WorldWideScience

Sample records for multiple damaged sites

  1. Multiple Site Damage in Flat Panel Testing

    Shrage, Daniel

    2000-01-01

    This report aimed to experimentally verify analytical models that predict the residual strength of representative aircraft structures, such as wide panels, that are subjected to Multiple Site Damage (MSD...

  2. Analysis and prediction of Multiple-Site Damage (MSD) fatigue crack growth

    Dawicke, D. S.; Newman, J. C., Jr.

    1992-08-01

    A technique was developed to calculate the stress intensity factor for multiple interacting cracks. The analysis was verified through comparison with accepted methods of calculating stress intensity factors. The technique was incorporated into a fatigue crack growth prediction model and used to predict the fatigue crack growth life for multiple-site damage (MSD). The analysis was verified through comparison with experiments conducted on uniaxially loaded flat panels with multiple cracks. Configuration with nearly equal and unequal crack distribution were examined. The fatigue crack growth predictions agreed within 20 percent of the experimental lives for all crack configurations considered.

  3. Analysis and prediction of Multiple-Site Damage (MSD) fatigue crack growth

    Dawicke, D. S.; Newman, J. C., Jr.

    1992-01-01

    A technique was developed to calculate the stress intensity factor for multiple interacting cracks. The analysis was verified through comparison with accepted methods of calculating stress intensity factors. The technique was incorporated into a fatigue crack growth prediction model and used to predict the fatigue crack growth life for multiple-site damage (MSD). The analysis was verified through comparison with experiments conducted on uniaxially loaded flat panels with multiple cracks. Configuration with nearly equal and unequal crack distribution were examined. The fatigue crack growth predictions agreed within 20 percent of the experimental lives for all crack configurations considered.

  4. Multiple-site damage crack growth behaviour in Fibre Metal Laminate structures

    Wang, W.

    2017-01-01

    Fibre metal laminates (FMLs)were developed and refined for their superior crack growth resistance and critical damage size that complimented the damage tolerance design philosophy utilized in the aerospace sector. Robust damage tolerance tools have been developed for FMLs. However, they tend to

  5. MSD in fuselage lap joints: Requirements for inspection intervals for typical fuselage lap joint panels with Multiple Site Damage

    Wit, G. P.

    1992-07-01

    Inspection of failed aircraft structures and fractography on fatigue specimens showed that after a high number of flights, cracks can appear simultaneously in riveted lap joints. When these crack tips approach each other, a mutual interaction causes an unexpected fast crack growth and new coalescence of cracks. The term Multiple Site Damage (MSD) is used when the mutual interaction of two or more damages is noticeable. A model to predict the fatigue life of a riveted lap joint and the minimum necessary inspection interval for safe aircraft operation is presented. The program was developed to simulate the fatigue process and aircraft inspection. Input for this analysis are scatter data for initiation, the stress distribution between frames and the geometry of the structure. Methods that can be used to avoid accidents due to MSD are reviewed. A test program to support the analysis is described.

  6. Core damage vulnerability due to the loss of ESW [essential service water] systems at multiplant sites: An assessment and options

    Kohut, P.; Musicki, Z.; Fitzpatrick, R.

    1989-01-01

    The main objective of this study is to establish the core damage vulnerability caused by the failure of the ESW systems in multiplant units that have only two sw pumps per unit with crosstie capability. Design and operating data have been surveyed to derive system failure frequency. A core damage model is constructed including operating configurations, specific recovery actions, and time and leak rate dependent RCP seal LOCA model. The estimated CDF SW = 2.55 x 10 -4 /yr is significant indicating the potential vulnerability of this particular SW design arrangement. A number of different potential improvements have been considered. The addition of a swing pump serving both units is shown to have the most significant CDF reduction potential (∼50%) combined with advantageous cost/benefit aspects. 2 refs., 2 tabs

  7. Liability for on-site nuclear property damage

    Neems, H.J.

    2000-01-01

    Typically, liability for on-site property addressed in contracts between operator and its suppliers. Nuclear power plant operators ordinarily protect themselves against risk of nuclear damage to on-site property by insurance. Nuclear liability laws do not specifically address liability for nuclear damage to on-site property. Nuclear plant owners should address risk of damage to on-site property when developing risk management program

  8. On multi-site damage identification using single-site training data

    Barthorpe, R. J.; Manson, G.; Worden, K.

    2017-11-01

    This paper proposes a methodology for developing multi-site damage location systems for engineering structures that can be trained using single-site damaged state data only. The methodology involves training a sequence of binary classifiers based upon single-site damage data and combining the developed classifiers into a robust multi-class damage locator. In this way, the multi-site damage identification problem may be decomposed into a sequence of binary decisions. In this paper Support Vector Classifiers are adopted as the means of making these binary decisions. The proposed methodology represents an advancement on the state of the art in the field of multi-site damage identification which require either: (1) full damaged state data from single- and multi-site damage cases or (2) the development of a physics-based model to make multi-site model predictions. The potential benefit of the proposed methodology is that a significantly reduced number of recorded damage states may be required in order to train a multi-site damage locator without recourse to physics-based model predictions. In this paper it is first demonstrated that Support Vector Classification represents an appropriate approach to the multi-site damage location problem, with methods for combining binary classifiers discussed. Next, the proposed methodology is demonstrated and evaluated through application to a real engineering structure - a Piper Tomahawk trainer aircraft wing - with its performance compared to classifiers trained using the full damaged-state dataset.

  9. Robust modal curvature features for identifying multiple damage in beams

    Ostachowicz, Wiesław; Xu, Wei; Bai, Runbo; Radzieński, Maciej; Cao, Maosen

    2014-03-01

    Curvature mode shape is an effective feature for damage detection in beams. However, it is susceptible to measurement noise, easily impairing its advantage of sensitivity to damage. To deal with this deficiency, this study formulates an improved curvature mode shape for multiple damage detection in beams based on integrating a wavelet transform (WT) and a Teager energy operator (TEO). The improved curvature mode shape, termed the WT - TEO curvature mode shape, has inherent capabilities of immunity to noise and sensitivity to damage. The proposed method is experimentally validated by identifying multiple cracks in cantilever steel beams with the mode shapes acquired using a scanning laser vibrometer. The results demonstrate that the improved curvature mode shape can identify multiple damage accurately and reliably, and it is fairly robust to measurement noise.

  10. Effect of site conditions on ground motion and damage

    Borcherdt, R.; Glassmoyer, G.; Andrews, M.; Cranswick, E.

    1989-01-01

    Results of seismologic studies conducted by the U.S. reconnaissance team in conjunction with Soviet colleagues following the tragic earthquakes of December 7, 1988, suggest that site conditions may have been a major factor in contributing to increased damage levels in Leninakan. As the potential severity of these effects in Leninakan had not been previously identified, this chapter presents results intended to provide a preliminary quantification of these effects on both damage and levels of ground motion observed in Leninakan. The article describes the damage distribution geologic setting, ground motion amplification in Leninakan, including analog amplifications and spectral amplifications. Preliminary model estimates for site response are presented. It is concluded that ground motion amplification in the 0.5-2.5-second period range was a major contributing factor to increased damage in Leninakan as compared with Kirovakan. Leninakan is located on thick water saturated alluvial deposits.

  11. Worldwide survey of damage from swallowing multiple magnets

    Oestreich, Alan E. [Cincinnati Children' s Hospital Medical Center, Radiology Department 5031, Cincinnati, OH (United States)

    2009-02-15

    It is increasingly recognized that in children swallowed multiple magnets cause considerable damage to the gastrointestinal tract. To emphasize that complications from swallowed magnets are extensive worldwide and throughout childhood. The author surveyed radiologists and researched cases of magnet swallowing in the literature and documented age and gender, numbers of magnets, nature of the magnets, reasons for swallowing, and clinical course. A total of 128 instances of magnet swallowing were identified, one fatal. Cases from 21 countries were found. Magnet swallowing occurred throughout childhood, with most children older than 3 years of age. Numbers of swallowed magnets ranged up to 100. Twelve children were known to be autistic. Many reasons were given for swallowing magnets, and a wide range of gastrointestinal damage was encountered. Considerable delay before seeking medical assistance was frequent, as was delay before obtaining radiographs or US imaging. Damage from swallowing multiple magnets is a considerable worldwide problem. More educational and preventative measures are needed. (orig.)

  12. Worldwide survey of damage from swallowing multiple magnets

    Oestreich, Alan E.

    2009-01-01

    It is increasingly recognized that in children swallowed multiple magnets cause considerable damage to the gastrointestinal tract. To emphasize that complications from swallowed magnets are extensive worldwide and throughout childhood. The author surveyed radiologists and researched cases of magnet swallowing in the literature and documented age and gender, numbers of magnets, nature of the magnets, reasons for swallowing, and clinical course. A total of 128 instances of magnet swallowing were identified, one fatal. Cases from 21 countries were found. Magnet swallowing occurred throughout childhood, with most children older than 3 years of age. Numbers of swallowed magnets ranged up to 100. Twelve children were known to be autistic. Many reasons were given for swallowing magnets, and a wide range of gastrointestinal damage was encountered. Considerable delay before seeking medical assistance was frequent, as was delay before obtaining radiographs or US imaging. Damage from swallowing multiple magnets is a considerable worldwide problem. More educational and preventative measures are needed. (orig.)

  13. A risk assessment method for multi-site damage

    Millwater, Harry Russell, Jr.

    This research focused on developing probabilistic methods suitable for computing small probabilities of failure, e.g., 10sp{-6}, of structures subject to multi-site damage (MSD). MSD is defined as the simultaneous development of fatigue cracks at multiple sites in the same structural element such that the fatigue cracks may coalesce to form one large crack. MSD is modeled as an array of collinear cracks with random initial crack lengths with the centers of the initial cracks spaced uniformly apart. The data used was chosen to be representative of aluminum structures. The structure is considered failed whenever any two adjacent cracks link up. A fatigue computer model is developed that can accurately and efficiently grow a collinear array of arbitrary length cracks from initial size until failure. An algorithm is developed to compute the stress intensity factors of all cracks considering all interaction effects. The probability of failure of two to 100 cracks is studied. Lower bounds on the probability of failure are developed based upon the probability of the largest crack exceeding a critical crack size. The critical crack size is based on the initial crack size that will grow across the ligament when the neighboring crack has zero length. The probability is evaluated using extreme value theory. An upper bound is based on the probability of the maximum sum of initial cracks being greater than a critical crack size. A weakest link sampling approach is developed that can accurately and efficiently compute small probabilities of failure. This methodology is based on predicting the weakest link, i.e., the two cracks to link up first, for a realization of initial crack sizes, and computing the cycles-to-failure using these two cracks. Criteria to determine the weakest link are discussed. Probability results using the weakest link sampling method are compared to Monte Carlo-based benchmark results. The results indicate that very small probabilities can be computed

  14. Multiple pulse nanosecond laser induced damage threshold on hybrid mirrors

    Vanda, Jan; Muresan, Mihai-George; Bilek, Vojtech; Sebek, Matej; Hanus, Martin; Lucianetti, Antonio; Rostohar, Danijela; Mocek, Tomas; Škoda, Václav

    2017-11-01

    So-called hybrid mirrors, consisting of broadband metallic surface coated with dielectric reflector designed for specific wavelength, becoming more important with progressing development of broadband mid-IR sources realized using parametric down conversion system. Multiple pulse nanosecond laser induced damage on such mirrors was tested by method s-on-1, where s stands for various numbers of pulses. We show difference in damage threshold between common protected silver mirrors and hybrid silver mirrors prepared by PVD technique and their variants prepared by IAD. Keywords: LIDT,

  15. Epilepsy in multiple sclerosis: The role of temporal lobe damage.

    Calabrese, M; Castellaro, M; Bertoldo, A; De Luca, A; Pizzini, F B; Ricciardi, G K; Pitteri, M; Zimatore, S; Magliozzi, R; Benedetti, M D; Manganotti, P; Montemezzi, S; Reynolds, R; Gajofatto, A; Monaco, S

    2017-03-01

    Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis. A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model. Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS ( ptemporal lobe, which exceeds what would be expected on the basis of the global GM damage observed.

  16. Improved pinning by multiple in-line damage

    Weinstein, Roy [Beam Particle Dynamics Laboratories, University of Houston, Houston, TX 77204-5005 (United States); Sawh, Ravi-Persad [Beam Particle Dynamics Laboratories, University of Houston, Houston, TX 77204-5005 (United States); Gandini, Alberto [Beam Particle Dynamics Laboratories, University of Houston, Houston, TX 77204-5005 (United States); Parks, Drew [Beam Particle Dynamics Laboratories, University of Houston, Houston, TX 77204-5005 (United States)

    2005-02-01

    Columnar pinning centres provide the largest pinning potential, U{sub pin}, but not the greatest J{sub c} or pinnable field, B{sub pin}. Characteristics of ion-generated columnar defects which limit J{sub c} and B{sub pin} are discussed, including reduction of the percolation path, and the need for a larger number of columns of damage, for pinning, than are usually estimated. It is concluded that columnar pinning centres limit B{sub pin} to less than 4 T, and also severely reduce J{sub c}. The goal of maximizing U{sub pin}, via columnar centres, appears to have obscured a more rewarding approach and resulted in neglect of a large regime of ion interactions. Evidence is reviewed that multiple in-line damage (MILD), described herein, can provide orders of magnitude higher J{sub c} and B{sub pin}, despite providing lower U{sub pin}. The MILD pinning centre morphology is discussed, and it is estimated that for present-day large grain high T{sub c} superconductors, a J{sub c} value of {approx}10{sup 6}Acm{sup -2} is obtainable at 77 K, even when crystal plane alignment and weak links are not improved. In addition, the pinned field is increased by over an order of magnitude. An experiment is proposed to confirm these calculations, directly compare MILD pinning to continuous columnar pinning, and determine the optimum MILD structure. Applications of MILD pinning are discussed.

  17. HPV Vaccine Effective at Multiple Anatomic Sites

    A new study from NCI researchers finds that the HPV vaccine protects young women from infection with high-risk HPV types at the three primary anatomic sites where persistent HPV infections can cause cancer. The multi-site protection also was observed at l

  18. White matter damage impairs access to consciousness in multiple sclerosis.

    Reuter, Françoise; Del Cul, Antoine; Malikova, Irina; Naccache, Lionel; Confort-Gouny, Sylviane; Cohen, Laurent; Cherif, André Ali; Cozzone, Patrick J; Pelletier, Jean; Ranjeva, Jean-Philippe; Dehaene, Stanislas; Audoin, Bertrand

    2009-01-15

    Global neuronal workspace theory predicts that damage to long-distance white matter (WM) tracts should impair access to consciousness during the perception of brief stimuli. To address this issue, we studied visual backward masking in 18 patients at the very first clinical stage of multiple sclerosis (MS), a neurological disease characterized by extensive WM damage, and in 18 matched healthy subjects. In our masking paradigm, the visibility of a digit stimulus increases non-linearly as a function of the interval duration between this target and a subsequent mask. In order to characterize quantitatively, for each subject, the transition between non-conscious and conscious perception of the stimulus, we used non-linear regression to fit a sigmoid curve to objective performance and subjective visibility reports as a function of target-mask delay. The delay corresponding to the inflexion point of the sigmoid, where visibility suddenly increases, was termed the "non-linear transition threshold" and used as a summary measure of masking efficiency. Objective and subjective non-linear transition thresholds were highly correlated across subjects in both groups, and were higher in patients compared to controls. In patients, variations in the non-linear transition threshold were inversely correlated to the Magnetization transfer ratio (MTR) values inside the right dorsolateral prefrontal WM, the right occipito-frontal fasciculus and the left cerebellum. This study provides clinical evidence of a relationship between impairments of conscious access and integrity of large WM bundles, particularly involving prefrontal cortex, as predicted by global neuronal workspace theory.

  19. Histone peptide AKRHRK enhances H2O2-induced DNA damage and alters its site specificity

    Midorikawa, Kaoru; Murata, Mariko; Kawanishi, Shosuke

    2005-01-01

    Histone proteins are involved in compaction of DNA and the protection of cells from oxygen toxicity. However, several studies have demonstrated that the metal-binding histone reacts with H 2 O 2 , leading to oxidative damage to a nucleobase. We investigated whether histone can accelerate oxidative DNA damage, using a minimal model for the N-terminal tail of histone H4, CH 3 CO-AKRHRK-CONH 2 , which has a metal-binding site. This histone peptide enhanced DNA damage induced by H 2 O 2 and Cu(II), especially at cytosine residues, and induced additional DNA cleavage at the 5'-guanine of GGG sequences. The peptide also enhanced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and ESR spin-trapping signal from H 2 O 2 and Cu(II). Cyclic redox reactions involving histone-bound Cu(II) and H 2 O 2 , may give rise to multiple production of radicals leading to multiple hits in DNA. It is noteworthy that the histone H4 peptide with specific sequence AKRHRK can cause DNA damage rather than protection under metal-overloaded condition

  20. Dynamics and heterogeneity of brain damage in multiple sclerosis

    Kotelnikova, Ekaterina

    2017-10-26

    Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less severely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a long-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an unsupervised clustering analysis. We found that by adjusting certain parameters, albeit within their biological range, the mathematical model reproduced the different disease courses, supporting the dynamic CNS damage hypothesis to explain MS heterogeneity. Our analysis suggests that the irreversible axon degeneration produced in the early stages of progressive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capacity for remyelination. However, and in agreement with recent pathological studies, degeneration of chronically demyelinated axons is not a key feature that distinguishes this phenotype. Moreover, the model reveals that lower rates of axon degeneration and more rapid remyelination make relapsing MS more resilient than the

  1. Dynamics and heterogeneity of brain damage in multiple sclerosis

    Kotelnikova, Ekaterina; Kiani, Narsis A.; Abad, Elena; Martinez-Lapiscina, Elena H.; Andorra, Magi; Zubizarreta, Irati; Pulido-Valdeolivas, Irene; Pertsovskaya, Inna; Alexopoulos, Leonidas G.; Olsson, Tomas; Martin, Roland; Paul, Friedemann; Tegner, Jesper; Garcia-Ojalvo, Jordi; Villoslada, Pablo

    2017-01-01

    Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less severely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a long-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an unsupervised clustering analysis. We found that by adjusting certain parameters, albeit within their biological range, the mathematical model reproduced the different disease courses, supporting the dynamic CNS damage hypothesis to explain MS heterogeneity. Our analysis suggests that the irreversible axon degeneration produced in the early stages of progressive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capacity for remyelination. However, and in agreement with recent pathological studies, degeneration of chronically demyelinated axons is not a key feature that distinguishes this phenotype. Moreover, the model reveals that lower rates of axon degeneration and more rapid remyelination make relapsing MS more resilient than the

  2. Seismic PSA method for multiple nuclear power plants in a site

    Hakata, Tadakuni [Nuclear Safety Commission, Tokyo (Japan)

    2007-07-15

    The maximum number of nuclear power plants in a site is eight and about 50% of power plants are built in sites with three or more plants in the world. Such nuclear sites have potential risks of simultaneous multiple plant damages especially at external events. Seismic probabilistic safety assessment method (Level-1 PSA) for multi-unit sites with up to 9 units has been developed. The models include Fault-tree linked Monte Carlo computation, taking into consideration multivariate correlations of components and systems from partial to complete, inside and across units. The models were programmed as a computer program CORAL reef. Sample analysis and sensitivity studies were performed to verify the models and algorithms and to understand some of risk insights and risk metrics, such as site core damage frequency (CDF per site-year) for multiple reactor plants. This study will contribute to realistic state of art seismic PSA, taking consideration of multiple reactor power plants, and to enhancement of seismic safety. (author)

  3. Probability of growth of small damage sites on the exit surface of fused silica optics.

    Negres, Raluca A; Abdulla, Ghaleb M; Cross, David A; Liao, Zhi M; Carr, Christopher W

    2012-06-04

    Growth of laser damage on fused silica optical components depends on several key parameters including laser fluence, wavelength, pulse duration, and site size. Here we investigate the growth behavior of small damage sites on the exit surface of SiO₂ optics under exposure to tightly controlled laser pulses. Results demonstrate that the onset of damage growth is not governed by a threshold, but is probabilistic in nature and depends both on the current size of a damage site and the laser fluence to which it is exposed. We also develop models for use in growth prediction. In addition, we show that laser exposure history also influences the behavior of individual sites.

  4. Modular risk analysis for assessing multiple waste sites

    Whelan, G.; Buck, J.W.; Nazarali, A.

    1994-06-01

    Human-health impacts, especially to the surrounding public, are extremely difficult to assess at installations that contain multiple waste sites and a variety of mixed-waste constituents (e.g., organic, inorganic, and radioactive). These assessments must address different constituents, multiple waste sites, multiple release patterns, different transport pathways (i.e., groundwater, surface water, air, and overland soil), different receptor types and locations, various times of interest, population distributions, land-use patterns, baseline assessments, a variety of exposure scenarios, etc. Although the process is complex, two of the most important difficulties to overcome are associated with (1) establishing an approach that allows for modifying the source term, transport, or exposure component as an individual module without having to re-evaluate the entire installation-wide assessment (i.e., all modules simultaneously), and (2) displaying and communicating the results in an understandable and useable maimer to interested parties. An integrated, physics-based, compartmentalized approach, which is coupled to a Geographical Information System (GIS), captures the regional health impacts associated with multiple waste sites (e.g., hundreds to thousands of waste sites) at locations within and surrounding the installation. Utilizing a modular/GIS-based approach overcomes difficulties in (1) analyzing a wide variety of scenarios for multiple waste sites, and (2) communicating results from a complex human-health-impact analysis by capturing the essence of the assessment in a relatively elegant manner, so the meaning of the results can be quickly conveyed to all who review them

  5. Grey matter damage in multiple sclerosis A pathology perspective

    Klaver, R.; de Vries, H.E.; Schenk, G.J.; Geurts, J.J.G.

    2013-01-01

    Over the past decade, immunohistochemical studies have provided compelling evidence that gray matter (GM) pathology in multiple sclerosis (MS) is extensive. Until recently, this GM pathology was difficult to visualize using standard magnetic resonance imaging (MRI ) techniques. However, with newly

  6. A method for estimating the local area economic damages of Superfund waste sites

    Walker, D.R.

    1992-01-01

    National Priority List (NPL) sites, or more commonly called Superfund sites, are hazardous waste sites (HWS) deemed by the Environmental Protection Agency (EPA) to impose the greatest risks to human health or welfare or to the environment. HWS are placed and ranked for cleanup on the NPL based on a score derived from the Hazard Ranking System (HRS), which is a scientific assessment of the health and environmental risks posed by HWS. A concern of the HRS is that the rank of sites is not based on benefit-cost analysis. The main objective of this dissertation is to develop a method for estimating the local area economic damages associated with Superfund waste sites. Secondarily, the model is used to derive county-level damage estimates for use in ranking the county level damages from Superfund sites. The conceptual model used to describe the damages associated with Superfund sites is a household-firm location decision model. In this model assumes that households and firms make their location choice based on the local level of wages, rents and amenities. The model was empirically implemented using 1980 census microdata on households and workers in 253 counties across the US. The household sample includes data on the value and structural characteristics of homes. The worker sample includes the annual earnings of workers and a vector worker attributes. The microdata was combined with county level amenity data, including the number of Superfund sites. The hedonic pricing technique was used to estimate the effect of Superfund sites on average annual wages per household and on monthly expenditures on housing. The results show that Superfund sites impose statistically significant damages on households. The annual county damages from Superfund sites for a sample of 151 counties was over 14 billion dollars. The ranking of counties using the damage estimates is correlated with the rank of counties using the HRS

  7. A strategy for health promotion at multiple corporate sites.

    Alexy, B; Eynon, D

    1991-02-01

    1. The logistical problems associated with delivery of health promotion programs at multiple corporate sites can be addressed through the use of health education packets. 2. The role of the nurse or health coordinator is critical in assisting and guiding the employee as the health plan is executed. 3. Problematic areas related to implementation of programs at remote sites can be alleviated through careful planning and extensive communication. 4. Advertising, input from employees and staff, and follow up are important in the success of a program.

  8. Extranodal Rosai Dorfman disease in multiple sites: A case report

    Shim, Jong Joon; Kim, Ho Kyun; Shim, Jae Chan; Lee, Kyoung Eun; Lee, Ghi Jai; Suh, Jung Ho; Hong, Seong Woo; Lee, Hye Kyung [Seoul Paik Hospital/Inje Univ. College of Medicine, Seoul (Korea, Republic of)

    2012-07-15

    Rosai Dorfman disease involves an abnormal proliferation of histiocytes. This abnormal growth tends to occur within the lymph nodes, with occasional extranodal presentation. Rosai Dorfman disease is a rare disease, and the extranodal cases are even more uncommon. We report a rare case of extranodal Rosai Dorfman disease in multiple sites in a 56 year old male patient. Abdominopelvic CT revealed soft tissue attenuation masses, encasing both the renal pelvis and both ureters, as well as the thoracic vertebra. Following the neck sonography, both submandibular glands had an enlarged honey combed appearance. Although Rosai Dorfman disease is rare, it should be considered as a potential differential diagnosis when multiple sites involving soft tissue attenuation masses are observed with sonogram and CT.

  9. Case report 554: Osteonecrosis at multiple sites as noted

    Archer, A G; Nelson, M C [Georgetown Univ., Washington, DC (USA). Dept. of Radiology; Abbondanzo, S L [Georgetown Univ., Washington, DC (USA). Dept. of Pathology; Bogumill, G P [Georgetown Univ., Washington, DC (USA). Div. of Orthopaedics

    1989-08-01

    This is a case of a 31-year-old man who presented with persistent pain of the left knee and was found to have avascular necrosis at multiple sites. Plain film roentgenograms with tomography, bone scanning and magnetic resonance imaging were utilized in the diagnostic work-up. The history of treatment with steroids eight years previously was elicited only after the diagnosis was made radiographically and pathologically. (orig./GDG).

  10. Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference.

    Geoffrey R Bennett

    Full Text Available Host base excision repair (BER proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1 and mutY homolog (MYH as well as DNA polymerase beta (Polβ. While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 5'dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggested Polβ DNA synthesis activity is not necessary while 5'dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level.

  11. Numerical analysis of laser ablation and damage in glass with multiple picosecond laser pulses.

    Sun, Mingying; Eppelt, Urs; Russ, Simone; Hartmann, Claudia; Siebert, Christof; Zhu, Jianqiang; Schulz, Wolfgang

    2013-04-08

    This study presents a novel numerical model for laser ablation and laser damage in glass including beam propagation and nonlinear absorption of multiple incident ultrashort laser pulses. The laser ablation and damage in the glass cutting process with a picosecond pulsed laser was studied. The numerical results were in good agreement with our experimental observations, thereby revealing the damage mechanism induced by laser ablation. Beam propagation effects such as interference, diffraction and refraction, play a major role in the evolution of the crater structure and the damage region. There are three different damage regions, a thin layer and two different kinds of spikes. Moreover, the electronic damage mechanism was verified and distinguished from heat modification using the experimental results with different pulse spatial overlaps.

  12. EPA True NO2 ground site measurements – multiple sites, TCEQ ground site measurements of meteorological and air pollution parameters – multiple sites ,GeoTASO NO2 Vertical Column

    U.S. Environmental Protection Agency — EPA True NO2 ground site measurements – multiple sites - http://www-air.larc.nasa.gov/cgi-bin/ArcView/discover-aq.tx-2013; TCEQ ground site measurements of...

  13. Tornado damage at the Grand Gulf, Mississippi nuclear power plant site: aerial and ground surveys

    Fujita, T.T.; McDonald, J.R.

    1978-05-01

    A tornado struck the Grand Gulf nuclear power generating station, Port Gibson, Mississippi, about 11:30 p.m. on April 17, 1978. Storm damage investigators from the University of Chicago and Texas Tech University were dispatched to survey the damage. The meteorological situation that spawned the Grand Gulf tornado and seven others in the area is discussed. Aerial surveys of the entire damage path and detailed surveys of the plant site are presented. An engineering evaluation of the damage is also presented based primarily on information gained from detailed ground surveys

  14. Stalled repair of lesions when present within a clustered DNA damage site

    Lomax, M.E.; Cunniffe, S.; O'Neill, P.

    2003-01-01

    Ionising radiation produces clustered DNA damages (two or more lesions within one or two helical turns of the DNA) which could challenge the repair mechanism(s) of the cell. Using purified base excision repair (BER) enzymes and synthetic oligonucleotides a number of recent studies have established the excision of a lesion within clustered damage sites is compromised. Evidence will be presented that the efficiency of repair of lesions within a clustered DNA damage site is reduced, relative to that of the isolated lesions, since the lifetime of both lesions is extended by up to four fold. Simple clustered damage sites, comprised of single-strand breaks, abasic sites and base damages, one or five bases 3' or 5' to each other, were synthesised in oligonucleotides and repair carried out in mammalian cell nuclear extracts. The rate of repair of the single-strand break/abasic site within these clustered damage sites is reduced, mainly due to inhibition of the DNA ligase. The mechanism of repair of the single-strand break/abasic site shows some asymmetry. Repair appears to be by the short-patch BER pathway when the lesions are 5' to each other. In contrast, when the lesions are 3' to each other repair appears to proceed along the long-patch BER pathway. The lesions within the cluster are processed sequentially, the single-strand break/abasic site being repaired before excision of 8-oxoG, limiting the formation of double-strand breaks to <2%. Stalled processing of clustered DNA damage extends the lifetime of the lesions to an extent that could have biological consequences, e.g. if the lesions are still present during transcription and/or at replication mutations could arise

  15. Detection of multiple damages employing best achievable eigenvectors under Bayesian inference

    Prajapat, Kanta; Ray-Chaudhuri, Samit

    2018-05-01

    A novel approach is presented in this work to localize simultaneously multiple damaged elements in a structure along with the estimation of damage severity for each of the damaged elements. For detection of damaged elements, a best achievable eigenvector based formulation has been derived. To deal with noisy data, Bayesian inference is employed in the formulation wherein the likelihood of the Bayesian algorithm is formed on the basis of errors between the best achievable eigenvectors and the measured modes. In this approach, the most probable damage locations are evaluated under Bayesian inference by generating combinations of various possible damaged elements. Once damage locations are identified, damage severities are estimated using a Bayesian inference Markov chain Monte Carlo simulation. The efficiency of the proposed approach has been demonstrated by carrying out a numerical study involving a 12-story shear building. It has been found from this study that damage scenarios involving as low as 10% loss of stiffness in multiple elements are accurately determined (localized and severities quantified) even when 2% noise contaminated modal data are utilized. Further, this study introduces a term parameter impact (evaluated based on sensitivity of modal parameters towards structural parameters) to decide the suitability of selecting a particular mode, if some idea about the damaged elements are available. It has been demonstrated here that the accuracy and efficiency of the Bayesian quantification algorithm increases if damage localization is carried out a-priori. An experimental study involving a laboratory scale shear building and different stiffness modification scenarios shows that the proposed approach is efficient enough to localize the stories with stiffness modification.

  16. Multiple [3H]-nemonapride binding sites in calf brain.

    Helmeste, D M; Tang, S W; Li, M; Fang, H

    1997-07-01

    [3H]-Nemonapride has been the ligand of choice to label D4 dopamine receptors. Its specificity was questioned when it was discovered that sigma (sigma) sites were also labeled by [3H]-nemonapride. To further characterize the binding of [3H]-nemonapride, three areas of calf brain (striatum, frontal cortex and cerebellum) were examined. In all three areas, [3H]-nemonapride labeled multiple sites. Dopaminergic and sigma sites were the most prominent. The sigma binding profile was sigma-1 like with a Ki binding profile as follows (in order of decreasing potency): haloperidol, PPAP, pentazocine, DTG, U-50488, R(+)-3-PPP. Experiments using sulpiride and pentazocine to block striatal dopaminergic and sigma sites, respectively, revealed additional, not previously characterized binding sites for [3H]-nemonapride. One component which was present in striatum but not in frontal cortex or cerebellum, had affinity for some neuroleptics and WB-4101, but not for typical serotonergic agents. Thus, [3H]-nemonapride has no selectivity for dopamine receptors unless stringent experimental conditions are met.

  17. The enigma of multiple sclerosis: inflammation and neurodegeneration cause heterogeneous dysfunction and damage

    Owens, Trevor

    2003-01-01

    progression correlate with axonal damage, and that brain atrophy resulting from axonal loss is a feature of early multiple sclerosis, and is not restricted to the secondary progressive forms of the disease. Inflammatory mediators (CD8 T cells and antibodies) are implicated in axonal damage, and treatment...... cells for oligodendrocytes. SUMMARY: Oligodendrocyte precursors are abundant in multiple sclerosis lesions, but fail to remyelinate. Oligodendrocyte growth and regeneration are probably compromised by the action of growth inhibitory signals and lack of growth stimuli. Inflammatory cells and mediators......PURPOSE OF REVIEW: The demyelinating disease multiple sclerosis has an autoimmune inflammatory component, which has dominated the description of multiple sclerosis. A degenerative component to multiple sclerosis was always apparent, but was underappreciated until recently. Recent work has brought...

  18. Hanford Site Tank 241-SY-101, damaged equipment removal

    Titzler, P.A.; Legare, D.E.; Barrus, H.G.

    1993-11-01

    Hanford Site Tank 241-SY-101 has a history of generating hydrogen-nitrous oxide gases. The gases are generated and trapped in the non-convective waste layer near the bottom of the 23-m- (75-ft-) diameter underground tank. Approximately every three months the pressure in the tank is relieved as the trapped gases are released through or around the surface crust into the tank dome. This process moves large amounts of liquid waste and crust material around in the tank. The moving waste displaced air lances and thermocouple assemblies (2-in. schedule-40 pipe) installed in four tank risers and permanently bent them to a maximum angle of 40 degrees. The bends were so severe that assemblies could not be removed from the tank using the originally designed hardware. Just after the tank releases the trapped gas, a 20-to-30-day work ''window'' opens

  19. Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

    Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

    2017-08-01

    Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  20. Parametric study of the damage ring pattern in fused silica induced by multiple longitudinal modes laser pulses

    Chambonneau, M., E-mail: maxime.chambonneau@hotmail.fr; Grua, P.; Rullier, J.-L.; Lamaignère, L. [CEA CESTA, 15 Avenue des Sablières, CS 60001, 33116 Le Barp Cedex (France); Natoli, J.-Y. [Aix Marseille Université, CNRS, Centrale Marseille, Institut Fresnel, UMR 7249, 13013 Marseille (France)

    2015-03-14

    With the use of multiple longitudinal modes nanosecond laser pulses at 1064 nm, laser damage sites at the exit surface of fused silica clearly and systematically exhibit ring patterns. It has been shown in our previous works that the apparent chronology of rings was closely related to the temporal shape of the laser pulses. This particular correspondence had suggested an explanation of the ring morphology formation based on the displacement of an ionization front in the surrounding air. To provide a former basis for this hypothesis and deeper understanding of ring pattern formation, additional experiments have been performed. First, the impact of fluence has been investigated, revealing that a wide variety of damage sites are produced within a very narrow fluence range; this fact involves the chronology of appearance of a surface plasma during the laser pulse. The sizes of the damage sites are proportional to the fluence of their expansion occurring between the beginning of the plasma and the end of the laser pulse. Second, specific experiments have been carried out at different angles of incidence, resulting in egg-shaped patterns rather than circular ones. This behavior can be explained by our previous hypothesis of creation of a plasma in air, its expansion being tightly conditioned by the illumination angle. This series of experiments, in which the angle of incidence is varied up to 80°, permits us to link quantitatively the working hypothesis of ionization front propagation with theoretical hydrodynamics modeling.

  1. Hanford Site Welding Program Successfully Providing A Single Site Function For Use By Multiple Contractors

    Cannell, G.R.

    2009-01-01

    The Department of Energy, Richland Operations (DOE-RL) recently restructured its Hanford work scope, awarding two new contracts over the past several months for a total of three contracts to manage the sites cleanup efforts. DOE-RL met with key contractor personnel prior to and during contract transition to ensure site welding activities had appropriate oversight and maintained code compliance. The transition also provided an opportunity to establish a single site-wide function that would provide welding and materials engineering services to the Hanford site contractors: CH2M HILL Plateau Remediation Company (CHPRC); Mission Support Alliance (MSA); Washington River Protection Solutions (WRPS); and Washington Closure Hanford (WCH). Over the years, multiple and separate welding programs (amongst the several contractors) existed at the Hanford site leading to inefficiencies resulting from duplication of administrative efforts, maintenance of welding procedures, welder performance certifications, etc. The new, single program eliminates these inefficiencies. The new program, co-managed by two of the sites' new contractors, the CHPRC ('owner' of the program and responsible for construction welding services) and the MSA (provides maintenance welding services), provides more than just the traditional construction and maintenance welding services. Also provided, are welding engineering, specialty welding development/qualification for the closure of radioactive materials containers and materials evaluation/failure analysis. The following describes the new Hanford site welding program.

  2. Incident laser modulation of a repaired damage site with a rim in fused silica rear subsurface

    Li Li; Xiang Xia; Zu Xiao-Tao; Yuan Xiao-Dong; He Shao-Bo; Jiang Xiao-Dong; Zheng Wan-Guo

    2012-01-01

    Local CO2 laser treatment has proved to be an effective method to prevent the 351-nm laser-induced damage sitesin a fused silica surface from exponentially growing,which is responsible for limiting the lifetime of optics in high fluence laser systems.However,the CO2 laser induced ablation crater is often surrounded by a raised rim at the edge,which can also result in the intensification of transmitted ultraviolet light that may damage the downstream optics.In this work,the three-dimensional finite-difference time-domain method is developed to simulate the distribution of electrical field intensity in the vicinity of the CO2 laser mitigated damage site located in the exit subsurface of fused silica.The simulated results show that the repaired damage sites with raised rims cause more notable modulation to the incident laser than those without rims.Specifically,we present a theoretical model of using dimpled patterning to control the rim structure around the edge of repaired damage sites to avoid damage to downstream optics.The calculated results accord well with previous experimental results and the underlying physical mechanism is analysed in detail.

  3. Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

    Scott Cukras

    Full Text Available Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

  4. Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

    Cukras, Scott; Morffy, Nicholas; Ohn, Takbum; Kee, Younghoon

    2014-01-01

    Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

  5. Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice.

    Alvarenga, T A; Ribeiro, D A; Araujo, P; Hirotsu, C; Mazaro-Costa, R; Costa, J L; Battisti, M C; Tufik, S; Andersen, M L

    2011-09-01

    The purpose of the present study was to characterize the genetic damage induced by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the platform technique for 72 hours, followed by drug administration and evaluation of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to induce genetic damage in the blood, brain and liver cells of sleep-deprived mice at the majority of the doses evaluated. Ecstasy also induced increased DNA migration in peripheral blood cells for all concentrations tested. Analysis of damaged cells by the tail moment data suggests that ecstasy is a genotoxic chemical at the highest concentrations tested, inducing damage in liver or brain cells after sleep deprivation in mice. Taken together, our results suggest that cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when associated with sleep loss.

  6. Satellite imagery-based monitoring of archaeological site damage in the Syrian civil war.

    Casana, Jesse; Laugier, Elise Jakoby

    2017-01-01

    Since the start of the Syrian civil war in 2011, the rich archaeological heritage of Syria and northern Iraq has faced severe threats, including looting, combat-related damage, and intentional demolition of monuments. However, the inaccessibility of the conflict zone to archaeologists or cultural heritage specialists has made it difficult to produce accurate damage assessments, impeding efforts to develop mitigation strategies and policies. This paper presents results of a project, undertaken in collaboration with the American Schools of Oriental Research (ASOR) and the US Department of State, to monitor damage to archaeological sites in Syria, northern Iraq, and southern Turkey using recent, high-resolution satellite imagery. Leveraging a large database of archaeological and heritage sites throughout the region, as well as access to continually updated satellite imagery from DigitalGlobe, this project has developed a flexible and efficient methodology to log observations of damage in a manner that facilitates spatial and temporal queries. With nearly 5000 sites carefully evaluated, analysis reveals unexpected patterns in the timing, severity, and location of damage, helping us to better understand the evolving cultural heritage crisis in Syria and Iraq. Results also offer a model for future remote sensing-based archaeological and heritage monitoring efforts in the Middle East and beyond.

  7. Satellite imagery-based monitoring of archaeological site damage in the Syrian civil war.

    Jesse Casana

    Full Text Available Since the start of the Syrian civil war in 2011, the rich archaeological heritage of Syria and northern Iraq has faced severe threats, including looting, combat-related damage, and intentional demolition of monuments. However, the inaccessibility of the conflict zone to archaeologists or cultural heritage specialists has made it difficult to produce accurate damage assessments, impeding efforts to develop mitigation strategies and policies. This paper presents results of a project, undertaken in collaboration with the American Schools of Oriental Research (ASOR and the US Department of State, to monitor damage to archaeological sites in Syria, northern Iraq, and southern Turkey using recent, high-resolution satellite imagery. Leveraging a large database of archaeological and heritage sites throughout the region, as well as access to continually updated satellite imagery from DigitalGlobe, this project has developed a flexible and efficient methodology to log observations of damage in a manner that facilitates spatial and temporal queries. With nearly 5000 sites carefully evaluated, analysis reveals unexpected patterns in the timing, severity, and location of damage, helping us to better understand the evolving cultural heritage crisis in Syria and Iraq. Results also offer a model for future remote sensing-based archaeological and heritage monitoring efforts in the Middle East and beyond.

  8. Multiple nucleophilic elbows leading to multiple active sites in a single module esterase from Sorangium cellulosum

    Udatha, D.B.R.K. Gupta; Madsen, Karina Marie; Panagiotou, Gianni

    2015-01-01

    The catalytic residues in carbohydrate esterase enzyme families constitute a highly conserved triad: serine, histidine and aspartic acid. This catalytic triad is generally located in a very sharp turn of the protein backbone structure, called the nucleophilic elbow and identified by the consensus...... sequence GXSXG. An esterase from Sorangium cellulosum Soce56 that contains five nucleophilic elbows was cloned and expressed in Escherichia coli and the function of each nucleophilic elbowed site was characterized. In order to elucidate the function of each nucleophilic elbow, site directed mutagenesis....... To our knowledge, this is the first report presenting the role of multiple nucleophilic elbows in the catalytic promiscuity of an esterase. Further structural analysis at protein unit level indicates the new evolutionary trajectories in emerging promiscuous esterases....

  9. Application of X-ray methods to assess grain vulnerability to damage resulting from multiple loads

    Zlobecki, A.

    1995-01-01

    The aim of the work is to describe wheat grain behavior under multiple dynamic loads with various multipliers. The experiments were conducted on Almari variety grain. Grain moisture was 11, 16, 21 and 28%. A special ram stand was used for loading the grain. The experiments were carried out using an 8 g weight, equivalent to impact energy of 4,6 x 10 -3 [J]. The X-ray method was used to assess damage. The exposure time was 8 minutes with X-ray lamp voltage equal to 15 kV. The position index was used as the measure of the damage. The investigation results were elaborated statistically. Based on the results of analysis of variance, regression analysis, the d-Duncan test and the Kolmogorov-Smirnov test, the damage number was shown to depend greatly on the number of impacts for the whole range of moisture of the grain loaded. (author)

  10. Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites

    Mortusewicz, Oliver; Roth, Wera; Li, Na; Cardoso, M. Cristina; Meisterernst, Michael; Leonhardt, Heinrich

    2008-01-01

    The multifunctional nuclear protein positive cofactor 4 (PC4) is involved in various cellular processes including transcription, replication, and chromatin organization. Recently, PC4 has been identified as a suppressor of oxidative mutagenesis in Escherichia coli and Saccharomyces cerevisiae. To investigate a potential role of PC4 in mammalian DNA repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. We found a clear accumulation of endogenous PC4 at DNA damage sites introduced by either chemical agents or laser microirradiation. Using fluorescent fusion proteins and specific mutants, we demonstrated that the rapid recruitment of PC4 to laser-induced DNA damage sites is independent of poly(ADP-ribosyl)ation and γH2AX but depends on its single strand binding capacity. Furthermore, PC4 showed a high turnover at DNA damages sites compared with the repair factors replication protein A and proliferating cell nuclear antigen. We propose that PC4 plays a role in the early response to DNA damage by recognizing single-stranded DNA and may thus initiate or facilitate the subsequent steps of DNA repair. PMID:19047459

  11. High EDSS can predict risk for upper urinary tract damage in patients with multiple sclerosis.

    Ineichen, Benjamin V; Schneider, Marc P; Hlavica, Martin; Hagenbuch, Niels; Linnebank, Michael; Kessler, Thomas M

    2018-04-01

    Neurogenic lower urinary tract dysfunction (NLUTD) is very common in patients with multiple sclerosis (MS), and it might jeopardize renal function and thereby increase mortality. Although there are well-known urodynamic risk factors for upper urinary tract damage, no clinical prediction parameters are available. We aimed to assess clinical parameters potentially predicting urodynamic risk factors for upper urinary tract damage. A consecutive series of 141 patients with MS referred from neurologists for primary neuro-urological work-up including urodynamics were prospectively evaluated. Clinical parameters taken into account were age, sex, duration, and clinical course of MS and Expanded Disability Status Scale (EDSS). Multivariate modeling revealed EDSS as a clinical parameter significantly associated with urodynamic risk factors for upper urinary tract damage (odds ratio = 1.34, 95% confidence interval (CI) = 1.06-1.71, p = 0.02). Using receiver operator characteristic (ROC) curves, an EDSS of 5.0 as cutoff showed a sensitivity of 86%-87% and a specificity of 52% for at least one urodynamic risk factor for upper urinary tract damage. High EDSS is significantly associated with urodynamic risk factors for upper urinary tract damage and allows a risk-dependent stratification in daily neurological clinical practice to identify MS patients requiring further neuro-urological assessment and treatment.

  12. New elements of molecular orchestra at radiation-induced damaged genomic sites

    Wani, Altaf A.; Battu, Aruna; Ray, Alo

    2012-01-01

    DNA damage promptly activates cell cycle checkpoints enabling cells to repair their genome. ATR and ATM kinases are central to the checkpoint activation in response to DNA damage and replication stress. Activated ATR and ATM phosphorylate several downstream proteins involved in DNA repair and cell cycle arrest. However, the nature of the signal, which initially activates these kinases in response to UV damage and how they interact with nucleotide excision repair (NER) pathway, is unclear. Our research has shown that DDB2 and XPC, two early damage recognition factors, promoted ATR and ATM recruitment and phosphorylation. ATR and ATM localized to the damage site and physically interact with XPC. ATR and ATM recruitment and their phosphorylation is negatively affected in cells defective in DDB2 and XPC functions while conversely ATR- and ATM-deficiency fail to influence the damage recruitment of DDB2 and XPC proteins. Consequently, the phosphorylation of ATR and ATM substrates, Chk1, Chk2, H2AX, and BRCA1 is significantly reduced or abrogated in mutant cells, indicating that defective DDB2 and XPC function impaired the checkpoint signal transduction cascade in response to UV damage. DDB2 and XPC also regulated the BRCA1 and Rad51 recruitment to the damage site, implicating their role in homologous recombination-mediated DNA repair pathway. Supporting data reveal that the depletion of ATR and ATM influenced the NER efficiency. Moreover, upon completion of NER, ordered restoration of chromatin structure and key epigenetic marks are necessary for resumption of the cell's normal function. We have demonstrated such a restoration role of H3K56 acetylation (H3K56Ac) mark in response to UV irradiation, In human cells a fast initial deacetylation of H3K56 is followed by full renewal of an acetylated state at ∼ 24-48 hr post-irradiation. Histone chaperone, anti-silencing function-1A (ASF1A), is crucial for post-repair H3K56Ac restoration, which in turn, is needed for the

  13. The use of historical data for the characterisation of multiple damaging hydrogeological events

    O. Petrucci

    2003-01-01

    Full Text Available Landslides, floods and secondary floods (hereinafter called phenomena triggered by rainfall and causing extensive damage are reviewed in this paper. Damaging Hydrogeological Events (DHEs are defined as the occurrence of one or more simultaneous aforementioned phenomena. A method for the characterisation of DHEs based upon historic data is proposed. The method is aimed at assessing DHE-related hazard in terms of recurrence, severity, damage, and extent of the affected area. Using GIS, the DHEs historical and climatic data collection, the geomorphological and hydrogeological characterisation of the hit areas, the characterisation of induced damage, the evaluation of triggering rainfall return period and critical duration of each DHE were carried out. The approach was applied to a test site in Southern Italy (Calabria for validation purposes. A database was set up including data from 24 events which have occurred during an 80-year period. The spatial distribution of phenomena was analysed together with the return period of cumulative rainfall. The trend of the occurred phenomena was also compared with the climatic trend. Four main types of Damaging Hydrogeological Events were identified in the study area.

  14. Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality

    Ruei-Tang Cheng

    2010-01-01

    Full Text Available When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4∘C±0.3∘C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15 and reduced the hypothermia (core temperature, 37.3∘C. The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediatedαUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality.

  15. Multiple repair pathways mediate cellular tolerance to resveratrol-induced DNA damage.

    Liu, Ying; Wu, Xiaohua; Hu, Xiaoqing; Chen, Ziyuan; Liu, Hao; Takeda, Shunichi; Qing, Yong

    2017-08-01

    Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects. Comparing the survival of WT with isogenic DNA-repair deficient DT40 cell lines demonstrated that single strand break repair (SSBR) deficient cell lines of Parp1 -/- , base excision repair (BER) deficient cell lines of Polβ -/- , homologous recombination (HR) mutants of Brca1 -/- and Brca2 -/- and translesion DNA synthesis (TLS) mutants of Rev3 -/- and Rad18 -/- were more sensitive to RSV. The sensitivities of cells were associated with enhanced DNA damage comparing the accumulation of γ-H2AX foci and number of CAs of isogenic DNA-repair deficient DT40 cell lines with WT cells. These results clearly demonstrated that RSV-induced DNA damage in DT40 cells, and multiple repair pathways including BER, SSBR, HR and TLS, play critical roles in response to RSV- induced genotoxicity. Copyright © 2017. Published by Elsevier Ltd.

  16. CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis

    Romme Christensen, Jeppe; Börnsen, Lars; Khademi, Mohsen

    2013-01-01

    BACKGROUND: The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage. OBJECTIVES: To study cerebrospinal fluid (CSF) biomarkers...... and clarify whether inflammation and axonal damage are associated in progressive MS. METHODS: Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing-remitting (RRMS) and 20 non-inflammatory neurological disease...... (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year. RESULTS: Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13...

  17. Melt damage simulation of W-macrobrush and divertor gaps after multiple transient events in ITER

    Bazylev, B.N. [Forschungszentrum Karlsruhe, IHM, P.O. Box 3640, 76021 Karlsruhe (Germany)]. E-mail: bazylev@ihm.fzk.de; Janeschitz, G. [Forschungszentrum Karlsruhe, Fusion, P.O. Box 3640, 76021 Karlsruhe (Germany); Landman, I.S. [Forschungszentrum Karlsruhe, IHM, P.O. Box 3640, 76021 Karlsruhe (Germany); Loarte, A. [EFDA-CSU, Max-Planck-Institut fuer Plasmaphysik, D-85748 Garching (Germany); Pestchanyi, S.E. [Forschungszentrum Karlsruhe, IHM, P.O. Box 3640, 76021 Karlsruhe (Germany)

    2007-06-15

    Tungsten in the form of macrobrush structure is foreseen as one of two candidate materials for the ITER divertor and dome. In ITER, even for moderate and weak ELMs when a thin shielding layer does not protect the armour surface from the dumped plasma, the main mechanisms of metallic target damage remain surface melting and melt motion erosion, which determines the lifetime of the plasma facing components. The melt erosion of W-macrobrush targets with different geometry of brush surface under the heat loads caused by weak ELMs is numerically investigated using the modified code MEMOS. The optimal angle of brush surface inclination that provides a minimum of surface roughness is estimated for given inclination angles of impacting plasma stream and given parameters of the macrobrush target. For multiple disruptions the damage of the dome gaps and the gaps between divertor cassettes caused by the radiation impact is estimated.

