMed Central

Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

2017-01-01

Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4+ T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects. PMID:28184367

Spatial Distribution of Coffee Wilt Disease Under Roguing and Replanting Conditions: A Case Study from Kaweri Estate in Uganda.

PubMed

Pinard, F; Makune, S E; Campagne, P; Mwangi, J

2016-11-01

Based on time and spatial dynamic considerations, this study evaluates the potential role of short- and long-distance dispersal in the spread of coffee wilt disease (CWD) in a large commercial Robusta coffee estate in Uganda (Kaweri, 1,755 ha) over a 4-year period (2008 to 2012). In monthly surveys, total disease incidence, expansion of infection foci, and the occurrence of isolated infected trees were recorded and submitted to spatial analysis. Incidence was higher and disease progression faster in old coffee plantings compared with young plantings, indicating a lack of efficiency of roguing for reducing disease development in old plantings. At large spatial scale (approximately 1 km), Moran indices (both global and local) revealed the existence of clusters characterized by contrasting disease incidences. This suggested that local environmental conditions were heterogeneous or there were spatial interactions among blocks. At finer spatial scale (approximately 200 m), O-ring statistics revealed positive correlation between distant infection sites across distances as great as 60 m. Although these observations indicate the role of short-distance dispersal in foci expansion, dispersal at greater distances (>20 m) appeared to also contribute to both initiation of new foci and disease progression at coarser spatial scales. Therefore, our results suggested the role of aerial dispersal in CWD progression.

A systematic assessment of the state of hazardous waste clean-up technologies. Quarterly technical progress report, April 1--June 30, 1993

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

Berg, M.T.; Reed, B.E.; Gabr, M.

1993-07-01

West Virginia University (WVU) and the US DOE Morgantown Energy Technology Center (METC) entered into a Cooperative Agreement on August 29, 1992 entitled ``Decontamination Systems Information and Research Programs.`` Stipulated within the Agreement is the requirement that WVU submit to METC a series of Technical Progress Report for Year 1 of the Agreement. This report reflects the progress and/or efforts performed on the following nine technical projects encompassed by the Year 1 Agreement for the period of April 1 through June 30, 1993: Systematic assessment of the state of hazardous waste clean-up technologies; site remediation technologies -- drain-enhanced soil flushingmore » (DESF) for organic contaminants removal; site remediation technologies -- in situ bioremediation of organic contaminants; excavation systems for hazardous waste sites; chemical destruction of polychlorinated biphenyls; development of organic sensors -- monolayer and multilayer self-assembled films for chemical sensors; Winfield lock and dam remediation; Assessments of Technologies for hazardous waste site remediation -- non-treatment technologies and pilot scale test facility implementation; and remediation of hazardous sites with stream reforming.« less

Measurement Sets and Sites Commonly Used for Characterization

NASA Technical Reports Server (NTRS)

Pagnutti, Mary; Holekamp, Kara; Ryan, Robert; Sellers, Richard; Davis, Bruce; Zanoni, Vicki

2002-01-01

Scientists at NASA's Earth Science Applications Directorate are creating a well-characterized Verification & Validation (V&V) site at the Stennis Space Center. This site enables the in-flight characterization of remote sensing systems and the data they acquire. The data are predominantly acquired by commercial, high spatial resolution satellite systems, such as IKONOS and QuickBird 2, and airborne systems. The smaller scale of these newer high resolution remote sensing systems allows scientists to characterize the geometric, spatial, and radiometric data properties using a single V&V site. The targets and techniques used to characterize data from these newer systems can differ significantly from the techniques used to characterize data from the earlier, coarser spatial resolution systems. Scientists are also using the SSC V&V site to characterize thermal infrared systems and active LIDAR systems. SSC employs geodetic targets, edge targets, radiometric tarps, and thermal calibration ponds to characterize remote sensing data products. This paper presents a proposed set of required measurements for visible through long-wave infrared remote sensing systems and a description of the Stennis characterization. Other topics discussed include: 1) The use of ancillary atmospheric and solar measurements taken at SSC that support various characterizations; 2) Additional sites used for radiometric, geometric, and spatial characterization in the continental United States; 3) The need for a standardized technique to be adopted by CEOS and other organizations.

Structural Characterization of the 1918 Influenza H1N1 Neuraminidase

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

Xu, X.; Zhu, X.; Dwek, R.A.

2009-05-28

Influenza virus neuraminidase (NA) plays a crucial role in facilitating the spread of newly synthesized virus in the host and is an important target for controlling disease progression. The NA crystal structure from the 1918 'Spanish flu' (A/Brevig Mission/1/18 H1N1) and that of its complex with zanamivir (Relenza) at 1.65-{angstrom} and 1.45-{angstrom} resolutions, respectively, corroborated the successful expression of correctly folded NA tetramers in a baculovirus expression system. An additional cavity adjacent to the substrate-binding site is observed in N1, compared to N2 and N9 NAs, including H5N1. This cavity arises from an open conformation of the 150 loop (Gly147more » to Asp151) and appears to be conserved among group 1 NAs (N1, N4, N5, and N8). It closes upon zanamivir binding. Three calcium sites were identified, including a novel site that may be conserved in N1 and N4. Thus, these high-resolution structures, combined with our recombinant expression system, provide new opportunities to augment the limited arsenal of therapeutics against influenza.« less

Shape and site dependent in vivo degradation of Mg-Zn pins in rabbit femoral condyle.

PubMed

Han, Pei; Tan, Moyan; Zhang, Shaoxiang; Ji, Weiping; Li, Jianan; Zhang, Xiaonong; Zhao, Changli; Zheng, Yufeng; Chai, Yimin

2014-02-20

A type of specially designed pin model of Mg-Zn alloy was implanted into the full thickness of lesions of New Zealand rabbits' femoral condyles. The recovery progress, outer surface healing and in vivo degradation were characterized by various methods including radiographs, Micro-CT scan with surface rendering, SEM (scanning electron microscope) with EDX (Energy Dispersive X-ray analysis) and so on. The in vivo results suggested that a few but not sufficient bridges for holding force were formed between the bone and the implant if there was a preexisting gap between them. The rapid degradation of the implantation in the condyle would result in the appearance of cavities. Morphological evaluation of the specially designed pins indicated that the cusp was the most vulnerable part during degradation. Furthermore, different implantation sites with distinct components and biological functions can lead to different degradation rates of Mg-Zn alloy. The rate of Mg-Zn alloy decreases in the following order: implantation into soft tissue, less trabecular bone, more trabecular bone, and cortical bone. Because of the complexities of in vivo degradation, it is necessary for the design of biomedical Mg-Zn devices to take into consideration the implantation sites used in clinics.

Polaron-mediated surface reconstruction in the reduced Rutile TiO2 (110) surface

NASA Astrophysics Data System (ADS)

Reticcioli, Michele; Setvin, Martin; Hao, Xianfeng; Diebold, Ulrike; Franchini, Cesare

The role of polarons is of key importance for the understanding of the fundamental properties and functionalities of TiO2. We use density functional theory with an on-site Coulomb interaction and molecular dynamics to study the formation and dynamics of small polarons in the reduced rutile (110) surface. We show that excess electrons donated by oxygen-vacancies (VO) form mobile small polarons that hop easily in subsurface and surface Ti-sites. The polaron formation becomes more favorable by increasing the VO concentration level (up to 20%) due to the progressively lower energy cost needed to distort the lattice. However, at higher VO concentration the shortening of the averaged polaron-polaron distance leads to an increased Coulomb repulsion among the trapped charges at the Ti-sites, which weakens this trend. This instability is overtaken by means of a structural 1 × 2 surface reconstruction, characterized by a distinctively more favorable polaron distribution. The calculations are validated by a direct comparison with experimental AFM and STM data. Our study identifies a fundamentally novel mechanism to drive surface reconstructions and resolves a long standing issue on the origin of the reconstruction in rutile (110) surface.

40 CFR 62.14356 - Compliance schedules and increments of progress.

Code of Federal Regulations, 2011 CFR

2011-07-01

... POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills That Commenced Construction Prior to...) to initiate on-site construction or initiate on-site installation of emission collection and/or control equipment. (3) Initiate on-site construction: Initiate on-site construction or initiate on-site...

40 CFR 62.14356 - Compliance schedules and increments of progress.

Code of Federal Regulations, 2013 CFR

2013-07-01

... POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills That Commenced Construction Prior to...) to initiate on-site construction or initiate on-site installation of emission collection and/or control equipment. (3) Initiate on-site construction: Initiate on-site construction or initiate on-site...

Frasier syndrome with childhood-onset renal failure.

PubMed

Buzi, F; Mella, P; Pilotta, A; Felappi, B; Camerino, G; Notarangelo, L D

2001-01-01

The Wilms' tumour 1 (WT1) gene encodes a protein which is believed to exert transcriptional and tumour-suppressor activities. Mutations of this gene have occasionally been associated with Wilms' tumour (<15% of cases) and, more consistently, with three syndromes characterized by urogenital abnormalities (WAGR, Denys-Drash and Frasier syndrome). SUBJECT/METHOD: A 25-year-old phenotypic female with a 46,XY karyotype presented with amenorrhoea. An ultrasound scan showed streak gonads and a rudimentary uterus. The patient had a history of post-streptococcal glomerulonephrosis, when aged 4 years, which had rapidly progressed to kidney failure, requiring transplantation at age 8. Frasier syndrome was suspected and confirmed by genetic analysis. In fact, direct sequencing of the PCR product of the intron 9 donor splice site revealed a substitution of guanine for adenine in position +5. Besides being one of the few Frasier syndrome cases to be genetically characterized, this case is interesting because of the unusually early-onset renal failure. Copyright 2001 S. Karger AG, Basel

In vitro characterizations of mesoporous hydroxyapatite as a controlled release delivery device for VEGF in orthopedic applications.

PubMed

Poh, Chye Khoon; Ng, Suxiu; Lim, Tee Yong; Tan, Hark Chuan; Loo, Joachim; Wang, Wilson

2012-11-01

Following bone implant surgery, prolonged ischemic conditions at the implant site often result in postsurgical complications like failure of osseointegration at the bone-implant interface which can lead to implant failure. Thus, restoration of the vascular supply is paramount to the proper development of the bone. High surface area mesostructured materials have been shown to be attractive candidates for bone regeneration to enhance cell adhesion and cell proliferation. This study uses hydroxyapatite, a naturally occurring mineral in the bone, fabricated to a range of suitable pore sizes, infused with vascular endothelial growth factor (VEGF), to be progressively released to stimulate revascularization. In this study, several characterizations including nitrogen adsorption analysis, Fourier-transformed infrared spectroscopy, X-ray diffraction, field emission scanning electron microscope, and transmission electron microscope were used to evaluate the synthesized mesoporous hydroxyapatite (MHA). The results showed that MHA can gradually release VEGF for enhancing revascularization, which is beneficial for orthopedic applications. Copyright © 2012 Wiley Periodicals, Inc.

Gulf Coast Salt Domes geologic Area Characterization Report, East Texas Study Area. Volume II. Technical report. [Contains glossary of geological terms; Oakwood, Keechi, and Palestine domes

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

Not Available

1982-07-01

The East Texas Area Characterization Report (ACR) is a compilation of data gathered during the Area Characterization phase of the Department of Energy's National Waste Terminal Storage program in salt. The characterization of Gulf Coast Salt Domes as a potential site for storage of nuclear waste is an ongoing process. This report summarizes investigations covering an area of approximately 2590 km/sup 2/ (1000 mi/sup 2/). Data on Oakwood, Keechi, and Palestine Domes are given. Subsequent phases of the program will focus on smaller land areas and fewer specific salt domes, with progressively more detailed investigations, possibly culminating with a licensemore » application to the Nuclear Regulatory Commission. The data in this report are a result of drilling and sampling, geophysical and geologic field work, and intensive literature review. The ACR contains text discussing data usage, interpretations, results and conclusions based on available geologic and hydrologic data, and figures including diagrams showing data point locations, geologic and hydrologic maps, geologic cross sections, and other geologic and hydrologic information. An appendix contains raw data gathered during this phase of the project and used in the preparation of these reports.« less

Characterization and Disposition of Legacy Low-Level Waste at the Y-12 National Security Complex - 12133

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

Tharp, Tim; Donnelly, Jim

2012-07-01

The Y-12 National Security Complex (Y-12) is concluding a multi-year program to characterize and dispose of all legacy low-level waste (LLW). The inventory of legacy waste at Y-12 has been reduced from over 3500 containers in Fiscal Year (FY) 2000 to 6 containers at the end of FY2011. In addition, the site recently eliminated the inventory of other low-level waste that is greater than 365 days old (i.e., >365-Day LLW), to be in full compliance with DOE Order 435.1. A consistent technical characterization approach emerged for both of these populations of backlogged waste: (1) compile existing historical data and processmore » knowledge and conduct interviews with site personnel; (2) inspect the containers and any tags, labels, or other markings to confirm or glean additional data; (3) with appropriate monitoring, open the container, visually inspect and photograph the contents while obtaining preliminary radiological surveys; (4) obtain gross weight and field non-destructive assay (NDA) data as needed; (5) use the non-public Oak Ridge Reservation Haul Road to ship the container to a local offsite vendor for waste sorting and segregation; (6) sort, drain, sample, and remove prohibited items; and (7) compile final data and prepare for shipment to disposal. After disposing of this backlog, the focus has now turned to avoiding the recurrence of this situation by maintaining low inventories of low-level waste and shortening the duration between waste generation and disposal. An enhanced waste tracking system and monthly metric charts are used to monitor and report progress to contractor and federal site office management. During the past 2 years, the average age of LLW onsite at Y-12 has decreased from more than 180 days to less than 60 days. (authors)« less

FIELD EVALUATION OF IN-SITU BIODEGRADATION OF CHLORINATED ETHENES: PART I, METHODOLOGY AND FIELD SITE CHARACTERIZATION

EPA Science Inventory

Careful site characterization and implementation of quantitative monitoring methods are prerequisites for a convincing evaluation of enhanced biostimulation for aquifer restoration. his paper describes the characterization of a site at Moffett Naval Air Station, Mountain View, Ca...

SITE CHARACTERIZATION AND ANALYSIS PENETROMETER SYSTEM(SCAPS) LAZER-INDUCED FLUORESCENCE (LIF) SENSOR AND SUPPORT SYSTEM

EPA Science Inventory

The Consortium for Site Characterization Technology (CSCT) has established a formal program to accelerate acceptance and application of innovative monitoring and site characterization technologies that improve the way the nation manages its environmental problems. In 1995 the CS...

Importance of geologic characterization of potential low-level radioactive waste disposal sites

USGS Publications Warehouse

Weibel, C.P.; Berg, R.C.

1991-01-01

Using the example of the Geff Alternative Site in Wayne County, Illinois, for the disposal of low-level radioactive waste, this paper demonstrates, from a policy and public opinion perspective, the importance of accurately determining site stratigraphy. Complete and accurate characterization of geologic materials and determination of site stratigraphy at potential low-level waste disposal sites provides the frame-work for subsequent hydrologic and geochemical investigations. Proper geologic characterization is critical to determine the long-term site stability and the extent of interactions of groundwater between the site and its surroundings. Failure to adequately characterize site stratigraphy can lead to the incorrect evaluation of the geology of a site, which in turn may result in a lack of public confidence. A potential problem of lack of public confidence was alleviated as a result of the resolution and proper definition of the Geff Alternative Site stratigraphy. The integrity of the investigation was not questioned and public perception was not compromised. ?? 1991 Springer-Verlag New York Inc.

Deep inferior epigastric artery perforator flap donor-site closure with cannula-assisted, limited undermining, and progressive high-tension sutures versus standard abdominoplasty: complications, sensitivity, and cosmetic outcomes.

PubMed

Visconti, Giuseppe; Tomaselli, Federica; Monda, Anna; Barone-Adesi, Liliana; Salgarello, Marzia

2015-01-01

In deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, abdominal donor-site cosmetic and sensibility outcomes and the closure technique have drawn little attention in the literature, with many surgeons still following the principles of standard abdominoplasty. In this article, the authors report their experience with the cannula-assisted, limited undermining, and progressive high-tension suture ("CALP") technique of DIEP donor-site closure compared with standard abdominoplasty. Between December of 2008 and January of 2013, 137 consecutive women underwent DIEP flap breast reconstruction. Of these, 82 patients (between December of 2008 and November of 2011) underwent DIEP flap donor-site closure by means of standard abdominoplasty (control group) and 55 patients (from December of 2011 to January of 2013) by means of cannula-assisted, limited undermining, and progressive high-tension suture (study group). The abdominal drainage daily output, donor-site complications, abdominal skin sensitivity at 1-year follow-up, cosmetic outcomes, and patient satisfaction were recorded and analyzed statistically. Daily drainage output was significantly lower in the study group. Donor-site complications were significantly higher in the control group (37.8 percent versus 9 percent). Seroma and wound healing problems were experienced in the control group. Abdominal skin sensibility was better preserved in the study group. Overall, abdominal wall aesthetic outcomes were similar in both groups, except for scar quality (better in the study group). According to the authors' experience, cannula-assisted, limited undermining, and progressive high-tension suture should be always preferred to standard abdominoplasty for DIEP donor-site closure to reduce the complication rate to improve abdominal skin sensitivity and scar quality. Therapeutic, II.

A FIELD EVALUATION OF IN-SITU BIODEGRADATION OF CHLORINATED ETHENES: PART I, METHODOLOGY AND FIELD SITE CHARACTERIZATION

EPA Science Inventory

Careful site characterization and implementation of quantitative monitoring methods are prerequisites for a convincing evaluation of enhanced biostimulation for aquifer restoration. This paper describes the characterization of a site at Moffett Naval Air Station, Mountain View, C...

10 CFR 60.16 - Site characterization plan required.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Site characterization plan required. 60.16 Section 60.16 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES Licenses Preapplication Review § 60.16 Site characterization plan required. Before proceeding to...

Measurement Sets and Sites Commonly used for Characterizations

NASA Technical Reports Server (NTRS)

Pagnutti, Mary; Holekamp, Kara; Ryan, Robert; Blonski, Slawomir; Sellers, Richard; Davis, Bruce; Zanoni, Vicki

2002-01-01

Scientists with NASA's Earth Science Applications Directorate are creating a well-characterized Verification & Validation (V&V) site at the Stennis Space Center (SSC). This site enables the in-flight characterization of remote sensing systems and the data that they require. The data are predominantly acquired by commercial, high-spatial resolution satellite systems, such as IKONOS and QuickBird 2, and airborne systems. The smaller scale of these newer high-resolution remote sensing systems allows scientists to characterize the geometric, spatial, and radiometric data properties using a single V&V site. The targets and techniques used to characterize data from these newer systems can differ significantly from the earlier, coarser spatial resolution systems. Scientists are also using the SSC V&V site to characterize thermal infrared systems and active Light Detection and Ranging (LIDAR) systems. SSC employs geodetic targets, edge targets, radiometric tarps, and thermal calibration ponds to characterize remote sensing data products. This paper presents a proposed set of required measurements for visible-through-longwave infrared remote sensing systems, and a description of the Stennis characterization. Other topics discussed inslude: 1) use of ancillary atmospheric and solar measurements taken at SSC that support various characterizations, 2) other sites used for radiometric, geometric, and spatial characterization in the continental United States,a nd 3) the need for a standardized technique to be adopted by the Committee on Earth Observation Satellites (CEOS) and other organizations.

Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases.

PubMed

Loriot, Y; Pagliaro, L; Fléchon, A; Mardiak, J; Geoffrois, L; Kerbrat, P; Chevreau, C; Delva, R; Rolland, F; Theodore, C; Roubaud, G; Gravis, G; Eymard, J C; Malhaire, J P; Linassier, C; Habibian, M; Martin, A L; Journeau, F; Reckova, M; Logothetis, C; Laplanche, A; Le Teuff, G; Culine, S; Fizazi, K

2017-12-01

The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of New Otic Enhancers of the Pou3f4 Gene Reveal Distinct Signaling Pathway Regulation and Spatio-Temporal Patterns

PubMed Central

Robert-Moreno, Àlex; Naranjo, Silvia; de la Calle-Mustienes, Elisa; Gómez-Skarmeta, José Luis; Alsina, Berta

2010-01-01

POU3F4 is a member of the POU-homedomain transcription factor family with a prominent role in inner ear development. Mutations in the human POU3F4 coding unit leads to X-linked deafness type 3 (DFN3), characterized by conductive hearing loss and progressive sensorineural deafness. Microdeletions found 1 Mb 5′ upstream of the coding region also displayed the same phenotype, suggesting that cis-regulatory elements might be present in that region. Indeed, we and others have recently identified several enhancers at the 1 Mb 5′ upstream interval of the pou3f4 locus. Here we characterize the spatio-temporal patterns of these regulatory elements in zebrafish transgenic lines. We show that the most distal enhancer (HCNR 81675) is activated earlier and drives GFP reporter expression initially to a broad ear domain to progressively restrict to the sensory patches. The proximal enhancer (HCNR 82478) is switched later during development and promotes expression, among in other tissues, in sensory patches from its onset. The third enhancer (HCNR 81728) is also active at later stages in the otic mesenchyme and in the otic epithelium. We also characterize the signaling pathways regulating these enhancers. While HCNR 81675 is regulated by very early signals of retinoic acid, HCNR 82478 is regulated by Fgf activity at a later stage and the HCNR 81728 enhancer is under the control of Hh signaling. Finally, we show that Sox2 and Pax2 transcription factors are bound to HCNR 81675 genomic region during otic development and specific mutations to these transcription factor binding sites abrogates HCNR 81675 enhancer activity. Altogether, our results suggest that pou3f4 expression in inner ear might be under the control of distinct regulatory elements that fine-tune the spatio-temporal activity of this gene and provides novel data on the signaling mechanisms controlling pou3f4 function. PMID:21209840

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2012 CFR

2012-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2011 CFR

2011-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2013 CFR

2013-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2010 CFR

2010-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2014 CFR

2014-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

SH-wave refraction/reflection and site characterization

USGS Publications Warehouse

Wang, Z.; Street, R.L.; Woolery, E.W.; Madin, I.P.

2000-01-01

Traditionally, nonintrusive techniques used to characterize soils have been based on P-wave refraction/reflection methods. However, near-surface unconsolidated soils are oftentimes water-saturated, and when groundwater is present at a site, the velocity of the P-waves is more related to the compressibility of the pore water than to the matrix of the unconsolidated soils. Conversely, SH-waves are directly relatable to the soil matrix. This makes SH-wave refraction/reflection methods effective in site characterizations where groundwater is present. SH-wave methods have been used extensively in site characterization and subsurface imaging for earthquake hazard assessments in the central United States and western Oregon. Comparison of SH-wave investigations with geotechnical investigations shows that SH-wave refraction/reflection techniques are viable and cost-effective for engineering site characterization.

Drinking, Socioemotional Functioning, and Academic Progress in Secondary School

PubMed Central

Crosnoe, Robert; Benner, Aprile D.; Schneider, Barbara

2017-01-01

Secondary schools are sites of academic instruction but also contexts of socioemotional development, and the intertwining of these two functions has consequences for adolescents’ future health and education. Drawing on nationally representative data from the National Longitudinal Study of Adolescent Health (n = 8,271), this study explored the bidirectional associations among indicators of adolescents’ alcohol use and their feelings of social integration at school. Socioemotional problems did not predict increased drinking over time, but drinking predicted declining socioemotional functioning, with negative implications for adolescents’ academic grades by the end of high school. These associations, however, were conditioned by aspects of school context, with drinkers feeling more marginalized in schools characterized by dense networks with low rates of drinking. PMID:22556380

Scleredema adultorum of Buschke presenting as periorbital edema: a diagnostic challenge.

PubMed

Ioannidou, Despina I; Krasagakis, Konstantin; Stefanidou, Maria P; Karampekios, Spyros; Panayiotidis, John; Tosca, Androniki D

2005-02-01

Scleredema adultorum is a rare sclerotic disorder characterized by diffuse swelling and nonpitting induration of the skin. Its occurrence has been documented in association with infections, diabetes mellitus, paraproteinemia, multiple myeloma, and monoclonal gammopathy. We report an unusual case of a 48-year-old man with an asymptomatic bilateral eyelid edema of sudden onset. During a period of 6 months, the condition slowly progressed to extensive nonpitting edematous swelling restricted to the periorbital sites. The presumptive diagnosis of scleredema adultorum was confirmed by the presence of typical histologic findings. This case is unique in that the periorbital swelling remained as the sole clinical manifestation of scleredema during the 5-year follow-up and was complicated with partial vision blockage.

Application of biocompatible magnetite nanoparticles for the removal of arsenic and copper from water

NASA Astrophysics Data System (ADS)

Iconaru, S. L.; Beuran, M.; Turculet, C. S.; Negoi, I.; Teleanu, G.; Prodan, A. M.; Motelica-Heino, M.; Guégan, R.; Ciobanu, C. S.; Jiga, G.; Predoi, Daniela

2018-02-01

The progress of nanotechnology made possible the use of nanomaterials as adsorbents and magnetic iron oxides represents one of the first generations of nanoscale materials used in environment technologies [1]. A systematic characterization of commercial magnetite (Fe3O4) is presented in this research. The commercial (Fe3O4) magnetic adsorbents were characterized by various characterizations methods such as X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX). This study was also focused on the study of adsorption isotherms and the kinetics evaluation. X-ray studies indicated that As3+ and Cu2+ removed by Fe3O4 did not seem to alter the structure of Fe3O4 but they were highlighted in the EDX analysis. In addition, the SEM studies were consistent with the XRD results. The rate of adsorption of contaminants, in contaminated solutions decreases when the amount of contaminant increases in all experiments performed. The results revealed that Fe3O4 nanoparticles are promising candidates which could be used as sorbents for the removal of arsenic from the marine environment, for site remediation and groundwater treatment.

Mars aqueous chemistry experiment

NASA Technical Reports Server (NTRS)

Clark, Benton C.; Mason, Larry W.

1994-01-01

Mars Aqueous Chemistry Experiment (MACE) is designed to conduct a variety of measurements on regolith samples, encompassing mineral phase analyses, chemical interactions with H2O, and physical properties determinations. From these data, much can be learned or inferred regarding the past weathering environment, the contemporaneous soil micro-environments, and the general chemical and physical state of the Martian regolith. By analyzing both soil and duricrust samples, the nature of the latter may become more apparent. Sites may be characterized for comparative purposes and criteria could be set for selection of high priority materials on future sample return missions. The second year of the MACE project has shown significant progress in two major areas. MACE Instrument concept definition is a baseline design that has been generated for the complete MACE instrument, including definition of analysis modes, mass estimates and thermal model. The design includes multiple reagent reservoirs, 10 discrete analysis cells, sample manipulation capability, and thermal control. The MACE Measurement subsystems development progress is reported regarding measurement capabilities for aqueous ion sensing, evolved gas sensing, solution conductivity measurement, reagent addition (titration) capabilities, and optical sensing of suspended particles.

Mars aqueous chemistry experiment

NASA Astrophysics Data System (ADS)

Clark, Benton C.; Mason, Larry W.

1994-06-01

Mars Aqueous Chemistry Experiment (MACE) is designed to conduct a variety of measurements on regolith samples, encompassing mineral phase analyses, chemical interactions with H2O, and physical properties determinations. From these data, much can be learned or inferred regarding the past weathering environment, the contemporaneous soil micro-environments, and the general chemical and physical state of the Martian regolith. By analyzing both soil and duricrust samples, the nature of the latter may become more apparent. Sites may be characterized for comparative purposes and criteria could be set for selection of high priority materials on future sample return missions. The second year of the MACE project has shown significant progress in two major areas. MACE Instrument concept definition is a baseline design that has been generated for the complete MACE instrument, including definition of analysis modes, mass estimates and thermal model. The design includes multiple reagent reservoirs, 10 discrete analysis cells, sample manipulation capability, and thermal control. The MACE Measurement subsystems development progress is reported regarding measurement capabilities for aqueous ion sensing, evolved gas sensing, solution conductivity measurement, reagent addition (titration) capabilities, and optical sensing of suspended particles.

Magnetic moment in single crystalline BaFe2-xZnxAs2

NASA Astrophysics Data System (ADS)

Guo, Yanfeng; Wang, Xia; Li, Jun; Yamaura, Kazunari; Takayama-Muromachi, Eiji

2012-02-01

Nature of the magnetism for iron-based superconductors (FeSCs) has been actively studied since the discovery of this new family of compounds in 2008, largely owing to its significance for interpreting the paring mechanism. The approach through impurity substitution to shed light into this issue is always one of major ways. The substitution shows distinct responses to species of impurities, where partially replacement of Fe in parent FeSCs with a variety of d-metals like Co, Ni Ru, Rh, Pd, Ir, and Pt generally results in superconductivity, while recent progress in Zn doped FeSCs gives rather contrary result, where Zn severely degenerates the TC. Herein we show the magnetic and electrical studies on BaFe2-xZnxAs2 single crystals. Nonmagnetic Zn doping progressively suppresses the SDW without resulting in superconductivity, while it alternatively develops the spin-glass state, possibly suggestive of local magnetic moment around the Fe sites induced by Zn. The characterizations by X-ray diffraction, magnetic and electrical transport properties, specific heat capacity, and Hall coefficient have been done and the results will be discussed in detail.

Exploiting Phenylpropanoid Derivatives to Enhance the Nutraceutical Values of Cereals and Legumes

PubMed Central

Dwivedi, Sangam L.; Upadhyaya, Hari D.; Chung, Ill-Min; De Vita, Pasquale; García-Lara, Silverio; Guajardo-Flores, Daniel; Gutiérrez-Uribe, Janet A.; Serna-Saldívar, Sergio O.; Rajakumar, Govindasamy; Sahrawat, Kanwar L.; Kumar, Jagdish; Ortiz, Rodomiro

2016-01-01

Phenylpropanoids are a diverse chemical class with immense health benefits that are biosynthesized from the aromatic amino acid L-phenylalanine. This article reviews the progress for accessing variation in phenylpropanoids in germplasm collections, the genetic and molecular basis of phenylpropanoid biosynthesis, and the development of cultivars dense in seed-phenylpropanoids. Progress is also reviewed on high-throughput assays, factors that influence phenylpropanoids, the site of phenylpropanoids accumulation in seed, Genotype × Environment interactions, and on consumer attitudes for the acceptance of staple foods rich in phenylpropanoids. A paradigm shift was noted in barley, maize, rice, sorghum, soybean, and wheat, wherein cultivars rich in phenylpropanoids are grown in Europe and North and Central America. Studies have highlighted some biological constraints that need to be addressed for development of high-yielding cultivars that are rich in phenylpropanoids. Genomics-assisted breeding is expected to facilitate rapid introgression into improved genetic backgrounds by minimizing linkage drag. More research is needed to systematically characterize germplasm pools for assessing variation to support crop genetic enhancement, and assess consumer attitudes to foods rich in phenylpropanoids. PMID:27375635

Mobilizing Foucault: history, subjectivity and autonomous learners in nurse education.

PubMed

Darbyshire, Chris; Fleming, Valerie E M

2008-12-01

In the past 20, years the impact of progressive educational theories have become influential in nurse education particularly in relation to partnership and empowerment between lecturers and students and the development of student autonomy. The introduction of these progressive theories was in response to the criticisms that nurse education was characterized by hierarchical and asymmetrical power relationships between lecturers and students that encouraged rote learning and stifled student autonomy. This article explores how the work of Michel Foucault can be mobilized to think about autonomy in three different yet overlapping ways: as a historical event; as a discursive practice; and as part of an overall strategy to produce a specific student subject position. The implications for educational practice are that, rather than a site where students are empowered, nurse education is both a factory and a laboratory where new subjectivities are continually being constructed. This suggests that empowering practices and disciplinary practices uneasily co-exist. Critical reflection needs to be directed not only at structural dimensions of power but also on ourselves as students and lecturers by asking a Foucauldian question: How are you interested in autonomy?

Innovations in Site Characterization Case Study: The Role of a Conceptual Site Model for Expedited Site Characterization Using the Triad Approach at the Poudre River Site, Fort Collins, Colorado

EPA Pesticide Factsheets

This case study examines how systematic planning, an evolving conceptual site model (CSM), dynamic work strategies, and real time measurement technologies can be used to unravel complex contaminant distribution patterns...

A Learning Progression for Elementary Students' Functional Thinking

ERIC Educational Resources Information Center

Stephens, Ana C.; Fonger, Nicole; Strachota, Susanne; Isler, Isil; Blanton, Maria; Knuth, Eric; Murphy Gardiner, Angela

2017-01-01

In this article we advance characterizations of and supports for elementary students' progress in generalizing and representing functional relationships as part of a comprehensive approach to early algebra. Our learning progressions approach to early algebra research involves the coordination of a curricular framework and progression, an…

Laser spectroscopy as a method for diagnosing cancer and assessing the efficacy of treatment of malignant neoplasms

NASA Astrophysics Data System (ADS)

Akleyev, Alexander; Romanskaya, Yulia; Kisselyov, Mikhail; Vazhenin, Andrei

2005-08-01

The issues of early diagnosis and effective treatment of malignant neoplasms are of vital importance for the Urals region which in 1950-1960 became the site of several radiation incidents with the resultant overexposures of dozens of thousands of residents who have manifested increased risks of leukemia and solid cancer incidence. The present study has demonstrated the efficacy of the method of laser-correlation spectrometry (LCS) of blood plasma and serum for early diagnosis of malignant neoplasms and prediction of relapses of tumor following radical treatment. The LCS method is characterized by a sufficiently high diagnostic sensitivity in relation to malignant tumors. It has been established that LC spectra obtained for patients with malignant neoplasms differ significantly from those for patients with non-cancer pathology of the same sites. The LCS methodology has manifested a sufficiently high prognostic sensitivity (76.6%) in relation to complete regression after radical treatment and progression (78.0%) of the tumor process. A positive prognostic criterion of the course of a malignant neoplasm after radical treatment in patients without relapse and metastases is a statistically significant (p

Model Validation and Site Characterization for Early Deployment MHK Sites and Establishment of Wave Classification Scheme

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

Kilcher, Levi F

Model Validation and Site Characterization for Early Deployment Marine and Hydrokinetic Energy Sites and Establishment of Wave Classification Scheme presentation from from Water Power Technologies Office Peer Review, FY14-FY16.

Recent Experience Using Active Love Wave Techniques to Characterize Seismographic Station Sites

NASA Astrophysics Data System (ADS)

Martin, A. J.; Yong, A.; Salomone, L.

2014-12-01

Active-source Love waves recorded by the multi-channel analysis of surface wave (MASLW) technique were recently analyzed in two site characterization projects. Between 2010 and 2011, the 2009 American Recovery and Reinvestment Act (ARRA) funded GEOVision to conduct geophysical investigations at 189 seismographic stations—185 in California and 4 in the Central Eastern U.S. (CEUS). The original project plan was to utilize active and passive Rayleigh wave-based techniques to obtain shear-wave velocity (VS) profiles to a minimum depth of 30 m and the time-averaged VS of the upper 30 meters (VS30). Early in the investigation it became evident that Rayleigh wave techniques, such as multi-channel analysis of surface waves (MASRW), were not effective at characterizing all sites. Shear-wave seismic refraction and MASLW techniques were therefore applied. The MASLW technique was deployed at a total of 38 sites, in addition to other methods, and used as the primary technique to characterize 22 sites, 5 of which were also characterized using Rayleigh wave techniques. In 2012, the Electric Power Research Institute funded characterization of 33 CEUS station sites. Based on experience from the ARRA investigation, both MASRW and MASLW data were acquired by GEOVision at 24 CEUS sites—the remaining 9 sites and 2 overlapping sites were characterized by University of Texas, Austin. Of the 24 sites characterized by GEOVision, 16 were characterized using MASLW data, 4 using both MASLW and MASRW data and 4 using MASRW data. Love wave techniques were often found to perform better, or at least yield phase velocity data that could be more readily modeled using the fundamental mode assumption, at shallow rock sites, sites with steep velocity gradients, and, sites with a thin, low velocity, surficial soil layer overlying stiffer sediments. These types of velocity structure often excite dominant higher modes in Rayleigh wave data, but not in Love wave data. At such sites, it may be possible to model Rayleigh wave data using multi- or effective-mode techniques; however, in many cases extraction of adequate Rayleigh wave dispersion data for modeling was difficult. These results imply that field procedures should include careful scrutiny of Rayleigh wave-based dispersion data in order to collect Love wave data when warranted.

Spectroscopic insights into the nature of active sites in iron–nitrogen–carbon electrocatalysts for oxygen reduction in acid

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

Jia, Qingying; Ramaswamy, Nagappan; Tylus, Urszula

Developing efficient and inexpensive catalysts for the sluggish oxygen reduction reaction (ORR) constitutes one of the grand challenges in the fabrication of commercially viable fuel cell devices and metal–air batteries for future energy applications. Despite recent achievements in designing advanced Pt-based and Pt-free catalysts, current progress primarily involves an empirical approach of trial-and-error combination of precursors and synthesis conditions, which limits further progress. Rational design of catalyst materials requires proper understanding of the mechanistic origin of the ORR and the underlying surface properties under operating conditions that govern catalytic activity. Herein, several different groups of iron-based catalysts synthesized via differentmore » methods and/or precursors were systematically studied by combining multiple spectroscopic techniques under ex situ and in situ conditions in an effort to obtain a comprehensive understanding of the synthesis-products correlations, nature of active sites, and the reaction mechanisms. These catalysts include original macrocycles, macrocycle-pyrolyzed catalysts, and Fe-N–C catalysts synthesized from individual Fe, N, and C precursors including polymer-based catalysts, metal organic framework (MOF)-based catalysts, and sacrificial support method (SSM)-based catalysts. The latter group of catalysts is most promising as not only they exhibit exceptional ORR activity and/or durability, but also the final products are controllable. We show that the high activity observed for most pyrolyzed Fe-based catalysts can mainly be attributed to a single active site: non-planar Fe–N 4 moiety embedded in distorted carbon matrix characterized by a high potential for the Fe 2+/3+ redox transition in acidic electrolyte/environment. The high intrinsic ORR activity, or turnover frequency (TOF), of this site is shown to be accounted for by redox catalysis mechanism that highlights the dominant role of the site-blocking effect. Moreover, a highly active MOF-based catalyst without Fe–N moieties was developed, and the active sites were identified as nitrogen-doped carbon fibers with embedded iron particles that are not directly involved in the oxygen reduction pathway. The high ORR activity and durability of catalysts involving this second site, as demonstrated in fuel cell, are attributed to the high density of active sites and the elimination or reduction of Fenton-type processes. The latter are initiated by hydrogen peroxide but are known to be accelerated by iron ions exposed to the surface, resulting in the formation of damaging free-radicals.« less

Alcohol-Binding Sites in Distinct Brain Proteins: The Quest for Atomic Level Resolution

PubMed Central

Howard, Rebecca J.; Slesinger, Paul A.; Davies, Daryl L.; Das, Joydip; Trudell, James R.; Harris, R. Adron

2011-01-01

Defining the sites of action of ethanol on brain proteins is a major prerequisite to understanding the molecular pharmacology of this drug. The main barrier to reaching an atomic-level understanding of alcohol action is the low potency of alcohols, ethanol in particular, which is a reflection of transient, low-affinity interactions with their targets. These mechanisms are difficult or impossible to study with traditional techniques such as radioligand binding or spectroscopy. However, there has been considerable recent progress in combining X-ray crystallography, structural modeling, and site-directed mutagenesis to define the sites and mechanisms of action of ethanol and related alcohols on key brain proteins. We review such insights for several diverse classes of proteins including inwardly rectifying potassium, transient receptor potential, and neurotransmit-ter-gated ion channels, as well as protein kinase C epsilon. Some common themes are beginning to emerge from these proteins, including hydrogen bonding of the hydroxyl group and van der Waals interactions of the methylene groups of ethanol with specific amino acid residues. The resulting binding energy is proposed to facilitate or stabilize low-energy state transitions in the bound proteins, allowing ethanol to act as a “molecular lubricant” for protein function. We discuss evidence for characteristic, discrete alcohol-binding sites on protein targets, as well as evidence that binding to some proteins is better characterized by an interaction region that can accommodate multiple molecules of ethanol. PMID:21676006

10 CFR 960.3-2-2 - Nomination of sites as suitable for characterization.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-2-2 Nomination of... of each repository site. For the second repository, at least three of the sites shall not have been nominated previously. Any site nominated as suitable for characterization for the first repository, but not...

Ames expedited site characterization demonstration at the former manufactured gas plant site, Marshalltown, Iowa

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

Bevolo, A.J.; Kjartanson, B.H.; Wonder, J.D.