  18. Melt damage simulation of W-macrobrush and divertor gaps after multiple transient events in ITER

    Bazylev, B. N.; Janeschitz, G.; Landman, I. S.; Loarte, A.; Pestchanyi, S. E.

    2007-06-01

    Tungsten in the form of macrobrush structure is foreseen as one of two candidate materials for the ITER divertor and dome. In ITER, even for moderate and weak ELMs when a thin shielding layer does not protect the armour surface from the dumped plasma, the main mechanisms of metallic target damage remain surface melting and melt motion erosion, which determines the lifetime of the plasma facing components. The melt erosion of W-macrobrush targets with different geometry of brush surface under the heat loads caused by weak ELMs is numerically investigated using the modified code MEMOS. The optimal angle of brush surface inclination that provides a minimum of surface roughness is estimated for given inclination angles of impacting plasma stream and given parameters of the macrobrush target. For multiple disruptions the damage of the dome gaps and the gaps between divertor cassettes caused by the radiation impact is estimated.

  19. Melt damage simulation of W-macrobrush and divertor gaps after multiple transient events in ITER

    Bazylev, B.N.; Janeschitz, G.; Landman, I.S.; Loarte, A.; Pestchanyi, S.E.

    2007-01-01

    Tungsten in the form of macrobrush structure is foreseen as one of two candidate materials for the ITER divertor and dome. In ITER, even for moderate and weak ELMs when a thin shielding layer does not protect the armour surface from the dumped plasma, the main mechanisms of metallic target damage remain surface melting and melt motion erosion, which determines the lifetime of the plasma facing components. The melt erosion of W-macrobrush targets with different geometry of brush surface under the heat loads caused by weak ELMs is numerically investigated using the modified code MEMOS. The optimal angle of brush surface inclination that provides a minimum of surface roughness is estimated for given inclination angles of impacting plasma stream and given parameters of the macrobrush target. For multiple disruptions the damage of the dome gaps and the gaps between divertor cassettes caused by the radiation impact is estimated

  20. [Operative treatment strategies for multiple trauma patients : early total care versus damage control].

    Klüter, T; Lippross, S; Oestern, S; Weuster, M; Seekamp, A

    2013-09-01

    The treatment of multiple trauma patients is a great challenge for an interdisciplinary team. After preclinical care and subsequent treatment in the emergency room the order of the interventions is prioritized depending of the individual risk stratification. For planning the surgery management it is essential to distinguish between absolutely essential operations to prevent life-threatening situations for the patient and interventions with shiftable indications, depending on the general condition of the patient. All interventions need to be done without causing significant secondary damage to prohibit hyperinflammation and systemic inflammatory response syndrome. The challenge consists in determination of the appropriate treatment at the right point in time. In general the early primary intervention, early total care, is differentiated from the damage control concept.

  1. Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli

    Shikazono, Naoya, E-mail: shikazono.naoya@jaea.go.jp [Japan Atomic Energy Agency, Advanced Research Science Center, 2-4 Shirakata-Shirane, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); O' Neill, Peter [Gray Institute for Radiation Oncology and Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2009-10-02

    Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Using a plasmid-based assay in Escherichia coli, we previously found significantly higher mutation frequencies for bistranded clusters containing 7,8-dihydro-8-oxoguanine (8-oxoG) and 5,6-dihydrothymine (DHT) than for either a single 8-oxoG or a single DHT in wild type and in glycosylase-deficient strains of E. coli. This indicates that the removal of an 8-oxoG from a clustered damage site is most likely retarded compared to the removal of a single 8-oxoG. To gain further insights into the processing of bistranded base lesions, several potential repair intermediates following 8-oxoG removal were assessed. Clusters, such as DHT + apurinic/apyrimidinic (AP) and DHT + GAP have relatively low mutation frequencies, whereas clusters, such as AP + AP or GAP + AP, significantly reduce the number of transformed colonies, most probably through formation of a lethal double strand break (DSB). Bistranded AP sites placed 3' to each other with various interlesion distances also blocked replication. These results suggest that bistranded base lesions, i.e., single base lesions on each strand, but not clusters containing only AP sites and strand breaks, are repaired in a coordinated manner so that the formation of DSBs is avoided. We propose that, when either base lesion is initially excised from a bistranded base damage site, the remaining base lesion will only rarely be converted into an AP site or a single strand break in vivo.

  2. Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli

    Shikazono, Naoya; O'Neill, Peter

    2009-01-01

    Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Using a plasmid-based assay in Escherichia coli, we previously found significantly higher mutation frequencies for bistranded clusters containing 7,8-dihydro-8-oxoguanine (8-oxoG) and 5,6-dihydrothymine (DHT) than for either a single 8-oxoG or a single DHT in wild type and in glycosylase-deficient strains of E. coli. This indicates that the removal of an 8-oxoG from a clustered damage site is most likely retarded compared to the removal of a single 8-oxoG. To gain further insights into the processing of bistranded base lesions, several potential repair intermediates following 8-oxoG removal were assessed. Clusters, such as DHT + apurinic/apyrimidinic (AP) and DHT + GAP have relatively low mutation frequencies, whereas clusters, such as AP + AP or GAP + AP, significantly reduce the number of transformed colonies, most probably through formation of a lethal double strand break (DSB). Bistranded AP sites placed 3' to each other with various interlesion distances also blocked replication. These results suggest that bistranded base lesions, i.e., single base lesions on each strand, but not clusters containing only AP sites and strand breaks, are repaired in a coordinated manner so that the formation of DSBs is avoided. We propose that, when either base lesion is initially excised from a bistranded base damage site, the remaining base lesion will only rarely be converted into an AP site or a single strand break in vivo.

  3. Direct detection and quantification of abasic sites for in vivo studies of DNA damage and repair

    Wang Yanming; Liu Lili; Wu Chunying; Bulgar, Alina; Somoza, Eduardo; Zhu Wenxia; Gerson, Stanton L.

    2009-01-01

    Use of chemotherapeutic agents to induce cytotoxic DNA damage and programmed cell death is a key strategy in cancer treatments. However, the efficacy of DNA-targeted agents such as temozolomide is often compromised by intrinsic cellular responses such as DNA base excision repair (BER). Previous studies have shown that BER pathway resulted in formation of abasic or apurinic/apyrimidinic (AP) sites, and blockage of AP sites led to a significant enhancement of drug sensitivity due to reduction of DNA base excision repair. Since a number of chemotherapeutic agents also induce formation of AP sites, monitoring of these sites as a clinical correlate of drug effect will provide a useful tool in the development of DNA-targeted chemotherapies aimed at blocking abasic sites from repair. Here we report an imaging technique based on positron emission tomography (PET) that allows for direct quantification of AP sites in vivo. For this purpose, positron-emitting carbon-11 has been incorporated into methoxyamine ([ 11 C]MX) that binds covalently to AP sites with high specificity. The binding specificity of [ 11 C]MX for AP sites was demonstrated by in vivo blocking experiments. Using [ 11 C]MX as a radiotracer, animal PET studies have been conducted in melanoma and glioma xenografts for quantification of AP sites. Following induction of AP sites by temozolomide, both tumor models showed significant increase of [ 11 C]MX uptake in tumor regions in terms of radioactivity concentration as a function of time, which correlates well with conventional aldehyde reactive probe (ARP)-based bioassays for AP sites.

  4. [Modular risk analysis for assessing multiple waste sites]: Proceedings

    Whelan, G.

    1994-01-01

    This document contains proceedings from the Integrated Planning Workshop from Strategic Planning to Baselining and Other Objectives. Topics discussed include: stakeholder involvement; regulations; future site use planning; site integration and baseline methods; risk analysis in decision making; land uses; and economics in decision making. Individual records have been processed separately for the database

  5. Damage threshold of lithium niobate crystal under single and multiple femtosecond laser pulses: theoretical and experimental study

    Meng, Qinglong; Zhang, Bin; Zhong, Sencheng; Zhu, Liguo

    2016-01-01

    The damage threshold of lithium niobate crystal under single and multiple femtosecond laser pulses has been studied theoretically and experimentally. Firstly, the model for the damage threshold prediction of crystal materials based on the improved rate equation has been proposed. Then, the experimental measure method of the damage threshold of crystal materials has been given in detail. On the basis, the variation of the damage threshold of lithium niobate crystal with the pulse duration has also been analyzed quantitatively. Finally, the damage threshold of lithium niobate crystal under multiple laser pulses has been measured and compared to the theoretical results. The results show that the transmittance of lithium niobate crystal is almost a constant when the laser pulse fluence is relative low, whereas it decreases linearly with the increase in the laser pulse fluence below the damage threshold. The damage threshold of lithium niobate crystal increases with the increase in the duration of the femtosecond laser pulse. And the damage threshold of lithium niobate crystal under multiple laser pulses is obviously lower than that irradiated by a single laser pulse. The theoretical data fall in good agreement with the experimental results. (orig.)

  6. Risk Prediction Models for Other Cancers or Multiple Sites

    Developing statistical models that estimate the probability of developing other multiple cancers over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. Miscoding and mutagenic properties of 8-oxoguanine and abasic sites: Ubiquitous lesions in damaged DNA

    Grollman, A.P.; Takeshita, Masaru

    1995-01-01

    More than twenty oxidatively-damaged bases, including 8-oxoguanine, have been found to occur in genomic DNA. Some of these lesions block DNA replication and are potentially lethal; others generate mutations which can initiate carcinogenesis and promote cellular aging. In this report, the authors focus attention on the mutagenicity and repair of 8-oxoguanine. Kasai and Nishimura's discovery that hydroxyl radicals react with guanine residues in DNA to form 8-oxoguanine and the development of sensitive methods for the detection and quantitation of this modified base led to the observation that approximately 1 in 10 5 guanine residues in mammalian DNA are oxidized at the C-8 position. DNA containing 8-oxoguanine and synthetic analogs of the abasic site have been used to investigate the miscoding and mutagenic potential of these ubiquitous lesions. Studies in the laboratory were facilitated by the development of solid state synthetic methods by which these lesions could be introduced at defined positions in DNA. In this paper, the authors review studies in which 8-oxoguanine and abasic sites have been used in model systems to explore various early events in the replication of selectively damaged DNA

  8. Time-dependent evolution of the excavation damaged zone in the argillaceous Tournemire site

    Rejeb, A.; Cabrera, J. [Institut de Radioprotection et de Surete Nucleaire (IRSN/DEI/SARG), Lab. d' Etude Hydrodynamique et Geotechnique, 92 - Fontenay-aux-Roses (France)

    2006-07-01

    The experimental Tournemire site enables the assessment of the Excavation Damaged Zones (EDZ) around three structures excavated in argilites: the century-old tunnel, the ten year-old east and west galleries, and the three year-old main gallery. This paper discusses the main experimental results concerning the EDZ characterisation and their interpretation. EDZ fracture analyses from the galleries (cartography) and the radial boreholes (core analyses) allow for accurate structural characterisation of the EDZs. The tunnel has an EDZ with dense, homogeneous fracturing parallel to the wall, resembling onion skins. However, the new galleries do not have an EDZ similar to that of the tunnel. Unsaturated micro-cracks, mainly parallel to the bedding planes are observed on the non covered walls of each gallery. The extent of the EDZ does not seem to be affected by the age of the structure. It is approximately 20 % of the mean radius of the structure. Based on the modelling and experimental characterisation work completed, it is considered that the EDZ in this argillaceous Tournemire site is due to a deferred failure. At first time, when the wall of the structures are not covered the desaturation/re-saturation phenomena induced a tensile failure around the new galleries. During the time, these desaturation/re-saturation phenomena cause a gradual weakening of the material. The EDZ tunnel fractures are explained by this possible hydric damage and a decreasing mechanical strength with the time. These assumptions remain to be confirmed through coupled numerical modelling in unsaturated medium. (authors)

  9. Time-dependent evolution of the excavation damaged zone in the argillaceous Tournemire site

    Rejeb, A.; Cabrera, J.

    2006-01-01

    The experimental Tournemire site enables the assessment of the Excavation Damaged Zones (EDZ) around three structures excavated in argilites: the century-old tunnel, the ten year-old east and west galleries, and the three year-old main gallery. This paper discusses the main experimental results concerning the EDZ characterisation and their interpretation. EDZ fracture analyses from the galleries (cartography) and the radial boreholes (core analyses) allow for accurate structural characterisation of the EDZs. The tunnel has an EDZ with dense, homogeneous fracturing parallel to the wall, resembling onion skins. However, the new galleries do not have an EDZ similar to that of the tunnel. Unsaturated micro-cracks, mainly parallel to the bedding planes are observed on the non covered walls of each gallery. The extent of the EDZ does not seem to be affected by the age of the structure. It is approximately 20 % of the mean radius of the structure. Based on the modelling and experimental characterisation work completed, it is considered that the EDZ in this argillaceous Tournemire site is due to a deferred failure. At first time, when the wall of the structures are not covered the desaturation/re-saturation phenomena induced a tensile failure around the new galleries. During the time, these desaturation/re-saturation phenomena cause a gradual weakening of the material. The EDZ tunnel fractures are explained by this possible hydric damage and a decreasing mechanical strength with the time. These assumptions remain to be confirmed through coupled numerical modelling in unsaturated medium. (authors)

  10. Fluids with highly directional attractive forces. III. Multiple attraction sites

    Wertheim, M.S.

    1986-01-01

    The authors derive a reformulation of statistical thermodynamics for fluids of molecules which interact by highly directional attraction. The molecular model consists of a repulsive core and several sites of very short-ranged attraction. The authors explore the relationship between graph cancellation in the fugacity expansion and three types of steric incompatibility between repulsive and attractive interactions involving several molecules. The steric effects are used to best advantage in a limited regrouping of bonds. This controls the density parameters which appear when articulation points are eliminated in the graphical representation. Each density parameter is a singlet density for a species consisting of molecules with a specified set of sites bonded. The densities satisfy subsidiary conditions of internal consistency. These conditions are equivalent to a minimization of the Helmholtz free energy A. Graphical expressions for A and for the pressure are derived. Analogs of the s-particle direct correlation functions and of the Ornstein-Zernike equation are found

  11. The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

    Averbeck, D.; Boucher, D.

    2006-01-01

    Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using 137 Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage into

  12. The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

    Averbeck, D.; Boucher, D. [Institut Curie-Section de Recherche, UMR2027 CNRS, LCR-V28 du CEA, Centre Universitaire, 91405 Orsay Cedex (France)

    2006-07-01

    Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using {sup 137}Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage

  13. Targeting Ongoing DNA Damage in Multiple Myeloma: Effects of DNA Damage Response Inhibitors on Plasma Cell Survival

    Ana Belén Herrero

    2017-05-01

    Full Text Available Human myeloma cell lines (HMCLs and a subset of myeloma patients with poor prognosis exhibit high levels of replication stress (RS, leading to DNA damage. In this study, we confirmed the presence of DNA double-strand breaks (DSBs in several HMCLs by measuring γH2AX and RAD51 foci and analyzed the effect of various inhibitors of the DNA damage response on MM cell survival. Inhibition of ataxia telangiectasia and Rad3-related protein (ATR, the main kinase mediating the response to RS, using the specific inhibitor VE-821 induced more cell death in HMCLs than in control lymphoblastoid cells and U266, an HMCL with a low level of DNA damage. The absence of ATR was partially compensated by ataxia telangiectasia-mutated protein (ATM, since chemical inhibition of both kinases using VE-821 and KU-55933 significantly increased the death of MM cells with DNA damage. We found that ATM and ATR are involved in DSB repair by homologous recombination (HR in MM. Inhibition of both kinases resulted in a stronger inhibition that may underlie cell death induction, since abolition of HR using two different inhibitors severely reduced survival of HMCLs that exhibit DNA damage. On the other hand, inhibition of the other route involved in DSB repair, non-homologous end joining (NHEJ, using the DNA-PK inhibitor NU7441, did not affect MM cell viability. Interestingly, we found that NHEJ inhibition did not increase cell death when HR was simultaneously inhibited with the RAD51 inhibitor B02, but it clearly increased the level of cell death when HR was inhibited with the MRE11 inhibitor mirin, which interferes with recombination before DNA resection takes place. Taken together, our results demonstrate for the first time that MM cells with ongoing DNA damage rely on an intact HR pathway, which thereby suggests therapeutic opportunities. We also show that inhibition of HR after the initial step of end resection might be more appropriate for inducing MM cell death, since it

  14. Spectroscopic study of site selective DNA damage induced by intense soft X-rays

    Fujii, K

    2003-01-01

    To investigate the mechanisms of DNA damage induced by direct photon impact, we observed the near edge X-ray absorption fine structures (NEXAFS) of DNA nucleobases using monochromatic synchrotron soft X-rays around nitrogen and oxygen K-shell excitation regions. Each spectrum obtained has unique structure corresponding to pi* excitation of oxygen or nitrogen 1s electron. These aspects open a way of nucleobase-selective photo-excitation in a DNA molecule using high resolution monochromatized soft X-rays. From the analysis of polarization-dependent intensities of the pi* resonance peak, it is clarified that adenine, guanine an uracil form orientated surface structure. Furthermore from the direct measurement of positive ions desorbed from photon irradiated DNA components, it is revealed that the sugar moiety is a fragile site in a DNA molecule. (author)

  15. Nonenzymatic glycosylation of human hemoglobin at multiple sites

    Shapiro, R.; McManus, M.; Garrick, L.; McDonald, M.J.; Bunn, H.F.

    1979-01-01

    The most abundant minor hemoglobin component of human hemolysate is Hb A1c, which has glucose bound to the N-terminus of the beta chain by a ketoamine linkage. Hb A1c is formed slowly and continuously throughout the 120 day lifespan of the red cell. It can be synthesized in vitro by incubating purified hemoglobin with 14C-glucose. Other minor components, Hb A1a1 and Hb A1a2 are adducts of sugar phosphates at the N-terminus of the beta chain. Hb A1b contains an unidentified nonphosphorylated sugar at the beta N-terminus. In addition, a significant portion of the major hemoglobin component (Hb Ao) is also glycosylated by a glucose ketoamine linkage at other sites on the molecule, including the N-terminus of the alpha chain and the epsilon-amino group of several lysine residues on both the alpha and the beta chains. The results indicate that the interaction of glucose and hemoglobin is rather nonspecific and suggests that other proteins are modified in a similar fashion

  16. Assessment of Multiple Types of DNA Damage in Human Placentas from Smoking and Non-smoking Women in the Czech Republic

    Margaret Pratt, M.; King, Leon C.; Adams, Linda D.; John, Kaarthik; Sirajuddin, Paul; Olivero, Ofelia A.; Manchester, David K.; Sram, Radim J.; DeMarini, David M.; Poirier, Miriam C.

    2010-01-01

    Three classes of DNA damage were assessed in human placentas collected (in 2000-4) from 51 women living in the Teplice region of the Czech Republic, a mining area considered to have some of the worst environmental pollution in Europe in the 1980s. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were localized and semiquantified using immunohistochemistry (IHC) and the Automated Cellular Imaging System (ACIS). More generalized DNA damage was measured both by 32P-postlabeling and by abasic (AB) site analysis. Placenta stained with antiserum elicited against DNA modified with r7, t8-dihydroxy-t-9, 10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) revealed PAH-DNA adduct localization in nuclei of the cytotrophoblast (CT) cells and syncytiotrophoblast (ST) knots lining the chorionic villi. The highest levels of DNA damage, 49–312 PAH-DNA adducts/108 nucleotides, were found by IHC/ACIS in 14 immediately-fixed placenta samples. An additional 37 placenta samples were stored frozen before fixation and embedding, and because PAH-DNA adducts were largely undetectable in these samples, freezing was implicated in the loss of IHC signal. The same placentas (n = 37) contained 1.7 – 8.6 stable/bulky DNA adducts/108 nucleotides and 0.6 – 47.2 AB sites/105 nucleotides. For all methods there was no correlation among types of DNA damage and no difference in extent of DNA damage between smokers and non-smokers. Therefore, the data show that DNA from placentas obtained in Teplice contained multiple types of DNA damage, which likely arose from various environmental exposures. In addition, PAH-DNA adducts were present at high concentrations in the CT cells and ST knots of the chorionic villi. PMID:20839217

  17. Site response, shallow shear-wave velocity, and damage in Los Gatos, California, from the 1989 Loma Prieta earthquake

    Hartzell, S.; Carver, D.; Williams, R.A.

    2001-01-01

    Aftershock records of the 1989 Loma Prieta earthquake are used to calculate site response in the frequency band of 0.5-10 Hz at 24 locations in Los Gatos, California, on the edge of the Santa Clara Valley. Two different methods are used: spectral ratios relative to a reference site on rock and a source/site spectral inversion method. These two methods complement each other and give consistent results. Site amplification factors are compared with surficial geology, thickness of alluvium, shallow shear-wave velocity measurements, and ground deformation and structural damage resulting from the Loma Prieta earthquake. Higher values of site amplification are seen on Quaternary alluvium compared with older Miocene and Cretaceous units of Monterey and Franciscan Formation. However, other more detailed correlations with surficial geology are not evident. A complex pattern of alluvial sediment thickness, caused by crosscutting thrust faults, is interpreted as contributing to the variability in site response and the presence of spectral resonance peaks between 2 and 7 Hz at some sites. Within the range of our field measurements, there is a correlation between lower average shear-wave velocity of the top 30 m and 50% higher values of site amplification. An area of residential homes thrown from their foundations correlates with high site response. This damage may also have been aggravated by local ground deformation. Severe damage to commercial buildings in the business district, however, is attributed to poor masonry construction.

  18. Detection and quantification of regional cortical gray matter damage in multiple sclerosis utilizing gradient echo MRI

    Jie Wen

    2015-01-01

    Full Text Available Cortical gray matter (GM damage is now widely recognized in multiple sclerosis (MS. The standard MRI does not reliably detect cortical GM lesions, although cortical volume loss can be measured. In this study, we demonstrate that the gradient echo MRI can reliably and quantitatively assess cortical GM damage in MS patients using standard clinical scanners. High resolution multi-gradient echo MRI was used for regional mapping of tissue-specific MRI signal transverse relaxation rate values (R2* in 10 each relapsing–remitting, primary-progressive and secondary-progressive MS subjects. A voxel spread function method was used to correct artifacts induced by background field gradients. R2* values from healthy controls (HCs of varying ages were obtained to establish baseline data and calculate ΔR2* values – age-adjusted differences between MS patients and HC. Thickness of cortical regions was also measured in all subjects. In cortical regions, ΔR2* values of MS patients were also adjusted for changes in cortical thickness. Symbol digit modalities (SDMT and paced auditory serial addition (PASAT neurocognitive tests, as well as Expanded Disability Status Score, 25-foot timed walk and nine-hole peg test results were also obtained on all MS subjects. We found that ΔR2* values were lower in multiple cortical GM and normal appearing white matter (NAWM regions in MS compared with HC. ΔR2* values of global cortical GM and several specific cortical regions showed significant (p < 0.05 correlations with SDMT and PASAT scores, and showed better correlations than volumetric measures of the same regions. Neurological tests not focused on cognition (Expanded Disability Status Score, 25-foot timed walk and nine-hole peg tests showed no correlation with cortical GM ΔR2* values. The technique presented here is robust and reproducible. It requires less than 10 min and can be implemented on any MRI scanner. Our results show that quantitative tissue-specific R2

  19. Unveiled: Interrogating the Use of Applied Drama in Multiple and Specific Sites

    Daboo, Jerri

    2007-01-01

    This article examines a view of site through postcolonial feminism to suggest that multiple and contradictory discourses of culture, location, gender and context are all vital in an understanding of a specific site when working with a community. These views are applied to a project undertaken with a group of Asian women in Britain exploring issues…

  20. Decommissioning strategy and schedule for a multiple reactor nuclear power plant site

    Monteiro, Deiglys Borges; Moreira, Joao M.L.; Maiorino, Jose Rubens, E-mail: deiglys.monteiro@ufabc.edu.br, E-mail: joao.moreira@ufabc.edu.br, E-mail: joserubens.maiorino@ufabc.edu.br [Universidade Federal do ABC (CECS/UFABC), Santo Andre, SP (Brazil). Centro de Engenharia, Modelagem e Ciencias Aplicadas

    2015-07-01

    The decommissioning is an important part of every Nuclear Power Plant life cycle gaining importance when there are more than one plant at the same site due to interactions that can arise from the operational ones and a decommissioning plant. In order to prevent undesirable problems, a suitable strategy and a very rigorous schedule should implemented and carried. In this way, decommissioning tasks such as fully decontamination and dismantling of activated and contaminated systems, rooms and structures could be delayed, posing as an interesting option to multiple reactor sites. The present work aims to purpose a strategy and a schedule for the decommissioning of a multiple reactor site highlighting the benefits of delay operational tasks and constructs some auxiliary services in the site during the stand by period of the shutdown plants. As a case study, will be presented a three-reactor site which the decommissioning process actually is in planning stage and that should start in the next decade. (author)

  1. Decommissioning strategy and schedule for a multiple reactor nuclear power plant site

    Monteiro, Deiglys Borges; Moreira, Joao M.L.; Maiorino, Jose Rubens

    2015-01-01

    The decommissioning is an important part of every Nuclear Power Plant life cycle gaining importance when there are more than one plant at the same site due to interactions that can arise from the operational ones and a decommissioning plant. In order to prevent undesirable problems, a suitable strategy and a very rigorous schedule should implemented and carried. In this way, decommissioning tasks such as fully decontamination and dismantling of activated and contaminated systems, rooms and structures could be delayed, posing as an interesting option to multiple reactor sites. The present work aims to purpose a strategy and a schedule for the decommissioning of a multiple reactor site highlighting the benefits of delay operational tasks and constructs some auxiliary services in the site during the stand by period of the shutdown plants. As a case study, will be presented a three-reactor site which the decommissioning process actually is in planning stage and that should start in the next decade. (author)

  2. Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response.

    Idit Hazan

    2016-12-01

    Full Text Available The role of common fragile sites (CFSs in cancer remains controversial. Two main views dominate the discussion: one suggests that CFS loci are hotspots of genomic instability leading to inactivation of genes encoded within them, while the other view proposes that CFSs are functional units and that loss of the encoded genes confers selective pressure, leading to cancer development. The latter view is supported by emerging evidence showing that expression of a given CFS is associated with genome integrity and that inactivation of CFS-resident tumor suppressor genes leads to dysregulation of the DNA damage response (DDR and increased genomic instability. These two viewpoints of CFS function are not mutually exclusive but rather coexist; when breaks at CFSs are not repaired accurately, this can lead to deletions by which cells acquire growth advantage because of loss of tumor suppressor activities. Here, we review recent advances linking some CFS gene products with the DDR, genomic instability, and carcinogenesis and discuss how their inactivation might represent a selective advantage for cancer cells.

  3. Structural health monitoring and damage assessment using measured FRFs from multiple sensors. Part I. The indicator of correlation criteria

    Zang, C.; Friswell, M.I. [Dept. of Aerospace Engineering, Univ. of Bristol, Bristol (United Kingdom); Imregun, M. [Dept. of Mechanical Engineering, Imperial Coll., London (United Kingdom)

    2003-07-01

    This paper presents two criteria for correlating measured frequency responses from multiple sensors and proposes to use them as indicators for structural damage detection. The first criterion is a global shape correlation (GSC) function that is sensitive to mode shape differences but not to relative scales. The second criterion, a global amplitude correlation (GAC) function, is based on actual response amplitudes. Both correlation criteria are a function of frequency and uniquely map a set of complex responses to a real scalar between zero and unity. The averaged integrations of GSC and GAC functions along the frequency points over the measurement range, also called damage indicators, are used to describe the correlation between two sets of vibration data. When a structure state remains unchanged, both correlation criteria are as close to unity simultaneously. Otherwise, the correlation with the reference data will be decreased with changes of structure states. Using GSC and GAC functions has the advantage of being able to deal with incomplete measurements. Also, all available response data are used and hence there is no critical selection of frequency points for damage detection. The above correlation criteria were applied to a bookshelf structure and various cases such as undamaged states, damage locations (single and multiple), damage levels, as well as environmental variability are discussed. As expected, it was found that indicators of correlation criteria were able to identify all various cases correctly. (orig.)

  4. Surface-based reconstruction and diffusion MRI in the assessment of gray and white matter damage in multiple sclerosis

    Caffini, Matteo; Bergsland, Niels; LaganÃ, Marcella; Tavazzi, Eleonora; Tortorella, Paola; Rovaris, Marco; Baselli, Giuseppe

    2014-03-01

    Despite advances in the application of nonconventional MRI techniques in furthering the understanding of multiple sclerosis pathogenic mechanisms, there are still many unanswered questions, such as the relationship between gray and white matter damage. We applied a combination of advanced surface-based reconstruction and diffusion tensor imaging techniques to address this issue. We found significant relationships between white matter tract integrity indices and corresponding cortical structures. Our results suggest a direct link between damage in white and gray matter and contribute to the notion of gray matter loss relating to clinical disability.

  5. Modeling the yield of double-strand breaks due to formation of multiply damaged sites in irradiated plasmid DNA

    Xapsos, M.A.; Pogozelski, W.K.

    1996-01-01

    Although double-strand breaks have long been recognized as an important type of DNa lesion, it is well established that this broad class of damage does not correlate well with indicators of the effectiveness of radiation as the cellular level. Assays of double-strand breaks do not distinguish the degree of complexity or clustering of singly damaged sites produced in a single energy deposition event, which is currently hypothesized to be key to understanding cellular end points. As a step toward this understanding, double-strand breaks that are formed proportionally to dose in plasmid DNA are analyzed from the mechanistic aspect to evaluate the yield that arises from multiply damaged sites as hypothesized by Ward (Prog. Nucleic Acid Res. Mol. Biol. 35, 95-125, 1988) and Goodhead (Int. J. Radiat. Biol. 65, 7-17, 1994) as opposed to the yield that arises form single hydroxyl radicals as hypothesized by Siddiqi and Bothe (Radiat. Res. 112, 449-463, 1987). For low-LET radiation such as γ rays, the importance of multiply damaged sites is shown to increase with the solution's hydroxyl radical scavenging capacity. For moderately high-LET radiation such as 100 keV/μm helium ions, a much different behavior is observed. In this case, a large fraction of double-strand breaks are formed as a result of multiply damaged sties over a broad range of scavenging conditions. Results also indicate that the RBE for common cellular end points correlates more closely with the RBE for common cellular end points correlates more closely with the RBE for multiply damaged sites than with the RBE for total double-strand breaks over a range of LET up to at least 100 keV/μm. 22 refs., 3 figs., 2 tabs

  6. Multiple Site-Directed and Saturation Mutagenesis by the Patch Cloning Method.

    Taniguchi, Naohiro; Murakami, Hiroshi

    2017-01-01

    Constructing protein-coding genes with desired mutations is a basic step for protein engineering. Herein, we describe a multiple site-directed and saturation mutagenesis method, termed MUPAC. This method has been used to introduce multiple site-directed mutations in the green fluorescent protein gene and in the moloney murine leukemia virus reverse transcriptase gene. Moreover, this method was also successfully used to introduce randomized codons at five desired positions in the green fluorescent protein gene, and for simple DNA assembly for cloning.

  7. Electric properties and carrier multiplication in breakdown sites in multi-crystalline silicon solar cells

    Schneemann, Matthias; Carius, Reinhard; Rau, Uwe [IEK5-Photovoltaics, Forschungszentrum Jülich, Jülich 52425 (Germany); Kirchartz, Thomas, E-mail: t.kirchartz@fz-juelich.de [IEK5-Photovoltaics, Forschungszentrum Jülich, Jülich 52425 (Germany); Faculty of Engineering and CENIDE, University of Duisburg-Essen, Carl-Benz-Str. 199, Duisburg 47057 (Germany)

    2015-05-28

    This paper studies the effective electrical size and carrier multiplication of breakdown sites in multi-crystalline silicon solar cells. The local series resistance limits the current of each breakdown site and is thereby linearizing the current-voltage characteristic. This fact allows the estimation of the effective electrical diameters to be as low as 100 nm. Using a laser beam induced current (LBIC) measurement with a high spatial resolution, we find carrier multiplication factors on the order of 30 (Zener-type breakdown) and 100 (avalanche breakdown) as new lower limits. Hence, we prove that also the so-called Zener-type breakdown is followed by avalanche multiplication. We explain that previous measurements of the carrier multiplication using thermography yield results higher than unity, only if the spatial defect density is high enough, and the illumination intensity is lower than what was used for the LBIC method. The individual series resistances of the breakdown sites limit the current through these breakdown sites. Therefore, the measured multiplication factors depend on the applied voltage as well as on the injected photocurrent. Both dependencies are successfully simulated using a series-resistance-limited diode model.

  8. Damage to Preheated Tungsten Targets after Multiple Plasma Impacts Simulating ITER ELMs

    Garkusha, I.E.; Bandura, A.N.; Byrka, O.V.; Chebotarev, V.V.; Makhlay, V.A.; Tereshin, V.I. [Kharkov Inst. of Physics and Technology, Inst. of Plasma Physics of National Science Center, Akademicheskaya street, 1, 61108 Kharkov (Ukraine); Landman, I.; Pestchanyi, S. [FZK-Forschungszentrum Karlsruhe, Association Euratom-FZK, Technik und Umwelt, Postfach 3640, D-7602 1 Karlsruhe (Germany)

    2007-07-01

    Full text of publication follows: The energy loads onto ITER divertor surfaces associated with the Type I ELMs are expected to be up to 1 MJ/m{sup 2} during 0.1-0.5 ms, with the number of pulses about 103 per discharge. Tungsten is a candidate material for major part of the surface, but its brittleness can result in substantial macroscopic erosion after the repetitive heat loads. To minimize the brittle destruction, tungsten may be preheated above the ductile-to-brittle transition temperature. In this work the behavior of preheated tungsten targets under repetitive ELM-like plasma pulses is studied in simulation experiments with the quasi-stationary plasma accelerator QSPA Kh-50. The targets have been exposed up to 450 pulses of the duration 0.25 ms and the heat loads either 0.45 MJ/m{sup 2} or 0.75 MJ/m{sup 2}, which is respectively below and above the melting threshold. During the exposures the targets were permanently kept preheated at 650 deg. C by a heater at target backside. In the course of exposures the irradiated surfaces were examined after regular numbers of pulses using the SEM and the optical microscopy. The profilometry, XRD, microhardness and weight loss measurements have been performed, as well as comparisons of surface damages after the heat loads both below and above the melting threshold. It is obtained that macro-cracks do not develop on the preheated surface. After the impacts with surface melting, a fine mesh of intergranular microcracks has appeared. The width of fine intergranular cracks grows with pulse number, achieving 1-1.5 microns after 100 pulses, and after 210 pulses the crack width increases up to 20 microns, which is comparable with grain sizes. Threshold changes in surface morphology resulting in corrugation structures and pits on the surface as well as importance of surface tension in resulted 'micro-brush' structures are discussed. Further evolution of the surface pattern is caused by loss of separated grains on exposed

  9. Moisture migration, microstructure damage and protein structure changes in porcine longissimus muscle as influenced by multiple freeze-thaw cycles.

    Zhang, Mingcheng; Li, Fangfei; Diao, Xinping; Kong, Baohua; Xia, Xiufang

    2017-11-01

    This study investigated the effects of multiple freeze-thaw (F-T) cycles on water mobility, microstructure damage and protein structure changes in porcine longissimus muscle. The transverse relaxation time T 2 increased significantly when muscles were subjected to multiple F-T cycles (Pcycles caused sarcomere shortening, Z line fractures, and I band weakening and also led to microstructural destruction of muscle tissue. The decreased free amino group content and increased dityrosine in myofibrillar protein (MP) revealed that multiple F-T cycles caused protein cross-linking and oxidation. In addition, the results of size exclusion chromatography, circular dichroism spectra, UV absorption spectra, and intrinsic fluorescence spectroscopy indirectly proved that multiple F-T cycles could cause protein aggregation and degradation, α-helix structure disruption, hydrophobic domain exposure, and conformational changes of MP. Overall, repeated F-T cycles changed the protein structure and water distribution within meat. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Categorization skills and recall in brain damaged children: a multiple case study.

    Mello, Claudia Berlim de; Muszkat, Mauro; Xavier, Gilberto Fernando; Bueno, Orlando Francisco Amodeo

    2009-09-01

    During development, children become capable of categorically associating stimuli and of using these relationships for memory recall. Brain damage in childhood can interfere with this development. This study investigated categorical association of stimuli and recall in four children with brain damages. The etiology, topography and timing of the lesions were diverse. Tasks included naming and immediate recall of 30 perceptually and semantically related figures, free sorting, delayed recall, and cued recall of the same material. Traditional neuropsychological tests were also employed. Two children with brain damage sustained in middle childhood relied on perceptual rather than on categorical associations in making associations between figures and showed deficits in delayed or cued recall, in contrast to those with perinatal lesions. One child exhibited normal performance in recall despite categorical association deficits. The present results suggest that brain damaged children show deficits in categorization and recall that are not usually identified in traditional neuropsychological tests.

  11. Some problems of neutron source multiplication method for site measurement technology in nuclear critical safety

    Shi Yongqian; Zhu Qingfu; Hu Dingsheng; He Tao; Yao Shigui; Lin Shenghuo

    2004-01-01

    The paper gives experiment theory and experiment method of neutron source multiplication method for site measurement technology in the nuclear critical safety. The measured parameter by source multiplication method actually is a sub-critical with source neutron effective multiplication factor k s , but not the neutron effective multiplication factor k eff . The experiment research has been done on the uranium solution nuclear critical safety experiment assembly. The k s of different sub-criticality is measured by neutron source multiplication experiment method, and k eff of different sub-criticality, the reactivity coefficient of unit solution level, is first measured by period method, and then multiplied by difference of critical solution level and sub-critical solution level and obtained the reactivity of sub-critical solution level. The k eff finally can be extracted from reactivity formula. The effect on the nuclear critical safety and different between k eff and k s are discussed

  12. Characterization of Multiple Light Damage Paradigms Reveals Regional Differences in Photoreceptor Loss

    Thomas, Jennifer L.; Nelson, Craig M.; Luo, Xixia; Hyde, David R.; Thummel, Ryan

    2012-01-01

    Zebrafish provide an attractive model to study the retinal response to photoreceptor apoptosis due to its remarkable ability to spontaneously regenerate retinal neurons following damage. There are currently two widely used light-induced retinal degeneration models to damage photoreceptors in the adult zebrafish. One model uses constant bright light, whereas the other uses a short exposure to extremely intense ultraviolet light. Although both models are currently used, it is unclear whether th...

  13. Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI

    Madeleine L. Barnett

    2018-01-01

    Conclusion: This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white matter injury.

  14. Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage.

    Deshpande, Ishan; Seeber, Andrew; Shimada, Kenji; Keusch, Jeremy J; Gut, Heinz; Gasser, Susan M

    2017-10-19

    Mec1-Ddc2 (ATR-ATRIP) is a key DNA-damage-sensing kinase that is recruited through the single-stranded (ss) DNA-binding replication protein A (RPA) to initiate the DNA damage checkpoint response. Activation of ATR-ATRIP in the absence of DNA damage is lethal. Therefore, it is important that damage-specific recruitment precedes kinase activation, which is achieved at least in part by Mec1-Ddc2 homodimerization. Here, we report a structural, biochemical, and functional characterization of the yeast Mec1-Ddc2-RPA assembly. High-resolution co-crystal structures of Ddc2-Rfa1 and Ddc2-Rfa1-t11 (K45E mutant) N termini and of the Ddc2 coiled-coil domain (CCD) provide insight into Mec1-Ddc2 homodimerization and damage-site targeting. Based on our structural and functional findings, we present a Mec1-Ddc2-RPA-ssDNA composite structural model. By way of validation, we show that RPA-dependent recruitment of Mec1-Ddc2 is crucial for maintaining its homodimeric state at ssDNA and that Ddc2's recruitment domain and CCD are important for Mec1-dependent survival of UV-light-induced DNA damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Decision-making system for registration and prioritisation of potentially polluted sites adaptable for management of war damage risks

    Lanczos, T.; Pedersen, K. E.

    2002-01-01

    We would like to present a decision-support system developed for identification and storing data concerning with potentially polluted sites and their prioritising. This system could also be adapted for reviewing and evaluation of the war damages. The operation of the system comprises of three procedures: data collection, data handling and the prioritisation of the sites. The relevant data could be collected from different sources, represented mainly by administrative institutions, by sending questionnaires to site owners/operators and by site visits. The collected data should be handled by appropriate database. For this purpose the Contaminated Land Module of the GeoEnviron database application was developed. This application is also designed for providing the preliminary risk assessment scores, which results are used for the site prioritisation. As an example implementation of this system, we shortly present our experiences from testing the system in Slovakia

  16. The site of potato leafroll virus multiplication in its vector, Myzus persicae : an anatomical study

    Ponsen, M.B.

    1972-01-01

    In search of the site of PLRV multiplication in its vector a detailed study was made of the anatomy of the aphid, Myzus persicae SULZ. The findings are summarized in the following lines:

    Alimentary canal

    The most anterior part of

  17. Multiple Site Action Research Case Studies: Practical and Theoretical Benefits and Challenges

    Pereira, Mary Delfin; Vallance, Roger

    2006-01-01

    A curriculum initiative project was implemented in four schools in Singapore over a span of five to six weeks during 2004. The project employed a number of different schools: girls only, boys only and co-educational schools; different levels of performance in a graded situation; multiple teachers and classes within each site; and control and…

  18. Characterization of multiple light damage paradigms reveals regional differences in photoreceptor loss.

    Thomas, Jennifer L; Nelson, Craig M; Luo, Xixia; Hyde, David R; Thummel, Ryan

    2012-04-01

    Zebrafish provide an attractive model to study the retinal response to photoreceptor apoptosis due to its remarkable ability to spontaneously regenerate retinal neurons following damage. There are currently two widely-used light-induced retinal degeneration models to damage photoreceptors in the adult zebrafish. One model uses constant bright light, whereas the other uses a short exposure to extremely intense ultraviolet light. Although both models are currently used, it is unclear whether they differ in regard to the extent of photoreceptor damage or the subsequent regeneration response. Here we report a thorough analysis of the photoreceptor damage and subsequent proliferation response elicited by each individual treatment, as well as by the concomitant use of both treatments. We show a differential loss of rod and cone photoreceptors with each treatment. Additionally, we show that the extent of proliferation observed in the retina directly correlates with the severity of photoreceptor loss. We also demonstrate that both the ventral and posterior regions of the retina are partially protected from light damage. Finally, we show that combining a short ultraviolet exposure followed by a constant bright light treatment largely eliminates the neuroprotected regions, resulting in widespread loss of rod and cone photoreceptors and a robust regenerative response throughout the retina. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Vascular nanomedicine: Site specific delivery of elastin stabilizing therapeutics to damaged arteries

    Sinha, Aditi

    improved resistance to elastolytic digestion. We further show that the same polyphenols interact with monomeric tropoelastin released by the vascular cells and dramatically increasing their self-assembly in-vitro. In addition, we demonstrate the elastogenic ability of these polyphenols in aiding the crosslinking of tropoelastin released by aneurysmal cells converting it into mature elastin. Finally, we developed a nanoparticle system functionalized with elastin antibody on the surface that, upon systemic delivery, can recognize and bind to sites of damaged elastin in the aorta. We are able to show that this nanoparticle system works in representative animal models for MAC and AAA. These nanoparticles demonstrated spatial and functional specificity for degraded elastin. In conclusion, our work is focused on understanding the role of elastin degradation in vascular calcification and aortic aneurysms. We tested approaches to halt elastin degradation and to regenerate elastin in arteries so that homeostasis can be achieved.

  20. Intraintestinal drainage as a damage control surgery adjunct in a hypothermic traumatic shock swine model with multiple bowel perforations.

    Ji, Wu; Ding, Weiwei; Liu, Xingdong; Kao, Xiaomin; Xu, Xingwei; Li, Ning; Li, Jieshou

    2014-11-01

    Temporary bowel ligation (TL) has been proposed to prevent contamination as a damage control procedure in multiple bowel perforations. However, bacteria translocation and intestinal ischemia may develop in a prolonged duration. We here hypothesized that intraintestinal drainage combined with temporary ligation (D-TL) would decrease intestinal injury and improve survivals in a gunshot multiple bowel perforation swine model in the setting of a damage control surgery. The abdomen was shot one time with an experimental modified gun whereas pigs were hemorrhaged to a mean arterial pressure of 40 mm Hg and maintained in shock for 40 min. Cold lactated Ringer solution was gradually infused to induce hypothermia. Animals were randomized to primary anastomosis, TL and intraintestinal D-TL groups (n = 8). Animals were resuscitated for 12 h with the shed blood and lactated Ringer solution. Delayed anastomosis was performed in TL and D-TL animals after resuscitation. Surviving animals were humanely killed 24 h after operation. Systemic hemodynamic parameters were recorded and blood samples were obtained for biochemical assays. Intra-abdominal pressure, portal vein and peripheral vein bacterial cultures, small intestine hematoxylin-eosin staining, and transmission electron microscopy examination were performed at 0, 2, 6, 12, and 24 h after the surgery. All animals suffered extreme physiologic conditions as follows: hypothermia, severe acidosis, hypotension, and depressed cardiac output. Compared with the primary anastomosis and TL group, D-TL animals required less resuscitation fluid, suffered a lower intra-abdominal hypertension and bacterial translocation, normalized lactate levels faster, had lower serum creatine kinase, aspartate aminotransferase levels and tissue TNF-α level, and nuclear factor-kB activations and thus had greater early survival. Compared with primary intestinal anastomosis and TL, rapid bowel ligation combined with intraintestinal drainage as a damage

  1. Chromosome damage in Chinese hamster cells produced by 125I-UdR at the site of its incorporation

    Hughes, W.L.; Weinblatt, A.C.; Prensky, W.

    1978-01-01

    Metaphase chromosomal aberrations were produced by 125 I-labeled iododeoxyuridine ( 125 I-UdR) incorporated into Chinese hamster Don cells at the end of the S-period of the cell cycle. Chromosome damage and the number of autoradiographic silver grains were recorded for whole cells, for chromosome pairs 4 and 5 and for the X and the Y chromosomes. The X and the Y chromosomes, which label late in S, were at least twice as heavily labeled as chromosome pairs 4 and 5 - two readily recognizable autosomes of similar size. The incidence of chromosome damage was at least six times that which would have been expected from equivalent doses of X-rays and the incidence of damage was directly related to the number of silver grains over each chromosome. It is estimated that it takes four to ten disintegrations to produce a visible chromosome aberration. The finding that chromosome damage is localized at the site of the 125 I decay is most readily explained by the high flux of low energy Auger electrons occurring at the site of the decay of the incorporated 125 I atom. (Auth.)

  2. Similar distributions of repaired sites in chromatin of normal and xeroderma pigmentosum variant cells damaged by ultraviolet light

    Cleaver, J.E.

    1979-01-01

    Excision repair of damage from ultraviolet light in both normal and xeroderma pigmentosum variant fibroblasts at early times after irradiation occurred preferentially in regions of DNA accessible to micrococcal nuclease digestion. These regions are predominantly the linker regions between nucleosomes in chromatin. The alterations reported at polymerization and ligation steps of excision repair in the variant are therefore not associated with changes in the relative distributions of repair sites in linker and core particle regions of DNA. (Auth.)

  3. Human embryonic stem cells have enhanced repair of multiple forms of DNA damage

    Maynard, Scott; Swistowska, Anna Maria; Lee, Jae Wan

    2008-01-01

    cells compared with various differentiated murine cells. Using single-cell gel electrophoresis (comet assay) we found that human embryonic stem cells (BG01, I6) have more efficient repair of different types of DNA damage (generated from H2O2, UV-C, ionizing radiation, or psoralen) than human primary...

  4. Structural health monitoring and damage assessment using measured FRFs from multiple sensors. Part II. Decision making with RBF networks

    Zang, C.; Friswell, M.I. [Dept. of Aerospace Engineering, Univ. of Bristol, Bristol (United Kingdom); Imregun, M. [Dept. of Mechanical Engineering, Imperial Coll., London (United Kingdom)

    2003-07-01

    This paper is the second of two papers concerned with structural health monitoring and damage assessment using measured FRFs from multiple sensors, and discusses the decision making technique with radial basis function (RBF) neural networks. In PART 1 of the paper, the correlation criteria showed their capability to indicate various changes to the structure's state. PART 2, presented here, develops the methodology of decision theory to identify precisely all of the structure states. Although, the statistical approach can be used for classification, interpreting the information is difficult. Neural network techniques have been proven to possess many advantages for classification due to their learning ability and good generalization. In this paper, the radial basis function neural network is applied for function approximation and recognition. The key idea is to partition the input space (the indicators of the correlation criteria) into a number of subspaces that are in the form of hyper spheres. Then, the widely used k-mean clustering algorithm was selected as a logical approach to detecting the structure states. A bookshelf structure with measured frequency responses from 24 accelerometers was used to demonstrate the effectiveness of the method. The results show the successful classification of all structure states, for instance, the undamaged and damage states, damage locations and damage levels, and the environmental variability. (orig.)

  5. Automatic progressive damage detection of rotor bar in induction motor using vibration analysis and multiple classifiers

    Cruz-Vega, Israel; Rangel-Magdaleno, Jose; Ramirez-Cortes, Juan; Peregrina-Barreto, Hayde

    2017-01-01

    There is an increased interest in developing reliable condition monitoring and fault diagnosis systems of machines like induction motors; such interest is not only in the final phase of the failure but also at early stages. In this paper, several levels of damage of rotor bars under different load conditions are identified by means of vibration signals. The importance of this work relies on a simple but effective automatic detection algorithm of the damage before a break occurs. The feature extraction is based on discrete wavelet analysis and auto- correlation process. Then, the automatic classification of the fault degree is carried out by a binary classification tree. In each node, com- paring the learned levels of the breaking off correctly identifies the fault degree. The best results of classification are obtained employing computational intelligence techniques like support vector machines, multilayer perceptron, and the k-NN algorithm, with a proper selection of their optimal parameters.

  6. Automatic progressive damage detection of rotor bar in induction motor using vibration analysis and multiple classifiers

    Cruz-Vega, Israel; Rangel-Magdaleno, Jose; Ramirez-Cortes, Juan; Peregrina-Barreto, Hayde [Santa María Tonantzintla, Puebla (Mexico)

    2017-06-15

    There is an increased interest in developing reliable condition monitoring and fault diagnosis systems of machines like induction motors; such interest is not only in the final phase of the failure but also at early stages. In this paper, several levels of damage of rotor bars under different load conditions are identified by means of vibration signals. The importance of this work relies on a simple but effective automatic detection algorithm of the damage before a break occurs. The feature extraction is based on discrete wavelet analysis and auto- correlation process. Then, the automatic classification of the fault degree is carried out by a binary classification tree. In each node, com- paring the learned levels of the breaking off correctly identifies the fault degree. The best results of classification are obtained employing computational intelligence techniques like support vector machines, multilayer perceptron, and the k-NN algorithm, with a proper selection of their optimal parameters.