1996-03-01

The goal of the Ames Expedited Site Characterization (ESC) project is to evaluate and promote both innovative technologies (IT) and state-of-the-practice technologies (SOPT) for site characterization and monitoring. In April and May 1994, the ESC project conducted site characterization, technology comparison, and stakeholder demonstration activities at a former manufactured gas plant (FMGP) owned by Iowa Electric Services (IES) Utilities, Inc., in Marshalltown, Iowa. Three areas of technology were fielded at the Marshalltown FMGP site: geophysical, analytical and data integration. The geophysical technologies are designed to assess the subsurface geological conditions so that the location, fate and transport of the targetmore » contaminants may be assessed and forecasted. The analytical technologies/methods are designed to detect and quantify the target contaminants. The data integration technology area consists of hardware and software systems designed to integrate all the site information compiled and collected into a conceptual site model on a daily basis at the site; this conceptual model then becomes the decision-support tool. Simultaneous fielding of different methods within each of the three areas of technology provided data for direct comparison of the technologies fielded, both SOPT and IT. This document reports the results of the site characterization, technology comparison, and ESC demonstration activities associated with the Marshalltown FMGP site. 124 figs., 27 tabs.« less

Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer*

PubMed Central

Khan, Amjad P.; Poisson, Laila M.; Bhat, Vadiraja B.; Fermin, Damian; Zhao, Rong; Kalyana-Sundaram, Shanker; Michailidis, George; Nesvizhskii, Alexey I.; Omenn, Gilbert S.; Chinnaiyan, Arul M.; Sreekumar, Arun

2010-01-01

Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of biomarkers of cancer invasion and disease aggressiveness. Although alterations in gene expression have been extensively quantified during neoplastic progression, complementary analyses of proteomic changes have been limited. Here we interrogate the proteomic alterations in a cohort of 15 prostate-derived tissues that included five each from adjacent benign prostate, clinically localized prostate cancer, and metastatic disease from distant sites. The experimental strategy couples isobaric tags for relative and absolute quantitation with multidimensional liquid phase peptide fractionation followed by tandem mass spectrometry. Over 1000 proteins were quantified across the specimens and delineated into clinically localized and metastatic prostate cancer-specific signatures. Included in these class-specific profiles were both proteins that were known to be dysregulated during prostate cancer progression and new ones defined by this study. Enrichment analysis of the prostate cancer-specific proteomic signature, to gain insight into the functional consequences of these alterations, revealed involvement of miR-128-a/b regulation during prostate cancer progression. This finding was validated using real time PCR analysis for microRNA transcript levels in an independent set of 15 clinical specimens. miR-128 levels were elevated in benign prostate epithelial cell lines compared with invasive prostate cancer cells. Knockdown of miR-128 induced invasion in benign prostate epithelial cells, whereas its overexpression attenuated invasion in prostate cancer cells. Taken together, our profiles of the proteomic alterations of prostate cancer progression revealed miR-128 as a potentially important negative regulator of prostate cancer cell invasion. PMID:19955085

Key Role of Sulfonylurea Receptor 1 in Progressive Secondary Hemorrhage after Brain Contusion

PubMed Central

Kilbourne, Michael; Tsymbalyuk, Orest; Tosun, Cigdem; Caridi, John; Ivanova, Svetlana; Keledjian, Kaspar; Bochicchio, Grant; Gerzanich, Volodymyr

2009-01-01

Abstract An important but poorly understood feature of traumatic brain injury (TBI) is the clinically serious problem of spatiotemporal progression (“blossoming”) of a hemorrhagic contusion, a phenomenon we term progressive secondary hemorrhage (PSH). Molecular mechanisms of PSH are unknown and efforts to reduce it by promoting coagulation have met with equivocal results. We hypothesized that PSH might be due to upregulation and activation of sulfonylurea receptor 1 (SUR1)-regulated NCCa-ATP channels in capillary endothelial cells, predisposing to oncotic death of endothelial cells and catastrophic failure of capillary integrity. Anesthetized adult male rats underwent left parietal craniectomy for induction of a focal cortical contusion. The regulatory subunit of the channel, SUR1, was prominently upregulated in capillaries of penumbral tissues surrounding the contusion. In untreated rats, PSH was characterized by progressive enlargement of the contusion deep into the site of cortical impact, including corpus callosum, hippocampus, and thalamus, by progressive accumulation of extravasated blood, with a doubling of the volume during the first 12 h after injury, and by capillary fragmentation in penumbral tissues. Block of SUR1 using low-dose (non-hypoglycemogenic) glibenclamide largely eliminated PSH and capillary fragmentation, and was associated with a significant reduction in the size of the necrotic lesion and in preservation of neurobehavioral function. Antisense oligodeoxynucleotide against SUR1, administered after injury, reduced both SUR1 expression and PSH, consistent with a requirement for transcriptional upregulation of SUR1. Our findings provide novel insights into molecular mechanisms responsible for PSH associated with hemorrhagic contusions, and point to SUR1 as a potential therapeutic target in TBI. PMID:19604096

Characterizing Disease Burden and Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration.

PubMed

Chakravarthy, Usha; Bailey, Clare C; Johnston, Robert L; McKibbin, Martin; Khan, Rehna S; Mahmood, Sajjad; Downey, Louise; Dhingra, Narendra; Brand, Christopher; Brittain, Christopher J; Willis, Jeffrey R; Rabhi, Sarah; Muthutantri, Anushini; Cantrell, Ronald A

2018-06-01

To understand levels of disease burden and progression in a real-world setting among patients from the United Kingdom with bilateral geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Retrospective cohort analysis of a multicenter electronic medical record (EMR) database. Patients who were aged ≥50 years with bilateral GA and no history of choroidal neovascularization (CNV) and who attended 1 of 10 clinical sites using the EMR. A deidentified data set was constructed from the records held at the 10 sites. An algorithm was used to extract cases with a GA diagnosis, of which 1901 had bilateral GA and form the basis of this report. A sample of records randomly selected from each center was used to validate disease definitions. Progression to blindness (visual acuity [VA] <20 letters or Snellen 3/60 in the better-seeing eye), driving ineligibility (VA ≤70 letters or Snellen 6/12 in the better-seeing eye), progression to CNV, loss of 10 or more letters, and mean change in VA over time. At first record of GA, 7.1% had a VA in the better-seeing eye equal to or lower than the cutoff for blindness registration and 71.1% had a VA that would have rendered them ineligible to drive. Over time, 16% became legally blind (median time to outcome, 6.2 years) and 66.7% became ineligible to drive (median time to outcome, 1.6 years). In the worse-seeing eye, 40.1% lost ≥10 letters in 2.4 years. Among patients with baseline and 24-month VA measurements, mean VA decline was 6.1 letters in the worse-seeing eye (n = 413) and 12.4 letters in the better-seeing eye (n = 414). The rate of progression to CNV in either eye was 7.4% per patient-year. At initial diagnosis, based on VA in the better-seeing eye, a high proportion of patients with bilateral GA were ineligible to drive and approximately 7% were eligible for UK blindness registration. The subsequent reduction in VA that occurred in the better-seeing eye would render a further two-thirds ineligible to drive. These findings emphasize the severity of the visual disability associated with GA secondary to AMD. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Electro-olfactogram and multiunit olfactory receptor responses to binary and trinary mixtures of amino acids in the channel catfish, Ictalurus punctatus

PubMed Central

1989-01-01

In vivo electrophysiological recordings from populations of olfactory receptor neurons in the channel catfish, Ictalurus punctatus, clearly showed that responses to binary and trinary mixtures of amino acids were predictable with knowledge obtained from previous cross-adaptation studies of the relative independence of the respective binding sites of the component stimuli. All component stimuli, from which equal aliquots were drawn to form the mixtures, were adjusted in concentration to provide for approximately equal response magnitudes. The magnitude of the response to a mixture whose component amino acids showed significant cross-reactivity was equivalent to the response to any single component used to form that mixture. A mixture whose component amino acids showed minimal cross-adaptation produced a significantly larger relative response than a mixture whose components exhibited considerable cross-reactivity. This larger response approached the sum of the responses to the individual component amino acids tested at the resulting concentrations in the mixture, even though olfactory receptor dose-response functions for amino acids in this species are characterized by extreme sensory compression (i.e., successive concentration increments produce progressively smaller physiological responses). Thus, the present study indicates that the response to sensory stimulation of olfactory receptor sites is more enhanced by the activation of different receptor site types than by stimulus interaction at a single site type. PMID:2703818

Magnetic exploration of a low-temperature ultramafic-hosted hydrothermal site (Lost City, 30°N, MAR)

NASA Astrophysics Data System (ADS)

Szitkar, Florent; Tivey, Maurice A.; Kelley, Deborah S.; Karson, Jeffrey A.; Früh-Green, Gretchen L.; Denny, Alden R.

2017-03-01

A 2003 high-resolution magnetic survey conducted by the Autonomous Underwater Vehicle ABE over the low-temperature, ultramafic-hosted hydrothermal field Lost City reveals a weak positive magnetic anomaly. This observation is in direct contrast to recent observations of strong positive magnetic anomalies documented over the high-temperature ultramafic-hosted hydrothermal vents fields Rainbow and Ashadze, which indicates that temperature may control the production of magnetization at these sites. The Lost City survey provides a unique opportunity to study a field that is, to date, one of a kind, and is an end member of ultramafic-hosted hydrothermal systems. Our results highlight the key contribution of temperature on magnetite production resulting from serpentinization reactions. Whereas high temperature promotes significant production and partitioning of iron into magnetite, low temperature favors iron partitioning into various alteration phases, resulting in a magnetite-poor rock. Moreover, the distribution of magnetic anomalies confirms results of a previous geological survey indicating the progressive migration of hydrothermal activity upslope. These discoveries contribute to the results of 25 yrs of magnetic exploration of a wide range of hydrothermal sites, from low- to high-temperature and from basalt- to ultramafic-hosted, and thereby validate using high-resolution magnetics as a crucial parameter for locating and characterizing hydrothermal sites hosting unique chemosynthetic-based ecosystems and potentially mineral-rich deposits.

Synchronized imaging and acoustic analysis of the upper airway in patients with sleep-disordered breathing.

PubMed

Chang, Yi-Chung; Huon, Leh-Kiong; Pham, Van-Truong; Chen, Yunn-Jy; Jiang, Sun-Fen; Shih, Tiffany Ting-Fang; Tran, Thi-Thao; Wang, Yung-Hung; Lin, Chen; Tsao, Jenho; Lo, Men-Tzung; Wang, Pa-Chun

2014-12-01

Progressive narrowing of the upper airway increases airflow resistance and can produce snoring sounds and apnea/hypopnea events associated with sleep-disordered breathing due to airway collapse. Recent studies have shown that acoustic properties during snoring can be altered with anatomic changes at the site of obstruction. To evaluate the instantaneous association between acoustic features of snoring and the anatomic sites of obstruction, a novel method was developed and applied in nine patients to extract the snoring sounds during sleep while performing dynamic magnetic resonance imaging (MRI). The degree of airway narrowing during the snoring events was then quantified by the collapse index (ratio of airway diameter preceding and during the events) and correlated with the synchronized acoustic features. A total of 201 snoring events (102 pure retropalatal and 99 combined retropalatal and retroglossal events) were recorded, and the collapse index as well as the soft tissue vibration time were significantly different between pure retropalatal (collapse index, 2 ± 11%; vibration time, 0.2 ± 0.3 s) and combined (retropalatal and retroglossal) snores (collapse index, 13 ± 7% [P ≤ 0.0001]; vibration time, 1.2 ± 0.7 s [P ≤ 0.0001]). The synchronized dynamic MRI and acoustic recordings successfully characterized the sites of obstruction and established the dynamic relationship between the anatomic site of obstruction and snoring acoustics.

Fiber-based modeling of in situ ankle ligaments with consideration of progressive failure.

PubMed

Nie, Bingbing; Forman, Jason L; Panzer, Matthew B; Mait, Alexander R; Donlon, John-Paul; Kent, Richard W

2017-08-16

Ligament sprains account for a majority of injuries to the foot and ankle complex among athletic populations. The infeasibility of measuring the in situ response and load paths of individual ligaments has precluded a complete characterization of their mechanical behavior via experiment. In the present study a fiber-based modeling approach of in situ ankle ligaments was developed and validated for determining the heterogeneous force-elongation characteristics and the consequent injury patterns. Nine major ankle ligaments were modeled as bundles of discrete elements, corresponding functionally to the structure of collagen fibers. To incorporate the progressive nature of ligamentous injury, the limit strain at the occurrence of fiber failure was described by a distribution function ranging from 12% to 18% along the width of the insertion site. The model was validated by comparing the structural kinetic and kinematic response obtained experimentally and computationally under well-controlled foot rotations. The simulation results replicated the 6 degree-of-freedom bony motion and ligamentous injuries and, by implication, the in situ deformations of the ligaments. Gross stiffness of the whole ligament derived from the fibers was comparable to existing experimental data. The present modeling approach provides a biomechanically realistic, interpretable and computationally efficient way to characterize the in situ ligament slack, sequential and heterogeneous uncrimping of collagen fascicles and failure propagation as the external load is applied. Applications of this model include functional ankle joint mechanics, injury prevention and countermeasure design for athletes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Site Characterization Technologies for DNAPL Investigations

EPA Pesticide Factsheets

This document is intended to help managers at sites with potential or confirmed DNAPL contamination identify suitable characterization technologies, screen the technologies for potential application, learn about applications at similar sites, and...

Problematising the Pursuit of Progress in Mathematics Education

ERIC Educational Resources Information Center

Llewellyn, Anna

2016-01-01

In this article, I use a Foucauldian poststructural analysis to examine productions of progress within key discursive spaces of mathematics education. These sites of production are educational policy, mathematics education research and case studies of primary school student-teachers in England. From my analysis, I show how progress governs what is…

IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

PubMed Central

Divatia, Mukul; Kim, Sun A

2012-01-01

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies. PMID:22187229

Bioremediation and phytoremediation: Chlorinated and recalcitrant compounds

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

NONE

1998-12-31

Bioremediation and phytoremediation have progressed, especially with regard to the treatment of hydrocarbon-contaminated sites. Sites contaminated with chlorinated and recalcitrant compounds have proven more resistant to these approaches, but exciting progress is being made both in the laboratory and in the field. This book brings together the latest breakthrough thinking and results in bioremediation, with chapters on cometabolic processes, aerobic and anaerobic mechanisms, biological reductive dechlorination processes, bioaugmentation, biomonitoring, and phytoremediation of recalcitrant organic compounds.

Framework for Site Characterization for Monitored Natural Attenuation of Volatile Organic Compounds in Ground Water

EPA Science Inventory

Monitored Natural Attenuation (MNA) is unique among remedial technologies in relying entirely on natural processes to achieve site-specific objectives. Site characterization is essential to provide site-specific data and interpretations for the decision-making process (i.e., to ...

Advances on the constitutive characterization of composites via multiaxial robotic testing and design optimization

Treesearch

John G. Michopoulos; John Hermanson; Athanasios Iliopoulos

2014-01-01

The research areas of mutiaxial robotic testing and design optimization have been recently utilized for the purpose of data-driven constitutive characterization of anisotropic material systems. This effort has been enabled by both the progress in the areas of computers and information in engineering as well as the progress in computational automation. Although our...

10 CFR 960.3-4 - Environmental impacts.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REPOSITORY Implementation Guidelines § 960.3-4 Environmental impacts. Environmental impacts shall be considered by the DOE throughout the site characterization, site selection, and repository development..., during site characterization and repository construction, operation, closure, and decommissioning. ...

Progress on Footprint Reduction at the Hanford Site - 12406

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

McKenney, Dale E.; Seeley, Paul; Farabee, Al

2012-07-01

The Department of Energy (DOE) Office of Environmental Management (EM) continues to reduce the footprint of legacy sites throughout the EM complex. Footprint reduction is being accomplished by focusing cleanup activities on decontamination and demolition of excess contaminated facilities, soil and groundwater remediation, and solid waste disposition. All of these initiatives are being accomplished with established technologies in proven regulatory frameworks. Ultimately, completion of these environmental cleanup activities will reduce the monitoring and maintenance costs associated with managing large federal facilities, allowing EM to place more focus on other high priority cleanup efforts and facilitate a successful transition to land-termmore » stewardship of these sites. Through the American Recovery and Reinvestment Act (ARRA) investment, the Department's cleanup footprint has been reduced by 45 percent to date, from 2411 km{sup 2} (931 mi{sup 2}) to 1336 km{sup 2} (516 mi{sup 2}s). With this significant progress on footprint reduction, the Department is on track towards their goal to reduce its overall footprint by approximately 90 percent by 2015. In addition, some areas cleaned up may become available for alternate uses (i.e. recreation, conservation, preservation, industrialization or development). Much of the work to reduce the complex's footprint occurred at the Savannah River Site in South Carolina and the Hanford Site in Washington, but cleanup continues across the complex. Footprint reduction is progressing well at the Hanford Site, supported predominantly through ARRA investment. To date, 994 km{sup 2} (384 mi{sup 2}) (65%) of footprint reduction have been achieved at Hanford, with a goal to achieve a 90% reduction by Fiscal Year 2015. The DOE EM and DOE Richland Operations Office, continue to make great progress to reduce the legacy footprint of the Hanford Site. Footprint reduction is being accomplished by focusing cleanup activities on decontamination and demolition of excess facilities, both contaminated and uncontaminated, waste site cleanup activities, and debris pile removal. All of these activities can be accomplished with proven technologies and within established regulatory frameworks. Footprint reduction goals for Fiscal Year 2011 were exceeded, largely with the help of ARRA funding. As cleanup projects are completed and the total area requiring cleanup shrinks, overall costs for surveillance and maintenance operations and infrastructure services decrease. This work completion and decrease in funding requirements to maintain waste sites and antiquated facilities allows more focus on high priority site missions (i.e. groundwater remediation, tank waste disposition, etc.) and moves Site areas closer to transition from EM to the Legacy Management program. The progress in the Hanford footprint reduction effort will help achieve success in these other important mission areas. (authors)« less

Proteomic characterization of intermediate and advanced glycation end-products in commercial milk samples.

PubMed

Renzone, Giovanni; Arena, Simona; Scaloni, Andrea

2015-03-18

The Maillard reaction consists of a number of chemical processes affecting the structure of the proteins present in foods. We previously accomplished the proteomic characterization of the lactosylation targets in commercial milk samples. Although characterizing the early modification derivatives, this analysis did not describe the corresponding advanced glycation end-products (AGEs), which may be formed from the further oxidation of former ones or by reaction of oxidized sugars with proteins, when high temperatures are exploited. To fill this gap, we have used combined proteomic procedures for the systematic characterization of the lactosylated and AGE-containing proteins from the soluble and milk fat globule membrane fraction of various milk products. Besides to confirm all lactulosyl-lysines described previously, 40 novel lactosylation sites were identified. More importantly, 308 additional intermediate and advanced glyco-oxidation derivatives (including cross-linking adducts) were characterized in 31 proteins, providing the widest qualitative inventory of modified species ascertained in commercial milk samples so far. Amadori adducts with glucose/galactose, their dehydration products, carboxymethyllysine and glyoxal-, 3-deoxyglucosone/3-deoxygalactosone- and 3-deoxylactosone-derived dihydroxyimidazolines and/or hemiaminals were the most frequent derivatives observed. Depending on thermal treatment, a variable number of modification sites was identified within each protein; their number increased with harder food processing conditions. Among the modified proteins, species involved in assisting the delivery of nutrients, defense response against pathogens and cellular proliferation/differentiation were highly affected by AGE formation. This may lead to a progressive decrease of the milk nutritional value, as it reduces the protein functional properties, abates the bioavailability of the essential amino acids and eventually affects food digestibility. These aspects are of particular importance in products intended for infant diet, such as milk powders and infant formulas. We used combined shotgun proteomic procedures for the systematic characterization of intermediate and advanced glycoxidation protein products in various raw and commercial milk samples. Several hundreds of modified species were characterized as deriving from 31 milk proteins, providing the widest qualitative inventory of assigned components in this fluid. Amadori adducts with glucose/galactose, their dehydration products, carboxymethyl-lysine, and glyoxal-, 3-deoxyglucosone/3-deoxygalactosone- and 3-deoxylactosone-derived dihydroxyimidazolines and/or hemiaminals were the most frequent derivatives observed. Proteins involved in nutrient delivery, defense response against pathogens and cellular proliferation/differentiation were highly subjected to intermediate and advanced glyco-oxidation modification. This may lead to a progressive decrease of the milk nutritional value, as it reduces the protein functional properties, diminishes the bioavailability of the essential amino acids, eventually affects food digestibility and determines a potential increase of specific allergens. These information are important points of interest to connect the extent of the Maillard reaction present in different commercial samples with the potential nutritional aspects mentioned above. These themes have to be fully evaluated in a next future for a complete estimation of the nutritional and toxicological properties of the dairy products deriving from severe heat processing. Copyright © 2015 Elsevier B.V. All rights reserved.

SUMMARY OF TECHNIQUES AND UNIQUE USES FOR DIRECT PUSH METHODS IN SITE CHARACTERIZATION ON CONTAMINATED FIELD SITES

EPA Science Inventory

Site characterization of subsurface contaminant transport is often hampered by a lack of knowledge of site heterogeneity and temporal variations in hydrogeochemistry. Two case studies are reviewed to illustrate the utility of macro-scale mapping information along with spatially-...

Chorea in Late-Infantile Neuronal Ceroid Lipofuscinosis: An Atypical Presentation.

PubMed

Saini, Arushi Gahlot; Sankhyan, Naveen; Singhi, Pratibha

2016-07-01

Classic late-infantile neuronal ceroid lipofuscinosis is characterized by progressive intellectual and motor deterioration, seizures, vision loss, and early death. Prominent chorea is an atypical feature and is rarely described in children. A four-year-old girl with seizures followed by a year-long progressive cognitive decline and a three month history of intermittent chorea leading to rapid motor deterioration. The onset of illness was marked by seizures occurring as generalized tonic-clonic seizures and myoclonic jerks. There was gradual regression of cognitive milestones with increasing forgetfulness and impaired quality and content of speech. Nine months later, she developed chorea. These movements were associated with clumsiness, incoordination, and progressive loss of motor milestones. She was unable to perform manual tasks or maintain antigravity posture resulting in unsteadiness and frequent falls. The movements were aggravated by action or excitement and were absent in sleep. Magnetic resonance imaging depicted diffuse cerebral and cerebellar atrophy. Sequencing analysis of TPP1 gene showed a novel, homozygous, splice site mutation c.89+1G>A which resulted in nil enzyme activity and a severe phenotype with onset of disease symptoms at an early age of three years. The presence of chorea in late-infantile neuronal ceroid lipofuscinoses is atypical but does not exclude the diagnosis of late-infantile neuronal ceroid lipofuscinoses, especially in children with psychomotor regression, seizures and diffuse brain atrophy. Copyright © 2016 Elsevier Inc. All rights reserved.

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

A postdoctoral training position in translational cancer biology is currently available in the Laboratory of Genitourinary Cancer Pathogenesis (LGCP) of the National Cancer Institute (NCI). The position is located in the laboratory of David VanderWeele M.D., Ph.D., whose research group uses in vitro and in vivo functional studies and pathology specimens and next-generation sequencing data to identify and target drivers of prostate cancer progression. The laboratory is interested in characterizing clinically significant, potentially lethal prostate cancer. We are specifically interested in molecular alterations that drive progression of subclones to dominance development of metastatic disease and characterizing therapeutic vulnerabilities. Current work is aimed at using xenograft and organoid models to further characterize the role of putative drivers of progression, and to develop ways to target these alterations.

Site preparation for wildlife

Treesearch

Ralph W. Dimmick

1989-01-01

Site preparation-whether for timber and/or wildlife objectives - can influence the quality of wildlife habitat on the site and surrounding forest for the entire rotation period of the regenerated stand. The site preparation you select will help determine the species and numbers of wildlife that use the stand as the stand progresses from regeneration through maturity....

Insisting on Digital Equity: Reframing the Dominant Discourse on Multicultural Education and Technology

ERIC Educational Resources Information Center

Gorski, Paul C.

2009-01-01

In the United States, where technological progress is portrayed as humanistic progress, computer technologies often are hailed as the great equalizers. Even within progressive education movements, such as multicultural education, the conversation about instructional technology tends to center more on this or that wonderful Web site or piece of…

EPIC'S PRODUCTS AND SERVICES

EPA Science Inventory

EPIC completes approximately 150 site characterizations annually using current and historical aerial photographs. This work is done in support of EPA Regional and Program
offices. Site characterization provides detailed information about a site and its history, often going ba...

Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 3, Groundwater hydrology report. Revised final report

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

Not Available

1991-12-01

The US Environmental Protection Agency (EPA) has established health and environmental protection regulations to correct and prevent groundwater contamination resulting from processing activities at inactive uranium milling sites. According to the Uranium Mill Tailings Radiation Control Act of 1978, (UMTRCA) the US Department of Energy (DOE) is responsible for assessing the inactive uranium processing sites. The DOE has determined this assessment shall include information on hydrogeologic site characterization. The water resources protection strategy that describes how the proposed action will comply with the EPA groundwater protection standards is presented in Attachment 4. Site characterization activities discussed in this section include:more » Characterization of the hydrogeologic environment; characterization of existing groundwater quality; definition of physical and chemical characteristics of the potential contaminant source; and description of local water resources.« less

Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris.

PubMed

Kossard, S; Lee, M S; Wilkinson, B

1997-01-01

Lichen planopilaris usually produces multifocal areas of scarring alopecia. Recently, a condition in postmenopausal women characterized by progressive frontal hairline recession associated with scarring has been described. Our purpose was to study the clinical and histopathologic features and results of treatment in a group of women with the frontal variant of lichen planopilaris and to compare the immunohistochemical profile of scalp biopsy specimens from this subset with that found in the multifocal variant of lichen planopilaris. The clinical data as well as the histopathologic findings in 16 women with frontal fibrosing alopecia were collated. The immunohistochemical profile of six scalp biopsy specimens from the frontal hairline were compared with six specimens from women with multifocal lichen planopilaris. In addition to the progressive frontal fibrosing alopecia in all 16 women, total loss or a marked decrease of the eyebrows was observed in 13. No evidence of lichen planus was observed at other sites. In one patient multifocal areas of lichen planopilaris developed in the scalp. The frontal fibrosing alopecia was slowly progressive but has stabilized in five patients. Biopsy specimens from the frontal hairline showed histologic changes identical to lichen planopilaris. Immunophenotyping failed to reveal any significant differences between the frontal and multifocal variants. No effective treatments emerged although oral steroids and antimalarials may temporarily slow the course. Hormone replacement therapy did not appear to influence the course of the alopecia. Progressive frontal fibrosing alopecia is a clinically distinct variant of lichen planopilaris that affects in particular elderly women and frequently involves the eyebrows. The basis for this lichenoid tissue reaction targeting frontal scalp follicles and eyebrows is unknown.

SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM: PROGRESS AND ACCOMPLISHMENTS - FISCAL YEAR 1991

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) program was the first major program for demonstrating and evaluating full-scale innovative treatment technologies at hazardous waste sites. Having concluded its fifth year, the SITE program is recognized as a leading advocate ...

SITE: INNOVATION ON THE MOVE

EPA Science Inventory

A recent review of the SITE Program indicated that operational shifts are necessary to maintain the program's position as a progressive, "state-of-the-art" leader in the environmental field. The SITE Program will shift from a technology-driven focus to a more integrated approach ...

Experimental Observation of Redox-Induced Fe-N Switching Behavior as a Determinant Role for Oxygen Reduction Activity.

PubMed

Jia, Qingying; Ramaswamy, Nagappan; Hafiz, Hasnain; Tylus, Urszula; Strickland, Kara; Wu, Gang; Barbiellini, Bernardo; Bansil, Arun; Holby, Edward F; Zelenay, Piotr; Mukerjee, Sanjeev

2015-12-22

The commercialization of electrochemical energy conversion and storage devices relies largely upon the development of highly active catalysts based on abundant and inexpensive materials. Despite recent achievements in this respect, further progress is hindered by the poor understanding of the nature of active sites and reaction mechanisms. Herein, by characterizing representative iron-based catalysts under reactive conditions, we identify three Fe-N4-like catalytic centers with distinctly different Fe-N switching behaviors (Fe moving toward or away from the N4-plane) during the oxygen reduction reaction (ORR), and show that their ORR activities are essentially governed by the dynamic structure associated with the Fe(2+/3+) redox transition, rather than the static structure of the bare sites. Our findings reveal the structural origin of the enhanced catalytic activity of pyrolyzed Fe-based catalysts compared to nonpyrolyzed Fe-macrocycle compounds. More generally, the fundamental insights into the dynamic nature of transition-metal compounds during electron-transfer reactions will potentially guide rational design of these materials for broad applications.

Construction of a Quantum Matter Synthesizer

NASA Astrophysics Data System (ADS)

Trisnadi, Jonathan; McDonald, Mickey; Chin, Cheng

2017-04-01

We report progress on the construction of a new platform to manipulate ultracold atoms. The ``Quantum Matter Synthesizer (QMS)'' will have the capability of deterministically preparing large 2D arrays of atoms with single site addressability. Cesium atoms are first transferred into a science cell (specially textured to reduce reflectance to 0.1% across a wide range of wavelengths and incident angles) via a moving 1D lattice, where they are loaded into a magic-wavelength, far-detuned 2D optical lattice. Two NA=0.8 microscope objectives surround the science cell from above and below. The lower objective will be used to project an array of optical tweezers created via a digital micromirror device (DMD) onto the atom-trapping plane, which will be used to rearrange atoms into a desired configuration after first taking a site-resolved fluorescence image of the initial atomic distribution with the upper objective. We provide updates on our magnetic-optical trap and Raman-sideband cooling performance, characterization of the resolution of our microscope objectives, and stability tests for the objective mounting structure.

PRP19 Transforms into a Sensor of RPA-ssDNA after DNA Damage and Drives ATR Activation via a Ubiquitin-Mediated Circuitry

PubMed Central

Maréchal, Alexandre; Wu, Ching-Shyi; Yazinski, Stephanie A.; Nguyen, Hai Dang; Liu, Shizhou; Jiménez, Amanda E.; Jin, Jianping; Zou, Lee

2014-01-01

Summary PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). While the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 binds RPA directly and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ATR kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, the recovery of stalled replication forks, and the progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. PMID:24332808

Mechanisms for Ductile Rupture - FY16 ESC Progress Report

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

Boyce, Brad L.; Carroll, Jay D.; Noell, Phillip

2017-01-01

Ductile rupture in metals is generally a multi-step process of void nucleation, growth, and coalescence. Particle decohesion and particle fracture are generally invoked as the primary microstructural mechanisms for room-temperature void nucleation. However, because high-purity materials also fail by void nucleation and coalescence, other microstructural features must also act as sites for void nucleation. Early studies of void initiation in high-purity materials, which included post-mortem fracture surface characterization using scanning electron microscopy (SEM) and high-voltage electron microscopy (HVEM) and in-situ HVEM observations of fracture, established the presence of dislocation cell walls as void initiation sites in high-purity materials. Direct experimentalmore » evidence for this contention was obtained during in-situ HVEM tensile tests of Be single crystals. Voids between 0.2 and 1 μm long appeared suddenly along dislocation cell walls during tensile straining. However, subsequent attempts to replicate these results in other materials, particularly α -Fe single crystals, were unsuccessful because of the small size of the dislocation cells, and these remain the only published in-situ HVEM observations of void nucleation at dislocation cell walls in the absence of a growing macrocrack. Despite this challenge, other approaches to studying void nucleation in high-purity metals also indicate that dislocation cell walls are nucleation sites for voids.« less

Shape and Site Dependent in Vivo Degradation of Mg-Zn Pins in Rabbit Femoral Condyle

PubMed Central

Han, Pei; Tan, Moyan; Zhang, Shaoxiang; Ji, Weiping; Li, Jianan; Zhang, Xiaonong; Zhao, Changli; Zheng, Yufeng; Chai, Yimin

2014-01-01

A type of specially designed pin model of Mg-Zn alloy was implanted into the full thickness of lesions of New Zealand rabbits’ femoral condyles. The recovery progress, outer surface healing and in vivo degradation were characterized by various methods including radiographs, Micro-CT scan with surface rendering, SEM (scanning electron microscope) with EDX (Energy Dispersive X-ray analysis) and so on. The in vivo results suggested that a few but not sufficient bridges for holding force were formed between the bone and the implant if there was a preexisting gap between them. The rapid degradation of the implantation in the condyle would result in the appearance of cavities. Morphological evaluation of the specially designed pins indicated that the cusp was the most vulnerable part during degradation. Furthermore, different implantation sites with distinct components and biological functions can lead to different degradation rates of Mg-Zn alloy. The rate of Mg-Zn alloy decreases in the following order: implantation into soft tissue, less trabecular bone, more trabecular bone, and cortical bone. Because of the complexities of in vivo degradation, it is necessary for the design of biomedical Mg-Zn devices to take into consideration the implantation sites used in clinics. PMID:24566138

Integrated metagenomic data analysis demonstrates that a loss of diversity in oral microbiota is associated with periodontitis.

PubMed

Ai, Dongmei; Huang, Ruocheng; Wen, Jin; Li, Chao; Zhu, Jiangping; Xia, Li Charlie

2017-01-25

Periodontitis is an inflammatory disease affecting the tissues supporting teeth (periodontium). Integrative analysis of metagenomic samples from multiple periodontitis studies is a powerful way to examine microbiota diversity and interactions within host oral cavity. A total of 43 subjects were recruited to participate in two previous studies profiling the microbial community of human subgingival plaque samples using shotgun metagenomic sequencing. We integrated metagenomic sequence data from those two studies, including six healthy controls, 14 sites representative of stable periodontitis, 16 sites representative of progressing periodontitis, and seven periodontal sites of unknown status. We applied phylogenetic diversity, differential abundance, and network analyses, as well as clustering, to the integrated dataset to compare microbiological community profiles among the different disease states. We found alpha-diversity, i.e., mean species diversity in sites or habitats at a local scale, to be the single strongest predictor of subjects' periodontitis status (P < 0.011). More specifically, healthy subjects had the highest alpha-diversity, while subjects with stable sites had the lowest alpha-diversity. From these results, we developed an alpha-diversity logistic model-based naive classifier able to perfectly predict the disease status of the seven subjects with unknown periodontal status (not used in training). Phylogenetic profiling resulted in the discovery of nine marker microbes, and these species are able to differentiate between stable and progressing periodontitis, achieving an accuracy of 94.4%. Finally, we found that the reduction of negatively correlated species is a notable signature of disease progression. Our results consistently show a strong association between the loss of oral microbiota diversity and the progression of periodontitis, suggesting that metagenomics sequencing and phylogenetic profiling are predictive of early periodontitis, leading to potential therapeutic intervention. Our results also support a keystone pathogen-mediated polymicrobial synergy and dysbiosis (PSD) model to explain the etiology of periodontitis. Apart from P. gingivalis, we identified three additional keystone species potentially mediating the progression of periodontitis progression based on pathogenic characteristics similar to those of known keystone pathogens.

The Human Skin Microbiome Associates with the Outcome of and Is Influenced by Bacterial Infection.

PubMed

van Rensburg, Julia J; Lin, Huaiying; Gao, Xiang; Toh, Evelyn; Fortney, Kate R; Ellinger, Sheila; Zwickl, Beth; Janowicz, Diane M; Katz, Barry P; Nelson, David E; Dong, Qunfeng; Spinola, Stanley M

2015-09-15

The influence of the skin microbiota on host susceptibility to infectious agents is largely unexplored. The skin harbors diverse bacterial species that may promote or antagonize the growth of an invading pathogen. We developed a human infection model for Haemophilus ducreyi in which human volunteers are inoculated on the upper arm. After inoculation, papules form and either spontaneously resolve or progress to pustules. To examine the role of the skin microbiota in the outcome of H. ducreyi infection, we analyzed the microbiomes of four dose-matched pairs of "resolvers" and "pustule formers" whose inoculation sites were swabbed at multiple time points. Bacteria present on the skin were identified by amplification and pyrosequencing of 16S rRNA genes. Nonmetric multidimensional scaling (NMDS) using Bray-Curtis dissimilarity between the preinfection microbiomes of infected sites showed that sites from the same volunteer clustered together and that pustule formers segregated from resolvers (P = 0.001, permutational multivariate analysis of variance [PERMANOVA]), suggesting that the preinfection microbiomes were associated with outcome. NMDS using Bray-Curtis dissimilarity of the endpoint samples showed that the pustule sites clustered together and were significantly different than the resolved sites (P = 0.001, PERMANOVA), suggesting that the microbiomes at the endpoint differed between the two groups. In addition to H. ducreyi, pustule-forming sites had a greater abundance of Proteobacteria, Bacteroidetes, Micrococcus, Corynebacterium, Paracoccus, and Staphylococcus species, whereas resolved sites had higher levels of Actinobacteria and Propionibacterium species. These results suggest that at baseline, resolvers and pustule formers have distinct skin bacterial communities which change in response to infection and the resultant immune response. Human skin is home to a diverse community of microorganisms, collectively known as the skin microbiome. Some resident bacteria are thought to protect the skin from infection by outcompeting pathogens for resources or by priming the immune system's response to invaders. However, the influence of the skin microbiome on the susceptibility to or protection from infection has not been prospectively evaluated in humans. We characterized the skin microbiome before, during, and after experimental inoculation of the arm with Haemophilus ducreyi in matched volunteers who subsequently resolved the infection or formed abscesses. Our results suggest that the preinfection microbiomes of pustule formers and resolvers have distinct community structures which change in response to the progression of H. ducreyi infection to abscess formation. Copyright © 2015 van Rensburg et al.

Climbing walls as multitasking sites of geo(morpho)logical interests: Italian examples from the Western Alps and Sardinia

NASA Astrophysics Data System (ADS)

Bollati, Irene; Fossati, Maria; Panizza, Valeria; Pelfini, Manuela; Zanoletti, Enrico; Zucali, Michele

2015-04-01

Geosites and in particular geomorphosites have been recently more and more used as base for educational activities in Earth Sciences and to enhance the geodiversity of a territory. Their attributes acquire a greater value and become especially appreciable when associated with field and outdoor activities. Frequently rock walls represent key sites for geological and gemorphological researches due to the wide outcrops of rocks where mineralogical composition and structures are very evident as well as landforms deriving from the modeling of outcrops surfaces. Where the rock walls are equipped for climbing activities they may be considered open-air laboratories useful to get in touch with the different features of rocks that condition progression on climbing routes. Due to these two aspects, geohistorical importance and educational exemplarity contribute to the increase of the scientific value and, as a consequence, of the global value of these sites as geosites. Geomorphosites from climbing sites allow to realize educational projects with different goals: 1) Recent researches in the Western Italian Alps have been conducted to make a census of climbing rock cliffs along the Ossola Valley (Verbanio-Cusio-Ossola Province, Italy) and to operate a choice of the ones characterized by high educational value (considering easy accessibility, grades for experts and beginners and the good exposition of rock features), representativeness, geohistorical importance, high cultural and socio-economic values, in order to propose an educational project addressed to students of an Italian secondary school aimed at introducing the three great families of rocks (magmatic, metamorphic and sedimentary); 2) The Eclogitic Micaschist Complex of the Austroalpine Domain (Montestrutto climbing wall, Turin Province, Italy) has been investigated in order to i) reconstruct the deformation stages at local scales along the sport climbing wall and the relationships between geological elements and physical elements necessary for vertical progression ii) elaborate an educational proposal; 3) Risk assessment and education has been approached through the analysis of site hazard on climbing routes, linked with both geomorphological processes, and to the variable meteorological conditions, at Monteleone Rocca Doria (Sardinia, Italy), a site sensitive to both the needs of the climbers and the environment. Here a particular attention was given to potential geomorphologically-related risks for climbers, the impacts linked to human presence and the specific features of the geomorphosite. In order to assess the possible risk situations related to the active geomorphological processes in a specific climbing site, a method for collecting data and information has been also proposed.

Transition Metal Oxides as Electrocatalysts for the Oxygen Evolution Reaction in Alkaline Solutions: An Application-Inspired Renaissance.

PubMed

Song, Fang; Bai, Lichen; Moysiadou, Aliki; Lee, Seunghwa; Hu, Chao; Liardet, Laurent; Hu, Xile

2018-06-27

Water splitting is the essential chemical reaction to enable the storage of intermittent energies such as solar and wind in the form of hydrogen fuel. The oxygen evolution reaction (OER) is often considered as the bottleneck in water splitting. Though metal oxides had been reported as OER electrocatalysts more than half a century ago, the recent interest in renewable energy storage has spurred a renaissance of the studies of transition metal oxides as Earth-abundant and nonprecious OER catalysts. This Perspective presents major progress in several key areas of the field such as theoretical understanding, activity trend, in situ and operando characterization, active site determination, and novel materials. A personal overview of the past achievements and future challenges is also provided.

Microbial ecology of the skin in the era of metagenomics and molecular microbiology.

PubMed

Hannigan, Geoffrey D; Grice, Elizabeth A

2013-12-01

The skin is the primary physical barrier between the body and the external environment and is also a substrate for the colonization of numerous microbes. Previously, dermatological microbiology research was dominated by culture-based techniques, but significant advances in genomic technologies have enabled the development of less-biased, culture-independent approaches to characterize skin microbial communities. These molecular microbiology approaches illustrate the great diversity of microbiota colonizing the skin and highlight unique features such as site specificity, temporal dynamics, and interpersonal variation. Disruptions in skin commensal microbiota are associated with the progression of many dermatological diseases. A greater understanding of how skin microbes interact with each other and with their host, and how we can therapeutically manipulate those interactions, will provide powerful tools for treating and preventing dermatological disease.

10 CFR 960.3-2-2-4 - The environmental assessment.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the site-characterization activities at the site on public health and safety and the environment; a discussion of alternative activities related to site characterization that may be taken to avoid such impact; and an assessment of the regional and local impacts of locating a repository at the site. The draft...

10 CFR 960.3-2-3 - Recommendation of sites for characterization.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Recommendation of sites for characterization. 960.3-2-3 Section 960.3-2-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-2-3 Recommendation of sites...

10 CFR 960.3-2-3 - Recommendation of sites for characterization.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Recommendation of sites for characterization. 960.3-2-3 Section 960.3-2-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-2-3 Recommendation of sites...

10 CFR 960.3-2-3 - Recommendation of sites for characterization.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Recommendation of sites for characterization. 960.3-2-3 Section 960.3-2-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-2-3 Recommendation of sites...

SUMMARY OF TECNIQUES AND UNIQUE USES FOR DIRECT PUSH METHODS IN SITE CHARACTERIZATION ON CONTAMINATED FIELD SITES

EPA Science Inventory

At many of the sites where we have been asked to assist in site characterization, we have discovered severe discrepancies that new technologies may be able to prevent. This presentation is designed to illustrate these new technologies or unique uses of existing technology and the...

AERIAL - MSC SITE - CONSTRUCTION PROGRESS - MSC

NASA Image and Video Library

1963-12-24

S63-23656 (1963) --- Aerial view of construction progress at the Manned Spacecraft Center, Houston, Texas. NOTE: The Manned Spacecraft Center was named Lyndon B. Johnson Space Center in memory of the late President following his death.

U.S. Department of Energy's site screening, site selection, and initial characterization for storage of CO2 in deep geological formations

USGS Publications Warehouse

Rodosta, T.D.; Litynski, J.T.; Plasynski, S.I.; Hickman, S.; Frailey, S.; Myer, L.

2011-01-01

The U.S. Department of Energy (DOE) is the lead Federal agency for the development and deployment of carbon sequestration technologies. As part of its mission to facilitate technology transfer and develop guidelines from lessons learned, DOE is developing a series of best practice manuals (BPMs) for carbon capture and storage (CCS). The "Site Screening, Site Selection, and Initial Characterization for Storage of CO2 in Deep Geological Formations" BPM is a compilation of best practices and includes flowchart diagrams illustrating the general decision making process for Site Screening, Site Selection, and Initial Characterization. The BPM integrates the knowledge gained from various programmatic efforts, with particular emphasis on the Characterization Phase through pilot-scale CO2 injection testing of the Validation Phase of the Regional Carbon Sequestration Partnership (RCSP) Initiative. Key geologic and surface elements that suitable candidate storage sites should possess are identified, along with example Site Screening, Site Selection, and Initial Characterization protocols for large-scale geologic storage projects located across diverse geologic and regional settings. This manual has been written as a working document, establishing a framework and methodology for proper site selection for CO2 geologic storage. This will be useful for future CO2 emitters, transporters, and storage providers. It will also be of use in informing local, regional, state, and national governmental agencies of best practices in proper sequestration site selection. Furthermore, it will educate the inquisitive general public on options and processes for geologic CO2 storage. In addition to providing best practices, the manual presents a geologic storage resource and capacity classification system. The system provides a "standard" to communicate storage and capacity estimates, uncertainty and project development risk, data guidelines and analyses for adequate site characterization, and guidelines for reporting estimates within the classification based on each project's status. 

Computational fluid dynamics tools can be used to predict the progression of coronary artery disease

NASA Astrophysics Data System (ADS)

Coşkun, A. Ümit; Chen, Caixia; Stone, Peter H.; Feldman, Charles L.

2006-03-01

Atherosclerosis is focal and individual plaques evolve in an independent manner. The endothelium regulates arterial behavior by responding to its local shear stress. In vitro studies indicate that low endothelial shear stress (ESS) upregulates the genetic and molecular responses leading to the initiation and progression of atherosclerosis and promotes inflammation and formation of other features characteristic of vulnerable plaque. Physiologic ESS is vasculoprotective and fosters quiescence of the endothelium and vascular wall. High ESS promotes platelet aggregation. ESS and vascular wall morphology along the course of human coronary arteries can now be characterized in vivo, and may predict the focal areas in which atherosclerosis progression occurs. Rapidly evolving methodologies are able to characterize the arterial wall and the local hemodynamic factors likely responsible for progression of coronary disease in man. These new diagnostic modalities allow for identification of plaque progression. Accurate identification of arterial segments at high-risk for progression may permit pre-emptive intervention strategies to avoid adverse coronary events.

Stennis Space Center Verification & Validation Capabilities

NASA Technical Reports Server (NTRS)

Pagnutti, Mary; Ryan, Robert E.; Holekamp, Kara; ONeal, Duane; Knowlton, Kelly; Ross, Kenton; Blonski, Slawomir

2005-01-01

Scientists within NASA s Applied Sciences Directorate have developed a well-characterized remote sensing Verification & Validation (V&V) site at the John C. Stennis Space Center (SSC). This site enables the in-flight characterization of satellite and airborne high spatial and moderate resolution remote sensing systems and their products. The smaller scale of the newer high resolution remote sensing systems allows scientists to characterize geometric, spatial, and radiometric data properties using a single V&V site. The targets and techniques used to characterize data from these newer systems can differ significantly from the techniques used to characterize data from the earlier, coarser spatial resolution systems. Scientists are also using the SSC V&V site to characterize thermal infrared systems and active lidar systems. SSC employs geodetic targets, edge targets, radiometric tarps, atmospheric monitoring equipment, and thermal calibration ponds to characterize remote sensing data products. The SSC Instrument Validation Lab is a key component of the V&V capability and is used to calibrate field instrumentation and to provide National Institute of Standards and Technology traceability. This poster presents a description of the SSC characterization capabilities and examples of calibration data.

Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets

NASA Astrophysics Data System (ADS)

Yoon, Hyeun Joong; Kim, Tae Hyun; Zhang, Zhuo; Azizi, Ebrahim; Pham, Trinh M.; Paoletti, Costanza; Lin, Jules; Ramnath, Nithya; Wicha, Max S.; Hayes, Daniel F.; Simeone, Diane M.; Nagrath, Sunitha

2013-10-01

The spread of cancer throughout the body is driven by circulating tumour cells (CTCs). These cells detach from the primary tumour and move from the bloodstream to a new site of subsequent tumour growth. They also carry information about the primary tumour and have the potential to be valuable biomarkers for disease diagnosis and progression, and for the molecular characterization of certain biological properties of the tumour. However, the limited sensitivity and specificity of current methods for measuring and studying these cells in patient blood samples prevents the realization of their full clinical potential. The use of microfluidic devices is a promising method for isolating CTCs. However, the devices are reliant on three-dimensional structures, which limits further characterization and expansion of cells on the chip. Here we demonstrate an effective approach to isolating CTCs from blood samples of pancreatic, breast and lung cancer patients, by using functionalized graphene oxide nanosheets on a patterned gold surface. CTCs were captured with high sensitivity at a low concentration of target cells (73 +/- 32.4% at 3-5 cells per ml blood).

Development of a Comprehensive Plan for Scientific Research, Exploration, and Design: Creation of an Undergroung Radioactive Waste Isloation Facility at the Nizhnekansky Rock Massif

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

Jardine, L J

2005-06-15

ISTC Partner Project No.2377, ''Development of a General Research and Survey Plan to Create an Underground RW Isolation Facility in Nizhnekansky Massif'', funded a group of key Russian experts in geologic disposal, primarily at Federal State Unitary Enterprise All-Russian Design and Research Institute of Engineering Production (VNIPIPT) and Mining Chemical Combine Krasnoyarsk-26 (MCC K-26) (Reference 1). The activities under the ISTC Partner Project were targeted to the creation of an underground research laboratory which was to justify the acceptability of the geologic conditions for ultimate isolation of high-level waste in Russia. In parallel to this project work was also undermore » way with Minatom's financial support to characterize alternative sections of the Nizhnekansky granitoid rock massif near the MCC K-26 site to justify the possibility of creating an underground facility for long-term or ultimate isolation of radioactive waste (RW) and spent nuclear fuel (SNF). (Reference 2) The result was a synergistic, integrated set of activities several years that advanced the geologic repository site characterization and development of a proposed underground research laboratory better than could have been expected with only the limited funds from ISTC Partner Project No.2377 funded by the U.S. DOE-RW. There were four objectives of this ISTC Partner Project 2377 geologic disposal work: (1) Generalize and analyze all research work done previously at the Nizhnekansky granitoid massif by various organizations; (2) Prepare and issue a declaration of intent (DOI) for proceeding with an underground research laboratory in a granite massif near the MCC K-26 site. (The DOI is similar to a Record of Decision in U.S. terminology). (3) Proceeding from the data obtained as a result of scientific research and exploration and design activities, prepare a justification of investment (JOI) for an underground research laboratory in as much detail as the available site characterization data allow. Consider the possibility of the substantiated selection of a specific site for the underground laboratory at this stage. (The JOI is similar to an advanced conceptual design or preliminary design in U.S. terminology). (4) Perform a preliminary safety assessment of the geologic isolation of radioactive waste and unreprocessable spent nuclear fuel (SNF) in the Nizhnekansky massif. Significant progress has been made toward fulfilling the joint project objectives. The results were documented in a series of quarterly reports and one final report over a period of {approx}2 3/4 years.« less

Public outreach supports the entire life-cycle of the Ketzin pilot site, Germany

NASA Astrophysics Data System (ADS)

Martens, Sonja; Kollersberger, Tanja; Möller, Fabian; Liebscher, Axel

2017-04-01

Interdisciplinary research at the Ketzin pilot site in Germany contributes to the understanding of the geological CO2 storage since 2004. In addition to the research activities, public outreach has been a key element through the entire life-cycle of the project including site assessment, characterization, development as well as operation (2008-2013) and post-closure. From the very beginning of the project, the research activities were accompanied by an open dialogue with the general public including locals and interested people from all over Germany and the world. The visitor centre at the Ketzin site is run by GFZ and the most important contact point to inform about first-hand experiences from the project. Up to now, about 3,000 visitors came to the Ketzin site for guided tours and the annual open house days. In addition, project status and progress are disseminated in brochures and on the public website www.co2ketzin.de. The Ketzin project is also presented in short films, e.g. on monitoring, drilling and well closure. As the post-closure and pre-transfer phase started after the cease of CO2 injection in August 2013 and the injection facility was dismantled in December 2013, we were looking for a tool to further inform about the previous operation and site infrastructure. A virtual tour was set up for the Ketzin site which is accessible via the website. This tour includes several videos which virtually guide you on site and provide information on the (former) facilities. Public acceptance is a key issue for the Ketzin project as it is for any other CO2 storage project. For example, an open communication with the local residents helped to conduct large-scale seismic campaigns without severe restrictions. The experience from the Ketzin pilot site shows that honest communication and a diverse dissemination program is able to overcome critical public perception even for highly debated technologies.

Dragonfly: In Situ Exploration of Titan's Organic Chemistry and Habitability

NASA Astrophysics Data System (ADS)

Turtle, E. P.; Barnes, J. W.; Trainer, M. G.; Lorenz, R. D.

2017-12-01

Titan's abundant complex carbon-rich chemistry, interior ocean, and past presence of liquid water on the surface make it an ideal destination to study prebiotic chemical processes and document the habitability of an extraterrestrial environment. Titan exploration is a high science priority due to the level of organic synthesis that it supports. Moreover, opportunities for organics to have interacted with liquid water at the surface (e.g., in impact melt sheets) increase the potential for chemical processes to progress further, providing an unparalleled opportunity to investigate prebiotic chemistry, as well as to search for signatures of potential water-based or even hydrocarbon-based life. The diversity of Titan's surface materials and environments drives the scientific need to be able to sample a variety of locations, thus mobility is key for in situ measurements. Titan's atmosphere is 4 times denser than Earth's reducing the wing/rotor area required to generate a given amount of lift, and the low gravity reduces the required magnitude of lift, making heavier-than-air mobility highly efficient. Dragonfly is a rotorcraft lander mission proposed to NASA's New Frontiers Program to take advantage of Titan's unique natural laboratory to understand how far chemistry can progress in environments that provide key ingredients for life. Measuring the compositions of materials in different environments will reveal how far organic chemistry has progressed. Surface material can be sampled into a mass spectrometer to identify the chemical components available and processes at work to produce biologically relevant compounds. Bulk elemental surface composition can be determined by a neutron-activated gamma-ray spectrometer. Meteorology measurements can characterize Titan's atmosphere and diurnal and spatial variations therein. Geologic features can be characterized via remote-sensing observations, which also provide context for samples. Seismic sensing can probe subsurface structure and activity. In addition to surface investigations, Dragonfly can perform measurements during flight, including atmospheric profiles and aerial observations of surface geology, which also provide sampling context and scouting for landing sites.

SOARCA Peach Bottom Atomic Power Station Long-Term Station Blackout Uncertainty Analysis: Knowledge Advancement.

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

Gauntt, Randall O.; Mattie, Patrick D.; Bixler, Nathan E.

2014-02-01

This paper describes the knowledge advancements from the uncertainty analysis for the State-of- the-Art Reactor Consequence Analyses (SOARCA) unmitigated long-term station blackout accident scenario at the Peach Bottom Atomic Power Station. This work assessed key MELCOR and MELCOR Accident Consequence Code System, Version 2 (MACCS2) modeling uncertainties in an integrated fashion to quantify the relative importance of each uncertain input on potential accident progression, radiological releases, and off-site consequences. This quantitative uncertainty analysis provides measures of the effects on consequences, of each of the selected uncertain parameters both individually and in interaction with other parameters. The results measure the modelmore » response (e.g., variance in the output) to uncertainty in the selected input. Investigation into the important uncertain parameters in turn yields insights into important phenomena for accident progression and off-site consequences. This uncertainty analysis confirmed the known importance of some parameters, such as failure rate of the Safety Relief Valve in accident progression modeling and the dry deposition velocity in off-site consequence modeling. The analysis also revealed some new insights, such as dependent effect of cesium chemical form for different accident progressions. (auth)« less

Feasibility study for underground coal gasification at the Krabi coal mine site, Thailand: Volume 1. Progress report, December 1--31, 1995; Export trade information

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

Young, B.C.; Schmit, C.R.

The report, conducted by Energy and Environmental Research Center, was funded by the US Trade and Development Agency. The objective of this report was to determine the technical, environmental and economic feasibility of developing, demonstrating, and commercializing underground coal gasification (UCG) at the Krabi coal mine site in Southern Thailand. This is Volume 1, the Progress Report for the period December 1, 1995, through December 31, 1995.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

PubMed

Eckstrand, C D; Sparger, E E; Pitt, K A; Murphy, B G

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

Ground-water monitoring compliance projects for Hanford Site facilities: Progress Report for the Period July 1 to September 30, 1987

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

Not Available

1987-11-01

This report documents the progress of four Hanford Site ground-water monitoring projects for the period from July 1 to September 310, 1987. The four disposal facilities are the 300 Area Process Trenches, 183-H Solar Evaporation Basins, 200 Area Low-Level Burial Grounds, and Nonradioactive Dangerous Waste (NRDW) Landfill. This report is the fifth in a series of periodic status reports. During this reporting period, field activities consisted of completing repairs on five monitoring wells originally present around the 183-H Basins and completing construction of 25 monitoring wells around the 200 Area Burial Grounds. The 14 wells in the 200 East Areamore » were completed by Kaiser Engineers Hanford (KEH) and the 11 wells in the 200 West Area were compelted by ONWEGO Well Drilling. The NRDW Landfill interim characterization report was submitted to the WDOE and the USEPA in August 1987. Analytical results for the 300 Area, 183-H, and the NRDW Landfill indicate no deviations from previously established trends. Results from the NRDW Land-fill indiate that the facility has no effect on the ground-water quality beneath the facility, except for the detection of coliform bacteria. A possible source of this contamination is the solid-waste lanfill (SWL) adjacent to the NRDW Landfill. Ground-water monitoring data for the NRDW and SWL will be evaluated together in the future. Aquifer testing was completed in the 25 new wells surrounding the 200 Area buiral grounds. 13 refs., 19 refs., 13 tabs.« less

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

PubMed Central

Sparger, E. E.; Pitt, K. A.

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs. PMID:28384338

Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

PubMed Central

McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.

2011-01-01

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection. PMID:21912520

Liver injury and fibrosis induced by dietary challenge in the Ossabaw miniature Swine.

PubMed

Liang, Tiebing; Alloosh, Mouhamad; Bell, Lauren N; Fullenkamp, Allison; Saxena, Romil; Van Alstine, William; Bybee, Phelan; Werling, Klára; Sturek, Michael; Chalasani, Naga; Masuoka, Howard C

2015-01-01

Ossabaw miniature swine when fed a diet high in fructose, saturated fat and cholesterol (NASH diet) develop metabolic syndrome and nonalcoholic steatohepatitis (NASH) characterized by liver injury and fibrosis. This study was conducted to further characterize the development of NASH in this large animal model. Ossabaw swine were fed standard chow (control group; n = 6) or NASH diet (n = 6) for 24 weeks. Blood and liver tissue were collected and liver histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention. Hepatic apoptosis and lipid levels were assessed at week 24. The NASH diet group developed metabolic syndrome and progressive histologic features of NASH including: (a) hepatocyte ballooning at 8 weeks which progressed to extensive ballooning (>90% hepatocytes), (b) hepatic fibrosis at week 16, which progressed to moderate fibrosis, and (c) Kupffer cell accumulation with vacuolization at 8 weeks which progressed through week 24. The NASH diet group showed increased hepatocyte apoptosis that correlated with hepatic total and free cholesterol and free fatty acids, but not esterified cholesterol or triglycerides. This report further characterizes the progression of diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet: (a) hepatocyte injury and fibrosis can occur without macrovesicular steatosis or excess triglyceride accumulation; (b) hepatocyte ballooning generally precedes the development of fibrosis; (c) there is increased hepatocyte apoptosis, and it is correlated more significantly with hepatic free cholesterol than hepatic free fatty acids and had no correlation with hepatic triglycerides.

10 CFR 960.3-1-4-3 - Site recommendation for characterization.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Site recommendation for characterization. 960.3-1-4-3 Section 960.3-1-4-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site recommendation...

10 CFR 960.3-1-4-3 - Site recommendation for characterization.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Site recommendation for characterization. 960.3-1-4-3 Section 960.3-1-4-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site recommendation...

10 CFR 960.3-1-4-3 - Site recommendation for characterization.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Site recommendation for characterization. 960.3-1-4-3 Section 960.3-1-4-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site recommendation...

10 CFR 960.3-1-4-3 - Site recommendation for characterization.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Site recommendation for characterization. 960.3-1-4-3 Section 960.3-1-4-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site recommendation...

Pulsed photothermal depth profiling of tattoos undergoing laser removal treatment

NASA Astrophysics Data System (ADS)

Milanic, Matija; Majaron, Boris

2012-02-01

Pulsed photothermal radiometry (PPTR) allows noninvasive determination of temperature depth profiles induced by pulsed laser irradiation of strongly scattering biological tissues and organs, including human skin. In present study, we evaluate the potential of this technique for investigational characterization and possibly quantitative evaluation of laser tattoo removal. The study involved 5 healthy volunteers (3 males, 2 females), age 20-30 years, undergoing tattoo removal treatment using a Q-switched Nd:YAG laser. There were four measurement and treatment sessions in total, separated by 2-3 months. Prior to each treatment, PPTR measurements were performed on several tattoo sites and one nearby healthy site in each patient, using a 5 ms Nd:YAG laser at low radiant exposure values and a dedicated radiometric setup. The laser-induced temperature profiles were then reconstructed by applying a custom numerical code. In addition, each tatoo site was documented with a digital camera and measured with a custom colorimetric system (in tristimulus color space), providing an objective evaluation of the therapeutic efficacy to be correlated with our PPTR results. The results show that the laser-induced temperature profile in untreated tattoos is invariably located at a subsurface depth of 300 μm. In tattoo sites that responded well to laser therapy, a significant drop of the temperature peak was observed in the profiles obtained from PPTR record. In several sites that appeared less responsive, as evidenced by colorimetric data, a progressive shift of the temperature profile deeper into the dermis was observed over the course of consecutive laser treatments, indicating that the laser tattoo removal was efficient.

Canopy reflectance related to marsh dieback onset and progression in Coastal Louisiana

USGS Publications Warehouse

Ramsey, Elijah W.; Rangoonwala, A.

2006-01-01

In this study, we extended previous work linking leaf spectral changes, dieback onset, and progression of Spartina alterniflora marshes to changes in site-specific canopy reflectance spectra. First, we obtained canopy reflectance spectra (approximately 20 m ground resolution) from the marsh sites occupied during the leaf spectral analyses and from additional sites exhibiting visual signs of dieback. Subsequently, the canopy spectra were analyzed at two spectral scales: the first scale corresponded to whole-spectra sensors, such as the NASA Earth Observing-1 (EO-1) Hyperion, and the second scale corresponded to broadband spectral sensors, such as the EO-1 Advanced Land Imager and the Landsat Enhanced Thematic Mapper. In the whole-spectra analysis, spectral indicators were generated from the whole canopy spectra (about 400 nm to 1,000 nm) by extracting typical dead and healthy marsh spectra, and subsequently using them to determine the percent composition of all canopy reflectance spectra. Percent compositions were then used to classify canopy spectra at each field site into groups exhibiting similar levels of dieback progression ranging from relatively healthy to completely dead. In the broadband reflectance analysis, blue, green, red, red-edge, and near infrared (NIR) spectral bands and NIR/green and NIR/red transforms were extracted from the canopy spectra. Spectral band and band transform indicators of marsh dieback and progression were generated by relating them to marsh status indicators derived from classifications of the 35 mm slides collected at the same time as the canopy reflectance recordings. The whole spectra and broadband spectral indicators were both able to distinguish (a) healthy marsh, (b) live marsh impacted by dieback, and (c) dead marsh, and they both provided some discrimination of dieback progression. Whole-spectra resolution sensors like the EO-1 Hyperion, however, offered an enhanced ability to categorize dieback progression. ?? 2006 American Society for Photogrammetry and Remote Sensing.

MX Siting Investigation. Prime Characterization Sites Central High Plains Candidate Siting Province.

DTIC Science & Technology

1979-02-15

information obtained from these studies , in combination with data obtained in the Screen- ing studies , has been used for geotechnical ranking (FN-TR-25). I...Plains Candi- date Siting Province (CSP), one of six provinces included in the geotechnical Characterization studies . The location of the sites within...remaining after Intermediate Screening were divided into CSPs based on similar geotechnical characteristics. Intermediate Screening studies (FN-TR-17

Systems integration of marketable subsystems: A collection of progress reports

NASA Technical Reports Server (NTRS)

1978-01-01

Monthly progress reports are given in the areas of marketable subsystems integration; development, design, and building of site data acquisition subsystems and data processing systems; operation of the solar test facility and a systems analysis.

A Task-oriented Approach for Hydrogeological Site Characterization

NASA Astrophysics Data System (ADS)

Rubin, Y.; Nowak, W.; de Barros, F.

2010-12-01

Hydrogeological site characterization is a challenging task from several reasons: (1) the large spatial variability and scarcity of prior information render the outcome of any planned sampling campaign uncertain; (2) there are no simple tools for comparing between the many alternative measurement techniques and data acquisition strategies, and (3) physical and budgetary constraints associated with data acquisition. This paper presents several ideas on how to plan sampling campaigns in a rational manner while addressing these challenges. The first idea is to recognize that different sites and different problems require different characterization strategies. Hence the idea is to plan data acquisition according to its capability for meeting site-specific goals. For example, the characterization needs at a “research problem” site (e.g., a site intended to investigate the transport of uranium in the subsurface such as in Hanford) are different from those of a “problem” site (e.g., contaminated site associated with a health risk to human such as Camp Lejeune, or determining the safe yield of an aquifer). This distinction requires planners to define the characterization goal(s) in a quantitative manner. The second idea is to define metrics that could link specific data types and data acquisition strategies with the site-specific goals in a way that would allow planners to compare between strongly different, alternatives strategies at the design stage (even prior to data acquisition) and to modify the strategies as more data become available. To meet this goal, we developed the concept of the (comparative) information yield curve. Finally, we propose to look at site characterization from the perspective of statistical hypothesis testing, whereby data acquisition strategies could be evaluated in terms of their ability to support or refute various hypotheses made with regard to the characterization goals, and the strategies could be modified once the test is completed. Accept/reject regions for hypothesis testing can be determined based on goals determined by regulations or by agreement between the stakeholders. Hypothesis-driven design could help in minimizing the chances of making wrong decision (false positives or false negatives) with regard to the site-specific goals.

Analytical methods for characterization of explosives-contaminated sites on U.S. Army installations

NASA Astrophysics Data System (ADS)

Jenkins, Thomas F.; Walsh, Marianne E.; Thorne, Philip G.

1995-10-01

The U.S. Army manufactures munitions at facilities throughout the United States. Many of these facilities are contaminated with residues of explosives from production, disposal of off- specification, and out-of-data munitions. The first step in remediating these sites is careful characterization. Currently sites are being characterized using a combination of on-site field screening and off-site laboratory analysis. Most of the contamination is associated with TNT (2,4,6-trinitrotoluene) and RDX (hexahydro-1,3,5-tri-nitro-1,3,5-triazine) and their manufacturing impurities and environmental transformation products. Both colorimetric and enzyme immunoassay-based field screening methods have been used successfully for on-site characterization. These methods have similar detection capabilities but differ in their selectivity. Although field screening is very cost-effective, laboratory analysis is still required to fully characterize a site. Laboratory analysis for explosives residues in the United States is generally conducted using high-performance liquid chromatography equipped with a UV detector. Air-dried soils are extracted with acetonitrile in an ultrasonic bath. Water is analyzed directly if detection limits in the range of 10 - 20 (mu) g/L are acceptable, or preconcentrated using either salting-out solvent extraction with acetonitrile or solid phase extraction.

Spatiotemporal progression of metastatic breast cancer: a Markov chain model highlighting the role of early metastatic sites

PubMed Central

Newton, Paul K; Mason, Jeremy; Venkatappa, Neethi; Jochelson, Maxine S; Hurt, Brian; Nieva, Jorge; Comen, Elizabeth; Norton, Larry; Kuhn, Peter

2015-01-01

Background: Cancer cell migration patterns are critical for understanding metastases and clinical evolution. Breast cancer spreads from one organ system to another via hematogenous and lymphatic routes. Although patterns of spread may superficially seem random and unpredictable, we explored the possibility that this is not the case. Aims: Develop a Markov based model of breast cancer progression that has predictive capability. Methods: On the basis of a longitudinal data set of 446 breast cancer patients, we created a Markov chain model of metastasis that describes the probabilities of metastasis occurring at a given anatomic site together with the probability of spread to additional sites. Progression is modeled as a random walk on a directed graph, where nodes represent anatomical sites where tumors can develop. Results: We quantify how survival depends on the location of the first metastatic site for different patient subcategories. In addition, we classify metastatic sites as “sponges” or “spreaders” with implications regarding anatomical pathway prediction and long-term survival. As metastatic tumors to the bone (main spreader) are most prominent, we focus in more detail on differences between groups of patients who form subsequent metastases to the lung as compared with the liver. Conclusions: We have found that spatiotemporal patterns of metastatic spread in breast cancer are neither random nor unpredictable. Furthermore, the novel concept of classifying organ sites as sponges or spreaders may motivate experiments seeking a biological basis for these phenomena and allow us to quantify the potential consequences of therapeutic targeting of sites in the oligometastatic setting and shed light on organotropic aspects of the disease. PMID:28721371

Necrotizing Fasciitis: How Reliable are the Cutaneous Signs?

PubMed Central

Kiat, Ho Jun; En Natalie, Yap Hui; Fatimah, Lateef

2017-01-01

Necrotizing fasciitis (NF) is a surgical emergency. It is often aggressive and characterized by the rapidly progressive inflammatory infection of the fascia that causes extensive necrosis of the subcutaneous tissue and fascia, relatively sparing the muscle and skin tissue. As the disease progresses, thrombosis of the affected cutaneous perforators subsequently devascularizes the overlying skin. The course indeed can be a fulminant one. The diagnosis of NF, especially in the early stages, is extremely challenging, and it can be very close in presentation to other skin and subcutaneous tissue infections. The primary site of the pathology is the deep fascia. Necrosis of the tissues and fascia may manifest as erythema without sharp margins, swelling, warmth, shiny, and exquisitely tender areas. Pain out of proportion to physical examination findings may be observed. The subcutaneous tissue may be firm and indurated such that the underlying muscle groups cannot be distinctly palpated. Eventually, as the overlying skin is stripped of its blood supply, skin necrosis ensues and hemorrhagic bullae form. Bacteremia and sepsis invariably develop when the infection is well established. This paper discusses some of issues related to the cutaneous signs found in NF and also provides a review the current, available literature on the subject matter. PMID:29097860

Progress of the Mars Array Technology Experiment (MATE) on the 2001 Lander

NASA Technical Reports Server (NTRS)

Scheiman, David A.; Baraona, Cosmo; Wilt, Dave; Jenkins, Phil; Krasowski, Michael; Greer, Lawrence; Lekki, John; Spina, Daniel; Landis, Geoff

2005-01-01

NASA is planning missions to Mars every two years until 2010, these missions will rely on solar power. Sunlight on the surface of Mars is altered by airborne dust and fluctuates from day to day. The MATE flight experiment was designed to evaluate solar cell performance and will fly on the Mars 2001 surveyor Lander as part of the Mars In-Situ Propellant Production Precursor (MIP) package. MATE will measure several solar cell technologies and characterize the Martian environment's solar power. This will be done by measuring full IV curvers on solar cells, direct and global insolation, temperature, and spectral content. The lander is scheduled to launch in April 2001 and arrive on Mars in January of 2002. The site location has not been identified but will be near the equator, is a powered landing, and is baselined for 90 sols. The intent of this paper is to provide a brief overview of the MATE experiment and progress to date. The MATE Development Unit (DU) hardware has been built and has completed testing, work is beginning in the Qualification Unit which will start testing later this year, Flight Hardware is to be delivered next spring.

Spousal Recollections of Early Signs of Primary Progressive Aphasia

ERIC Educational Resources Information Center

Pozzebon, Margaret; Douglas, Jacinta; Ames, David

2018-01-01

Background: Although primary progressive aphasia (PPA) is characterized by progressive loss of language and communication skills, knowledge about the earliest emerging signs announcing the onset of this condition is limited. Aims: To explore spousal recollections regarding the earliest signs of PPA and to compare the nature of the earliest…

Site Characterization and Monitoring Technical Support Center FY16 Report

EPA Science Inventory

SCMTSC’s primary goal is to provide technical assistance to regional programs on complex hazardous waste site characterization issues. This annual report illustrates the range and extent of projects that SCMTSC supported in FY 2016. Our principal audiences are site project manage...

Baseline Ecological Risk Assessment for the Upland at the LCP Chemical Site, Brunswick, Georgia - Site Investigation/Analysis and Risk Characterization (Final)

EPA Pesticide Factsheets

Site Investigation/Analysis and Risk Characterization (Final) Prepared for Honeywell International Inc. Prepared by CDR Environmental Specialists, Inc. August 2010 Region ID: 04 DocID: 10746263, DocDate: 08-01-2010

Identification of the antiepileptic racetam binding site in the synaptic vesicle protein 2A by molecular dynamics and docking simulations.

PubMed

Correa-Basurto, José; Cuevas-Hernández, Roberto I; Phillips-Farfán, Bryan V; Martínez-Archundia, Marlet; Romo-Mancillas, Antonio; Ramírez-Salinas, Gema L; Pérez-González, Óscar A; Trujillo-Ferrara, José; Mendoza-Torreblanca, Julieta G

2015-01-01

Synaptic vesicle protein 2A (SV2A) is an integral membrane protein necessary for the proper function of the central nervous system and is associated to the physiopathology of epilepsy. SV2A is the molecular target of the anti-epileptic drug levetiracetam and its racetam analogs. The racetam binding site in SV2A and the non-covalent interactions between racetams and SV2A are currently unknown; therefore, an in silico study was performed to explore these issues. Since SV2A has not been structurally characterized with X-ray crystallography or nuclear magnetic resonance, a three-dimensional (3D) model was built. The model was refined by performing a molecular dynamics simulation (MDS) and the interactions of SV2A with the racetams were determined by docking studies. A reliable 3D model of SV2A was obtained; it reached structural equilibrium during the last 15 ns of the MDS (50 ns) with remaining structural motions in the N-terminus and long cytoplasmic loop. The docking studies revealed that hydrophobic interactions and hydrogen bonds participate importantly in ligand recognition within the binding site. Residues T456, S665, W666, D670 and L689 were important for racetam binding within the trans-membrane hydrophilic core of SV2A. Identifying the racetam binding site within SV2A should facilitate the synthesis of suitable radio-ligands to study treatment response and possibly epilepsy progression.

Identification of the antiepileptic racetam binding site in the synaptic vesicle protein 2A by molecular dynamics and docking simulations

PubMed Central

Correa-Basurto, José; Cuevas-Hernández, Roberto I.; Phillips-Farfán, Bryan V.; Martínez-Archundia, Marlet; Romo-Mancillas, Antonio; Ramírez-Salinas, Gema L.; Pérez-González, Óscar A.; Trujillo-Ferrara, José; Mendoza-Torreblanca, Julieta G.

2015-01-01

Synaptic vesicle protein 2A (SV2A) is an integral membrane protein necessary for the proper function of the central nervous system and is associated to the physiopathology of epilepsy. SV2A is the molecular target of the anti-epileptic drug levetiracetam and its racetam analogs. The racetam binding site in SV2A and the non-covalent interactions between racetams and SV2A are currently unknown; therefore, an in silico study was performed to explore these issues. Since SV2A has not been structurally characterized with X-ray crystallography or nuclear magnetic resonance, a three-dimensional (3D) model was built. The model was refined by performing a molecular dynamics simulation (MDS) and the interactions of SV2A with the racetams were determined by docking studies. A reliable 3D model of SV2A was obtained; it reached structural equilibrium during the last 15 ns of the MDS (50 ns) with remaining structural motions in the N-terminus and long cytoplasmic loop. The docking studies revealed that hydrophobic interactions and hydrogen bonds participate importantly in ligand recognition within the binding site. Residues T456, S665, W666, D670 and L689 were important for racetam binding within the trans-membrane hydrophilic core of SV2A. Identifying the racetam binding site within SV2A should facilitate the synthesis of suitable radio-ligands to study treatment response and possibly epilepsy progression. PMID:25914622

Synthesis and characterization of (18)F-labeled active site inhibited factor VII (ASIS).

PubMed

Erlandsson, Maria; Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Jesper B; Petersen, Lars C; Madsen, Jacob; Kjaer, Andreas

2015-05-15

Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an (18)F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[(18)F]fluorobenzoate, and the [(18)F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [(18)F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [(18)F]ASIS and ASIS could be detected. Furthermore, [(18)F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [(18)F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [(18)F]ASIS are in progress. Copyright © 2015 John Wiley & Sons, Ltd.

Clinical and Demographic Characteristics Related to Onset

PubMed Central

Norris, Scott A; Jinnah, H A; Espay, Alberto J.; Klein, Christine; Brüggemann, Norbert; Barbano, Richard L.; Malaty, Irene; Rodriguez, Ramon L.; Vidailhet, Marie; Roze, Emmanuel; Reich, Stephen G.; Berman, Brian D.; LeDoux, Mark S.; Richardson, Sarah Pirio; Agarwal, Pinky; Mari, Zoltan; Ondo, William; Shih, Ludy C; Fox, Susan; Berardelli, Alfredo; Testa, Claudia M; Chang, Florence CF; Troung, Daniel; Nahab, Fatta; Xie, Tao; Hallett, Mark; Rosen, Ami R; Wright, Laura J; Perlmutter, JS

2016-01-01

Background Clinical characteristics of isolated, idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. Objectives To characterize clinical characteristics and demographics of isolated, idiopathic cervical dystonia in the largest standardized, multicenter cohort. Methods The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe and Australia recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread. Results Site of dystonia onset was: a) focal neck only (78.5%), b) focal onset elsewhere with later segmental spread to neck (13.3%), and c) segmental onset with initial neck involvement (8.2%).Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, is associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age. Conclusions Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. PMID:27753188

Discrimination Report ESTCP Project #MM-0437

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

Gasperikova, Erika

2008-10-01

The FY06 Defense Appropriation contains funding for the 'Development of Advanced, Sophisticated, and Discrimination Technologies for UXO Cleanup' in the Environmental Security Technology Certification Program. In 2003, the Defense Science Board observed: 'The...problem is that instruments that can detect the buried UXOs also detect numerous scrap metal objects and other artifacts, which leads to an enormous amount of expensive digging. Typically 100 holes may be dug before a real UXO is unearthed. The Task Force assessment is that much of this wasteful digging can be eliminated by the use of more advanced technology instruments that exploit modern digital processing andmore » advanced multi-mode sensors to achieve an improved level of discrimination of scrap from UXOs'. Significant progress has been made in discrimination technology. To date, testing of these approaches has been primarily limited to test sites with only limited application at live sites. Acceptance of discrimination technologies requires demonstration of system capabilities at UXO sites under real world conditions. FE Warren Air Force Base (AFB) in Cheyenne, WY is one such site. The demonstration objective was to determine the discrimination capabilities, cost and reliability of the Berkeley UXO Discriminator (BUD) in discrimination of UXO from scrap metal in real life conditions. Lawrence Berkeley National Laboratory performed a detection and discrimination survey of the Priority 1 area ({approx}5 acres) of the FE Warren AFB. The data included a system characterization with the emplaced calibration items and targets in the Geophysical Prove Out (GPO) area.« less

Milestones for Selection, Characterization, and Analysis of the Performance of a Repository for Spent Nuclear Fuel and High-Level Radioactive Waste at Yucca Mountain.

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

Rechard, Robert P.

This report presents a concise history in tabular form of events leading up to site identification in 1978, site selection in 1987, subsequent characterization, and ongoing analysis through 2009 of the performance of a repository for spent nuclear fuel and high - level radioactive waste at Yucca Mountain in southern Nevada. The tabulated events generally occurred in five periods: (1) commitment to mined geologic disposal and identification of sites; (2) site selection and analysis, based on regional geologic characterization through literature and analogous data; (3) feasibility analysis demonstrating calculation procedures and importance of system components, based on rough measures ofmore » performance using surface exploration, waste process knowledge, and general laboratory experiments; (4) suitability analysis demonstrating viability of disposal system, based on environment - specific laboratory experiments, in - situ experiments, and underground disposal system characterization; and (5) compliance analysis, based on completed site - specific characterization . The current sixth period beyond 2010 represents a new effort to set waste management policy in the United States. Because the relationship is important to understanding the evolution of the Yucca Mountain Project , the tabulation also shows the interaction between the policy realm and technical realm using four broad categories of events : (a) Regulatory requirements and related federal policy in laws and court decisions, (c) Presidential and agency directives, (c) technical milestones of implementing institutions, and (d) critiques of the Yucca Mountain Project and pertinent national and world events related to nuclear energy and radioactive waste. Preface The historical progression of technical milestones for the Yucca Mountain Project was originally developed for 10 journal articles in a special issue of Reliability Engineering System Safety on the performance assessment for the Yucca Mountain license application [1-10]. The listing of mile stones, a distinct feature of those articles, has been collected and tabulated here. A lthough a brief description is presented here (based on the summaries in the 10 journal articles), the emphasis remains on the tabulation because of its usefulness in providing a comprehensive but concise history of the Yucca Mountain Project. The tabulation presented here is more elaborate than originally presented in that many of the interactions that occurred between the technical realm and policy realm can be depicted in separate columns. The usefulness of the milestones table is due in part to L.A. Connolly, for editorial and reference support, and S.K. Best, Raytheon, and L. Mays, Sandia National Laboratories (SNL), for illustration support. Reviewers P.N. Swift, SNL, and K. Gupta, University of Oklahoma, helped improve the discussion. The historical perspective presented is that of the author and is not necessarily held by reviewers, Sandia National Laboratories , and the US Department of Energy. As a historic perspective, the author is reporting on the work of others; however, any interpretative error s of the documentation are those of the author alone. The characterization and modeling of the Yucca Mountain disposal system required numerous participants with expertise in many areas of science and technology, as evident from the extensive reference list. Their diligent efforts are generally acknowledged here and through the many references to their impressive work, but the 10 journal articles acknowledge by name many of the numerous participants that contributed to the Yucca Mountain Project .« less

Stennis Space Center Verification & Validation Capabilities

NASA Technical Reports Server (NTRS)

Pagnutti, Mary; Ryan, Robert E.; Holekamp, Kara; O'Neal, Duane; Knowlton, Kelly; Ross, Kenton; Blonski, Slawomir

2007-01-01

Scientists within NASA#s Applied Research & Technology Project Office (formerly the Applied Sciences Directorate) have developed a well-characterized remote sensing Verification & Validation (V&V) site at the John C. Stennis Space Center (SSC). This site enables the in-flight characterization of satellite and airborne high spatial resolution remote sensing systems and their products. The smaller scale of the newer high resolution remote sensing systems allows scientists to characterize geometric, spatial, and radiometric data properties using a single V&V site. The targets and techniques used to characterize data from these newer systems can differ significantly from the techniques used to characterize data from the earlier, coarser spatial resolution systems. Scientists have used the SSC V&V site to characterize thermal infrared systems. Enhancements are being considered to characterize active lidar systems. SSC employs geodetic targets, edge targets, radiometric tarps, atmospheric monitoring equipment, and thermal calibration ponds to characterize remote sensing data products. Similar techniques are used to characterize moderate spatial resolution sensing systems at selected nearby locations. The SSC Instrument Validation Lab is a key component of the V&V capability and is used to calibrate field instrumentation and to provide National Institute of Standards and Technology traceability. This poster presents a description of the SSC characterization capabilities and examples of calibration data.