  7. Correlation between white matter damage and gray matter lesions in multiple sclerosis patients

    Xue-mei Han

    2017-01-01

    Full Text Available We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe (superior frontal, middle frontal, precentral, and orbital gyri, right parietal lobe (postcentral and inferior parietal gyri, right temporal lobe (caudate nucleus, right occipital lobe (middle occipital gyrus, right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

  8. Atuoradiographic detection of multiple sclerosis plaques with an ω3 (peripheral type benzodiazepine) binding site radiogland

    HAUW, J.J.; Sazdovitch, V.; Cornu, P.; Dubois, A.; Benavides, J.; Mac Kenzie, E.; Scatton, B.

    1989-01-01

    In Multiple Sclerosis (MS), the presence of monocyte-macrophages and microglial cells in active plaques is a constant feature. They are numerous at the border of active lesions where they constiture, with other cell types such as lymphocytes and oligodendrocytes the so-called flial wall. Monocyte-macrophages and microglial cells are thought to be directly involved in the process of demyelination. Some macrophages laden with meylin degradation products are also seen in the center of the plaqie, often located in the perivascular cuffs. In addition, astrocytic gliosis occurs in the center of the plaques. As all these cell types are richly endowed with ω3 sites, the feasibility of using ω3 site autoradiagraphy to detect the demyelination plaques in the brain of post-mortem cases of Multiple Sclerosis has been investigated. (Author). 8 refs

  9. Fukushima Daiichi nuclear acccident. Damaged facilities of the site - Situation as on March 2018

    2018-03-01

    After a recall of the events that led to the Fukushima Daiichi accident, this note presents the situation in March 2018 of the actions of control of the damaged facilities and of their effluents. The last part presents the three steps of the facility control recovery plan retained by TEPCO

  10. Visualizing multiple inter-organelle contact sites using the organelle-targeted split-GFP system.

    Kakimoto, Yuriko; Tashiro, Shinya; Kojima, Rieko; Morozumi, Yuki; Endo, Toshiya; Tamura, Yasushi

    2018-04-18

    Functional integrity of eukaryotic organelles relies on direct physical contacts between distinct organelles. However, the entity of organelle-tethering factors is not well understood due to lack of means to analyze inter-organelle interactions in living cells. Here we evaluate the split-GFP system for visualizing organelle contact sites in vivo and show its advantages and disadvantages. We observed punctate GFP signals from the split-GFP fragments targeted to any pairs of organelles among the ER, mitochondria, peroxisomes, vacuole and lipid droplets in yeast cells, which suggests that these organelles form contact sites with multiple organelles simultaneously although it is difficult to rule out the possibilities that these organelle contacts sites are artificially formed by the irreversible associations of the split-GFP probes. Importantly, split-GFP signals in the overlapped regions of the ER and mitochondria were mainly co-localized with ERMES, an authentic ER-mitochondria tethering structure, suggesting that split-GFP assembly depends on the preexisting inter-organelle contact sites. We also confirmed that the split-GFP system can be applied to detection of the ER-mitochondria contact sites in HeLa cells. We thus propose that the split-GFP system is a potential tool to observe and analyze inter-organelle contact sites in living yeast and mammalian cells.

  11. Anaerobic digester systems (ADS) for multiple dairy farms: A GIS analysis for optimal site selection

    Thompson, Ethan; Wang, Qingbin; Li, Minghao

    2013-01-01

    While anaerobic digester systems (ADS) have been increasingly adopted by large dairy farms to generate marketable energy products, like electricity, from animal manure, there is a growing need for assessing the feasibility of regional ADS for multiple farms that are not large enough to capitalize their own ADS. Using geographical information system (GIS) software, this study first identifies potential sites in a dairy region in Vermont, based on geographical conditions, current land use types, and energy distribution infrastructure criteria, and then selects the optimal sites for a given number of ADS, based on the number of dairy farms to be served, the primary energy input to output (PEIO) ratio of ADS, and the existing transportation network. This study suggests that GIS software is a valid technical tool for identifying the potential and optimal sites for ADS. The empirical findings provide useful information for assessing the returns of alternative numbers of ADS in this region, and the research procedures can be modified easily to incorporate any changes in the criteria for this region and can be applied in other regions with different conditions and criteria. - Highlights: • This study examines the feasibility of regional ADS for multiple dairy farms. • GIS is used to identify candidate sites and optimal locations for ADS in a dairy region. • Model includes environmental, social, infrastructure, and energy return criteria. • Empirical analysis provides scenario results on 1–15 ADS in the study region. • Method could be applied to other regions with different conditions and criteria

  12. CosmoQuest Year 1.5: Citizen Scientist Behaviors and Site Usage Across Multiple Projects

    Gugliucci, Nicole E.; Gay, P. L.; Bracey, G.; CosmoQuest Team

    2013-06-01

    CosmoQuest launched as a citizen science portal in January 2012 and has since expanded to include three projects in planetary surface mapping, one completed project searching for KBOs, and several more on the way with various astrophysical science goals. We take a close look at how our users move through the site, how much time they spend on various tasks, project retention rate, and how many use multiple projects on the site. We are also piloting a citizen science motivation survey given to random site users to find out why citizen scientists join new projects and continue to participate. This is part of a larger project using online and real-life interactions to study citizen scientist behaviors, motivations, and learning with a goal of building better community with researchers, volunteers, educators, and developers.

  13. A method of risk assessment for a multi-plant site

    White, R.F.

    1983-06-01

    A model is presented which can be used in conjunction with probabilistic risk assessment to estimate whether a site on which there are several plants (reactors or chemical plants containing radioactive materials) meets whatever risk acceptance criteria or numerical risk guidelines are applied at the time of the assessment in relation to various groups of people and for various sources of risk. The application of the multi-plant site model to the direct and inverse methods of risk assessment is described. A method is proposed by which the potential hazard rating associated with a given plant can be quantified so that an appropriate allocation can be made when assessing the risks associated with each of the plants on a site. (author)

  14. The Effects of Multiple Cold Water Immersions on Indices of Muscle Damage

    Goodall, Stuart; Howatson, Glyn

    2008-01-01

    The aim of this investigation was to elucidate the efficacy of repeated cold water immersions (CWI) in the recovery of exercise induced muscle damage. A randomised group consisting of eighteen males, mean ± s age, height and body mass were 24 ± 5 years, 1.82 ± 0.06 m and 85.7 ± 16.6 kg respectively, completed a bout of 100 drop jumps. Following the bout of damaging exercise, participants were randomly but equally assigned to either a 12 min CWI (15 ± 1 °C; n = 9) group who experienced immersions immediately post-exercise and every 24 h thereafter for the following 3 days, or a control group (no treatment; n = 9). Maximal voluntary contraction (MVC) of the knee extensors, creatine kinase activity (CK), muscle soreness (DOMS), range of motion (ROM) and limb girth were measured pre-exercise and then for the following 96 h at 24 h increments. In addition MVC was also recorded immediately post-exercise. Significant time effects were seen for MVC, CK, DOMS and limb girth (p 0.05). These results suggest that repeated CWI do not enhance recovery from a bout of damaging eccentric contractions. Key pointsCryotherapy, particularly cold water immersions are one of the most common interventions used in order to enhance recovery post-exercise.There is little empirical evidence demonstrating benefits from cold water immersions. Research evidence is equivocal, probably due to methodological inconsistencies.Our results show that the cryotherapy administered did not attenuate any markers of EIMD or enhance the recovery of function.We conclude that repeated cold water immersions are ineffective in the recovery from heavy plyometric exercise and suggest athletes and coaches should use caution before using this intervention as a recovery strategy PMID:24149455

  15. The formation of double-strand breaks at multiply damaged sites is driven by the kinetics of excision/incision at base damage in eukaryotic cells

    Kozmin, S.G.; Sedletska, Y.; Reynaud-Angelin, A.; Sage, E.; Kozmin, S.G.; Sedletska, Y.; Reynaud-Angelin, A.; Sage, E.; Gasparutto, D.

    2009-01-01

    It has been stipulated that repair of clustered DNA lesions may be compromised, possibly leading to the formation of double-strand breaks (DSB) and, thus, to deleterious events. Using a variety of model multiply damaged sites (MDS), we investigated parameters that govern the formation of DSB during the processing of MDS. Duplexes carrying MDS were inserted into replicative or integrative vectors, and used to transform yeast Saccharomyces cerevisiae. Formation of DSB was assessed by a relevant plasmid survival assay. Kinetics of excision/incision and DSB formation at MDS was explored using yeast cell extracts. We show that MDS composed of two uracils or abasic sites, were rapidly incised and readily converted into DSB in yeast cells. In marked contrast, none of the MDS carrying opposed oG and hU separated by 38 bp gave rise to DSB, despite the fact that some of them contained preexisting single-strand break (a 1-nt gap). Interestingly, the absence of DSB formation in this case correlated with slow excision/incision rates of lesions. We propose that the kinetics of the initial repair steps at MDS is a major parameter that direct towards the conversion of MDS into DSB. Data provides clues to the biological consequences of MDS in eukaryotic cells. (authors)

  16. Multi-method Near-surface Geophysical Surveys for Site Response and Earthquake Damage Assessments at School Sites in Washington, USA

    Cakir, R.; Walsh, T. J.; Norman, D. K.

    2017-12-01

    We, Washington Geological Survey (WGS), have been performing multi-method near surface geophysical surveys to help assess potential earthquake damage at public schools in Washington. We have been conducting active and passive seismic surveys, and estimating Shear-wave velocity (Vs) profiles, then determining the NEHRP soil classifications based on Vs30m values at school sites in Washington. The survey methods we have used: 1D and 2D MASW and MAM, P- and S-wave refraction, horizontal-to-vertical spectral ratio (H/V), and 2ST-SPAC to measure Vs and Vp at shallow (0-70m) and greater depths at the sites. We have also run Ground Penetrating Radar (GPR) surveys at the sites to check possible horizontal subsurface variations along and between the seismic survey lines and the actual locations of the school buildings. The seismic survey results were then used to calculate Vs30m for determining the NEHRP soil classifications at school sites, thus soil amplification effects on the ground motions. Resulting shear-wave velocity profiles generated from these studies can also be used for site response and liquefaction potential studies, as well as for improvement efforts of the national Vs30m database, essential information for ShakeMap and ground motion modeling efforts in Washington and Pacific Northwest. To estimate casualties, nonstructural, and structural losses caused by the potential earthquakes in the region, we used these seismic site characterization results associated with structural engineering evaluations based on ASCE41 or FEMA 154 (Rapid Visual Screening) as inputs in FEMA Hazus-Advanced Engineering Building Module (AEBM) analysis. Compelling example surveys will be presented for the school sites in western and eastern Washington.

  17. CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage.

    Romme Christensen, Jeppe; Komori, Mika; von Essen, Marina Rode; Ratzer, Rikke; Börnsen, Lars; Bielekova, Bibi; Sellebjerg, Finn

    2018-05-01

    Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA). In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL. These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.

  18. Assessing the correlation between grey and white matter damage with motor and cognitive impairment in multiple sclerosis patients.

    Emilia Sbardella

    Full Text Available BACKGROUND: Multiple sclerosis (MS is characterized by demyelinating and degenerative processes within the central nervous system. Unlike conventional MRI,new advanced imaging techniques improve pathological specificity and better highlight the relationship between anatomical damage and clinical impairment. OBJECTIVE: To investigate the relationship between clinical disability and both grey (GM and white matter (WM regional damage in MS patients. METHODS: Thirty-six relapsing remitting-MS patients and 25 sex- and age-matched controls were enrolled. All patients were clinically evaluated by the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite (MSFC scale, which includes the 9-hole peg test (9HPT, the timed 25-feet walking test (T25FW and the paced auditory serial addition test (PASAT. All subjects were imaged by a 3.0 T scanner: dual-echo fast spin-echo, 3DT1-weighted and diffusion-tensor imaging (DTI sequences were acquired. Voxel-based morphometry (VBM and tract-based spatial statistics (TBSS analyses were run for regional GM and WM assessment, respectively. T2 lesion volumes were also calculated, by using a semi-automated technique. RESULTS: Brain volumetric assessment of GM and DTI measures revealed significant differences between patients and controls. In patients, different measures of WM damage correlated each-other (p<0.0001, whereas none of them correlated with GM volume. In patients, focal GM atrophy and widespread WM damage significantly correlated with clinical measures. In particular, VBM analysis revealed a significant correlation (p<0.05 between GM volume and 9HPT in cerebellum and between GM volume and PASAT in orbito-frontal cortex. TBSS showed significant correlations between DTI metrics with 9HPT and PASAT scores in many WM bundles (p<0.05, including corpus callosum, internal capsule, posterior thalamic radiations, cerebral peduncles. CONCLUSIONS: Selective GM atrophy and widespread WM tracts

  19. Multiple factors affect pest and pathogen damage on 31 Populus clones in South Carolina

    David R. Coyle; Mark D. Coleman; Jaclin A. Durant; Lee A. Newman

    2006-01-01

    Populus species and hybrids have many practical applications, but there is a paucity of data regarding selections that perform well in the southeastern US. We compared pest susceptibility of 31 Populus clones over 3 years in South Carolina, USA. Cuttings were planted in spring 2001 on two study sites. Clones planted in the...

  20. BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair

    Chapman, J. Ross; Sossick, Alex J.; Boulton, Simon J.; Jackson, Stephen P.

    2012-01-01

    Summary Following irradiation, numerous DNA-damage-responsive proteins rapidly redistribute into microscopically visible subnuclear aggregates, termed ionising-radiation-induced foci (IRIF). How the enrichment of proteins on damaged chromatin actually relates to DNA repair remains unclear. Here, we use super-resolution microscopy to examine the spatial distribution of BRCA1 and 53BP1 proteins within single IRIF at subdiffraction-limit resolution, yielding an unprecedented increase in detail that was not previously apparent by conventional microscopy. Consistent with a role for 53BP1 in promoting DNA double-strand break repair by non-homologous end joining, 53BP1 enrichment in IRIF is most prominent in the G0/G1 cell cycle phases, where it is enriched in dense globular structures. By contrast, as cells transition through S phase, the recruitment of BRCA1 into the core of IRIF is associated with an exclusion of 53BP1 to the focal periphery, leading to an overall reduction of 53BP1 occupancy at DNA damage sites. Our data suggest that the BRCA1-associated IRIF core corresponds to chromatin regions associated with repair by homologous recombination, and the enrichment of BRCA1 in IRIF represents a temporal switch in the DNA repair program. We propose that BRCA1 antagonises 53BP1-dependent DNA repair in S phase by inhibiting its interaction with chromatin proximal to damage sites. Furthermore, the genomic instability exhibited by BRCA1-deficient cells might result from a failure to efficiently exclude 53BP1 from such regions during S phase. PMID:22553214

  1. Multidisciplinary approaches to managing osteoarthritis in multiple joint sites: a systematic review.

    Finney, Andrew; Healey, Emma; Jordan, Joanne L; Ryan, Sarah; Dziedzic, Krysia S

    2016-07-08

    The National Institute for Health and Care Excellence's Osteoarthritis (OA) guidelines recommended that future research should consider the benefits of combination therapies in people with OA across multiple joint sites. However, the clinical effectiveness of such approaches to OA management is unknown. This systematic review therefore aimed to identify the clinical and cost effectiveness of multidisciplinary approaches targeting multiple joint sites for OA in primary care. A systematic review of randomised controlled trials. Computerised bibliographic databases were searched (MEDLINE, EMBASE, CINAHL, PsychINFO, BNI, HBE, HMIC, AMED, Web of Science and Cochrane). Studies were included if they met the following criteria; a randomised controlled trial (RCT), a primary care population with OA across at least two different peripheral joint sites (multiple joint sites), and interventions undertaken by at least two different health disciplines (multidisciplinary). The Cochrane 'Risk of Bias' tool and PEDro were used for quality assessment of eligible studies. Clinical and cost effectiveness was determined by extracting and examining self-reported outcomes for pain, function, quality of life (QoL) and health care utilisation. The date range for the search was from database inception until August 2015. The search identified 1148 individual titles of which four were included in the review. A narrative review was conducted due to the heterogeneity of the included trials. Each of the four trials used either educational or exercise interventions facilitated by a range of different health disciplines. Moderate clinical benefits on pain, function and QoL were reported across the studies. The beneficial effects of exercise generally decreased over time within all studies. Two studies were able to show a reduction in healthcare utilisation due to a reduction in visits to a physiotherapist or a reduction in x-rays and orthopaedic referrals. The intervention that showed the most

  2. Second-site prosthetic joint infection in patients with multiple prosthetic joints.

    Clesham, Kevin; Hughes, Andrew J; O' hEireamhoin, Sven; Fleming, Catherine; Murphy, Colin G

    2018-04-10

    Prosthetic joint infections (PJIs) are among the most serious complications in arthroplasty. A second-site PJI in patients with multiple prosthetic joints increases morbidity, with many requiring further revision procedures. We aimed to establish why some patients with multiple joints develop second-site infections. Our institution's arthroplasty database was reviewed from 2004 to 2017. All PJIs were identified, and all patients with more than one prosthetic joint in situ were included. We recorded risk factors, causative organisms, number of procedures and length of stay. Forty-four patients meeting the criteria were identified. Four patients (9.1%) developed second-site infection. Eight patients (18.2%) developed re-infection of the primary PJI. Positive MRSA carrier status and PJI of a total knee replacement were associated with an increased risk of a second episode of infection. Patients who developed further infection had more frequent admission and longer lengths of stay than isolated PJIs. Higher morbidity and use of hospital resources are associated with this cohort of patients. PJIs in total knee replacements and positive MRSA status are associated with higher rates of second infection. Identifying this vulnerable cohort of patients at an early stage is critical to ensure measures are taken to reduce the risks of further infection.

  3. Study of laser-induced damage on the exit surface of silica components in the nanosecond regime in a multiple wavelengths configuration

    Chambonneau, Maxime

    2014-01-01

    In this thesis, laser-induced damage phenomenon on the surface of fused silica components is investigated in the nanosecond regime. This phenomenon consists in an irreversible modification of the material. In the nanosecond regime, laser damage is tightly correlated to the presence of non-detectable precursor defects which are a consequence of the synthesis and the polishing of the components. In this thesis, we investigate laser damage in a multiple wavelengths configuration. In order to better understand this phenomenon in these conditions of irradiation, three studies are conducted. The first one focuses on damage initiation. The results obtained in the single wavelength configurations highlight a coupling in the multiple wavelengths one. A comparison between the experiments and a model developed during this thesis enables us to improve the knowledge of the fundamental processes involved during this damage phase. Then, we show that post mortem characterizations of damage morphology coupled to an accurate metrology allow us to understand both the nature and also the chronology of the physical mechanisms involved during damage formation. The proposed theoretical scenario is confirmed through various experiments. Finally, we study damage growth in both the single and the multiple wavelengths cases. Once again, this last configuration highlights a coupling between the wavelengths. We show the necessity to account for the spatial characteristics of the laser beams during a growth session. (author) [fr

  4. Multi-site damage localization in anisotropic plate-like structures using an active guided wave structural health monitoring system

    Moll, J; Schulte, R T; Fritzen, C-P; Hartmann, B; Nelles, O

    2010-01-01

    A new approach for structural health monitoring using guided waves in plate-like structures has been developed. In contrast to previous approaches, which mainly focused on isotropic or quasi-isotropic plates, the proposed algorithm does not assume any simplifications regarding anisotropic wave propagation. Thus, it can be used to improve the probability of detection. In this paper the mathematical background for damage localization in anisotropic plates will be introduced. This is an extension of the widely known ellipse method. The formalism is based on a distributed sensor network, where each piezoelectric sensor acts in turn as an actuator. The automatic extraction of the onset time of the first waveform in the differential signal in combination with a statistical post-processing via a two-dimensional probability density function and the application of the expectation-maximization algorithm allows a completely automatic localization procedure. Thus, multiple damages can be identified at the same time. The present study uses ultrasonic signals provided by the spectral element method. This simulation approach shows good agreement with experimental measurements. A local linear neural network is used to model the nonlinear dispersion curves. The benefit of using a neural network approach is to increase the angular resolution that results from the sparse sensor network. Furthermore, it can be used to shorten the computational time for the damage localization procedure

  5. A defined role for multiple Fanconi anemia gene products in DNA-damage-associated ubiquitination.

    Tan, Winnie; Deans, Andrew J

    2017-06-01

    Fanconi anemia (FA) is an inherited blood disorder that causes bone marrow failure and high predisposition to cancers. The FA pathway guards the cell's genome stability by orchestrating the repair of interstrand cross-linking during the S phase of the cell cycle, preventing the chromosomal instability that is a key event in bone marrow failure syndrome. Central to the FA pathway is loss of monoubiquitinated forms of the Fanconi proteins FANCI and FANCD2, a process that is normally mediated by a "core complex" of seven other Fanconi proteins. Each protein, when mutated, can cause FA. The FA core-complex-catalyzed reaction is critical for signaling DNA cross-link damage such as that induced by chemotherapies. Here, we present a perspective on the current understanding of FANCI and FANCD2 monoubiquitination-mediated DNA repair. Our recent biochemical reconstitution of the monoubiquitination (and deubiquitination) reactions creates a paradigm for understanding FA. Further biochemical analysis will create new opportunities to address the leukemic phenotype of FA patients. Copyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  6. Forward-looking farmers owning multiple potential wetland restoration sites: implications for efficient restoration

    Schroder (Kushch), Svetlana; Lang, Zhengxin; Rabotyagov, Sergey

    2018-04-01

    Wetland restoration can increase the provision of multiple non-market ecosystem services. Environmental and socio-economic factors need to be accounted for when land is withdrawn from agriculture and wetlands are restored. We build multi-objective optimization models to provide decision support for wetland restoration in the Le Sueur river watershed in Southern Minnesota. We integrate environmental objectives of sediment reduction and habitat protection with socio-economic factors associated with the overlap of private land with potential wetland restoration sites in the watershed and the costs representing forward-looking farmers voluntarily taking land out of agricultural production in favor of wetland restoration. Our results demonstrate that the inclusion of these factors early on in the restoration planning process affects both the total costs of the restoration project and the spatial distribution of optimally selected wetland restoration sites.

  7. Seeing the forest through the trees: Considering roost-site selection at multiple spatial scales

    Jachowski, David S.; Rota, Christopher T.; Dobony, Christopher A.; Ford, W. Mark; Edwards, John W.

    2016-01-01

    Conservation of bat species is one of the most daunting wildlife conservation challenges in North America, requiring detailed knowledge about their ecology to guide conservation efforts. Outside of the hibernating season, bats in temperate forest environments spend their diurnal time in day-roosts. In addition to simple shelter, summer roost availability is as critical as maternity sites and maintaining social group contact. To date, a major focus of bat conservation has concentrated on conserving individual roost sites, with comparatively less focus on the role that broader habitat conditions contribute towards roost-site selection. We evaluated roost-site selection by a northern population of federally-endangered Indiana bats (Myotis sodalis) at Fort Drum Military Installation in New York, USA at three different spatial scales: landscape, forest stand, and individual tree level. During 2007–2011, we radiotracked 33 Indiana bats (10 males, 23 females) and located 348 roosting events in 116 unique roost trees. At the landscape scale, bat roost-site selection was positively associated with northern mixed forest, increased slope, and greater distance from human development. At the stand scale, we observed subtle differences in roost site selection based on sex and season, but roost selection was generally positively associated with larger stands with a higher basal area, larger tree diameter, and a greater sugar maple (Acer saccharum) component. We observed no distinct trends of roosts being near high-quality foraging areas of water and forest edges. At the tree scale, roosts were typically in American elm (Ulmus americana) or sugar maple of large diameter (>30 cm) of moderate decay with loose bark. Collectively, our results highlight the importance of considering day roost needs simultaneously across multiple spatial scales. Size and decay class of individual roosts are key ecological attributes for the Indiana bat, however, larger-scale stand structural

  8. Brazilian nuclear power plants decommissioning plan for a multiple reactor site

    Monteiro, Deiglys B.; Moreira, Joao M.L.; Maiorino, Jose R., E-mail: deiglys.monteiro@ufabc.edu.br, E-mail: joao.moreira@ufabc.edu.br, E-mail: joserubens.maiorino@ufabc.edu.br [Universidade Federal do ABC (CECS/UFABC), Santo Andre, SP (Brazil). Centro de Engenharia, Modelagem e Ciencias Aplicadas. Programa de Pos-Graduacao em Energia e Engenharia da Energia

    2015-07-01

    Actually, Brazil has two operating Nuclear Power Plants and a third one under construction, all at Central Nuclear Almirante Alvaro Alberto - CNAAA. To comply with regulatory aspects the power plants operator, Eletronuclear, must present to Brazilian Nuclear Regulatory Agency, CNEN, a decommissioning plan. Brazilian experience with decommissioning is limited because none of any nuclear reactor at the country was decommissioned. In literature, decommissioning process is well described despite few nuclear power reactors have been decommissioned around the world. Some different approach is desirable for multiple reactors sites, case of CNAAA site. During the decommissioning, a great amount of wastes will be produced and have to be properly managed. Particularly, the construction of Auxiliary Services on the site could be a good choice due to the possibility of reducing costs. The present work intends to present to the Eletronuclear some aspects of the decommissioning concept and decommissioning management, storage and disposal de wastes, based on the available literature, regulatory standards of CNEN and international experience as well as to suggest some solutions to be implemented at CNAAA site before starts the decommissioning project in order to maximize the benefits. (author)

  9. Brazilian nuclear power plants decommissioning plan for a multiple reactor site

    Monteiro, Deiglys B.; Moreira, Joao M.L.; Maiorino, Jose R.

    2015-01-01

    Actually, Brazil has two operating Nuclear Power Plants and a third one under construction, all at Central Nuclear Almirante Alvaro Alberto - CNAAA. To comply with regulatory aspects the power plants operator, Eletronuclear, must present to Brazilian Nuclear Regulatory Agency, CNEN, a decommissioning plan. Brazilian experience with decommissioning is limited because none of any nuclear reactor at the country was decommissioned. In literature, decommissioning process is well described despite few nuclear power reactors have been decommissioned around the world. Some different approach is desirable for multiple reactors sites, case of CNAAA site. During the decommissioning, a great amount of wastes will be produced and have to be properly managed. Particularly, the construction of Auxiliary Services on the site could be a good choice due to the possibility of reducing costs. The present work intends to present to the Eletronuclear some aspects of the decommissioning concept and decommissioning management, storage and disposal de wastes, based on the available literature, regulatory standards of CNEN and international experience as well as to suggest some solutions to be implemented at CNAAA site before starts the decommissioning project in order to maximize the benefits. (author)

  10. Radionuclide toxicity in cultured mammalian cells: elucidation of the primary site of radiation damage

    Warters, R.L.; Hofer, K.G.; Harris, C.R.; Smith, J.M.

    1978-01-01

    Synchronized suspension cultures of Chinese hamster ovary cells (CHO) were labeled with various doses of 3 H-thymidine or 125 I-iododeoxyuridine to evaluate the cytocidal effects of intranuclear radionuclide decay. Damage produced by radionuclide decay outside the cell nucleus was studied on cells exposed to 125 I labeled, monovalent concanavalin A. After labeling, the cells were resynchronized in G 1 -phase and incubated for 36 h at 4 0 C to permit dose accumulation. Cell lethality was evaluated by the standard colony assay. Based on radionuclide incorporation data, cellular dimensions, and subcellular radionuclide distributions, the cumulative dose to whole cells, cell nuclei, and cellular cytoplasm was calculated from the known decay properties of 3 H and 125 I. (Auth.)

  11. Short-term evolution of spinal cord damage in multiple sclerosis: a diffusion tensor MRI study

    Theaudin, M.; Denier, C.; Adams, D. [AP-HP, CHU Bicetre, Service de Neurologie Adultes, Le Kremlin-Bicetre (France); INSERM, UMR788, Faculte de Medecine Paris Sud, Le Kremlin-Bicetre (France); Saliou, G. [AP-HP, CHU Bicetre, Service de Neuroradiologie, Le Kremlin-Bicetre (France); Ducot, B. [INSERM, U1018, CESP Centre for Research in Epidemiology and Population Health, Faculte de Medecine Paris Sud, Le Kremlin-Bicetre (France); Deiva, K. [Service de Neuropediatrie, Le Kremlin-Bicetre (France); Ducreux, D. [INSERM, UMR788, Faculte de Medecine Paris Sud, Le Kremlin-Bicetre (France); AP-HP, CHU Bicetre, Service de Neuroradiologie, Le Kremlin-Bicetre (France)

    2012-10-15

    The potential of diffusion tensor imaging (DTI) to detect spinal cord abnormalities in patients with multiple sclerosis has already been demonstrated. The objective of this study was to apply DTI techniques to multiple sclerosis patients with a recently diagnosed spinal cord lesion, in order to demonstrate a correlation between variations of DTI parameters and clinical outcome, and to try to identify DTI parameters predictive of outcome. A prospective single-centre study of patients with spinal cord relapse treated by intravenous steroid therapy was made. Patients were assessed clinically and by conventional MRI with DTI sequences at baseline and at 3 months. Sixteen patients were recruited. At 3 months, 12 patients were clinically improved. All but one patient had lower fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values than normal subjects in either inflammatory lesions or normal-appearing spinal cord. Patients who improved at 3 months presented a significant reduction in the radial diffusivity (p = 0.05) in lesions during the follow-up period. They also had a significant reduction in the mean ADC (p = 0.002), axial diffusivity (p = 0.02), radial diffusivity (p = 0.02) and a significant increase in FA values (p = 0.02) in normal-appearing spinal cord. Patients in whom the American Spinal Injury Association sensory score improved at 3 months showed a significantly higher FA (p = 0.009) and lower radial diffusivity (p = 0.04) in inflammatory lesion at baseline compared to patients with no improvement. DTI MRI detects more extensive abnormalities than conventional T2 MRI. A less marked decrease in FA value and more marked decreased in radial diffusivity inside the inflammatory lesion were associated with better outcome. (orig.)

  12. Short-term evolution of spinal cord damage in multiple sclerosis: a diffusion tensor MRI study

    Theaudin, M.; Denier, C.; Adams, D.; Saliou, G.; Ducot, B.; Deiva, K.; Ducreux, D.

    2012-01-01

    The potential of diffusion tensor imaging (DTI) to detect spinal cord abnormalities in patients with multiple sclerosis has already been demonstrated. The objective of this study was to apply DTI techniques to multiple sclerosis patients with a recently diagnosed spinal cord lesion, in order to demonstrate a correlation between variations of DTI parameters and clinical outcome, and to try to identify DTI parameters predictive of outcome. A prospective single-centre study of patients with spinal cord relapse treated by intravenous steroid therapy was made. Patients were assessed clinically and by conventional MRI with DTI sequences at baseline and at 3 months. Sixteen patients were recruited. At 3 months, 12 patients were clinically improved. All but one patient had lower fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values than normal subjects in either inflammatory lesions or normal-appearing spinal cord. Patients who improved at 3 months presented a significant reduction in the radial diffusivity (p = 0.05) in lesions during the follow-up period. They also had a significant reduction in the mean ADC (p = 0.002), axial diffusivity (p = 0.02), radial diffusivity (p = 0.02) and a significant increase in FA values (p = 0.02) in normal-appearing spinal cord. Patients in whom the American Spinal Injury Association sensory score improved at 3 months showed a significantly higher FA (p = 0.009) and lower radial diffusivity (p = 0.04) in inflammatory lesion at baseline compared to patients with no improvement. DTI MRI detects more extensive abnormalities than conventional T2 MRI. A less marked decrease in FA value and more marked decreased in radial diffusivity inside the inflammatory lesion were associated with better outcome. (orig.)

  13. Protein kinase CK2 localizes to sites of DNA double-strand break regulating the cellular response to DNA damage

    Olsen Birgitte B

    2012-03-01

    Full Text Available Abstract Background The DNA-dependent protein kinase (DNA-PK is a nuclear complex composed of a large catalytic subunit (DNA-PKcs and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the non-homologous end-joining (NHEJ repair mechanism, which is activated in the presence of DNA double-strand breaks induced by ionizing radiation, reactive oxygen species and radiomimetic drugs. We have recently reported that down-regulation of protein kinase CK2 by siRNA interference results in enhanced cell death specifically in DNA-PKcs-proficient human glioblastoma cells, and this event is accompanied by decreased autophosphorylation of DNA-PKcs at S2056 and delayed repair of DNA double-strand breaks. Results In the present study, we show that CK2 co-localizes with phosphorylated histone H2AX to sites of DNA damage and while CK2 gene knockdown is associated with delayed DNA damage repair, its overexpression accelerates this process. We report for the first time evidence that lack of CK2 destabilizes the interaction of DNA-PKcs with DNA and with Ku80 at sites of genetic lesions. Furthermore, we show that CK2 regulates the phosphorylation levels of DNA-PKcs only in response to direct induction of DNA double-strand breaks. Conclusions Taken together, these results strongly indicate that CK2 plays a prominent role in NHEJ by facilitating and/or stabilizing the binding of DNA-PKcs and, possibly other repair proteins, to the DNA ends contributing to efficient DNA damage repair in mammalian cells.

  14. Analysis of potential urban unstable areas and landslide-induced damages on Volterra historical site through a remote sensing approach

    Del Soldato, Matteo; Bianchini, Silvia; Nolesini, Teresa; Frodella, William; Casagli, Nicola

    2017-04-01

    Multisystem remote sensing techniques were exploited to provide a comprehensive overview of Volterra (Italy) site stability with regards to its landscape, urban fabric and cultural heritage. Interferometric Synthetic Aperture Radar (InSAR) techniques allow precise measurements of Earth surface displacement, as well as the detection of building deformations on large urban areas. In the field of cultural heritage conservation Infrared thermography (IRT) provides surface temperature mapping and therefore detects various potential criticalities, such as moisture, seepage areas, cracks and structural anomalies. Between winter 2014 and spring 2015 the historical center and south-western sectors of Volterra (Tuscany region, central Italy) were affected by instability phenomena. The spatial distribution, typology and effect on the urban fabrics of the landslide phenomena were investigated by analyzing the geological and geomorphological settings, traditional geotechnical monitoring and advanced remote sensing data such as Persistent Scatterers Interferometry (PSI). The ground deformation rates and the maximum settlement values derived from SAR acquisitions of historical ENVISAT and recent COSMO-SkyMed sensors, in 2003-2009 and 2010-2015 respectively, were compared with background geological data, constructive features, in situ evidences and detailed field inspections in order to classify landslide-damaged buildings. In this way, the detected movements and their potential correspondences with recognized damages were investigated in order to perform an assessment of the built-up areas deformations and damages on Volterra. The IRT technique was applied in order to survey the surface temperature of the historical Volterra wall-enclosure, and allowed highlighting thermal anomalies on this cultural heritage element of the site. The obtained results permitted to better correlate the landslide effects of the recognized deformations in the urban fabric, in order to provide useful

  15. A Bayesian joint probability modeling approach for seasonal forecasting of streamflows at multiple sites

    Wang, Q. J.; Robertson, D. E.; Chiew, F. H. S.

    2009-05-01

    Seasonal forecasting of streamflows can be highly valuable for water resources management. In this paper, a Bayesian joint probability (BJP) modeling approach for seasonal forecasting of streamflows at multiple sites is presented. A Box-Cox transformed multivariate normal distribution is proposed to model the joint distribution of future streamflows and their predictors such as antecedent streamflows and El Niño-Southern Oscillation indices and other climate indicators. Bayesian inference of model parameters and uncertainties is implemented using Markov chain Monte Carlo sampling, leading to joint probabilistic forecasts of streamflows at multiple sites. The model provides a parametric structure for quantifying relationships between variables, including intersite correlations. The Box-Cox transformed multivariate normal distribution has considerable flexibility for modeling a wide range of predictors and predictands. The Bayesian inference formulated allows the use of data that contain nonconcurrent and missing records. The model flexibility and data-handling ability means that the BJP modeling approach is potentially of wide practical application. The paper also presents a number of statistical measures and graphical methods for verification of probabilistic forecasts of continuous variables. Results for streamflows at three river gauges in the Murrumbidgee River catchment in southeast Australia show that the BJP modeling approach has good forecast quality and that the fitted model is consistent with observed data.

  16. Occurrence of cancer at multiple sites: Towards distinguishing multigenesis from metastasis

    Zhang Chun

    2008-04-01

    Full Text Available Abstract Background Occurrence of tumors at multiple sites is a hallmark of malignant cancers and contributes to the high mortality of cancers. The formation of multi-site cancers (MSCs has conventionally been regarded as a result of hematogenous metastasis. However, some MSCs may appear as unusual in the sense of vascular dissemination pattern and therefore be explained by alternative metastasis models or even by non-metastatic independent formation mechanisms. Results Through literature review and incorporation of recent advance in understanding aging and development, we identified two alternative mechanisms for the independent formation of MSCs: 1 formation of separate tumors from cancer-initiating cells (CICs mutated at an early stage of development and then diverging as to their physical locations upon further development, 2 formation of separate tumors from different CICs that contain mutations in some convergent ways. Either of these processes does not require long-distance migration and/or vascular dissemination of cancer cells from a primary site to a secondary site. Thus, we classify the formation of these MSCs from indigenous CICs (iCICs into a new mechanistic category of tumor formation – multigenesis. Conclusion A multigenesis view on multi-site cancer (MSCs may offer explanations for some "unusual metastasis" and has important implications for designing expanded strategies for the diagnosis and treatment of cancers. Reviewers This article was reviewed by Carlo C. Maley nominated by Laura F. Landweber and Razvan T. Radulescu nominated by David R. Kaplan. For the full reviews, please go to the Reviewers' comments section.

  17. Application of diffusional kurtosis imaging to detect occult brain damage in multiple sclerosis and neuromyelitis optica.

    Qian, Wenshu; Chan, Koon Ho; Hui, Edward S; Lee, Chi Yan; Hu, Yong; Mak, Henry Ka-Fung

    2016-11-01

    Multiple sclerosis (MS) and neuromyelitis optica (NMO) are two common types of inflammatory demyelinating disease of the central nervous system. Early distinction of NMO from MS is crucial but quite challenging. In this study, 13 NMO spectrum disorder patients (Expanded Disability Status Scale (EDSS) of 3.0 ± 1.7, ranging from 2 to 6.5; disease duration of 5.3 ± 4.7 years), 17 relapsing-remitting MS patients (EDSS of 2.6 ± 1.4, ranging from 1 to 5.5; disease duration of 7.9 ± 7.8 years) and 18 healthy volunteers were recruited. Diffusional kurtosis imaging was employed to discriminate NMO and MS patients at the early or stable stage from each other, and from healthy volunteers. The presence of alterations in diffusion and diffusional kurtosis metrics in normal-appearing white matter (NAWM) and diffusely increased mean diffusivity (MD) in the cortical normal-appearing gray matter (NAGM) favors the diagnosis of MS rather than NMO. Meanwhile, normal diffusivities and kurtosis metrics in all NAWM as well as increases in MD in the frontal and temporal NAGM suggest NMO. Our results suggest that diffusion and diffusional kurtosis metrics may well aid in discriminating the two diseases. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Spatial deficits in an amnesic patient with hippocampal damage: questioning the multiple trace theory.

    Gomez, A; Rousset, S; Charnallet, A

    2012-06-01

    Mediotemporal lobe structures are involved in both spatial processing and long-term memory. Patient M.R. suffers from amnesia, due to bilateral hippocampal lesion and temporoparietal atrophy following carbon monoxide poisoning. We compared his performance in immediate spatial memory tasks with the performance of ten healthy matched participants. Using an immediate reproduction of path, we observed a dissociation between his performance in three allocentric tasks and in five egocentric-updating tasks. His performance was always impaired on tasks requiring the use of an egocentric-updating representation but remained preserved on allocentric tasks. These results fit with the hypothesis that the hippocampus plays a role in spatial memory, but they also suggest that allocentric deficits previously observed in amnesia might actually reflect deficits in egocentric-updating processes. Furthermore, the co-occurrence of deficits in episodic long-term memory and short-term egocentric-updating representation without any short-term allocentric deficit suggests a new link between the mnemonic and navigational roles of the hippocampus. The Cognitive Map theory, the Multiple Trace theory, as well as further models linking spatial and nonspatial functions of the hippocampus are discussed. Copyright © 2011 Wiley Periodicals, Inc.

  19. Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability

    Antonio Giorgio

    2017-11-01

    Full Text Available Pediatric-onset multiple sclerosis (POMS may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15 in comparison with age- and disability-matched AOMS patients (n = 14 and to normal controls (NC, n = 20. We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space. POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.

  20. Radiation exposure and health damage of residents at Semipalatinsk nuclear test site

    Tolebay, Rakhypbekov; Noso, Yoshihiro; Takechi, Nobuo

    2016-01-01

    Although the nuclear test site of Semipalatinsk (former Soviet Union and presently the Republic of Kazakhstan) stopped nuclear tests 25 years ago, there are presumably more than 200,000 victims near the site, including persons with a low dose and a high dose. Semey Medical University and Shimane University, together with the Kazakh Scientific Institute for Radiation Medicine and Ecology, have been conducting the measurement of radiation concentration of soil and the thyroid screening of residents. The following were surveyed: (1) chromosomal abnormality for 55 female residents (average 45 years in age) in heavily polluted areas and 25 female residents (average 42 years in age) in non-polluted areas, (2) mental abnormality of residents in polluted areas and non-polluted areas of Semey City, and (3) changes in the frequency of surgery cases for cancer between 1989 and 2014 at Semey Medical University Cancer Center. As for chromosomal abnormality, 3-5 times many mutation cases were observed in heavily polluted areas than in non-polluted areas. The nodules of thyroid gland were four times more frequent in heavily polluted areas. The frequency of a whole variety of cancers was nearly twice in polluted areas compared with in non-polluted areas, most of which were digestive system cancer, lung cancer, and breast cancer in the order. The frequency of mental abnormality has also increased nearly twice as compared to non-polluted areas, and it included neurological disorder, adjustment disorder, neuralgia, moderate depression, and learning disability. These results suggest that some physical effects can be caused by exposure. In the future, this study will investigate the effects of radiation exposure at the nuclear test site. (A.O.)

  1. Prevention of adolescent reoccurring violence and alcohol abuse: a multiple site evaluation.

    Wodarski, John S

    2010-07-01

    "Prevention of Adolescent Reoccurring Violence and Alcohol Abuse: A Multiple Site Evaluation" is a multiple component alcohol abuse and violent behavior prevention strategy, targeted to adolescents ages 16-21 who have high levels of anger, or who are victims/perpetrators of violence, and their families. Three community centers located in upstate New York provided group participants (N = 210) known to have conduct disorder and substance abuse history. The centers were used as the intervention sites over a seven-week period with the youth assessment staff using objective screening measures. The participants were exposed to a two-pronged intervention, using a parental involvement cohort with approximately half of the study participants. The Teams, Games, and Tournaments strategy was the intervention method. Teams, Games, and Tournaments is a Social Learning Theory-based intervention with demonstrated empirical evidence of the model's effectiveness. A 2 x 3 factorial design with two follow-up points encompassed: anger control, alcohol/substance abuse, and family interactive education. The goals of the study were to help adolescents reduce their alcohol use, to increase productive family interaction, and ultimately to reduce the adolescents' aggression levels and subsequently reduce the possibility of their becoming victims or perpetrators of a violent crime. Consistent with Social Learning Theory, the Teams, Games, and Tournaments treatment intervention makes use of adolescents as peer counselors. The practical implications include that professionals or students in our public schools, juvenile courts, correctional institutions, and residential treatment centers can easily implement this program. A standardized treatment manual is available. It offers a complete, ready-to-use, and cost-effective tool for reducing adolescent violence and alcohol abuse. Further, the data provide support for a hypothesis of social learning theory, that is: interventions using multiple

  2. Drug eruptions presenting at sites of prior radiation damage (sunlight and electron beam)

    Shelley, W.B.; Shelley, E.D.; Campbell, A.C.; Weigensberg, I.J.

    1984-01-01

    Two patients are described in whom sunburn and electron beam radiodermatitis, respectively, were critical determinants in localizing the initial presentation of drug eruptions. In the first instance, a severe sunburn of the back and thighs was followed 7 months later by the appearance of a toxic epidermal necrolysis drug reaction to trimethoprim-sulfamethoxazole in the exact sites of the previous bullous sunburn reaction. In the second patient, a radiodermatitis of the left upper arm due to electron beam therapy for metastatic breast cancer was followed 7 weeks later by a codeine drug reaction confined to the area of the radiodermatitis. In both instances, oral rechallenge with the offending drug reproduced the eruption

  3. Leghemoglobin-derived radicals. Evidence for multiple protein-derived radicals and the initiation of peribacteroid membrane damage

    Moreau, S; Davies, Michael Jonathan; Mathieu, C

    1996-01-01

    , with the consequent generation of lipid-derived radicals. The formation of such radicals may result in the depletion of membrane antioxidants and the initiation of lipid peroxidation. This transfer of damage from the heme center via the protein surface to neighboring membranes may be of considerable biological......-derived phenoxyl radical present at Tyr-133 in the soybean protein and Tyr-138 in the lupin protein. To obtain further information on these protein radicals and their potential interaction with the physiologically important peribacteroid membrane (which surrounds the microsymbiont in vivo), EPR spin trapping......); these radicals may be side chain- or alpha-carbon-derived, their exact sites have not been determined. Some of these radicals are on the protein surface and may be key intermediates in the formation of protein dimers. These radicals have been shown to be capable of reacting with peribacteroid membrane fractions...

  4. Identification of Multiple Druggable Secondary Sites by Fragment Screening against DC-SIGN.

    Aretz, Jonas; Baukmann, Hannes; Shanina, Elena; Hanske, Jonas; Wawrzinek, Robert; Zapol'skii, Viktor A; Seeberger, Peter H; Kaufmann, Dieter E; Rademacher, Christoph

    2017-06-12

    DC-SIGN is a cell-surface receptor for several pathogenic threats, such as HIV, Ebola virus, or Mycobacterium tuberculosis. Multiple attempts to develop inhibitors of the underlying carbohydrate-protein interactions have been undertaken in the past fifteen years. Still, drug-like DC-SIGN ligands are sparse, which is most likely due to its hydrophilic, solvent-exposed carbohydrate-binding site. Herein, we report on a parallel fragment screening against DC-SIGN applying SPR and a reporter displacement assay, which complements previous screenings using 19 F NMR spectroscopy and chemical fragment microarrays. Hit validation by SPR and 1 H- 15 N HSQC NMR spectroscopy revealed that although no fragment bound in the primary carbohydrate site, five secondary sites are available to harbor drug-like molecules. Building on key interactions of the reported fragment hits, these pockets will be targeted in future approaches to accelerate the development of DC-SIGN inhibitors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Identification of multiple sites suitable for insertion of foreign genes in herpes simplex virus genomes.

    Morimoto, Tomomi; Arii, Jun; Akashi, Hiroomi; Kawaguchi, Yasushi

    2009-03-01

    Information on sites in HSV genomes at which foreign gene(s) can be inserted without disrupting viral genes or affecting properties of the parental virus are important for basic research on HSV and development of HSV-based vectors for human therapy. The intergenic region between HSV-1 UL3 and UL4 genes has been reported to satisfy the requirements for such an insertion site. The UL3 and UL4 genes are oriented toward the intergenic region and, therefore, insertion of a foreign gene(s) into the region between the UL3 and UL4 polyadenylation signals should not disrupt any viral genes or transcriptional units. HSV-1 and HSV-2 each have more than 10 additional regions structurally similar to the intergenic region between UL3 and UL4. In the studies reported here, it has been demonstrated that insertion of a reporter gene expression cassette into several of the HSV-1 and HSV-2 intergenic regions has no effect on viral growth in cell culture or virulence in mice, suggesting that these multiple intergenic regions may be suitable HSV sites for insertion of foreign genes.

  6. Disaster damage detection through synergistic use of deep learning and 3D point cloud features derived from very high resolution oblique aerial images, and multiple-kernel-learning

    Vetrivel, Anand; Gerke, Markus; Kerle, Norman; Nex, Francesco; Vosselman, George

    2018-06-01

    Oblique aerial images offer views of both building roofs and façades, and thus have been recognized as a potential source to detect severe building damages caused by destructive disaster events such as earthquakes. Therefore, they represent an important source of information for first responders or other stakeholders involved in the post-disaster response process. Several automated methods based on supervised learning have already been demonstrated for damage detection using oblique airborne images. However, they often do not generalize well when data from new unseen sites need to be processed, hampering their practical use. Reasons for this limitation include image and scene characteristics, though the most prominent one relates to the image features being used for training the classifier. Recently features based on deep learning approaches, such as convolutional neural networks (CNNs), have been shown to be more effective than conventional hand-crafted features, and have become the state-of-the-art in many domains, including remote sensing. Moreover, often oblique images are captured with high block overlap, facilitating the generation of dense 3D point clouds - an ideal source to derive geometric characteristics. We hypothesized that the use of CNN features, either independently or in combination with 3D point cloud features, would yield improved performance in damage detection. To this end we used CNN and 3D features, both independently and in combination, using images from manned and unmanned aerial platforms over several geographic locations that vary significantly in terms of image and scene characteristics. A multiple-kernel-learning framework, an effective way for integrating features from different modalities, was used for combining the two sets of features for classification. The results are encouraging: while CNN features produced an average classification accuracy of about 91%, the integration of 3D point cloud features led to an additional

  7. Numerical Evaluation and Optimization of Multiple Hydraulically Fractured Parameters Using a Flow-Stress-Damage Coupled Approach

    Yu Wang

    2016-04-01

    Full Text Available Multiple-factor analysis and optimization play a critical role in the the ability to maximizethe stimulated reservoir volume (SRV and the success of economic shale gas production. In this paper, taking the typical continental naturally fractured silty laminae shale in China as anexample, response surface methodology (RSM was employed to optimize multiple hydraulic fracturing parameters to maximize the stimulated area in combination with numerical modeling based on the coupled flow-stress-damage (FSD approach. This paper demonstrates hydraulic fracturing effectiveness by defining two indicesnamelythe stimulated reservoir area (SRA and stimulated silty laminae area (SLA. Seven uncertain parameters, such as laminae thickness, spacing, dip angle, cohesion, internal friction angle (IFA, in situ stress difference (SD, and an operational parameter-injection rate (IR with a reasonable range based on silty Laminae Shale, Southeastern Ordos Basin, are used to fit a response of SRA and SLA as the objective function, and finally identity the optimum design under the parameters based on simultaneously maximizingSRA and SLA. In addition, asensitivity analysis of the influential factors is conducted for SRA and SLA. The aim of the study is to improve the artificial ability to control the fracturing network by means of multi-parameteroptimization. This work promises to provide insights into the effective exploitation of unconventional shale gas reservoirs via optimization of the fracturing design for continental shale, Southeastern Ordos Basin, China.

  8. Multiple and variable NHEJ-like genes are involved in resistance to DNA damage in Streptomyces ambofaciens

    Grégory Hoff

    2016-11-01

    Full Text Available Non homologous end-joining (NHEJ is a double strand break (DSB repair pathway which does not require any homologous template and can ligate two DNA ends together. The basic bacterial NHEJ machinery involves two partners: the Ku protein, a DNA end binding protein for DSB recognition and the multifunctional LigD protein composed a ligase, a nuclease and a polymerase domain, for end processing and ligation of the broken ends. In silico analyses performed in the 38 sequenced genomes of Streptomyces species revealed the existence of a large panel of NHEJ-like genes. Indeed, ku genes or ligD domain homologues are scattered throughout the genome in multiple copies and can be distinguished in two categories: the core NHEJ gene set constituted of conserved loci and the variable NHEJ gene set constituted of NHEJ-like genes present in only a part of the species. In Streptomyces ambofaciens ATCC 23877, not only the deletion of core genes but also that of variable genes led to an increased sensitivity to DNA damage induced by electron beam irradiation. Multiple mutants of ku, ligase or polymerase encoding genes showed an aggravated phenotype compared to single mutants. Biochemical assays revealed the ability of Ku-like proteins to protect and to stimulate ligation of DNA ends. RT-qPCR and GFP fusion experiments suggested that ku-like genes show a growth phase dependent expression profile consistent with their involvement in DNA repair during spores formation and/or germination.

  9. SiteBinder: an improved approach for comparing multiple protein structural motifs.

    Sehnal, David; Vařeková, Radka Svobodová; Huber, Heinrich J; Geidl, Stanislav; Ionescu, Crina-Maria; Wimmerová, Michaela; Koča, Jaroslav

    2012-02-27

    There is a paramount need to develop new techniques and tools that will extract as much information as possible from the ever growing repository of protein 3D structures. We report here on the development of a software tool for the multiple superimposition of large sets of protein structural motifs. Our superimposition methodology performs a systematic search for the atom pairing that provides the best fit. During this search, the RMSD values for all chemically relevant pairings are calculated by quaternion algebra. The number of evaluated pairings is markedly decreased by using PDB annotations for atoms. This approach guarantees that the best fit will be found and can be applied even when sequence similarity is low or does not exist at all. We have implemented this methodology in the Web application SiteBinder, which is able to process up to thousands of protein structural motifs in a very short time, and which provides an intuitive and user-friendly interface. Our benchmarking analysis has shown the robustness, efficiency, and versatility of our methodology and its implementation by the successful superimposition of 1000 experimentally determined structures for each of 32 eukaryotic linear motifs. We also demonstrate the applicability of SiteBinder using three case studies. We first compared the structures of 61 PA-IIL sugar binding sites containing nine different sugars, and we found that the sugar binding sites of PA-IIL and its mutants have a conserved structure despite their binding different sugars. We then superimposed over 300 zinc finger central motifs and revealed that the molecular structure in the vicinity of the Zn atom is highly conserved. Finally, we superimposed 12 BH3 domains from pro-apoptotic proteins. Our findings come to support the hypothesis that there is a structural basis for the functional segregation of BH3-only proteins into activators and enablers.

  10. Uncertainty analysis of the Operational Simplified Surface Energy Balance (SSEBop) model at multiple flux tower sites

    Chen, Mingshi; Senay, Gabriel B.; Singh, Ramesh K.; Verdin, James P.

    2016-01-01

    Evapotranspiration (ET) is an important component of the water cycle – ET from the land surface returns approximately 60% of the global precipitation back to the atmosphere. ET also plays an important role in energy transport among the biosphere, atmosphere, and hydrosphere. Current regional to global and daily to annual ET estimation relies mainly on surface energy balance (SEB) ET models or statistical and empirical methods driven by remote sensing data and various climatological databases. These models have uncertainties due to inevitable input errors, poorly defined parameters, and inadequate model structures. The eddy covariance measurements on water, energy, and carbon fluxes at the AmeriFlux tower sites provide an opportunity to assess the ET modeling uncertainties. In this study, we focused on uncertainty analysis of the Operational Simplified Surface Energy Balance (SSEBop) model for ET estimation at multiple AmeriFlux tower sites with diverse land cover characteristics and climatic conditions. The 8-day composite 1-km MODerate resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) was used as input land surface temperature for the SSEBop algorithms. The other input data were taken from the AmeriFlux database. Results of statistical analysis indicated that the SSEBop model performed well in estimating ET with an R2 of 0.86 between estimated ET and eddy covariance measurements at 42 AmeriFlux tower sites during 2001–2007. It was encouraging to see that the best performance was observed for croplands, where R2 was 0.92 with a root mean square error of 13 mm/month. The uncertainties or random errors from input variables and parameters of the SSEBop model led to monthly ET estimates with relative errors less than 20% across multiple flux tower sites distributed across different biomes. This uncertainty of the SSEBop model lies within the error range of other SEB models, suggesting systematic error or bias of the SSEBop model is within

  11. Concept and methodology for evaluating core damage frequency considering failure correlation at multi units and sites and its application

    Ebisawa, K.; Teragaki, T.; Nomura, S. [Former Incorporated Administrative Agency, Japan Nuclear Safety Organization (Japan); Abe, H., E-mail: Hiroshi_abe@nsr.go.jp [Former Incorporated Administrative Agency, Japan Nuclear Safety Organization (Japan); Shigemori, M.; Shimomoto, M. [Mizuho Information & Research Institute, 2-3, Kanda-Nishikicho, Chiyoda-ku, Tokyo (Japan)

    2015-07-15

    Highlights: • We develop a method to evaluate CDF considering failure correlation at multi units. • We develop a procedure to evaluate correlation coefficient between multi components. • We evaluate CDF at two different BWR units using correlation coefficients. • We confirm the validity of method and correlation coefficient through the evaluation. - Abstract: The Tohoku earthquake (Mw9.0) occurred on March 11, 2011 and caused a large tsunami. The Fukushima Daiichi Nuclear Power Plant with six units were overwhelmed by the tsunami and core damage occurred. Authors proposed the concept and method for evaluating core damage frequency (CDF) considering failure correlation at the multi units and sites. Based on the above method, one of authors developed the procedure for evaluating the failure correlation coefficient and response correlation coefficient between the multi components under the strong seismic motion. These method and failure correlation coefficients were applied to two different BWR units and their CDF was evaluated by seismic probabilistic risk assessment technology. Through this quantitative evaluation, the validity of the method and failure correlation coefficient was confirmed.

  12. Concept and methodology for evaluating core damage frequency considering failure correlation at multi units and sites and its application

    Ebisawa, K.; Teragaki, T.; Nomura, S.; Abe, H.; Shigemori, M.; Shimomoto, M.

    2015-01-01

    Highlights: • We develop a method to evaluate CDF considering failure correlation at multi units. • We develop a procedure to evaluate correlation coefficient between multi components. • We evaluate CDF at two different BWR units using correlation coefficients. • We confirm the validity of method and correlation coefficient through the evaluation. - Abstract: The Tohoku earthquake (Mw9.0) occurred on March 11, 2011 and caused a large tsunami. The Fukushima Daiichi Nuclear Power Plant with six units were overwhelmed by the tsunami and core damage occurred. Authors proposed the concept and method for evaluating core damage frequency (CDF) considering failure correlation at the multi units and sites. Based on the above method, one of authors developed the procedure for evaluating the failure correlation coefficient and response correlation coefficient between the multi components under the strong seismic motion. These method and failure correlation coefficients were applied to two different BWR units and their CDF was evaluated by seismic probabilistic risk assessment technology. Through this quantitative evaluation, the validity of the method and failure correlation coefficient was confirmed

  13. Spore membrane(s) as the site of damage within heated Clostridium perfringens spores.

    Flowers, R S; Adams, D M

    1976-02-01

    Clostridium perfringens spores were injured by ultrahigh-temperature treatment at 105 C for 5 min. Injury was manifested as an increased sensitivity to polymyxin and neomycin. Since many of the survivors could not germinate normally the ultrahigh-temperature-treated spores were sensitized to and germinated by lysozyme. Polymyxin reportedly acts upon the cell membrane. Neomycin may inhibit protein synthesis and has surface-active properties. Injured spores were increasingly sensitive to known surface-active agents, sodium lauryl sulfate, sodium deoxycholate, and Roccal, a quaternary ammonium compound. Injured spores sensitive to polymyxin and neomycin also were osmotically fragile and died during outgrowth in a liquid medium unless the medium was supplemented with 20% sucrose, 10% dextran, or 10% polyvinylpyrrolidone. The results suggested that a spore structure destined to become cell membrane or cell wall was the site of injury. Repair of injury during outgrowth in the presence of protein, deoxyribonucleic acid, ribonucleic acid and cell wall synthesis inhibitors was consistent with this hypothesis.

  14. The in vivo phosphorylation sites in multiple isoforms of amphiphysin I from rat brain nerve terminals

    Craft, George E; Graham, Mark E; Bache, Nicolai

    2008-01-01

    : serines 250, 252, 262, 268, 272, 276, 285, 293, 496, 514, 539, and 626 and Thr-310. These were distributed into two clusters around the proline-rich domain and the C-terminal Src homology 3 domain. Hierarchical phosphorylation of Ser-262 preceded phosphorylation of Ser-268, -272, -276, and -285. Off......, incorporating 16 and 23% of the 32P. The multiple phosphopeptides containing Ser-268, Ser-276, Ser-272, and Ser-285 had 27% of the 32P. Evidence for a role for at least one proline-directed protein kinase and one non-proline-directed kinase was obtained. Four phosphosites predicted for non-proline...... that are either dynamically turning over or constitutively phosphorylated in nerve terminals and improve understanding of the role of individual amphI sites or phosphosite clusters in synaptic SVE....

  15. Extracorporeal shock wave therapy for injection site panniculitis in multiple sclerosis patients.

    Stieger, Marco; Schmid, Jean-Paul; Yawalkar, Nikhil; Hunziker, Thomas

    2015-01-01

    Painful cutaneous injection site reactions may hamper treatment with interferon β (IFN-β) and glatiramer acetate (GA) in multiple sclerosis (MS) patients. To maintain therapy adherence, efficient therapeutic modalities for these subcutaneous inflammatory lesions are urgently needed. We tested the application of local extracorporeal shock wave therapy (ESWT). We applied 5 sessions of ESWT to 8 patients suffering from MS who had developed painful panniculitis at the injection sites of either IFN-β or GA. Clinical outcomes, i.e. pain reduction and regression of induration, were assessed 3 and 6 months after completion of the ESWT using a visual analogue score. All patients showed both significant pain reduction and reduction of the skin induration in the treated lesions, while in untreated control lesions there was no improvement. ESWT proved to be a non-invasive, safe and efficient physical treatment modality for injection-induced painful cutaneous side effects of disease-modifying drugs in MS. © 2014 S. Karger AG, Basel.

  16. Engineering a horseradish peroxidase C stable to radical attacks by mutating multiple radical coupling sites.

    Kim, Su Jin; Joo, Jeong Chan; Song, Bong Keun; Yoo, Young Je; Kim, Yong Hwan

    2015-04-01

    Peroxidases have great potential as industrial biocatalysts. In particular, the oxidative polymerization of phenolic compounds catalyzed by peroxidases has been extensively examined because of the advantage of this method over other conventional chemical methods. However, the industrial application of peroxidases is often limited because of their rapid inactivation by phenoxyl radicals during oxidative polymerization. In this work, we report a novel protein engineering approach to improve the radical stability of horseradish peroxidase isozyme C (HRPC). Phenylalanine residues that are vulnerable to modification by the phenoxyl radicals were identified using mass spectrometry analysis. UV-Vis and CD spectra showed that radical coupling did not change the secondary structure or the active site of HRPC. Four phenylalanine (Phe) residues (F68, F142, F143, and F179) were each mutated to alanine residues to generate single mutants to examine the role of these sites in radical coupling. Despite marginal improvement of radical stability, each single mutant still exhibited rapid radical inactivation. To further reduce inactivation by radical coupling, the four substitution mutations were combined in F68A/F142A/F143A/F179A. This mutant demonstrated dramatic enhancement of radical stability by retaining 41% of its initial activity compared to the wild-type, which was completely inactivated. Structure and sequence alignment revealed that radical-vulnerable Phe residues of HPRC are conserved in homologous peroxidases, which showed the same rapid inactivation tendency as HRPC. Based on our site-directed mutagenesis and biochemical characterization, we have shown that engineering radical-vulnerable residues to eliminate multiple radical coupling can be a good strategy to improve the stability of peroxidases against radical attack. © 2014 Wiley Periodicals, Inc.

  17. Imaging San Jacinto Fault damage zone structure using dense linear arrays: application of ambient noise tomography, Rayleigh wave ellipticity, and site amplification

    Wang, Y.; Lin, F. C.; Allam, A. A.; Ben-Zion, Y.

    2017-12-01

    The San Jacinto fault is presently the most seismically active component of the San Andreas Transform system in Southern California. To study the damage zone structure, two dense linear geophone arrays (BS and RR) were deployed across the Clark segment of the San Jacinto Fault between Anza and Hemet during winter 2015 and Fall 2016, respectively. Both arrays were 2 km long with 20 m station spacing. Month-long three-component ambient seismic noise data were recorded and used to calculate multi-channel cross-correlation functions. All three-component noise records of each array were normalized simultaneously to retain relative amplitude information between different stations and different components. We observed clear Rayleigh waves and Love waves on the cross-correlations of both arrays at 0.3 - 1 s period. The phase travel times of the Rayleigh waves on both arrays were measured by frequency-time analysis (FTAN), and inverted for Rayleigh wave phase velocity profiles of the upper 500 m depth. For both arrays, we observe prominent asymmetric low velocity zones which narrow with depth. At the BS array near the Hemet Stepover, an approximately 250m wide slow zone is observed to be offset by 75m to the northeast of the surface fault trace. At the RR array near the Anza segment of the fault, a similar low velocity zone width and offset are observed, along with a 10% across-fault velocity contrast. Analyses of Rayleigh wave ellipticity (H/V ratio), Love wave phase travel times, and site amplification are in progress. By using multiple measurements from ambient noise cross-correlations, we can obtain strong constraints on the local damage zone structure of the San Jacinto Fault. The results contribute to improved understanding of rupture directivity, maximum earthquake magnitude and more generally seismic hazard associated with the San Jacinto fault zone.

  18. Hydrologic test plans for large-scale, multiple-well tests in support of site characterization at Hanford, Washington

    Rogers, P.M.; Stone, R.; Lu, A.H.

    1985-01-01

    The Basalt Waste Isolation Project is preparing plans for tests and has begun work on some tests that will provide the data necessary for the hydrogeologic characterization of a site located on a United States government reservation at Hanford, Washington. This site is being considered for the Nation's first geologic repository of high level nuclear waste. Hydrogeologic characterization of this site requires several lines of investigation which include: surface-based small-scale tests, testing performed at depth from an exploratory shaft, geochemistry investigations, regional studies, and site-specific investigations using large-scale, multiple-well hydraulic tests. The large-scale multiple-well tests are planned for several locations in and around the site. These tests are being designed to provide estimates of hydraulic parameter values of the geologic media, chemical properties of the groundwater, and hydrogeologic boundary conditions at a scale appropriate for evaluating repository performance with respect to potential radionuclide transport

  19. Investigation of hair dye deposition, hair color loss, and hair damage during multiple oxidative dyeing and shampooing cycles.

    Zhang, Guojin; McMullen, Roger L; Kulcsar, Lidia

    2016-01-01

    Color fastness is a major concern for consumers and manufacturers of oxidative hair dye products. Hair dye loss results from multiple wash cycles in which the hair dye is dissolved by water and leaches from the hair shaft. In this study, we carried out a series of measurements to help us better understand the kinetics of the leaching process and pathways associated with its escape from the fiber. Hair dye leaching kinetics was measured by suspending hair in a dissolution apparatus and monitoring the dye concentration in solution (leached dye) with an ultraviolet-visible spectrophotometer. The physical state of dye deposited in hair fibers was evaluated by a reflectance light microscopy technique, based on image stacking, allowing enhanced depth of field imaging. The dye distribution within the fiber was monitored by infrared spectroscopic imaging of hair fiber cross sections. Damage to the ultrafine structure of the hair cuticle (surface, endocuticle, and cell membrane complex) and cortex (cell membrane complex) was determined in hair cross sections and on the hair fiber surface with atomic force microscopy. Using differential scanning calorimetry, we investigated how consecutive coloring and leaching processes affect the internal proteins of hair. Further, to probe the surface properties of hair we utilized contact angle measurements. This study was conducted on both pigmented and nonpigmented hair to gain insight into the influence of melanin on the hair dye deposition and leaching processes. Both types of hair were colored utilizing a commercial oxidative hair dye product based on pyrazole chemistry.

  20. New Insights in the Pathogenesis of Multiple Sclerosis—Role of Acrolein in Neuronal and Myelin Damage

    Riyi Shi

    2013-10-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic β-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients.

  1. EUV soft X-ray characterization of a FEL multilayer optics damaged by multiple shot laser beam

    Giglia, A.; Mahne, N.; Bianco, A.; Svetina, C.; Nannarone, S.

    2011-01-01

    We have investigated the damaging effects of a femtosecond pulsed laser beam with 400 nm wavelength on a Mo/Si EUV multilayer. The exposures have been done in vacuum with multiple pulses (5 pulses/mm 2 ) of 120 fs varying the laser fluence in the 38-195 mJ/cm 2 range. The analysis of the different irradiated regions has been performed ex-situ by means of different techniques, including specular and diffuse reflectivity, X-ray photoemission spectroscopy (XPS) and total electron yield (TEY) in the EUV and soft X-ray range. Surface images have been acquired by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Results clearly indicate a progressive degradation of the EUV multilayer performances with the increase of the laser fluence. Spectroscopic analysis allowed to correlate the decrease of reflectivity with the degradation of the multilayer stacking, ascribed to Mo-Si intermixing at the Mo/Si interfaces of the first layers, close to the surface of the mirror.

  2. How and why discontinuous multiple-in-line-damage results in much higher Jc than continuous columnar pinning centres

    Weinstein, Roy; Gandini, Alberto; Sawh, Ravi; Mayes, Bill; Parks, Drew

    2006-01-01

    We review a recent experiment in which pinning centres, composed of discontinuous multiple-in-line damage (MILD), were compared to continuous columnar pinning centres (CCPCs). The methods used, results of the experiment, and the initial steps taken toward a phenomenological theory explaining the unusual results, are discussed. Experimental results show that MILD pinning centres, despite their reduced pinning potential, are far superior to CCPCs. Using MILD pinning, a new record J c has been achieved in large grain YBCO. The value of H irr (MILD) is comparable to, or larger, than H irr (CCPCs). Pinning effects alone, with no modification of texture, weak links or oxygenation of the YBCO, increase J c by as much as a factor of 17. Splay is expected to further increase this factor. The experimental dependence of J c on the energy lost by the ion per unit length is approximately reproduced by a phenomenological theory, including only the effects of diminished percolation, critical temperature, and pinning potential

  3. Multiple Nonspecific Sites of Joint Pain Outside the Knees Develop in Persons With Knee Pain.

    Felson, David T; Niu, Jingbo; Quinn, Emily K; Neogi, Tuhina; Lewis, Cara L; Lewis, Cora E; Frey Law, Laura; McCulloch, Chuck; Nevitt, Michael; LaValley, Michael

    2017-02-01

    Many persons with knee pain have joint pain outside the knee, but despite the impact and high frequency of this pain, its distribution and causes have not been studied. We undertook this study to test the hypothesis of those studying gait abnormalities who have suggested that knee pain causes pain in adjacent joints but that pain adaptation strategies are highly individualized. We studied persons ages 50-79 years with or at high risk of knee osteoarthritis who were recruited from 2 community-based cohorts, the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative, and we followed them up for 5-7 years. We excluded those with knee pain at baseline and compared those who had developed knee pain at the first follow-up examination (the index visit) with those who had not. We examined pain on most days at joint regions outside the knee in examinations after the index visit. Logistic regression analyses examined the risk of joint-specific pain adjusted for age, sex, body mass index, and symptoms of depression, and we performed sensitivity analyses excluding those with widespread pain. In the combined cohorts, 693 persons had knee pain at the index visit and 2,793 did not. A total of 79.6% of those with bilateral knee pain and 63.8% of those with unilateral knee pain had pain during follow-up in a joint region outside the knee, compared with 49.9% of those without knee pain. There was an increased risk of pain at most extremity joint sites, without a predilection for specific sites. Results were unchanged when those with widespread pain were excluded. Persons with chronic knee pain are at increased risk of pain in multiple joints in no specific pattern. © 2016, American College of Rheumatology.

  4. Single and multiple in-season measurements as indicators of at-harvest cotton boll damage caused by verde plant bug (Hemiptera: Miridae).

    Brewer, Michael J; Armstrong, J Scott; Parker, Roy D

    2013-06-01

    The ability to monitor verde plant bug, Creontiades signatus Distant (Hemiptera: Miridae), and the progression of cotton, Gossypium hirsutum L., boll responses to feeding and associated cotton boll rot provided opportunity to assess if single in-season measurements had value in evaluating at-harvest damage to bolls and if multiple in-season measurements enhanced their combined use. One in-season verde plant bug density measurement, three in-season plant injury measurements, and two at-harvest damage measurements were taken in 15 cotton fields in South Texas, 2010. Linear regression selected two measurements as potentially useful indicators of at-harvest damage: verde plant bug density (adjusted r2 = 0.68; P = 0.0004) and internal boll injury of the carpel wall (adjusted r2 = 0.72; P = 0.004). Considering use of multiple measurements, a stepwise multiple regression of the four in-season measurements selected a univariate model (verde plant bug density) using a 0.15 selection criterion (adjusted r2 = 0.74; P = 0.0002) and a bivariate model (verde plant bug density-internal boll injury) using a 0.25 selection criterion (adjusted r2 = 0.76; P = 0.0007) as indicators of at-harvest damage. In a validation using cultivar and water regime treatments experiencing low verde plant bug pressure in 2011 and 2012, the bivariate model performed better than models using verde plant bug density or internal boll injury separately. Overall, verde plant bug damaging cotton bolls exemplified the benefits of using multiple in-season measurements in pest monitoring programs, under the challenging situation when at-harvest damage results from a sequence of plant responses initiated by in-season insect feeding.

  5. T cells in multiple myeloma display features of exhaustion and senescence at the tumor site

    Claudia Zelle-Rieser

    2016-11-01

    Full Text Available Abstract Background Multiple myeloma is an incurable plasma cell malignancy that is mostly restricted to the bone marrow. Cancer-induced dysfunction of cytotoxic T cells at the tumor site may be responsible for immune evasion and therapeutical failure of immunotherapies. Therefore, enhanced knowledge about the actual status of T cells in myeloma bone marrow is urgently needed. Here, we assessed the expression of inhibitory molecules PD-1, CTLA-4, 2B4, CD160, senescence marker CD57, and CD28 on T cells of naive and treated myeloma patients in the bone marrow and peripheral blood and collected data on T cell subset distribution in both compartments. In addition, T cell function concerning proliferation and expression of T-bet, IL-2, IFNγ, and CD107a was investigated after in vitro stimulation by CD3/CD28. Finally, data was compared to healthy, age-matched donor T cells from both compartments. Methods Multicolor flow cytometry was utilized for the analyses of surface molecules, intracellular staining of cytokines was also performed by flow cytometry, and proliferation was assessed by 3H-thymidine incorporation. Statistical analyses were performed utilizing unpaired T test and Mann-Whitney U test. Results We observed enhanced T cell exhaustion and senescence especially at the tumor site. CD8+ T cells expressed several molecules associated with T cell exhaustion (PD-1, CTLA-4, 2B4, CD160 and T cell senescence (CD57, lack of CD28. This phenotype was associated with lower proliferative capacity and impaired function. Despite a high expression of the transcription factor T-bet, CD8+ T cells from the tumor site failed to produce IFNγ after CD3/CD28 in vitro restimulation and displayed a reduced ability to degranulate in response to T cell stimuli. Notably, the percentage of senescent CD57+CD28− CD8+ T cells was significantly lower in treated myeloma patients when compared to untreated patients. Conclusions T cells from the bone marrow of myeloma

  6. Multiple Comorbidities and Interest in Research Participation Among Clients of a Nonprofit Food Distribution Site.

    Higashi, Robin T; Craddock Lee, Simon J; Leonard, Tammy; Cuate, Erica L; Cole, Jay; Pruitt, Sandi L

    2015-10-01

    Persons accessing food from nonprofit distribution sites face numerous challenges and typically have significant unmet health needs. However, given limited and intermittent healthcare system engagement, this vulnerable population is underrepresented in clinical research. We sought to better understand the health needs of a nonclinical population to inform future research and interventions. Focus groups were conducted in English (n = 4) and Spanish (n = 4) with clients of Crossroads Community Services (CCS), the largest distributor of North Texas Food Bank. Discussions probed participants' health status, healthcare utilization, understanding and utilization of mammography, and attitudes toward participation in research. Participants included 42 CCS clients, primarily Hispanic or African American women. Participants reported multiple comorbid conditions among household members, yet utilization of health services was often limited by cost. The majority expressed interest in participating in research to communicate their health concerns and obtain emotional support. CCS clients represent a high-need, under-reached population willing to engage in health-related research that affords them opportunity to connect with peers in group settings and obtain information to improve management of daily life challenges. The Community Assistance Research (CARe) Initiative, a community-academic collaboration, establishes a much-needed opportunity for ongoing clinical research and intervention among this underserved population. © 2015 Wiley Periodicals, Inc.

  7. Presence of multiple sites containing polar material in spherical Escherichia coli cells that lack MreB.

    Nilsen, Trine; Yan, Arthur W; Gale, Gregory; Goldberg, Marcia B

    2005-09-01

    In rod-shaped bacteria, certain proteins are specifically localized to the cell poles. The nature of the positional information that leads to the proper localization of these proteins is unclear. In a screen for factors required for the localization of the Shigella sp. actin assembly protein IcsA to the bacterial pole, a mutant carrying a transposon insertion in mreB displayed altered targeting of IcsA. The phenotype of cells containing a transposon insertion in mreB was indistinguishable from that of cells containing a nonpolar mutation in mreB or that of wild-type cells treated with the MreB inhibitor A22. In cells lacking MreB, a green fluorescent protein (GFP) fusion to a cytoplasmic derivative of IcsA localized to multiple sites. Secreted full-length native IcsA was present in multiple faint patches on the surfaces of these cells in a pattern similar to that seen for the cytoplasmic IcsA-GFP fusion. EpsM, the polar Vibrio cholerae inner membrane protein, also localized to multiple sites in mreB cells and colocalized with IcsA, indicating that localization to multiple sites is not unique to IcsA. Our results are consistent with the requirement, either direct or indirect, for MreB in the restriction of certain polar material to defined sites within the cell and, in the absence of MreB, with the formation of ectopic sites containing polar material.

  8. Economic Valuation of On Site Material Damages of High Water on Economic Activities based in the City of Venice: Results from a Dose-Response-Expert-Based Valuation Approach

    Paulo A.L.D. Nunes; Margaretha Breil; Gretel Gambarelli

    2005-01-01

    The paper focuses on the economic assessment of damages caused by high water in the city of Venice. In particular, we focus our attention on a valuation exercise that addresses the estimation of monetary, short period, on-site damages due to high water events on the different business activities located in Venice. On-site damages include both mitigation costs, which refer to all types of financial expenditure undergone to avert physical and material damages caused by flooding, and remediation...

  9. FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2.

    Maria Castella

    2015-10-01

    Full Text Available The Fanconi anemia (FA-BRCA pathway mediates repair of DNA interstrand crosslinks. The FA core complex, a multi-subunit ubiquitin ligase, participates in the detection of DNA lesions and monoubiquitinates two downstream FA proteins, FANCD2 and FANCI (or the ID complex. However, the regulation of the FA core complex itself is poorly understood. Here we show that the FA core complex proteins are recruited to sites of DNA damage and form nuclear foci in S and G2 phases of the cell cycle. ATR kinase activity, an intact FA core complex and FANCM-FAAP24 were crucial for this recruitment. Surprisingly, FANCI, but not its partner FANCD2, was needed for efficient FA core complex foci formation. Monoubiquitination or ATR-dependent phosphorylation of FANCI were not required for the FA core complex recruitment, but FANCI deubiquitination by USP1 was. Additionally, BRCA1 was required for efficient FA core complex foci formation. These findings indicate that FANCI functions upstream of FA core complex recruitment independently of FANCD2, and alter the current view of the FA-BRCA pathway.

  10. Computational study of hydration at the TD damaged site of DNA in complex with repair enzyme T4 endonuclease V

    Pinak, Miroslav

    2000-02-01

    An analysis of the distribution of water around DNA surface focusing on the role of the distribution of water molecules in the proper recognition of damaged site by repair enzyme T4 Endonuclease V was performed. The native DNA dodecamer, dodecamer with the thymine dimer (TD) and complex of DNA and part of repair enzyme T4 Endonuclease V were examined throughout the 500 ps of molecular dynamics simulation. During simulation the number of water molecules close to the DNA atoms and the residence time were calculated. There is an increase in number of water molecules lying in the close vicinity to TD if compared with those lying close to two native thymines (TT). Densely populated area with water molecules around TD is one of the factors detected by enzyme during scanning process. The residence time was found higher for molecule of the complex and the six water molecules were found occupying the stabile positions between the TD and catalytic center close to atoms P, C3' and N3. These molecules originate water mediated hydrogen bond network that contribute to the stability of complex required for the onset of repair process. (author)

  11. Computational study of hydration at the TD damaged site of DNA in complex with repair enzyme T4 endonuclease V

    Pinak, Miroslav [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2000-02-01

    An analysis of the distribution of water around DNA surface focusing on the role of the distribution of water molecules in the proper recognition of damaged site by repair enzyme T4 Endonuclease V was performed. The native DNA dodecamer, dodecamer with the thymine dimer (TD) and complex of DNA and part of repair enzyme T4 Endonuclease V were examined throughout the 500 ps of molecular dynamics simulation. During simulation the number of water molecules close to the DNA atoms and the residence time were calculated. There is an increase in number of water molecules lying in the close vicinity to TD if compared with those lying close to two native thymines (TT). Densely populated area with water molecules around TD is one of the factors detected by enzyme during scanning process. The residence time was found higher for molecule of the complex and the six water molecules were found occupying the stabile positions between the TD and catalytic center close to atoms P, C3' and N3. These molecules originate water mediated hydrogen bond network that contribute to the stability of complex required for the onset of repair process. (author)

  12. Lymphocytes with multiple chromosomal damages in a large cohort of West Siberia residents: Results of long-term monitoring

    Druzhinin, Vladimir [Kemerovo State University, Kemerovo (Russian Federation); Federal State Budget Scientific Institution «The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences», Kemerovo (Russian Federation); Bakanova, Maria [Federal State Budget Scientific Institution «The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences», Kemerovo (Russian Federation); Fucic, Aleksandra, E-mail: afucic@imi.hr [Institute for Medical Research and Occupational Health, Zagreb (Croatia); Golovina, Tatiana [Kemerovo State University, Kemerovo (Russian Federation); Savchenko, Yana [Federal State Budget Scientific Institution «The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences», Kemerovo (Russian Federation); Sinitsky, Maxim; Volobaev, Valentin [Kemerovo State University, Kemerovo (Russian Federation)

    2016-02-15

    Highlights: • Study reports RC frequency in lymphocytes in the group of 3242 subjects. • The highest RC frequency was present in children environmentally exposed to radon. • In 85% of RCs double minutes were observed. • Results suggests that radon may be the leading factors causing RC. • RC may be a candidate biomarker for exposure to α-emitters. - Abstract: Cells with specific multiple chromosome aberrations, defined as rogue cells (RC) have been described in different populations, predominantly those exposed to radiation. The frequency, etiology and related health risks have still not been elucidated due to their low frequency of occurrences and rarely performed studies. This study reports RC frequency using chromosome aberration (CA) assay in peripheral lymphocytes in the group of 3242 subjects, during a 30-year long follow-up study in a general rural and urban population, children environmentally exposed to radon, occupationally exposed population and lung cancer patients from the Kemerovo region (Siberia, Russian Federation). Results show that the highest RC frequency was present in children environmentally exposed to radon and the lowest in the general urban population. Total frequency of CA did not correlate with frequency of RC. Genotoxic analysis of air and water samples excluded anthropogenic pollution as a possible cause of genome damage and RC frequency. In 85% of RCs, double minutes, observed in a large number of human tumors, were present. Results of CA analysis suggested that radon and its decay products (alpha-emitters) were the leading factors causing RC in subjects exposed to high LET radiation. Thus, RC may be a candidate biomarker for exposure to this type of radiation.

  13. Different damage observed in the villages of Pescara del Tronto and Vezzano after the M6.0 August 24, 2016 central Italy earthquake and site effects analysis

    Angelo Masi

    2017-01-01

    Full Text Available The authors have surveyed many damaged villages located at the epicentre of the ML=6.0 earthquake which occurred on August 24, 2016 in central Italy. Some unexpected anomalies were discovered such as very different levels of damage in Vezzano and Pescara del Tronto villages (Arquata del Tronto Municipality, Ascoli Piceno province. The two villages are situated just 1300 meters from each other. Pescara del Tronto suffered very heavy damage with many masonry building collapses and 48 fatalities, while Vezzano suffered only light damage to few buildings. This paper provides a preliminar analysis from an engineering and geophysics perspective. Particularly, rapid visual surveys were carried out in the two villages in order to detect possible significant differences in the vulnerability of their building stocks and site geophysical investigations were performed to detect possible local amplification effects.

  14. Infrared multiple photon dissociation spectroscopy of ciprofloxacin: Investigation of the protonation site

    Bodo, E. [Dip. Di Chimica, Universita di Roma ' La Sapienza' , p.le A. Moro 5, 00185 Rome (Italy); Ciavardini, A. [Dip. di Chimica e Tecnologie del Farmaco, Universita di Roma ' ' La Sapienza' ' , p.le A. Moro 5, 00185 Rome (Italy); Dip. di Scienze e Tecnologie Chimiche, Universita di Roma ' ' Tor Vergata' ' , via della Ricerca Scientifica, 00133 Rome (Italy); Giardini, A.; Paladini, A. [CNR - IMIP, Tito Scalo (PZ) (Italy); Piccirillo, S., E-mail: picciril@uniroma2.it [Dip. di Scienze e Tecnologie Chimiche, Universita di Roma ' ' Tor Vergata' ' , via della Ricerca Scientifica, 00133 Rome (Italy); Rondino, F. [ENEA, C.R. Casaccia, (UTT-MAT), Via Anguillarese, 301, 00123 Rome (Italy); Scuderi, D. [Laboratoire de Chimie Physique, Universite Paris Sud 11, UMR 8000, Orsay (France)

    2012-04-04

    Highlights: Black-Right-Pointing-Pointer IRMPD spectroscopy of protonated ciprofloxacin electrosprayed from methanol solution. Black-Right-Pointing-Pointer Quantum chemical calculations to identify the possible isomers differing in the protonation site. Black-Right-Pointing-Pointer Bands are assigned to the isomer protonated. Black-Right-Pointing-Pointer Bands are assigned to the isomer protonated at the piperazinyl amino group. - Abstract: The vibrational spectrum of isolated protonated ciprofloxacin was recorded in the range 1100-2000 cm{sup -1} by means of infrared multiple photon dissociation (IRMPD) spectroscopy. The spectrum was obtained by electrospraying a methanol solution of ciprofloxacin in a Paul ion trap, coupled to the tunable IR radiation of a free electron laser. This spectroscopic study has been complemented by quantum chemical calculations at the DFT and MP2 levels of theory to identify the possible structures present under our experimental conditions. Several low-energy isomers with protonation occurring at the piperazinyl amino group and at the carbonyl group are predicted in the energy range 0-84 kJ mol{sup -1}. A good agreement between the measured IRMPD spectrum and the calculated absorption spectrum is observed for the isomer protonated at the piperazinyl amino group. This isomer is calculated at MP2 level of theory to lie about 76 kJ/mol above the most stable isomer which is protonated at the quinone carbonyl group. This discrepancy can be rationalized by assuming that the protonation at the piperazinyl amino group, typical of the zwitterionic form that is found in protic solvents, is retained in the ESI process. The vibrational bands observed in the IRMPD spectrum are assigned to normal modes of the isomer protonated at the piperazinyl amino group, with deviations of less than 20 cm{sup -1} between measured and calculated frequencies.

  15. 15 CFR 921.33 - Boundary changes, amendments to the management plan, and addition of multiple-site components.

    2010-01-01

    ... management plan, and addition of multiple-site components. (a) Changes in the boundary of a Reserve and major changes to the final management plan, including state laws or regulations promulgated specifically for the... management plan change. Changes in the boundary of a Reserve involving the acquisition of properties not...

  16. Site-directed alkylation of multiple opioid receptors. I. Binding selectivity

    James, I.F.; Goldstein, A.

    1984-01-01

    A method for measuring and expressing the binding selectivity of ligands for mu, delta, and kappa opioid binding sites is reported. Radioligands are used that are partially selective for these sites in combination with membrane preparations enriched in each site. Enrichment was obtained by treatment of membranes with the alkylating agent beta-chlornaltrexamine in the presence of appropriate protecting ligands. After enrichment for mu receptors, [ 3 H] dihydromorphine bound to a single type of site as judged by the slope of competition binding curves. After enrichment for delta or kappa receptors, binding sites for [ 3 H] [D-Ala2, D-Leu5]enkephalin and [3H]ethylketocyclazocine, respectively, were still not homogeneous. There were residual mu sites in delta-enriched membranes but no evidence for residual mu or delta sites in kappa-enriched membranes were found. This method was used to identify ligands that are highly selective for each of the three types of sites

  17. (/sup 3/H)Spiperone binding sites in brain: autoradiographic localization of multiple receptors

    Palacios, J M; Niehoff, D L; Kuhar, M J [Johns Hopkins Univ., Baltimore, MD (USA). School of Medicine

    1981-01-01

    (/sup 3/H)Spiperone ((/sup 3/H)SP) binding sites were localized by light microscopic autoradiography, after in vitro labelling. The kinetic and pharmacological characteristics of these binding sites were studied in slide-mounted sections of rat forebrain, and optimal labeling conditions were defined. Autoradiograms were obtained by apposing emulsion-coated coverslips to labeled sections. Differential drug sensitivity allowed the selective displacement of (/sup 3/H)SP from dopamine receptors by ADTN, from serotonin receptors by cinanserin, from both by haloperidol and from unique spiperone sites by unlabeled spiperone. The various sites presented a differential anatomical localization. For example, only dopaminergic sites were found in the glomerular layer of the olfactory bulb; only serotonergic sites were found in lamina IV of the neocortex, and a high concentration of unique spiperone sites were found in parts of the hippocampus.

  18. The contribution to site core damage frequency from independent occurrences of initiators in two or more units: How low is it?

    Kim, Dong-San; Park, Jin Hee; Lim, Ho Gon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    Stutzke estimated the site risk by summing the contribution from common cause initiators and the contribution from single-unit initiators. He considered some kinds of multi-unit accident sequences caused by single-unit initiators. However, the contribution from independent occurrences of initiators in two or more units at a site was not taken into account. The purpose of this study is to estimate the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site. Some assumptions and methods used in this analysis are firstly described, and the results and conclusions of the analysis are described. In this study, the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site was estimated. A Korean six-unit site was selected as the reference site and the at-power internal events Level 1 PSA model for an OPR1000 unit at the reference site was used as the base model, and was modified to deal with some major dependencies between units at the site. Specifically, the availability of the AAC D/G, dependencies between offsite power recovery actions in different unis, and inter-unit CCF modeling for risk-significant components such as diesel generators were taken into account. As a result, the sum of dual-unit CDF due to independent occurrences of initiators in two units at the reference site was estimated to be sufficiently low to be neglected.

  19. CUTANEOUS INVOLVEMENT IN MULTIPLE MYELOMA AT AN UNUSUAL SITE: A RARE CASE REPORT

    Lohit Kumar

    2015-05-01

    Full Text Available Multiple myeloma is a rare cancer. According to the most recent data from the Surveillance, Epidemiology, and End Results (SEER program, multiple myeloma is the second most common haematological malignancy in the U.S. (after non - Hodgkin lymphoma, constitutes 1% of all cancers and constitutes 2% of all cancer deaths. Cutaneous involvement of multiple myeloma during treatment period is uncommon with fewer described in literature. Moreover, metastatic cutaneous involvement at the sole of the foot during treatment period of a IgA kappa type multiple myeloma patient followed by death has not encountered in literature. We have reported such a case

  20. Benefits of Multiple Methods for Evaluating HIV Counseling and Testing Sites in Pennsylvania.

    Encandela, John A.; Gehl, Mary Beth; Silvestre, Anthony; Schelzel, George

    1999-01-01

    Examines results from two methods used to evaluate publicly funded human immunodeficiency virus (HIV) counseling and testing in Pennsylvania. Results of written mail surveys of all sites and interviews from a random sample of 30 sites were similar in terms of questions posed and complementary in other ways. (SLD)

  1. Estimated airborne release of plutonium from Westinghouse Cheswick site as a result of postulated damage from severe wind and seismic hazard

    Mishima, J.; Schwendiman, L.C.; Ayer, J.E.

    1979-06-01

    The potential airborne releases of plutonium (source terms) from postulated damage sustained by the Westinghouse Plutonium Fuel Development Laboratories at the Cheswick site in Pennsylvania as a result of various levels of wind and seismic hazard are estimated. The source terms are based on damage scenarios originated by other specialists and range up to 260 mph for wind hazard and in excess of 0.39 g ground acceleration for seismic hazard. The approaches and factors used to estimate the source terms (inventories of dispersible materials at risk, damage levels and ratios, fractional airborne releases of dispersible materials under stress, atmosphere exchange rates, and source term ranges) are discussed. Source term estimates range from less than 10 -7 g plutonium to greater than 130 g plutonium over a four-day period

  2. Prediction of P53 mutants (multiple sites transcriptional activity based on structural (2D&3D properties.

    R Geetha Ramani

    Full Text Available Prediction of secondary site mutations that reinstate mutated p53 to normalcy has been the focus of intense research in the recent past owing to the fact that p53 mutants have been implicated in more than half of all human cancers and restoration of p53 causes tumor regression. However laboratory investigations are more often laborious and resource intensive but computational techniques could well surmount these drawbacks. In view of this, we formulated a novel approach utilizing computational techniques to predict the transcriptional activity of multiple site (one-site to five-site p53 mutants. The optimal MCC obtained by the proposed approach on prediction of one-site, two-site, three-site, four-site and five-site mutants were 0.775,0.341,0.784,0.916 and 0.655 respectively, the highest reported thus far in literature. We have also demonstrated that 2D and 3D features generate higher prediction accuracy of p53 activity and our findings revealed the optimal results for prediction of p53 status, reported till date. We believe detection of the secondary site mutations that suppress tumor growth may facilitate better understanding of the relationship between p53 structure and function and further knowledge on the molecular mechanisms and biological activity of p53, a targeted source for cancer therapy. We expect that our prediction methods and reported results may provide useful insights on p53 functional mechanisms and generate more avenues for utilizing computational techniques in biological data analysis.

  3. National Register of Historic Places multiple property documentation form -- Historic, archaeological, and traditional cultural properties of the Hanford Site, Washington

    Nickens, P.R.

    1997-08-01

    The US Department of Energy`s Hanford Site encompasses an area of 560 square miles on the Columbia River in southeastern Washington. Since 1943, the Hanford Site has existed as a protected area for activities primarily related to the production of radioactive materials for national defense uses. For cultural resources on the Hanford Site, establishment of the nuclear reservation as a high security area, with public access restricted, has resulted in a well-protected status, although no deliberate resource protection measures were in effect to mitigate effects of facilities construction and associated activities. Thus, the Hanford Site contains an extensive record of aboriginal archaeological sites and Native American cultural properties, along with pre-Hanford Euro-American sites (primarily archaeological in nature with the removal of most pre-1943 structures), and a considerable number of Manhattan Project/Cold War era buildings and structures. The recent mission change from production to clean up and disposal of DOE lands created a critical need for development and implementation of new and different cultural resource management strategies. DOE-RL has undertaken a preservation planning effort for the Hanford Site. The intent of this Plan is to enable DOE-RL to organize data and develop goals, objectives, and priorities for the identification, evaluation, registration, protection, preservation, and enhancement of the Site`s historical and cultural properties. Decisions made about the identification, evaluation, registration and treatment of historic properties are most aptly made when relationships between individual properties and other similar properties are considered. The historic context and the multiple property documentation (NTD) process provides DOE-RL the organizational framework for these decisions. Once significant patterns are identified, contexts developed, and expected properties are defined, the NTD process provides the foundation for future

  4. Quantitative study of the cervical spinal cord damage in patients with multiple sclerosis and neuromyelitis optica using diffusion tensor imaging

    Hou Huanxin; Li Yongmei; Lu Fajin; Luo Tianyou; Ouyang Yu; Zeng Chun; Zhang Zhiwei

    2012-01-01

    Objective: To investigate the changes of the cervical spinal cord in patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing neuromyelitis optica (RNMO) using diffusion tensor imaging (DTI) and to analyze its correlations with clinical disability scores. Methods: Thirty patients with MS (MS group),28 patients with NMO (NMO group) and 20 healthy volunteers were imaged using DTI on a 3.0 Tesla scanner. DTI indices of cervical spinal cord from all participants were measured, including mean diffusivity (MD) and fractional anisotropy (FA), and the correlations between the DTI metrics and the expanded disability status scale (EDSS) scores were assessed. One-way ANOVA, Dunnett-t test and Spearman correlation analysis were used for statistics. Results: (1) The values of MD among three groups were different at C3 level for left lateral and dorsal columns, C4 level for the central gray substance and dorsal columns, and C5-C6 level for all structures. There were significant differences among them (F=4.006-36.814, P<0.05). The values of FA were significantly different at all levels (F=5.561-98.128, P<0.05). (2) Compared with the control group, the values of MD were increased and FA were decreased for both MS and NMO groups, there were significant differences among them (t=-0.320-3.138, P<0.05). In MS and NMO groups, there were no significant differences of MD (t=-1.183-0.069, P>0.05), while the FA at C4-C6 levels (including the central gray substance, dorsal columns,right lateral columns and left lateral columns) for NMO group were 0.57 ± 0.09, 0.56 ± 0.11, 0.54 ±0.10, 0.57±0.09, 0.55 ±0.11, 0.52 ±0.13, 0.55 ±0.11, 0.54 ±0.13, 0.54±0.10, 0.54±0.11, 0.53 ±0.13, 0.52 ±0.11; and for MS group were 0.67 ±0.10, 0.68 ±0.10, 0.68 ±0.10, 0.70 ±0.12, 0.68 ±0.11, 0.69±0.10, 0.68 ±0.11, 0.69 ±0.12, 0.67 ±0.14, 0.68 ±0.15, 0.69 ±0.14, 0.69 ±0.16, and there were significant differences between two groups (t=-0.011-0.169, P<0.05). (3) Univariate

  5. DNA damage, acetylcholinesterase activity and lysosomal stability in native and transplanted mussels (Mytilus edulis) in areas close to coastal chemical dumping sites in Denmark

    Rank, J.; Lehtonen, K. K.; Strand, J.

    2007-01-01

    of chemical pollution complex, as seen especially in the variability in results on DNA damage, and also in regard to AChE activity. These investigations further stress the importance of understanding the effects of natural factors (salinity, temperature, water levels, rain and storm events) in correct......Biomarkers of genotoxicity (DNA damage, measured as tail moment in the Comet assay), neurotoxicity (acetylcholinesterase inhibition, AChE) and general stress (lysosomal membrane stability, LMS) were studied in native and transplanted blue mussels (Mytilus edulis) in coastal areas of western Denmark...... potentially affected by anthropogenic pollution originating from chemical dumping sites. The results indicate responses to pollution in all the biomarkers applied at the suspected areas, but the results were not consistent. Seasonal fluctuations in exposure situations at the study sites make interpretation...

  6. Direct Binding to Replication Protein A (RPA)-coated Single-stranded DNA Allows Recruitment of the ATR Activator TopBP1 to Sites of DNA Damage*

    Acevedo, Julyana; Yan, Shan; Michael, W. Matthew

    2016-01-01

    A critical event for the ability of cells to tolerate DNA damage and replication stress is activation of the ATR kinase. ATR activation is dependent on the BRCT (BRCA1 C terminus) repeat-containing protein TopBP1. Previous work has shown that recruitment of TopBP1 to sites of DNA damage and stalled replication forks is necessary for downstream events in ATR activation; however, the mechanism for this recruitment was not known. Here, we use protein binding assays and functional studies in Xenopus egg extracts to show that TopBP1 makes a direct interaction, via its BRCT2 domain, with RPA-coated single-stranded DNA. We identify a point mutant that abrogates this interaction and show that this mutant fails to accumulate at sites of DNA damage and that the mutant cannot activate ATR. These data thus supply a mechanism for how the critical ATR activator, TopBP1, senses DNA damage and stalled replication forks to initiate assembly of checkpoint signaling complexes. PMID:27129245

  7. The genealogy of sequences containing multiple sites subject to strong selection in a subdivided population.

    Nordborg, Magnus; Innan, Hideki

    2003-03-01

    A stochastic model for the genealogy of a sample of recombining sequences containing one or more sites subject to selection in a subdivided population is described. Selection is incorporated by dividing the population into allelic classes and then conditioning on the past sizes of these classes. The past allele frequencies at the selected sites are thus treated as parameters rather than as random variables. The purpose of the model is not to investigate the dynamics of selection, but to investigate effects of linkage to the selected sites on the genealogy of the surrounding chromosomal region. This approach is useful for modeling strong selection, when it is natural to parameterize the past allele frequencies at the selected sites. Several models of strong balancing selection are used as examples, and the effects on the pattern of neutral polymorphism in the chromosomal region are discussed. We focus in particular on the statistical power to detect balancing selection when it is present.

  8. Inference Generation during Text Comprehension by Adults with Right Hemisphere Brain Damage: Activation Failure Versus Multiple Activation.

    Tompkins, Connie A.; Fassbinder, Wiltrud; Blake, Margaret Lehman; Baumgaertner, Annette; Jayaram, Nandini

    2004-01-01

    ourse comprehensionEvidence conflicts as to whether adults with right hemisphere brain damage (RHD) generate inferences during text comprehension. M. Beeman (1993) reported that adults with RHD fail to activate the lexical-semantic bases of routine bridging inferences, which are necessary for comprehension. But other evidence indicates that adults…

  9. Significant accumulation of persistent organic pollutants and dysregulation in multiple DNA damage repair pathways in the electronic-waste-exposed populations

    He, Xiaobo; Jing, Yaqing; Wang, Jianhai; Li, Keqiu [Basic Medical College, Tianjin Medical University, Tianjin 300070 (China); Yang, Qiaoyun [Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070 (China); Zhao, Yuxia [Basic Medical College, Tianjin Medical University, Tianjin 300070 (China); Li, Ran [State Key Joint Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering and Center for Environment and Health, Peking University, Beijing 100871 (China); Ge, Jie [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060 (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060 (China); Qiu, Xinghua, E-mail: xhqiu@pku.edu.cn [State Key Joint Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering and Center for Environment and Health, Peking University, Beijing 100871 (China); Li, Guang, E-mail: lig@tijmu.edu.cn [Basic Medical College, Tianjin Medical University, Tianjin 300070 (China)

    2015-02-15

    Electronic waste (e-waste) has created a worldwide environmental and health problem, by generating a diverse group of hazardous compounds such as persistent organic pollutants (POPs). Our previous studies demonstrated that populations from e-waste exposed region have a significantly higher level of chromosomal aberrancy and incidence of DNA damage. In this study, we further demonstrated that various POPs persisted at a significantly higher concentration in the exposed group than those in the unexposed group. The level of reactive oxygen species and micronucleus rate were also significantly elevated in the exposed group. RNA sequencing analysis revealed 31 genes in DNA damage responses and repair pathways that were differentially expressed between the two groups (Log 2 ratio >1 or <−1). Our data demonstrated that both females and males of the exposed group have activated a series of DNA damage response genes; however many important DNA repair pathways have been dysregulated. Expressions of NEIL1/3 and RPA3, which are critical in initiating base pair and nucleotide excision repairs respectively, have been downregulated in both females and males of the exposed group. In contrast, expression of RNF8, an E3 ligase involved in an error prone non-homologous end joining repair for DNA double strand break, was upregulated in both genders of the exposed group. The other genes appeared to be differentially expressed only when the males or females of the two groups were compared respectively. Importantly, the expression of cell cycle regulatory gene CDC25A that has been implicated in multiple kinds of malignant transformation was significantly upregulated among the exposed males while downregulated among the exposed females. In conclusion, our studies have demonstrated significant correlations between e-waste disposing and POPs accumulation, DNA lesions and dysregulation of multiple DNA damage repair mechanisms in the residents of the e-waste exposed region. - Highlights:

  10. Evaluation of simultaneous binding of Chromomycin A3 to the multiple sites of DNA by the new restriction enzyme assay.