A-3 Cleared Site

NASA Image and Video Library

2007-06-18

Work to clear the site for the A-3 Test Stand progresses quickly, as seen in this photo taken June 18 from atop the A-1 Test Stand. The next step in construction at 19-acre site will be the arrival of fill dirt in mid-July, followed by pilings and piling caps.

THE SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM: PROGRESS AND ACCOMPLISHMENTS - FISCAL YEAR 1990 A FOURTH REPORT TO CONGRESS

EPA Science Inventory

The SITE Program was the first major program for demonstrating and evaluating fullscale innovative treatment technologies at hazardous waste sites. Having concluded its fourth year, the SITE Program is recognized as a leading advocate of innovative technology development and comm...

A-3 Cleared Site

NASA Technical Reports Server (NTRS)

2007-01-01

Work to clear the site for the A-3 Test Stand progresses quickly, as seen in this photo taken June 18 from atop the A-1 Test Stand. The next step in construction at 19-acre site will be the arrival of fill dirt in mid-July, followed by pilings and piling caps.

Information Architecture for Bilingual Web Sites.

ERIC Educational Resources Information Center

Cunliffe, Daniel; Jones, Helen; Jarvis, Melanie; Egan, Kevin; Huws, Rhian; Munro, Sian

2002-01-01

Discusses creating an information architecture for a bilingual Web site and reports work in progress on the development of a content-based bilingual Web site to facilitate shared resources between speech and language therapists. Considers a structural analysis of existing bilingual Web designs and explains a card-sorting activity conducted with…

Prion protein gene analysis in three kindreds with fatal familial insomnia (FFI): Codon 178 mutation and codon 129 polymorphism

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

Medori, R.; Tritschler, H.J.

1993-10-01

Fatal familial insomnia (FFI) is a disease linked to a GAC(Asp) [yields] AAC(Asn) mutation in codon 178 of the prion protein (PrP) gene. FFI is characterized clinically by untreatable progressive insomnia, dysautonomia, and motor dysfunctions and is characterized pathologically by selective thalamic atrophy. The authors confirmed the 178[sup Asn] mutation in the PrP gene of a third FFI family of French ancestry. Three family members who are under 40 years of age and who inherited the mutation showed only reduced perfusion in the basal ganglia on single photon emission computerized tomography. Some FFI features differ from the clinical and neuropathologicmore » findings associated with 178[sup Asn] reported elsewhere. However, additional intragenic mutations accounting for the phenotypic differences were not observed in two affected individuals. In other sporadic and familial forms of Creutzfeldt-Jakob disease and Gerstmann-Straeussler syndrome, Met or Val homozygosity at polymorphic codon 129 is associated with a more severe phenotype, younger age at onset, and faster progression. In FFI, young and old individuals at disease onset had 129[sup Met/Val]. Moreover, of five 178[sup Asn] individuals who are above age-at-onset range and who are well, two have 129[sup Met] and three have 129[sup Met/Val], suggesting that polymorphic site 129 does not modulate FFI phenotypic expression. Genetic heterogeneity and environment may play an important role in inter- and intrafamilial variability of the 178[sup Asn] mutation. 32 refs., 5 figs., 1 tab.« less

Ka-Band Atmospheric Phase Stability Measurements in Goldstone, CA; White Sands, NM; and Guam

NASA Technical Reports Server (NTRS)

Zemba, Michael J.; Morse, Jacquelynne Rose; Nessel, James A.

2014-01-01

As spacecraft communication links are driven to higher frequencies (e.g. Ka-band) both by spectrum congestion and the appeal of higher data rates, the propagation phenomena at these frequencies must be well characterized for effective system design. In particular, the phase stability of a site at a given frequency will govern whether or not the site is a practical location for an antenna array, particularly if uplink capabilities are desired. Propagation studies to characterize such phenomena must be done on a site-by-site basis due to the wide variety of climates and weather conditions at each ground terminal. Accordingly, in order to statistically characterize the atmospheric effects on Ka-Band links, site test interferometers (STIs) have been deployed at three of NASA's operational sites to directly measure each site's tropospheric phase stability. Using three years of results from these experiments, this paper will statistically characterize the simultaneous atmospheric phase noise measurements recorded by the STIs deployed at the following ground station sites: the Goldstone Deep Space Communications Complex near Barstow, CA; the White Sands Ground Terminal near Las Cruces, NM; and the Guam Remote Ground Terminal on the island of Guam.

RAWP Progress Report August 19, 2011 - Combined

EPA Pesticide Factsheets

Combines cover letter and Progress Report #2 as required in Residential Soil Remedial Action Work Plan (RAWP)-Phase 1, with the Analytical Laboratory Report of Walter Coke Inc site in Birmingham AL, August 16, 2011, prepared by TestAmerica Laboratories.

Notification: EPA Progress in Reducing Taxpayer Environmental Liabilities

EPA Pesticide Factsheets

Project #OPE-FY15-0052, May 28, 2015. The EPA OIG plans to begin preliminary research on the EPA’s progress in reducing taxpayer liabilities through the use of financial assurance instruments for RCRA facilities and Superfund sites.

Progress Update: Stack Project Complete

ScienceCinema

Cody, Tom

2017-12-12

Progress update from the Savannah River Site. The 75 foot 293 F Stack, built for plutonium production, was cut down to size in order to prevent injury or release of toxic material if the structure were to collapse due to harsh weather.

Gene mapping of the Usher syndromes.

PubMed

Kimberling, W; Smith, R J

1992-10-01

USH is an autosomal recessive group of diseases characterized by auditory impairment and visual loss owing to RP. Two common types of USH are known, types I and II. USH type I is characterized by a congenital severe to profound hearing impairment, absent vestibular function, and a progressive pigmentary retinopathy. Persons with type I do not find hearing aids useful, have delayed motor development, and experience progressive night blindness and peripheral visual loss, which usually begins in their second decade. USH type II is characterized by a congenital moderate to severe hearing loss with a down-sloping audiogram, normal vestibular function, and a progressive pigmentary retinopathy. Persons with USH2 find hearing aids beneficial, have normal psychomotor development, and experience progressive night blindness and peripheral visual loss, which usually begins in their third decade. Vestibular dysfunction is the best distinguishing hallmark to differentiate USH type I from type II. One USH type II gene (called USH2) has been assigned to chromosome 1q. One USH type I gene has been tentatively assigned to chromosome 14q. There are other USH genes that have not yet been localized.

Science to Support DOE Site Cleanup: The Pacific Northwest National Laboratory Environmental Management Science Program Awards-Fiscal Year 1999 Mid-Year Progress Report

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

Peurrung, L.M.

1999-06-30

Pacific Northwest National Laboratory was awarded ten Environmental Management Science Program (EMSP) research grants in fiscal year 1996, six in fiscal year 1997, and eight in fiscal year 1998. This section summarizes how each grant addresses significant U.S. Department of Energy (DOE) cleanup issues, including those at the Hanford Site. The technical progress made to date in each of these research projects is addressed in more detail in the individual progress reports contained in this document. This research is focused primarily in five areas: Tank Waste Remediation, Decontamination and Decommissioning, Spent Nuclear Fuel and Nuclear Materials, Soil and Groundwater Cleanmore » Up, and Health Effects.« less

Environmental waste site characterization utilizing aerial photographs and satellite imagery: Three sites in New Mexico, USA

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

Van Eeckhout, E.; Pope, P.; Becker, N.

1996-04-01

The proper handling and characterization of past hazardous waste sites is becoming more and more important as world population extends into areas previously deemed undesirable. Historical photographs, past records, current aerial satellite imagery can play an important role in characterizing these sites. These data provide clear insight into defining problem areas which can be surface samples for further detail. Three such areas are discussed in this paper: (1) nuclear wastes buried in trenches at Los Alamos National Laboratory, (2) surface dumping at one site at Los Alamos National Laboratory, and (3) the historical development of a municipal landfill near Lasmore » Cruces, New Mexico.« less

CO{sub 2} Sequestration Capacity and Associated Aspects of the Most Promising Geologic Formations in the Rocky Mountain Region: Local-Scale Analyses

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

Laes, Denise; Eisinger, Chris; Morgan, Craig

2013-07-30

The purpose of this report is to provide a summary of individual local-­scale CCS site characterization studies conducted in Colorado, New Mexico and Utah. These site-­ specific characterization analyses were performed as part of the “Characterization of Most Promising Sequestration Formations in the Rocky Mountain Region” (RMCCS) project. The primary objective of these local-­scale analyses is to provide a basis for regional-­scale characterization efforts within each state. Specifically, limits on time and funding will typically inhibit CCS projects from conducting high-­ resolution characterization of a state-­sized region, but smaller (< 10,000 km{sup 2}) site analyses are usually possible, and suchmore » can provide insight regarding limiting factors for the regional-­scale geology. For the RMCCS project, the outcomes of these local-­scale studies provide a starting point for future local-­scale site characterization efforts in the Rocky Mountain region.« less

Multiscale Structure of UXO Site Characterization: Spatial Estimation and Uncertainty Quantification

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

Ostrouchov, George; Doll, William E.; Beard, Les P.

2009-01-01

Unexploded ordnance (UXO) site characterization must consider both how the contamination is generated and how we observe that contamination. Within the generation and observation processes, dependence structures can be exploited at multiple scales. We describe a conceptual site characterization process, the dependence structures available at several scales, and consider their statistical estimation aspects. It is evident that most of the statistical methods that are needed to address the estimation problems are known but their application-specific implementation may not be available. We demonstrate estimation at one scale and propose a representation for site contamination intensity that takes full account of uncertainty,more » is flexible enough to answer regulatory requirements, and is a practical tool for managing detailed spatial site characterization and remediation. The representation is based on point process spatial estimation methods that require modern computational resources for practical application. These methods have provisions for including prior and covariate information.« less

FATE AND TRANSPORT MODELING OF CONTAMINANTS OF CONCERN FROM A CAFO IN AN AGRICULTURAL WATERSHED

EPA Science Inventory

The groundwater flow and transport modeling effort will require hydrogeological site characterization and the development of a conceptual flow model for the site. Site characterization will involve an assessment of both the surface and subsurface and be accomplished through joint...

Draft environmental assessment: Davis Canyon site, Utah. Nuclear Waste Policy Act (Section 112). [Contains glossary

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

Not Available

1984-12-01

In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah, as one of nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for Nuclear Waste Repositories. These evaluations are reported in this draft environmental assessment (EA), which is being issued for public review and comment. The DOE findings and determinations that are based on these evaluationsmore » are preliminary and subject to public review and comment. A final EA will be prepared after considering the comments received. On the basis of the evaluations reported in this draft EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. The site is in the Paradox Basin, which is one of five distinct geohydrologic settings considered for the first repository. This setting contains one other potentially acceptable site - the Lavender Canyon site. Although the Lavender Canyon site appears to be suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. Furthermore, the DOE finds that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is proposing to nominate the Davis Canyon site as one of five sites suitable for characterization. Having compared the Davis Canyon site with the other four sites proposed for nomination, the DOE has determined that the Davis Canyon site is not one of the three preferred sites for recommendation to the President as candidates for characterization.« less

Airborne and Ground-Based Optical Characterization of Legacy Underground Nuclear Test Sites

NASA Astrophysics Data System (ADS)

Vigil, S.; Craven, J.; Anderson, D.; Dzur, R.; Schultz-Fellenz, E. S.; Sussman, A. J.

2015-12-01

Detecting, locating, and characterizing suspected underground nuclear test sites is a U.S. security priority. Currently, global underground nuclear explosion monitoring relies on seismic and infrasound sensor networks to provide rapid initial detection of potential underground nuclear tests. While seismic and infrasound might be able to generally locate potential underground nuclear tests, additional sensing methods might be required to further pinpoint test site locations. Optical remote sensing is a robust approach for site location and characterization due to the ability it provides to search large areas relatively quickly, resolve surface features in fine detail, and perform these tasks non-intrusively. Optical remote sensing provides both cultural and surface geological information about a site, for example, operational infrastructure, surface fractures. Surface geological information, when combined with known or estimated subsurface geologic information, could provide clues concerning test parameters. We have characterized two legacy nuclear test sites on the Nevada National Security Site (NNSS), U20ak and U20az using helicopter-, ground- and unmanned aerial system-based RGB imagery and light detection and ranging (lidar) systems. The multi-faceted information garnered from these different sensing modalities has allowed us to build a knowledge base of how a nuclear test site might look when sensed remotely, and the standoff distances required to resolve important site characteristics.

Measurement Sets and Sites Commonly Used for High Spatial Resolution Image Product Characterization

NASA Technical Reports Server (NTRS)

Pagnutti, Mary

2006-01-01

Scientists within NASA's Applied Sciences Directorate have developed a well-characterized remote sensing Verification & Validation (V&V) site at the John C. Stennis Space Center (SSC). This site has enabled the in-flight characterization of satellite high spatial resolution remote sensing system products form Space Imaging IKONOS, Digital Globe QuickBird, and ORBIMAGE OrbView, as well as advanced multispectral airborne digital camera products. SSC utilizes engineered geodetic targets, edge targets, radiometric tarps, atmospheric monitoring equipment and their Instrument Validation Laboratory to characterize high spatial resolution remote sensing data products. This presentation describes the SSC characterization capabilities and techniques in the visible through near infrared spectrum and examples of calibration results.

Uncertainty and Variability in Physiologically-Based ...

EPA Pesticide Factsheets

EPA announced the availability of the final report, Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies. This report summarizes some of the recent progress in characterizing uncertainty and variability in physiologically-based pharmacokinetic models and their predictions for use in risk assessment. This report summarizes some of the recent progress in characterizing uncertainty and variability in physiologically-based pharmacokinetic models and their predictions for use in risk assessment.

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

Ruzic, David

The Thermoelectric-Driven Liquid-Metal Plasma-Facing Structures (TELS) project was able to establish the experimental conditions necessary for flowing liquid metal surfaces in order to be utilized as surfaces facing fusion relevant energetic plasma flux. The work has also addressed additional developments along with progressing along the timeline detailed in the proposal. A no-cost extension was requested to conduct other relevant experiment- specifically regarding the characterization droplet ejection during energetic plasma flux impact. A specially designed trench module, which could accommodate trenches with different aspect ratios was fabricated and installed in the TELS setup and plasma gun experiments were performed. Droplet ejectionmore » was characterized using high speed image acquisition and also surface mounted probes were used to characterize the plasma. The Gantt chart below had been provided with the original proposal, indicating the tasks to be performed in the third year of funding. These tasks are listed above in the progress report outline, and their progress status is detailed below.« less

Mitochondrial transfer RNA(Phe) mutation associated with a progressive neurodegenerative disorder characterized by psychiatric disturbance, dementia, and akinesia-rigidity.

PubMed

Young, Tim M; Blakely, Emma L; Swalwell, Helen; Carter, Janet E; Kartsounis, Luke D; O'Donovan, Dominic G; Turnbull, Douglass M; Taylor, Robert W; de Silva, Rajith N

2010-11-01

Mitochondrial diseases are characterized by wide phenotypic and genetic variability, but presentations in adults with akinetic rigidity and hyperkinetic movement disorders are rare. To describe clinically a subject with progressive neurodegeneration characterized by psychosis, dementia, and akinesia-rigidity, and to associate this phenotype with a novel mitochondrial transfer RNA(Phe) (tRNA(Phe)) (MTTF) mutation. Case description and detailed laboratory investigations of a 57-year-old woman at a university teaching hospital and a specialist mitochondrial diagnostic laboratory. Histopathological findings indicated that an underlying mitochondrial abnormality was responsible for the subject's progressive neurological disorder, with mitochondrial genome sequencing revealing a novel m.586G>A MTTF mutation. The clinical phenotypes associated with mitochondrial disorders may include akinesia-rigidity and psychosis. Our findings further broaden the spectrum of neurological disease associated with mitochondrial tRNA(Phe) mutations.

Site Characterization for a Deep Borehole Field Test

NASA Astrophysics Data System (ADS)

Kuhlman, K. L.; Hardin, E. L.; Freeze, G. A.; Sassani, D.; Brady, P. V.

2015-12-01

The US Department of Energy Office of Nuclear Energy is at the beginning of 5-year Deep Borehole Field Test (DBFT) to investigate the feasibility of constructing and characterizing two boreholes in crystalline basement rock to a depth of 5 km (16,400 ft). The concept of deep borehole disposal for radioactive waste has some advantages over mined repositories, including incremental construction and loading, the enhanced natural barriers provided by deep continental crystalline basement, and reduced site characterization. Site characterization efforts need to determine an eligible site that does not have the following disqualifying characteristics: greater than 2 km to crystalline basement, upward vertical fluid potential gradients, presence of economically exploitable natural resources, presence of high permeability connection to the shallow subsurface, and significant probability of future seismic or volcanic activity. Site characterization activities for the DBFT will include geomechanical (i.e., rock in situ stress state, and fluid pressure), geological (i.e., rock and fracture infill lithology), hydrological (i.e., quantity of fluid, fluid convection properties, and solute transport mechanisms), and geochemical (i.e., rock-water interaction and natural tracers) aspects. Both direct (i.e., sampling and in situ testing) and indirect (i.e., borehole geophysical) methods are planned for efficient and effective characterization of these site aspects and physical processes. Borehole-based characterization will be used to determine the variability of system state (i.e., stress, pressure, temperature, and chemistry) with depth, and interpretation of material and system parameters relevant to numerical site simulation. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Building dismantlement and site remediation at the Apollo Fuel Plant: When is technology the answer?

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

Walton, L.

1995-01-01

The Apollo fuel plant was located in Pennsylvania on a site known to have been used continuously for stell production from before the Civil War until after World War II. Then the site became a nuclear fuel chemical processing plants. Finally it was used to convert uranium hexafluoride to various oxide fuel forms. After the fuel manufacturing operations were teminated, the processing equipment was partially decontaminated, removed, packaged and shipped to a licensed low-level radioactive waste burial site. The work was completed in 1984. In 1990 a detailed site characterization was initiated to establishe the extent of contamination and tomore » plan the building dismantlement and soil remediation efforts. This article discusses the site characterization and remedial action at the site in the following subsections: characterization; criticality control; mobile containment; soil washing; in-process measurements; and the final outcome of the project.« less

Beneficial uses program. Progress report ending December 31, 1979

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

None

1980-06-01

Progress is reported in research on uses of irradiated sewage sludge, particularly as a cattle feed supplement and commercial fertilizer additive, on potential sites for irradiator demonstration plants, and on the inactivation of enteric bacteria by radiation treatment. (LCL)

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.

Does sediment geochemistry (based on selective extractions of Al and Fe and REE) provide a record of soil evolution?

NASA Astrophysics Data System (ADS)

Mourier, B.; Poulenard, J.; Blarquez, O.; Williamson, D.; Arnaud, F.; Carcaillet, C.

2009-04-01

Soil is a natural body occurring at the interface between the lithosphere, atmosphere and biosphere. As a result, the physical and chemical properties of soils evolve with time, and the reconstruction of their history represents a key to understand past environmental changes. Palaeolimnological techniques such as sediment geochemistry can be used to investigate changes in catchment history by providing information about soil development. However, due to the lack of conservative pedosignatures (soil proxies), only few paleoecological studies have attempted to reconstruct the history of soil genesis using geochemical analyses of lacustrine sediments. Here we present a multidisciplinary study which aims to use pedosignatures, defined by a previous soil study, in order to characterize the history of soil genesis, podzolization and chemical weathering processes in two sediment sequences. Moreover, we aim to compare the timing of soil evolution with other paleoenvironmental markers (macroremains, charcoals…) in order to infer the role of climate, vegetation and possible human activities as forcing factors. In a first step, the geochemical investigation of eight subalpine soil profiles from the inner Alps allowed to define relevant proxies of two major soil processes. Parent material normalized REE patterns provide a precise tracer of chemical weathering whereas the proportions of secondary Al- and Fe-bearing phases provide a tracer of the podzolisation process. Then, the same tracers were assessed on two lacustrine and peat sediment sequences (Loup and Thyl lakes) from the subalpine domain. The proxy records, spanning ca. 4.500 yr at the Thyl lake and ca. 13.500 yr at the Loup lake, indicate that both progressive and regressive pedogenesis occurred after the deglaciation. The Thyl record is highly contrasted: the progressive setting of the mixed cembra pine ecosystem is associated to the podzolisation process (secondary Al- and Fe-bearing phases are maximal) and the increase of chemical weathering (enrichments of specific REE's fractions) that lasted totally ca. 1500 to 2000 years. Then, these progressive pathways are followed by abrupt and rapid secondary processes that could result from drastic transformation of the plant cover. The flat normalized REE patterns associated with low secondary Al and Fe values suggest a decrease of chemical weathering and podzolization. Moreover, the higher variability in cembra pine and the enrichment in sedge and other herbs remains in the lake suggest the setting of semi-open vegetation associated to the evidence of regressive soil processes. On the other hand, Loup environment and soil history are characterized by a progressive and stable evolution leading to present day old growing forests and Podzol soil type. Whereas the major sedimentological changes are sensitive to climate, the soil proxy records may be more triggered by the natural dynamic of the plant cover. At this site, human disturbances seem to have lower importance than at the Thyl site.

Soil erosion at agricultural land in Moravia loess region estimated by using magnetic properties

NASA Astrophysics Data System (ADS)

Kapicka, Ales; Dlouha, Sarka; Petrovsky, Eduard; Jaksik, Ondrej; Grison, Hana; Kodesova, Radka

2014-05-01

A detailed field study on a small test site of agricultural land situated in loess region in Southern Moravia (Czech Republic) and subsequent laboratory analyses have been carried out in order to test the applicability of magnetic methods for the estimation of soil erosion. Chernozem, the original dominant soil unit in the wider area, is nowadays progressively transformed into different soil units along with intensive soil erosion. As a result, an extremely diversified soil cover structure has resulted from the erosion. The site was characterized by a flat upper part while the middle part, formed by a substantive side valley, is steeper (up to 15°). We carried out field measurements of magnetic susceptibility on a regular grid, resulting in 101 data points. The bulk soil material for laboratory investigation was gathered from all the grid points. We found a strong correlation between the volume magnetic susceptibility (field measurement) and mass specific magnetic susceptibility measured in the laboratory (R2 = 0.80). Values of the magnetic susceptibility are spatially distributed depending on the terrain. Higher values were measured in the flat upper part (where the original top horizon remained). The lowest values of magnetic susceptibility were obtained on the steep valley sides. Here the original topsoil was eroded and mixed by tillage with the soil substrate (loess). The soil profile that was unaffected by erosion was investigated in detail. The vertical distribution of magnetic susceptibility along this "virgin" profile was measured in laboratory on the samples from layers along the whole profile with 2-cm spacing. The undisturbed profile shows several soil horizons. Horizons Ac and A show a slight increase in magnetic susceptibility up to a depth of about 70 cm. Horizon A/Ck is characterized by a decrease in susceptibility, and the underlying C horizon (h > 103 cm) has a very low value of magnetic susceptibility. The differences between the values of susceptibility in the undisturbed soil profile and the magnetic signal after uniform mixing the soil material as a result of tillage and erosion are fundamental for the estimation of soil loss in the studied test field. Using the uneroded profile from the studied locality as a basis for examining the changes in cultivated soils, tillage homogenization model can be applied to predict changes in the surface soil magnetism with progressive soil erosion. The model is very well applicable at the studied site. Acknowledgement: This study was supported by NAZV Agency of the Ministry of Agriculture of the Czech Republic through grant No QJ1230319

Common Progress Monitoring Omissions: Planning and Practice. Progress Monitoring Brief #1

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring, one of the essential components of Response to Intervention (RTI), is characterized by repeated measurement of academic performance that is conducted at least monthly. The process may be used to assess students' academic performance over time, to quantify student rates of improvement or responsiveness to instruction, and to…

Common Progress Monitoring Omissions: Reporting Information to Parents. Progress Monitoring Brief #4

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring, one of the essential components of Response to Intervention (RTI), is characterized by repeated measurement of academic performance that is conducted at least monthly. The process may be used to assess students' academic performance over time, to quantify student rates of improvement or responsiveness to instruction, and to…

Liver Injury and Fibrosis Induced by Dietary Challenge in the Ossabaw Miniature Swine

PubMed Central

Liang, Tiebing; Alloosh, Mouhamad; Bell, Lauren N.; Fullenkamp, Allison; Saxena, Romil; Van Alstine, William; Bybee, Phelan; Werling, Klára; Sturek, Michael; Chalasani, Naga; Masuoka, Howard C.

2015-01-01

Background Ossabaw miniature swine when fed a diet high in fructose, saturated fat and cholesterol (NASH diet) develop metabolic syndrome and nonalcoholic steatohepatitis (NASH) characterized by liver injury and fibrosis. This study was conducted to further characterize the development of NASH in this large animal model. Methods Ossabaw swine were fed standard chow (control group; n = 6) or NASH diet (n = 6) for 24 weeks. Blood and liver tissue were collected and liver histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention. Hepatic apoptosis and lipid levels were assessed at week 24. Results The NASH diet group developed metabolic syndrome and progressive histologic features of NASH including: (a) hepatocyte ballooning at 8 weeks which progressed to extensive ballooning (>90% hepatocytes), (b) hepatic fibrosis at week 16, which progressed to moderate fibrosis, and (c) Kupffer cell accumulation with vacuolization at 8 weeks which progressed through week 24. The NASH diet group showed increased hepatocyte apoptosis that correlated with hepatic total and free cholesterol and free fatty acids, but not esterified cholesterol or triglycerides. Conclusions This report further characterizes the progression of diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet: (a) hepatocyte injury and fibrosis can occur without macrovesicular steatosis or excess triglyceride accumulation; (b) hepatocyte ballooning generally precedes the development of fibrosis; (c) there is increased hepatocyte apoptosis, and it is correlated more significantly with hepatic free cholesterol than hepatic free fatty acids and had no correlation with hepatic triglycerides. PMID:25978364

Learning of speckle statistics for in vivo and noninvasive characterization of cutaneous wound regions using laser speckle contrast imaging.

PubMed

Basak, Kausik; Dey, Goutam; Mahadevappa, Manjunatha; Mandal, Mahitosh; Sheet, Debdoot; Dutta, Pranab Kumar

2016-09-01

Laser speckle contrast imaging (LSCI) provides a noninvasive and cost effective solution for in vivo monitoring of blood flow. So far, most of the researches consider changes in speckle pattern (i.e. correlation time of speckle intensity fluctuation), account for relative change in blood flow during abnormal conditions. This paper introduces an application of LSCI for monitoring wound progression and characterization of cutaneous wound regions on mice model. Speckle images are captured on a tumor wound region at mice leg in periodic interval. Initially, raw speckle images are converted to their corresponding contrast images. Functional characterization begins with first segmenting the affected area using k-means clustering, taking wavelet energies in a local region as feature set. In the next stage, different regions in wound bed are clustered based on progressive and non-progressive nature of tissue properties. Changes in contrast due to heterogeneity in tissue structure and functionality are modeled using LSCI speckle statistics. Final characterization is achieved through supervised learning of these speckle statistics using support vector machine. On cross evaluation with mice model experiment, the proposed approach classifies the progressive and non-progressive wound regions with an average sensitivity of 96.18%, 97.62% and average specificity of 97.24%, 96.42% respectively. The clinical information yield with this approach is validated with the conventional immunohistochemistry result of wound to justify the ability of LSCI for in vivo, noninvasive and periodic assessment of wounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of Electrical Conductivity Logging to Characterize the Geological Context of Releases at UST Sites

EPA Science Inventory

Risk is the combination of hazard and exposure. Risk characterization at UST release sites has traditionally emphasized hazard (presence of residual fuel) with little attention to exposure. Exposure characterization often limited to a one-dimensional model such as the RBCA equa...

Lunar site characterization and mining

NASA Technical Reports Server (NTRS)

Glass, Charles E.

1992-01-01

Lunar mining requirements do not appear to be excessively demanding in terms of volume of material processed. It seems clear, however, that the labor-intensive practices that characterize terrestrial mining will not suffice at the low-gravity, hard-vacuum, and inaccessible sites on the Moon. New research efforts are needed in three important areas: (1) to develop high-speed, high-resolution through-rock vision systems that will permit more detailed and efficient mine site investigation and characterization; (2) to investigate the impact of lunar conditions on our ability to convert conventional mining and exploration equipment to lunar prototypes; and (3) to develop telerobotic or fully robotic mining systems for operations on the Moon and other bodies in the inner solar system. Other aspects of lunar site characterization and mining are discussed.

Usher Syndrome Type III: Revised Genomic Structure of the USH3 Gene and Identification of Novel Mutations

PubMed Central

Fields, Randall R.; Zhou, Guimei; Huang, Dali; Davis, Jack R.; Möller, Claes; Jacobson, Samuel G.; Kimberling, William J.; Sumegi, Janos

2002-01-01

Usher syndrome type III is an autosomal recessive disorder characterized by progressive sensorineural hearing loss, vestibular dysfunction, and retinitis pigmentosa. The disease gene was localized to 3q25 and recently was identified by positional cloning. In the present study, we have revised the structure of the USH3 gene, including a new translation start site, 5′ untranslated region, and a transcript encoding a 232–amino acid protein. The mature form of the protein is predicted to contain three transmembrane domains and 204 residues. We have found four new disease-causing mutations, including one that appears to be relatively common in the Ashkenazi Jewish population. We have also identified mouse (chromosome 3) and rat (chromosome 2) orthologues, as well as two human paralogues on chromosomes 4 and 10. PMID:12145752

The Personal Human Oral Microbiome Obscures the Effects of Treatment on Periodontal Disease

PubMed Central

Schwarzberg, Karen; Le, Rosalin; Bharti, Balambal; Lindsay, Suzanne; Casaburi, Giorgio; Salvatore, Francesco; Saber, Mohamed H.; Alonaizan, Faisal; Slots, Jørgen; Gottlieb, Roberta A.; Caporaso, J. Gregory; Kelley, Scott T.

2014-01-01

Periodontitis is a progressive disease of the periodontium with a complex, polymicrobial etiology. Recent Next-Generation Sequencing (NGS) studies of the microbial diversity associated with periodontitis have revealed strong, community-level differences in bacterial assemblages associated with healthy or diseased periodontal sites. In this study, we used NGS approaches to characterize changes in periodontal pocket bacterial diversity after standard periodontal treatment. Despite consistent changes in the abundance of certain taxa in individuals whose condition improved with treatment, post-treatment samples retained the highest similarity to pre-treatment samples from the same individual. Deeper phylogenetic analysis of periodontal pathogen-containing genera Prevotella and Fusobacterium found both unexpected diversity and differential treatment response among species. Our results highlight how understanding interpersonal variability among microbiomes is necessary for determining how polymicrobial diseases respond to treatment and disturbance. PMID:24489772

European Extremely Large Telescope: progress report

NASA Astrophysics Data System (ADS)

Tamai, R.; Spyromilio, J.

2014-07-01

The European Extremely Large Telescope is a project of the European Southern Observatory to build and operate a 40-m class optical near-infrared telescope. The telescope design effort is largely concluded and construction contracts are being placed with industry and academic/research institutes for the various components. The siting of the telescope in Northern Chile close to the Paranal site allows for an integrated operation of the facility providing significant economies. The progress of the project in various areas is presented in this paper and references to other papers at this SPIE meeting are made.

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

Effects of Social Networking on Adolescent Education

ERIC Educational Resources Information Center

Miah, Muhammed; Omar, Adnan; Allison-Golding, Monique

2013-01-01

In recent years, the use of social networking sites has grown tremendously especially among the teens and high school students. However, very little is known about the scale of use, the purpose, how students use these sites and, more specifically, whether these sites help or hurt their academic progress. This study investigates how high school…

Increasing the vocational focus of the community mental health team.

PubMed

Seebohm, Patience; Secker, Jenny

2003-08-01

Despite increasing interest in the UK in enabling community mental health teams to support clients' vocational aspirations, surveys suggest that progress to date has been slow. This study aimed to identify factors that facilitate or create barriers to teams engaging in vocational work by exploring experiences and perceptions at three sites where progress had been made. Semi-structured interviews were carried out with on-site and off-site vocational specialists, care coordinators and other professionals identified locally as supportive of vocational work. Participants' accounts were compared with a framework derived from previous research into effective vocational services. The framework encompassed partnership working, attention to clients' needs, choices and mental health, and enabling clients to access and retain employment. Interprofessional partnership working emerged as particularly strong at one site and in turn was key to facilitating attention to the other elements of the framework. Conversely, at the other two sites less well-developed partnership working could create barriers to addressing these elements. Across all three sites access to expert welfare benefits advice was problematic, with evidence of widespread ignorance about the crucial issues involved.

EG-07CELL CYCLE SIGNATURE AND TUMOR PHYLOGENY ARE ENCODED IN THE EVOLUTIONARY DYNAMICS OF DNA METHYLATION IN GLIOMA

PubMed Central

Mazor, Tali; Pankov, Aleksandr; Johnson, Brett E.; Hong, Chibo; Bell, Robert J.A.; Smirnov, Ivan V.; Reis, Gerald F.; Phillips, Joanna J.; Barnes, Michael; Bollen, Andrew W.; Taylor, Barry S.; Molinaro, Annette M.; Olshen, Adam B.; Song, Jun S.; Berger, Mitchel S.; Chang, Susan M.; Costello, Joseph F.

2014-01-01

The clonal evolution of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast, tumor epigenetic states, including DNA methylation, are reversible and sensitive to the tumor microenvironment, presumably precluding the use of epigenetics to discover tumor phylogeny. Here we examined the spatial and temporal dynamics of DNA methylation in a clinically and genetically characterized cohort of IDH1-mutant low-grade gliomas and their patient-matched recurrences. WHO grade II gliomas are diffuse, infiltrative tumors that frequently recur and may undergo malignant progression to a higher grade with a worse prognosis. The extent to which epigenetic alterations contribute to the evolution of low-grade gliomas, including malignant progression, is unknown. While all gliomas in the cohort exhibited the hypermethylation signature associated with IDH1 mutation, low-grade gliomas that underwent malignant progression to high-grade glioblastoma (GBM) had a unique signature of DNA hypomethylation enriched for active enhancers, as well as sites of age-related hypermethylation in the brain. Genes with promoter hypomethylation and concordant transcriptional upregulation during evolution to GBM were enriched in cell cycle function, evolving in concert with genetic alterations that deregulate the G1/S cell cycle checkpoint. Despite the plasticity of tumor epigenetic states, phyloepigenetic trees robustly recapitulated phylogenetic trees derived from somatic mutations in the same patients. These findings highlight widespread co-dependency of genetic and epigenetic events throughout the clonal evolution of initial and recurrent glioma.

Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q.

PubMed

Sankila, E M; Pakarinen, L; Kääriäinen, H; Aittomäki, K; Karjalainen, S; Sistonen, P; de la Chapelle, A

1995-01-01

Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to severe, and the vestibular function is normal. Progressive pigmentary retinopathy (PPR) is present in both types. A third type (USH3) differing from USH2 by the progressive nature of its hearing loss has been suggested. USH3 has previously been estimated to comprise 2% of all USH. However, based on clinical criteria, in Finland 42% of USH patients have progressive hearing loss suggesting enrichment of an USH3 gene. We excluded the four previously mapped USH regions as the site of the USH3 disease locus. Systematic search for USH3 by genetic linkage analyses in 10 multiple affected families using polymorphic microsatellite markers revealed significant linkage with markers mapping to chromosome 3q. Pairwise lod scores at zero recombination distance were 7.87 for D3S1308, and 11.29 for D3S1299, incorporating the observed linkage disequilibrium. Conventional multipoint linkage analysis gave a maximum lod score of 9.88 at D3S1299 assigning USH3 to the 5 cM interval between markers D3S1555 and D3S1279 in 3q21-25.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphic site index curves for white pine in the southern Appalachians

Treesearch

Donald E. Beck

1971-01-01

Site index curves are presented for natural stands of even-aged white pine in the southern Appalachians. The curves are based on measured height-growth trends in 42 stands. Shape of the height-growth curves was shown to change progressively with the level of site index, and these polymorphic trends are incorporated in the finished site-index curves. Comparison of the...

Characterization of mitosis-specific phosphorylation of tumor-associated microtubule-associated protein.

PubMed

Hong, Kyung Uk; Kim, Hyun-Jun; Bae, Chang-Dae; Park, Joobae

2009-11-30

Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2), has been recently shown to be involved in the assembly and maintenance of mitotic spindle and also plays an essential role in maintaining the fidelity of chromosome segregation during mitosis. We have previously reported that TMAP is phosphorylated at multiple residues specifically during mitosis, and characterized the mechanism and functional importance of phosphorylation at one of the mitosis-specific phosphorylation residues (i.e., Thr-622). However, the phosphorylation events at the remaining mitotic phosphorylation sites of TMAP have not been fully characterized in detail. Here, we report on generation and characterization of phosphorylated Thr-578- and phosphorylated Thr-596-specific antibodies. Using the antibodies, we show that phosphorylation of TMAP at Thr-578 and Thr-596 indeed occurs specifically during mitosis. Immunofluorescent staining using the antibodies shows that these residues become phosphorylated starting at prophase and then become rapidly dephosphorylated soon after initiation of anaphase. Subtle differences in the kinetics of phosphorylation between Thr-578 and Thr-596 imply that they may be under different mechanisms of phosphorylation during mitosis. Unlike the phosphorylation-deficient mutant form for Thr-622, the mutant in which both Thr-578 and Thr-596 had been mutated to alanines did not induce significant delay in progression of mitosis. These results show that the majority of mitosis-specific phosphorylation of TMAP is limited to pre-anaphase stages and suggest that the multiple phosphorylation may not act in concert but serve diverse functions.

RESOLVE Projects: Lunar Water Resource Demonstration and Regolith Volatile Characterization

NASA Technical Reports Server (NTRS)

2008-01-01

To sustain affordable human and robotic space exploration, the ability to live off the land at the exploration site will be essential. NASA calls this ability in situ resource utilization (ISRU) and is focusing on finding ways to sustain missions first on the Moon and then on Mars. The ISRU project aims to develop capabilities to technology readiness level 6 for the Robotic Lunar Exploration Program and early human missions returning to the Moon. NASA is concentrating on three primary areas of ISRU: (1) excavating, handling, and moving lunar regolith, (2) extracting oxygen from lunar regolith, and (3) finding, characterizing, extracting, separating, and storing volatile lunar resources, especially in the permanently shadowed polar craters. To meet the challenges related to technology development for these three primary focus areas, the Regolith and Environment Science and Oxygen and Lunar Volatile Extraction (RESOLVE) project was initiated in February 2005, through funding by the Exploration Systems Mission Directorate. RESOLVE's objectives are to develop requirements and conceptual designs and to perform breadboard concept verification testing of each experiment module. The final goal is to deliver a flight prototype unit that has been tested in a relevant lunar polar environment. Here we report progress toward the third primary area creating ways to find, characterize, extract, separate, and store volatile lunar resources. The tasks include studying thermal, chemical, and electrical ways to collect such volatile resources as hydrogen, water, nitrogen, methane, and ammonia. We approached this effort through two subtasks: lunar water resource demonstration (LWRD) and regolith volatile characterization (RVC).

Development of a Methodology for Hydrogeological Characterization of Faults: Progress of the Project in Berkeley, California

NASA Astrophysics Data System (ADS)

Goto, J.; Moriya, T.; Yoshimura, K.; Tsuchi, H.; Karasaki, K.; Onishi, T.; Ueta, K.; Tanaka, S.; Kiho, K.