    Murase, Hirotaka; Noguchi, Tomoharu; Sasaki, Shigeki

    2018-06-01

    Chromomycin A3 (CMA3) is an aureolic acid-type antitumor antibiotic. CMA3 forms dimeric complexes with divalent cations, such as Mg 2+ , which strongly binds to the GC rich sequence of DNA to inhibit DNA replication and transcription. In this study, the binding property of CMA3 to the DNA sequence containing multiple GC-rich binding sites was investigated by measuring the protection from hydrolysis by the restriction enzymes, AccII and Fnu4HI, for the center of the CGCG site and the 5'-GC↓GGC site, respectively. In contrast to the standard DNase I footprinting method, the DNA substrates are fully hydrolyzed by the restriction enzymes, therefore, the full protection of DNA at all the cleavable sites indicates that CMA3 simultaneously binds to all the binding sites. The restriction enzyme assay has suggested that CMA3 has a high tendency to bind the successive CGCG sites and the CGG repeat. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning - an ultrahigh-field MR pilot study

    Sinnecker, Tim; Oberwahrenbrock, Timm; Zimmermann, Hanna; Ramien, Caren; Brandt, Alexander U.; Metz, Imke; Brueck, Wolfgang; Pfueller, Caspar F.; Doerr, Jan; Harms, Lutz; Ruprecht, Klemens; Hahn, Katrin; Niendorf, Thoralf; Paul, Friedemann; Wuerfel, Jens

    2015-01-01

    To investigate posterior visual pathway damage in multiple sclerosis using ultrahigh-field magnetic resonance imaging (MRI) at 7 Tesla (7 T), and to determine its correlation with visual disability and retinal fibre layer (RNFL) damage detectable by optic coherence tomography (OCT). We studied 7 T MRI, OCT, functional acuity contrast testing (FACT), and visually evoked potentials (VEP, n = 16) in 30 patients (including 26 relapsing-remitting MS and four clinically isolated syndrome patients) and 12 healthy controls to quantify RNFL thickness, optic radiation lesion volume, and optic radiation thickness. Optic radiation lesion volume was associated with thinning of the optic radiation (p < 0.001), delayed VEP (p = 0.031), and visual disability indicated by FACT (p = 0.020). Furthermore, we observed an inverse correlation between optic radiation lesion volume and RNFL thickness (p < 0.001), including patients without previous optic neuritis (p < 0.001). Anterior visual pathway damage, but also (subclinical) optic radiation integrity loss detectable by 7 T MRI are common findings in MS that are mutually affected. Given the association between optic radiation damage, visual impairment, and increased VEP latency in this exploratory study of a limited sample size, clinicians should be aware of acute lesions within the optic radiation in patients with (bilateral) visual disturbances. (orig.)

  12. Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning - an ultrahigh-field MR pilot study

    Sinnecker, Tim [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Asklepios Fachklinikum Teupitz, Department of Neurology, Teupitz (Germany); Oberwahrenbrock, Timm; Zimmermann, Hanna; Ramien, Caren; Brandt, Alexander U. [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Metz, Imke; Brueck, Wolfgang [University Medicine Goettingen, Institute of Neuropathology, Goettingen (Germany); Pfueller, Caspar F.; Doerr, Jan [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Clinical and Experimental Multiple Sclerosis Research Center, Berlin (Germany); Harms, Lutz; Ruprecht, Klemens [Charite - Universitaetsmedizin Berlin, Clinical and Experimental Multiple Sclerosis Research Center, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Hahn, Katrin [Charite - Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Niendorf, Thoralf [Max Delbrueck Center for Molecular Medicine, Berlin Ultrahigh Field Facility (B.U.F.F), Berlin (Germany); Charite - Universitaetsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Experimental and Clinical Research Center, Berlin (Germany); Paul, Friedemann [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Clinical and Experimental Multiple Sclerosis Research Center, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Experimental and Clinical Research Center, Berlin (Germany); Wuerfel, Jens [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine, Berlin Ultrahigh Field Facility (B.U.F.F), Berlin (Germany); University Medicine Goettingen, Institute of Neuroradiology, Goettingen (Germany)

    2015-01-15

    To investigate posterior visual pathway damage in multiple sclerosis using ultrahigh-field magnetic resonance imaging (MRI) at 7 Tesla (7 T), and to determine its correlation with visual disability and retinal fibre layer (RNFL) damage detectable by optic coherence tomography (OCT). We studied 7 T MRI, OCT, functional acuity contrast testing (FACT), and visually evoked potentials (VEP, n = 16) in 30 patients (including 26 relapsing-remitting MS and four clinically isolated syndrome patients) and 12 healthy controls to quantify RNFL thickness, optic radiation lesion volume, and optic radiation thickness. Optic radiation lesion volume was associated with thinning of the optic radiation (p < 0.001), delayed VEP (p = 0.031), and visual disability indicated by FACT (p = 0.020). Furthermore, we observed an inverse correlation between optic radiation lesion volume and RNFL thickness (p < 0.001), including patients without previous optic neuritis (p < 0.001). Anterior visual pathway damage, but also (subclinical) optic radiation integrity loss detectable by 7 T MRI are common findings in MS that are mutually affected. Given the association between optic radiation damage, visual impairment, and increased VEP latency in this exploratory study of a limited sample size, clinicians should be aware of acute lesions within the optic radiation in patients with (bilateral) visual disturbances. (orig.)

  13. DC-Analyzer-facilitated combinatorial strategy for rapid directed evolution of functional enzymes with multiple mutagenesis sites.

    Wang, Xiong; Zheng, Kai; Zheng, Huayu; Nie, Hongli; Yang, Zujun; Tang, Lixia

    2014-12-20

    Iterative saturation mutagenesis (ISM) has been shown to be a powerful method for directed evolution. In this study, the approach was modified (termed M-ISM) by combining the single-site saturation mutagenesis method with a DC-Analyzer-facilitated combinatorial strategy, aiming to evolve novel biocatalysts efficiently in the case where multiple sites are targeted simultaneously. Initially, all target sites were explored individually by constructing single-site saturation mutagenesis libraries. Next, the top two to four variants in each library were selected and combined using the DC-Analyzer-facilitated combinatorial strategy. In addition to site-saturation mutagenesis, iterative saturation mutagenesis also needed to be performed. The advantages of M-ISM over ISM were that the screening effort is greatly reduced, and the entire M-ISM procedure was less time-consuming. The M-ISM strategy was successfully applied to the randomization of halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) when five interesting sites were targeted simultaneously. After screening 900 clones in total, six positive mutants were obtained. These mutants exhibited 4.0- to 9.3-fold higher k(cat) values than did the wild-type HheC toward 1,3-dichloro-2-propanol. However, with the ISM strategy, the best hit showed a 5.9-fold higher k(cat) value toward 1,3-DCP than the wild-type HheC, which was obtained after screening 4000 clones from four rounds of mutagenesis. Therefore, M-ISM could serve as a simple and efficient version of ISM for the randomization of target genes with multiple positions of interest.

  14. Benzo(a)pyrene metabolism, DNA-binding and UV-induced repair of DNA damage in cultured skin fibroblasts from a patient with unilateral multiple basal cell carcinoma

    Don, P.S.C.; Mukhtar, H.; Das, M.; Berger, N.A.; Bickers, D.R.

    1989-01-01

    The metabolism of benzo(a)pyrene (BP), and its subsequent binding to DNA, and the repair of UV-induced DNA damage were studied in fibroblasts cultured from the skin of a 61-year-old male who had multiple basal cell carcinoma (BCC) (>100) on his left upper trunk. Results suggest that BP metabolism and repair of DNA are altered in tumor-bearing site (TSB) cells and that patients with this type of metabolic profile may be at higher risk of the development of cutaneous neoplasms. It is also possible that fibroblasts from tumour bearing skin undergo some as yet unexplained alteration in carcinogen metabolism as a consequence of the induction of neoplasia. (author)

  15. Multiple Sclerosis

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  16. Lead induces DNA damage and alteration of ALAD and antioxidant genes mRNA expression in construction site workers.

    Akram, Zertashia; Riaz, Sadaf; Kayani, Mahmood Akhtar; Jahan, Sarwat; Ahmad, Malik Waqar; Ullah, Muhammad Abaid; Wazir, Hizbullah; Mahjabeen, Ishrat

    2018-01-16

    Oxidative stress and DNA damage are considered as possible mechanisms involved in lead toxicity. To test this hypothesis, DNA damage and expression variations of aminolevulinic acid dehydratase (ALAD), superoxide dismutase 2 (SOD2), and 8-oxoguanine DNA glycosylase 2a (OGG1-2a) genes was studied in a cohort of 100 exposed workers and 100 controls with comet assay and real-time polymerse chain reaction (PCR). Results indicated that increased number of comets was observed in exposed workers versus controls (p gene.

  17. A New Neutron Multiplicity Counter for the Measurement of Impure Plutonium Metal at Westinghouse Savannah River Site

    Baker, L.B.; Faison, D.M.; Langner, D.G.; Sweet, M.R.; Salazar, S.D.; Kroncke, K.E.

    1998-07-01

    A new neutron multiplicity counter has been designed, fabricated, characterized, and installed for use in the assay of impure plutonium metal buttons from the FB-Line at the Westinghouse Savannah River Site (WSRS). This instrument incorporates the performance characteristics of the Pyrochemical or In-plant Multiplicity Counter with the package size of the Plutonium Scrap Multiplicity Counter. In addition, state-of-the art features such as the de-randomizer circuit and separate ring outputs have been added. The counter consists of 113, 71 cm active length 3He tubes in a polyethylene moderator. Its efficiency for 252Cf is 57.8 percent, the highest of any multiplicity counter to date. Its die-away time is 50.4 ms and its deadtime is 50 ns. In this paper we will present the characterization data for the counter and the results of preliminary metal measurements at WSRS. We will also discuss the new challenges the impure metal buttons from FB-Line are presenting to the multiplicity counting technique

  18. Evaluation of the feasibility for detecting hidden corrosion damage in multi-layer gusset plates using multiple inspection techniques

    Cobb, Adam C.; Duffer, Charles E.; Light, Glenn M.

    2014-01-01

    Gusset plates are used to connect the members in truss bridges and they are usually inspected using calipers or conventional thickness measurement ultrasonic testing (UT) devices. The damage mechanism of particular concern in gusset plates is corrosion and the regions most susceptible to corrosion damage are on the gusset interior surface where it intersects the chord, diagonal, and vertical members from water collecting at the interfaces. For heavily loaded gusset plates, one or more shingle plates are used to reinforce the gusset plate, creating a multi-layer structure. While the areas with corrosion damage remain near the members on the gusset plate, the shingle plates cover the gusset plate and greatly limit the surface access to the gusset plate, making UT thickness measurement impractical. Because of the critical nature of the gussets, a viable inspection strategy for multi-layer gusset assemblies must be developed. The premise of this research and development effort was to develop viable, field-deployable inspection approaches for this problem area. This paper presents three separate inspection approaches: two ultrasonic-based techniques and one radiographic approach. Each of these techniques was evaluated on a mock-up specimen provided by the Federal Highway Administration (FHWA) that is representative of gusseted connection from a truss bridge

  19. Evaluation of the feasibility for detecting hidden corrosion damage in multi-layer gusset plates using multiple inspection techniques

    Cobb, Adam C.; Duffer, Charles E.; Light, Glenn M. [Southwest Research Institute, 6220 Culebra Road, San Antonio, TX 78238-5166 (United States)

    2014-02-18

    Gusset plates are used to connect the members in truss bridges and they are usually inspected using calipers or conventional thickness measurement ultrasonic testing (UT) devices. The damage mechanism of particular concern in gusset plates is corrosion and the regions most susceptible to corrosion damage are on the gusset interior surface where it intersects the chord, diagonal, and vertical members from water collecting at the interfaces. For heavily loaded gusset plates, one or more shingle plates are used to reinforce the gusset plate, creating a multi-layer structure. While the areas with corrosion damage remain near the members on the gusset plate, the shingle plates cover the gusset plate and greatly limit the surface access to the gusset plate, making UT thickness measurement impractical. Because of the critical nature of the gussets, a viable inspection strategy for multi-layer gusset assemblies must be developed. The premise of this research and development effort was to develop viable, field-deployable inspection approaches for this problem area. This paper presents three separate inspection approaches: two ultrasonic-based techniques and one radiographic approach. Each of these techniques was evaluated on a mock-up specimen provided by the Federal Highway Administration (FHWA) that is representative of gusseted connection from a truss bridge.

  20. Brief communication: On-site data collection of damage caused by flash floods: Experiences from Braunsbach, Germany, in May/June 2016

    Laudan, Jonas; Rözer, Viktor; Sieg, Tobias; Vogel, Kristin; Thieken, Annegret

    2017-04-01

    At the end of May and beginning of June 2016, several municipalities in Southern Germany suffered from severe flash floods and debris flows which have been triggered by intense rainfall in Central Europe. Overall, the insured losses of these events amounted to EUR 1.2 billion in Germany. Especially the strong and unexpected flash flood on May 29th in Braunsbach (Baden Wurttemberg) - a small village counting about 1,000 residents - attracted media and policymakers due to its devastating character. The understanding of damage caused by flash floods requires ex-post collection of relevant but yet sparsely available information, linking process intensities to damage by using adequate methods of data gathering. Thus, on-site data collection was carried out after the flash flood event in Braunsbach, using open source software as helpful and efficient tool for data acquisition and evaluation. A digital survey was designed and conducted by a team of five researchers who investigated all buildings affected by water and debris flows. The collected data includes an estimation of a particular damage class, the inundation depth, and other relevant information. A post - hoc data analysis was done with R 3.3.1 and QGIS 2.14.3, performing both, a Random Forest Model (RF) and Random Generalized Linear Model (RGLM) as well as preparing a Spearman's rank correlation matrix. For visual interpretation and better overview of the study area and analysis results, a "process intensity" map was created, revealing important links of damage driving factors. We find that not only the water depth, which is often considered as only damage driving factor in riverine flood loss modelling, but also the exposition of a building to the flow direction and susceptible building parts like e.g. shop windows seem to be risk factors in flash-flood prone regions. Although no significant correlations were found, the analyses indicate that also building material (i.e. half-timbered or masonry) and structural

  1. Ensemble approach combining multiple methods improves human transcription start site prediction.

    Dineen, David G

    2010-01-01

    The computational prediction of transcription start sites is an important unsolved problem. Some recent progress has been made, but many promoters, particularly those not associated with CpG islands, are still difficult to locate using current methods. These methods use different features and training sets, along with a variety of machine learning techniques and result in different prediction sets.

  2. Biochemical study of multiple drug recognition sites on central benzodiazepine receptors

    Trifiletti, R.R.

    1986-01-01

    The benzodiazepine receptor complex of mammalian brain possesses recognition sites which mediate (at least in part) the pharmacologic actions of the 1,4-benzodiazepines and barbiturates. Evidence is provided suggesting the existence of least seven distinct drug recognition sites on this complex. Interactions between the various recognition sites have been explored using radioligand binding techniques. This information is utilized to provide a comprehensive scheme for characterizing receptor-active drugs on an anxiolytic-anticonvulsant/proconvulsant continuum using radioligand binding techniques, as well as a comprehensive program for identifying potential endogenous receptor-active substances. Further evidence is provided here supporting the notion of benzodiazepine recognition site heterogeneity. Classical 1,4-benzodiazepines do not appear to differentiate two populations of benzodiazepine receptors in an equilibrium sense, but appear to do so in a kinetic sense. An apparent physical separation of the two receptor subtypes can be achieved by differential solubilization. The benzodiazepine binding subunit can be identified by photoaffinity labeling with the benzodiazepine agonist (/sup 3/H)flunitrazepan. Conditions for reproducible partial proteolytic mapping of (/sup 3/H)flunitrazepam photoaffinity labeled receptors are established. From these maps, it is concluded that there are probably no major differences in the primary sequence of the benzodiazepine binding subunit in various regions of the rat central nervous system.

  3. Pacemaker activity in a sensory ending with multiple encoding sites : The cat muscle spindle primary ending

    Banks, RW; Hulliger, M; Scheepstra, KA; Otten, E

    1997-01-01

    1. A combined physiological, histological and computer modelling study was carried out on muscle spindles of the cat tenuissimus muscle to examine whether there was any correlation between the functional interaction of putative encoding sites, operated separately by static and dynamic fusimotor

  4. Assessment of multiple geophysical techniques for the characterization of municipal waste deposit sites

    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.

  5. Assessing the quality of websites providing information on multiple sclerosis: evaluating tools and comparing sites.

    Harland, Juliet; Bath, Peter

    2007-09-01

    The quality of health information available on the Internet has proved difficult to assess objectively. The Internet's growing popularity as a source of health information, accompanied by the lack of regulation of websites, has resulted in research that has developed and tested tools to evaluate health website quality. However, only a few studies have tested the validity and reliability of these tools. There is a lack of consensus about appropriate indicators with which to operationalize the concept of quality health information. This study aimed to contribute to this research by testing the validity and reliability of existing tools, through their application to websites that provided information about multiple sclerosis. Furthermore, a specific tool for evaluating multiple sclerosis information was developed, contributing to the debate about suitable criteria for measuring the ;quality' of health information on the web.

  6. Interim guidelines for protecting fire-fighting personnel from multiple hazards at nuclear plant sites

    Klein, A.R.; Bloom, C.W.

    1989-07-01

    This report provides interim guidelines for reducing the impact to fire fighting and other supporting emergency response personnel from the multiple hazards of radiation, heat stress, and trauma when fighting a fire in a United States commercial nuclear power plant. Interim guidelines are provided for fire brigade composition, training, equipment, procedures, strategies, heat stress and trauma. In addition, task definitions are provided to evaluate and further enhance the interim guidelines over the long term. 19 refs

  7. Assessment of DNA Damage by RAPD in Paracentrotus lividus Embryos Exposed to Amniotic Fluid from Residents Living Close to Waste Landfill Sites

    Maurizio Guida

    2010-01-01

    Full Text Available The aim of this study was to assess the genotoxic effects of environmental chemicals on residents living near landfills. The study was based on samples of amniotic fluid from women living in the intensely polluted areas around the Campania region of Italy compared to a nonexposed control group. We evaluated the genetic effects that this amniotic fluids collected in contaminated sites had on Paracentrotus lividus embryos. DNA damage was detected through changes in RAPD (Random Amplified Polymorphism DNA profiles. The absence of the amplified DNA fragments indicated deletions in Paracentrotus lividus DNA exposed to the contaminated amniotic fluids when compared to equal exposure to uncontaminated fluids. These results show the ability of RAPD-PCR to detect and isolate DNA sequences representing genetic alterations induced in P. lividus embryos. Using this method, we identified two candidate target regions for DNA alterations in the genome of P. lividus. Our research indicates that RAPD-PCR in P. lividus embryo DNA can provide a molecular approach for studying DNA damage from pollutants that can impact human health. To our knowledge, this is the first time that assessment of DNA damage in P. lividus embryos has been tested using the RAPD strategy after exposure to amniotic fluid from residents near waste landfill sites.

  8. Dendrochemistry of multiple releases of chlorinated solvents at a former industrial site

    Balouet, Jean Christophe; Burken, Joel G.; Karg, Frank; Vroblesky, Don; Smith, Kevin T.; Grudd, Hakan; Rindby, Anders; Beaujard, Francois; Chalot, Michel

    2012-01-01

    Trees can take up and assimilate contaminants from the soil, subsurface, and groundwater. Contaminants in the transpiration stream can become bound or incorporated into the annual rings formed in trees of the temperate zones. The chemical analysis of precisely dated tree rings, called dendrochemistry, can be used to interpret past plant interactions with contaminants. This investigation demonstrates that dendrochemistry can be used to generate historical scenarios of past contamination of groundwater by chlorinated solvents at a site in Verl, Germany. Increment cores from trees at the Verl site were collected and analyzed by energy-dispersive X-ray fluorescence (EDXRF) line scanning. The EDXRF profiles showed four to six time periods where tree rings had anomalously high concentrations of chlorine (Cl) as an indicator of potential contamination by chlorinated solvents.

  9. Comparing the use of 4.6 um lasers versus 10.6 um lasers for mitigating damage site growth on fused silica surfaces

    Yang, S T; Matthews, M J; Elhadj, S; Cooke, D; Guss, G M; Draggoo, V G; Wegner, P J

    2010-10-21

    The advantage of using mid-infrared (IR) 4.6 {micro}m lasers, versus far-infrared 10.6 {micro}m lasers, for mitigating damage growth on fused silica is investigated. In contrast to fused silica's high absorption at 10.6 {micro}m, silica absorption at 4.6 {micro}m is two orders of magnitude less. The much reduced absorption at 4.6 {micro}m enables deep heat penetration into fused silica when it is heated using the mid-IR laser, which in turn leads to more effective mitigation of damage sites with deep cracks. The advantage of using mid-IR versus far-IR laser for damage growth mitigation under non-evaporative condition is quantified by defining a figure of merit (FOM) that relates the crack healing depth to laser power required. Based on our FOM, we show that for damage cracks up to at least 500 {micro}m in depth, mitigation using a 4.6 {micro}m mid-IR laser is more efficient than mitigation using a 10.6 {micro}m far-IR laser.

  10. Evolution of the Florida Launch Site Architecture: Embracing Multiple Customers, Enhancing Launch Opportunities

    Colloredo, Scott; Gray, James A.

    2011-01-01

    The impending conclusion of the Space Shuttle Program and the Constellation Program cancellation unveiled in the FY2011 President's budget created a large void for human spaceflight capability and specifically launch activity from the Florida launch Site (FlS). This void created an opportunity to re-architect the launch site to be more accommodating to the future NASA heavy lift and commercial space industry. The goal is to evolve the heritage capabilities into a more affordable and flexible launch complex. This case study will discuss the FlS architecture evolution from the trade studies to select primary launch site locations for future customers, to improving infrastructure; promoting environmental remediation/compliance; improving offline processing, manufacturing, & recovery; developing range interface and control services with the US Air Force, and developing modernization efforts for the launch Pad, Vehicle Assembly Building, Mobile launcher, and supporting infrastructure. The architecture studies will steer how to best invest limited modernization funding from initiatives like the 21 st elSe and other potential funding.

  11. Screening Mixtures of Small Molecules for Binding to Multiple Sites on the Surface Tetanus Toxin C Fragment by Bioaffinity NMR

    Cosman, M; Zeller, L; Lightstone, F C; Krishnan, V V; Balhorn, R

    2002-01-01

    also contains 3-sialyllactose (another predicted site 1 binder) and bisbenzimide 33342 (non-binder). A series of five predicted Site-2 binders were then screened sequentially in the presence of the Site-1 binder doxorubicin. These experiments showed that the compounds lavendustin A and naphthofluorescein-di-(β-D-galactopyranoside) binds along with doxorubicin to TetC. Further experiments indicate that doxorubicin and lavendustin are potential candidates to use in preparing a bidendate inhibitor specific for TetC. The simultaneous binding of two different predicted Site-2 ligands to TetC suggests that they may bind multiple sites. Another possibility is that the conformations of the binding sites are dynamic and can bind multiple diverse ligands at a single site depending on the pre-existing conformation of the protein, especially when doxorubicin is already bound

  12. [Total brain T2-hyperintense lesion-volume and the axonal damage in the normal-appearing white matter of brainstem in early lapsing-remitting multiple sclerosis].

    Pascual-Lozano, A M; Martínez-Bisbal, M C; Boscá-Blasco, I; Valero-Merino, C; Coret-Ferrer, F; Martí-Bonmatí, L; Martínez-Granados, B; Celda, B; Casanova-Estruch, B

    To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonal damage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. 40 relapsing-remitting multiple sclerosis patients and ten sex- and age-matched healthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired at time of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. At basal study we obtained an axonal loss (as a decrement of NAA/ Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation between the basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). Our data suggest that axonal damage is early in multiple sclerosis and higher in patients high basal TBT2LV, suggesting a possible relationship between these two phenomena.

  13. Investigation of reactive-ion-etch-induced damage of InP/InGaAs multiple quantum wells by photoluminescence

    Steffensen, O. M.; Birkedal, Dan; Hanberg, J.

    1995-01-01

    The effects of CH4/H2 reactive ion etching (RIE) on the optical properties of an InP/InGaAs multiple-quantum-well structure have been investigated by low-temperature photoluminescence (PL). The structure consisted of eight InGaAs quantum wells, lattice matched to InP, with nominal thicknesses of 0...

  14. Wisdom tooth extraction causing lingual nerve and styloglossus muscle damage: a mimic of multiple cranial nerve palsies

    Carr, A. S.; Evans, M.; Shah, S.; Catania, S.; Warren, J. D.; Gleeson, M. J.; Reilly, M. M.

    2017-01-01

    The combination of tongue hemianaesthesia, dysgeusia, dysarthria and dysphagia suggests the involvement of multiple cranial nerves. We present a case with sudden onset of these symptoms immediately following wisdom tooth extraction and highlight the clinical features that allowed localisation of the lesion to a focal, iatrogenic injury of the lingual nerve and adjacent styloglossus muscle.

  15. HPV Prevalence in Multiple Anatomical Sites among Men Who Have Sex with Men in Peru.

    Magaly M Blas

    Full Text Available Human Papilloma Virus (HPV infection is the most common sexually transmitted viral infection worldwide. HPV is highly prevalent in sexually active men who have sex with men (MSM and has been associated with anal cancer, penile cancer, and oropharyngeal cancer.From March to September 2011, we conducted a cross-sectional study of HPV prevalence among MSM above age 18 years. Participants were recruited using respondent driven sampling at Clinica Cayetano Heredia. All participants provided anal, genital, and oral samples for HPV DNA testing, and blood for HIV and HPV antibody testing.A total of 200 MSM were recruited in the study. The mean age was 34 years (range 18-59 years, SD = 9.4 and101 participants were HIV negative (99 HIV positive. HPV 6/11/16/18 or quadrivalent HPV vaccine (HPV4 genotype seroprevalence among HIV negative and positive MSM was 64.3% (55%-75.9% and 93.8% (87.6%-99.2% respectively (p<0.001. HIV positivity was associated with a higher prevalence of HPV4 and HPV 16/18 DNA at external genital sites and the anal canal. HPV4 DNA prevalence at external genital sites among HIV negative and positive MSM was 14.9% and 28.7% (p = 0.02 respectively, at anal canal was 50.9% and 79.0% (p = 0.001, and at the oral cavity was 9.9% and 8.5% (p = 0.6.HPV4 seroprevalence was high in our study among both HIV positives and negatives, with HPV DNA prevalence much lower, and the anal canal being the anatomical site with the highest HPV DNA prevalence. HPV prevention interventions are needed among MSM at high-risk for HIV infection.

  16. Site Assessment of Multiple-Sensor Approaches for Buried Utility Detection

    Alexander C. D. Royal

    2011-01-01

    Full Text Available The successful operation of buried infrastructure within urban environments is fundamental to the conservation of modern living standards. Open-cut methods are predominantly used, in preference to trenchless technology, to effect a repair, replace or install a new section of the network. This is, in part, due to the inability to determine the position of all utilities below the carriageway, making open-cut methods desirable in terms of dealing with uncertainty since the buried infrastructure is progressively exposed during excavation. However, open-cut methods damage the carriageway and disrupt society's functions. This paper describes the progress of a research project that aims to develop a multi-sensor geophysical platform that can improve the probability of complete detection of the infrastructure buried beneath the carriageway. The multi-sensor platform is being developed in conjunction with a knowledge-based system that aims to provide information on how the properties of the ground might affect the sensing technologies being deployed. The fusion of data sources (sensor data and utilities record data is also being researched to maximize the probability of location. This paper describes the outcome of the initial phase of testing along with the development of the knowledge-based system and the fusing of data to produce utility maps.

  17. A compact microelectrode array chip with multiple measuring sites for electrochemical applications

    Dimaki, Maria; Vergani, Marco; Heiskanen, Arto

    2014-01-01

    In this paper we demonstrate the fabrication and electrochemical characterization of a microchip with 12 identical but individually addressable electrochemical measuring sites, each consisting of a set of interdigitated electrodes acting as a working electrode as well as two circular electrodes...... functioning as a counter and reference electrode in close proximity. The electrodes are made of gold on a silicon oxide substrate and are passivated by a silicon nitride membrane. A method for avoiding the creation of high edges at the electrodes (known as lift-off ears) is presented. The microchip design...

  18. Use of multiple-site performance-contingent SEMG reward programming in pediatric rehabilitation: a retrospective review.

    Bolek, Jeffrey E

    2006-09-01

    We completed a retrospective review of the effectiveness of multi-site, performance-contingent reward programming on functional change in motor performance of 16 treatment resistant children. Patients were previously treated in physical or occupational therapy for head control, standing balance training, sitting and upper extremity use (brachial plexus injury). They then participated in a program that utilized multiple surface electromyography sites the use of which was rewarded with videos for performing the correct constellation of recruitment pattern (e.g., contracting some muscles while relaxing others). Onset of reward was calibrated for each patient and transfer of skill to outside the clinic was encouraged by linking a verbal cue to the correct motor plan. Fourteen of the 16 patients improved. The implications of the use of this technique in the treatment of motor dysfunction is discussed.

  19. Site specific X-ray induced changes in organic and metal organic compounds and their influence on global radiation damage

    Heintz, Desiree Ellen

    2012-07-01

    The aim of this work was to systematically investigate the effects of specific and global X-ray radiation damage to biological samples and obtain a conclusive model to describe the underlying principles. Based on the systematic studies performed in this work, it was possible to propose two conclusive mechanisms to describe X-ray induced photoreduction and global radiation damage. The influence of chemical composition, temperature and solvent on X-ray induced photoreduction was investigated by X-ray Absorption Near Edge Spectroscopy and single crystal X-ray diffraction of two B12 cofactors - cyano- and methylcobalamin - as well as iron(II) and iron(III) complexes. The obtained results revealed that X-ray induced photoreduction is a ligand dependent process, with a redox reaction taking place within the complex. It could further be shown that selective hydrogen abstraction plays an important role in the process of X-ray induced photoreduction. Based on the experimental results of this work, a model to describe X-ray induced photoreduction of metal organic complexes could be proposed. The process of X-ray induced hydrogen abstraction was further investigated in a combined X-ray and neutron diffraction study on the amino acids L-serine and L-alanine, which were used as model compounds for proteins, and the nucleoside deoxythymidine (thymidine) as a model for DNA. A damage mechanism for L-serine could be found. It involves the abstraction of two hydrogen atoms, one from the hydroxyl group and one from the adjacent methylene group. Such a hydrogen abstraction results in the formation of a carbonyl group. X-ray diffraction measurements on cyano- and methylcobalamin as well as on three metal amino acid complexes, containing nickel(II) and copper(II), respectively, were conducted to investigate the contribution of X-ray induced photoreduction to global radiation damage. Results from these measurements combined with the results from L-serine, L-alanine and thymidine allowed

  20. Site specific X-ray induced changes in organic and metal organic compounds and their influence on global radiation damage

    Heintz, Desiree Ellen

    2012-07-15

    The aim of this work was to systematically investigate the effects of specific and global X-ray radiation damage to biological samples and obtain a conclusive model to describe the underlying principles. Based on the systematic studies performed in this work, it was possible to propose two conclusive mechanisms to describe X-ray induced photoreduction and global radiation damage. The influence of chemical composition, temperature and solvent on X-ray induced photoreduction was investigated by X-ray Absorption Near Edge Spectroscopy and single crystal X-ray diffraction of two B12 cofactors - cyano- and methylcobalamin - as well as iron(II) and iron(III) complexes. The obtained results revealed that X-ray induced photoreduction is a ligand dependent process, with a redox reaction taking place within the complex. It could further be shown that selective hydrogen abstraction plays an important role in the process of X-ray induced photoreduction. Based on the experimental results of this work, a model to describe X-ray induced photoreduction of metal organic complexes could be proposed. The process of X-ray induced hydrogen abstraction was further investigated in a combined X-ray and neutron diffraction study on the amino acids L-serine and L-alanine, which were used as model compounds for proteins, and the nucleoside deoxythymidine (thymidine) as a model for DNA. A damage mechanism for L-serine could be found. It involves the abstraction of two hydrogen atoms, one from the hydroxyl group and one from the adjacent methylene group. Such a hydrogen abstraction results in the formation of a carbonyl group. X-ray diffraction measurements on cyano- and methylcobalamin as well as on three metal amino acid complexes, containing nickel(II) and copper(II), respectively, were conducted to investigate the contribution of X-ray induced photoreduction to global radiation damage. Results from these measurements combined with the results from L-serine, L-alanine and thymidine allowed

  1. Multiple ETS family proteins regulate PF4 gene expression by binding to the same ETS binding site.

    Yoshiaki Okada

    Full Text Available In previous studies on the mechanism underlying megakaryocyte-specific gene expression, several ETS motifs were found in each megakaryocyte-specific gene promoter. Although these studies suggested that several ETS family proteins regulate megakaryocyte-specific gene expression, only a few ETS family proteins have been identified. Platelet factor 4 (PF4 is a megakaryocyte-specific gene and its promoter includes multiple ETS motifs. We had previously shown that ETS-1 binds to an ETS motif in the PF4 promoter. However, the functions of the other ETS motifs are still unclear. The goal of this study was to investigate a novel functional ETS motif in the PF4 promoter and identify proteins binding to the motif. In electrophoretic mobility shift assays and a chromatin immunoprecipitation assay, FLI-1, ELF-1, and GABP bound to the -51 ETS site. Expression of FLI-1, ELF-1, and GABP activated the PF4 promoter in HepG2 cells. Mutation of a -51 ETS site attenuated FLI-1-, ELF-1-, and GABP-mediated transactivation of the promoter. siRNA analysis demonstrated that FLI-1, ELF-1, and GABP regulate PF4 gene expression in HEL cells. Among these three proteins, only FLI-1 synergistically activated the promoter with GATA-1. In addition, only FLI-1 expression was increased during megakaryocytic differentiation. Finally, the importance of the -51 ETS site for the activation of the PF4 promoter during physiological megakaryocytic differentiation was confirmed by a novel reporter gene assay using in vitro ES cell differentiation system. Together, these data suggest that FLI-1, ELF-1, and GABP regulate PF4 gene expression through the -51 ETS site in megakaryocytes and implicate the differentiation stage-specific regulation of PF4 gene expression by multiple ETS factors.

  2. IMPLANTABLE RESONATORS – A TECHNIQUE FOR REPEATED MEASUREMENT OF OXYGEN AT MULTIPLE DEEP SITES WITH IN VIVO EPR

    Li, Hongbin; Hou, Huagang; Sucheta, Artur; Williams, Benjamin B.; Lariviere, Jean P.; Khan, Nadeem; Lesniewski, Piotr N.; Swartz, Harold M.

    2013-01-01

    EPR oximetry using implantable resonators allow measurements at much deeper sites than are possible with surface resonators (> 80 mm vs. 10 mm) and have greater sensitivity at any depth. We report here the development of an improvement of the technique that now enables us to obtain the information from multiple sites and at a variety of depths. The measurements from the various sites are resolved using a simple magnetic field gradient. In the rat brain multi-probe implanted resonators measured pO2 at several sites simultaneously for over 6 months to record under normoxic, hypoxic and hyperoxic conditions. This technique also facilitates measurements in moving parts of the animal such as the heart, because the orientation of the paramagnetic material relative to the sensitive small loop is not altered by the motion. The measured response is very fast, enabling measurements in real time of physiological and pathological changes such as experimental cardiac ischemia in the mouse heart. The technique also is quite useful for following changes in tumor pO2, including applications with simultaneous measurements in tumors and adjacent normal tissues. PMID:20204802

  3. Heat, sight and scent: multiple cues influence foraging site selection by an ambush-foraging snake Hoplocephalus bungaroides (Elapidae

    Weiguo DU, Jonathan K. WEBB, Richard SHINE

    2009-08-01

    Full Text Available Most mobile organisms respond to multiple cues when selecting habitat types, and laboratory experiments that manipulate only single cues may fail to reveal the true complexity of habitat-selection behaviour. In south-eastern Australia, broad-headed snakes Hoplocephalus bungaroides (Elapidae lie in wait under sun-warmed rocks to ambush velvet geckos Oedura leseuerii (Gekkonidae. Previous laboratory work has shown that both the geckos and the snakes actively select hotter rather than colder rocks, and that the snakes actively select rocks scented by geckos. We manipulated rock temperature and the presence of two types of cues from geckos (chemical and visual information to clarify the causal basis for foraging site selection by the juveniles of this snake. When given a choice between cold lizard-scented rocks and hot unscented rocks, our captive snakes gave a higher priority to lizard scent than to temperature. The snakes also selected shelter-sites that provided visual as well as scent cues from lizards, rather than shelter-sites with scent cues alone. Thus, although broad-headed snakes show a direct preference for hotter rather than colder rocks in the laboratory, their choice of foraging site in the field may also be influenced by the presence of scent cues from prey. Our laboratory results suggest that habitat selection by broad-headed snakes may be more complex than has been suggested by previous single-factor laboratory trials[Current Zoology 55(4: 266–271, 2009].

  4. Multiple-Site Trimethylation of Ribosomal Protein L11 by the PrmA Methyltransferase

    Demirci,H.; Gregory, S.; Dahlberg, A.; Jogl, G.

    2008-01-01

    Ribosomal protein L11 is a universally conserved component of the large subunit, and plays a significant role during initiation, elongation, and termination of protein synthesis. In Escherichia coli, the lysine methyltransferase PrmA trimethylates the N-terminal a-amino group and the -amino groups of Lys3 and Lys39. Here, we report four PrmA-L11 complex structures in different orientations with respect to the PrmA active site. Two structures capture the L11 N-terminal a-amino group in the active site in a trimethylated postcatalytic state and in a dimethylated state with bound S-adenosyl-L-homocysteine. Two other structures show L11 in a catalytic orientation to modify Lys39 and in a noncatalytic orientation. The comparison of complex structures in different orientations with a minimal substrate recognition complex shows that the binding mode remains conserved in all L11 orientations, and that substrate orientation is brought about by the unusual interdomain flexibility of PrmA.

  5. Hypervariability of ribosomal DNA at multiple chromosomal sites in lake trout (Salvelinus namaycush).

    Zhuo, L; Reed, K M; Phillips, R B

    1995-06-01

    Variation in the intergenic spacer (IGS) of the ribosomal DNA (rDNA) of lake trout (Salvelinus namaycush) was examined. Digestion of genomic DNA with restriction enzymes showed that almost every individual had a unique combination of length variants with most of this variation occurring within rather than between populations. Sequence analysis of a 2.3 kilobase (kb) EcoRI-DraI fragment spanning the 3' end of the 28S coding region and approximately 1.8 kb of the IGS revealed two blocks of repetitive DNA. Putative transcriptional termination sites were found approximately 220 bases (b) downstream from the end of the 28S coding region. Comparison of the 2.3-kb fragments with two longer (3.1 kb) fragments showed that the major difference in length resulted from variation in the number of short (89 b) repeats located 3' to the putative terminator. Repeat units within a single nucleolus organizer region (NOR) appeared relatively homogeneous and genetic analysis found variants to be stably inherited. A comparison of the number of spacer-length variants with the number of NORs found that the number of length variants per individual was always less than the number of NORs. Examination of spacer variants in five populations showed that populations with more NORs had more spacer variants, indicating that variants are present at different rDNA sites on nonhomologous chromosomes.

  6. Coordinating bifurcated remediation of soil and groundwater at sites containing multiple operable units

    Laney, D.F.

    1996-01-01

    On larger and/or more complex sites, remediation of soil and groundwater is sometimes bifurcated. This presents some unique advantages with respect to expedited cleanup of one medium, however, it requires skillful planning and significant forethought to ensure that initial remediation efforts do not preclude some long-term options, and/or unduly influence the subsequent selection of a technology for the other operable units and/or media. this paper examines how the decision to bifurcate should be approached, the various methods of bifurcation, the advantages and disadvantages of bifurcation, and the best methods to build flexibility into the design of initial remediation systems so as to allow for consideration of a fuller range of options for remediation of other operable units and/or media at a later time. Pollutants of concern include: metals; petroleum hydrocarbons; and chlorinated solvents

  7. Ensemble approach combining multiple methods improves human transcription start site prediction

    Dineen, David G

    2010-11-30

    Abstract Background The computational prediction of transcription start sites is an important unsolved problem. Some recent progress has been made, but many promoters, particularly those not associated with CpG islands, are still difficult to locate using current methods. These methods use different features and training sets, along with a variety of machine learning techniques and result in different prediction sets. Results We demonstrate the heterogeneity of current prediction sets, and take advantage of this heterogeneity to construct a two-level classifier (\\'Profisi Ensemble\\') using predictions from 7 programs, along with 2 other data sources. Support vector machines using \\'full\\' and \\'reduced\\' data sets are combined in an either\\/or approach. We achieve a 14% increase in performance over the current state-of-the-art, as benchmarked by a third-party tool. Conclusions Supervised learning methods are a useful way to combine predictions from diverse sources.

  8. A Compact Microelectrode Array Chip with Multiple Measuring Sites for Electrochemical Applications

    Maria Dimaki

    2014-05-01

    Full Text Available In this paper we demonstrate the fabrication and electrochemical characterization of a microchip with 12 identical but individually addressable electrochemical measuring sites, each consisting of a set of interdigitated electrodes acting as a working electrode as well as two circular electrodes functioning as a counter and reference electrode in close proximity. The electrodes are made of gold on a silicon oxide substrate and are passivated by a silicon nitride membrane. A method for avoiding the creation of high edges at the electrodes (known as lift-off ears is presented. The microchip design is highly symmetric to accommodate easy electronic integration and provides space for microfluidic inlets and outlets for integrated custom-made microfluidic systems on top.

  9. Efficacy of plastic mesh tubes in reducing herbivory damage by the invasive nutria (Myocastor coypus) in an urban restoration site

    Sheffels, Trevor R.; Systma, Mark D.; Carter, Jacoby; Taylor, Jimmy D.

    2014-01-01

    The restoration of stream corridors is becoming an increasingly important component of urban landscape planning, and the high cost of these projects necessitates the need to understand and address potential ecological obstacles to project success. The nutria(Myocastor coypus) is an invasive, semi-aquatic rodent native to South America that causes detrimental ecological impacts in riparian and wetland habitats throughout its introduced range, and techniques are needed to reduce nutria herbivory damage to urban stream restoration projects. We assessed the efficacy of standard Vexar® plastic mesh tubes in reducing nutria herbivory damage to newly established woody plants. The study was conducted in winter-spring 2009 at Delta Ponds, a 60-ha urban waterway in Eugene, Oregon. Woody plants protected by Vexar® tubes demonstrated 100% survival over the 3-month initial establishment period, while only 17% of unprotected plantings survived. Nutria demonstrated a preference for black cottonwood (Populus balsamifera ssp trichocarpa) over red osier dogwood (Cornussericea) and willow (Salix spp). Camera surveillance showed that nutria were more active in unprotected rather than protected treatments. Our results suggest that Vexar® plastic mesh tubing can be an effective short-term herbivory mitigation tool when habitat use by nutria is low. Additionally, planting functionally equivalent woody plant species that are less preferred by nutria, and other herbivores, may be another method for reducing herbivory and improving revegetation success. This study highlights the need to address potential wildlife damage conflicts in the planning process for stream restoration in urban landscapes.

  10. The gingival vein as a minimally traumatic site for multiple blood sampling in guinea pigs and hamsters.

    Rodrigues, Mariana Valotta; de Castro, Simone Oliveira; de Albuquerque, Cynthia Zaccanini; Mattaraia, Vânia Gomes de Moura; Santoro, Marcelo Larami

    2017-01-01

    Laboratory animals are still necessary in scientific investigation and vaccine testing, but while novel methodological approaches are not available for their replacement, the search for new, humane, easy, and painless methods is necessary to diminish their stress and pain. When multiple blood samples are to be collected from hamsters and guinea pigs, the number of available venipuncture sites-which are greatly diminished in these species in comparison with other rodents due to the absence of a long tail-, harasses animal caregivers and researchers. Thus, this study aimed to evaluate if gingival vein puncture could be used as an additional route to obtain multiple blood samples from anesthetized hamsters and guinea pigs in such a way that animal behavior, well-being or hematological parameters would not be altered. Thus, twelve anesthetized Syrian golden hamsters and English guinea pigs were randomly allocated in two groups: a control group, whose blood samples were not collected, and an experimental group in which blood samples (200 microliters) were collected by gingival vein puncture at weekly intervals over six weeks. Clinical assessment, body weight gain and complete blood cell count were evaluated weekly, and control and experimental animals were euthanized at week seven, when the mentolabial region was processed to histological analyses. Multiple blood sampling from the gingival vein evoked no clinical manifestations or alteration in the behavioral repertoire, nor a statistically significant difference in weight gain in both species. Guinea pigs showed no alteration in red blood cell, leukocyte or platelet parameters over time. Hamsters developed a characteristic pattern of age-related physiological changes, which were considered normal. Histological analyses showed no difference in morphological structures in the interdental gingiva, confirming that multiple blood sampling is barely traumatic. Thus, these results evidence that blood collection from multiple

  11. Damage estimates for European and U.S.sites using the U.S. high-cycle fatigue data base

    Sutherland, H J [Wind Energy Technology, Sandia National Lab., Albuquerque, NM (United States)

    1996-09-01

    This paper uses two high-cycle fatigue data bases, one for typical U.S. blade materials and one for European materials, to analyze the service lifetime of a wind turbine blade subjected to the WISPER load spectrum for northern European sites and the WISPER protocol load spectrum for U.S. wind farm sites. The U.S. data base contains over 2200 data points that were obtained using coupon testing procedures. These data are used to construct a Goodman diagram that is suitable for analyzing wind turbine blades. This result is compared to the Goodman diagram derived from the European fatigue data base FACT. The LIFE2 fatigue analysis code for wind turbines is then used to predict the service lifetime of a turbine blade subjected to the two loading histories. The results of this study indicate that the WISPER load spectrum from northern European sites significantly underestimates the WISPER protocol load spectrum from a U.S. wind farm site, i.e., the WISPER load spectrum significantly underestimates the number and magnitude of the loads observed at a U.S. wind farm site. Further, the analysis demonstrate that the European and the U.S. fatigue material data bases are in general agreement for the prediction of tensile failures. However, for compressive failures, the two data bases are significantly different, with the U.S. data base predicting significantly shorter service lifetimes than the European data base. (au) 14 refs.

  12. Multiple complex odontomas and subsequent occurrence of an ossifying fibroma at the same site as the removed odontoma

    Kou Matsuo

    2013-06-01

    Full Text Available We report a rare case of multiple complex odontomas and the subsequent occurrence of an ossifying fibroma at the same site as one of the removed odontomas. A 3-year-old Japanese boy presented three complex odontomas at the unerupted deciduous first and second molars and permanent first molar on the left side of the mandible. The two odontomas at the deciduous teeth were immediately extirpated, and, after 2 years of follow-up, the odontoma at the unerupted permanent first molar was removed. At the age of 7 years, a small odontoma surrounding the deciduous second molar emerged as a recurrence. When the patient was 9 years old, an ossifying fibroma occurred near the apex of the first premolar, i.e., the site where one of the original odontomas existed. Furthermore, a small radiopaque mass over the crown of the unerupted permanent second molar was observed at the age of 10 years; this mass was probably an additional fourth complex odontoma. This is not only a rare case report of ossifying fibroma associated with multiple complex odontomas but also a valuable time course observation of the development of such odontogenic tumors.

  13. Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL

    Hastie C James

    2006-01-01

    Full Text Available Abstract Background Pim-1, 2 and 3 are a group of enzymes related to the calcium calmodulin family of protein kinases. Over-expression of Pim-1 and Pim-2 in mice promotes the development of lymphomas, and up-regulation of Pim expression has been observed in several human cancers. Results Here we show that the pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells. In vitro mapping showed that Pim-2 predominantly phosphorylated Ser112, while Pim-1 phosphorylated Ser112, but also Ser136 and Ser155 at a reduced rate compared to Ser112. Pim-3 was found to be the least specific for Ser112, and the most effective at phosphorylating Ser136 and Ser155. Pim-3 was also able to phosphorylate other sites in Bad in vitro, including Ser170, another potential in vivo site. Mutation of Ser136 to alanine prevented the phosphorylation of Ser112 and Ser155 by Pim kinases in HEK-293 cells, suggesting that this site must be phosphorylated first in order to make the other sites accessible. Pim phosphorylation of Bad was also found to promote the 14-3-3 binding of Bad and block its association with Bcl-XL. Conclusion All three Pim kinase family members predominantly phosphorylate Bad on Ser112 and in addition are capable of phosphorylating Bad on multiple sites associated with the inhibition of the pro-apoptotic function of Bad in HEK-293 cells. This would be consistent with the proposed function of Pim kinases in promoting cell proliferation and preventing cell death.

  14. [Multiple sites extrapodal actinomycetoma: Favorable outcome to treatment with a combination of cotrimoxazole and NSAI].

    Diallo, B; Barro-Traoré, F; Bamba, S; Sanou-Lamien, A; Traoré, S S; Andonaba, J-B; Konaté, I; Niamba, P; Traoré, A; Guiguemdé, T R

    2015-12-01

    Mycetoma is a bacteriological or fungal infectious disease affecting the skin and/or soft tissues, which can be complicated by bone involvement. The most common feature is a tumor of the foot, but extrapodal localizations have been described. We report one case of a 47-year-old man who presented with tumefaction of a leg with multiple skin fistulae. Histopathological examination permitted to confirm the diagnosis of actinomycetoma and TDM showed the degree of bone and soft tissues involvement. Our case was characterized by the very inflammatory aspect of the tumor, its localization to the leg without foot involvement, the modest functional signs compared to the importance of radiological bone involvements, the deep destruction of the fibula while the tibia was apparently intact and the good response to treatment. In spite of its characteristic features, diagnosis of mycetoma is still late in our country, often with bone and/or articular spread. Priority may be given to measures for reduction of mycetoma diagnosis lateness. Copyright © 2015. Published by Elsevier Masson SAS.

  15. Does wine glass size influence sales for on-site consumption? A multiple treatment reversal design

    Rachel Pechey

    2016-06-01

    Full Text Available Abstract Background Wine glass size can influence both perceptions of portion size and the amount poured, but its impact upon purchasing and consumption is unknown. This study aimed to examine the impact of wine glass size on wine sales for on-site consumption, keeping portion size constant. Methods In one establishment (with separate bar and restaurant areas in Cambridge, England, wine glass size (Standard; Larger; Smaller was changed over eight fortnightly periods. The bar and restaurant differ in wine sales by the glass vs. by the bottle (93 % vs. 63 % by the glass respectively. Results Daily wine volume purchased was 9.4 % (95 % CI: 1.9, 17.5 higher when sold in larger compared to standard-sized glasses. This effect seemed principally driven by sales in the bar area (bar: 14.4 % [3.3, 26.7]; restaurant: 8.2 % [−2.5, 20.1]. Findings were inconclusive as to whether sales were different with smaller vs. standard-sized glasses. Conclusions The size of glasses in which wine is sold, keeping the portion size constant, can affect consumption, with larger glasses increasing consumption. The hypothesised mechanisms for these differential effects need to be tested in a replication study. If replicated, policy implications could include considering glass size amongst alcohol licensing requirements. Trial registration ISRCTN registry: ISRCTN12018175 . Registered 12th May 2015.