2010-12-01

The Nuclear Waste Management Organization of Japan (NUMO), in collaboration with Lawrence Berkeley National Laboratory (LBNL), has carried out a project to develop an efficient and practical methodology to characterize hydrologic property of faults since 2007, exclusively for the early stage of siting a deep underground repository. A preliminary flowchart of the characterization program and a classification scheme of fault hydrology based on the geological feature have been proposed. These have been tested through the field characterization program on the Wildcat Fault in Berkeley, California. The Wildcat Fault is a relatively large non-active strike-slip fault which is believed to be a subsidiary of the active Hayward Fault. Our classification scheme assumes the contrasting hydrologic features between the linear northern part and the split/spread southern part of the Wildcat Fault. The field characterization program to date has been concentrated in and around the LBNL site on the southern part of the fault. Several lines of electrical and reflection seismic surveys, and subsequent trench investigations, have revealed the approximate distribution and near-surface features of the Wildcat Fault (see also Onishi, et al. and Ueta, et al.). Three 150m deep boreholes, WF-1 to WF-3, have been drilled on a line normal to the trace of the fault in the LBNL site. Two vertical holes were placed to characterize the undisturbed Miocene sedimentary formations at the eastern and western sides of the fault (WF-1 and WF-2 respectively). WF-2 on the western side intersected the rock formation, which was expected only in WF-1, and several of various intensities. Therefore, WF-3, originally planned as inclined to penetrate the fault, was replaced by the vertical hole further to the west. It again encountered unexpected rocks and faults. Preliminary results of in-situ hydraulic tests suggested that the transmissivity of WF-1 is ten to one hundred times higher than WF-2. The monitoring of hydraulic pressure displayed different head distribution patterns between WF-1 and WF-2 (see also Karasaki, et al.). Based on these results, three hypotheses on the distribution of the Wildcat Fault were proposed: (a) a vertical fault in between WF-1 and WF-2, (b) a more gently dipping fault intersected in WF-2 and WF-3, and (c) a wide zone of faults extending between WF-1 and WF-3. At present, WF-4, an inclined hole to penetrate the possible (eastern?) master fault, is ongoing to test these hypotheses. After the WF-4 investigation, hydrologic and geochemical analyses and modeling of the southern part of the fault will be carried out. A simpler field characterization program will also be carried out in the northern part of the fault. Finally, all the results will be synthesized to improve the comprehensive methodology.

Assessment of remote sensing technologies to discover and characterize waste sites

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

NONE

1992-03-11

This report presents details about waste management practices that are being developed using remote sensing techniques to characterize DOE waste sites. Once the sites and problems have been located and characterized and an achievable restoration and remediation program have been established, efforts to reclaim the environment will begin. Special problems to be considered are: concentrated waste forms in tanks and pits; soil and ground water contamination; ground safety hazards for workers; and requirement for long-term monitoring.

Predictors of Recurrence, Progression, and Retreatment in Basilar Tip Aneurysms: A Location-Controlled Analysis.

PubMed

Abecassis, Isaac Josh; Sen, Rajeev D; Barber, Jason; Shetty, Rakshith; Kelly, Cory M; Ghodke, Basavaraj V; Hallam, Danial K; Levitt, Michael R; Kim, Louis J; Sekhar, Laligam N

2018-06-14

Endovascular treatment of intracranial aneurysms is associated with higher rates of recurrence and retreatment, though contemporary rates and risk factors for basilar tip aneurysms (BTAs) are less well-described. To characterize progression, retreatement, and retreated progression of BTAs treated with microsurgical or endovascular interventions. We retrospectively reviewed records for 141 consecutive BTA patients. We included 158 anterior communicating artery (ACoA) and 118 middle cerebral artery (MCA) aneurysms as controls. Univariate and multivariate analyses were used to calculate rates of progression (recurrence of previously obliterated aneurysms and progression of known residual aneurysm dome or neck), retreatment, and retreated progression. Kaplan-Meier analysis was used to characterize 24-mo event rates for primary outcome prediction. Of 141 BTA patients, 62.4% were ruptured and 37.6% were unruptured. Average radiographical follow-up was 33 mo. Among ruptured aneurysms treated with clipping, there were 2 rehemorrhages due to recurrence (6.1%), and none in any other cohorts. Overall rates of progression (28.9%), retreatment (28.9%), and retreated progression (24.7%) were not significantly different between surgical and endovascular subgroups, though ruptured aneurysms had higher event rates. Multivariate modeling confirmed rupture status (P = .003, hazard ratio = 0.14) and aneurysm dome width (P = .005, hazard ratio = 1.23) as independent predictors of progression requiring retreatment. In a separate multivariate analysis with ACoA and MCA aneurysms, basilar tip location was an independent predictor of progression, retreatment, and retreated progression. BTAs have higher rates of progression and retreated progression than other aneurysm locations, independent of treatment modality. Rupture status and dome width are risk factors for progression requiring retreatment.

Hyperfractionated Low-Dose (21 Gy) Radiotherapy for Cranial Skeletal Metastases in Patients With High-Risk Neuroblastoma

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

Kushner, Brian H., E-mail: kushnerb@mskcc.or; Cheung, Nai-Kong V.; Barker, Christopher A.

2009-11-15

Purpose: To present a large experience (73 patients) using a standard radiotherapy (RT) protocol to prevent relapse in cranial sites where measurable metastatic neuroblastoma (NB), an adverse prognostic marker, is common. Methods and Materials: High-risk NB patients with measurable cranial disease at diagnosis or residual cranial disease after induction therapy had those sites irradiated with hyperfractionated 21 Gy; a brain-sparing technique was used for an extensive field. The patients were grouped according to the response to systemic therapy. Thus, when irradiated, Group 1 patients were in complete remission and Group 2 patients had primary refractory disease. Follow-up was from themore » start of cranial RT. Results: At 3 years, the 39 Group 1 patients had a progression-free survival rate of 51%; control of cranial disease was 79%. Two relapses involved irradiated cranial sites. Two other patients relapsed in the irradiated cranial sites 6 and 12 months after a systemic relapse. At 3 years, the 34 Group 2 patients had a progression-free survival rate of 33%; control of cranial disease was 52%. Group 2 included 19 patients who had residual cranial (with or without extracranial) disease. The cranial sites showed major (n = 13), minor (n = 2), or no response (n = 4) to RT. Five patients had progression in the cranial RT field at 10-27 months. Group 2 also included 15 patients who had persistent NB in extracranial, but not cranial, sites. Of these 15 patients, 2 relapsed in the irradiated cranial sites and elsewhere at 8 and 14 months. Cranial RT was well tolerated, with no Grade 2 or greater toxicity. Conclusion: Hyperfractionated 21-Gy cranial RT might help control NB and is feasible without significant toxicity in children.« less

SITE CHARACTERIZATION TO SUPPORT DEVELOPMENT OF CONCEPTUAL SITE MODELS AND TRANSPORT MODELS FOR MONITORING CONTAMINANTS IN GROUND WATER

EPA Science Inventory

The development of conceptual and predictive models is an important tool to guide site characterization in support of monitoring contaminants in ground water. The accuracy of predictive models is limited by the adequacy of the input data and the assumptions made to constrain mod...

New methods to characterize site amplification

USGS Publications Warehouse

Safak, Erdal

1993-01-01

Methods alternative to spectral ratios are introduced to characterize site amplification. The methods are developed by using a range of models, from the simple constant amplification model to the time-varying filter model. Examples are given for each model by using a pair of rock- and soil-site recordings from the Loma Prieta earthquake.

Nitrate in the Mississippi River and its tributaries, 1980 to 2008: Are we making progress?

USGS Publications Warehouse

Sprague, Lori A.; Hirsch, Robert M.; Aulenbach, Brent T.

2011-01-01

Changes in nitrate concentration and flux between 1980 and 2008 at eight sites in the Mississippi River basin were determined using a new statistical method that accommodates evolving nitrate behavior over time and produces flow-normalized estimates of nitrate concentration and flux that are independent of random variations in streamflow. The results show that little consistent progress has been made in reducing riverine nitrate since 1980, and that flow-normalized concentration and flux are increasing in some areas. Flow-normalized nitrate concentration and flux increased between 9 and 76% at four sites on the Mississippi River and a tributary site on the Missouri River, but changed very little at tributary sites on the Ohio, Iowa, and Illinois Rivers. Increases in flow-normalized concentration and flux at the Mississippi River at Clinton and Missouri River at Hermann were more than three times larger than at any other site. The increases at these two sites contributed much of the 9% increase in flow-normalized nitrate flux leaving the Mississippi River basin. At most sites, concentrations increased more at low and moderate streamflows than at high streamflows, suggesting that increasing groundwater concentrations are having an effect on river concentrations.

Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils.

PubMed

Camp, Jeremy V; Bagci, Ulas; Chu, Yong-Kyu; Squier, Brendan; Fraig, Mostafa; Uriarte, Silvia M; Guo, Haixun; Mollura, Daniel J; Jonsson, Colleen B

2015-09-01

Infection of the lower respiratory tract by influenza A viruses results in increases in inflammation and immune cell infiltration in the lung. The dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 H1N1 pandemic influenza A virus (H1N1pdm virus). Neutrophil levels rose in the lungs of H1N1pdm virus-infected ferrets 6 h postinfection and became concentrated at areas of the H1N1pdm virus-infected bronchiolar epithelium by 1 day postinfection (dpi). In addition, neutrophil levels were increased throughout the alveolar spaces during the first 3 dpi and returned to baseline by 6 dpi. Histochemical staining revealed that neutrophil infiltration in the lungs occurred in two waves, at 1 and 3 dpi, and gene expression within microenvironments suggested two types of neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) levels, were higher within discrete lung microenvironments and coincided with increased infiltration of neutrophils into the lung. We used live imaging of ferrets to monitor host responses within the lung over time with [(18)F]fluorodeoxyglucose (FDG). Sites in the H1N1pdm virus-infected ferret lung with high FDG uptake had high levels of proliferative epithelium. In summary, neutrophils invaded the H1N1pdm virus-infected ferret lung globally and focally at sites of infection. Increased neutrophil levels in microenvironments did not correlate with increased FDG uptake; hence, FDG uptake may reflect prior infection and inflammation of lungs that have experienced damage, as evidenced by bronchial regeneration of tissues in the lungs at sites with high FDG levels. Severe influenza disease is characterized by an acute infection of the lower airways that may progress rapidly to organ failure and death. Well-developed animal models that mimic human disease are essential to understanding the complex relationships of the microenvironment, organ, and system in controlling virus replication, inflammation, and disease progression. Employing the ferret model of H1N1pdm virus infection, we used live imaging and comprehensive histological analyses to address specific hypotheses regarding spatial and temporal relationships that occur during the progression of infection and inflammation. We show the general invasion of neutrophils at the organ level (lung) but also a distinct pattern of localized accumulation within the microenvironment at the site of infection. Moreover, we show that these responses were biphasic within the lung. Finally, live imaging revealed an early and sustained host metabolic response at sites of infection that may reflect damage and repair of tissues in the lungs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils

PubMed Central

Camp, Jeremy V.; Bagci, Ulas; Chu, Yong-Kyu; Squier, Brendan; Fraig, Mostafa; Uriarte, Silvia M.; Guo, Haixun; Mollura, Daniel J.

2015-01-01

ABSTRACT Infection of the lower respiratory tract by influenza A viruses results in increases in inflammation and immune cell infiltration in the lung. The dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 H1N1 pandemic influenza A virus (H1N1pdm virus). Neutrophil levels rose in the lungs of H1N1pdm virus-infected ferrets 6 h postinfection and became concentrated at areas of the H1N1pdm virus-infected bronchiolar epithelium by 1 day postinfection (dpi). In addition, neutrophil levels were increased throughout the alveolar spaces during the first 3 dpi and returned to baseline by 6 dpi. Histochemical staining revealed that neutrophil infiltration in the lungs occurred in two waves, at 1 and 3 dpi, and gene expression within microenvironments suggested two types of neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) levels, were higher within discrete lung microenvironments and coincided with increased infiltration of neutrophils into the lung. We used live imaging of ferrets to monitor host responses within the lung over time with [18F]fluorodeoxyglucose (FDG). Sites in the H1N1pdm virus-infected ferret lung with high FDG uptake had high levels of proliferative epithelium. In summary, neutrophils invaded the H1N1pdm virus-infected ferret lung globally and focally at sites of infection. Increased neutrophil levels in microenvironments did not correlate with increased FDG uptake; hence, FDG uptake may reflect prior infection and inflammation of lungs that have experienced damage, as evidenced by bronchial regeneration of tissues in the lungs at sites with high FDG levels. IMPORTANCE Severe influenza disease is characterized by an acute infection of the lower airways that may progress rapidly to organ failure and death. Well-developed animal models that mimic human disease are essential to understanding the complex relationships of the microenvironment, organ, and system in controlling virus replication, inflammation, and disease progression. Employing the ferret model of H1N1pdm virus infection, we used live imaging and comprehensive histological analyses to address specific hypotheses regarding spatial and temporal relationships that occur during the progression of infection and inflammation. We show the general invasion of neutrophils at the organ level (lung) but also a distinct pattern of localized accumulation within the microenvironment at the site of infection. Moreover, we show that these responses were biphasic within the lung. Finally, live imaging revealed an early and sustained host metabolic response at sites of infection that may reflect damage and repair of tissues in the lungs. PMID:26063430

Robotics for mixed waste operations, demonstration description

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

Ward, C.R.

The Department of Energy (DOE) Office of Technology Development (OTD) is developing technology to aid in the cleanup of DOE sites. Included in the OTD program are the Robotics Technology Development Program and the Mixed Waste Integrated Program. These two programs are working together to provide technology for the cleanup of mixed waste, which is waste that has both radioactive and hazardous constituents. There are over 240,000 cubic meters of mixed low level waste accumulated at DOE sites and the cleanup is expected to generate about 900,000 cubic meters of mixed low level waste over the next five years. Thismore » waste must be monitored during storage and then treated and disposed of in a cost effective manner acceptable to regulators and the states involved. The Robotics Technology Development Program is developing robotics technology to make these tasks safer, better, faster and cheaper through the Mixed Waste Operations team. This technology will also apply to treatment of transuranic waste. The demonstration at the Savannah River Site on November 2-4, 1993, showed the progress of this technology by DOE, universities and industry over the previous year. Robotics technology for the handling, characterization and treatment of mixed waste as well robotics technology for monitoring of stored waste was demonstrated. It was shown that robotics technology can make future waste storage and waste treatment facilities better, faster, safer and cheaper.« less

Single-molecule localization microscopy reveals molecular transactions during RAD51 filament assembly at cellular DNA damage sites

PubMed Central

Haas, Kalina T; Lee, MiYoung; Esposito, Alessandro; Venkitaraman, Ashok R

2018-01-01

Abstract RAD51 recombinase assembles on single-stranded (ss)DNA substrates exposed by DNA end-resection to initiate homologous recombination (HR), a process fundamental to genome integrity. RAD51 assembly has been characterized using purified proteins, but its ultrastructural topography in the cell nucleus is unexplored. Here, we combine cell genetics with single-molecule localization microscopy and a palette of bespoke analytical tools, to visualize molecular transactions during RAD51 assembly in the cellular milieu at resolutions approaching 30–40 nm. In several human cell types, RAD51 focalizes in clusters that progressively extend into long filaments, which abut—but do not overlap—with globular bundles of replication protein A (RPA). Extended filaments alter topographically over time, suggestive of succeeding steps in HR. In cells depleted of the tumor suppressor protein BRCA2, or overexpressing its RAD51-binding BRC repeats, RAD51 fails to assemble at damage sites, although RPA accumulates unhindered. By contrast, in cells lacking a BRCA2 carboxyl (C)-terminal region targeted by cancer-causing mutations, damage-induced RAD51 assemblies initiate but do not extend into filaments. We suggest a model wherein RAD51 assembly proceeds concurrently with end-resection at adjacent sites, via an initiation step dependent on the BRC repeats, followed by filament extension through the C-terminal region of BRCA2. PMID:29309696

SITE CHARACTERIZATION OF AREA 6, DOVER AIR FORCE BASE, IN SUPPORT OF NATURAL ATTENUATION AND ENHANCED ANAEROBIC BIOREMEDIATION PROJECTS

EPA Science Inventory

A field program for site characterization of targeted study areas at the Dover Air Force Base was conducted between January 16, 1995, and March 9, 1995. The stated objectives of the investigation, "to characterize the stratigraphy, depth to groundwater, groundwater flow directio...

Characterization of Damage Progression in SCS-6/timetal 21S (0)4 Under Thermomechanical Fatigue Loadings

NASA Technical Reports Server (NTRS)

Castelli, Michael G.

1994-01-01

A detailed experimental investigation was performed at a single maximum cyclic stress (sigma max) level to physically characterize the progression of thermomechanical fatigue (lW) damage in continuously reinforced (0 deg) SCS-6/Timetal 21S, a titanium matrix composite. In-phase (IP) and out of-phase (OP) loadings were investigated at sigma max = 1000 MPa with a temperature cycle from 150 to 6500 C. Damage progression, in terms of macroscopic property degradation, was experimentally quantified through an advanced TMF test methodology which incorporates explicit measurements of the isothermal static moduli at the TMF temperature extremes and the coefficient of thermal expansion (CTE) as functions of the TMF cycles. Detailed characterization of the physical damage progression at the microstructural level was performed by interrupting multiple TMF tests at various stages of mechanical property degradation and analyzing the microstructure through extensive destructive metallography. Further, the extent of damage was also quantified through residual static strength measurements. Results indicated that damage initiation occurred very early in cyclic life (N less than 0.1Nf) for both the IP and OP TMF loadings. IP TMF damage was found to be dominated by fiber breakage with a physical damage progression in the microstructure which was difficult to quantify. OP TMF loadings produced matrix cracking exclusively associated with surface initiations. Here, damage progression was easily distinguished in terms of both the number of cracks and their relative inward progressions toward the outer fiber rows with increased cycling. The point at which the leading cracks reached the outer fiber rows (when localized fiber/matrix de-bonding and matrix crack bridging occurred) appeared to be reflected in the macroscopic property degradation curves.

Restoration progress and flood disturbance at IDOT wetland mitigation sites.

DOT National Transportation Integrated Search

2013-04-01

As required under Section 404 of the Clean Water Act and the Illinois Interagency Wetland Policy Act of 1989, the Illinois : Department of Transportation (IDOT) has established wetlands at mitigation sites throughout Illinois to compensate for : impa...

Seismic site-response characterization of high-velocity sites using advanced geophysical techniques: application to the NAGRA-Net

NASA Astrophysics Data System (ADS)

Poggi, V.; Burjanek, J.; Michel, C.; Fäh, D.

2017-08-01

The Swiss Seismological Service (SED) has recently finalised the installation of ten new seismological broadband stations in northern Switzerland. The project was led in cooperation with the National Cooperative for the Disposal of Radioactive Waste (Nagra) and Swissnuclear to monitor micro seismicity at potential locations of nuclear-waste repositories. To further improve the quality and usability of the seismic recordings, an extensive characterization of the sites surrounding the installation area was performed following a standardised investigation protocol. State-of-the-art geophysical techniques have been used, including advanced active and passive seismic methods. The results of all analyses converged to the definition of a set of best-representative 1-D velocity profiles for each site, which are the input for the computation of engineering soil proxies (traveltime averaged velocity and quarter-wavelength parameters) and numerical amplification models. Computed site response is then validated through comparison with empirical site amplification, which is currently available for any station connected to the Swiss seismic networks. With the goal of a high-sensitivity network, most of the NAGRA stations have been installed on stiff-soil sites of rather high seismic velocity. Seismic characterization of such sites has always been considered challenging, due to lack of relevant velocity contrast and the large wavelengths required to investigate the frequency range of engineering interest. We describe how ambient vibration techniques can successfully be applied in these particular conditions, providing practical recommendations for best practice in seismic site characterization of high-velocity sites.

Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation.

PubMed

Cho, Seong-Jun; Kang, Hana; Kim, Min Young; Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun; Pyo, Suhkneung; Yang, Kwang Hee

2016-04-01

To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Splenocytes and IM-9 cells were uniformly irradiated with various doses of a (137)Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast. Copyright © 2016 Elsevier Inc. All rights reserved.

10 CFR 60.7 - License not required for certain preliminary activities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... WASTES IN GEOLOGIC REPOSITORIES General Provisions § 60.7 License not required for certain preliminary... repository: (a) For purposes of site characterization; or (b) For use, during site characterization or...

Evolving the US Climate Resilience Toolkit to Support a Climate-Smart Nation

NASA Astrophysics Data System (ADS)

Tilmes, C.; Niepold, F., III; Fox, J. F.; Herring, D.; Dahlman, L. E.; Hall, N.; Gardiner, N.

2015-12-01

Communities, businesses, resource managers, and decision-makers at all levels of government need information to understand and ameliorate climate-related risks. Likewise, climate information can expose latent opportunities. Moving from climate science to social and economic decisions raises complex questions about how to communicate the causes and impacts of climate variability and change; how to characterize and quantify vulnerabilities, risks, and opportunities faced by communities and businesses; and how to make and implement "win-win" adaptation plans at local, regional, and national scales. A broad coalition of federal agencies launched the U.S. Climate Resilience Toolkit (toolkit.climate.gov) in November 2014 to help our nation build resilience to climate-related extreme events. The site's primary audience is planners and decision makers in business, resource management, and government (at all levels) who seek science-based climate information and tools to help them in their near- and long-term planning. The Executive Office of the President assembled a task force of dozens of subject experts from across the 13 agencies of the U.S. Global Change Research Program to guide the site's development. The site's ongoing evolution is driven by feedback from the target audience. For example, based on feedback, climate projections will soon play a more prominent role in the site's "Climate Explorer" tool and case studies. The site's five-step adaptation planning process is being improved to better facilitate people getting started and to provide clear benchmarks for evaluating progress along the way. In this session, we will share lessons learned from a series of user engagements around the nation and evidence that the Toolkit couples climate information with actionable decision-making processes in ways that are helping Americans build resilience to climate-related stressors.

Analysis of rotation sensor data from the SINAPS@ Kefalonia (Greece) post-seismic experiment—link to surface geology and wavefield characteristics

NASA Astrophysics Data System (ADS)

Sbaa, Sarah; Hollender, Fabrice; Perron, Vincent; Imtiaz, Afifa; Bard, Pierre-Yves; Mariscal, Armand; Cochard, Alain; Dujardin, Alain

2017-09-01

Although rotational seismology has progressed in recent decades, the links between rotational ground motion and site soil conditions are poorly documented. New experiments were performed on Kefalonia Island (Greece) following two large earthquakes ( M W = 6.0, M W = 5.9) in early 2014 on two well-characterized sites (soft soil, V S30 250 m/s; rock, V S30 830 m/s, V S30 being harmonic average shear-wave velocity between 0 and 30 m depth). These earthquakes led to large six-component (three translations and three rotations) datasets of hundreds of well-recorded events. The relationship between peak translational acceleration versus peak rotational velocity is found sensitive to the site conditions mainly for the rotation around the vertical axis (torsion; dominated by Love waves): the stiffer the soil, the lower the torsion, for a given level of translational acceleration. For rotation around the horizontal axes (rocking; dominated by Rayleigh waves), this acceleration/rotation relationship exhibits much weaker differences between soft and rock sites. Using only the rotation sensor, an estimate of the Love-to-Rayleigh energy ratios could be carried out and provided the same results as previous studies that have analyzed the Love- and Rayleigh-wave energy proportions using data from translational arrays deployed at the same two sites. The coupling of translational and rotational measurements appears to be useful, not only for direct applications of engineering seismology, but also to investigate the composition of the wavefield, while avoiding deployment of dense arrays. The availability of new, low-noise rotation sensors that are easy to deploy in the field is of great interest and should extend the use of rotation sensors and expand their possible applications.[Figure not available: see fulltext.

Environmental assessment: Davis Canyon site, Utah

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

none,

1986-05-01

In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOEmore » prepared the final EA. The Davis Canyon site is in the Paradox Basin, which is one of five distinct geohydrologic settings considering for the first repository. This setting contains one other potentially acceptable site -- the Lavender Canyon site. Although the Lavender Canyon site is suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. On the basis of the evaluations reported in this EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. Furthermore, the DOE has found that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Davis Canyon site as one of five sites suitable for characterization.« less

Exercise and Bone Density: Meta-Analysis

DTIC Science & Technology

2007-01-01

Statistically significant site-specific changes were also observed at the femur, lumbar , and os calcis sites. The results of this study suggest that site...specific exercise may help improve and maintain BMD at the femur, lumbar , and os calcis sites in older men. However, the biological importance of...examined the effects of progressive resistance training on BMD at the femur, lumbar spine, and radius in pre- and postmenopausal women.6 Twenty-nine

Genome-wide analysis of AR binding and comparison with transcript expression in primary human fetal prostate fibroblasts and cancer associated fibroblasts.

PubMed

Nash, Claire; Boufaied, Nadia; Mills, Ian G; Franco, Omar E; Hayward, Simon W; Thomson, Axel A

2017-05-05

The androgen receptor (AR) is a transcription factor, and key regulator of prostate development and cancer, which has discrete functions in stromal versus epithelial cells. AR expressed in mesenchyme is necessary and sufficient for prostate development while loss of stromal AR is predictive of prostate cancer progression. Many studies have characterized genome-wide binding of AR in prostate tumour cells but none have used primary mesenchyme or stroma. We applied ChIPseq to identify genomic AR binding sites in primary human fetal prostate fibroblasts and patient derived cancer associated fibroblasts, as well as the WPMY1 cell line overexpressing AR. We identified AR binding sites that were specific to fetal prostate fibroblasts (7534), cancer fibroblasts (629), WPMY1-AR (2561) as well as those common among all (783). Primary fibroblasts had a distinct AR binding profile versus prostate cancer cell lines and tissue, and showed a localisation to gene promoter binding sites 1 kb upstream of the transcriptional start site, as well as non-classical AR binding sequence motifs. We used RNAseq to define transcribed genes associated with AR binding sites and derived cistromes for embryonic and cancer fibroblasts as well as a cistrome common to both. These were compared to several in vivo ChIPseq and transcript expression datasets; which identified subsets of AR targets that were expressed in vivo and regulated by androgens. This analysis enabled us to deconvolute stromal AR targets active in stroma within tumour samples. Taken together, our data suggest that the AR shows significantly different genomic binding site locations in primary prostate fibroblasts compared to that observed in tumour cells. Validation of our AR binding site data with transcript expression in vitro and in vivo suggests that the AR target genes we have identified in primary fibroblasts may contribute to clinically significant and biologically important AR-regulated changes in prostate tissue. Copyright © 2017. Published by Elsevier B.V.

Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

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

Gan, Gregory N., E-mail: gregory.gan@ucdenver.edu; Weickhardt, Andrew J.; Scheier, Benjamin

Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progressionmore » meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.« less

α-Synuclein amyloid fibrils with two entwined, asymmetrically associated protofibrils [α-Synuclein amyloid fibrils with two entwined, asymmetrically associated, protofibrils and axially stacked metal binding sites

DOE PAGES

Dearborn, Altaira D.; Wall, Joseph S.; Cheng, Naiqian; ...

2015-12-07

Parkinson disease and other progressive neurodegenerative conditions are characterized by the intracerebral presence of Lewy bodies, containing amyloid fibrils of α-synuclein. We used cryo-electron microscopy and scanning transmission electron microscopy (STEM) to study in vitro-assembled fibrils. These fibrils are highly polymorphic. Focusing on twisting fibrils with an inter-crossover spacing of 77 nm, our reconstructions showed them to consist of paired protofibrils. STEM mass per length data gave one subunit per 0.47 nm axial rise per protofibril, consistent with a superpleated β-structure. The STEM images show two thread-like densities running along each of these fibrils, which we interpret as ladders ofmore » metal ions. These threads confirmed the two-protofibril architecture of the 77-nm twisting fibrils and allowed us to identify this morphotype in STEM micrographs. Some other, but not all, fibril morphotypes also exhibit dense threads, implying that they also present a putative metal binding site. As a result, we propose a molecular model for the protofibril and suggest that polymorphic variant fibrils have different numbers of protofibrils that are associated differently.« less

PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.

PubMed

Maréchal, Alexandre; Li, Ju-Mei; Ji, Xiao Ye; Wu, Ching-Shyi; Yazinski, Stephanie A; Nguyen, Hai Dang; Liu, Shizhou; Jiménez, Amanda E; Jin, Jianping; Zou, Lee

2014-01-23

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. Copyright © 2014 Elsevier Inc. All rights reserved.

Dynamic autophosphorylation of mps1 kinase is required for faithful mitotic progression.

PubMed

Wang, Xinghui; Yu, Huijuan; Xu, Leilei; Zhu, Tongge; Zheng, Fan; Fu, Chuanhai; Wang, Zhiyong; Dou, Zhen

2014-01-01

The spindle assembly checkpoint (SAC) is a surveillance mechanism monitoring cell cycle progression, thus ensuring accurate chromosome segregation. The conserved mitotic kinase Mps1 is a key component of the SAC. The human Mps1 exhibits comprehensive phosphorylation during mitosis. However, the related biological relevance is largely unknown. Here, we demonstrate that 8 autophosphorylation sites within the N-terminus of Mps1, outside of the catalytic domain, are involved in regulating Mps1 kinetochore localization. The phospho-mimicking mutant of the 8 autophosphorylation sites impairs Mps1 localization to kinetochore and also affects the kinetochore recruitment of BubR1 and Mad2, two key SAC effectors, subsequently leading to chromosome segregation errors. Interestingly, the non-phosphorylatable mutant of the 8 autophosphorylation sites enhances Mps1 kinetochore localization and delays anaphase onset. We further show that the Mps1 phospho-mimicking and non-phosphorylatable mutants do not affect metaphase chromosome congression. Thus, our results highlight the importance of dynamic autophosphorylation of Mps1 in regulating accurate chromosome segregation and ensuring proper mitotic progression.

Dynamic Autophosphorylation of Mps1 Kinase Is Required for Faithful Mitotic Progression

PubMed Central

Wang, Xinghui; Yu, Huijuan; Xu, Leilei; Zhu, Tongge; Zheng, Fan; Fu, Chuanhai; Wang, Zhiyong; Dou, Zhen

2014-01-01

The spindle assembly checkpoint (SAC) is a surveillance mechanism monitoring cell cycle progression, thus ensuring accurate chromosome segregation. The conserved mitotic kinase Mps1 is a key component of the SAC. The human Mps1 exhibits comprehensive phosphorylation during mitosis. However, the related biological relevance is largely unknown. Here, we demonstrate that 8 autophosphorylation sites within the N-terminus of Mps1, outside of the catalytic domain, are involved in regulating Mps1 kinetochore localization. The phospho-mimicking mutant of the 8 autophosphorylation sites impairs Mps1 localization to kinetochore and also affects the kinetochore recruitment of BubR1 and Mad2, two key SAC effectors, subsequently leading to chromosome segregation errors. Interestingly, the non-phosphorylatable mutant of the 8 autophosphorylation sites enhances Mps1 kinetochore localization and delays anaphase onset. We further show that the Mps1 phospho-mimicking and non-phosphorylatable mutants do not affect metaphase chromosome congression. Thus, our results highlight the importance of dynamic autophosphorylation of Mps1 in regulating accurate chromosome segregation and ensuring proper mitotic progression. PMID:25265012

Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1)

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

Lalioti, M.D.; Mirotsou, M.; Rossier, C.

1997-02-01

Progressive myoclonus epilepsy (EPM1) is an autosomal recessive disorder, characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The EPM1 locus was mapped to within 0.3 cM from PFKL in chromosome 21q22.3. The gene for the proteinase inhibitor cystatin B was recently localized in the EPM1 critical region, and mutations were identified in two EPM1 families. We have identified six nucleotide changes in the cystatin B gene of non-Finnish EPM1 families from northern Africa and Europe. The 426G{r_arrow}C change in exon 1 results in a Gly4Arg substitution and is the first missense mutation described that is associated with EPM1. Molecular modelingmore » predicts that this substitution severely affects the contact of cystatin B with papain. Mutations in the invariant AG dinucleotides of the acceptor sites of introns 1 and 2 probably result in abnormal splicing. A deletion of two nucleotides in exon 3 produces a frameshift and truncates the protein. Therefore, these four mutations are all predicted to impair the production of functional protein. These mutations were found in 7 of the 29 unrelated EPM1 patients analyzed, in homozygosity in 1, and in heterozygosity in the others. The remaining two sequence changes, 431G{r_arrow}T and 2575A{r_arrow}G, probably represent polymorphic variants. In addition, a tandem repeat in the 5{prime} UTR (CCCCGCCCCGCG) is present two or three times in normal alleles. It is peculiar that in the majority of patients no mutations exist within the exons and splice sites of the cystatin B gene. 23 refs., 5 figs., 3 tabs.« less

Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

PubMed Central

Weiss, Scott L.; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C.; Salloo, Asma; Singhi, Sunit C.; Erickson, Simon; Roy, Jason A.; Bush, Jenny L.; Nadkarni, Vinay M.; Thomas, Neal J.

2015-01-01

Rationale: Limited data exist about the international burden of severe sepsis in critically ill children. Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. Methods: A point prevalence study was conducted on 5 days throughout 2013–2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Measurements and Main Results: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6–8.9%). The patients’ median age was 3.0 (interquartile range [IQR], 0.7–11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0–25), and vasoactive-free days were 23 (IQR, 12–28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5–10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,437 patients per group. Conclusions: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted. PMID:25734408

Physical and hydrologic properties of outcrop samples from a nonwelded to welded tuff transition, Yucca Mountain, Nevada

USGS Publications Warehouse

Rautman, C.A.; Flint, L.E.; Flint, A.L.; Istok, J.D.

1995-01-01

Quantitative material-property data are needed to describe lateral and vertical spatial variability of physical and hydrologic properties and to model ground-water flow and radionuclide transport at the potential Yucca Mountain nuclear-waste repository site in Nevada. As part of ongoing site characterization studies of Yucca Mountain directed toward this understanding of spatial variability, laboratory measurements of porosity, bull* and particle density, saturated hydraulic conductivity, and sorptivity have been obtained for a set of outcrop samples that form a systematic,two dimensional grid that covers a large exposure of the basal Tiva Canyon Tuff of the Paintbrush Group of Miocene age at Yucca Mountain. The samples form a detailed vertical grid roughly parallel to the transport direction of the parent ash flows, and they exhibit material-property varia- tions in an interval of major lithologic change overlying a potential nuclear-waste repository at Yucca Mountain. The observed changes in hydrologic properties were systematic and consistent with the changes expected for the nonwelded to welded transition at the base of a major ash-flow sequence. Porosity, saturated hydraulic conductivity, and sorptivity decreased upward from the base of the Tiva Canyon Tuff, indicating the progressive compaction of ash- rich volcanic debris and the onset of welding with increased overburden pressure from the accumulating ash-flow sheet. The rate of decrease in the values of these material properties varied with vertical position within the transition interval. In contrast, bulk-density values increased upward, a change that also is consistent with progressive compaction and the onset of welding. Particle-density values remained almost constant throughout the transition interval, probably indicating compositional (chemical) homogeneity.

Continuous subcutaneous insulin infusion allows tolerance induction and diabetes treatment in a type 1 diabetic child with insulin allergy.

PubMed

Hasselmann, C; Pecquet, C; Bismuth, E; Raverdy, C; Sola-Gazagnes, A; Lobut, J-B; Carel, J-C; Tubiana-Rufi, N

2013-04-01

Insulin allergy is a rare but serious and challenging condition in patients with type 1 diabetes (T1D). This is a case report of an 8-year-old boy with T1D and an allergy to insulin. Three months after being diagnosed with T1D, the patient developed progressive skin reactions to insulin, characterized by small 1.5-cm pruritic wheals at injection sites that persisted for several days. Seven months after diagnosis, he experienced two episodes of generalized urticaria with systemic symptoms that were seen within a few seconds of insulin injection. Examination revealed lipoatrophy of the thighs. Intradermal skin tests were positive for protamine, glargine and lispro. The patient was started on a continuous subcutaneous insulin infusion (CSII) tolerance induction protocol, consisting of a very low basal rate that was progressively increased, with the first bolus given under medical supervision, and was well tolerated for 4 months. After this period of time, the skin wheals reappeared, localized to the infusion sites, but without urticaria or any other generalized reactions. Intradermal skin tests were repeated and were again positive. Serum insulin-specific IgE measured 30 months after the first allergic reactions were positive. After 3 years, pump therapy is ongoing and blood glucose control has remained relatively good (HbA1c 7.6%). In T1D children with insulin allergy, CSII can successfully be used to both induce insulin tolerance and allow diabetes insulin therapy, although insulin desensitization cannot always be fully achieved. The induction protocol was easily manageable partly due to the "honeymoon" period that the patient was still in, but it should nonetheless be used even when the patient has higher insulin requirements. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study.

PubMed

Weiss, Scott L; Fitzgerald, Julie C; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C; Salloo, Asma; Singhi, Sunit C; Erickson, Simon; Roy, Jason A; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J

2015-05-15

Limited data exist about the international burden of severe sepsis in critically ill children. To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range [IQR], 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR, 12-28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,471 [corrected] patients per group. Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.

Microbiomes of Site-Specific Dental Plaques from Children with Different Caries Status.

PubMed

Richards, Vincent P; Alvarez, Andres J; Luce, Amy R; Bedenbaugh, Molly; Mitchell, Mary Lyn; Burne, Robert A; Nascimento, Marcelle M

2017-08-01

The oral microbiota associated with the initiation and progression of dental caries has yet to be fully characterized. The Human Oral Microbe Identification Using Next-Generation Sequencing (HOMI NGS ) approach was used to analyze the microbiomes of site-specific supragingival dental plaques from children with different caries status. Fifty-five children (2 to 7 years of age) were assessed at baseline and at 12 months and grouped as caries free (CF), caries active with enamel lesions (CAE), and caries active with dentin carious lesions (CA). Plaque samples from caries-free tooth surfaces (PF) and from enamel carious lesions (PE) and dentin carious lesions (PD) were collected. 16S community profiles were obtained by HOMI NGS , and 408 bacterial species and 84 genus probes were assigned. Plaque bacterial communities showed temporal stability, as there was no significant difference in beta diversity values between the baseline and 12-month samples. Irrespective of collection time points, the microbiomes of healthy tooth surfaces differed substantially from those found during caries activity. All pairwise comparisons of beta diversity values between groups were significantly different ( P < 0.05), except for comparisons between the CA-PF, CAE-PE, and CA-PE groups. Streptococcus genus probe 4 and Neisseria genus probe 2 were the most frequently detected taxa across the plaque groups, followed by Streptococcus sanguinis , which was highly abundant in CF-PF. Well-known acidogenic/aciduric species such as Streptococcus mutans , Scardovia wiggsiae , Parascardovia denticolens , and Lactobacillus salivarius were found almost exclusively in CA-PD. The microbiomes of supragingival dental plaque differ substantially among tooth surfaces and children of different caries activities. In support of the ecological nature of caries etiology, a steady transition in community species composition was observed with disease progression. Copyright © 2017 American Society for Microbiology.

Microbiomes of Site-Specific Dental Plaques from Children with Different Caries Status

PubMed Central

Alvarez, Andres J.; Luce, Amy R.; Bedenbaugh, Molly; Mitchell, Mary Lyn

2017-01-01

ABSTRACT The oral microbiota associated with the initiation and progression of dental caries has yet to be fully characterized. The Human Oral Microbe Identification Using Next-Generation Sequencing (HOMINGS) approach was used to analyze the microbiomes of site-specific supragingival dental plaques from children with different caries status. Fifty-five children (2 to 7 years of age) were assessed at baseline and at 12 months and grouped as caries free (CF), caries active with enamel lesions (CAE), and caries active with dentin carious lesions (CA). Plaque samples from caries-free tooth surfaces (PF) and from enamel carious lesions (PE) and dentin carious lesions (PD) were collected. 16S community profiles were obtained by HOMINGS, and 408 bacterial species and 84 genus probes were assigned. Plaque bacterial communities showed temporal stability, as there was no significant difference in beta diversity values between the baseline and 12-month samples. Irrespective of collection time points, the microbiomes of healthy tooth surfaces differed substantially from those found during caries activity. All pairwise comparisons of beta diversity values between groups were significantly different (P < 0.05), except for comparisons between the CA-PF, CAE-PE, and CA-PE groups. Streptococcus genus probe 4 and Neisseria genus probe 2 were the most frequently detected taxa across the plaque groups, followed by Streptococcus sanguinis, which was highly abundant in CF-PF. Well-known acidogenic/aciduric species such as Streptococcus mutans, Scardovia wiggsiae, Parascardovia denticolens, and Lactobacillus salivarius were found almost exclusively in CA-PD. The microbiomes of supragingival dental plaque differ substantially among tooth surfaces and children of different caries activities. In support of the ecological nature of caries etiology, a steady transition in community species composition was observed with disease progression. PMID:28507066

10 CFR 960.3-2-3 - Recommendation of sites for characterization.

Code of Federal Regulations, 2010 CFR

2010-01-01

... POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-2-3 Recommendation of sites... characterization for the selection of the first repository, the Secretary shall recommend in writing to the..., and, after the first repository, consideration of regionality in §§ 960.3-1-1, 960.3-1-2, and 960.3-1...

Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication

PubMed Central

Stetz, Gabrielle; Verkhivker, Gennady M.

2017-01-01

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of allostery, we introduced a community-hopping model of allosteric communication. Atomistic reconstruction of signaling pathways in the DnaK structures captured a direction-specific mechanism and molecular details of signal transmission that are fully consistent with the mutagenesis experiments. The results of our study reconciled structural and functional experiments from a network-centric perspective by showing that global properties of the residue interaction networks and coevolutionary signatures may be linked with specificity and diversity of allosteric regulation mechanisms. PMID:28095400

Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication.