  16. Projecting future precipitation and temperature at sites with diverse climate through multiple statistical downscaling schemes

    Vallam, P.; Qin, X. S.

    2017-10-01

    Anthropogenic-driven climate change would affect the global ecosystem and is becoming a world-wide concern. Numerous studies have been undertaken to determine the future trends of meteorological variables at different scales. Despite these studies, there remains significant uncertainty in the prediction of future climates. To examine the uncertainty arising from using different schemes to downscale the meteorological variables for the future horizons, projections from different statistical downscaling schemes were examined. These schemes included statistical downscaling method (SDSM), change factor incorporated with LARS-WG, and bias corrected disaggregation (BCD) method. Global circulation models (GCMs) based on CMIP3 (HadCM3) and CMIP5 (CanESM2) were utilized to perturb the changes in the future climate. Five study sites (i.e., Alice Springs, Edmonton, Frankfurt, Miami, and Singapore) with diverse climatic conditions were chosen for examining the spatial variability of applying various statistical downscaling schemes. The study results indicated that the regions experiencing heavy precipitation intensities were most likely to demonstrate the divergence between the predictions from various statistical downscaling methods. Also, the variance computed in projecting the weather extremes indicated the uncertainty derived from selection of downscaling tools and climate models. This study could help gain an improved understanding about the features of different downscaling approaches and the overall downscaling uncertainty.

  17. Wisdom tooth extraction causing lingual nerve and styloglossus muscle damage: a mimic of multiple cranial nerve palsies.

    Carr, Aisling S; Evans, Matthew; Shah, Sachit; Catania, Santi; Warren, Jason D; Gleeson, Michael J; Reilly, Mary M

    2017-06-01

    The combination of tongue hemianaesthesia, dysgeusia, dysarthria and dysphagia suggests the involvement of multiple cranial nerves. We present a case with sudden onset of these symptoms immediately following wisdom tooth extraction and highlight the clinical features that allowed localisation of the lesion to a focal, iatrogenic injury of the lingual nerve and adjacent styloglossus muscle. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Does Pre-Operative Multiple Immunosuppressive Therapy Associate with Surgical Site Infection in Surgery for Ulcerative Colitis.

    Uchino, Motoi; Ikeuchi, Hiroki; Bando, Toshihiro; Hirose, Kei; Hirata, Akihiro; Chohno, Teruhiro; Sasaki, Hirofumi; Takahashi, Yoshiko; Takesue, Yoshio; Hida, Nobuyuki; Hori, Kazutoshi; Nakamura, Shiro

    2015-01-01

    Almost all surgeries for ulcerative colitis (UC) are performed under immunosuppressive conditions. Immunomodulators or biologics, with the exception of corticosteroids, do not appear to be risk factors for post-operative infectious complications. However, many patients are on multiagent immunosuppressive therapy at the time of surgery. Therefore, we evaluated the influence of pre-operative multiple immunosuppressives on the occurrence of surgical site infection (SSI) in UC. We reviewed surveillance data from 181 patients who underwent restorative proctocolectomy between January 2012 and March 2014. The incidences of SSI and the possible risk factors among patients receiving different immunosuppressive therapies were compared and analyzed. The incidence of incisional (INC) SSI was 13.3% and that of organ/space (O/S) SSI was 7.2%. The number of immunosuppressives did not significantly correlate with each incidence. Total prednisolone administration ≥12,000 mg (OR 2.6) and an American Society of Anesthesiologists score ≥3 (OR 2.8) were shown to be independent risk factors for overall SSI, whereas corticosteroid use in INC SSI (OR 17.4) and severe disease (OR 5.2) and a large amount of blood loss (OR 3.9) in O/S SSI were identified as risk factors. Although a correlation between multiple immunosuppressive therapy and SSIs was not found, it is not recommended that all patients be treated with multiple immunosuppressive therapy. Treatment strategy should be applied based on the patient's condition. © 2015 S. Karger AG, Basel.

  19. Proliferating Cell Nuclear Antigen-dependent Rapid Recruitment of Cdt1 and CRL4Cdt2 at DNA-damaged Sites after UV Irradiation in HeLa Cells*

    Ishii, Takashi; Shiomi, Yasushi; Takami, Toshihiro; Murakami, Yusuke; Ohnishi, Naho; Nishitani, Hideo

    2010-01-01

    The licensing factor Cdt1 is degraded by CRL4Cdt2 ubiquitin ligase dependent on proliferating cell nuclear antigen (PCNA) during S phase and when DNA damage is induced in G1 phase. Association of both Cdt2 and PCNA with chromatin was observed in S phase and after UV irradiation. Here we used a micropore UV irradiation assay to examine Cdt2 accumulation at cyclobutane pyrimidine dimer-containing DNA-damaged sites in the process of Cdt1 degradation in HeLa cells. Cdt2, present in the nucleus throughout the cell cycle, accumulated rapidly at damaged DNA sites during G1 phase. The recruitment of Cdt2 is dependent on prior PCNA chromatin binding because Cdt2 association was prevented when PCNA was silenced. Cdt1 was also recruited to damaged sites soon after UV irradiation through its PIP-box. As Cdt1 was degraded, the Cdt2 signal at damaged sites was reduced, but PCNA, cyclobutane pyrimidine dimer, and XPA (xeroderma pigmentosum, complementation group A) signals remained at the same levels. These findings suggest that Cdt1 degradation following UV irradiation occurs rapidly at damaged sites due to PCNA chromatin loading and the recruitment of Cdt1 and CRL4Cdt2, before DNA damage repair is completed. PMID:20929861

  20. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  1. Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites

    Wong, Ka-Chun; Peng, Chengbin; Li, Yue

    2015-01-01

    With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP-Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene's function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/∼wkc/FullSignalRanker/ © 2015 IEEE.

  2. Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites

    Wong, Ka-Chun

    2015-04-20

    With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP-Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene\\'s function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins\\' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/∼wkc/FullSignalRanker/ © 2015 IEEE.

  3. A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly.

    Ishida, M; Cullup, T; Boustred, C; James, C; Docker, J; English, C; Lench, N; Copp, A J; Moore, G E; Greene, N D E; Stanier, P

    2018-04-01

    Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N = 509), we identified 397 rare variants (minor allele frequency, MAF < 1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly. © 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Use of the SSHAC methodology within regulated environments: Cost-effective application for seismic characterization at multiple sites

    Coppersmith, Kevin J.; Bommer, Julian J.

    2012-01-01

    Highlights: ► SSHAC processes provide high levels of regulatory assurance in hazard assessments for purposes of licensing and safety review. ► SSHAC projects provide structure to the evaluation of available data, models, and methods for building hazard input models. ► Experience on several nuclear projects in the past 15 years leads to the identification of key essential procedural steps. ► Conducting a regional SSHAC Level 3 study, followed by Level 2 site-specific studies can be time and cost effective. - Abstract: Essential elements of license applications and safety reviews for nuclear facilities are quantifications of earthquake and other natural hazards. A Senior Seismic Hazard Analysis Committee (SSHAC) Level 3 or 4 process provides regulatory assurance that the hazard assessment considers all data and models proposed by members of the technical community and the associated uncertainties have been properly quantified. The SSHAC process has been endorsed as an acceptable hazard assessment methodology in US NRC regulatory guidance. Where hazard studies are required for multiple sites, regional SSHAC Level 3 or 4 studies followed by site-specific Level 2 refinements can provide major benefits in cost and duration.

  5. Identification of multiple binding sites for the THAP domain of the Galileo transposase in the long terminal inverted-repeats☆

    Marzo, Mar; Liu, Danxu; Ruiz, Alfredo; Chalmers, Ronald

    2013-01-01

    Galileo is a DNA transposon responsible for the generation of several chromosomal inversions in Drosophila. In contrast to other members of the P-element superfamily, it has unusually long terminal inverted-repeats (TIRs) that resemble those of Foldback elements. To investigate the function of the long TIRs we derived consensus and ancestral sequences for the Galileo transposase in three species of Drosophilids. Following gene synthesis, we expressed and purified their constituent THAP domains and tested their binding activity towards the respective Galileo TIRs. DNase I footprinting located the most proximal DNA binding site about 70 bp from the transposon end. Using this sequence we identified further binding sites in the tandem repeats that are found within the long TIRs. This suggests that the synaptic complex between Galileo ends may be a complicated structure containing higher-order multimers of the transposase. We also attempted to reconstitute Galileo transposition in Drosophila embryos but no events were detected. Thus, although the limited numbers of Galileo copies in each genome were sufficient to provide functional consensus sequences for the THAP domains, they do not specify a fully active transposase. Since the THAP recognition sequence is short, and will occur many times in a large genome, it seems likely that the multiple binding sites within the long, internally repetitive, TIRs of Galileo and other Foldback-like elements may provide the transposase with its binding specificity. PMID:23648487

  6. Identification of multiple binding sites for the THAP domain of the Galileo transposase in the long terminal inverted-repeats.

    Marzo, Mar; Liu, Danxu; Ruiz, Alfredo; Chalmers, Ronald

    2013-08-01

    Galileo is a DNA transposon responsible for the generation of several chromosomal inversions in Drosophila. In contrast to other members of the P-element superfamily, it has unusually long terminal inverted-repeats (TIRs) that resemble those of Foldback elements. To investigate the function of the long TIRs we derived consensus and ancestral sequences for the Galileo transposase in three species of Drosophilids. Following gene synthesis, we expressed and purified their constituent THAP domains and tested their binding activity towards the respective Galileo TIRs. DNase I footprinting located the most proximal DNA binding site about 70 bp from the transposon end. Using this sequence we identified further binding sites in the tandem repeats that are found within the long TIRs. This suggests that the synaptic complex between Galileo ends may be a complicated structure containing higher-order multimers of the transposase. We also attempted to reconstitute Galileo transposition in Drosophila embryos but no events were detected. Thus, although the limited numbers of Galileo copies in each genome were sufficient to provide functional consensus sequences for the THAP domains, they do not specify a fully active transposase. Since the THAP recognition sequence is short, and will occur many times in a large genome, it seems likely that the multiple binding sites within the long, internally repetitive, TIRs of Galileo and other Foldback-like elements may provide the transposase with its binding specificity. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

    Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

    2017-12-01

    Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

  8. How to eliminate non-damaging earthquakes from the results of a probabilistic seismic hazard analysis (PSHA)-A comprehensive procedure with site-specific application

    Kluegel, Jens-Uwe

    2009-01-01

    The results of probabilistic seismic hazard analyses are frequently presented in terms of uniform hazard spectra or hazard curves with spectral accelerations as the output parameter. The calculation process is based on the evaluation of the probability of exceedance of specified acceleration levels without consideration of the damaging effects of the causative earthquakes. The same applies to the empirical attenuation equations for spectral accelerations used in PSHA models. This makes interpreting and using the results in engineering or risk applications difficult. Uniform hazard spectra and the associated hazard curves may contain a significant amount of contributions of weak, low-energy earthquakes not able to damage the seismically designed structures of nuclear power plants. For the development of realistic engineering designs and for realistic seismic probabilistic risk assessments (seismic PRA) it is necessary to remove the contribution of non-damaging earthquakes from the results of a PSHA. A detailed procedure for the elimination of non-damaging earthquakes based on the CAV (Cumulative Absolute Velocity)-filtering approach was developed and applied to the results of the large-scale PEGASOS probabilistic seismic hazard study for the site of the Goesgen nuclear power plant. The procedure considers the full scope of epistemic uncertainty and aleatory variability present in the PEGASOS study. It involves the development of a set of empirical correlations for CAV and the subsequent development of a composite distribution for the probability of exceedance of the damaging threshold of 0.16 gs. Additionally, a method was developed to measure the difference in the damaging effects of earthquakes of different strengths by the ratio of a power function of ARIAS-intensity or, in the ideal case, by the ratio of the square roots of the associated strong motion durations. The procedure was applied for the update of the Goesgen seismic PRA and for the confirmation of a

  9. Simulation Analysis of the Mutual Influence of the Stress Intensity Factor on the Multiple Blisters Caused by Hydrogen Induced Damage

    Ji, Congwei; Zhang, Shaojie; Wang, Hehui

    2018-03-01

    Hydrogen blisters are taken as the research object by using the finite element software ABAQUS. The stress intensity factors of blister cracks are numerically calculated at varying depths and different edge distances for established three-dimensional finite element models of single-blister and double-blisters, respectively. The mutual influence of the stress intensity factors of the multiple blisters is obtained. It shows that the blister crack is easier to expand when the crack is closer to inner wall of the cylinder. What’s more, the crack growth rate increases firstly and then decreases as the increasing of the distance between two blisters cracks. The investigated result is of great reference value for predicting the trend of blister crack growth.

  10. An active site aromatic triad in Escherichia coli DNA Pol IV coordinates cell survival and mutagenesis in different DNA damaging agents.

    Ryan W Benson

    Full Text Available DinB (DNA Pol IV is a translesion (TLS DNA polymerase, which inserts a nucleotide opposite an otherwise replication-stalling N(2-dG lesion in vitro, and confers resistance to nitrofurazone (NFZ, a compound that forms these lesions in vivo. DinB is also known to be part of the cellular response to alkylation DNA damage. Yet it is not known if DinB active site residues, in addition to aminoacids involved in DNA synthesis, are critical in alkylation lesion bypass. It is also unclear which active site aminoacids, if any, might modulate DinB's bypass fidelity of distinct lesions. Here we report that along with the classical catalytic residues, an active site "aromatic triad", namely residues F12, F13, and Y79, is critical for cell survival in the presence of the alkylating agent methyl methanesulfonate (MMS. Strains expressing dinB alleles with single point mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in addition to its role in TLS, modulates DinB's accuracy in bypassing distinct lesions. The high bypass fidelity of prevalent alkylation lesions is evident even when the DinB active site performs error-prone NFZ-induced lesion bypass. The analyses carried out with the active site aromatic triad suggest that the DinB active site residues are poised to proficiently bypass distinctive DNA lesions, yet they are also malleable so that the accuracy of the bypass is lesion-dependent.

  11. Uric acid in multiple sclerosis

    Koch, M; De Keyser, J

    Peroxynitrite, a reactive oxidant formed by the reaction of nitric oxide with superoxide at sites of inflammation in multiple sclerosis (MS), is capable of damaging tissues and cells. Uric acid, a natural scavenger of peroxynitrite, reduces inflammatory demyelination in experimental allergic

  12. The Abridgment and Relaxation Time for a Linear Multi-Scale Model Based on Multiple Site Phosphorylation.

    Shuo Wang

    Full Text Available Random effect in cellular systems is an important topic in systems biology and often simulated with Gillespie's stochastic simulation algorithm (SSA. Abridgment refers to model reduction that approximates a group of reactions by a smaller group with fewer species and reactions. This paper presents a theoretical analysis, based on comparison of the first exit time, for the abridgment on a linear chain reaction model motivated by systems with multiple phosphorylation sites. The analysis shows that if the relaxation time of the fast subsystem is much smaller than the mean firing time of the slow reactions, the abridgment can be applied with little error. This analysis is further verified with numerical experiments for models of bistable switch and oscillations in which linear chain system plays a critical role.

  13. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers.

    Mohsen Khademi

    Full Text Available Inflammatory mediators have crucial roles in leukocyte recruitment and subsequent central nervous system (CNS neuroinflammation. The extent of neuronal injury and axonal loss are associated with the degree of CNS inflammation and determine physical disability in multiple sclerosis (MS. The aim of this study was to explore possible associations between a panel of selected cerebrospinal fluid biomarkers and robust clinical and demographic parameters in a large cohort of patients with MS and controls (n = 1066 using data-driven multivariate analysis. Levels of matrix metalloproteinase 9 (MMP9, chemokine (C-X-C motif ligand 13 (CXCL13, osteopontin (OPN and neurofilament-light chain (NFL were measured by ELISA in 548 subjects comprising different MS subtypes (relapsing-remitting, secondary progressive and primary progressive, clinically isolated syndrome and persons with other neurological diseases with or without signs of inflammation/infection. Principal component analyses and orthogonal partial least squares methods were used for unsupervised and supervised interrogation of the data. Models were validated using data from a further 518 subjects in which one or more of the four selected markers were measured. There was a significant association between increased patient age and lower levels of CXCL13, MMP9 and NFL. CXCL13 levels correlated well with MMP9 in the younger age groups, but less so in older patients, and after approximately 54 years of age the levels of CXCL13 and MMP9 were consistently low. CXCL13 and MMP9 levels also correlated well with both NFL and OPN in younger patients. We demonstrate a strong effect of age on both inflammatory and neurodegenerative biomarkers in a large cohort of MS patients. The findings support an early use of adequate immunomodulatory disease modifying drugs, especially in younger patients, and may provide a biological explanation for the relative inefficacy of such treatments in older patients at later

  14. Progression of a fracture site impaction as a prognostic indicator of impacted femoral neck fracture treated with multiple pinning.

    Yoon, Pil Whan; Shin, Young Ho; Yoo, Jeong Joon; Yoon, Kang Sup; Kim, Hee Joong

    2012-03-01

    We evaluated the clinical and radiologic results of impacted femoral neck fractures treated with multiple pinning and determined the influence of the progression of impaction at the fracture site on clinical outcome. There were 34 patients with a mean age of 65.5 years. The mean follow-up period was 3.4 years. Progression of fracture site impaction was measured using an articulo-trochanteric distance index and the percentage decrease in the articulo-trochanteric distance index between follow-up intervals. The failure of treatment was clarified as non-union and avascular necrosis. Other characteristics of the patients, including mean waiting time for surgery, preoperative Singh index score, and body mass index, were also measured to evaluate the influence on the clinical outcome of surgery. There were 6 fractures which were not treated successfully (3 non-union, 8.8% and 3 avascular necrosis, 8.8%). The mean percentage decrease of the articulo-trochanteric distance index within the first 6 weeks after surgery was 4.5% in the successful group and 25.1% in the failure group (p articulo-trochanteric distance index between 6 weeks and 3 months (p articulo-trochanteric distance index between the successful group and the failure group, we could not verify it as a risk factor for failure of treatment because the odds ratio was not statistically significant.

  15. An efficient method to transcription factor binding sites imputation via simultaneous completion of multiple matrices with positional consistency.

    Guo, Wei-Li; Huang, De-Shuang

    2017-08-22

    Transcription factors (TFs) are DNA-binding proteins that have a central role in regulating gene expression. Identification of DNA-binding sites of TFs is a key task in understanding transcriptional regulation, cellular processes and disease. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) enables genome-wide identification of in vivo TF binding sites. However, it is still difficult to map every TF in every cell line owing to cost and biological material availability, which poses an enormous obstacle for integrated analysis of gene regulation. To address this problem, we propose a novel computational approach, TFBSImpute, for predicting additional TF binding profiles by leveraging information from available ChIP-seq TF binding data. TFBSImpute fuses the dataset to a 3-mode tensor and imputes missing TF binding signals via simultaneous completion of multiple TF binding matrices with positional consistency. We show that signals predicted by our method achieve overall similarity with experimental data and that TFBSImpute significantly outperforms baseline approaches, by assessing the performance of imputation methods against observed ChIP-seq TF binding profiles. Besides, motif analysis shows that TFBSImpute preforms better in capturing binding motifs enriched in observed data compared with baselines, indicating that the higher performance of TFBSImpute is not simply due to averaging related samples. We anticipate that our approach will constitute a useful complement to experimental mapping of TF binding, which is beneficial for further study of regulation mechanisms and disease.

  16. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites.

    Daniel R Feikin

    Full Text Available BACKGROUND: Vaccine-serotype (VT invasive pneumococcal disease (IPD rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7 into national immunization programs. Increases in non-vaccine-serotype (NVT IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. METHODS AND FINDINGS: Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥ 2 years before and ≥ 1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0.55, 95% CI 0.46-0.65 and remained relatively stable through year 7 (RR 0.49, 95% CI 0.35-0.68. Point estimates for VT IPD decreased annually through year 7 (RR 0.03, 95% CI 0.01-0.10, while NVT IPD increased (year 7 RR 2.81, 95% CI 2.12-3.71. Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18-49 year-olds [RR 0.52, 95% CI 0.29-0.91], 50-64 year-olds [RR 0.84, 95% CI 0.77-0.93], and ≥ 65 year-olds [RR 0.74, 95% CI 0.58-0.95]. CONCLUSIONS: Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not

  17. Intercomparison of 30+ years of AVHRR and Landsat-5 TM Surface Reflectance using Multiple Pseudo-Invariant Calibration Sites

    Santamaría-Artigas, A. E.; Franch, B.; Vermote, E.; Roger, J. C.; Justice, C. O.

    2017-12-01

    The 30+ years daily surface reflectance long term data record (LTDR) from the Advanced Very High Resolution Radiometer (AVHRR) is a valuable source of information for long-term studies of the Earth surface. This LTDR was generated by combining observations from multiple AVHRR sensors aboard different NOAA satellites starting from the early 1980s, and due to the lack of on-board calibration its quality should be evaluated. Previous studies have used observations from the Moderate Resolution Imaging Spectroradiometer (MODIS) over pseudo-invariant calibration sites (PICS) as a calibrated reference to assess the performance of AVHRR products. However, this limits the evaluation to the period after MODIS launch. In this work, the AVHRR surface reflectance LTDR was evaluated against Landsat-5 Thematic Mapper (TM) data using observations from 4 well known pseudo-invariant calibration sites (i.e. Sonoran, Saharan, Sudan1, and Libya4) over an extended time period (1984-2011). For the intercomparison, AVHRR and TM observations of each site were extracted and averaged over a 20 km x 20 km area and aggregated to monthly mean values. In order to account for the spectral differences between sensors, Hyperion hyperspectral data from the Sonoran and Libya4 sites were convolved with sensor-specific relative spectral responses, and used to compute spectral band adjustment factors (SBAFs). Results of the intercomparison are reported in terms of the root mean square difference (RMSD) and determination coefficient (r2). In general, there is good agreement between the surface reflectance products from both sensors. The overall RMSD and r2 for all the sites and AVHRR/TM combinations were 0.03 and 0.85 for the red band, and 0.04 and 0.81 for the near-infrared band. These results show the strong performance of the AVHRR surface reflectance LTDR through all of the considered period. Thus, remarking its usefulness and value for long term Earth studies. Figure 1 shows the red (filled markers

  18. Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage.

    Nicolas Grandchamp

    Full Text Available Gene transfer allows transient or permanent genetic modifications of cells for experimental or therapeutic purposes. Gene delivery by HIV-derived lentiviral vector (LV is highly effective but the risk of insertional mutagenesis is important and the random/uncontrollable integration of the DNA vector can deregulate the cell transcriptional activity. Non Integrative Lentiviral Vectors (NILVs solve this issue in non-dividing cells, but they do not allow long term expression in dividing cells. In this context, obtaining stable expression while avoiding the problems inherent to unpredictable DNA vector integration requires the ability to control the integration site. One possibility is to use the integrase of phage phiC31 (phiC31-int which catalyzes efficient site-specific recombination between the attP site in the phage genome and the chromosomal attB site of its Streptomyces host. Previous studies showed that phiC31-int is active in many eukaryotic cells, such as murine or human cells, and directs the integration of a DNA substrate into pseudo attP sites (pattP which are homologous to the native attP site. In this study, we combined the efficiency of NILV for gene delivery and the specificity of phiC31-int for DNA substrate integration to engineer a hybrid tool for gene transfer with the aim of allowing long term expression in dividing and non-dividing cells preventing genotoxicity. We demonstrated the feasibility to target NILV integration in human and murine pattP sites with a dual NILV vectors system: one which delivers phiC31-int, the other which constitute the substrate containing an attB site in its DNA sequence. These promising results are however alleviated by the occurrence of significant DNA damages. Further improvements are thus required to prevent chromosomal rearrangements for a therapeutic use of the system. However, its use as a tool for experimental applications such as transgenesis is already applicable.

  19. Site Features

    U.S. Environmental Protection Agency — This dataset consists of various site features from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different times...

  20. Desleucyl-Oritavancin with a Damaged d-Ala-d-Ala Binding Site Inhibits the Transpeptidation Step of Cell-Wall Biosynthesis in Whole Cells of Staphylococcus aureus.

    Kim, Sung Joon; Singh, Manmilan; Sharif, Shasad; Schaefer, Jacob

    2017-03-14

    We have used solid-state nuclear magnetic resonance to characterize the exact nature of the dual mode of action of oritavancin in preventing cell-wall assembly in Staphylococcus aureus. Measurements performed on whole cells labeled selectively in vivo have established that des-N-methylleucyl-N-4-(4-fluorophenyl)benzyl-chloroeremomycin, an Edman degradation product of [ 19 F]oritavancin, which has a damaged d-Ala-d-Ala binding aglycon, is a potent inhibitor of the transpeptidase activity of cell-wall biosynthesis. The desleucyl drug binds to partially cross-linked peptidoglycan by a cleft formed between the drug aglycon and its biphenyl hydrophobic side chain. This type of binding site is present in other oritavancin-like glycopeptides, which suggests that for these drugs a similar transpeptidase inhibition occurs.

  1. Size of and damage on shoots of Passiflora suberosa (Passifloraceae influence oviposition site selection of Heliconius erato phyllis (Fabricius (Lepidoptera, Nymphalidae

    Elna Mugrabi-Oliveira

    1996-01-01

    Full Text Available Oviposition site selection of Heliconius erato phyllis (Fabricius, 1775 (Lepidoptera, Nymphalidae was studied when size of and damage on shoots were variable in a natural population of Passiflora suberosa Linnaeus (Passifloraceae, and through sequential and simultaneous choice experiments performed under insectary conditions. Females showed marked oviposition preference for undamaged and largest shoots of P. suberosa. Eggs were mostly laid on the terminal buds of intact shoots under natural conditions. In simultaneous choice trials, females preferred to oviposit on shoots from which leaves (ten were removed but the terminal bud maintained to those where leaves were kept but the terminal bud was cut out. In sequential choice trials, they did not lay eggs on shoots from which the terminal bud was removed. Females preferred to oviposit on large to short intact shoots in both sequential and simultaneous choice trials. Females laid eggs preferentially on shoots with the greatest leaf area when most plants were intact in the field during early spring. Later in fall, when mostly large, old shoots were damaged or in a reproductive stage (less desirable for oviposition, oviposition intensity was highest on the shortest, youngest shoots of P. suberosa. Thus, females might rank these quality attributes higher than size while selecting shoots for oviposition. The consequences of ovipositing selectively on intact, large shoots of P. suberosa are discussed from the view point of H. erato phyllis larval performance.

  2. Updated synthesis of the knowledge about the impact on marine environment of the radioactive releases from Fukushima Dai-ichi damaged site - October 26, 2011

    2011-01-01

    A strong radioactive contamination of the marine environment close to the damaged Fukushima Dai-ichi power plant has been observed since March 21. The high concentration of some nuclides ( 131 I, 137 Cs, 134 Cs, 136 Cs, 132 Te, 132 I) comes from three possible sources: the liquid effluents from the damaged site, the atmospheric fallouts, and the weathering of contaminated soils. This information note presents and comments the most recent informations gathered by the French institute of radiation protection and nuclear safety (IRSN) since the previous information note from July 11 and devoted to the same topic. It presents the estimation of the relative contribution of each contamination source and the evolution with time of the marine contamination. The mapping of 137 Cs concentrations in surface seawater allows to estimate the amount of total 137 Cs in the marine environment and its evolution with time. 137 Cs and 134 Cs concentrations were measured both in samples of surface coastal sediments and in river fishes and seafood products (mainly fishes and molluscs). Results are reported in graphs showing their evolution with time. (J.S.)

  3. Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients.

    Yanagisawa, Katsuyuki; Ashihara, Junya; Obara, Shinji; Wada, Norio; Takeuchi, Masayoshi; Nishino, Yuri; Maeda, Sayaka; Ishibashi, Yuji; Yamagishi, Sho-ichi

    2014-11-01

    Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c  > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Association of oxidative stress and DNA damage with grafting time in patients with multiple myeloma and lymphoma submitted to autologous hematopoietic stem cell transplantation

    Thayna Nogueira dos Santos

    Full Text Available ABSTRACT The aim of the study was to investigate the association between oxidative stress and DNA damage with grafting time in patients submitted to autologous hematopoietic stem-cell transplantation (HSCT. The study included 37 patients submitted to autologous HSCT diagnosed with Multiple Myeloma (MM and lymphoma (Hodgkin’s and non-Hodgkin’s. Biomarkers of oxidative stress and DNA damage index (DI were performed at baseline (pre-CR of the disease and during the conditioning regimen (CR, one day after the HSCT, ten days after HSCT and twenty days after HSCT, as well as in the control group consisting of 30 healthy individuals. The outcomes showed that both groups of patients had an hyperoxidative state with high DI when compared to baseline and to the control group and that the CR exacerbated this condition. However, after the follow-up period of the study, this picture was re-established to the baseline levels of each pathology. The study patients with MM showed a mean grafting time of 10.75 days (8 to 13 days, with 10.15 days (8 to 15 days for the lymphoma patients. In patients with MM, there was a negative correlation between the grafting time and the basal levels of GPx (r = -0.54; p = 0.034, indicating that lower levels of this important enzyme are associated with a longer grafting time. For the DI, the correlation was a positive one (r = 0.529; p = 0.030. In the group with lymphoma, it was observed that the basal levels of NOx were positively correlated with grafting time (r = 0.4664, p = 0.032. The data indicate the potential of these biomarkers as predictors of toxicity and grafting time in patients with MM and Lymphomas submitted to autologous HSCT.

  5. DECOVALEX-THMC Project. Task C. Excavation Damaged Zone (EDZ) in argillaceous rock at Tournemire site (France). Report of Task C1

    Rejeb, A. (comp.) [Inst. of Radioprotection and Nuclear Safety (France); Stephansson, O. (comp.) [GeoForschungsZentrum-Potsdam (Germany); Millard, A. [CEA/IRSN (France); Ziefle, G.; Kohlmeier, M.; Massmann, J.; Zielke, W. [ISEB/BGR (Germany); Uehara, S.; Kobayashi, A.; Chijimatsu, M.; Fujita, T. [KU/JAEA (Japan)

    2007-02-15

    The DECOVALEX-THMC project is an ongoing international co-operative project that was stared in 2004 to support the development of mathematical models of coupled Thermal (T), Hydrological (H), Mechanical (M) and Chemical (C) processes in geological media for siting potential nuclear fuel waste repositories. The general objective is to characterise and evaluate the coupled THMC processes in the near field and far field of a geological repository and to assess their impact on performance assessment: - during the three phases of repository development: excavation phase, operation phase and post-closure phase; - for three different rocks types: crystalline, argillaceous and tuff; - with specific focus on the issues of: Excavation Damaged Zone (EDZ), permanent property changes of rock masses, and glaciation and permafrost phenomena. This report describes the results of Task C1 of the project devoted to Excavation Damage Zone (EDZ) in argillaceous rock at the Tournemire site in France. The task is to develop adequate numerical models for interpretation of observed damaged zones around three different openings excavated at different time at the Tournemire site. The research teams are asked to model the evolution of the EDZ with time and to compare the results with measurements performed at the site. Three research teams are participating in this task: - CEA (Commissariat of Atomic Energy, France) and the IRSN (Institute of Radioprotection and Nuclear safety, France) ; - ISEB (Institute of Fluid Mechanics and Computer Applications in Civil Engineering, University of Hanover, Germany) supported by the BGR (Federal Institute for Geosciences and Natural Resources, Germany); - KU (Department of Urban and Environmental Engineering, Kyoto University, Japan) supported by the JAEA (Japan Atomic Energy Agency, Japan). This report presents a description and definition of Task C including a geological description of the site, the geomechanical characterisation of the argillaceous

  6. Compact Solar Spectrometer Column CO2, and CH4 Observations: Performance Evaluation at Multiple North American TCCON Sites

    Parker, H. A.; Hedelius, J.; Viatte, C.; Wunch, D.; Wennberg, P. O.; Chen, J.; Wofsy, S.; Jones, T.; Franklin, J.; Dubey, M. K.; Roehl, C. M.; Podolske, J. R.; Hillyard, P. W.; Iraci, L. T.

    2015-12-01

    Measurement, reporting and verification (MRV) of anthropogenic emissions and natural sources and sinks of carbon dioxide (CO2) and methane (CH4) are crucial to predict climate change and develop transparent accounting policies to contain climate forcing. Remote sensing technologies are monitoring column averaged dry air mole fractions of CO2 and CH4 (XCO2 & XCH4) from ground and space (OCO-2 and GOSAT) with solar spectroscopy enabling direct MRV. However, current ground based coverage is sparse due to the need for large and expensive high-resolution spectrometers that are part of the Total Column Carbon Observing Network (TCCON, Bruker 125HR). This limits our MRV and satellite validation abilities, both regionally and globally. There are striking monitoring gaps in Asia, South America and Africa where the CO2 emissions are growing and there is a large uncertainty in fluxes from land use change, biomass burning and rainforest vulnerability. To fill this gap we evaluate the precision, accuracy and stability of compact, affordable and easy to use low-resolution spectrometers (Bruker EM27/SUN) by comparing with XCO2 and XCH4 retrieved from much larger high-resolution TCCON instruments. As these instruments will be used in a variety of locations, we evaluate their performance by comparing with 2 previous and 4 current United States TCCON sites in different regions up to 2700 km apart. These sites range from polluted to unpolluted, latitudes of 32 to 46°N, and altitudes of 230 to 2241 masl. Comparisons with some of these sites cover multiple years allowing assessment of the EM27/SUN performance not only in various regions, but also over an extended period of time and with different seasonal influences. Results show that our 2 EM27/SUN instruments capture the diurnal variability of the aforementioned constituents very well, but with offsets from TCCON and long-term variability which may be due in part to the extensive movement these spectrometers were subjected to. These

  7. The Cerebellar-Cerebral Microstructure Is Disrupted at Multiple Sites in Very Preterm Infants with Cerebellar Haemorrhage.

    Neubauer, Vera; Djurdjevic, Tanja; Griesmaier, Elke; Biermayr, Marlene; Gizewski, Elke Ruth; Kiechl-Kohlendorfer, Ursula

    2018-01-01

    Recent advances in magnetic resonance imaging (MRI) techniques have prompted reconsideration of the anatomical correlates of adverse outcomes in preterm infants. The importance of the contribution made by the cerebellum is now increasingly appreciated. The effect of cerebellar haemorrhage (CBH) on the microstructure of the cerebellar-cerebral circuit is largely unexplored. To investigate the effect of CBH on the microstructure of cerebellar-cerebral connections in preterm infants aged microstructure (fractional anisotropy [FA] and apparent diffusion coefficient) were quantified in 5 vulnerable regions (the centrum semiovale, posterior limb of the internal capsule, corpus callosum, and superior and middle cerebellar peduncles). Group differences between infants with CBH and infants without CBH were assessed. There were 267 infants included in the study. Infants with CBH (isolated and combined) had significantly lower FA values in all regions investigated. Infants with isolated CBH showed lower FA in the middle and superior cerebellar peduncles and in the posterior limb of the internal capsule. This study provides evidence that CBH causes alterations in localised and remote WM pathways in the developing brain. The disruption of the cerebellar-cerebral microstructure at multiple sites adds further support for the concept of developmental diaschisis, which is propagated as an explanation for the consequences of early cerebellar injury on cognitive and affective domains. © 2017 S. Karger AG, Basel.

  8. Record-low primary productivity and high plant damage in the Nordic Arctic Region in 2012 caused by multiple weather events and pest outbreaks

    Bjerke, Jarle W; Jepsen, Jane U; Lovibond, Sarah; Tømmervik, Hans; Rune Karlsen, Stein; Arild Høgda, Kjell; Malnes, Eirik; Vikhamar-Schuler, Dagrun

    2014-01-01

    The release of cold temperature constraints on photosynthesis has led to increased productivity (greening) in significant parts (32–39%) of the Arctic, but much of the Arctic shows stable (57–64%) or reduced productivity (browning, <4%). Summer drought and wildfires are the best-documented drivers causing browning of continental areas, but factors dampening the greening effect of more maritime regions have remained elusive. Here we show how multiple anomalous weather events severely affected the terrestrial productivity during one water year (October 2011–September 2012) in a maritime region north of the Arctic Circle, the Nordic Arctic Region, and contributed to the lowest mean vegetation greenness (normalized difference vegetation index) recorded this century. Procedures for field data sampling were designed during or shortly after the events in order to assess both the variability in effects and the maximum effects of the stressors. Outbreaks of insect and fungal pests also contributed to low greenness. Vegetation greenness in 2012 was 6.8% lower than the 2000–11 average and 58% lower in the worst affected areas that were under multiple stressors. These results indicate the importance of events (some being mostly neglected in climate change effect studies and monitoring) for primary productivity in a high-latitude maritime region, and highlight the importance of monitoring plant damage in the field and including frequencies of stress events in models of carbon economy and ecosystem change in the Arctic. Fourteen weather events and anomalies and 32 hypothesized impacts on plant productivity are summarized as an aid for directing future research. (letter)

  9. Damage to tungsten macro-brush targets under multiple ELM-like heat loads. Experiments vs. numerical simulations and extrapolation to ITER

    Bazylev, B.; Landman, I. [Forschungszentrum Karlsruhe (Germany). IHM; Janeschitz, G. [Forschungszentrum Karlsruhe (DE). Fusion EURATOM] (and others)

    2007-07-01

    -Taylor instabilities are analyzed. To eliminate a large damage to brush edges, large melt splashing, and intense formation of the bridges between brushes optimization of the W-brush geometry is carried out. Damage of W-brush targets with both standard and optimized geometry was simulated for ITER ELM-like heat loads in the range 0.5-3.5 MJ/m{sup 2} and the timescales of 0.3-0.6 ms using the codes MEMOS and PHEMOBRID. Transformations of the brushes under multiple heat loads were also analyzed in the paper for different load conditions. (orig.)

  10. Application of multiple tracers (SF6 and chloride) to identify the transport by characteristics of contaminant at two separate contaminated sites

    Lee, K. K.; Lee, S. S.; Kim, H. H.; Koh, E. H.; Kim, M. O.; Lee, K.; Kim, H. J.

    2016-12-01

    Multiple tracers were applied for source and pathway detection at two different sites. CO2 gas injected in the subsurface for a shallow-depth CO2 injection and leak test can be regarded as a potential contaminant source. Therefore, it is necessary to identify the migration pattern of CO2 gas. Also, at a DNAPL contaminated site, it is important to figure out the characteristics of plume evolution from the source zone. In this study, multiple tracers (SF6 and chloride) were used to evaluate the applicability of volatile and non-volatile tracers and to identify the characteristics of contaminant transport at each CO2 injection and leak test site and DNAPL contaminated site. Firstly, at the CO2 test site, multiple tracers were used to perform the single well push-drift-pull tracer test at total 3 specific depth zones. As results of tests, volatile and non-volatile tracers showed different mass recovery percentage. Most of chloride mass was recovered but less than half of SF6 mass was recovered due to volatile property. This means that only gaseous SF6 leak out to unsaturated zone. However, breakthrough curves of both tracers indicated similar peak time, effective porosity, and regional groundwater velocity. Also, at both contaminated sites, natural gradient tracer tests were performed with multiple tracers. With the results of natural gradient tracer test, it was possible to confirm the applicability of multiple tracers and to understand the contaminant transport in highly heterogeneous aquifer systems through the long-term monitoring of tracers. Acknowledgement: financial support was provided by the R&D Project on Environmental Management of Geologic CO2 Storage)" from the KEITI (Project Number: 2014001810003) and Korea Ministry of Environment as "The GAIA project (2014000540010)".

  11. pLoc-mAnimal: predict subcellular localization of animal proteins with both single and multiple sites.

    Cheng, Xiang; Zhao, Shu-Guang; Lin, Wei-Zhong; Xiao, Xuan; Chou, Kuo-Chen

    2017-11-15

    Cells are deemed the basic unit of life. However, many important functions of cells as well as their growth and reproduction are performed via the protein molecules located at their different organelles or locations. Facing explosive growth of protein sequences, we are challenged to develop fast and effective method to annotate their subcellular localization. However, this is by no means an easy task. Particularly, mounting evidences have indicated proteins have multi-label feature meaning that they may simultaneously exist at, or move between, two or more different subcellular location sites. Unfortunately, most of the existing computational methods can only be used to deal with the single-label proteins. Although the 'iLoc-Animal' predictor developed recently is quite powerful that can be used to deal with the animal proteins with multiple locations as well, its prediction quality needs to be improved, particularly in enhancing the absolute true rate and reducing the absolute false rate. Here we propose a new predictor called 'pLoc-mAnimal', which is superior to iLoc-Animal as shown by the compelling facts. When tested by the most rigorous cross-validation on the same high-quality benchmark dataset, the absolute true success rate achieved by the new predictor is 37% higher and the absolute false rate is four times lower in comparison with the state-of-the-art predictor. To maximize the convenience of most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc-mAnimal/, by which users can easily get their desired results without the need to go through the complicated mathematics involved. xxiao@gordonlifescience.org or kcchou@gordonlifescience.org. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  12. Evaluation of the role of 8-iso-PGF levels at multiple sites during intracranial hemorrhage in pediatric patients.

    Qi, B-X; Yao, H; Shang, L; Sheng, L-P; Wang, X-C; Zhu, L; Zhang, X-X; Wang, J-P; Fang, D-H

    2017-09-01

    The present study was planned to explore the role of 8-isomeric-prostaglandinF2α (8-iso-PGF2α) levels at the multiple sites of cerebrospinal fluid in children with intracranial hemorrhage. 90 children with intracranial hemorrhage were admitted to Surgery Intensive Care Unit (SICU) of our hospital from January to December 2013 and were selected as study subjects. They were divided into group A (n=30), group B (n=30) and group C (n=30). The group A was given conventional treatment, the group B was treated with minimally invasive puncture and the group C was treated with cerebrospinal fluid decompression. After 1 d, 2 d, 3 d, and 7 d of hospitalization, enzyme-linked immunosorbent assay (ELISA) was used to detect the 8-iso-PGF2α levels in peripheral blood of children in all groups. On the day of admission and 10 d after treatment, 3 groups of children were implemented with brain nuclear magnetic resonance spectroscopy for metabolite analyses. On the day of admission there were no significant differences in the 8-iso-PGF2α levels among group A, B and C. Further, after 1 d, 3 d, 7 d of hospital stay, the 8-iso-PGF2α levels in peripheral blood showed a gradual downward trend, and decline range of the group C was greater than that of group A and B (p iso-PGF2α in peripheral blood (r = 0.546, p iso-PGF2α plays an important role in the pathogenesis of intracranial hemorrhage, and could be utilized as a biomarker of oxidative stress in children with intracranial hemorrhage. Further, cerebrospinal fluid decompression is a better method of treatment for intracranial hemorrhage.

  13. Damage analysis: damage function development and application

    Simons, R.L.; Odette, G.R.

    1975-01-01

    The derivation and application of damage functions, including recent developments for the U.S. LMFBR and CTR programs, is reviewed. A primary application of damage functions is in predicting component life expectancies; i.e., the fluence required in a service spectrum to attain a specified design property change. An important part of the analysis is the estimation of the uncertainty in such fluence limit predictions. The status of standardizing the procedures for the derivation and application of damage functions is discussed. Improvements in several areas of damage function development are needed before standardization can be completed. These include increasing the quantity and quality of the data used in the analysis, determining the limitations of the analysis due to the presence of multiple damage mechanisms, and finally, testing of damage function predictions against data obtained from material surveillance programs in operating thermal and fast reactors. 23 references. (auth)

  14. Effects on Jc of Pinning Center Morphology for Multiple-in-Line-Damage in Coated Conductor and Bulk, Melt-Textured HTS

    Weinstein, R. [University of Houston, Houston; Parks, D. [University of Houston, Houston; Sawh, R.-P. [University of Houston, Houston; Mayes, B. [University of Houston, Houston; Gandini, A. [University of Houston, Houston; Goyal, Amit [ORNL; Chen, Y. [SuperPower Incorporated, Schenectady, New York; Selvamanickam, V. [SuperPower Incorporated, Schenectady, New York

    2009-01-01

    The properties of discontinuous aligned pinning centers (PCs) created by high-energy heavy-ions are compared for bulk melt-textured and coated conductor HTS. Properties of PCs, which increase J{sub c} (pinning potential and entanglement), and negative properties which decrease J{sub c} (e.g., decreased T{sub c} and percolation paths) are evaluated. Mechanisms are proposed to explain the very large increases in J{sub c} resulting from multiple-in-line-damage (MILD) compared to continuous columnar pinning centers (CCPC). In particular, a mechanism which results in fluxoid entanglement, even for parallel (unsplayed) PCs, is discussed. The same mechanism is found to also account for restoration of much of the pinning potential expected to be lost due to the gaps in MILD PCs. It also accounts for the fact that at high fluence, J{sub c} increases as fluence is increased, instead of decreasing as expected. The very low self-field in coated conductor permits separation of the negative and positive effects of PCs. It is found that parameters developed to quantify the negative effects in bulk melt-textured YBCO, by 63 GeV U{sup 238} ions, successfully describe damage to 2.1 {micro}m thick coated conductor by 1 GeV Ru{sup 44} ions. Coated conductor at 77 K and self-field is generally known to have J{sub c} about 100 times that of melt-textured YBCO. However, at 77 K and applied field of 1 T, when both forms of HTS are processed with comparable numbers of near-optimum MILD PCs, the difference in J{sub c} is reduced to a factor of 1.3-2. Whereas J{sub c} for melt-textured YBCO increased sharply, by a factor of up to 16.8 for high-fluence MILD PCs, J{sub c} in coated conductor increased by a smaller factor of 2.5-3.0. Nevertheless, 2.1 {micro}m thick coated conductor, with near-optimum MILD PCs, exhibits J{sub c} = 543 kA/cm{sup 2} at 77 K and applied field of 1.0 T, and I{sub c} = 114 A/cm-width of conductor. This is the highest value we find in the literature. The

  15. Effects on Jc of pinning center morphology for multiple-in-line-damage in coated conductor and bulk, melt-textured HTS

    Weinstein, R.; Parks, D.; Sawh, R.-P.; Mayes, B.; Gandini, A.; Goyal, A.; Chen, Y.; Selvamanickam, V.

    2009-01-01

    The properties of discontinuous aligned pinning centers (PCs) created by high-energy heavy-ions are compared for bulk melt-textured and coated conductor HTS. Properties of PCs, which increase J c (pinning potential and entanglement), and negative properties which decrease J c (e.g., decreased T c and percolation paths) are evaluated. Mechanisms are proposed to explain the very large increases in J c resulting from multiple-in-line-damage (MILD) compared to continuous columnar pinning centers (CCPC). In particular, a mechanism which results in fluxoid entanglement, even for parallel (unsplayed) PCs, is discussed. The same mechanism is found to also account for restoration of much of the pinning potential expected to be lost due to the gaps in MILD PCs. It also accounts for the fact that at high fluence, J c increases as fluence is increased, instead of decreasing as expected. The very low self-field in coated conductor permits separation of the negative and positive effects of PCs. It is found that parameters developed to quantify the negative effects in bulk melt-textured YBCO, by 63 GeV U 238 ions, successfully describe damage to 2.1 μm thick coated conductor by 1 GeV Ru 44 ions. Coated conductor at 77 K and self-field is generally known to have J c about 100 times that of melt-textured YBCO. However, at 77 K and applied field of 1 T, when both forms of HTS are processed with comparable numbers of near-optimum MILD PCs, the difference in J c is reduced to a factor of 1.3-2. Whereas J c for melt-textured YBCO increased sharply, by a factor of up to 16.8 for high-fluence MILD PCs, J c in coated conductor increased by a smaller factor of 2.5-3.0. Nevertheless, 2.1 μm thick coated conductor, with near-optimum MILD PCs, exhibits J c = 543 kA/cm 2 at 77 K and applied field of 1.0 T, and I c = 114 A/cm-width of conductor. This is the highest value we find in the literature. The phenomenology developed indicates that for optimum MILD PCs in coated conductor, J c ∼ 700

  16. The complexity of DNA damage: relevance to biological consequences

    Ward, J.F.

    1994-01-01

    Ionizing radiation causes both singly and multiply damaged sites in DNA when the range of radical migration is limited by the presence of hydroxyl radical scavengers (e.g. within cells). Multiply damaged sites are considered to be more biologically relevant because of the challenges they present to cellular repair mechanisms. These sites occur in the form of DNA double-strand breaks (dsb) but also as other multiple damages that can be converted to dsb during attempted repair. The presence of a dsb can lead to loss of base sequence information and/or can permit the two ends of a break to separate and rejoin with the wrong partner. (Multiply damaged sites may also be the biologically relevant type of damage caused by other agents, such as UVA, B and/or C light, and some antitumour antibiotics). The quantitative data available from radiation studies of DNA are shown to support the proposed mechanisms for the production of complex damage in cellular DNA, i.e. via scavengable and non-scavengable mechanisms. The yields of complex damages can in turn be used to support the conclusion that cellular mutations are a consequence of the presence of these damages within a gene. (Author)

  17. RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination.

    Inano, Shojiro; Sato, Koichi; Katsuki, Yoko; Kobayashi, Wataru; Tanaka, Hiroki; Nakajima, Kazuhiro; Nakada, Shinichiro; Miyoshi, Hiroyuki; Knies, Kerstin; Takaori-Kondo, Akifumi; Schindler, Detlev; Ishiai, Masamichi; Kurumizaka, Hitoshi; Takata, Minoru

    2017-06-01

    RFWD3 is a recently identified Fanconi anemia protein FANCW whose E3 ligase activity toward RPA is essential in homologous recombination (HR) repair. However, how RPA ubiquitination promotes HR remained unknown. Here, we identified RAD51, the central HR protein, as another target of RFWD3. We show that RFWD3 polyubiquitinates both RPA and RAD51 in vitro and in vivo. Phosphorylation by ATR and ATM kinases is required for this activity in vivo. RFWD3 inhibits persistent mitomycin C (MMC)-induced RAD51 and RPA foci by promoting VCP/p97-mediated protein dynamics and subsequent degradation. Furthermore, MMC-induced chromatin loading of MCM8 and RAD54 is defective in cells with inactivated RFWD3 or expressing a ubiquitination-deficient mutant RAD51. Collectively, our data reveal a mechanism that facilitates timely removal of RPA and RAD51 from DNA damage sites, which is crucial for progression to the late-phase HR and suppression of the FA phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Characterisation of Beaver Habitat Parameters That Promote the Use of Culverts as Dam Construction Sites: Can We Limit the Damage to Forest Roads?

    Geneviève Tremblay

    2017-12-01

    Full Text Available The use of forest roads as foundations for dam construction by beavers is a recurrent problem in the management of forest road networks. In order to limit the damage to forest roads, our goal was to calculate the probability of beaver dam installation on culverts, according to surrounding habitat parameters, which could allow for improvement in the spatial design of new roads that minimise conflicts with beavers. Comparisons of culverts with (n = 77 and without (n = 51 dams in northwestern Quebec showed that catchment surface, cumulate length of all local streams within a 2-km radius, and road embankment height had a negative effect on the probability of dam construction on culverts, while flow level and culvert diameter ratio had a positive effect. Nevertheless, predicted probabilities of dam construction on culverts generally exceeded 50%, even on sites that were less favourable to beavers. We suggest that it would be more reasonable to take their probable subsequent presence into account at the earliest steps of road conception. Installing mitigation measures such as pre-dams during road construction would probably reduce the occurrence of conflicts with beavers and thus reduce the maintenance costs of forest roads.