PubMed

Stetz, Gabrielle; Verkhivker, Gennady M

2017-01-01

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of allostery, we introduced a community-hopping model of allosteric communication. Atomistic reconstruction of signaling pathways in the DnaK structures captured a direction-specific mechanism and molecular details of signal transmission that are fully consistent with the mutagenesis experiments. The results of our study reconciled structural and functional experiments from a network-centric perspective by showing that global properties of the residue interaction networks and coevolutionary signatures may be linked with specificity and diversity of allosteric regulation mechanisms.

Electromagnetic packable technology (EMPACT) for detection and characterization of ordnance in post-conflict areas

NASA Astrophysics Data System (ADS)

Schultz, Gregory; Miller, Jonathan; Keranen, Joe

2013-06-01

Land reclamation efforts in post-conflict regions are often hampered by the presence of Unexploded Ordnance (UXO) or other Explosive Remnants of War (ERW). Surface geophysical methods, such as Electromagnetic Induction (EMI) and magnetometry, are typically applied to screen rehabilitation areas for UXO prior to excavation; however, the prevalence of innocuous magnetic clutter related to indigenous scrap, fragmentation, or geology can severely impede the progress and efficiency of these remediation efforts. Additionally, the variability in surface conditions and local topography necessitates the development of sensor technologies that can be applied to a range of sites including those that prohibit the use of vehicle-mounted or large array systems. We present a man-portable EMI sensor known as the Electromagnetic Packable Technology (EMPACT) system that features a multi-axis sensor configuration in a compact form factor. The system is designed for operation in challenging site conditions and can be used in low ground-standoff modes to detect small and low-metal content objects. The EMPACT acquires high spatial density, multi-axis data that enable high resolution of small objects. This high density data can also be used to provide characterization of target physical features, such as size, material content, and shape. We summarize the development of this system for humanitarian demining operations and present results from preliminary system evaluations against a range of target types. Specifically, we assess the general detection capabilities of the EMPACT system and we evaluate the potential for target classification based on analysis of data and target model features.

CHARACTERIZING SITE HYDROLOGY (REGION 5)

EPA Science Inventory

Hydrogeology is the foundation of subsurface site characterization for evaluations of monitored natural attenuation (MNA). Three case studies are presented. Examples of the potentially detrimental effects of drilling additives on ground-water samples from monitoring wells are d...

Selection for avian leukosis virus integration sites determines the clonal progression of B-cell lymphomas

PubMed Central

Malhotra, Sanandan; Justice, James; Morgan, Robin

2017-01-01

Avian leukosis virus (ALV) is a simple retrovirus that causes a wide range of tumors in chickens, the most common of which are B-cell lymphomas. The viral genome integrates into the host genome and uses its strong promoter and enhancer sequences to alter the expression of nearby genes, frequently inducing tumors. In this study, we compare the preferences for ALV integration sites in cultured cells and in tumors, by analysis of over 87,000 unique integration sites. In tissue culture we observed integration was relatively random with slight preferences for genes, transcription start sites and CpG islands. We also observed a preference for integrations in or near expressed and spliced genes. The integration pattern in cultured cells changed over the course of selection for oncogenic characteristics in tumors. In comparison to tissue culture, ALV integrations are more highly selected for proximity to transcription start sites in tumors. There is also a significant selection of ALV integrations away from CpG islands in the highly clonally expanded cells in tumors. Additionally, we utilized a high throughput method to quantify the magnitude of clonality in different stages of tumorigenesis. An ALV-induced tumor carries between 700 and 3000 unique integrations, with an average of 2.3 to 4 copies of proviral DNA per infected cell. We observed increasing tumor clonality during progression of B-cell lymphomas and identified gene players (especially TERT and MYB) and biological processes involved in tumor progression. PMID:29099869

Cone penetrometer testing and discrete-depth ground water sampling techniques: A cost-effective method of site characterization in a multiple-aquifer setting

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

Zemo, D.A.; Pierce, Y.G.; Gallinatti, J.D.

Cone penetrometer testing (CPT), combined with discrete-depth ground water sampling methods, can significantly reduce the time and expense required to characterize large sites that have multiple aquifers. Results from the screening site characterization can then be used to design and install a cost-effective monitoring well network. At a site in northern California, it was necessary to characterize the stratigraphy and the distribution of volatile organic compounds (VOCs). To expedite characterization, a five-week field screening program was implemented that consisted of a shallow ground water survey, CPT soundings and pore-pressure measurements, and discrete-depth ground water sampling. Based on continuous lithologic informationmore » provided by the CPT soundings, four predominantly coarse-grained, water yielding stratigraphic packages were identified. Seventy-nine discrete-depth ground water samples were collected using either shallow ground water survey techniques, the BAT Enviroprobe, or the QED HydroPunch I, depending on subsurface conditions. Using results from these efforts, a 20-well monitoring network was designed and installed to monitor critical points within each stratigraphic package. Good correlation was found for hydraulic head and chemical results between discrete-depth screening data and monitoring well data. Understanding the vertical VOC distribution and concentrations produced substantial time and cost savings by minimizing the number of permanent monitoring wells and reducing the number of costly conductor casings that had to be installed. Additionally, significant long-term cost savings will result from reduced sampling costs, because fewer wells comprise the monitoring network. The authors estimate these savings to be 50% for site characterization costs, 65% for site characterization time, and 60% for long-term monitoring costs.« less

Task 10 - technology development integration. Semi-annual report, April 1--September 30, 1996

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

Hendrikson, J.G.; Daly, D.J.

1997-05-01

The Energy and Environmental Research Center (EERC), in conjunction with the Waste Policy Institute (WPI), will identify and integrate new technologies to meet site-specific environmental management (EM) requirements at contaminated sites appropriate to U.S. Department of Energy (DOE) interests. This paper briefly reports overall progress for three activities: technology management, project management, and technology integration. Work performed over the reporting period has focused on providing logistical and administrative support. In addition, six monthly WPI reports to the EERC are included as appendices. The WPI reports contained detailed information for progress in each activity.

Analysis of aberrant pre-messenger RNA splicing resulting from mutations in ATP8B1 and efficient in vitro rescue by adapted U1 small nuclear RNA.

PubMed

van der Woerd, Wendy L; Mulder, Johanna; Pagani, Franco; Beuers, Ulrich; Houwen, Roderick H J; van de Graaf, Stan F J

2015-04-01

ATP8B1 deficiency is a severe autosomal recessive liver disease resulting from mutations in the ATP8B1 gene characterized by a continuous phenotypical spectrum from intermittent (benign recurrent intrahepatic cholestasis; BRIC) to progressive familial intrahepatic cholestasis (PFIC). Current therapeutic options are insufficient, and elucidating the molecular consequences of mutations could lead to personalized mutation-specific therapies. We investigated the effect on pre-messenger RNA splicing of 14 ATP8B1 mutations at exon-intron boundaries using an in vitro minigene system. Eleven mutations, mostly associated with a PFIC phenotype, resulted in aberrant splicing and a complete absence of correctly spliced product. In contrast, three mutations led to partially correct splicing and were associated with a BRIC phenotype. These findings indicate an inverse correlation between the level of correctly spliced product and disease severity. Expression of modified U1 small nuclear RNAs (snRNA) complementary to the splice donor sites strongly improved or completely rescued splicing for several ATP8B1 mutations located at donor, as well as acceptor, splice sites. In one case, we also evaluated exon-specific U1 snRNAs that, by targeting nonconserved intronic sequences, might reduce possible off-target events. Although very effective in correcting exon skipping, they also induced retention of the short downstream intron. We systematically characterized the molecular consequences of 14 ATP8B1 mutations at exon-intron boundaries associated with ATP8B1 deficiency and found that the majority resulted in total exon skipping. The amount of correctly spliced product inversely correlated with disease severity. Compensatory modified U1 snRNAs, complementary to mutated donor splice sites, were able to improve exon definition very efficiently and could be a novel therapeutic strategy in ATP8B1 deficiency as well as other genetic diseases. © 2014 by the American Association for the Study of Liver Diseases.

A New Approach to Standardize Multicenter Studies: Mobile Lab Technology for the German Environmental Specimen Bank

PubMed Central

Lermen, Dominik; Schmitt, Daniel; Bartel-Steinbach, Martina; Schröter-Kermani, Christa; Kolossa-Gehring, Marike; von Briesen, Hagen; Zimmermann, Heiko

2014-01-01

Technical progress has simplified tasks in lab diagnosis and improved quality of test results. Errors occurring during the pre-analytical phase have more negative impact on the quality of test results than errors encountered during the total analytical process. Different infrastructures of sampling sites can highly influence the quality of samples and therewith of analytical results. Annually the German Environmental Specimen Bank (ESB) collects, characterizes, and stores blood, plasma, and urine samples of 120–150 volunteers each on four different sampling sites in Germany. Overarching goal is to investigate the exposure to environmental pollutants of non-occupational exposed young adults combining human biomonitoring with questionnaire data. We investigated the requirements of the study and the possibility to realize a highly standardized sampling procedure on a mobile platform in order to increase the required quality of the pre-analytical phase. The results lead to the development of a mobile epidemiologic laboratory (epiLab) in the project “Labor der Zukunft” (future’s lab technology). This laboratory includes a 14.7 m2 reception area to record medical history and exposure-relevant behavior, a 21.1 m2 examination room to record dental fillings and for blood withdrawal, a 15.5 m2 biological safety level 2 laboratory to process and analyze samples on site including a 2.8 m2 personnel lock and a 3.6 m2 cryofacility to immediately freeze samples. Frozen samples can be transferred to their final destination within the vehicle without breaking the cold chain. To our knowledge, we herewith describe for the first time the implementation of a biological safety laboratory (BSL) 2 lab and an epidemiologic unit on a single mobile platform. Since 2013 we have been collecting up to 15.000 individual human samples annually under highly standardized conditions using the mobile laboratory. Characterized and free of alterations they are kept ready for retrospective analyses in their final archive, the German ESB. PMID:25141120

A new approach to standardize multicenter studies: mobile lab technology for the German Environmental Specimen Bank.

PubMed

Lermen, Dominik; Schmitt, Daniel; Bartel-Steinbach, Martina; Schröter-Kermani, Christa; Kolossa-Gehring, Marike; von Briesen, Hagen; Zimmermann, Heiko

2014-01-01

Technical progress has simplified tasks in lab diagnosis and improved quality of test results. Errors occurring during the pre-analytical phase have more negative impact on the quality of test results than errors encountered during the total analytical process. Different infrastructures of sampling sites can highly influence the quality of samples and therewith of analytical results. Annually the German Environmental Specimen Bank (ESB) collects, characterizes, and stores blood, plasma, and urine samples of 120-150 volunteers each on four different sampling sites in Germany. Overarching goal is to investigate the exposure to environmental pollutants of non-occupational exposed young adults combining human biomonitoring with questionnaire data. We investigated the requirements of the study and the possibility to realize a highly standardized sampling procedure on a mobile platform in order to increase the required quality of the pre-analytical phase. The results lead to the development of a mobile epidemiologic laboratory (epiLab) in the project "Labor der Zukunft" (future's lab technology). This laboratory includes a 14.7 m(2) reception area to record medical history and exposure-relevant behavior, a 21.1 m(2) examination room to record dental fillings and for blood withdrawal, a 15.5 m(2) biological safety level 2 laboratory to process and analyze samples on site including a 2.8 m(2) personnel lock and a 3.6 m2 cryofacility to immediately freeze samples. Frozen samples can be transferred to their final destination within the vehicle without breaking the cold chain. To our knowledge, we herewith describe for the first time the implementation of a biological safety laboratory (BSL) 2 lab and an epidemiologic unit on a single mobile platform. Since 2013 we have been collecting up to 15.000 individual human samples annually under highly standardized conditions using the mobile laboratory. Characterized and free of alterations they are kept ready for retrospective analyses in their final archive, the German ESB.

Enzymatic characterization of novel arylsulfatase A variants using human arylsulfatase A-deficient immortalized mesenchymal stromal cells.

PubMed

Böhringer, Judith; Santer, René; Schumacher, Neele; Gieseke, Friederike; Cornils, Kerstin; Pechan, Maria; Kustermann-Kuhn, Birgit; Handgretinger, Rupert; Schöls, Ludger; Harzer, Klaus; Krägeloh-Mann, Ingeborg; Müller, Ingo

2017-11-01

Metachromatic leukodystrophy (MLD) is an autosomal-recessive lysosomal storage disease caused by mutations in the ARSA gene leading to arylsulfatase A (ARSA) deficiency and causing sulfatide accumulation. Main symptoms of the disease are progressive demyelination, neurological dysfunction, and reduced life expectancy. To date, more than 200 different ARSA variants have been reported in MLD patients. Here, we report the biochemical characterization of seven novel pathogenic variants (c.98T > C, c.195delC, c.229G > C, c.545C > G, c.674A > G, c.852T > A, and c.1274A > G), which were found when sequencing a cohort of 31 German MLD families. For that purpose, the ARSA cDNAs carrying the respective mutations inserted by site-directed mutagenesis were cloned into a MigR1 (MSCV, IRES, GFP, retrovirus-1) vector. The constructs were overexpressed using retroviral gene transfer in immortalized, human multipotent mesenchymal stromal cells prepared from a patient deficient in ARSA activity (late infantile MLD). In this novel ARSA -/- cell system, the seven ARSA mutants showed ARSA activity of less than 10% when compared with wild type, which is evidence for the pathogenicity of all seven variants. In conclusion, the system of ARSA -/- -immortalized MSC turned out to be a helpful novel tool for the biochemical characterization of ARSA variants. © 2017 Wiley Periodicals, Inc.

Design and characterization of the Large-aperture Experiment to Detect the Dark Age (LEDA) radiometer systems

NASA Astrophysics Data System (ADS)

Price, D. C.; Greenhill, L. J.; Fialkov, A.; Bernardi, G.; Garsden, H.; Barsdell, B. R.; Kocz, J.; Anderson, M. M.; Bourke, S. A.; Craig, J.; Dexter, M. R.; Dowell, J.; Eastwood, M. W.; Eftekhari, T.; Ellingson, S. W.; Hallinan, G.; Hartman, J. M.; Kimberk, R.; Lazio, T. Joseph W.; Leiker, S.; MacMahon, D.; Monroe, R.; Schinzel, F.; Taylor, G. B.; Tong, E.; Werthimer, D.; Woody, D. P.

2018-05-01

The Large-Aperture Experiment to Detect the Dark Age (LEDA) was designed to detect the predicted O(100) mK sky-averaged absorption of the Cosmic Microwave Background by Hydrogen in the neutral pre- and intergalactic medium just after the cosmological Dark Age. The spectral signature would be associated with emergence of a diffuse Lyα background from starlight during `Cosmic Dawn'. Recently, Bowman et al. (2018) have reported detection of this predicted absorption feature, with an unexpectedly large amplitude of 530 mK, centered at 78 MHz. Verification of this result by an independent experiment, such as LEDA, is pressing. In this paper, we detail design and characterization of the LEDA radiometer systems, and a first-generation pipeline that instantiates a signal path model. Sited at the Owens Valley Radio Observatory Long Wavelength Array, LEDA systems include the station correlator, five well-separated redundant dual polarization radiometers and backend electronics. The radiometers deliver a 30-85 MHz band (16 < z < 34) and operate as part of the larger interferometric array, for purposes ultimately of in situ calibration. Here, we report on the LEDA system design, calibration approach, and progress in characterization as of January 2016. The LEDA systems are currently being modified to improve performance near 78 MHz in order to verify the purported absorption feature.

Periodic Application of Stochastic Cost Optimization Methodology to Achieve Remediation Objectives with Minimized Life Cycle Cost

NASA Astrophysics Data System (ADS)

Kim, U.; Parker, J.

2016-12-01

Many dense non-aqueous phase liquid (DNAPL) contaminated sites in the U.S. are reported as "remediation in progress" (RIP). However, the cost to complete (CTC) remediation at these sites is highly uncertain and in many cases, the current remediation plan may need to be modified or replaced to achieve remediation objectives. This study evaluates the effectiveness of iterative stochastic cost optimization that incorporates new field data for periodic parameter recalibration to incrementally reduce prediction uncertainty and implement remediation design modifications as needed to minimize the life cycle cost (i.e., CTC). This systematic approach, using the Stochastic Cost Optimization Toolkit (SCOToolkit), enables early identification and correction of problems to stay on track for completion while minimizing the expected (i.e., probability-weighted average) CTC. This study considers a hypothetical site involving multiple DNAPL sources in an unconfined aquifer using thermal treatment for source reduction and electron donor injection for dissolved plume control. The initial design is based on stochastic optimization using model parameters and their joint uncertainty based on calibration to site characterization data. The model is periodically recalibrated using new monitoring data and performance data for the operating remediation systems. Projected future performance using the current remediation plan is assessed and reoptimization of operational variables for the current system or consideration of alternative designs are considered depending on the assessment results. We compare remediation duration and cost for the stepwise re-optimization approach with single stage optimization as well as with a non-optimized design based on typical engineering practice.

ILRS: Current Status and Future Challenges

NASA Astrophysics Data System (ADS)

Pearlman, M. R.; Bianco, G.; Merkowitz, S.; Noll, C. E.; Pavlis, E. C.; Shargorodsky, V.; Zhongping, Z.

2016-12-01

The International Laser Ranging Service (ILRS) is expanding its ground tracking capability with new stations and upgrades to current stations. Our Russian colleagues have installed new stations in Brasilia and South Africa, and have several other sites in process or in planning. The NASA Space Geodesy Program is preparing equipment for U.S. sites (McDonald and Haleakala) and with the Norwegian National Mapping Agency in Ny Ålesund; further deployments are planned. Upgrades continue at sites in China, and new sites are underway or planned in Europe and India. Stations are moving to higher repetition rates and more efficient detection to enhance satellite interleaving capability; some stations have already implemented automated processes that could lead to around-the-clock operation to increase temporal coverage and to make more efficient use of personnel. The ILRS roster of supported satellites continues to grow with the addition of the LARES satellite to augment tracking for the improvement of the ITRF. New GNSS constellations and geosynchronous satellites now bring the total roster to over 80 satellites - so much so, that new tracking strategies and time and location multiplexing are under consideration. There continues to be strong interest in Lunar Ranging. New applications of one-way and two-way laser ranging include ps-accurate time transfer, laser transponders for interplanetary ranging, and tracking of space debris. New laser ranging data products are being developed, including satellite orbit products, satellite orientation, gravity field products, and products to characterize the quality of data and station performance. This talk will give a brief summary of recent progress, current challenges and a view of the path ahead.

Scanning laser Doppler imaging may predict disease progression of localized scleroderma in children and young adults.

PubMed

Shaw, L J; Shipley, J; Newell, E L; Harris, N; Clinch, J G; Lovell, C R

2013-07-01

Localized scleroderma is a rare but potentially disfiguring and disabling condition. Systemic treatment should be started early in those with active disease in key functional and cosmetic sites, but disease activity is difficult to determine clinically. Superficial blood flow has been shown to correlate with disease activity in localized scleroderma. To examine whether superficial blood flow measured by laser Doppler imaging (LDI) has the potential to predict disease progression and therefore select patients for early systemic treatment. A group of 20 individuals had clinical assessment and scanning LDI blood-flow measurements of 32 affected body sites. After a mean follow-up of 8.7 months their clinical outcome was compared with the results of the initial LDI assessment. Eleven out of 15 patients with an assessment of active LDI had progressed clinically, and 16 out of the 17 scans with inactive LDI assessment had not progressed, giving a positive predictive value of 73% and a negative predictive value of 94%. We believe that LDI can be a useful tool in predicting disease progression in localized scleroderma, and it may help clinicians to decide which patients to treat early. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

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

Kahl, S.B.

Although significant progress toward the application of boronated LDL for site selective boron drug delivery has been made during the past year, the loss of our animal and cell culture testing site at WSU has seriously hampered progress on this project. Results are reported of one in vivo biodistribution study in B16BL6-bearing mice and a series of in vitro studies that demonstrate very substantial uptake of boronated LDL in certain cell lines. The influence of 17{alpha}-ethinyl estradiol (EE) on cellular uptake has also been probed. Most significantly LDL loaded with HC was demonstrated to be taken up with exceptional ariditymore » in several lines. Significant progress has also been made in the development of a rapid infrared analysis of boron in boronated LDL solution, which may be useful for clinical BNCT studies in Finland.« less

Bicuspid aortic valve hemodynamics: a fluid-structure interaction study

NASA Astrophysics Data System (ADS)

Chandra, Santanu; Seaman, Clara; Sucosky, Philippe

2011-11-01

The bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve forms with two leaflets instead of three. While calcific aortic valve disease (CAVD) also develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more rapid. Although studies have suggested a mechano-potential root for the disease, the native BAV hemodynamics remains largely unknown. This study aimed at characterizing BAV hemodynamics and quantifying the degree of wall-shear stress (WSS) abnormality on BAV leaflets. Fluid-structure interaction models validated with particle-image velocimetry were designed to predict the flow and leaflet dynamics in idealized TAV and BAV anatomies. Valvular function was quantified in terms of the effective orifice area. The regional leaflet WSS was characterized in terms of oscillatory shear index, temporal shear magnitude and temporal shear gradient. The predictions indicate the intrinsic degree of stenosis of the BAV anatomy, reveal drastic differences in shear stress magnitude and pulsatility on BAV and TAV leaflets and confirm the side- and site-specificity of the leaflet WSS. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, these results support the existence of a mechano-etiology of CAVD in the BAV.

Can enzyme engineering benefit from the modulation of protein motions? Lessons learned from NMR relaxation dispersion experiments.

PubMed

Doucet, Nicolas

2011-04-01

Despite impressive progress in protein engineering and design, our ability to create new and efficient enzyme activities remains a laborious and time-consuming endeavor. In the past few years, intricate combinations of rational mutagenesis, directed evolution and computational methods have paved the way to exciting engineering examples and are now offering a new perspective on the structural requirements of enzyme activity. However, these structure-function analyses are usually guided by the time-averaged static models offered by enzyme crystal structures, which often fail to describe the functionally relevant 'invisible states' adopted by proteins in space and time. To alleviate such limitations, NMR relaxation dispersion experiments coupled to mutagenesis studies have recently been applied to the study of enzyme catalysis, effectively complementing 'structure-function' analyses with 'flexibility-function' investigations. In addition to offering quantitative, site-specific information to help characterize residue motion, these NMR methods are now being applied to enzyme engineering purposes, providing a powerful tool to help characterize the effects of controlling long-range networks of flexible residues affecting enzyme function. Recent advancements in this emerging field are presented here, with particular attention to mutagenesis reports highlighting the relevance of NMR relaxation dispersion tools in enzyme engineering.

Expression and Characterization of Hyperthermostable Exo-polygalacturonase TtGH28 from Thermotoga thermophilus.

PubMed

Wagschal, Kurt; Rose Stoller, J; Chan, Victor J; Lee, Charles C; Grigorescu, Arabela A; Jordan, Douglas B

2016-07-01

D-galacturonic acid is a potential platform chemical comprising the principal component of pectin in the citrus processing waste stream. Several enzyme activities are required for the enzymatic production of galacturonic acid from pectin, including exo- and endo-polygalacturonases. The gene TtGH28 encoding a putative GH28 polygalacturonase from Pseudothermotoga thermarum DSM 5069 (Theth_0397, NCBI# AEH50492.1) was synthesized, expressed in Escherichia coli, and characterized. Alignment of the amino acid sequence of gene product TtGH28 with other GH28 proteins whose structures and details of their catalytic mechanism have been elucidated shows that three catalytic Asp residues and several other key active site residues are strictly conserved. Purified TtGH28 was dimeric and hyperthermostable, with K t (0.5)  = 86.3 °C. Kinetic parameters for activity on digalacturonic acid, trigalacturonic acid, and polygalacturonic acid were obtained. No substrate inhibition was observed for polygalacturonate, while the K si values for the oligogalacturonides were in the low mM range, and K i for product galacturonic acid was in the low μM range. Kinetic modeling of the progress of reaction showed that the enzyme is both fully exo- and fully non-processional.

SkinChip, a new tool for investigating the skin surface in vivo.

PubMed

Lévêque, Jean Luc; Querleux, Bernard

2003-11-01

Non-invasive methods used for characterizing skin micro-relief and skin surface hydration were developed in the 1980s. Although they allowed some progress in the knowledge of skin properties, they are not completely satisfactory in many aspects. Today, new technologies are emerging that may address such issues. We adapted the technology produced by the ST Microelectronics Company for sensing fingerprint for the measurement of skin surface properties. Accordingly, we developed acquisition software for obtaining routinely the distribution of skin surface capacitance along different body sites. Image analysis softwares were also processed for collecting both the main orientations of the micro-relief lines and their density. The average value of skin capacitance is also obtained. The images allow a highly precise observation of the skin topography that can be easily quantified in terms of line density and line orientation. The mean gray levels of the images appear much closely correlated to the Corneometer values. This new device appears to be a very convenient way for characterizing the properties of the skin surface. With regard to hydration, it usefully provides both the average value and the hydration chart of the investigated skin zones.

CHARACTERIZING SITE HYDROLOGY (WORKSHOP MSA PRESENTATION)

EPA Science Inventory

Hydrogeology is the foundation of subsurface site characterization for evaluations of monitored natural attenuation (MNA). Three case studies are presented. Examples of the potentially detrimental effects of drilling additives on ground-water samples from monitoring wells are d...

Characterizing Site Hydrology (Region 10, Seattle, WA)

EPA Science Inventory

Hydrogeology is the foundation of subsurface site characterization for evaluations of monitored natural attenuation (MNA). Three case studies are presented. Examples of the potentially detrimental effects of drilling additives on ground-water samples from monitoring wells are d...

CHARACTERIZING SITE HYDROLOGY (REGION 8 WORKSHOP)

EPA Science Inventory

Hydrogeology is the foundation of subsurface site characterization for evaluations of monitored natural attenuation (MNA). Three case studies are presented. Examples of the potentially detrimental effects of drilling additives on ground-water samples from monitoring wells are d...

Magnetic spectroscopy and microscopy of functional materials

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

Jenkins, Catherine Ann

2011-05-01

Heusler intermetallics Mn 2Y Ga and X 2MnGa (X; Y =Fe, Co, Ni) undergo tetragonal magnetostructural transitions that can result in half metallicity, magnetic shape memory, or the magnetocaloric effect. Understanding the magnetism and magnetic behavior in functional materials is often the most direct route to being able to optimize current materials for todays applications and to design novel ones for tomorrow. Synchrotron soft x-ray magnetic spectromicroscopy techniques are well suited to explore the the competing effects from the magnetization and the lattice parameters in these materials as they provide detailed element-, valence-, and site-specifc information on the coupling ofmore » crystallographic ordering and electronic structure as well as external parameters like temperature and pressure on the bonding and exchange. Fundamental work preparing the model systems of spintronic, multiferroic, and energy-related compositions is presented for context. The methodology of synchrotron spectroscopy is presented and applied to not only magnetic characterization but also of developing a systematic screening method for future examples of materials exhibiting any of the above effects. The chapter progression is as follows: an introduction to the concepts and materials under consideration (Chapter 1); an overview of sample preparation techniques and results, and the kinds of characterization methods employed (Chapter 2); spectro- and microscopic explorations of X 2MnGa/Ge (Chapter 3); spectroscopic investigations of the composition series Mn 2Y Ga to the logical Mn 3Ga endpoint (Chapter 4); and a summary and overview of upcoming work (Chapter 5). Appendices include the results of a Think Tank for the Graduate School of Excellence MAINZ (Appendix A) and details of an imaging project now in progress on magnetic reversal and domain wall observation in the classical Heusler material Co 2FeSi (Appendix B).« less

Progress of the Mars Array Technology Experiment (MATE) on the '01 Lander

NASA Technical Reports Server (NTRS)

Scheiman, D. A.; Baraona, C. R.; Jenkins, P.; Wilt, D.; Krasowski, M.; Greer, L.; Lekki, J.; Spina, D.

1999-01-01

Future missions to Mars will rely heavily on solar power from the sun, various solar cell types and structures must be evaluated to find the optimum. Sunlight on the surface of Mars is altered by air-borne dust that fluctuates in density from day to day. The dust affects both the intensity and spectral content of the sunlight. The MATE flight experiment was designed for this purpose and will fly on the Mars 2001 Surveyor Lander as part of the Mars In-Situ Propellant Production Precursor (MIP) package. MATE will measure the performance of several solar cell technologies and characterize the Martian environment in terms of solar power. This will be done by measuring full IV curves on solar cells, direct and global insolation, temperature, and spectral content. The Lander is is scheduled to launch in April 2001 and arrive on Mars in January of 2002. The site location has not been identified but will be near the equator and last from 100 to 300 days. The intent of this of this paper is to describe and update the progress on MATE. MATE has four main objectives for its mission to Mars. First is to measure the performance of solar cells daily on the surface of Mars, this will determine the day to day fluctuations in sunlight and temperature and provide a nominal power output. Second, in addition to measuring solar cell performance, it will allow for an intercomparison of different solar cell technologies. Third, It will study the long term effects of dust on the solar cells. Fourth and last, it will characterize the mars environment as viewed by the solar cell, measuring spectrum, insolation, and temperature. Additional information is contained in the original extended abstract.

Paired high-content analysis of prostate cancer cells in bone marrow and blood characterizes increased androgen receptor expression in tumor cell clusters

PubMed Central

Carlsson, Anders; Kuhn, Peter; Luttgen, Madelyn S.; Dizon, Kevin K.; Troncoso, Patricia; Corn, Paul G.; Kolatkar, Anand; Hicks, James B.; Logothetis, Christopher J.; Zurita., Amado J.

2017-01-01

Purpose Recent studies demonstrate that prostate cancer clones from different metastatic sites are dynamically represented in the blood of patients over time, suggesting that the paired evaluation of tumor cells in circulation and bone marrow, the primary target for prostate cancer metastasis, may provide complementary information. Experimental Design We adapted our single-cell high-content liquid biopsy platform to bone marrow aspirates (BMA), to concurrently identify and characterize prostate cancer cells in patients’ blood and bone and thus discern features associated to tumorigenicity and dynamics of metastatic progression. Results The incidence of tumor cells in BMAs increased as the disease advanced: 0% in biochemically-recurrent (n=52), 26% in newly diagnosed metastatic hormone-naïve (n=26), and 39% in metastatic castration-resistant (mCRPC; n=63) patients, and their number was often higher than in paired blood. Tumor cell detection in metastatic patients’ BMAs was concordant but 45% more sensitive than using traditional histopathologic interpretation of core bone marrow biopsies. Tumor cell clusters were more prevalent and bigger in BMAs than in blood, expressed higher levels of the androgen receptor protein per tumor cell and were prognostic in mCRPC. Moreover, the patterns of genomic copy number variation in single tumor cells in paired blood and BMAs showed significant inter and intrapatient heterogeneity. Conclusions Paired analysis of single prostate cancer cells in blood and bone shows promise for clinical application and provides complementary information. The high prevalence and prognostic significance of tumor cell clusters particularly in BMAs, suggest that these structures are key mediators of prostate cancer’s metastatic progression. PMID:27702818

Isolation and characterization of adrenoleukodystrophy protein (ALDP) related sequences in the human genome

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

Geraghty, M.T.; Stetten, G.; Kearns, W.

1994-09-01

X-linked adrenoleukodystrophy (ALD) is a disorder of peroxisomal {beta}-oxidation of very long chain fatty acids. It presents either as progressive dementia in childhood or as progressive paraparesis in later years. Adrenal insufficiency occurs in both phenotypes. The gene of the ALD protein has been mapped to Xq28 and has recently been cloned and characterized. The ALD protein has significant homology to the peroxisomal membrane protein, PMP70 and belongs to the ATP binding cassette superfamily of transporters. We screened a human genomic library with an ALDP cDNA and isolated 5 different but highly similar clones containing sequences corresponding to the 3{prime}more » end of the ALDP gene. Comparison of the sequences over the region corresponding to exon 9 through the 3{prime} end of the ALDP gene reveals {approximately}96% nucleotide identity in both exonic and intronic regions. Splice sites and open reading frames are maintained. Using both FISH and human-rodent DNA mapping panels, we positively assign these ALDP-related sequences to chromosomes 2, 16 and 22, and provisionally to 1 and 20. Southern blot of primate DNA probed with a partial ALDP cDNA (exon 2-10) shows that expansion of ALDP-related sequences occurred in higher primates (chimp, gorilla and human). Although Northern blots show multiple ALDP-hybridizing transcripts in certain tissues, we have no evidence to date for expression of these ALDP-related sequences. In conclusion, our data show there has been an unusual and recent dispersal to multiple chromosomes of structural gene sequences related to the ALDP gene. The functional significance of these sequences remains to be determined but their existence complicates PCR and mutation analysis of the ALDP gene.« less

Yucca Mountain Biological Resources Monitoring Program; Annual report, FY91

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

NONE

1992-01-01

The US Department of Energy (DOE) is required by the Nuclear Waste Policy Act of 1982 (as amended in 1987) to study and characterize Yucca Mountain as a possible site for a geologic repository for high-level nuclear waste. During site characterization, the DOE will conduct a variety of geotechnical, geochemical, geological, and hydrological studies to determine the suitability of Yucca Mountain as a repository. To ensure that site characterization activities (SCA) do not adversely affect the Yucca Mountain area, an environmental program has been implemented to monitor and mitigate potential impacts and to ensure that activities comply with applicable environmentalmore » regulations. This report describes the activities and accomplishments during fiscal year 1991 (FY91) for six program areas within the Terrestrial Ecosystem component of the YMP environmental program. The six program areas are Site Characterization Activities Effects, Desert Tortoises, Habitat Reclamation, Monitoring and Mitigation, Radiological Monitoring, and Biological Support.« less

Characterization of the Tumor Microenvironment and Tumor–Stroma Interaction by Non-invasive Preclinical Imaging

PubMed Central

Ramamonjisoa, Nirilanto; Ackerstaff, Ellen

2017-01-01

Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression. The resulting altered metabolic content in tumors has the ability to affect cell signaling and block cellular differentiation. Additional emerging evidence reveals that the interaction between tumor and stroma cells can alter tumor metabolism (leading to metabolic reprograming) as well as tumor growth and vascular features. This review will summarize previous and current preclinical, non-invasive, multimodal imaging efforts to characterize the tumor microenvironment, including its stromal components and understand tumor–stroma interaction in cancer development, progression, and treatment response. PMID:28197395

Infrared Imaging and Characterization of Exoplanets: Can we Detect Earth-Twins on a Budget?

NASA Technical Reports Server (NTRS)

Danchi, William

2010-01-01

During the past decade considerable progress has been made developing techniques that can be used to detect and characterize Earth twins in the mid- infrared (7-20 microns). The principal technique is called nulling interferometry, and it was invented by Bracewell in the late 1970's. The nulling technique is an interferometric equivalent of an optical coronagraph. At the present time most of the technological hurdles have been overcome for a space mission to be able to begin Phase A early in the next decade, and it is possible to detect and characterize Earth-twins on a mid- sized strategic mission budget ($600-800 million). I will review progress on this exciting method of planet detection in the context of recent work on the Exoplanet Community Forum and the US Decadal Survey (Astro2010), including biomarkers, technological progress, mission concepts, the theory of these instruments, and a.comparison of the discovery space of this technique with others also under consideration.

Adaptive Sampling approach to environmental site characterization at Joliet Army Ammunition Plant: Phase 2 demonstration

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

Bujewski, G.E.; Johnson, R.L.

1996-04-01

Adaptive sampling programs provide real opportunities to save considerable time and money when characterizing hazardous waste sites. This Strategic Environmental Research and Development Program (SERDP) project demonstrated two decision-support technologies, SitePlanner{trademark} and Plume{trademark}, that can facilitate the design and deployment of an adaptive sampling program. A demonstration took place at Joliet Army Ammunition Plant (JAAP), and was unique in that it was tightly coupled with ongoing Army characterization work at the facility, with close scrutiny by both state and federal regulators. The demonstration was conducted in partnership with the Army Environmental Center`s (AEC) Installation Restoration Program and AEC`s Technology Developmentmore » Program. AEC supported researchers from Tufts University who demonstrated innovative field analytical techniques for the analysis of TNT and DNT. SitePlanner{trademark} is an object-oriented database specifically designed for site characterization that provides an effective way to compile, integrate, manage and display site characterization data as it is being generated. Plume{trademark} uses a combination of Bayesian analysis and geostatistics to provide technical staff with the ability to quantitatively merge soft and hard information for an estimate of the extent of contamination. Plume{trademark} provides an estimate of contamination extent, measures the uncertainty associated with the estimate, determines the value of additional sampling, and locates additional samples so that their value is maximized.« less

Molecular Characterization of Transgene Integration by Next-Generation Sequencing in Transgenic Cattle

PubMed Central

Zhang, Ran; Yin, Yinliang; Zhang, Yujun; Li, Kexin; Zhu, Hongxia; Gong, Qin; Wang, Jianwu; Hu, Xiaoxiang; Li, Ning

2012-01-01

As the number of transgenic livestock increases, reliable detection and molecular characterization of transgene integration sites and copy number are crucial not only for interpreting the relationship between the integration site and the specific phenotype but also for commercial and economic demands. However, the ability of conventional PCR techniques to detect incomplete and multiple integration events is limited, making it technically challenging to characterize transgenes. Next-generation sequencing has enabled cost-effective, routine and widespread high-throughput genomic analysis. Here, we demonstrate the use of next-generation sequencing to extensively characterize cattle harboring a 150-kb human lactoferrin transgene that was initially analyzed by chromosome walking without success. Using this approach, the sites upstream and downstream of the target gene integration site in the host genome were identified at the single nucleotide level. The sequencing result was verified by event-specific PCR for the integration sites and FISH for the chromosomal location. Sequencing depth analysis revealed that multiple copies of the incomplete target gene and the vector backbone were present in the host genome. Upon integration, complex recombination was also observed between the target gene and the vector backbone. These findings indicate that next-generation sequencing is a reliable and accurate approach for the molecular characterization of the transgene sequence, integration sites and copy number in transgenic species. PMID:23185606

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

Link, P.K.

A total of 48 papers were presented at the Engineering Geology and Geotechnical Engineering 30th Symposium. These papers are presented in this proceedings under the following headings: site characterization--Pocatello area; site characterization--Boise Area; site assessment; Idaho National Engineering Laboratory; geophysical methods; remediation; geotechnical engineering; and hydrogeology, northern and western Idaho. Individual papers have been processed separately for inclusion in the Energy Science and Technology Database.

Establishing Benchmarks and Measuring Progress at "HSTW" Sites.

ERIC Educational Resources Information Center

Southern Regional Education Board (SREB), 2010

2010-01-01

Schools that join the "High Schools That Work (HSTW)" network are expected to show progress in changing school and classroom practices in ways that improve student achievement and readiness for postsecondary studies and careers. They are expected to focus on practices that have proven most effective in advancing student achievement.…

Spectral Induced Polarization monitoring of the groundwater physico-chemical parameters daily variations for stream-groundwater interactions

NASA Astrophysics Data System (ADS)

Jougnot, Damien; Camerlynck, Christian; Robain, Henri; Tallec, Gaëlle; Ribolzi, Olivier; Gaillardet, Jérôme

2017-04-01

During the last decades, geophysical methods have been attracting an increasing interest in hydrology and environmental sciences given their sensitivity to parameters of interests and their non-intrusive nature. The Spectral Induced Polarization (SIP) is a low frequency electro-magnetic method that allows the characterization of the subsurface through its complex electrical conductivity. It reports the modulus of the conductivity and the phase between an injected current and a measured voltage over a rather large frequency range (from few millihertz to few tens of kilohertz). The real part of the conductivity is sensitive to lithological (porosity, specific surface area) and hydrological (water saturation, water salinity) parameters, while the imaginary part is linked to electrochemical polarizations, that have been shown to be largely influenced by the chemistry of the pore water. In the present contribution, we aim at better characterizing the exchanges between a stream and the surrounding groundwater using the SIP method and its sensitivity to pore water changes over time. Two sites from the OZCAR Research Infrastructure (French Critical Zone observatories) have been chosen for this study: the Houay Pano catchment (Laos) and the Orgeval catchment (France). These two sites have a good existing infrastructure and have been already studied extensively in terms of hydrology, geophysics, and hydrochemistry. They constitute perfect experimental sites to develop novel methodologies for the assessment of stream-groundwater exchanges. We propose to obtain a vertical description of the changes in complex electrical conductivity with depth based on SIP soundings undertaken with the multi-channel system SIP Fuchs III. We conducted a high-frequency monitoring close to a river stream (one vertical profiles every 30 min). In parallel, a high frequency monitoring of the physico-chemical parameters (temperature, conductivity, ionic concentrations) in the river stream has been performed. Relating the daily fluctuations of the groundwater complex conductivity and the river physico-chemical parameters could therefore establish a new proxy to characterize stream-groundwater interactions. In parallel to the field measurements, laboratory experiments have been conducted on soil samples from the two sites. These measurements provide a better understanding of the complex conductivity signature of the samples submitted to saturation and pore water physico-chemical changes. This work is in progress but the first results already show that the method has a real interest for the monitoring of daily variations of the physico-chemistry properties of the groundwater and their relations to those of the stream.

Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0548 TITLE: Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression PRINCIPAL...Sep 2015 4. TITLE AND SUBTITLE Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression 5a. CONTRACT NUMBER 5b. GRANT...they are produced, but can also signal intercellularly to other cells and tissues at distant sites via exosomal transport. We hypothesize that miRNAs

Environmental assessment: Davis Canyon site, Utah

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

none,

1986-05-01

In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOEmore » prepared the final EA. The Davis Canyon site is in the Paradox Basin, which is one of five distinct geohydrologic settings considered for the first repository. This setting contains one other potentially acceptable site -- the Lavender Canyon site. Although the Lavender Canyon site is suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. On the basis of the evaluations reported in this EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. Furthermore, the DOE has fond that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Davis Canyon site as one of five sites suitable for characterization. 181 figs., 175 tabs.« less

Environmental assessment: Davis Canyon site, Utah

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

none,

1986-05-01

In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high- level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, themore » DOE prepared the final EA. The Davis Canyon site is in the Paradox Basin, which is one of five distinct geohydrologic settings considered for the first repository. This setting contains one other potentially acceptable site -- the Lavender Canyon site. Although the Lavender Canyon site is suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. On the basis of the evaluations reported in this EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. Furthermore, the DOE has found that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Davis Canyon site as one of the five sites suitable for characterization.« less

Report: EPA Has Made Progress in Assessing Historical Lead Smelter Sites But Needs to Strengthen Procedures

EPA Pesticide Factsheets

Report #14-P-0302, June 17, 2014. Improvements in guidance and procedures for managing contaminated sites could result in more efficient and effective use of limited resources and result in public health and economic benefits.

SP-100 ground engineering system test site description and progress update

NASA Astrophysics Data System (ADS)

Baxter, William F.; Burchell, Gail P.; Fitzgibbon, Davis G.; Swita, Walter R.

1991-01-01

The SP-100 Ground Engineering System Test Site will provide the facilities for the testing of an SP-100 reactor, which is technically prototypic of the generic design for producing 100 kilowatts of electricity. This effort is part of the program to develop a compact, space-based power system capable of producing several hundred kilowatts of electrical power. The test site is located on the U.S. Department of Energy's Hanford Site near Richland, Washington. The site is minimizing capital equipment costs by utilizing existing facilities and equipment to the maximum extent possible. The test cell is located in a decommissioned reactor containment building, and the secondary sodium cooling loop will use equipment from the Fast Flux Test Facility plant which has never been put into service. Modifications to the facility and special equipment are needed to accommodate the testing of the SP-100 reactor. Definitive design of the Ground Engineering System Test Site facility modifications and systems is in progress. The design of the test facility and the testing equipment will comply with the regulations and specifications of the U.S. Department of Energy and the State of Washington.

Environmental Technology Verification (ETV) Program: Site Characterization and Monitoring Technologies Center

EPA Pesticide Factsheets

The ETV Site Characterization and Monitoring Technology Pilot is composed of EPA, DoD, DOE, other Federal agencies, state regulators, technology evaluation and verification entities, and potential end users of these technologies to facilitate independent..

Role of Imaging Specrometer Data for Model-based Cross-calibration of Imaging Sensors

NASA Technical Reports Server (NTRS)

Thome, Kurtis John

2014-01-01

Site characterization benefits from imaging spectrometry to determine spectral bi-directional reflectance of a well-understood surface. Cross calibration approaches, uncertainties, role of imaging spectrometry, model-based site characterization, and application to product validation.

Location of subventricular zone recurrence and its radiation dose predicts survival in patients with glioblastoma.

PubMed

Weinberg, Brent D; Boreta, Lauren; Braunstein, Steve; Cha, Soonmee

2018-07-01

Glioblastomas are aggressive brain tumors that frequently recur in the subventricular zone (SVZ) despite maximal treatment. The purpose of this study was to evaluate imaging patterns of subventricular progression and impact of recurrent subventricular tumor involvement and radiation dose to patient outcome. Retrospective review of 50 patients diagnosed with glioblastoma and treated with surgery, radiation, and concurrent temozolomide from January 2012 to June 2013 was performed. Tumors were classified based on location, size, and cortical and subventricular zone involvement. Survival was compared based on recurrence type, distance from the initial enhancing tumor (local ≤ 2 cm, distant > 2 cm), and the radiation dose at the recurrence site. Progression of enhancing subventricular tumor was common at both local (58%) and distant (42%) sites. Median survival was better after local SVZ recurrence than distant SVZ recurrence (8.7 vs. 4.3 months, p = 0.04). Radiation doses at local SVZ recurrence sites recurrence averaged 57.0 ± 4.0 Gy compared to 44.7 ± 6.7 Gy at distant SVZ recurrence sites (p = 0.008). Distant subventricular progression at a site receiving ≤ 45 Gy predicted worse subsequent survival (p = 0.05). Glioblastomas frequently recurred in the subventricular zone, and patient survival was worse when enhancing tumor occurred at sites that received lower radiation doses. This recurrent disease may represent disease undertreated at the time of diagnosis, and further study is needed to determine if improved treatment strategies, such as including the subventricular zone in radiation fields, could improve clinical outcomes.

Geotechnical support and topical studies for nuclear waste geologic repositories

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

Not Available

1989-01-01

The present report lists the technical reviews and comments made during the fiscal year 1988 and summarizes the technical progress of the topical studies. In the area of technical assistance, there were numerous activities detailed in the next section. These included 24 geotechnical support activities, including reviews of 6 Study Plans (SP) and participation in 6 SP Review Workshops, review of one whole document Site Characterization Plan (SCP) and participation in the Assembled Document SCP Review Workshops by 6 LBL reviewers; the hosting of a DOE program review, the rewriting of the project statement of work, 2 trips to technicalmore » and planning meetings; preparation of proposed work statements for two new topics for DOE, and 5 instances of technical assistance to DOE. These activities are described in a Table in the following section entitled Geoscience Technical Support for Nuclear Waste Geologic Repositories.''« less

Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics.

PubMed

Howard, Rebecca J; Trudell, James R; Harris, R Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy.

Molecular organization of excitatory chemical synapses in the mammalian brain

NASA Astrophysics Data System (ADS)

Gundelfinger, E. D.; tom Dieck, S.

Chemical synapses are highly specialized cell-cell junctions designed for efficient signaling between nerve cells. Distinct cytoskeletal matrices are assembled at either side of the synaptic junction. The presynaptic cytomatrix at the active zone (CAZ) defines and organizes the site of neurotransmitter release from presynaptic nerve terminals. The postsynaptic density (PSD) tethers neurotransmitter receptors and the postsynaptic signal transduction machinery. Recent progress in the identification and characterization of novel CAZ and PSD components has revealed new insights into the molecular organization and assembly mechanisms of the synaptic neurotransmission apparatus. On the presynaptic side, Bassoon and Piccolo, two related giant proteins, are crucially involved in scaffolding the CAZ. On the postsynaptic side, two families of multi-domain adaptor proteins, the MAGuKs (membrane-associated guanylate kinase homologs) and the ProSAP (proline-rich synapse-associated protein, also termed Shank) family members are thought to be major organizing molecules of the PSD.

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

PubMed Central

Trudell, James R.; Harris, R. Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy. PMID:24515646

Contribution of neutrophils to acute lung injury.

PubMed

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Catalysis by clusters with precise numbers of atoms

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

Tyo, Eric C.; Vajda, Stefan

2015-07-03

Clusters that contain only a small number of atoms can exhibit unique and often unexpected properties. The clusters are of particular interest in catalysis because they can act as individual active sites, and minor changes in size and composition – such as the addition or removal of a single atom – can have a substantial influence on the activity and selectivity of a reaction. Here we review recent progress in the synthesis, characterization and catalysis of well-defined sub-nanometre clusters. We examine work on size-selected supported clusters in ultra-high vacuum environments and under realistic reaction conditions, and explore the use ofmore » computational methods to provide a mechanistic understanding of their catalytic properties. We also highlight the potential of size-selected clusters to provide insights into important catalytic processes and their use in the development of novel catalytic systems.« less

Evaluation of point mutations in dystrophin gene in Iranian Duchenne and Becker muscular dystrophy patients: introducing three novel variants.

PubMed

Haghshenas, Maryam; Akbari, Mohammad Taghi; Karizi, Shohreh Zare; Deilamani, Faravareh Khordadpoor; Nafissi, Shahriar; Salehi, Zivar

2016-06-01

Duchenne and Becker muscular dystrophies (DMD and BMD) are X-linked neuromuscular diseases characterized by progressive muscular weakness and degeneration of skeletal muscles. Approximately two-thirds of the patients have large deletions or duplications in the dystrophin gene and the remaining one-third have point mutations. This study was performed to evaluate point mutations in Iranian DMD/BMD male patients. A total of 29 DNA samples from patients who did not show any large deletion/duplication mutations following multiplex polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) screening were sequenced for detection of point mutations in exons 50-79. Also exon 44 was sequenced in one sample in which a false positive deletion was detected by MLPA method. Cycle sequencing revealed four nonsense, one frameshift and two splice site mutations as well as two missense variants.

Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both β-amyloid production and clearance.

PubMed

Zhu, Zhiyuan; Yan, Jianming; Jiang, Wei; Yao, Xin-gang; Chen, Jing; Chen, Lili; Li, Chenjing; Hu, Lihong; Jiang, Hualiang; Shen, Xu

2013-08-07

Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The β-amyloid (Aβ)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aβ production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aβ formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.

A Secreted Effector Protein of Ustilago maydis Guides Maize Leaf Cells to Form Tumors

PubMed Central

Redkar, Amey; Hoser, Rafal; Schilling, Lena; Zechmann, Bernd; Krzymowska, Magdalena; Walbot, Virginia; Doehlemann, Gunther

2015-01-01

The biotrophic smut fungus Ustilago maydis infects all aerial organs of maize (Zea mays) and induces tumors in the plant tissues. U. maydis deploys many effector proteins to manipulate its host. Previously, deletion analysis demonstrated that several effectors have important functions in inducing tumor expansion specifically in maize leaves. Here, we present the functional characterization of the effector See1 (Seedling efficient effector1). See1 is required for the reactivation of plant DNA synthesis, which is crucial for tumor progression in leaf cells. By contrast, See1 does not affect tumor formation in immature tassel floral tissues, where maize cell proliferation occurs independent of fungal infection. See1 interacts with a maize homolog of SGT1 (Suppressor of G2 allele of skp1), a factor acting in cell cycle progression in yeast (Saccharomyces cerevisiae) and an important component of plant and human innate immunity. See1 interferes with the MAPK-triggered phosphorylation of maize SGT1 at a monocot-specific phosphorylation site. We propose that See1 interferes with SGT1 activity, resulting in both modulation of immune responses and reactivation of DNA synthesis in leaf cells. This identifies See1 as a fungal effector that directly and specifically contributes to the formation of leaf tumors in maize. PMID:25888589

Genetic resources offer efficient tools for rice functional genomics research.

PubMed

Lo, Shuen-Fang; Fan, Ming-Jen; Hsing, Yue-Ie; Chen, Liang-Jwu; Chen, Shu; Wen, Ien-Chie; Liu, Yi-Lun; Chen, Ku-Ting; Jiang, Mirng-Jier; Lin, Ming-Kuang; Rao, Meng-Yen; Yu, Lin-Chih; Ho, Tuan-Hua David; Yu, Su-May

2016-05-01

Rice is an important crop and major model plant for monocot functional genomics studies. With the establishment of various genetic resources for rice genomics, the next challenge is to systematically assign functions to predicted genes in the rice genome. Compared with the robustness of genome sequencing and bioinformatics techniques, progress in understanding the function of rice genes has lagged, hampering the utilization of rice genes for cereal crop improvement. The use of transfer DNA (T-DNA) insertional mutagenesis offers the advantage of uniform distribution throughout the rice genome, but preferentially in gene-rich regions, resulting in direct gene knockout or activation of genes within 20-30 kb up- and downstream of the T-DNA insertion site and high gene tagging efficiency. Here, we summarize the recent progress in functional genomics using the T-DNA-tagged rice mutant population. We also discuss important features of T-DNA activation- and knockout-tagging and promoter-trapping of the rice genome in relation to mutant and candidate gene characterizations and how to more efficiently utilize rice mutant populations and datasets for high-throughput functional genomics and phenomics studies by forward and reverse genetics approaches. These studies may facilitate the translation of rice functional genomics research to improvements of rice and other cereal crops. © 2015 John Wiley & Sons Ltd.

Kinetic characteristics of euflammation: the induction of controlled inflammation without overt sickness behavior.

PubMed

Tarr, Andrew J; Liu, Xiaoyu; Reed, Nathaniel S; Quan, Ning

2014-11-01

We found recently that controlled progressive challenge with subthreshold levels of E. coli can confer progressively stronger resistance to future reinfection-induced sickness behavior to the host. We have termed this type of inflammation "euflammation". In this study, we further characterized the kinetic changes in the behavior, immunological, and neuroendocrine aspects of euflammation. Results show euflammatory animals only display transient and subtle sickness behaviors of anorexia, adipsia, and anhedonia upon a later infectious challenge which would have caused much more severe and longer lasting sickness behavior if given without prior euflammatory challenges. Similarly, infectious challenge-induced corticosterone secretion was greatly ameliorated in euflammatory animals. At the site of E.coli priming injections, which we termed euflammation induction locus (EIL), innate immune cells displayed a partial endotoxin tolerant phenotype with reduced expression of innate activation markers and muted inflammatory cytokine expression upon ex vivo LPS stimulation, whereas innate immune cells outside EIL displayed largely opposite characteristics. Bacterial clearance function, however, was enhanced both inside and outside EIL. Finally, sickness induction by an infectious challenge placed outside the EIL was also abrogated. These results suggest euflammation could be used as an efficient method to "train" the innate immune system to resist the consequences of future infectious/inflammatory challenges. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of structural determinants controlling human and mouse stromelysin-3 proteolytic activities.

PubMed

Noël, A; Santavicca, M; Stoll, I; L'Hoir, C; Staub, A; Murphy, G; Rio, M C; Basset, P

1995-09-29

Matrix metalloproteinases (matrixins) constitute a group of extracellular proteinases belonging to the metzincin superfamily. They are involved in both physiological and pathological tissue remodeling processes, including those associated with cancer progression. Stromelysin-3, which is expressed in most invasive human carcinomas, is a matrix metalloproteinase with unusual functional properties. In particular, its mature form does not cleave any of the major extracellular matrix components. To define critical structural determinants involved in controlling stromelysin-3 proteolytic activity, we have used site-directed mutagenesis. We show that the deletion of at least 175 C-terminal amino-acids is sufficient to endow mouse stromelysin-3 with activities against casein, laminin, and type IV collagen. In the case of the human enzyme, however, a further and single Ala-235-->Pro substitution is necessary to observe similar activities. Ala-235, which characterizes human stromelysin-3 among matrixins, is located immediately after the C terminus of the "Met-turn," which forms a hydrophobic basis for the catalytic zinc atom in the metzincin family. We conclude that human stromelysin-3 has gained specific functional properties during evolution by amino acid substitution in the catalytic zinc environment, and that it represents an attractive target for specific inhibitors that may be used to prevent cancer progression.

Dispersal-competition tradeoff in microbiomes in the quest for land colonization.

PubMed

Dini-Andreote, Francisco; van Elsas, Jan Dirk; Olff, Han; Salles, Joana Falcão

2018-06-21

Ancestor microbes started colonizing inland habitats approximately 2.7 to 3.5 billion years ago. With some exceptions, the key physiological adaptations of microbiomes associated with marine-to-land transitions have remained elusive. This is essentially caused by the lack of suitable systems that depict changes in microbiomes across sufficiently large time scales. Here, we investigate the adaptive routes taken by microbiomes along a contemporary gradient of land formation. Using functional trait-based metagenomics, we show that a switch from a microbial 'dispersal' to a 'competition' response modus best characterizes the microbial trait changes during this eco-evolutionary trajectory. The 'dispersal' modus prevails in microbiomes at the boundary sites between land and sea. It encompasses traits conferring cell chemosensory and motile behaviors, thus allowing the local microbes to exploit short-lived nutritional patches in high-diffusion microhabitats. A systematic transition towards the 'competition' modus occurs progressively as the soil matures, which is likely due to forces of viscosity or strain that favor traits for competition and chemical defense. Concomitantly, progressive increases in the abundances of genes encoding antibiotic resistance and complex organic substrate degradation were found. Our findings constitute a novel perspective on the ecology and evolution of microbiome traits, tracking back one of the most seminal transitions in the evolutionary history of life.

Drilling and geophysical logs of the tophole at an oil-and-gas well site, Central Venango County, Pennsylvania

USGS Publications Warehouse

Williams, John H.; Bird, Philip H.; Conger, Randall W.; Anderson, J. Alton

2014-01-01

Collection and integrated analysis of drilling and geophysical logs provided an efficient and effective means for characterizing the geohydrologic framework and conditions penetrated by the tophole at the selected oil-and-gas well site. The logging methods and lessons learned at this well site could be applied at other oil-and-gas drilling sites to better characterize the shallow subsurface with the overall goal of protecting freshwater aquifers during hydrocarbon development.

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

Not Available

The Nuclear Waste Policy Act of 1982 (42 USC sections 10101-10226) requires the environmental assessment of a proposed site to include a statement of the basis for nominating a site as suitable for characterization. Volume 2 provides a detailed statement evaluating the site suitability of the Deaf Smith County Site under DOE siting guidelines, as well as a comparison of the Deaf Smith County Site to the other sites under consideration. The evaluation of the Deaf Smith County Site is based on the impacts associated with the reference repository design, but the evaluation will not change if based on themore » Mission Plan repository concept. The second part of this document compares the Deaf Smith County Site to Davis Canyon, Hanford, Richton Dome and Yucca Mountain. This comparison is required under DOE guidelines and is not intended to directly support subsequent recommendation of three sites for characterization as candidate sites. 259 refs., 29 figs., 66 refs. (MHB)« less

Progress on the decommissioning of Zion nuclear generating station

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

Moloney, B. P.; Hess, J.

2013-07-01

The decommissioning of the twin 1040 MWe PWRs at Zion, near Chicago USA is a ground breaking programme. The original owner, Exelon Nuclear Corporation, transferred the full responsibility for reactor dismantling and site license termination to a subsidiary of EnergySolutions. The target end state of the Zion site for return to Exelon will be a green field with the exception of the dry fuel storage pad. In return, ZionSolutions has access to the full value of the decommissioning trust fund. There are two potential attractions of this model: lower overall cost and significant schedule acceleration. The Zion programme which commencedmore » in September 2010 is designed to return the cleared site with an Independent Spent Fuel Storage Installation (ISFSI) pad in 2020, 12 years earlier than planned by Exelon. The overall cost, at $500 M per full size power reactor is significantly below the long run trend of $750 M+ per PWR. Implementation of the accelerated programme has been underway for nearly three years and is making good progress. The programme is characterised by numerous projects proceeding in parallel. The critical path is defined by the inspection and removal of fuel from the pond and transfer into dry fuel storage casks on the ISFSI pad and completion of RPV segmentation. Fuel loading is expected to commence in mid- 2013 with completion in late 2014. In parallel, ZionSolutions is proceeding with the segmentation of the Reactor Vessel (RV) and internals in both Units. Removal of large components from Unit 1 is underway. Numerous other projects are underway or have been completed to date. They include access openings into both containments, installation of heavy lift crane capacity, rail upgrades to support waste removal from the site, radiological characterization of facilities and equipment and numerous related tasks. As at February 2013, the programme is just ahead of schedule and within the latest budget. The paper will provide a fuller update. The first two years of the Zion programme offer some interesting learning opportunities. The critical importance of leadership and project control systems will be emphasised in the paper. Strong supplier relationships and good community cooperation are essential. A learning and adaptable team, incentivised to meet schedule and budget, drives affordability of the whole programme. Our key lessons so far concern organisation and people as much as engineering and technology. (authors)« less

Environmental characterization of two potential locations at Hanford for a new production reactor

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

Watson, E.C.; Becker, C.D.; Fitzner, R.E.

This report describes various environmental aspects of two areas on the Hanford Site that are potential locations for a New Production Reactor (NPR). The area known as the Skagit Hanford Site is considered the primary or reference site. The second area, termed the Firehouse Site, is considered the alternate site. The report encompasses an environmental characterization of these two potential NPR locations. Eight subject areas are covered: geography and demography; ecology; meteorology; hydrology; geology; cultural resources assessment; economic and social effects of station construction and operation; and environmental monitoring. 80 refs., 68 figs., 109 tabs.

Remediation management of complex sites using an adaptive site management approach.

PubMed

Price, John; Spreng, Carl; Hawley, Elisabeth L; Deeb, Rula

2017-12-15

Complex sites require a disproportionate amount of resources for environmental remediation and long timeframes to achieve remediation objectives, due to their complex geologic conditions, hydrogeologic conditions, geochemical conditions, contaminant-related conditions, large scale of contamination, and/or non-technical challenges. A recent team of state and federal environmental regulators, federal agency representatives, industry experts, community stakeholders, and academia worked together as an Interstate Technology & Regulatory Council (ITRC) team to compile resources and create new guidance on the remediation management of complex sites. This article summarizes the ITRC team's recommended process for addressing complex sites through an adaptive site management approach. The team provided guidance for site managers and other stakeholders to evaluate site complexities and determine site remediation potential, i.e., whether an adaptive site management approach is warranted. Adaptive site management was described as a comprehensive, flexible approach to iteratively evaluate and adjust the remedial strategy in response to remedy performance. Key aspects of adaptive site management were described, including tools for revising and updating the conceptual site model (CSM), the importance of setting interim objectives to define short-term milestones on the journey to achieving site objectives, establishing a performance model and metrics to evaluate progress towards meeting interim objectives, and comparing actual with predicted progress during scheduled periodic evaluations, and establishing decision criteria for when and how to adapt/modify/revise the remedial strategy in response to remedy performance. Key findings will be published in an ITRC Technical and Regulatory guidance document in 2017 and free training webinars will be conducted. More information is available at www.itrc-web.org. Copyright © 2017 Elsevier Ltd. All rights reserved.

Connected Vehicle Pilot Positioning and Timing Report: Summary of Positioning and Timing Approaches in CV Pilot Sites

DOT National Transportation Integrated Search

2018-01-25

This document summarizes positioning and timing related information from the three Connected Vehicle Pilot Deployment Sites (NYCDOT, Tampa/THEA, and WYDOT) as discussed during technical roundtables. Information is largely based on progress to date du...

Methods to characterize environmental settings of stream and groundwater sampling sites for National Water-Quality Assessment

USGS Publications Warehouse

Nakagaki, Naomi; Hitt, Kerie J.; Price, Curtis V.; Falcone, James A.

2012-01-01

Characterization of natural and anthropogenic features that define the environmental settings of sampling sites for streams and groundwater, including drainage basins and groundwater study areas, is an essential component of water-quality and ecological investigations being conducted as part of the U.S. Geological Survey's National Water-Quality Assessment program. Quantitative characterization of environmental settings, combined with physical, chemical, and biological data collected at sampling sites, contributes to understanding the status of, and influences on, water-quality and ecological conditions. To support studies for the National Water-Quality Assessment program, a geographic information system (GIS) was used to develop a standard set of methods to consistently characterize the sites, drainage basins, and groundwater study areas across the nation. This report describes three methods used for characterization-simple overlay, area-weighted areal interpolation, and land-cover-weighted areal interpolation-and their appropriate applications to geographic analyses that have different objectives and data constraints. In addition, this document records the GIS thematic datasets that are used for the Program's national design and data analyses.

Protein-protein docking with binding site patch prediction and network-based terms enhanced combinatorial scoring.

PubMed

Gong, Xinqi; Wang, Panwen; Yang, Feng; Chang, Shan; Liu, Bin; He, Hongqiu; Cao, Libin; Xu, Xianjin; Li, Chunhua; Chen, Weizu; Wang, Cunxin

2010-11-15

Protein-protein docking has made much progress in recent years, but challenges still exist. Here we present the application of our docking approach HoDock in CAPRI. In this approach, a binding site prediction is implemented to reduce docking sampling space and filter out unreasonable docked structures, and a network-based enhanced combinatorial scoring function HPNCscore is used to evaluate the decoys. The experimental information was combined with the predicted binding site to pick out the most likely key binding site residues. We applied the HoDock method in the recent rounds of the CAPRI experiments, and got good results as predictors on targets 39, 40, and 41. We also got good results as scorers on targets 35, 37, 40, and 41. This indicates that our docking approach can contribute to the progress of protein-protein docking methods and to the understanding of the mechanism of protein-protein interactions. © 2010 Wiley-Liss, Inc.

Highway runoff stormwater management potential (HRSMP) site characterization using NASA public domain imagery.

DOT National Transportation Integrated Search

2016-04-01

The focus of this research project was the development of geospatial technology (GST) methodology to : characterize and evaluate highway runoff stormwater management potential (HRSMP) sites in order to : reduce their impact on properties, save lives ...

Site characterization plan: Yucca Mountain Site, Nevada Research and Development Area, Nevada: Volume 8, Part B: Chapter 8, Sections 8.3.5 through 8.3.5.20

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

NONE

1988-12-01

This site characterization plan (SCP) has been developed for the candidate repository site at Yucca Mountain in the State of Nevada. The SCP includes a description of the Yucca Mountain site (Chapters 1-5), a conceptual design for the repository (Chapter 6), a description of the packaging to be used for the waste to be emplaced in the repository (Chapter 7), and a description of the planned site characterization activities (Chapter 8). The schedules and milestones presented in Sections 8.3 and 8.5 of the SCP were developed to be consistent with the June 1988 draft Amendment to the DOE`s Mission Planmore » for the Civilian Radioactive Waste Management Program. The five month delay in the scheduled start of exploratory shaft construction that was announced recently is not reflected in these schedules. 68 figs., 102 tabs.« less

State preemption of local smoke-free laws in government work sites, private work sites, and restaurants - United States, 2005-2009.

PubMed

2010-02-05

Smoke-free policies (i.e., policies that completely eliminate smoking in indoor workplaces and public places) result in health benefits, including preventing heart attacks. Preemptive legislation at the state level prohibits localities from enacting laws that vary from state law or are more stringent. A Healthy People 2010 objective (27-19) is to eliminate state laws that preempt stronger local tobacco control laws. A 2005 CDC review found that little progress was being made toward reducing the number of state laws preempting local smoking restrictions in three indoor settings: government work sites, private-sector work sites, and restaurants. These three settings were selected for analysis because they are settings that often are addressed by state and local smoking restrictions and because they are major settings where nonsmoking workers and patrons are exposed to secondhand smoke. This report updates the previous analysis and summarizes changes that occurred from December 31, 2004, to December 31, 2009, in state laws that preempt local smoke-free laws for the same three settings. During that period, the number of states preempting local smoking restrictions in at least one of these three settings decreased from 19 to 12. In contrast with the 2005 findings, this decrease indicates progress toward achieving the goal of eliminating state laws preempting local smoking restrictions. Further progress could result in additional reductions in secondhand smoke exposure.

VS30 – A site-characterization parameter for use in building Codes, simplified earthquake resistant design, GMPEs, and ShakeMaps

USGS Publications Warehouse

Borcherdt, Roger D.

2012-01-01

VS30, defined as the average seismic shear-wave velocity from the surface to a depth of 30 meters, has found wide-spread use as a parameter to characterize site response for simplified earthquake resistant design as implemented in building codes worldwide. VS30 , as initially introduced by the author for the US 1994 NEHRP Building Code, provides unambiguous definitions of site classes and site coefficients for site-dependent response spectra based on correlations derived from extensive borehole logging and comparative ground-motion measurement programs in California. Subsequent use of VS30 for development of strong ground motion prediction equations (GMPEs) and measurement of extensive sets of VS borehole data have confirmed the previous empirical correlations and established correlations of SVS30 with VSZ at other depths. These correlations provide closed form expressions to predict S30 V at a large number of additional sites and further justify S30 V as a parameter to characterize site response for simplified building codes, GMPEs, ShakeMap, and seismic hazard mapping.

Massive plexiform neurofibromas in childhood: natural history and management issues.

PubMed

Serletis, Demitre; Parkin, Patricia; Bouffet, Eric; Shroff, Manohar; Drake, James M; Rutka, James T

2007-05-01

The authors review their experience with massive plexiform neurofibromas (PNs) in patients with pediatric neurofibromatosis Type 1 (NF1) to better characterize the natural history and management of these complex lesions. The authors performed a retrospective review of data obtained in seven patients with NF1 in whom massive PNs were diagnosed at The Hospital for Sick Children in Toronto, Ontario, Canada. These patients attended routine follow-up examinations conducted by a number of specialists, and serial neuroimaging studies were obtained to monitor disease progression. The most common presenting feature of PN was that of a painful, expanding lesion. Furthermore, two patients harbored multiple, distinct PNs affecting different body sites. With respect to management, two patients were simply observed, undergoing serial neuroimaging studies; two patients underwent biopsy sampling of their plexiform lesions; two patients underwent attempted medical treatment (farnesyl transferase inhibitor, R11577, and cyclophosphamide chemotherapy); and three patients required surgical debulking of their PNs because the massive growth of these tumors caused functional compromise. Ultimately, one patient died of respiratory complications due to progressive growth of the massive PN lesion. In this review of their experience, the authors found certain features that underscore the presentation and natural history of PNs. The management of these complex lesions, however, remains unclear. Slow-growing PNs may be observed conservatively, but the authors' experience suggests that resection should be considered in selected cases involving significant deterioration or functional compromise. Nevertheless, patients with massive PNs will benefit from close surveillance by a team of specialists to monitor for ongoing disease progression.

Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy

PubMed Central

Böhm, Johann; Vasli, Nasim; Maurer, Marie; Cowling, Belinda; Shelton, G. Diane; Kress, Wolfram; Toussaint, Anne; Prokic, Ivana; Schara, Ulrike; Anderson, Thomas James; Weis, Joachim; Tiret, Laurent; Laporte, Jocelyn

2013-01-01

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies. PMID:23754947

Progress in the characterization of diamond thin films prepared by a laser plasma discharge

NASA Astrophysics Data System (ADS)

Davanloo, F.; Juengerman, E. M.; Jander, D. R.; Lee, T. J.; Collins, C. B.

Progress in the characterization of diamond thin films produced by a unique laser plasma discharge source at practical growth rates of 0.7 micron/hr is reported. Optical properties, mass densities, and electrical resistivities of deposited films are given and their relationship to the power density of the laser at the graphite target is discussed. Examination of films with scanning tunneling microscopy show the clear prevalence of the structure recently predicted by Angus et al. (1990) in which sp3 clusters are bonded together with the carbon polytypes.

A far-infrared spatial/spectral Fourier interferometry laboratory-based testbed instrument

NASA Astrophysics Data System (ADS)

Spencer, Locke D.; Naylor, David A.; Scott, Jeremy P.; Weiler, Vince F.; MacCrimmon, Roderick K.; Sitwell, Geoffrey R. H.; Ade, Peter A. R.

2016-07-01

We describe the current status, including preliminary design, characterization efforts, and recent progress, in the development of a spatial/spectral double Fourier laboratory-based interferometer testbed instrument within the Astronomical Instrumentation Group (AIG) laboratories at the University of Lethbridge, Canada (UL). Supported by CRC, CFI, and NSERC grants, this instrument development will provide laboratory demonstration of spatial-spectral interferometry with a concentration of furthering progress in areas including the development of spatial/spectral interferometry observation, data processing, characterization, and analysis techniques in the Far-Infrared (FIR) region of the electromagnetic spectrum.

An alternative approach to characterize nonlinear site effects

USGS Publications Warehouse

Zhang, R.R.; Hartzell, S.; Liang, J.; Hu, Y.

2005-01-01

This paper examines the rationale of a method of nonstationary processing and analysis, referred to as the Hilbert-Huang transform (HHT), for its application to a recording-based approach in quantifying influences of soil nonlinearity in site response. In particular, this paper first summarizes symptoms of soil nonlinearity shown in earthquake recordings, reviews the Fourier-based approach to characterizing nonlinearity, and offers justifications for the HHT in addressing nonlinearity issues. This study then uses the HHT method to analyze synthetic data and recordings from the 1964 Niigata and 2001 Nisqually earthquakes. In doing so, the HHT-based site response is defined as the ratio of marginal Hilbert amplitude spectra, alternative to the Fourier-based response that is the ratio of Fourier amplitude spectra. With the Fourier-based approach in studies of site response as a reference, this study shows that the alternative HHT-based approach is effective in characterizing soil nonlinearity and nonlinear site response.

Statistical Profiling of One Promiscuous Protein Binding Site: Illustrated by Urokinase Catalytic Domain.

PubMed

Cerisier, Natacha; Regad, Leslie; Triki, Dhoha; Petitjean, Michel; Flatters, Delphine; Camproux, Anne-Claude

2017-10-01

While recent literature focuses on drug promiscuity, the characterization of promiscuous binding sites (ability to bind several ligands) remains to be explored. Here, we present a proteochemometric modeling approach to analyze diverse ligands and corresponding multiple binding sub-pockets associated with one promiscuous binding site to characterize protein-ligand recognition. We analyze both geometrical and physicochemical profile correspondences. This approach was applied to examine the well-studied druggable urokinase catalytic domain inhibitor binding site, which results in a large number of complex structures bound to various ligands. This approach emphasizes the importance of jointly characterizing pocket and ligand spaces to explore the impact of ligand diversity on sub-pocket properties and to establish their main profile correspondences. This work supports an interest in mining available 3D holo structures associated with a promiscuous binding site to explore its main protein-ligand recognition tendency. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimal management of ALK-positive NSCLC progressing on crizotinib.

PubMed

Metro, Giulio; Tazza, Marco; Matocci, Roberta; Chiari, Rita; Crinò, Lucio

2017-04-01

Crizotinib is an anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (-TKI) that represents the standard first-line treatment of patients with ALK-rearranged (ALK-positive) advanced non-small cell lung cancer (NSCLC). In this setting, crizotinib has demonstrated a response rate of roughly 75% and a median progression-free survival just under one year. However, acquired resistance will emerge in virtually all crizotinib-treated patients, whose management may require a diversified approach according to the pace of the disease and/or the site(s) of disease progression. Crizotinib beyond disease progression is an option in patients with oligoprogressive disease, especially in presence of isolated central nervous system (CNS) relapse, provided that local ablative therapy (mainly radiotherapy) to the brain is administered. On the other hand, novel more potent and highly selective ALK-TKIs with demonstrated anti-tumor activity (CNS included) in crizotinib-refractory patients have been made available in recent years. Therefore, clinicians may well consider switching to a second-generation ALK-TKI as treatment option in case of progression on crizotinib. Therapeutic chances are more limited for patients who progress after crizotinib and a second-generation ALK-TKI, for whom both a third-generation ALK-TKI or pemetrexed-based chemotherapy could prove beneficial, while evidence in support of the use of immunotherapy in patients pretreated with ≥1 ALK-TKI is lacking. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of mitosis-specific phosphorylation of tumor-associated microtubule-associated protein

PubMed Central

Hong, Kyung Uk; Kim, Hyun-Jun

2009-01-01

Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2), has been recently shown to be involved in the assembly and maintenance of mitotic spindle and also plays an essential role in maintaining the fidelity of chromosome segregation during mitosis. We have previously reported that TMAP is phosphorylated at multiple residues specifically during mitosis, and characterized the mechanism and functional importance of phosphorylation at one of the mitosis-specific phosphorylation residues (i.e., Thr-622). However, the phosphorylation events at the remaining mitotic phosphorylation sites of TMAP have not been fully characterized in detail. Here, we report on generation and characterization of phosphorylated Thr-578- and phosphorylated Thr-596-specific antibodies. Using the antibodies, we show that phosphorylation of TMAP at Thr-578 and Thr-596 indeed occurs specifically during mitosis. Immunofluorescent staining using the antibodies shows that these residues become phosphorylated starting at prophase and then become rapidly dephosphorylated soon after initiation of anaphase. Subtle differences in the kinetics of phosphorylation between Thr-578 and Thr-596 imply that they may be under different mechanisms of phosphorylation during mitosis. Unlike the phosphorylation-deficient mutant form for Thr-622, the mutant in which both Thr-578 and Thr-596 had been mutated to alanines did not induce significant delay in progression of mitosis. These results show that the majority of mitosis-specific phosphorylation of TMAP is limited to pre-anaphase stages and suggest that the multiple phosphorylation may not act in concert but serve diverse functions. PMID:19641375

Foraging habitat quality constrains effectiveness of artificial nest-site provisioning in reversing population declines in a colonial cavity nester.

PubMed

Catry, Inês; Franco, Aldina M A; Rocha, Pedro; Alcazar, Rita; Reis, Susana; Cordeiro, Ana; Ventim, Rita; Teodósio, Joaquim; Moreira, Francisco

2013-01-01

Among birds, breeding numbers are mainly limited by two resources of major importance: food supply and nest-site availability. Here, we investigated how differences in land-use and nest-site availability affected the foraging behaviour, breeding success and population trends of the colonial cavity-dependent lesser kestrel Falco naumanni inhabiting two protected areas. Both areas were provided with artificial nests to increase nest-site availability. The first area is a pseudo-steppe characterized by traditional extensive cereal cultivation, whereas the second area is a previous agricultural zone now abandoned or replaced by forested areas. In both areas, lesser kestrels selected extensive agricultural habitats, such as fallows and cereal fields, and avoided scrubland and forests. In the second area, tracked birds from one colony travelled significantly farther distances (6.2 km ± 1.7 vs. 1.8 km ± 0.4 and 1.9 km ± 0.6) and had significant larger foraging-ranges (144 km(2) vs. 18.8 and 14.8 km(2)) when compared to the birds of two colonies in the extensive agricultural area. Longer foraging trips were reflected in lower chick feeding rates, lower fledging success and reduced chick fitness. Availability and occupation of artificial nests was high in both areas but population followed opposite trends, with a positive increment recorded exclusively in the first area with a large proportion of agricultural areas. Progressive habitat loss around the studied colony in the second area (suitable habitat decreased from 32% in 1990 to only 7% in 2002) is likely the main driver of the recorded population decline and suggests that the effectiveness of bird species conservation based on nest-site provisioning is highly constrained by habitat quality in the surrounding areas. Therefore, the conservation of cavity-dependent species may be enhanced firstly by finding the best areas of remaining habitat and secondly by increasing the carrying capacity of high-quality habitat areas through safe nest-site provisioning.

Foraging Habitat Quality Constrains Effectiveness of Artificial Nest-Site Provisioning in Reversing Population Declines in a Colonial Cavity Nester

PubMed Central

Catry, Inês; Franco, Aldina M. A.; Rocha, Pedro; Alcazar, Rita; Reis, Susana; Cordeiro, Ana; Ventim, Rita; Teodósio, Joaquim; Moreira, Francisco

2013-01-01

Among birds, breeding numbers are mainly limited by two resources of major importance: food supply and nest-site availability. Here, we investigated how differences in land-use and nest-site availability affected the foraging behaviour, breeding success and population trends of the colonial cavity-dependent lesser kestrel Falco naumanni inhabiting two protected areas. Both areas were provided with artificial nests to increase nest-site availability. The first area is a pseudo-steppe characterized by traditional extensive cereal cultivation, whereas the second area is a previous agricultural zone now abandoned or replaced by forested areas. In both areas, lesser kestrels selected extensive agricultural habitats, such as fallows and cereal fields, and avoided scrubland and forests. In the second area, tracked birds from one colony travelled significantly farther distances (6.2 km ±1.7 vs. 1.8 km ±0.4 and 1.9 km ±0.6) and had significant larger foraging-ranges (144 km2 vs. 18.8 and 14.8 km2) when compared to the birds of two colonies in the extensive agricultural area. Longer foraging trips were reflected in lower chick feeding rates, lower fledging success and reduced chick fitness. Availability and occupation of artificial nests was high in both areas but population followed opposite trends, with a positive increment recorded exclusively in the first area with a large proportion of agricultural areas. Progressive habitat loss around the studied colony in the second area (suitable habitat decreased from 32% in 1990 to only 7% in 2002) is likely the main driver of the recorded population decline and suggests that the effectiveness of bird species conservation based on nest-site provisioning is highly constrained by habitat quality in the surrounding areas. Therefore, the conservation of cavity-dependent species may be enhanced firstly by finding the best areas of remaining habitat and secondly by increasing the carrying capacity of high-quality habitat areas through safe nest-site provisioning. PMID:23484016

ACHP | The Protection of Indian Sacred Sites

Science.gov Websites

signatories issued an action plan for implementation of the MOU and in March 2014, issued a progress report , Action Plan, Progress Report, and other information may be accessed by clicking the links below: 2016 Action Plan ACHP News Announcement Department of the Interior Press Release DOI/Forest Service Updates

Thermodynamic analysis of water molecules at the surface of proteins and applications to binding site prediction and characterization.