  19. Mosquito breeding sites and People’s knowledge of mosquitoes and mosquito borne diseases: A comparison of temporary housing and non-damaged village areas in Sri Lanka after the tsunami strike in 2004

    Ohba, Shin-ya; Kashima, Saori; Matsubara, Hiromi; Higa, Yukiko; Piyaseeli, Udage Kankanamge D.; Yamamoto, Hideki; Nakasuji, Fusao

    2010-01-01

    Although it is very important in view of public health to understand the mosquito breeding sites and key reservoirs existing around residential areas, such information is lacking in temporary housing sites constructed after the serious tsunami strikes on 26 December 2004 in Sri Lanka. This study clarified the situation regarding mosquito breeding 14 months after the tsunami in Sri Lanka by surveying temporary housing and non-damaged village areas, and also by examining people‘s knowledge rela...

  20. Selective labeling of serotonin uptake sites in rat brain by [3H]citalopram contrasted to labeling of multiple sites by [3H]imipramine

    D'Amato, R.J.; Largent, B.L.; Snowman, A.M.; Snyder, S.H.

    1987-01-01

    Citalopram is a potent and selective inhibitor of neuronal serotonin uptake. In rat brain membranes [ 3 H]citalopram demonstrates saturable and reversible binding with a KD of 0.8 nM and a maximal number of binding sites (Bmax) of 570 fmol/mg of protein. The drug specificity for [ 3 H]citalopram binding and synaptosomal serotonin uptake are closely correlated. Inhibition of [ 3 H]citalopram binding by both serotonin and imipramine is consistent with a competitive interaction in both equilibrium and kinetic analyses. The autoradiographic pattern of [ 3 H]citalopram binding sites closely resembles the distribution of serotonin. By contrast, detailed equilibrium-saturation analysis of [ 3 H]imipramine binding reveals two binding components, i.e., high affinity (KD = 9 nM, Bmax = 420 fmol/mg of protein) and low affinity (KD = 553 nM, Bmax = 8560 fmol/mg of protein) sites. Specific [ 3 H]imipramine binding, defined as the binding inhibited by 100 microM desipramine, is displaced only partially by serotonin. Various studies reveal that the serotonin-sensitive portion of binding corresponds to the high affinity sites of [ 3 H]imipramine binding whereas the serotonin-insensitive binding corresponds to the low affinity sites. Lesioning of serotonin neurons with p-chloroamphetamine causes a large decrease in [ 3 H]citalopram and serotonin-sensitive [ 3 H]imipramine binding with only a small effect on serotonin-insensitive [ 3 H]imipramine binding. The dissociation rate of [ 3 H]imipramine or [ 3 H]citalopram is not altered by citalopram, imipramine or serotonin up to concentrations of 10 microM. The regional distribution of serotonin sensitive [ 3 H]imipramine high affinity binding sites closely resembles that of [ 3 H]citalopram binding

  1. Natural Attenuation of Chlorinated Solvents Performance and Cost Results from Multiple Air Force Demonstration Sites, Technology Demonstration Slide Presentation

    Wiedemeier, Todd

    1999-01-01

    This slide presentation summarizes the results of natural attenuation treatability studies at 14 Air Force sites contaminated with chlorinated solvents and their associated biodegradation daughter products...

  2. Source apportionment of PM2.5 at multiple Northwest U.S. sites: Assessing regional winter wood smoke impacts from residential wood combustion

    Kotchenruther, Robert A.

    2016-10-01

    Wood smoke from residential wood combustion is a significant source of elevated PM2.5 in many communities across the Northwest U.S. Accurate representation of residential wood combustion in source-oriented regional scale air quality models is challenging because of multiple uncertainties. As an alternative to source-oriented source apportionment, this work provides, through receptor-oriented source apportionment, an assessment of winter residential wood combustion impacts at multiple Northwest U.S. locations. Source apportionment was performed on chemically speciated PM2.5 from 19 monitoring sites using the Positive Matrix Factorization (PMF) receptor model. Each site was modeled independently, but a common data preparation and modeling protocol was used so that results were as comparable as possible across sites. Model solutions had from 4 to 8 PMF factors, depending on the site. PMF factors at each site were associated with a source classification (e.g., primary wood smoke), a dominant chemical composition (e.g., ammonium nitrate), or were some mixture. 15 different sources or chemical compositions were identified as contributing to PM2.5 across the 19 sites. The 6 most common were; aged wood smoke and secondary organic carbon, motor vehicles, primary wood smoke, ammonium nitrate, ammonium sulfate, and fugitive dust. Wood smoke was identified at every site, with both aged and primary wood smoke identified at most sites. Wood smoke contributions to PM2.5 were averaged for the two winter months of December and January, the months when wood smoke in the Northwest U.S. is mainly from residential wood combustion. The total contribution of residential wood combustion, that from primary plus aged smoke, ranged from 11.4% to 92.7% of average December and January PM2.5 depending on the site, with the highest percent contributions occurring in smaller towns that have fewer expected sources of winter PM2.5. Receptor modeling at multiple sites, such as that conducted in this

  3. Scheduling the Remediation of Port Hope: Logistical and Regulatory Challenges of a Multiple Site Urban Remediation Project - 13119

    Ferguson Jones, Andrea; Lee, Angela; Palmeter, Tim

    2013-01-01

    The Port Hope Project is part of the larger CAN$1.28 billion Port Hope Area Initiative (PHAI), a community-based program for the development and implementation of a safe, local, long-term management solution for historic Low-Level Radioactive Waste (LLRW) in the Municipalities of Port Hope and Clarington, Ontario, Canada. Atomic Energy of Canada (AECL) is the Project Proponent, Public Works and Government Services (PWGSC) is managing the procurement of services and the MMM Group Limited - Conestoga Rovers and Associates Joint Venture (MMM-CRA Joint Venture) is providing detailed design and construction oversight and administration services for the Project. The Port Hope Project includes the construction of a long-term waste management facility (LTWMF) in the Municipality of Port Hope and the remediation of 18 (eighteen) large-scale LLRW, numerous small-scale sites still being identified and industrial sites within the Municipality. The total volume to be remediated is over one million cubic metres and will come from sites that include temporary storage sites, ravines, beaches, parks, private commercial and residential properties and vacant industrial sites all within the urban area of Port Hope. Challenges that will need to be overcome during this 10 year project include: - Requirements stipulated by the Environmental Assessment (EA) that affect Project logistics and schedule. - Coordination of site remediation with the construction schedule at the LTWMF. - Physical constraints on transport routes and at sites affecting production rates. - Despite being an urban undertaking, seasonal constrains for birds and fish (i.e., nesting and spawning seasons). - Municipal considerations. - Site-specific constraints. - Site interdependencies exist requiring consideration in the schedule. Several sites require the use of an adjacent site for staging. (authors)

  4. Scheduling the Remediation of Port Hope: Logistical and Regulatory Challenges of a Multiple Site Urban Remediation Project - 13119

    Ferguson Jones, Andrea; Lee, Angela [MMM Group Limited, 100 Commerce Valley Drive West, Thornhill, Ontario, L3T 0A1 (Canada); Palmeter, Tim [Public Works and Government Services Canada, 4900 Yonge Street, Toronto, Ontario, M2N 6A6 (Canada)

    2013-07-01

    The Port Hope Project is part of the larger CAN$1.28 billion Port Hope Area Initiative (PHAI), a community-based program for the development and implementation of a safe, local, long-term management solution for historic Low-Level Radioactive Waste (LLRW) in the Municipalities of Port Hope and Clarington, Ontario, Canada. Atomic Energy of Canada (AECL) is the Project Proponent, Public Works and Government Services (PWGSC) is managing the procurement of services and the MMM Group Limited - Conestoga Rovers and Associates Joint Venture (MMM-CRA Joint Venture) is providing detailed design and construction oversight and administration services for the Project. The Port Hope Project includes the construction of a long-term waste management facility (LTWMF) in the Municipality of Port Hope and the remediation of 18 (eighteen) large-scale LLRW, numerous small-scale sites still being identified and industrial sites within the Municipality. The total volume to be remediated is over one million cubic metres and will come from sites that include temporary storage sites, ravines, beaches, parks, private commercial and residential properties and vacant industrial sites all within the urban area of Port Hope. Challenges that will need to be overcome during this 10 year project include: - Requirements stipulated by the Environmental Assessment (EA) that affect Project logistics and schedule. - Coordination of site remediation with the construction schedule at the LTWMF. - Physical constraints on transport routes and at sites affecting production rates. - Despite being an urban undertaking, seasonal constrains for birds and fish (i.e., nesting and spawning seasons). - Municipal considerations. - Site-specific constraints. - Site interdependencies exist requiring consideration in the schedule. Several sites require the use of an adjacent site for staging. (authors)

  5. Roles of multiple surface sites, long substrate binding clefts, and carbohydrate binding modules in the action of amylolytic enzymes on polysaccharide substrates

    Nielsen, Morten Munch; Seo, E.S.; Dilokpimol, Adiphol

    2008-01-01

    Germinating barley seeds contain multiple forms of alpha-amylase, which are subject to both differential gene expression and differential degradation as part of the repertoire of starch-degrading enzymes. The alpha-amylases are endo-acting and possess a long substrate binding cleft with a charact......Germinating barley seeds contain multiple forms of alpha-amylase, which are subject to both differential gene expression and differential degradation as part of the repertoire of starch-degrading enzymes. The alpha-amylases are endo-acting and possess a long substrate binding cleft...... will address surface sites in both barley alpha-amylase 1 and in the related isozyme 2....

  6. Estimated airborne release of plutonium from Atomics International's Nuclear Materials Development Facility in the Santa Susana site, California, as a result of postulated damage from severe wind and earthquake hazard

    Mishima, J.; Ayer, J.E.

    1981-09-01

    The potential mass of airborne releases of plutonium (source term) that could result from wind and seismic damage is estimated for the Atomics International Company's Nuclear Materials Development Facility (NMDF) at the Santa Susana site in California. The postulated source terms will be useful as the basis for estimating the potential dose to the maximum exposed individual by inhalation and to the total population living within a prescribed radius of the site. The respirable fraction of airborne particles is thus the principal concern. The estimated source terms are based on the damage ratio, and the potential airborne releases if all enclosures suffer particular levels of damage. In an attempt to provide a realistic range of potential source terms that include most of the normal processing conditions, a best estimate bounded by upper and lower limits is provided. The range of source terms is calculated by combining a high best estimate and a low damage ratio, based on a fraction of enclosures suffering crush or perforation, with the airborne release from enclosures based upon an upper limit, average, and lower limit inventory of dispersible materials at risk. Two throughput levels are considered. The factors used to evaluate the fractional airborne release of materials and the exchange rates between enclosed and exterior atmospheres are discussed. The postulated damage and source terms are discussed for wind and earthquake hazard scenarios in order of their increasing severity

  7. SigniSite: Identification of residue-level genotype-phenotype correlations in protein multiple sequence alignments

    Jessen, Leon Ivar; Hoof, Ilka; Lund, Ole

    2013-01-01

    Site does not require any pre-definition of subgroups or binary classification. Input is a set of protein sequences where each sequence has an associated real number, quantifying a given phenotype. SigniSite will then identify which amino acid residues are significantly associated with the data set......) using a set of human immunodeficiency virus protease-inhibitor genotype–phenotype data and corresponding resistance mutation scores from the Stanford University HIV Drug Resistance Database, and a data set of protein families with experimentally annotated SDPs. For both data sets, SigniSite was found...

  8. Assessment of Accrued Damage and Remaining Useful Life in Leadfree Electronics Subjected to Multiple Thermal Environments of Thermal Aging and Thermal Cycling

    National Aeronautics and Space Administration — A method has been developed for prognostication of accrued prior damage in electronics subjected to overlapping sequential environments of thermal aging and thermal...

  9. Assigning Quantitative Function to Post-Translational Modifications Reveals Multiple Sites of Phosphorylation That Tune Yeast Pheromone Signaling Output

    Pincus, David; Ryan, Christopher J.; Smith, Richard D.; Brent, Roger; Resnekov, Orna; Hakimi, Mohamed Ali

    2013-03-12

    Cell signaling systems transmit information by post-­translationally modifying signaling proteins, often via phosphorylation. While thousands of sites of phosphorylation have been identified in proteomic studies, the vast majority of sites have no known function. Assigning functional roles to the catalog of uncharacterized phosphorylation sites is a key research challenge. Here we present a general approach to address this challenge and apply it to a prototypical signaling pathway, the pheromone response pathway in Saccharomyces cerevisiae. The pheromone pathway includes a mitogen activated protein kinase (MAPK) cascade activated by a G-­protein coupled receptor (GPCR). We used mass spectrometry-based proteomics to identify sites whose phosphorylation changed when the system was active, and evolutionary conservation to assign priority to a list of candidate MAPK regulatory sites. We made targeted alterations in those sites, and measured the effects of the mutations on pheromone pathway output in single cells. Our work identified six new sites that quantitatively tuned system output. We developed simple computational models to find system architectures that recapitulated the quantitative phenotypes of the mutants. Our results identify a number of regulated phosphorylation events that contribute to adjust the input-­output relationship of this model eukaryotic signaling system. We believe this combined approach constitutes a general means not only to reveal modification sites required to turn a pathway on and off, but also those required for more subtle quantitative effects that tune pathway output. Our results further suggest that relatively small quantitative influences from individual regulatory phosphorylation events endow signaling systems with plasticity that evolution may exploit to quantitatively tailor signaling outcomes.

  10. Imbalanced multi-modal multi-label learning for subcellular localization prediction of human proteins with both single and multiple sites.

    Jianjun He

    Full Text Available It is well known that an important step toward understanding the functions of a protein is to determine its subcellular location. Although numerous prediction algorithms have been developed, most of them typically focused on the proteins with only one location. In recent years, researchers have begun to pay attention to the subcellular localization prediction of the proteins with multiple sites. However, almost all the existing approaches have failed to take into account the correlations among the locations caused by the proteins with multiple sites, which may be the important information for improving the prediction accuracy of the proteins with multiple sites. In this paper, a new algorithm which can effectively exploit the correlations among the locations is proposed by using gaussian process model. Besides, the algorithm also can realize optimal linear combination of various feature extraction technologies and could be robust to the imbalanced data set. Experimental results on a human protein data set show that the proposed algorithm is valid and can achieve better performance than the existing approaches.

  11. Involvement of individual subsites and secondary substrate binding sites in multiple attack on amylose by barley alpha-amylase

    Kramhøft, Birte; Bak-Jensen, Kristian Sass; Mori, Haruhide

    2005-01-01

    Barley alpha-amylase 1 (AMY1) hydrolyzed amylose with a degree of multiple attack (DMA) of 1.9; that is, on average, 2.9 glycoside bonds are cleaved per productive enzyme-substrate encounter. Six AMY1 mutants, spanning the substrate binding cleft from subsites -6 to +4, and a fusion protein, AMY1...... translocation of substrate in the binding cleft upon the initial cleavage to produce G6-G10, essentially independent of subsite mutations, and short-distance moves resulting in individually very different rates of release of G1-G4. Accordingly, the degree of multiple attack as well as the profile of products...

  12. Carbon monoxide adsorption on low-silica zeolites: from single to dual and to multiple cation sites.

    Otero Areán, C; Rodríguez Delgado, M; López Bauçà, C; Vrbka, L; Nachtigall, P

    2007-09-07

    Infrared spectra of CO adsorbed on the Al-rich Na-A zeolite were analysed by using a combined theoretical and experimental approach, showing that such spectra cannot be interpreted by assigning each IR band to CO interacting with a specific type of single cation site. This concept, which usually works well for high-silica zeolites, should not be uncritically extended to Al-rich zeolites that are crowded with cations in configurations which lead to preferential formation of CO adsorption complexes involving more than one cation site.

  13. A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors.

    Izhar, Lior; Adamson, Britt; Ciccia, Alberto; Lewis, Jedd; Pontano-Vaites, Laura; Leng, Yumei; Liang, Anthony C; Westbrook, Thomas F; Harper, J Wade; Elledge, Stephen J

    2015-06-09

    Localization to sites of DNA damage is a hallmark of DNA damage response (DDR) proteins. To identify DDR factors, we screened epitope-tagged proteins for localization to sites of chromatin damaged by UV laser microirradiation and found >120 proteins that localize to damaged chromatin. These include the BAF tumor suppressor complex and the amyotrophic lateral sclerosis (ALS) candidate protein TAF15. TAF15 contains multiple domains that bind damaged chromatin in a poly-(ADP-ribose) polymerase (PARP)-dependent manner, suggesting a possible role as glue that tethers multiple PAR chains together. Many positives were transcription factors; > 70% of randomly tested transcription factors localized to sites of DNA damage, and of these, ∼90% were PARP dependent for localization. Mutational analyses showed that localization to damaged chromatin is DNA-binding-domain dependent. By examining Hoechst staining patterns at damage sites, we see evidence of chromatin decompaction that is PARP dependent. We propose that PARP-regulated chromatin remodeling at sites of damage allows transient accessibility of DNA-binding proteins. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors

    Lior Izhar

    2015-06-01

    Full Text Available Localization to sites of DNA damage is a hallmark of DNA damage response (DDR proteins. To identify DDR factors, we screened epitope-tagged proteins for localization to sites of chromatin damaged by UV laser microirradiation and found >120 proteins that localize to damaged chromatin. These include the BAF tumor suppressor complex and the amyotrophic lateral sclerosis (ALS candidate protein TAF15. TAF15 contains multiple domains that bind damaged chromatin in a poly-(ADP-ribose polymerase (PARP-dependent manner, suggesting a possible role as glue that tethers multiple PAR chains together. Many positives were transcription factors; > 70% of randomly tested transcription factors localized to sites of DNA damage, and of these, ∼90% were PARP dependent for localization. Mutational analyses showed that localization to damaged chromatin is DNA-binding-domain dependent. By examining Hoechst staining patterns at damage sites, we see evidence of chromatin decompaction that is PARP dependent. We propose that PARP-regulated chromatin remodeling at sites of damage allows transient accessibility of DNA-binding proteins.

  15. A Study of How Young Adults Leverage Multiple Profile Management Functionality in Managing Their Online Reputation on Social Networking Sites

    McCune, T. John

    2017-01-01

    With privacy settings on social networking sites (SNS) perceived as complex and difficult to use and maintain, young adults can be left vulnerable to others accessing and using their personal information. Consequences of not regulating the boundaries their information on SNS include the ability for current and future employers to make…

  16. Repetitive, Marker-Free, Site-Specific Integration as a Novel Tool for Multiple Chromosomal Integration of DNA

    Petersen, Kia Vest; Martinussen, Jan; Jensen, Peter Ruhdal

    2013-01-01

    of a minimal bacterial attachment site (attBmin), two mutated loxP sequences (lox66 and lox71) allowing for removal of undesirable vector elements (antibiotic resistance marker), and a counterselection marker (oroP) for selection of loxP recombination on the pKV6 vector. When transformed into L. lactis...

  17. Site-specific RNase A activity was dramatically reduced in serum from multiple types of cancer patients.

    Weiyan Huang

    Full Text Available Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5'-U/A-3' and 5'-C/A-3' dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10(-5 mg/ml- 10(-1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types.

  18. Site-Specific RNase A Activity Was Dramatically Reduced in Serum from Multiple Types of Cancer Patients

    Huang, Weiyan; Zhao, Mei; Wei, Na; Wang, Xiaoxia; Cao, Huqing; Du, Quan; Liang, Zicai

    2014-01-01

    Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5′-U/A-3′ and 5′-C/A-3′ dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10−5 mg/ml- 10−1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types. PMID:24805924

  19. Correlation between particle multiplicity and location on virion RNA of the assembly initiation site for viruses of the tobacco mosaic virus group.

    Fukuda, M; Meshi, T; Okada, Y; Otsuki, Y; Takebe, I

    1981-07-01

    The initiation site for reconstitution on genome RNA was determined by electron microscopic serology for a watermelon strain of cucumber green mottle mosaic virus (CGMMV-W), which is chemically and serologically related to tobacco mosaic virus (TMV). The initiation site was located at the same position as that of the cowpea strain, a virus that produces short rods of encapsidated subgenomic messenger RNA for the coat protein (a two-component TMV), being about 320 nucleotides away from the 3' terminus, and hence within the coat protein cistron. Although CGMMV-W was until now believed to be a single-component TMV, the location of the initiation site indicated the presence of short rods containing coat protein messenger RNA in CGMMV-W-infected tissue, as in the case for the cowpea strain. We found such short rods in CGMMV-W-infected tissue. The results confirmed our previous hypothesis that the site of the initiation region for reconstitution determines the rod multiplicity of TMV. The finding of the second two-component TMV, CGMMV, indicates that the cowpea strain of TMV is not unique in being a two-component virus and that the location of the assembly initiation site on the genome RNA can be a criterion for grouping of viruses.

  20. Fine tuning of RFX/DAF-19-regulated target gene expression through binding to multiple sites in Caenorhabditis elegans

    Chu, Jeffery S. C.; Tarailo-Graovac, Maja; Zhang, Di; Wang, Jun; Uyar, Bora; Tu, Domena; Trinh, Joanne; Baillie, David L.; Chen, Nansheng

    2011-01-01

    In humans, mutations of a growing list of regulatory factor X (RFX) target genes have been associated with devastating genetics disease conditions including ciliopathies. However, mechanisms underlying RFX transcription factors (TFs)-mediated gene expression regulation, especially differential gene expression regulation, are largely unknown. In this study, we explore the functional significance of the co-existence of multiple X-box motifs in regulating differential gene expression in Caenorha...

  1. Cone penetrometer testing and discrete-depth groundwater sampling techniques: A cost-effective method of site characterization in a multiple-aquifer setting

    Zemo, D.A.; Pierce, Y.G.; Gallinatti, J.D.

    1992-01-01

    Cone penetrometer testing (CPT), combined with discrete-depth groundwater sampling methods, can reduce significantly the time and expense required to characterize large sites that have multiple aquifers. Results from the screening site characterization can 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 a depth of 80 feet within a 1/2 mile-by-1/4-mile residential and commercial area in a complex alluvial fan setting. To expedite site characterization, a five-week field screening program was implemented that consisted of a shallow groundwater survey, CPT soundings, and discrete-depth groundwater sampling. Based on continuous lithologic information provided by the CPT soundings, four coarse-grained water-yielding sedimentary packages were identified. Eighty-three discrete-depth groundwater samples were collected using shallow groundwater survey techniques, the BAT Enviroprobe, or the QED HydroPunch 1, depending on subsurface conditions. A 20-well monitoring network was designed and installed to monitor critical points within each sedimentary package. Understanding the vertical VOC distribution and concentrations produced substantial cost savings by minimizing the number of permanent monitoring wells and reducing the number of costly conductor casings to be installed. Significant long-term cost savings will result from reduced sampling costs. Where total VOC concentrations exceeded 20 φg/l in the screening samples, a good correlation was found between the discrete-depth screening data and data from monitoring wells. Using a screening program to characterize the site before installing monitoring wells resulted in an estimated 50-percent reduction in costs for site characterization, 65-percent reduction in time for site characterization, and 50-percent reduction in long-term monitoring costs

  2. Analysis of quadrupole splitting of multiple Fe sites intermixed in Si(111) with Mössbauer spectroscopy

    Kawauchi, Taizo, E-mail: kawauchi@iis.u-tokyo.ac.jp [Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505 (Japan); Zhang, Xiaowei [Institute of Materials Structure Science, High Energy Accelerator Research Organization, 1-1, Oho, Tsukuba, Ibaraki 305-0801 (Japan); Fukutani, Katsuyuki [Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505 (Japan)

    2016-12-01

    The iron silicide has various interesting phases both fundamentally and technologically, which have acquired much attention to date. Iron silicides are often fabricated on a Si substrate by a solid phase epitaxy method, and the initial stage of intermixing of iron atoms with substrate Si is of crucial importance for silicide fabrication, which remains to be clarified. Here, we have investigated the initial stage of the iron-silicide formation before crystallization with Mössbauer spectroscopy suited to characterization of magnetic and chemical properties of {sup 57}Fe atoms in materials. The sample was prepared by deposition of {sup 57}Fe of 1 nm on a Si(111) surface at 450 K. Conventional Mössbauer spectroscopy in the energy domain revealed presence of two iron sites with similar quadrupole splits and isomer shifts, which hampered complete analysis of this system. By combining the time-domain spectroscopy using polarized synchrotron radiation, we have separately analyzed the quadrupole splits and isomer shifts for the two iron sites. By using the theoretical simulation, furthermore, we successfully reproduced the experimentally observed time spectrum of the nuclear resonant scattering on the assumption that iron atoms randomly occupy the substitutional sites for Si at the initial stage of intermixing before crystallization of an iron silicide. - Highlights: • Quadrupole split of Fe in an iron silicide is measured by Mossbauer spectroscopy. • Two components are separately analyzed with time- and energy-domain spectra. • The time spectrum is well reproduced by numerical simulation. • Results indicate that Fe atoms randomly occupy two possible sites in Fe silicide.

  3. Closure Strategy for a Waste Disposal Facility with Multiple Waste Types and Regulatory Drivers at the Nevada Test Site - 8422

    D Wieland; V Yucel; L Desotell; G Shott; J Wrapp

    2008-01-01

    The U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) plans to close the waste and classified material storage cells in the southeast quadrant of the Area 5 Radioactive Waste Management Site (RWMS), informally known as the '92-Acre Area', by 2011. The 25 shallow trenches and pits and the 13 Greater Confinement Disposal (GCD) borings contain various waste streams including low-level waste (LLW), low-level mixed waste (LLMW), transuranic (TRU), mixed transuranic (MTRU), and high specific activity LLW. The cells are managed under several regulatory and permit programs by the U.S. Department of Energy (DOE) and the Nevada Division of Environmental Protection (NDEP). Although the specific closure requirements for each cell vary, 37 closely spaced cells will be closed under a single integrated monolayer evapotranspirative (ET) final cover. One cell will be closed under a separate cover concurrently. The site setting and climate constrain transport pathways and are factors in the technical approach to closure and performance assessment. Successful implementation of the integrated closure plan requires excellent communication and coordination between NNSA/NSO and the regulators

  4. DEVELOPING SITE-SPECIFIC DERIVED CONCENTRATION GUIDELINE LEVELS FOR MULTIPLE MEDIA AT THE CONNECTICUT YANKEE HADDAM NECK PLANT

    Taylor, S.W.; Smith, L.C.; Carr, R.K.; Carson, A.; Darois, E.

    2003-01-01

    As part of the license termination process, site-specific Derived Concentration Guideline Levels for the Haddam Neck Plant site are developed for soil, groundwater, concrete left standing, and concrete demolished that satisfy the radiological criteria for unrestricted use as defined in 10 CFR 20.1402. Background information on the license termination process and characteristics of the Haddam Neck Plant site are presented. The dose models and associated resident farmer and building occupancy scenarios, applicable pathways, and critical groups developed to establish the Derived Concentration Guideline Levels are described. A parameter assignment process is introduced wherein general population values are used to establish behavioral and metabolic parameters representative of an average member of the critical group, while the uncertainty associated with important physical parameters is considered. A key element of the parameter assignment process is the use of sensitivity analysis to identify the dose sensitive physical parameters and to ensure that such parameters are assigned conservative values. Structuring the parameter assignment process, completing the formal sensitivity analyses, and assigning conservative values to the sensitive physical parameters in a consistent way establishes a calculation framework that lead to Derived Concentration Guideline Levels with a uniform level of conservatism across all media and all radionuclides

  5. Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.

    Scally, Stephen W; McLeod, Brandon; Bosch, Alexandre; Miura, Kazutoyo; Liang, Qi; Carroll, Sean; Reponen, Sini; Nguyen, Ngan; Giladi, Eldar; Rämisch, Sebastian; Yusibov, Vidadi; Bradley, Allan; Lemiale, Franck; Schief, William R; Emerling, Daniel; Kellam, Paul; King, C Richter; Julien, Jean-Philippe

    2017-11-16

    The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.

  6. Ferromanganese nodules from MANOP Sites H, S, and R-Control of mineralogical and chemical composition by multiple accretionary processes

    Dymond, J.; Lyle, M.; Finney, B.; Piper, D.Z.; Murphy, K.; Conard, R.; Pisias, N.

    1984-01-01

    The chemical composition of ferromanganese nodules from the three nodule-bearing MANOP sites in the Pacific can be accounted for in a qualitative way by variable contributions of distinct accretionary processes. These accretionary modes are: 1. (1) hydrogenous, i.e., direct precipitation or accumulation of colloidal metal oxides in seawater, 2. (2) oxic diagenesis which refers to a variety of ferromanganese accretion processes occurring in oxic sediments; and 3. (3) suboxic diagenesis which results from reduction of Mn+4 by oxidation of organic matter in the sediments. Geochemical evidence suggests processes (1) and (2) occur at all three MANOP nodule-bearing sites, and process (3) occurs only at the hemipelagic site, H, which underlies the relatively productive waters of the eastern tropical Pacific. A normative model quantitatively accounts for the variability observed in nearly all elements. Zn and Na, however, are not well explained by the three end-member model, and we suggest that an additional accretionary process results in greater variability in the abundances of these elements. Variable contributions from the three accretionary processes result in distinct top-bottom compositional differences at the three sites. Nodule tops from H are enriched in Ni, Cu, and Zn, instead of the more typical enrichments of these elements in nodule bottoms. In addition, elemental correlations typical of most pelagic nodules are reversed at site H. The three accretionary processes result in distinct mineralogies. Hydrogenous precipitation produces ??MnO2. Oxic diagenesis, however, produces Cu-Ni-rich todorokite, and suboxic diagenesis results in an unstable todorokite which transforms to a 7 A?? phase ("birnessite") upon dehydration. The presence of Cu and Ni as charge-balancing cations influence the stability of the todorokite structure. In the bottoms of H nodules, which accrete dominantly by suboxic diagenesis, Na+ and possibly Mn+2 provide much of the charge balance for

  7. DNA damage, acetylcholinesterase activity and lysosomal stability in native and transplanted mussels (Mytilus edulis) in areas close to coastal chemical dumping sites in Denmark

    Rank, Jette; Lehtonen, Kari K.; Strand, Jakob

    2007-01-01

    Biomarkers of genotoxicity (DNA damage, measured as tail moment in the Comet assay), neurotoxicity (acetylcholinesterase inhibition, AChE) and general stress (lysosomal membrane stability, LMS) were studied in native and transplanted blue mussels (Mytilus edulis) in coastal areas of western Denmark...... of chemical pollution complex, as seen especially in the variability in results on DNA damage, and also in regard to AChE activity. These investigations further stress the importance of understanding the effects of natural factors (salinity, temperature, water levels, rain and storm events) in correct...

  8. A tumefactive multiple sclerosis lesion in the brain: An uncommon site with atypical magnetic resonance image findings

    Jeong, Min Sun; Kim, Hyun Sook; Kim, Jae Hoon; Kim, Eun Kyung; Choi, Yun Sun [Eulji Hospital, Eulji University, Seoul (Korea, Republic of)

    2013-11-15

    Tumefactive multiple sclerosis (MS) is a rare type of demyelinating disease. Typical magnetic resonance (MR) image findings show incomplete ring enhancement with a mild mass effect. This lesion is otherwise indistinguishable from other mass-like lesions in the brain. Knowledge of the MR imaging findings for tumefactive MS is thus helpful for correct diagnosis and appropriate therapy. In this report we describe the MR image findings for pathology-confirmed tumefactive MS in an uncommon location, alongside a discussion of its aggressive features.

  9. Evaluating multiple indices of agricultural water use efficiency and productivity to improve comparisons between sites and trends

    Levy, M. C.

    2012-12-01

    Approximately 70% of global available freshwater supplies are used in the agricultural sector. Increased demands for water to meet growing population food requirements, and expected changes in the reliability of freshwater supplies due to climate change, threaten the sustainability of water supplies worldwide - not only on farms, but in connected cities and industries. Researchers concerned with agricultural water use sustainability use a variety of theoretical and empirical measures of efficiency and productivity to gain insight into the sustainability of agricultural water use. However, definitions of measures, or indices, vary between different natural and political boundaries, across regions, states and nations and between their respective research, industry, and environmental groups. Index development responds to local data availability and local agendas, and there is debate about the validity of various indices. However, real differences in empirical index measures are not well-understood across the multiple disciplines that study agricultural water use, including engineering and hydrology, agronomy, climate and soil sciences, and economics. Nevertheless reliable, accessible, and generalizable indices are required for planners and policymakers to promote sustainable water use systems. This study synthesizes a set of water use efficiency and productivity indices based on academic, industry and government literature in California and Australia, two locations with similarly water-stressed and valuable agricultural industries under pressure to achieve optimal water use efficiency and productivity. Empirical data at the irrigation district level from the California San Joaquin Valley and Murray Darling Basin states of Victoria and New South Wales in Australia are used to compute indices that estimate efficiency, yield productivity, and economic productivity of agricultural water use. Multiple index estimates of same time-series data demonstrate historical spread

  10. Interpretation of Ocular Melanin Drug Binding Assays. Alternatives to the Model of Multiple Classes of Independent Sites.

    Manzanares, José A; Rimpelä, Anna-Kaisa; Urtti, Arto

    2016-04-04

    Melanin has a high binding affinity for a wide range of drugs. The determination of the melanin binding capacity and its binding affinity are important, e.g., in the determination of the ocular drug distribution, the prediction of drug effects in the eye, and the trans-scleral drug delivery. The binding parameters estimated from a given data set vary significantly when using different isotherms or different nonlinear fitting methods. In this work, the commonly used bi-Langmuir isotherm, which assumes two classes of independent sites, is confronted with the Sips isotherm. Direct, log-log, and Scatchard plots are used, and the interpretation of the binding curves in the latter is critically analyzed. In addition to the goodness of fit, the emphasis is placed on the physical meaning of the binding parameters. The bi-Langmuir model imposes a bimodal distribution of binding energies for the sites on the melanin granules, but the actual distribution is most likely continuous and unimodal, as assumed by the Sips isotherm. Hence, the latter describes more accurately the distribution of binding energies and also the experimental results of melanin binding to drugs and metal ions. Simulations are used to show that the existence of two classes of sites cannot be confirmed on the sole basis of the shape of the binding curve in the Scatchard plot, and that serious doubts may appear on the meaning of the binding parameters of the bi-Langmuir model. Experimental results of melanin binding to chloroquine and metoprolol are used to illustrate the importance of the choice of the binding isotherm and of the method used to evaluate the binding parameters.

  11. Affinity for, and localization of, PEG-functionalized silica nanoparticles to sites of damage in an ex vivo spinal cord injury model

    Chen Bojun

    2012-09-01

    Full Text Available Abstract Background Traumatic spinal cord injury (SCI leads to serious neurological and functional deficits through a chain of pathophysiological events. At the molecular level, progressive damage is initially revealed by collapse of plasma membrane organization and integrity produced by breaches. Consequently, the loss of its role as a semi-permeable barrier that generally mediates the regulation and transport of ions and molecules eventually results in cell death. In previous studies, we have demonstrated the functional recovery of compromised plasma membranes can be induced by the application of the hydrophilic polymer polyethylene glycol (PEG after both spinal and brain trauma in adult rats and guinea pigs. Additionally, efforts have been directed towards a nanoparticle-based PEG application. The in vivo and ex vivo applications of PEG-decorated silica nanoparticles following CNS injury were able to effectively and efficiently enhance resealing of damaged cell membranes. Results The possibility for selectivity of tetramethyl rhodamine-dextran (TMR dye-doped, PEG-functionalized silica nanoparticles (TMR-PSiNPs to damaged spinal cord was evaluated using an ex vivo model of guinea pig SCI. Crushed and nearby undamaged spinal cord tissues exhibited an obvious difference in both the imbibement and accumulation of the TMR-PSiNPs, revealing selective labeling of compression-injured tissues. Conclusions These data show that appropriately functionalized nanoparticles can be an efficient means to both 1. carry drugs, and 2. apply membrane repair agents where they are needed in focally damaged nervous tissue.

  12. Three-Dimensional Protein Fold Determination from Backbone Amide Pseudocontact Shifts Generated by Lanthanide Tags at Multiple Sites

    Yagi, Hiromasa

    2013-06-01

    Site-specific attachment of paramagnetic lanthanide ions to a protein generates pseudocontact shifts (PCS) in the nuclear magnetic resonance (NMR) spectra of the protein that are easily measured as changes in chemical shifts. By labeling the protein with lanthanide tags at four different sites, PCSs are observed for most amide protons and accurate information is obtained about their coordinates in three-dimensional space. The approach is demonstrated with the chaperone ERp29, for which large differences have been reported between X-ray and NMR structures of the C-terminal domain, ERp29-C. The results unambiguously show that the structure of rat ERp29-C in solution is similar to the crystal structure of human ERp29-C. PCSs of backbone amides were the only structural restraints required. Because these can be measured for more dilute protein solutions than other NMR restraints, the approach greatly widens the range of proteins amenable to structural studies in solution. © 2013 Elsevier Ltd. All rights reserved.

  13. Investigation of confined placental mosaicism (CPM) at multiple sites in post-delivery placentas derived through intracytoplasmic sperm injection (ICSI).

    Minor, Agata; Harmer, Karynn; Peters, Nicole; Yuen, Basil Ho; Ma, Sai

    2006-01-01

    Although earlier studies on pregnancies derived through intracytoplasmic sperm injection (ICSI) reported increased non-mosaic aneuploidy among ICSI children, undetected mosaicism, such as confined placental mosaicism (CPM) has not been evaluated. We investigated the incidence of CPM in post-delivery placentas derived from ICSI, evaluated whether CPM was increased and whether it was a contributing factor to negative pregnancy outcome. [Fifty-one post-delivery placentas were collected from patients who underwent ICSI with a normal or negative pregnancy outcome]. Trophoblast and chorionic stroma from three sites were analyzed by comparative genomic hybridization (CGH) and flow cytometry. Detected abnormalities were confirmed by fluorescence in situ hybridization (FISH). The incidence of CPM in the ICSI population was compared to the general population from published data. We detected three cases of CPM in our study. One abnormality was found by CGH analysis; partial trisomy 7q and a partial monosomy Xp limited to the trophoblast at two sites. The abnormality was associated with a child affected by spina bifida. Two cases of mosaic tetraploidy were observed by flow cytometry in pregnancies with a normal outcome. All three abnormalities were confirmed by FISH analysis. The incidence of CPM in the ICSI study population was 5.88% (3/51), which was not statistically different from published reports in the general population (5.88% (42/714), Chi square, P > 0.05). The post-ICSI population was not at risk for CPM in this study. (c) 2005 Wiley-Liss, Inc.

  14. Multi-site assessment of the precision and reproducibility of multiple reaction monitoring–based measurements of proteins in plasma

    Addona, Terri A; Abbatiello, Susan E; Schilling, Birgit; Skates, Steven J; Mani, D R; Bunk, David M; Spiegelman, Clifford H; Zimmerman, Lisa J; Ham, Amy-Joan L; Keshishian, Hasmik; Hall, Steven C; Allen, Simon; Blackman, Ronald K; Borchers, Christoph H; Buck, Charles; Cardasis, Helene L; Cusack, Michael P; Dodder, Nathan G; Gibson, Bradford W; Held, Jason M; Hiltke, Tara; Jackson, Angela; Johansen, Eric B; Kinsinger, Christopher R; Li, Jing; Mesri, Mehdi; Neubert, Thomas A; Niles, Richard K; Pulsipher, Trenton C; Ransohoff, David; Rodriguez, Henry; Rudnick, Paul A; Smith, Derek; Tabb, David L; Tegeler, Tony J; Variyath, Asokan M; Vega-Montoto, Lorenzo J; Wahlander, Åsa; Waldemarson, Sofia; Wang, Mu; Whiteaker, Jeffrey R; Zhao, Lei; Anderson, N Leigh; Fisher, Susan J; Liebler, Daniel C; Paulovich, Amanda G; Regnier, Fred E; Tempst, Paul; Carr, Steven A

    2010-01-01

    Verification of candidate biomarkers relies upon specific, quantitative assays optimized for selective detection of target proteins, and is increasingly viewed as a critical step in the discovery pipeline that bridges unbiased biomarker discovery to preclinical validation. Although individual laboratories have demonstrated that multiple reaction monitoring (MRM) coupled with isotope dilution mass spectrometry can quantify candidate protein biomarkers in plasma, reproducibility and transferability of these assays between laboratories have not been demonstrated. We describe a multilaboratory study to assess reproducibility, recovery, linear dynamic range and limits of detection and quantification of multiplexed, MRM-based assays, conducted by NCI-CPTAC. Using common materials and standardized protocols, we demonstrate that these assays can be highly reproducible within and across laboratories and instrument platforms, and are sensitive to low µg/ml protein concentrations in unfractionated plasma. We provide data and benchmarks against which individual laboratories can compare their performance and evaluate new technologies for biomarker verification in plasma. PMID:19561596

  15. Quantitative detection of multiple fluorophore sites as a tool for diagnosis and monitoring disease progression in salivary glands

    Gannot, Israel; Bonner, Robert F.; Gannot, Gallya; Fox, Philip C.; You, Joon S.; Waynant, Ronald W.; Gandjbakhche, Amir H.

    1997-08-01

    A series of fluorescent surface images were obtained from physical models of localized fluorophores embedded at various depths and separations in tissue phantoms. Our random walk theory was applied to create an analytical model of multiple flurophores embedded in tissue-like phantom. Using this model, from acquired set of surface images, the location of the fluorophores was reconstructed and compared it to their known 3-D distributions. A good correlation was found, and the ability to resolve fluorophores as a function of depth and separation was determined. In parallel in in-vitro study, specific coloring of sections of minor salivary glands was also demonstrated. These results demonstrate the possibility of using inverse methods to reconstruct unknown locations and concentrations of optical probes specifically bound to infiltrating lymphocytes in minor salivary glands of patients with Sjogren's syndrome.

  16. Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt.

    Bisanz, Jordan E; Enos, Megan K; PrayGod, George; Seney, Shannon; Macklaim, Jean M; Chilton, Stephanie; Willner, Dana; Knight, Rob; Fusch, Christoph; Fusch, Gerhard; Gloor, Gregory B; Burton, Jeremy P; Reid, Gregor

    2015-08-01

    The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Previous Fractures at Multiple Sites Increase the Risk for Subsequent Fractures: The Global Longitudinal Study of Osteoporosis in Women

    Gehlbach, Stephen; Saag, Kenneth G.; Adachi, Jonathan D.; Hooven, Fred H.; Flahive, Julie; Boonen, Steven; Chapurlat, Roland D.; Compston, Juliet E.; Cooper, Cyrus; Díez-Perez, Adolfo; Greenspan, Susan L.; LaCroix, Andrea Z.; Netelenbos, J. Coen; Pfeilschifter, Johannes; Rossini, Maurizio; Roux, Christian; Sambrook, Philip N.; Silverman, Stuart; Siris, Ethel S.; Watts, Nelson B.; Lindsay, Robert

    2016-01-01

    Previous fractures of the hip, spine, or wrist are well-recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women ≥ 55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow-up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures since age 45. During the first 2 years of follow-up, 3149 women suffered 3683 incident fractures. Compared with women with no prior fractures, women with 1, 2, or ≥ 3 prior fractures were 1.8-, 3.0-, and 4.8-fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1-fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio 7.3) and hip (hazard ratio 3.5). Prior rib fractures were associated with a 2.3-fold risk of subsequent vertebral fracture, previous upper leg fracture predicted a 2.2-fold increased risk of hip fracture; women with a history of ankle fracture were at 1.8-fold risk of future fracture of a weight-bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development. PMID:22113888

  18. Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt

    Bisanz, Jordan E.; Enos, Megan K.; PrayGod, George; Seney, Shannon; Macklaim, Jean M.; Chilton, Stephanie; Willner, Dana; Knight, Rob; Fusch, Christoph; Fusch, Gerhard; Gloor, Gregory B.; Burton, Jeremy P.

    2015-01-01

    The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study. PMID:25979893

  19. A site study of the multiple effects of thermal releases on the aquatic life in an estuarine area

    Borgese, D.; Dinelli, G.; Guzzi, L.; Smedile, E.

    1975-01-01

    The estuarine area of a river represents a typical site where different factors have to be considered when trying to assess the actual impact on the aquatic life of industrial thermal releases. These factors may be physical (river flow, sea currents, tides, residence time of waters in marshes and lagoons), biological (bio-mass production, mutual organic matter exchange between fresh and sea waters) and economic such as the commercial importance of fishing. In this respect the siting of a large power station in the Po river delta may cause serious problems for the conservation of the existing ecosystem. Thus a multidisciplinary approach with a view to predicting the final thermal impact of a power station on the environment seems fully justified despite its complexity. Therefore a detailed research programme has been established in order to study the following main points: (a) structure of the plant and animal populations; (b) primary production and bacterial activity; (c) physical and chemical characteristics of estuarine waters; (d) coastal characterization; (e) thermal effects on the biocenosis entering the condenser of existing plants operating under similar conditions. Together with conventional experimental techniques, airborne infra-red (IR) and multi-spectra (MS) surveys are planned as, according to preliminary investigations, they provide essential information for the recognition of water flow patterns and aquatic plant growth. The behaviour of the particular ecosystem will be simulated using mathematical models defined on a system theory approach, where the descriptive functions and rate constants come from experimental studies conducted in situ and with laboratory tests. In fact results of preliminary airborne scanning IR and MS surveys combined with biological studies confirm the need for systematic research on the Po river delta. (author)

  20. High-definition fiber tracking for assessment of neurological deficit in a case of traumatic brain injury: finding, visualizing, and interpreting small sites of damage.

    Shin, Samuel S; Verstynen, Timothy; Pathak, Sudhir; Jarbo, Kevin; Hricik, Allison J; Maserati, Megan; Beers, Sue R; Puccio, Ava M; Boada, Fernando E; Okonkwo, David O; Schneider, Walter

    2012-05-01

    For patients with traumatic brain injury (TBI), current clinical imaging methods generally do not provide highly detailed information about the location of axonal injury, severity of injury, or expected recovery. In a case of severe TBI, the authors applied a novel high-definition fiber tracking (HDFT) to directly visualize and quantify the degree of axonal fiber damage and predict functional deficits due to traumatic axonal injury and loss of cortical projections. This 32-year-old man sustained a severe TBI. Computed tomography and MRI revealed an area of hemorrhage in the basal ganglia with mass effect, but no specific information on the location of axonal injury could be obtained from these studies. Examinations of the patient at Week 3 and Week 8 after TBI revealed motor weaknesses of the left extremities. Four months postinjury, 257-direction diffusion spectrum imaging and HDFT analysis was performed to evaluate the degree of axonal damage in the motor pathway and quantify asymmetries in the left and right axonal pathways. High-definition fiber tracking was used to follow corticospinal and corona radiata pathways from the cortical surface to the midbrain and quantify projections from motor areas. Axonal damage was then localized by assessing the number of descending fibers at the level of the cortex, internal capsule, and midbrain. The motor deficit apparent in the clinical examinations correlated with the axonal losses visualized using HDFT. Fiber loss estimates at 4 months postinjury accurately predicted the nature of the motor deficits (severe, focal left-hand weakness) when other standard clinical imaging modalities did not. A repeat scan at 10 months postinjury, when edema and hemorrhage had receded, replicated the fiber loss. Using HDFT, the authors accurately identified the presence and location of damage to the underlying white matter in this patient with TBI. Detailed information of injury provided by this novel technique holds future potential for

  1. Inhibitors of acid secretion can benefit gastric wound repair independent of luminal pH effects on the site of damage

    Demitrack, Elise S; Aihara, Eitaro; Kenny, Susan; Varro, Andrea; Montrose, Marshall H

    2012-01-01

    Background and aims The authors’ goal was to measure pH at the gastric surface (pHo) to understand how acid secretion affects the repair of microscopic injury to the gastric epithelium. Methods Microscopic gastric damage was induced by laser light, during confocal/two-photon imaging of pH-sensitive dyes (Cl-NERF, BCECF) that were superfused over the mucosal surface of the exposed gastric corpus of anaesthetised mice. The progression of repair was measured in parallel with pHo. Experimental conditions included varying pH of luminal superfusates, and using omeprazole (60 mg/kg ip) or famotidine (30 mg/kg ip) to inhibit acid secretion. Results Similar rates of epithelial repair and resting pHo values (~pH 4) were reported in the presence of luminal pH 3 or pH 5. Epithelial repair was unreliable at luminal pH 2 and pHo was lower (2.5±0.2, P pH 3). Epithelial repair was slower at luminal pH 7 and pHo was higher (6.4±0.1, PpH 3 or pH 7, omeprazole reduced maximal damage size and accelerated epithelial repair, although only at pH 3 did omeprazole further increase surface pH above the level caused by imposed damage. At luminal pH 7, famotidine also reduced maximal damage size and accelerated epithelial repair. Neither famotidine nor omeprazole raised plasma gastrin levels during the time course of the experiments. Conclusions Epithelial repair in vivo is affected by luminal pH variation, but the beneficial effects of acutely blocking acid secretion extend beyond simply raising luminal and/or surface pH. PMID:21997560

  2. Quasichemical theory and the description of associating fluids relative to a reference: Multiple bonding of a single site solute

    Bansal, Artee; Chapman, Walter G.; Asthagiri, D.

    2017-09-01

    We derive an expression for the chemical potential of an associating solute in a solvent relative to the value in a reference fluid using the quasichemical organization of the potential distribution theorem. The fraction of times the solute is not associated with the solvent, the monomer fraction, is expressed in terms of (a) the statistics of occupancy of the solvent around the solute in the reference fluid and (b) the Widom factors that arise because of turning on solute-solvent association. Assuming pair-additivity, we expand the Widom factor into a product of Mayer f-functions and the resulting expression is rearranged to reveal a form of the monomer fraction that is analogous to that used within the statistical associating fluid theory (SAFT). The present formulation avoids all graph-theoretic arguments and provides a fresh, more intuitive, perspective on Wertheim's theory and SAFT. Importantly, multi-body effects are transparently incorporated into the very foundations of the theory. We illustrate the generality of the present approach by considering examples of multiple solvent association to a colloid solute with bonding domains that range from a small patch on the sphere to a Janus particle to a solute whose entire surface is available for association.

  3. The adipose organ and multiple myeloma: Impact of adipokines on tumor growth and potential sites for therapeutic intervention.

    Allegra, Alessandro; Innao, Vanessa; Gerace, Demetrio; Allegra, Andrea Gaetano; Vaddinelli, Doriana; Bianco, Oriana; Musolino, Caterina

    2018-07-01

    In addition to its capacity to store lipids the adipose tissue is now identified as a real organ with both endocrine and metabolic roles. Preclinical results indicate that modifying adipose tissue and bone marrow adipose tissue (BMAT) could be a successful multiple myeloma (MM) therapy. BMAT interrelates with bone marrow cells and other immune cells, and may influence MM disease progression. The BM adipocytes may have a role in MM progression, bone homing, chemoresistance, and relapse, due to local endocrine, paracrine, or metabolic factors. BM adipocytes isolated from MM subjects have been shown to increase myeloma growth in vitro and may preserve cells from chemotherapy-induced apoptosis. By producing free fatty acids and emitting signaling molecules such as growth factors and adipokines, BM adipocytes are both an energy font and an endocrine signaling factory. This review should suggest future research approaches toward developing novel treatments to target MM by targeting BMAT and its products. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  4. Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo

    Grüner, Sabine; Prostredna, Miroslava; Schulte, Valerie

    2003-01-01

    by intravital fluorescence microscopy that platelet adhesion and thrombus growth on the exposed ECM of the injured carotid artery is not significantly altered in alpha2-null mice and even in mice with a Cre/loxP-mediated loss of all beta1 integrins on their platelets. In contrast, inhibition of alphaIIbbeta3...... integrin on platelets in wild-type mice blocked aggregate formation and reduced platelet adhesion by 60.0%. Strikingly, alphaIIbbeta3 inhibition had a comparable effect in alpha2-null mice, demonstrating that other receptors mediate shear-resistant adhesion in the absence of functional alpha2beta1...... and alphaIIbbeta3. These were identified to be alpha5beta1 and/or alpha6beta1 as alphaIIbbeta3 inhibition abrogated platelet adhesion in beta1-null mice. We conclude that shear-resistant platelet adhesion on the injured vessel wall in vivo is a highly integrated process involving multiple integrin...