PubMed

Beuming, Thijs; Che, Ye; Abel, Robert; Kim, Byungchan; Shanmugasundaram, Veerabahu; Sherman, Woody

2012-03-01

Water plays an essential role in determining the structure and function of all biological systems. Recent methodological advances allow for an accurate and efficient estimation of the thermodynamic properties of water molecules at the surface of proteins. In this work, we characterize these thermodynamic properties and relate them to various structural and functional characteristics of the protein. We find that high-energy hydration sites often exist near protein motifs typically characterized as hydrophilic, such as backbone amide groups. We also find that waters around alpha helices and beta sheets tend to be less stable than waters around loops. Furthermore, we find no significant correlation between the hydration site-free energy and the solvent accessible surface area of the site. In addition, we find that the distribution of high-energy hydration sites on the protein surface can be used to identify the location of binding sites and that binding sites of druggable targets tend to have a greater density of thermodynamically unstable hydration sites. Using this information, we characterize the FKBP12 protein and show good agreement between fragment screening hit rates from NMR spectroscopy and hydration site energetics. Finally, we show that water molecules observed in crystal structures are less stable on average than bulk water as a consequence of the high degree of spatial localization, thereby resulting in a significant loss in entropy. These findings should help to better understand the characteristics of waters at the surface of proteins and are expected to lead to insights that can guide structure-based drug design efforts. Copyright © 2011 Wiley Periodicals, Inc.

Radiation Therapy to the Primary and Postinduction Chemotherapy MIBG-Avid Sites in High-Risk Neuroblastoma

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

Mazloom, Ali; Louis, Chrystal U.; Nuchtern, Jed

2014-11-15

Purpose: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Methods and Materials: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dosemore » chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. Results: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). Conclusions: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.« less

Progressive CD4+ central–memory T cell decline results in CD4+ effector–memory insufficiency and overt disease in chronic SIV infection

PubMed Central

Okoye, Afam; Meier-Schellersheim, Martin; Brenchley, Jason M.; Hagen, Shoko I.; Walker, Joshua M.; Rohankhedkar, Mukta; Lum, Richard; Edgar, John B.; Planer, Shannon L.; Legasse, Alfred; Sylwester, Andrew W.; Piatak, Michael; Lifson, Jeffrey D.; Maino, Vernon C.; Sodora, Donald L.; Douek, Daniel C.; Axthelm, Michael K.; Grossman, Zvi; Picker, Louis J.

2007-01-01

Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4+ CCR5+ effector–memory T (TEM) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4+ memory T cell proliferation appears to prevent collapse of effector site CD4+ TEM cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4+ TEM cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4+ TEM cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4+ TEM cells from central–memory T (TCM) cell precursors. The instability of effector site CD4+ TEM cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5− CD4+ TCM cells. These data suggest that although CD4+ TEM cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4+ TCM cells. PMID:17724130

Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection.

PubMed

Okoye, Afam; Meier-Schellersheim, Martin; Brenchley, Jason M; Hagen, Shoko I; Walker, Joshua M; Rohankhedkar, Mukta; Lum, Richard; Edgar, John B; Planer, Shannon L; Legasse, Alfred; Sylwester, Andrew W; Piatak, Michael; Lifson, Jeffrey D; Maino, Vernon C; Sodora, Donald L; Douek, Daniel C; Axthelm, Michael K; Grossman, Zvi; Picker, Louis J

2007-09-03

Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4(+) CCR5(+) effector-memory T (T(EM)) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4(+) memory T cell proliferation appears to prevent collapse of effector site CD4(+) T(EM) cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4(+) T(EM) cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4(+) T(EM) cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4(+) T(EM) cells from central-memory T (T(CM)) cell precursors. The instability of effector site CD4(+) T(EM) cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5(-) CD4(+) T(CM) cells. These data suggest that although CD4(+) T(EM) cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4(+) T(CM) cells.

An overview of geophysical technologies appropriate for characterization and monitoring at fractured-rock sites

EPA Science Inventory

Geophysical methods are used increasingly for characterization and monitoring at remediation sites in fractured-rock aquifers. The complex heterogeneity of fractured rock poses enormous challenges to groundwater remediation professionals, and new methods are needed to cost-effect...

Characterization of naïve, memory and effector T cells in progressive multiple sclerosis.

PubMed

Nielsen, Birgitte Romme; Ratzer, Rikke; Börnsen, Lars; von Essen, Marina Rode; Christensen, Jeppe Romme; Sellebjerg, Finn

2017-09-15

We characterized naïve, central memory (CM), effector memory (EM) and terminally differentiated effector memory (TEMRA) CD4 + and CD8 + T cells and their expression of CD49d and CD26 in peripheral blood in patients with multiple sclerosis (MS) and healthy controls. CD26 + CD28 + CD4 + TEMRA T cells were increased in all subtypes of MS, and CD26 + CD28 + CD8 + TEMRA T cells were increased in relapsing-remitting and secondary progressive MS. Conversely, in progressive MS, CD49d + CM T cells were decreased and natalizumab increased the circulating number of all six subsets but reduced the frequency of most subsets expressing CD49d and CD26. Copyright © 2017 Elsevier B.V. All rights reserved.

Reading, Language Arts & Literacy. [SITE 2001 Section].

ERIC Educational Resources Information Center

Matthew, Kathy, Ed.

This document contains the following papers on reading, language arts, and literacy from the SITE (Society for Information Technology & Teacher Education) 2001 conference: (1) "Improving the Teaching of Reading, Language Arts and Literacy through WebCT: A Work in Progress" (Linda Akanbi); (2) "A Survey of Computer Software…

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

NaK-ATPase pump sites in cultured bovine corneal endothelium of varying cell density at confluence.

PubMed

Crawford, K M; Ernst, S A; Meyer, R F; MacCallum, D K

1995-06-01

The driving force for ion and water flow necessary for efficient deturgesence of the corneal stroma resides in the ouabain-sensitive sodium (Na) pump of corneal endothelial cells. Using a cell culture model of corneal endothelial cell hypertrophy, the authors examined the expression of Na pumps at the cell surface to see how this central element of the endothelial pump changed as corneal endothelial cell density decreased to a level associated with corneal decompensation in vivo. 3H-ouabain binding to NaK-ATPase at saturating conditions was used to quantitate the number of Na pump sites on cultured bovine corneal endothelial cells as the confluent density decreased from approximately 2750 cells/mm2 to approximately 275 cells/mm2. The mean number of Na pump sites per cell at confluence (1.92 +/- 0.07 x 10(6)) did not change as the cell density decreased 2.7-fold from 2763 cells/mm2 to 1000 cells/mm2. However, pump site expression doubled to approximately 4 x 10(6) sites/cell as the cell density decreased from 1000 cells/mm2 to 275 cells/mm2. Despite the incremental increase in Na pump site expression that occurred as the cells hypertrophied below a density of 1000/mm2 to achieve confluence, this increase was insufficient to prevent a decrease in Na pump site density of the intact monolayer, expressed as pump sites/mm2. The confluent cell density of cultured bovine corneal endothelial cells can be varied from that found in the normal native cornea to that associated with corneal decompensation. In confluent cultures with cell densities ranging from 2750 cells/mm2 to 1000 cells/mm2, the number of pump sites per cell remains relatively unchanged. Below cell densities of 1000 cells/mm2, the number of pump sites per cell progressively increases. The increased Na pump site abundance in markedly hypertrophied endothelial cells cannot adequately compensate for the progressive reduction in the number of transporting cells per unit area within the intact monolayer. Even when considered with the decrease in the size of the paracellular ion conductive pathway that is a consequence of progressive endothelial hypertrophy, the overall pumping capacity of the intact endothelial monolayer declines.

Technical Analysis and Characterization of Southern Cayo, Belize for Tropical Testing and Evaluation of Foliage Penetration Remote Sensing Systems

DTIC Science & Technology

2011-05-01

Characterization of Test Sites 57 Appendix 4 – Interactive Maps and Images...issued by the tropical test study panel, reporting the results of work conducted at 24 sites. The evolution of tropical testing to the suite of sites...macrophylla, Terminalia amazonia, Virola brachycarpa, and the palm Astrocaryum mexicanum. The mangrove and littoral forest are ecologically important to the

Developing Carbon Nanotube Standards at NASA

NASA Technical Reports Server (NTRS)

Nikolaev, Pasha; Arepalli, Sivaram; Sosa, Edward; Gorelik, Olga; Yowell, Leonard

2007-01-01

Single wall carbon nanotubes (SWCNTs) are currently being produced and processed by several methods. Many researchers are continuously modifying existing methods and developing new methods to incorporate carbon nanotubes into other materials and utilize the phenomenal properties of SWCNTs. These applications require availability of SWCNTs with known properties and there is a need to characterize these materials in a consistent manner. In order to monitor such progress, it is critical to establish a means by which to define the quality of SWCNT material and develop characterization standards to evaluate of nanotube quality across the board. Such characterization standards should be applicable to as-produced materials as well as processed SWCNT materials. In order to address this issue, NASA Johnson Space Center has developed a protocol for purity and dispersion characterization of SWCNTs (Ref.1). The NASA JSC group is currently working with NIST, ANSI and ISO to establish purity and dispersion standards for SWCNT material. A practice guide for nanotube characterization is being developed in cooperation with NIST (Ref.2). Furthermore, work is in progress to incorporate additional characterization methods for electrical, mechanical, thermal, optical and other properties of SWCNTs.

Developing Carbon Nanotube Standards at NASA

NASA Technical Reports Server (NTRS)

Nikolaev, Pasha; Arepalli, Sivaram; Sosa, Edward; Gorelik, Olga; Yowell, Leonard

2007-01-01

Single wall carbon nanotubes (SWCNTs) are currently being produced and processed by several methods. Many researchers are continuously modifying existing methods and developing new methods to incorporate carbon nanotubes into other materials and utilize the phenomenal properties of SWCNTs. These applications require availability of SWCNTs with known properties and there is a need to characterize these materials in a consistent manner. In order to monitor such progress, it is critical to establish a means by which to define the quality of SWCNT material and develop characterization standards to evaluate of nanotube quality across the board. Such characterization standards should be applicable to as-produced materials as well as processed SWCNT materials. In order to address this issue, NASA Johnson Space Center has developed a protocol for purity and dispersion characterization of SWCNTs. The NASA JSC group is currently working with NIST, ANSI and ISO to establish purity and dispersion standards for SWCNT material. A practice guide for nanotube characterization is being developed in cooperation with NIST. Furthermore, work is in progress to incorporate additional characterization methods for electrical, mechanical, thermal, optical and other properties of SWCNTs.

Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

PubMed

Akram, Afia Muhammad; Iqbal, Zafar; Akhtar, Tanveer; Khalid, Ahmed Mukhtar; Sabar, Muhammad Farooq; Qazi, Mahmood Hussain; Aziz, Zeba; Sajid, Nadia; Aleem, Aamer; Rasool, Mahmood; Asif, Muhammad; Aloraibi, Saleh; Aljamaan, Khaled; Iqbal, Mudassar

2017-04-03

BCR-ABL kinase domain (K D ) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-K D mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-K D . Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-K D mutation screening in late chronic phase CML patients for improved clinical management of disease.

Initial Geochemistry Data of the Lake Ohrid (Macedonia, Albania) DEEP -Site Sediment Record: The ICDP Scopsco Drilling Project

NASA Astrophysics Data System (ADS)

Francke, A.; Wagner, B.; Sulpizio, R.; Zanchetta, G.; Leicher, N.; Gromig, R.; Krastel, S.; Lindhorst, K.; Wilke, T.

2014-12-01

Ancient lakes, with sediment records spanning >1 million years, are very rare. The UNESCO World Heritage site of Lake Ohrid on the Balkans is thought to be the oldest lake in Europe. With 212 endemic species described to date, it is also a hotspot of evolution. In order to unravel the geological and evolutionary history of the lake, an international group of scientists, conducted a deep drilling campaign in spring 2013 under the umbrella of the ICDP SCOPSCO project (Scientific Collaboration on Past Speciation Conditions in Lake Ohrid). Overall, about 2,100 m of sediments were recovered from four drill sites. At the main drill site (DEEP-site) in central parts of the lake where seismic data indicated a maximum sediment fill of ca. 700 m, a total of more than 1,500 m of sediments were recovered until a penetration depth of 569 m. Currently, core opening, core description, XRF and MSCL scanning, sub-sampling (16 cm resolution), and inorganic and organic geochemical as well as sedimentological analyses of the sediment cores from the DEEP site are in progress at the University of Cologne. Previous studies at Lake Ohrid have shown that interglacial periods are characterized by high TIC and TOC contents, likely associated with high contents of calcite and organic matter in the sediments. In contrast, during glacial periods negligible TIC and low TOC contents correspond to high K counts indicating enhanced supply of clastic material. Similar patterns can be observed in the biogeochemical analyses of the subsamples and in the XRF data of the DEEP site record. Following these variations on a glacial-interglacial time scale, TIC and TOC data obtained from the subsamples and from core catcher samples indicate that the DEEP site sequence provides a 1.2 million year old continuous record of environmental and climatological variability in the Balkan Region. The age control can be further improved by first findings of macroscopic tephra horizons. Peaks in K, Sr, Zr, and magnetic susceptibility might indicate the occurrence of additional cryptotephra layers in the sediment sequence.

A Further Characterization of Empirical Research Related to Learning Outcome Achievement in Remote and Virtual Science Labs

NASA Astrophysics Data System (ADS)

Brinson, James R.

2017-10-01

This paper further characterizes recently reviewed literature related to student learning outcome achievement in non-traditional (virtual and remote) versus traditional (hands-on) science labs, as well as factors to consider when evaluating the state and progress of research in this field as a whole. Current research is characterized according to (1) participant nationality and culture, (2) participant education level, (3) participant demography, (4) scientific discipline, and (5) research methodology, which could provide avenues for further research and useful dialog regarding the measurement and interpretation of data related to student learning outcome achievement in, and thus the efficacy of, non-traditional versus traditional science labs. Current research is also characterized by (6) research publication media and (7) availability of non-traditional labs used, which demonstrate some of the obstacles to progress and consensus in this research field.

Remote Sensor Application Studies Progress Report, July L, 1968 to June 30, 1969. Controlled Field Experiments

USGS Publications Warehouse

Rowan, L.C.; Offield, T.W.; Watson, R.D.; Cannon, P.J.; Grolier, H.J.; Pohn, H.A.; Watson, Kenneth

1970-01-01

Field Sites have been selected for controlled experiments to analyze physical and chemical parameters affecting the response of electromagnetic radiation to geological materials. Considerations in the selection of the sites are the availability of good exposures of nearly monomineralic rocks, level of geologic understanding, and ease of access. Seven sites, where work is underway or planned, contain extensive outcrops of the following rocks: stanstone, limestone, dolomite, and gypsum. Field measurement of quartz have been conducted at four sites.

Site Characterization To Support Use Of Monitored Natural Attentuation For Remediation Of Inorganic Contaminants In Groundwater

EPA Science Inventory

Technical recommendations have recently been published by the U.S. Environmental Protection Agency to address site characterization needed to support selection of Monitored Natural Attenuation (MNA) for cleanup of inorganic contaminant plumes in groundwater. Immobilization onto ...

Integrated Pore-Water and Geophysical Investigations StreamlineCharacterization of Ground-Water Discharges to Surface Water

EPA Science Inventory

This issue of Technology News and Trends highlights strategies and tools for characterizing or monitoring remediation of sites with contaminated sediment. Addressing these sites often relies upon dynamic workplans that involve more efficient, cost-effective, and practical methods...

10 CFR 60.17 - Contents of site characterization plan.

Code of Federal Regulations, 2010 CFR

2010-01-01

... GEOLOGIC REPOSITORIES Licenses Preapplication Review § 60.17 Contents of site characterization plan. The... construction authorization for a geologic repository operations area; (4) Criteria, developed pursuant to... area for the location of a geologic repository; and (5) Any other information which the Commission, by...

A CASE STUDY ILLUSTRATING THE IMPORTANCE OF ACCURATE SITE CHARACTERIZATION

EPA Science Inventory

Too frequently, researchers rely on incomplete site characterization data to determine the placement of the sampling wells. They forget that it is these sampling wells that will be used to evaluate the effectiveness of their research efforts. This case study illustrates the eff...

ARM Research in the Equatorial Western Pacific: A Decade and Counting

NASA Technical Reports Server (NTRS)

Long, C. N.; McFarlane, S. A.; DelGenio, A.; Minnis, P.; Ackerman, T. S.; Mather, J.; Comstock, J.; Mace, G. G.; Jensen, M.; Jakob, C.

2013-01-01

The tropical western Pacific (TWP) is an important climatic region. Strong solar heating, warm sea surface temperatures, and the annual progression of the intertropical convergence zone (ITCZ) across this region generate abundant convective systems, which through their effects on the heat and water budgets have a profound impact on global climate and precipitation. In order to accurately evaluate tropical cloud systems in models, measurements of tropical clouds, the environment in which they reside, and their impact on the radiation and water budgets are needed. Because of the remote location, ground-based datasets of cloud, atmosphere, and radiation properties from the TWP region have come primarily from short-term field experiments. While providing extremely useful information on physical processes, these short-term datasets are limited in statistical and climatological information. To provide longterm measurements of the surface radiation budget in the tropics and the atmospheric properties that affect it, the Atmospheric Radiation Measurement program established a measurement site on Manus Island, Papua New Guinea, in 1996 and on the island republic of Nauru in late 1998. These sites provide unique datasets now available for more than 10 years on Manus and Nauru. This article presents examples of the scientific use of these datasets including characterization of cloud properties, analysis of cloud radiative forcing, model studies of tropical clouds and processes, and validation of satellite algorithms. New instrumentation recently installed at the Manus site will provide expanded opportunities for tropical atmospheric science.

In Silico Detection of Sequence Variations Modifying Transcriptional Regulation

PubMed Central

Andersen, Malin C; Engström, Pär G; Lithwick, Stuart; Arenillas, David; Eriksson, Per; Lenhard, Boris; Wasserman, Wyeth W; Odeberg, Jacob

2008-01-01

Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN (regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation. PMID:18208319

Yucca Mountain biological resources monitoring program; Annual report FY92

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

NONE

1993-02-01

The US Department of Energy (DOE) is required by the Nuclear Waste Policy Act of 1982 (as amended in 1987) to study and characterize Yucca Mountain as a potential site for a geologic repository for high-level nuclear waste. During site characterization, the DOE will conduct a variety of geotechnical, geochemical, geological, and hydrological studies to determine the suitability of Yucca Mountain as a potential repository. To ensure that site characterization activities (SCA) do not adversely affect the environment at Yucca Mountain, an environmental program has been implemented to monitor and mitigate potential impacts and ensure activities comply with applicable environmentalmore » regulations. This report describes the activities and accomplishments of EG&G Energy Measurements, Inc. (EG&G/EM) during fiscal year 1992 (FY92) for six program areas within the Terrestrial Ecosystem component of the YMP environmental program. The six program areas are Site Characterization Effects, Desert Tortoises, Habitat Reclamation, Monitoring and Mitigation, Radiological Monitoring, and Biological Support.« less

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

R. L. VanHorn; N. L. Hampton; R. C. Morris

This document presents reference material for conducting screening level ecological risk assessments (SLERAs)for the waste area groups (WAGs) at the Idaho National Engineering Laboratory. Included in this document are discussions of the objectives of and processes for conducting SLERAs. The Environmental Protection Agency ecological risk assessment framework is closely followed. Guidance for site characterization, stressor characterization, ecological effects, pathways of contaminant migration, the conceptual site model, assessment endpoints, measurement endpoints, analysis guidance, and risk characterization are included.

Integrated Remote Sensing Modalities for Classification at a Legacy Test Site

NASA Astrophysics Data System (ADS)

Lee, D. J.; Anderson, D.; Craven, J.

2016-12-01

Detecting, locating, and characterizing suspected underground nuclear test sites is of interest to the worldwide nonproliferation monitoring community. Remote sensing provides both cultural and surface geological information over a large search area in a non-intrusive manner. We have characterized a legacy nuclear test site at the Nevada National Security Site (NNSS) using an aerial system based on RGB imagery, light detection and ranging, and hyperspectral imaging. We integrate these different remote sensing modalities to perform pattern recognition and classification tasks on the test site. These tasks include detecting cultural artifacts and exotic materials. We evaluate if the integration of different remote sensing modalities improves classification performance.

Site Environmental Report for 2015

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

Pauer, Ron O.; Baskin, David A.; Borglin, Ned K.

The annual Site Environmental Report documents Lawrence Berkeley National Laboratory’s performance in reducing its environmental impacts, progress toward cleaning up groundwater contamination, and compliance with applicable Department of Energy, federal, state, and local environmental regulations. The report is required by DOE Order 231.1B, Environment, Safety, and Health Reporting.

Report: Progress Made, but Improvements Needed at CTS of Asheville Superfund Site in North Carolina to Advance Cleanup Pace and Reduce Potential Exposure

EPA Pesticide Factsheets

Report #16-P-0296, August 31, 2016. EPA Region 4 can accelerate the cleanup and completeness of work, and improve public communications, to better control human exposure to unsafe industrial contamination at the CTS site.

The Eggen Card Project

NASA Astrophysics Data System (ADS)

Silvis, G.

2014-06-01

(Abstract only) Olin Eggen, noted astronomer (1919-1998), left to us all his raw observation records recorded on 3x5 cards. This project is to make all this data available as an online resource. History and progress of the project will be presented. Project details available at: https://sites.google.com/site/eggencards/home.

Telecommunications: Systems and Services. [SITE 2002 Section].

ERIC Educational Resources Information Center

Abramson, Gertrude, Ed.

This document contains the following papers on telecommunications systems and services from the SITE (Society for Information Technology & Teacher Education) 2002 conference: (1) "Using the Web To Provide Parent Progress Reports on Standards for All Students: Developing the System" (Kevin M. Anderson and Cindy L. Anderson); (2) "Computer and…

Progression marker of Parkinson's disease: a 4-year multi-site imaging study.

PubMed

Burciu, Roxana G; Ofori, Edward; Archer, Derek B; Wu, Samuel S; Pasternak, Ofer; McFarland, Nikolaus R; Okun, Michael S; Vaillancourt, David E

2017-08-01

Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year decrease in striatal binding ratio in the putamen. Importantly, all longitudinal results were consistent across sites. In summary, this study demonstrates an increase over 1 year in free water in the posterior substantia nigra in a large cohort of de novo patients with Parkinson's disease from a multi-site cohort study and no change in healthy controls, and further demonstrates an increase of free water in Parkinson's disease over the course of 4 years. A key finding was that results are consistent across sites and the 1-year and 2-year increase in free water in the posterior substantia nigra predicts subsequent long-term progression on the Hoehn and Yahr staging system. Collectively, these findings demonstrate that free water in the posterior substantia nigra is a valid, progression imaging marker of Parkinson's disease, which may be used in clinical trials of disease-modifying therapies. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Clinical risk factors associated with incidence and progression of periodontal conditions in pregnant women.

PubMed

Moss, Kevin L; Beck, James D; Offenbacher, Steven

2005-05-01

Few large studies have investigated the progression of periodontal conditions during pregnancy in a comprehensive manner. This study aimed to identify clinical factors that were predictive of incidence/progression of periodontal measures in pregnant women adjusting for relevant predictors. Periodontal examinations were conducted on 891 pregnant women prior to 26 weeks gestational age and within 48 h after delivery. Gingivitis/periodontitis incidence/progression (GPIP) was defined as four plus sites with 2+ mm increase in probing depth (PD) that resulted in PD of at least 4 mm at delivery. Multivariable models including relevant clinical variables and significant covariates were developed. While several clinical measures were significantly associated with the outcome, having >/=10% of sites with bleeding on probing (BOP) and four plus sites with PD >/=4 mm (PD4) were the best two predictors of GPIP (odds ratio (OR)=2.8, 95% confidence interval (CI)=1.8-4.2; OR=2.0, 95% CI=1.4-2.9, respectively), adjusting for maternal race, age, enrollment weight, smoking during pregnancy, marital status, food stamp eligibility, and private health insurance. Multivariable models assessed the impact of BOP on the PD4-GPIP relationship. PD4 was significant in the presence of BOP (low BOP OR=1.3, 95% CI=0.5-3.3; high BOP OR=3.0, 95% CI=2.2-4.3). Enrollment BOP and PD4 were significant predictors of PD in pregnant women, however; PD4 is only a predictor with BOP.

Identification of a novel K311 ubiquitination site critical for androgen receptor transcriptional activity

PubMed Central

Cork, David M.W.; Darby, Steven; Ryan-Munden, Claudia A.; Nakjang, Sirintra; Mendes Côrtes, Leticia; Treumann, Achim; Gaughan, Luke

2017-01-01

Abstract The androgen receptor (AR) is the main driver of prostate cancer (PC) development and progression, and the primary therapeutic target in PC. To date, two functional ubiquitination sites have been identified on AR, both located in its C-terminal ligand binding domain (LBD). Recent reports highlight the emergence of AR splice variants lacking the LBD that can arise during disease progression and contribute to castrate resistance. Here, we report a novel N-terminal ubiquitination site at lysine 311. Ubiquitination of this site plays a role in AR stability and is critical for its transcriptional activity. Inactivation of this site causes AR to accumulate on chromatin and inactivates its transcriptional function as a consequence of inability to bind to p300. Additionally, mutation at lysine 311 affects cellular transcriptome altering the expression of genes involved in chromatin organization, signaling, adhesion, motility, development and metabolism. Even though this site is present in clinically relevant AR-variants it can only be ubiquitinated in cells when AR retains LBD suggesting a role for AR C-terminus in E2/E3 substrate recognition. We report that as a consequence AR variants lacking the LBD cannot be ubiquitinated in the cellular environment and their protein turnover must be regulated via an alternate pathway. PMID:27903893

Functional diversification of the dehydrin gene family in apple and its contribution to cold acclimation during dormancy.

PubMed

Falavigna, Vítor da Silveira; Miotto, Yohanna Evelyn; Porto, Diogo Denardi; Anzanello, Rafael; Santos, Henrique Pessoa dos; Fialho, Flávio Bello; Margis-Pinheiro, Márcia; Pasquali, Giancarlo; Revers, Luís Fernando

2015-11-01

Dehydrins (DHN) are proteins involved in plant adaptive responses to abiotic stresses, mainly dehydration. Several studies in perennial crops have linked bud dormancy progression, a process characterized by the inability to initiate growth from meristems under favorable conditions, with DHN gene expression. However, an in-depth characterization of DHNs during bud dormancy progression is still missing. An extensive in silico characterization of the apple DHN gene family was performed. Additionally, we used five different experiments that generated samples with different dormancy status, including genotypes with contrasting dormancy traits, to analyze how DHN genes are being regulated during bud dormancy progression in apple by real-time quantitative polymerase chain reaction (RT-qPCR). Duplication events took place in the diversification of apple DHN family. Additionally, MdDHN genes presented tissue- and bud dormant-specific expression patterns. Our results indicate that MdDHN genes are highly divergent in function, with overlapping levels, and that their expressions are fine-tuned by the environment during the dormancy process in apple. © 2015 Scandinavian Plant Physiology Society.

THE RAPID OPTICAL TOOL (TM) LASER-INDUCED FLUORESCENCE SYSTEM FOR SCREENING OF PETROLEUM HYDROCARBONS IN SUBSURFACE SOILS

EPA Science Inventory

The Consortium for Site Characterization Technology (CSCT) has established a formal program to accelerate acceptance and application of innovative monitoring and site characterization technologies that improve the way the nation manages its environmental problems. In 1995 the CS...

SITE CHARACTERIZATION TO SUPPORT MODEL DEVELOPMENT FOR CONTAMINANTS IN GROUND WATER

EPA Science Inventory

The development of conceptual and predictive models is an important tool to guide site characterization in support of monitoring contaminants in ground water. The accuracy of predictive models is limited by the adequacy of the input data and the assumptions made to constrain mod...

TECHNICAL APPROACHES TO CHARACTERIZING AND CLEANING UP BROWNFIELDS SITES: GUIDANCE DOCUMENT

EPA Science Inventory

NRMRL-CIN-1741 SAIC. Technical Approaches to Characterizing and Cleaning up Brownfields Sites. EPA/625/R/00/009 (NTIS PB2002-105021) , Available: 68-C7-0011. The guidance document gives assistance to communities, decision-makers, states and municipalities, academia, and the p...

Innovations in Site Characterization: Streamlining Cleanup at Vapor Intrusion and Product Removal Sites Using the Triad Approach: Hartford Plume Site, Hartford, Illinois

EPA Pesticide Factsheets

The Hartford Plume Site case study provides a detailed example of the strategies and technologies used at the site that are available to environmental practitioners to use at large and small hydrocarbon sites.

Development of method to characterize emissions from spray polyurethane foam insulation

EPA Science Inventory

This presentation updates symposium participants re EPA progress towards development of SPF insulation emissions characterization methods. The presentation highlights evaluation of experiments investigating emissions after application of SPF to substrates in micro chambers and i...

Geoscientific Characterization of the Bruce Site, Tiverton, Ontario

NASA Astrophysics Data System (ADS)

Raven, K.; Jackson, R.; Avis, J.; Clark, I.; Jensen, M.

2009-05-01

Ontario Power Generation is proposing a Deep Geologic Repository (DGR) for the long-term management of its Low and Intermediate Level Radioactive Waste (L&ILW) within a Paleozoic-age sedimentary sequence beneath the Bruce site near Tiverton, Ontario, Canada. The concept envisions that the DGR would be excavated at a depth of approximately 680 m within the Ordovician Cobourg Formation, a massive, dense, low- permeability, argillaceous limestone. Characterization of the Bruce site for waste disposal is being conducted in accordance with a four year multi-phase Geoscientific Site Characterization Plan (GSCP). The GSCP, initially developed in 2006 and later revised in 2008 to account for acquired site knowledge based on successful completion of Phase I investigations, describes the tools and methods selected for geological, hydrogeological and geomechanical site characterization. The GSCP was developed, in part, on an assessment of geoscience data needs and collection methods, review of the results of detailed geoscientific studies completed in the same bedrock formations found off the Bruce site, and recent international experience in geoscientific characterization of similar sedimentary rocks for long-term radioactive waste management purposes. Field and laboratory work related to Phase 1 and Phase 2A are nearing completion and have focused on the drilling, testing and monitoring of four continuously cored vertical boreholes through Devonian, Silurian, Ordovician and Cambrian bedrock to depths of about 860 mBGS. Work in 2009 will focus on drilling and testing of inclined boreholes to assess presence of vertical structure. The available geological, hydrogeological and hydrogeochemical data indicate the presence of remarkably uniform and predictable geology, physical hydrogeologic and geochemical properties over well separation distances exceeding 1 km. The current data set including 2-D seismic reflection surveys, field and lab hydraulic testing, lab petrophysical and diffusion testing, lab porewater and field groundwater characterization, and field head monitoring confirm the anticipated favourable characteristics of the Bruce site for long-term waste management. These favourable characteristics include a tight geomechanically stable host formation that is overlain and underlain by thick, massive, very low permeability shale and argillaceous limestone formations where radionuclide transport appears to be very limited and dominated by diffusion.

Spaceport Performance Measures

NASA Technical Reports Server (NTRS)

Finger, G. Wayne

2010-01-01

Spaceports have traditionally been characterized by performance measures associated with their site characteristics. Measures such as "Latitude" (proximity to the equator), "Azimuth" (range of available launch azimuths) and "Weather" (days of favorable weather) are commonly used to characterize a particular spaceport. However, other spaceport performance measures may now be of greater value. These measures can provide insight into areas of operational differences between competing spaceports and identify areas for improving the performance of spaceports. This paper suggests Figures of Merit (FOMs) for spaceport "Capacity" (number of potential launch opportunities per year and / or potential mass' to low earth orbit (LEO) per year); "Throughput" (actual mass to orbit per year compared to capacity); "Productivity" (labor effort hours per unit mass to orbit); "Energy Efficiency" (joules expended at spaceport per unit mass to orbit); "Carbon Footprint" tons CO2 per unit mass to orbit). Additional FOMS are investigated with regards to those areas of special interest to commercial launch operators, such as "Assignment Schedule" (days required for a binding assignment of a launch site from the spaceport); "Approval Schedule" (days to complete a range safety assessment leading to an approval or disapproval of a launch vehicle); "Affordability" (cost for a spaceport to assess a new launch vehicle); "Launch Affordability" (fixed range costs per launch); "Reconfigure Time" (hours to reconfigure the range from one vehicle's launch ready configuration to another vehicle's configuration); "Turn,Around Time" (minimum range hours required between launches of an identical type launch vehicle). Available or notional data is analyzed for the KSC/CCAFS area and other spaceports. Observations regarding progress over the past few decades are made. Areas where improvement are needed or indicated are suggested.

Immunization Against Specific Fragments of Neurotrophin p75 Receptor Protects Forebrain Cholinergic Neurons in the Olfactory Bulbectomized Mice

PubMed Central

Bobkova, Natalia; Vorobyov, Vasily; Medvinskaya, Natalia; Nesterova, Inna; Tatarnikova, Olga; Nekrasov, Pavel; Samokhin, Alexander; Deev, Alexander; Sengpiel, Frank; Koroev, Dmitry; Volpina, Olga

2016-01-01

Alzheimer’s disease (AD) is characterized by progressive cognitive impairment associated with marked cholinergic neuron loss and amyloid-β (Aβ) peptide accumulation in the brain. The cytotoxicity in AD is mediated, at least in part, by Aβ binding with the extracellular domain of the p75 neurotrophin receptor (p75NTR), localized predominantly in the membranes of acetylcholine-producing neurons in the basal forebrain. Hypothesizing that an open unstructured loop of p75NTR might be the effective site for Aβ binding, we have immunized both olfactory bulbectomized (OBX) and sham-operated (SO) mice (n = 82 and 49, respectively) with synthetic peptides, structurally similar to different parts of the loops, aiming to block them by specific antibodies. OBX-mice have been shown in previous studies, and confirmed in the present one, to be characterized by typical behavioral, morphological, and biochemical AD hallmarks, including cholinergic deficits in forebrain neurons. Immunization of OBX- or SO-mice with KLH conjugated fragments of p75NTR induced high titers of specific serum antibodies for each of nine chosen fragments. However, maximal protective effects on spatial memory, evaluated in a Morris water maze, and on activity of choline acetyltransferase in forebrain neurons, detected by immunoreactivity to specific antibodies, were revealed only for peptides with amino acid residue sequences of 155–164 and 167–176. We conclude that the approach based on immunological blockade of specific p75NTR sites, linked with the cytotoxicity, is a useful and effective tool for study of AD-associated mechanisms and for development of highly selective therapy of cholinergic malfunctioning in AD patients. PMID:27163825

Enhancer‐promoter Activity of Human Papillomavirus Type 16 Long Control Regions Isolated from Cell Lines SiHa and CaSki and Cervical Cancer Biopsies

PubMed Central

Kozuka, Takuyo; Aoki, Yukimasa; Nakagawa, Keiichi; Ohtomo, Kuni; Yoshikawa, Hiroyuki; Matsumoto, Koji; Yoshiike, Kunito

2000-01-01

Expression of human papillomavirus 16 (HPV‐16) oncogenes is markedly higher in cervical cancer cells than in precancerous cells, and the elevated expression is believed to be required for the malignant phenotypes. We compared cancer cell lines CaSki (with 200 to 400 copies of HPV‐16 DNA per cell) and SiHa (with one to two copies of HPV‐16 DNA per cell) for the E7 expression in cells and the enhancer‐promoter activity of the isolated viral long control region (LCR). Although these parameters per cell were 10‐fold higher in CaSki than in SiHa, the levels of the E7 mRNA and protein per HPV DNA copy were 10‐ to 20‐fold higher in SiHa than in CaSki. Characterization of the isolated LCRs showed that, whereas the LCR from CaSki resembled the prototype in structure and activity, the LCR from SiHa, with a deletion of 38 base pairs, enhanced transcription from P97 as assayed by using a plasmid capable of expressing luciferase. The upregulation appeared to be due to removal of one of the silencer YY1‐binding sites. Furthermore, we isolated and characterized LCRs from 51 cervical cancer patients’ biopsies. Among them, one with a deletion including YY1‐binding sites and the other with a substitution in a YY1‐motif were found to enhance the transcription. These findings suggest that mutation affecting YY1‐motifs in the LCR is one of the mechanisms enhancing the viral oncogene expression in the course of progression of cancer cells. PMID:10760685

Reactivity and Specificity of RNase T1, RNase A, and RNase H toward Oligonucleotides of RNA Containing 8-Oxo-7,8-dihydroguanosine.

PubMed

Herbert, Cassandra; Dzowo, Yannick Kokouvi; Urban, Anthony; Kiggins, Courtney N; Resendiz, Marino J E

2018-05-22

Understanding how oxidatively damaged RNA interacts with ribonucleases is important because of its proposed role in the development and progression of disease. Thus, understanding structural aspects of RNA containing lesions generated under oxidative stress, as well as its interactions with other biopolymers, is fundamental. We explored the reactivity of RNase A, RNase T 1 , and RNase H toward oligonucleotides of RNA containing 8-oxo-7,8-dihydroguanosine (8oxoG). This is the first example that addresses this relationship and will be useful for understanding (1) how these RNases can be used to characterize the structural impact that this lesion has on RNA and (2) how oxidatively modified RNA may be handled intracellularly. 8-OxoG was incorporated into 10-16-mers of RNA, and its reactivity with each ribonuclease was assessed via electrophoretic analyses, circular dichroism, and the use of other C8-purine-modified analogues (8-bromoguanosine, 8-methoxyguanosine, and 8-oxoadenosine). RNase T 1 does not recognize sites containing 8-oxoG, while RNase A recognizes and cleaves RNA at positions containing this lesion while differentiating if it is involved in H-bonding. The selectivity of RNase A followed the order C > 8-oxoG ≈ U. In addition, isothermal titration calorimetry showed that an 8-oxoG-C3'-methylphosphate derivative can inhibit RNase A activity. Cleavage patterns obtained from RNase H displayed changes in reactivity in a sequence- and concentration-dependent manner and displayed recognition at sites containing the modification in some cases. These data will aid in understanding how this modification affects reactivity with ribonucleases and will enable the characterization of global and local structural changes in oxidatively damaged RNA.

Assessment of multiple geophysical techniques for the characterization of municipal waste deposit sites

NASA Astrophysics Data System (ADS)

Gaël, Dumont; Tanguy, Robert; Nicolas, Marck; Frédéric, Nguyen

2017-10-01

In this study, we tested the ability of geophysical methods to characterize a large technical landfill installed in a former sand quarry. The geophysical surveys specifically aimed at delimitating the deposit site horizontal extension, at estimating its thickness and at characterizing the waste material composition (the moisture content in the present case). The site delimitation was conducted with electromagnetic (in-phase and out-of-phase) and magnetic (vertical gradient and total field) methods that clearly showed the transition between the waste deposit and the host formation. Regarding waste deposit thickness evaluation, electrical resistivity tomography appeared inefficient on this particularly thick deposit site. Thus, we propose a combination of horizontal to vertical noise spectral ratio (HVNSR) and multichannel analysis of the surface waves (MASW), which successfully determined the approximate waste deposit thickness in our test landfill. However, ERT appeared to be an appropriate tool to characterize the moisture content of the waste, which is of prior information for the organic waste biodegradation process. The global multi-scale and multi-method geophysical survey offers precious information for site rehabilitation studies, water content mitigation processes for enhanced biodegradation or landfill mining operation planning.

Differential gene expression revealed with RNA-Seq and parallel genotype selection of the ornithine decarboxylase gene in fish inhabiting polluted areas.

PubMed

Vega-Retter, C; Rojas-Hernandez, N; Vila, I; Espejo, R; Loyola, D E; Copaja, S; Briones, M; Nolte, A W; Véliz, D

2018-03-19

How organisms adapt to unfavorable environmental conditions by means of plasticity or selection of favorable genetic variants is a central issue in evolutionary biology. In the Maipo River basin, the fish Basilichthys microlepidotus inhabits polluted and non-polluted areas. Previous studies have suggested that directional selection drives genomic divergence between these areas in 4% of Amplified Fragment Length Polymorphism (AFLP) loci, but the underlying genes and functions remain unknown. We hypothesized that B. microlepidotus in this basin has plastic and/or genetic responses to these conditions. Using RNA-Seq, we identified differentially expressed genes in individuals from two polluted sites compared with fish inhabiting non-polluted sites. In one polluted site, the main upregulated genes were related to cellular proliferation as well as suppression and progression of tumors, while biological processes and molecular functions involved in apoptotic processes were overrepresented in the upregulated genes of the second polluted site. The ornithine decarboxylase gene (related to tumor promotion and progression), which was overexpressed in both polluted sites, was sequenced, and a parallel pattern of a heterozygote deficiency and increase of the same homozygote genotype in both polluted sites compared with fish inhabiting the non-polluted sites was detected. These results suggest the occurrence of both a plastic response in gene expression and an interplay between phenotypic change and genotypic selection in the face of anthropogenic pollution.

Progressive Educational Practices and Environments in Sweden: Preparing Students to Live and Work in the Global Age

ERIC Educational Resources Information Center

Nordgren, R. D.

2006-01-01

A multi-site case study of three Swedish schools examined the dimensions of trust, responsibility, shared power (democracy), and global workforce competence as required by a decade-old national education reforms. A key finding was the existence of progressive educational practices including constructivist epistemology, evidenced by the schools'…