  5. Hispanic health disparities after a flood disaster: results of a population-based survey of individuals experiencing home site damage in El Paso (Texas, USA).

    Collins, Timothy W; Jimenez, Anthony M; Grineski, Sara E

    2013-04-01

    In 2006, El Paso County, a predominantly Hispanic urban area, was affected by a flood disaster; 1,500 homes were damaged. We assessed the health impacts of the disaster upon 475 individuals whose homes were flood-damaged using mail survey data and logistic regression. Substantial proportions of individuals had one or more physical (43 %) or mental (18 %) health problem in the four months following the floods; 28 % had one or more injury or acute effect related to post-flood cleanup. Adverse event experiences, older age, and lower socioeconomic status were significantly associated with negative post-flood health outcomes in all three logistic regression models. A lack of access to healthcare, non-US citizenship, and English proficiency were significant predictors of negative outcomes in both the physical and mental health models, while Hispanic ethnicity (physical), native-birth (mental), and more serious home damage (cleanup) were significant predictors in one model each. The disaster had disproportionate negative health impacts on those who were more exposed, poorer, older, and with constrained resource-access. While a lack of US citizenship and Hispanic ethnicity were associated with higher risks, being less acculturated (i.e., English-deficient, foreign-born) may have protected against health impacts.

  6. Comparative Genomic Hybridization of Human Malignant Gliomas Reveals Multiple Amplification Sites and Nonrandom Chromosomal Gains and Losses

    Schròck, Evelin; Thiel, Gundula; Lozanova, Tanka; du Manoir, Stanislas; Meffert, Marie-Christine; Jauch, Anna; Speicher, Michael R.; Nürnberg, Peter; Vogel, Siegfried; Janisch, Werner; Donis-Keller, Helen; Ried, Thomas; Witkowski, Regine; Cremer, Thomas

    1994-01-01

    Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue ImagesFigure 1Figure 4Figure 6 PMID:8203461

  7. Crystal structure of Bombyx mori arylphorins reveals a 3:3 heterohexamer with multiple papain cleavage sites

    Hou, Yong; Li, Jianwei; Li, Yi; Dong, Zhaoming; Xia, Qingyou; Yuan, Y Adam

    2014-01-01

    In holometabolous insects, the accumulation and utilization of storage proteins (SPs), including arylphorins and methionine-rich proteins, are critical for the insect metamorphosis. SPs function as amino acids reserves, which are synthesized in fat body, secreted into the larval hemolymph and taken up by fat body shortly before pupation. However, the detailed molecular mechanisms of digestion and utilization of SPs during development are largely unknown. Here, we report the crystal structure of Bombyx mori arylphorins at 2.8 Å, which displays a heterohexameric structural arrangement formed by trimerization of dimers comprising two structural similar arylphorins. Our limited proteolysis assay and microarray data strongly suggest that papain-like proteases are the major players for B. mori arylphorins digestion in vitro and in vivo. Consistent with the biochemical data, dozens of papain cleavage sites are mapped on the surface of the heterohexameric structure of B. mori arylphorins. Hence, our results provide the insightful information to understand the metamorphosis of holometabolous insects at molecular level. PMID:24639361

  8. Significant geographic gradients in particulate sulfate over Japan determined from multiple-site measurements and a chemical transport model: Impacts of transboundary pollution from the Asian continent

    Aikawa, Masahide; Ohara, Toshimasa; Hiraki, Takatoshi; Oishi, Okihiro; Tsuji, Akihiro; Yamagami, Makiko; Murano, Kentaro; Mukai, Hitoshi

    2010-01-01

    We found a significant geographic gradient (longitudinal and latitudinal) in the sulfate (SO 42-) concentrations measured at multiple sites over the East Asian Pacific Rim region. Furthermore, the observed gradient was well reproduced by a regional chemical transport model. The observed and modeled SO 42- concentrations were higher at the sites closer to the Asian continent. The concentrations of SO 42- from China as calculated by the model also showed the fundamental features of the longitudinal/latitudinal gradient. The proportional contribution of Chinese SO 42- to the total in Japan throughout the year was above 50-70% in the control case, using data for Chinese sulfur dioxide (SO 2) emission from the Regional Emission Inventory in Asia (40-60% in the low Chinese emissions case, using Chinese SO 2 emissions data from the State Environmental Protection Administration of China), with a winter maximum of approximately 65-80%, although the actual concentrations of SO 42- from China were highest in summer. The multiple-site measurements and the model analysis strongly suggest that the SO 42- concentrations in Japan were influenced by the outflow from the Asian continent, and this influence was greatest in the areas closer to the Asian continent. In contrast, we found no longitudinal/latitudinal gradient in SO 2 concentrations; instead SO 2 concentrations were significantly correlated with local SO 2 emissions. Our results show that large amounts of particulate sulfate are transported over long distances from the East Asian Pacific Rim region, and consequently the SO 42- concentrations in Japan are controlled by the transboundary outflow from the Asian continent.

  9. Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio.

    Hagiwara, A; Hori, M; Yokoyama, K; Nakazawa, M; Ueda, R; Horita, M; Andica, C; Abe, O; Aoki, S

    2017-10-01

    Myelin and axon volume fractions can now be estimated via MR imaging in vivo, as can the g-ratio, which equals the ratio of the inner to the outer diameter of a nerve fiber. The purpose of this study was to evaluate WM damage in patients with MS via this novel MR imaging technique. Twenty patients with relapsing-remitting MS with a combined total of 149 chronic plaques were analyzed. Myelin volume fraction was calculated based on simultaneous tissue relaxometry. Intracellular and CSF compartment volume fractions were quantified via neurite orientation dispersion and density imaging. Axon volume fraction and g-ratio were calculated by combining these measurements. Myelin and axon volume fractions and g-ratio were measured in plaques, periplaque WM, and normal-appearing WM. All metrics differed significantly across the 3 groups ( P ratio between periplaque WM and normal-appearing WM). Those in plaques differed most from those in normal-appearing WM. The percentage changes in plaque and periplaque WM metrics relative to normal-appearing WM were significantly larger in absolute value for myelin volume fraction than for axon volume fraction and g-ratio ( P ratio may potentially be useful for evaluating WM damage in patients with MS. © 2017 by American Journal of Neuroradiology.

  10. Rational design of a conformation-switchable Ca2+- and Tb3+-binding protein without the use of multiple coupled metal-binding sites.

    Li, Shunyi; Yang, Wei; Maniccia, Anna W; Barrow, Doyle; Tjong, Harianto; Zhou, Huan-Xiang; Yang, Jenny J

    2008-10-01

    Ca2+, as a messenger of signal transduction, regulates numerous target molecules via Ca2+-induced conformational changes. Investigation into the determinants for Ca2+-induced conformational change is often impeded by cooperativity between multiple metal-binding sites or protein oligomerization in naturally occurring proteins. To dissect the relative contributions of key determinants for Ca2+-dependent conformational changes, we report the design of a single-site Ca2+-binding protein (CD2.trigger) created by altering charged residues at an electrostatically sensitive location on the surface of the host protein rat Cluster of Differentiation 2 (CD2).CD2.trigger binds to Tb3+ and Ca2+ with dissociation constants of 0.3 +/- 0.1 and 90 +/- 25 microM, respectively. This protein is largely unfolded in the absence of metal ions at physiological pH, but Tb3+ or Ca2+ binding results in folding of the native-like conformation. Neutralization of the charged coordination residues, either by mutation or protonation, similarly induces folding of the protein. The control of a major conformational change by a single Ca2+ ion, achieved on a protein designed without reliance on sequence similarity to known Ca2+-dependent proteins and coupled metal-binding sites, represents an important step in the design of trigger proteins.

  11. Floating Chip Mounting System Driven by Repulsive Force of Permanent Magnets for Multiple On-Site SPR Immunoassay Measurements

    Horiuchi, Tsutomu; Tobita, Tatsuya; Miura, Toru; Iwasaki, Yuzuru; Seyama, Michiko; Inoue, Suzuyo; Takahashi, Jun-ichi; Haga, Tsuneyuki; Tamechika, Emi

    2012-01-01

    We have developed a measurement chip installation/removal mechanism for a surface plasmon resonance (SPR) immunoassay analysis instrument designed for frequent testing, which requires a rapid and easy technique for changing chips. The key components of the mechanism are refractive index matching gel coated on the rear of the SPR chip and a float that presses the chip down. The refractive index matching gel made it possible to optically couple the chip and the prism of the SPR instrument easily via elastic deformation with no air bubbles. The float has an autonomous attitude control function that keeps the chip parallel in relation to the SPR instrument by employing the repulsive force of permanent magnets between the float and a float guide located in the SPR instrument. This function is realized by balancing the upward elastic force of the gel and the downward force of the float, which experiences a leveling force from the float guide. This system makes it possible to start an SPR measurement immediately after chip installation and to remove the chip immediately after the measurement with a simple and easy method that does not require any fine adjustment. Our sensor chip, which we installed using this mounting system, successfully performed an immunoassay measurement on a model antigen (spiked human-IgG) in a model real sample (non-homogenized milk) that included many kinds of interfering foreign substances without any sample pre-treatment. The ease of the chip installation/removal operation and simple measurement procedure are suitable for frequent on-site agricultural, environmental and medical testing. PMID:23202030

  12. Multiple insecticide resistance mechanisms involving metabolic changes and insensitive target sites selected in anopheline vectors of malaria in Sri Lanka

    Karunaratne SHP Parakrama

    2008-08-01

    Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies

  13. Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

    Minglong Shao

    Full Text Available Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.Mice were fed with a high-fat diet (HFD, 40% of calories from fat for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2 expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

  14. Hydraulic characterization of volcanic rocks in Pahute Mesa using an integrated analysis of 16 multiple-well aquifer tests, Nevada National Security Site, 2009–14

    Garcia, C. Amanda; Jackson, Tracie R.; Halford, Keith J.; Sweetkind, Donald S.; Damar, Nancy A.; Fenelon, Joseph M.; Reiner, Steven R.

    2017-01-20

    An improved understanding of groundwater flow and radionuclide migration downgradient from underground nuclear-testing areas at Pahute Mesa, Nevada National Security Site, requires accurate subsurface hydraulic characterization. To improve conceptual models of flow and transport in the complex hydrogeologic system beneath Pahute Mesa, the U.S. Geological Survey characterized bulk hydraulic properties of volcanic rocks using an integrated analysis of 16 multiple-well aquifer tests. Single-well aquifer-test analyses provided transmissivity estimates at pumped wells. Transmissivity estimates ranged from less than 1 to about 100,000 square feet per day in Pahute Mesa and the vicinity. Drawdown from multiple-well aquifer testing was estimated and distinguished from natural fluctuations in more than 200 pumping and observation wells using analytical water-level models. Drawdown was detected at distances greater than 3 miles from pumping wells and propagated across hydrostratigraphic units and major structures, indicating that neither faults nor structural blocks noticeably impede or divert groundwater flow in the study area.Consistent hydraulic properties were estimated by simultaneously interpreting drawdown from the 16 multiple-well aquifer tests with an integrated groundwater-flow model composed of 11 well-site models—1 for each aquifer test site. Hydraulic properties were distributed across volcanic rocks with the Phase II Pahute Mesa-Oasis Valley Hydrostratigraphic Framework Model. Estimated hydraulic-conductivity distributions spanned more than two orders of magnitude in hydrostratigraphic units. Overlapping hydraulic conductivity ranges among units indicated that most Phase II Hydrostratigraphic Framework Model units were not hydraulically distinct. Simulated total transmissivity ranged from 1,600 to 68,000 square feet per day for all pumping wells analyzed. High-transmissivity zones exceeding 10,000 square feet per day exist near caldera margins and extend

  15. Analysis of high resolution scatter images from laser damage experiments performed on KDP

    Runkel, M.; Woods, B.; Yan, M.

    1996-01-01

    Interest in producing high damage threshold KH 2 PO 4 (KDP) and (D x H 1-x ) 2 PO 4 (KD*P, DKDP) for optical switching and frequency conversion applications is being driven by the system requirements for the National Ignition Facility (NIF) at Lawrence Livermore National Lab (LLNL). Historically, the path to achieving higher damage thresholds has been to improve the purity of crystal growth solutions. Application of advanced filtration technology has increased the damage threshold, but gives little insight into the actual mechanisms of laser damage. We have developed a laser scatter diagnostic to better study bulk defects and laser damage mechanisms in KDP and KD*P crystals. This diagnostic consists of a cavity doubled, kilohertz class, Nd:YLF laser (527 nm) and high dynamic range CCD camera which allows imaging of bulk scatter signals. With it, we have performed damage tests at 355 nm on four different open-quotes vintagesclose quotes of KDP crystals, concentrating on crystals produced via fast growth methods. We compare the diagnostic's resolution to LLNL's standard damage detection method of 100X darkfield microscopy and discuss its impact on damage threshold determination. We have observed the disappearance of scatter sites upon exposure to subthreshold irradiation. In contrast, we have seen scatterers appear where none previously existed. This includes isolated, large (high signal) sites as well as multiple small scatter sites which appear at fluences above 7 J/cm 2 (fine tracking). However, we have not observed a strong correlation of preexisting scatter sites and laser damage sites. We speculate on the connection between the laser-induced disappearance of scatter sites and the observed increase in damage threshold with laser conditioning

  16. A novel system for simultaneous or sequential integration of multiple gene-loading vectors into a defined site of a human artificial chromosome.

    Suzuki, Teruhiko; Kazuki, Yasuhiro; Oshimura, Mitsuo; Hara, Takahiko

    2014-01-01

    Human artificial chromosomes (HACs) are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV) into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system) via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming.

  17. A novel system for simultaneous or sequential integration of multiple gene-loading vectors into a defined site of a human artificial chromosome.

    Teruhiko Suzuki

    Full Text Available Human artificial chromosomes (HACs are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming.

  18. Development of multiple strain competitive index assays for Listeria monocytogenes using pIMC; a new site-specific integrative vector

    Cronin Michael

    2008-06-01

    Full Text Available Abstract Background The foodborne, gram-positive pathogen, Listeria monocytogenes, is capable of causing lethal infections in compromised individuals. In the post genomic era of L. monocytogenes research, techniques are required to identify and validate genes involved in the pathogenicity and environmental biology of the organism. The aim here was to develop a widely applicable method to tag L. monocytogenes strains, with a particular emphasis on the development of multiple strain competitive index assays. Results We have constructed a new site-specific integrative vector, pIMC, based on pPL2, for the selection of L. monocytogenes from complex samples. The pIMC vector was further modified through the incorporation of IPTG inducible markers (antibiotic and phenotypic to produce a suite of four vectors which allowed the discrimination of multiple strains from a single sample. We were able to perform murine infection studies with up to four EGDe isolates within a single mouse and showed that the tags did not impact upon growth rate or virulence. The system also allowed the identification of subtle differences in virulence between strains of L. monocytogenes commonly used in laboratory studies. Conclusion This study has developed a competitive index assay that can be broadly applied to all L. monocytogenes strains. Improved statistical robustness of the data was observed, resulting in fewer mice being required for virulence assays. The competitive index assays provide a powerful method to analyse the virulence or fitness of L. monocytogenes in complex biological samples.

  19. The C-terminal region of Rad52 is essential for Rad52 nuclear and nucleolar localization, and accumulation at DNA damage sites immediately after irradiation

    Koike, Manabu, E-mail: m_koike@nirs.go.jp [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Yutoku, Yasutomo [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Koike, Aki [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2013-05-31

    Highlights: •Rad52 might play a key role in the repair of DSB immediately after irradiation. •EYFP-Rad52 accumulates rapidly at DSB sites and colocalizes with Ku80. •Accumulation of Rad52 at DSB sites is independent of the core NHEJ factors. •Localization and recruitment of Rad52 to DSB sites are dependent on the Rad52 CTR. •Basic amino acids in Rad52 CTR are highly conserved among vertebrate species. -- Abstract: Rad52 plays essential roles in homologous recombination (HR) and repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae. However, in vertebrates, knockouts of the Rad52 gene show no hypersensitivity to agents that induce DSBs. Rad52 localizes in the nucleus and forms foci at a late stage following irradiation. Ku70 and Ku80, which play an essential role in nonhomologous DNA-end-joining (NHEJ), are essential for the accumulation of other core NHEJ factors, e.g., XRCC4, and a HR-related factor, e.g., BRCA1. Here, we show that the subcellular localization of EYFP-Rad52(1–418) changes dynamically during the cell cycle. In addition, EYFP-Rad52(1–418) accumulates rapidly at microirradiated sites and colocalizes with the DSB sensor protein Ku80. Moreover, the accumulation of EYFP-Rad52(1–418) at DSB sites is independent of the core NHEJ factors, i.e., Ku80 and XRCC4. Furthermore, we observed that EYFP-Rad52(1–418) localizes in nucleoli in CHO-K1 cells and XRCC4-deficient cells, but not in Ku80-deficient cells. We also found that Rad52 nuclear localization, nucleolar localization, and accumulation at DSB sites are dependent on eight amino acids (411–418) at the end of the C-terminal region of Rad52 (Rad52 CTR). Furthermore, basic amino acids on Rad52 CTR are highly conserved among mammalian, avian, and fish homologues, suggesting that Rad52 CTR is important for the regulation and function of Rad52 in vertebrates. These findings also suggest that the mechanism underlying the regulation of subcellular localization of Rad52 is

  20. Site Area Boundaries

    U.S. Environmental Protection Agency — This dataset consists of site boundaries from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different times and...

  1. 3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

    Cui, P.X.; Lian, F.L.; Wang, Y.; Wen, Yi; Chu, W.S.; Zhao, H.F.; Zhang, S.; Li, J.; Lin, D.H.; Wu, Z.Y.

    2014-01-01

    Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrP C ) to the post-translationally modified form (PrP Sc ) is thought to be relevant to Cu 2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrP C ) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases. - Highlights: ► The first structure of the metal ion binding site in RaPrP fifth copper-binding site. ► Quantitative determination by XANES spectroscopy combined with ab initio calculations. ► Provide a proof of the roles of copper in prion conformation conversions. ► Provide a proof of the molecular mechanisms of prion-involved diseases

  2. The dependence of natural regeneration of forest trees on upper soil conditions and acidity at damaged sites in the Black Forest, Germany

    Littek, T.

    1993-06-01

    It was the goal of this study to investigate the influence of different upper soil conditions on the germination and establishment, as well as the growth, of young plants of various tree species. For this purpose, four test plots in the region of the Black Forest were laid out, in which, by various means of site preparation and fertilization, the upper soils were changed. Natural seeding of common spruce, European silver-fir, beech, sycamore maple, European mountainash, and grey alder was simulated by means of controlled sowing. For comparison, a greenhouse experiment was carried out, examining the germination and development of the same tree species in various soil substrata, using different fertilizers, and under the influence of artificial acid rain. The most important results - with a high level of variation depending on the tree species examined - can be summarized as follows: Based on the results of field and greenhouse experiments, as well as on the investigations of other authors, it can be concluded that natural regeneration of forest stands is considerably impeded under conditions of increasing soil acidity and by high acid depositions. This is seen directly as the result of unfavorable chemical conditions in the upper soil, as well as indirectly due to deteriorating competitiveness against other vegetation. Site preparation and lime or dolomite fertilization can be important measures in the practice of forestry, to encourage natural regeneration in highly acidic sites with an unfavourable humus layer and a high presence of competing vegetation. (orig./UWA). 2 figs., 85 tabs., 269 refs [de

  3. After facial nerve damage, regenerating axons become aberrant throughout the length of the nerve and not only at the site of the lesion: an experimental study.

    Choi, D; Raisman, G

    2004-02-01

    After facial nerve trauma, aberrant regeneration is associated with synkinesis. Animal models of mechanical nerve guides or reparative cell transplants at the site of a lesion have not been shown to improve disorganized regeneration. We examined whether this is because regenerating axons become disorganized throughout the length of the nerve and not only at the site of the lesion. In rats (n = 12), retrograde fluorescent tracer techniques were used to establish that most of the temporal branch fibres were carried in the superior half of the facial nerve trunk. In two further groups of rats (n = 24) a complete proximal facial nerve lesion was made, and the nerve immediately repaired by suture. After 4 weeks, at a second operation, the superior half of the facial nerve trunk was cut, either proximal or distal to the original lesion, and retrograde tracers were applied to distal branches of the nerve. It was possible to localize the points at which regenerating fibres became aberrant in their course by studying the number of labelled motoneurons in the facial nucleus after application of the tracer to the temporal branch of the nerve: this was similar in the distal and proximal hemisection groups, suggesting that aberrant axonal development occurred throughout the length of the nerve. Future strategies aimed at improving the organization of regeneration need to provide guidance cues not only at the site of the lesion as previously thought, but also throughout the length of the nerve.

  4. MULTIPLE DAMAGE OF THE TIBIAL POLYETHYLENE INSERT IN KNEE JOINT PROSTHESIS (CAN EXCELLENT POSTOPERATIVE OUTCOME BE THE CAUSE OF FRACTURE OF THE TIBIAL INSERT? CASE REPORT AND LITERATURE REVIEW

    E. Song

    2016-01-01

    Full Text Available Despite improvements in prosthesis technology and use of high-quality materials in recent years, the number of revisions related to implant failures (4.7% remains high. Several phenomena were reported in literature as reasons for dislocation and fracture of tibial insert in mobile bearing prosthesis: incorrect positioning of components, discrepancy of extension and flexion balancing or ligament weakness. However, in our cases neither of these causes were observed. The authors consider that bio-physiological and biomechanical aspects of total knee arthroplasty and knee joint prosthesis should be thoroughly studied and implemented into the clinical practice. In the described cases, multiple damage of the insert due to flexion instability and “twist-hyperflexion” in overweight patients is perceived as the reason for failures.

  5. Updated synthesis of knowledge related to the impact of radioactive releases from the damaged nuclear site of Fukushima Dai-Ichi on the marine environment - 13 July 2012

    2012-01-01

    Illustrated by tables, figures and graphs, this report first comments the evolution of the radioactive pollution of sea water: main radionuclides notices in sea water since the 21 March 2011 (with two main origins: atmospheric fallouts, liquid releases from the site), evolution of sea water contamination along the coast at the vicinity of the power station, simulation of caesium 137 dispersion in sea water off Japan. Then, it comments the evolution of the presence of radionuclides in sediments and in marine species (species with contamination level exceeding the admissible level for consumption, concentrations noticed by sea animals, expected evolution for marine species, other published data)

  6. Biologically important radiation damage in DNA

    Ward, J.F.

    1994-01-01

    Most DNA damage by the hydroxyl radical is confined to the bases, and this base damage represents an important component of locally multiply demanded sites (LMOS). The yields of the major damaged bases have been determined by gas chromatography mass spectrometry. For our propose, it was necessary to convert a known fraction of these damaged bases to strand breaks and then assay these labile sites as the increase in strand break yield over the normally observed level. Three potential agents by which this strategy of conversion of base damage to strand break could be implemented were identified in the original application: 1, Sl nuclease; 2, piperidine; and 3, base damage specific enzymes

  7. Modeling laser damage to the retina

    Clark, Clifton D.

    This dissertation presents recent progress in several areas related to modeling laser damage to the retina. In Chapter 3, we consider the consequences of using the Arrhenius damage model to predict the damage thresholds of multiple pulse, or repetitive pulse, exposures. We have identified a few fundamental trends associated with the multiple pulse damage predictions made by the Arrhenius model. These trends differ from what would be expected by non-thermal mechanisms, and could prove useful in differentiating thermal and non-thermal damage. Chapter 4 presents a new rate equation damage model hypothesized to describe photochemical damage. The model adds a temperature dependent term to the simple rate equation implied by the principle of reciprocity that is characteristic of photochemical damage thresholds. A recent damage threshold study, conducted in-vitro, has revealed a very sharp transition between thermal and photochemical damage threshold trends. For the wavelength used in the experiment (413 nm), thermal damage thresholds were observed at exposure levels that were twice the expected photochemical damage threshold, based on the traditional understanding of photochemical damage. Our model accounts for this observed trend by introducing a temperature dependent quenching, or repair, rate to the photochemical damage rate. For long exposures that give a very small temperature rise, the model reduces to the principle of reciprocity. Near the transition region between thermal and photochemical damage, the model allows the damage threshold to be set by thermal mechanisms, even at exposure above the reciprocity exposure. In Chapter 5, we describe a retina damage model that includes thermal lensing in the eye by coupling beam propagation and heat transfer models together. Thermal lensing has recently been suggested as a contributing factor to the large increase in measured retinal damage thresholds in the near infrared. The transmission of the vitreous decreases

  8. The mutation frequency of 8-oxo-7,8 dihydroguanine (8-oxoG) situated in a multiply damaged site: comparison of a single and two closely opposed 8-oxodG in Escherichia coli

    Malyarchuk, S.G.; Youngblood, R.C.; Landry, A.M.; Quillin, E.; Harrison, L.

    2003-01-01

    Full text: A multiply damaged site (MDS) is defined as >= two lesions within a distance of 10-15 base pairs (bp). MDS generated by ionizing radiation contains oxidative base damage, and in vitro studies have indicated that if the base damage is less than 3 bp apart, repair of one lesion is inhibited until repair of the lesion in the opposite strand is completed. Inhibition of repair could result in an increase in the mutation frequency of the base damage. We have designed an assay to determine whether a closely opposed lesion causes an increase in adenine insertion opposite an 8-oxodG in bacteria. The double-stranded oligonucleotides (with no damage, each single 8-oxodG or the MDS) were ligated into the firefly luciferase coding region of a reporter vector and transformed into wild type or MutY-deficient bacteria. The MDS contained an 8-oxodG in the transcribed strand (T) and a second 8-oxodG immediately 5' to this lesion in the non-transcribed strand (NT). During two rounds of replication, insertion of adenine opposite the 8-oxodG in the T or NT strand results in a translation termination codon at position 444 or 445, respectively. In wild-type bacteria, we detected a translation stop at a frequency of 0.15% (codon 444) and 0.09% (codon 445) with a single 8-oxodG in the T or NT strand, respectively. This was enhanced ∼3 fold when single lesions were replicated in MutY-deficient bacteria. Positioning an 8-oxodG in the T strand within the MDS enhanced the mutation frequency by ∼2 fold in wild-type bacteria and 8 fold in Mut Y-deficient bacteria, while the mutation frequency of the 8-oxodG in the NT strand increased by 6 fold in Mut Y-deficient bacteria. This enhancement of mutation frequency supports the in vitro MDS studies, which demonstrated the inability of base excision repair to completely repair closely opposed lesions

  9. Assessment of DNA Damage in Peripheral Blood Lymphocytes of Radiation Workers at Al-Tuwaitha Site by Using the Sister Chromatid Exchange and the Comet Assay

    Ali, A.K.; Muttar, A.J.; Khayon, S.K.; Haider, Y.L.; Ali, H.F.; Abdullah, A.K.

    2015-01-01

    The sister chromatid exchange was performed on peripheral blood lymphocytes obtained from 40 individuals of workers occupationally exposed to low ionizing radiation doses in Al-Tuwaitha site due to decommissioning to radioactive contamination then compared with 40 control individuals living in Baghdad. SCEs were scored in metaphase chromosomes were identified by fluorescent plus Giemsa staining (Figure 2).The mean frequencies of SCEs per cell differed significantly (p≺0 0.05) between individuals of radiation workers and control, being 7.78 0.45 SCE/cells and 6.28 0.22 SCE/cells , respectively. However SCE frequency was statistically significant (P≺0 0.05) among radiation workers as compared to control individuals.

  10. Use of molecular cytogenetic analysis as bio marker in assessment of DNA damage in radiation workers at Al-Twuathia site Iraq

    Abdulsahib, K. A.; Amel, J. M.; Abdullah, A.K.; Haider, Y.L.; Ali, H.F.; Khawla, A.B.

    2012-12-01

    The present study aims to use the biological techniques in a genotoxicity assessment of low doses of radiation in samples of workers in Al-Tuwatha site due to decommissioning to radioactive contamination as a result of work. Used three molecular genetic techniques as included micronuclei in cytoplasm of reticulocytes cells, buccal micronuclei cymate assay and alkaline comet assay. this study including 50 blood samples, aged (35 - 63) as well as 50 blood samples which are not smokers and alcohol as control group which including (35 and 15) aged (25 - 57 year) for the test of micronuclei in cytoplasm of reticulocytes. While the comet assay and buccal micronuclei cymate assay which including blood and cheek swab samples from 25 aged (30 - 56), as well as 25 blood and cheek swab samples which are not smokers and alcohol as control group which including (15 and 10) aged (25 - 57 year). The frequencies of micronuclei in cytoplasm of reticulocytes observed for the radiation workers at Tl-Tuwaith site were significantly (P<0.05) higher than in the control group. Similarly, the comet parameter were statistically higher (P<0.05) in the radiation workers group in comparison with the control group. Also, the results obtained showed statistically significant differences (P-<0.05 between comet tail length and tail moment values measured in radiation worker and control groups. In the case of buccal micronuclei assay, no significant (P<0.05) differences between both group was found. In conclusion, the results indicated that there is a possibility of using the changes in the levels of micronuclei in cytoplasm of reticulocytes, and comet assay useful as results obtained confirmed usefulness of the alkaline comet assay as a sensitive additional bio marker in the regular health screening of workers occupationally exposed to low doses of ionizing radiation.(Author)

  11. Mental stress and psychosocial factors at work in relation to multiple-site musculoskeletal pain: a longitudinal study of kitchen workers.

    Haukka, Eija; Leino-Arjas, Päivi; Ojajärvi, Anneli; Takala, Esa-Pekka; Viikari-Juntura, Eira; Riihimäki, Hilkka

    2011-04-01

    Among 385 female kitchen workers, we examined (1) whether mental stress and psychosocial factors at work (job control, skill discretion, supervisor support, co-worker relationships, and hurry) predict multiple-site musculoskeletal pain (MSP; defined as pain at ≥ 3 of seven sites) and (2) reversedly, whether MSP predicts these psychosocial factors. Data were collected by questionnaire at 3-month intervals during 2 years. Trajectory analysis was applied. Four trajectories of MSP prevalence emerged: Low, Descending, Ascending, and High. For the psychosocial factors, a two-trajectory model (Ascending or High vs. Low) yielded the best fit. In logistic regression analysis, with the Low MSP trajectory as reference, poor co-worker relationships (odds ratio [OR] 3.9), mental stress (3.1) and hurry (2.1) at baseline predicted belonging to the High MSP trajectory. Also MSP at baseline predicted the trajectories (Ascending vs. Low) of low job control (2.2) and mental stress (3.2). Adverse changes in most psychosocial factors were associated with belonging to the High (ORs between 2.3 and 8.6) and Ascending (2.7-5.5) MSP trajectories. In generalized estimating equations, time-lagged by 3 months, all psychosocial factors but two predicted MSP (1.4-2.1), allowing, e.g. for MSP at baseline, and vice versa, MSP predicted low job control, low supervisor support, and mental stress (1.4-2.0), after adjustment for e.g. the relevant psychosocial factor at baseline. In conclusion, we found that several psychosocial factors predicted MSP and that MSP predicted several psychosocial factors. The results suggest a cumulative process in which adverse psychosocial factors and MSP influence each other. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  12. MULTIPLE OBJECTS

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

  13. Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape

    Wang, Lingshu; Shi, Wei; Chappell, James D.; Joyce, M. Gordon; Zhang, Yi; Kanekiyo, Masaru; Becker, Michelle M.; van Doremalen, Neeltje; Fischer, Robert; Wang, Nianshuang; Corbett, Kizzmekia S.; Choe, Misook; Mason, Rosemarie D.; Van Galen, Joseph G.; Zhou, Tongqing; Saunders, Kevin O.; Tatti, Kathleen M.; Haynes, Lia M.; Kwong, Peter D.; Modjarrad, Kayvon; Kong, Wing-Pui; McLellan, Jason S.; Denison, Mark R.; Munster, Vincent J.; Mascola, John R.; Graham, Barney S.; Gallagher, Tom

    2018-03-07

    ABSTRACT

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ~35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell cloning strategy, we have identified and characterized multiple neutralizing monoclonal antibodies (MAbs) specifically binding to the receptor-binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific MAbs tended to have greater neutralizing potency than non-RBD S1-specific MAbs. Six RBD-specific and five S1-specific MAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined cocrystal structures for two MAbs targeting the RBD from different angles and show they can bind the RBD only in the “out” position. We then showed that selected RBD-specific, non-RBD S1-specific, and S2-specific MAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD MAbs delayed the emergence of escape mutations in a cell-based virus escape assay. These studies identify MAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization and for developing more effective interventions to prevent or treat MERS-CoV infections.

    IMPORTANCEMERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using

  14. Estimated airborne release of radionuclides from the Battelle Memorial Institute Columbus Laboratories JN-1b building at the West Jefferson site as a result of postulated damage from severe wind and earthquake hazard

    Mishima, J.; Ayer, J.E.

    1981-11-01

    The potential airborne releases of radionuclides (source terms) that could result from wind and earthquake dmage are estimated for the Battelle Memorial Institute Columbus Laboratories JN-1b Building at the West Jefferson site in Ohio. The estimated source terms are based on the damage to barriers containing the radionuclides, the inventory of radionuclides at risk, and the fraction of the inventory made airborne as a result of the loss of containment. In an attempt to provide a realistic range of potential source terms that include most of the normal operating conditions, a best estimate bounded by upper and lower limits is calculated by combining the upper-bound, best-estimate, and lower-bound inventories-at-risk with an airborne release factor (upper-bound, best-estimate, and lower-bound if possible) for the situation. The factors used to evaluate the fractional airborne release of materials and the exchange rates between enclosed and exterior atmospheres are discussed. The postulated damage and source terms are discussed for wind and earthquake hazard scenarios in order of their increasing severity

  15. 3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

    Cui, P. X.; Lian, F. L.; Wang, Y.; Wen, Yi; Chu, W. S.; Zhao, H. F.; Zhang, S.; Li, J.; Lin, D. H.; Wu, Z. Y.

    2014-02-01

    Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrPC) to the post-translationally modified form (PrPSc) is thought to be relevant to Cu2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases.

  16. Targeted Quantitation of Site-Specific Cysteine Oxidation in Endogenous Proteins Using a Differential Alkylation and Multiple Reaction Monitoring Mass Spectrometry Approach

    Held, Jason M.; Danielson, Steven R.; Behring, Jessica B.; Atsriku, Christian; Britton, David J.; Puckett, Rachel L.; Schilling, Birgit; Campisi, Judith; Benz, Christopher C.; Gibson, Bradford W.

    2010-01-01

    Reactive oxygen species (ROS) are both physiological intermediates in cellular signaling and mediators of oxidative stress. The cysteine-specific redox-sensitivity of proteins can shed light on how ROS are regulated and function, but low sensitivity has limited quantification of the redox state of many fundamental cellular regulators in a cellular context. Here we describe a highly sensitive and reproducible oxidation analysis approach (OxMRM) that combines protein purification, differential alkylation with stable isotopes, and multiple reaction monitoring mass spectrometry that can be applied in a targeted manner to virtually any cysteine or protein. Using this approach, we quantified the site-specific cysteine oxidation status of endogenous p53 for the first time and found that Cys182 at the dimerization interface of the DNA binding domain is particularly susceptible to diamide oxidation intracellularly. OxMRM enables analysis of sulfinic and sulfonic acid oxidation levels, which we validate by assessing the oxidation of the catalytic Cys215 of protein tyrosine phosphatase-1B under numerous oxidant conditions. OxMRM also complements unbiased redox proteomics discovery studies as a verification tool through its high sensitivity, accuracy, precision, and throughput. PMID:20233844

  17. Radiation damage

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  18. Single thrombopoietin dose alleviates hematopoietic stem cells intrinsic short- and long-term ionizing radiation damage. In vivo identification of anatomical cell expansion sites.

    Tronik-Le Roux, Diana; Nicola, Marie-Anne; Vaigot, Pierre; Nurden, Paquita

    2015-01-01

    Hematopoietic stem cells (HSC) are essential for maintaining the integrity of complex and long-lived organisms. HSC, which are self-renewing, reconstitute the hematopoietic system through out life and facilitate long-term repopulation of myeloablated recipients. We have previously demonstrated that when mice are exposed to sublethal doses of ionizing radiation, subsets of the stem/progenitor compartment are affected. In this study we examine the role of thrombopoietin (TPO) on the regenerative capacities of HSC after irradiation and report the first demonstration of efficacy of a single injection of TPO shortly after in vivo exposure to ionizing radiation for reducing HSC injury and improving their functional outcome. Our results demonstrate that TPO treatment not only reduced the number of apoptotic cells but also induced a significant modification of their intrinsic characteristics. These findings were supported by transplantation assays with long-term HSC that were irradiated or unirradiated, TPO treated or untreated, in CD45.1/CD45.2 systems and by using luciferase-labeled HSC for direct bioluminescence imaging in living animals. Of particular importance, our data demonstrate the skull to be a highly favorable site for the TPO-induced emergence of hematopoietic cells after irradiation, suggesting a TPO-mediated relationship of primitive hematopoietic cells to an anatomical component. Together, the data presented here: provide novel findings about aspects of TPO action on stem cells, open new areas of investigation for therapeutic options in patients who are treated with radiation therapy, and show that early administration of a clinically suitable TPO-agonist counteracts the previously observed adverse effects.

  19. Tort Damages

    L.T. Visscher (Louis)

    2008-01-01

    textabstractAbstract: In this Chapter, I provide an overview of Law and Economics literature regarding tort damages. Where necessary, attention is also spent to rules of tort liability. Both types of rules provide behavioral incentives to both injurers and victims, with respect to their level of

  20. Boring crustaceans damage polystyrene floats under docks polluting marine waters with microplastic.

    Davidson, Timothy M

    2012-09-01

    Boring isopods damage expanded polystyrene floats under docks and, in the process, expel copious numbers of microplastic particles. This paper describes the impacts of boring isopods in aquaculture facilities and docks, quantifies and discusses the implications of these microplastics, and tests if an alternate foam type prevents boring. Floats from aquaculture facilities and docks were heavily damaged by thousands of isopods and their burrows. Multiple sites in Asia, Australia, Panama, and the USA exhibited evidence of isopod damage. One isopod creates thousands of microplastic particles when excavating a burrow; colonies can expel millions of particles. Microplastics similar in size to these particles may facilitate the spread of non-native species or be ingested by organisms causing physical or toxicological harm. Extruded polystyrene inhibited boring, suggesting this foam may prevent damage in the field. These results reveal boring isopods cause widespread damage to docks and are a novel source of microplastic pollution. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Multiple Perspectives / Multiple Readings

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  2. Growth behavior of laser-induced damage on fused silica optics under UV, ns laser irradiation.

    Negres, Raluca A; Norton, Mary A; Cross, David A; Carr, Christopher W

    2010-09-13

    The growth behavior of laser-induced damage sites is affected by a large number of laser parameters as well as site morphology. Here we investigate the effects of pulse duration on the growth rate of damage sites located on the exit surface of fused silica optics. Results demonstrate a significant dependence of the growth parameters on laser pulse duration at 351 nm from 1 ns to 15 ns, including the observation of a dominant exponential versus linear, multiple-shot growth behavior for long and short pulses, respectively. These salient behaviors are tied to the damage morphology and suggest a shift in the fundamental growth mechanisms for pulses in the 1-5 ns range.

  3. The prevalence of injection-site reactions with disease-modifying therapies and their effect on adherence in patients with multiple sclerosis: an observational study

    Beer Karsten

    2011-11-01

    Full Text Available Abstract Background Interferon beta (IFNβ and glatiramer acetate (GA are administered by subcutaneous (SC or intramuscular (IM injection. Patients with multiple sclerosis (MS often report injection-site reactions (ISRs as a reason for noncompliance or switching therapies. The aim of this study was to compare the proportion of patients on different formulations of IFNβ or GA who experienced ISRs and who switched or discontinued therapy because of ISRs. Methods The Swiss MS Skin Project was an observational multicenter study. Patients with MS or clinically isolated syndrome who were on the same therapy for at least 2 years were enrolled. A skin examination was conducted at the first study visit and 1 year later. Results The 412 patients enrolled were on 1 of 4 disease-modifying therapies for at least 2 years: IM IFNβ-1a (n = 82, SC IFNβ-1b (n = 123, SC IFNβ-1a (n = 184, or SC GA (n = 23. At first evaluation, ISRs were reported by fewer patients on IM IFNβ-1a (13.4% than on SC IFNβ-1b (57.7%; P P P = not significant [NS]. No patient on IM IFNβ-1a missed a dose in the previous 4 weeks because of ISRs, compared with 5.7% of patients on SC IFNβ-1b (P = 0.044, 7.1% of patients on SC IFNβ-1a (P = 0.011, and 4.3% of patients on SC GA (P = NS. Primary reasons for discontinuing or switching therapy were ISRs or lack of efficacy. Similar patterns were observed at 1 year. Conclusions Patients on IM IFNβ-1a had fewer ISRs and were less likely to switch therapies than patients on other therapies. This study may have implications in selecting initial therapy or, for patients considering switching or discontinuing therapy because of ISRs, selecting an alternative option.

  4. A genomic library-based amplification approach (GL-PCR) for the mapping of multiple IS6110 insertion sites and strain differentiation of Mycobacterium tuberculosis.

    Namouchi, Amine; Mardassi, Helmi

    2006-11-01

    Evidence suggests that insertion of the IS6110 element is not without consequence to the biology of Mycobacterium tuberculosis complex strains. Thus, mapping of multiple IS6110 insertion sites in the genome of biomedically relevant clinical isolates would result in a better understanding of the role of this mobile element, particularly with regard to transmission, adaptability and virulence. In the present paper, we describe a versatile strategy, referred to as GL-PCR, that amplifies IS6110-flanking sequences based on the construction of a genomic library. M. tuberculosis chromosomal DNA is fully digested with HincII and then ligated into a plasmid vector between T7 and T3 promoter sequences. The ligation reaction product is transformed into Escherichia coli and selective PCR amplification targeting both 5' and 3' IS6110-flanking sequences are performed on the plasmid library DNA. For this purpose, four separate PCR reactions are performed, each combining an outward primer specific for one IS6110 end with either T7 or T3 primer. Determination of the nucleotide sequence of the PCR products generated from a single ligation reaction allowed mapping of 21 out of the 24 IS6110 copies of two 12 banded M. tuberculosis strains, yielding an overall sensitivity of 87,5%. Furthermore, by simply comparing the migration pattern of GL-PCR-generated products, the strategy proved to be as valuable as IS6110 RFLP for molecular typing of M. tuberculosis complex strains. Importantly, GL-PCR was able to discriminate between strains differing by a single IS6110 band.

  5. A donor splice site mutation in CISD2 generates multiple truncated, non-functional isoforms in Wolfram syndrome type 2 patients.

    Cattaneo, Monica; La Sala, Lucia; Rondinelli, Maurizio; Errichiello, Edoardo; Zuffardi, Orsetta; Puca, Annibale Alessandro; Genovese, Stefano; Ceriello, Antonio

    2017-12-13

    Mutations in the gene that encodes CDGSH iron sulfur domain 2 (CISD2) are causative of Wolfram syndrome type 2 (WFS2), a rare autosomal recessive neurodegenerative disorder mainly characterized by diabetes mellitus, optic atrophy, peptic ulcer bleeding and defective platelet aggregation. Four mutations in the CISD2 gene have been reported. Among these mutations, the homozygous c.103 + 1G > A substitution was identified in the donor splice site of intron 1 in two Italian sisters and was predicted to cause a exon 1 to be skipped. Here, we employed molecular assays to characterize the c.103 + 1G > A mutation using the patient's peripheral blood mononuclear cells (PBMCs). 5'-RACE coupled with RT-PCR were used to analyse the effect of the c.103 + 1G > A mutation on mRNA splicing. Western blot analysis was used to analyse the consequences of the CISD2 mutation on the encoded protein. We demonstrated that the c.103 + 1G > A mutation functionally impaired mRNA splicing, producing multiple splice variants characterized by the whole or partial absence of exon 1, which introduced amino acid changes and a premature stop. The affected mRNAs resulted in either predicted targets for nonsense mRNA decay (NMD) or non-functional isoforms. We concluded that the c.103 + 1G > A mutation resulted in the loss of functional CISD2 protein in the two Italian WFS2 patients.

  6. Experimental Autoimmune Encephalomyelitis (EAE-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1: Implications in Multiple Sclerosis (MS-Induced Neurological Disability and Associated Myelin Damage

    Tina Khorshid Ahmad

    2017-06-01

    Full Text Available Multiple sclerosis (MS is a chronic neurological disease characterized by the destruction of central nervous system (CNS myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2 called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC and active control (AC animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC. The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG. Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC

  7. Experimental Autoimmune Encephalomyelitis (EAE)-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1): Implications in Multiple Sclerosis (MS)-Induced Neurological Disability and Associated Myelin Damage.

    Khorshid Ahmad, Tina; Zhou, Ting; AlTaweel, Khaled; Cortes, Claudia; Lillico, Ryan; Lakowski, Ted Martin; Gozda, Kiana; Namaka, Michael Peter

    2017-06-12

    Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS) over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC) and active control (AC) animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC). The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG). Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC may arise

  8. Fast damage imaging using the time-reversal technique in the frequency–wavenumber domain

    Zhu, R; Huang, G L; Yuan, F G

    2013-01-01

    The time-reversal technique has been successfully used in structural health monitoring (SHM) for quantitative imaging of damage. However, the technique is very time-consuming when it is implemented in the time domain. In this paper, we study the technique in the frequency–wavenumber (f–k) domain for fast real-time imaging of multiple damage sites in plates using scattered flexural plate waves. Based on Mindlin plate theory, the time reversibility of dispersive flexural waves in an isotropic plate is theoretically investigated in the f–k domain. A fast damage imaging technique is developed by using the cross-correlation between the back-propagated scattered wavefield and the incident wavefield in the frequency domain. Numerical simulations demonstrate that the proposed technique cannot only localize multiple damage sites but also potentially identify their sizes. Moreover, the time-reversal technique in the f–k domain is about two orders of magnitude faster than the method in the time domain. Finally, experimental testing of an on-line SHM system with a sparse piezoelectric sensor array is conducted for fast multiple damage identification using the proposed technique. (paper)

  9. Earthquake damage to underground facilities

    Pratt, H.R.; Hustrulid, W.A.; Stephenson, D.E.

    1978-11-01

    The potential seismic risk for an underground nuclear waste repository will be one of the considerations in evaluating its ultimate location. However, the risk to subsurface facilities cannot be judged by applying intensity ratings derived from the surface effects of an earthquake. A literature review and analysis were performed to document the damage and non-damage due to earthquakes to underground facilities. Damage from earthquakes to tunnels, s, and wells and damage (rock bursts) from mining operations were investigated. Damage from documented nuclear events was also included in the study where applicable. There are very few data on damage in the subsurface due to earthquakes. This fact itself attests to the lessened effect of earthquakes in the subsurface because mines exist in areas where strong earthquakes have done extensive surface damage. More damage is reported in shallow tunnels near the surface than in deep mines. In mines and tunnels, large displacements occur primarily along pre-existing faults and fractures or at the surface entrance to these facilities.Data indicate vertical structures such as wells and shafts are less susceptible to damage than surface facilities. More analysis is required before seismic criteria can be formulated for the siting of a nuclear waste repository

  10. New 40Ar/39Ar age of the Bishop Tuff from multiple sites and sediment rate calibration for the Matuyama-Brunhes boundary

    Sarna-Wojcicki, A. M.; Pringle, M.S.; Wijbrans, J.

    2000-01-01

    Precise dating of sanidine from proximal ash flow Bishop Tuff and air fall Bishop pumice and ash, California, can be used to derive an absolute age of the Matuyama Reversed-Brunhes Normal (M-B) paleomagnetic transition, identified stratigraphically close beneath the Bishop Tuff and ash at many sites in the western United States. An average age of 758.9 ?? 1.8 ka, standard error of the mean (SEM), was obtained for individual sanidine crystals or groups of several crystals, determined from ???70 individual analyses of sanidine separates from 11 sample groups obtained at five localities. The basal air fall pumice (757.7 ?? 1.8 ka) and overlying ash flow tuff (762.2 ?? 4.7 ka) from near the source yield essentially the same dates within errors of analysis, suggesting that the two units were emplaced close in time. A date on distal Bishop air fall ash bed at Friant, California, ???100 km to the west of the source area, is younger, 750.1 ?? 4.3 ka, but not significantly different within analytical error (??1 standard deviation). Previous dates of the Bishop Tuff, obtained by others using conventional K-Ar and the fission track method on zircons, ranged from ???650 ka to ???1.0 Ma. The most recent, generally accepted date by the K-Ar method on sanidine was 738 ?? 3 ka. We infer, as others before, that many K-Ar dates on sanidine feldspar are too young owing to incomplete degassing of radiogenic Ar during fusion in the K-Ar technique and that many older K-Ar dates are too old owing to detrital or xenocrystic contamination in the larger samples that are necessary for the technique. The new dates are similar to recent 40Ar/39Ar ages of the Bishop Tuff determined on individual samples by others but are derived from a larger proximal sample population and from multiple analysis of each sample. The results provide a definitive and precise age calibration of this widespread chronostratigraphic marker in the western United States and northeastern Pacific Ocean. We calculated the

  11. Validity of Torque-Data Collection at Multiple Sites: A Framework for Collaboration on Clinical-Outcomes Research in Sports Medicine.

    Kuenze, Christopher; Eltouhky, Moataz; Thomas, Abbey; Sutherlin, Mark; Hart, Joseph

    2016-05-01

    Collecting torque data using a multimode dynamometer is common in sports-medicine research. The error in torque measurements across multiple sites and dynamometers has not been established. To assess the validity of 2 calibration protocols across 3 dynamometers and the error associated with torque measurement for each system. Observational study. 3 university laboratories at separate institutions. 2 Biodex System 3 dynamometers and 1 Biodex System 4 dynamometer. System calibration was completed using the manufacturer-recommended single-weight method and an experimental calibration method using a series of progressive weights. Both calibration methods were compared with a manually calculated theoretical torque across a range of applied weights. Relative error, absolute error, and percent error were calculated at each weight. Each outcome variable was compared between systems using 95% confidence intervals across low (0-65 Nm), moderate (66-110 Nm), and high (111-165 Nm) torque categorizations. Calibration coefficients were established for each system using both calibration protocols. However, within each system the calibration coefficients generated using the single-weight (System 4 = 2.42 [0.90], System 3a = 1.37 [1.11], System 3b = -0.96 [1.45]) and experimental calibration protocols (System 4 = 3.95 [1.08], System 3a = -0.79 [1.23], System 3b = 2.31 [1.66]) were similar and displayed acceptable mean relative error compared with calculated theoretical torque values. Overall, percent error was greatest for all 3 systems in low-torque conditions (System 4 = 11.66% [6.39], System 3a = 6.82% [11.98], System 3b = 4.35% [9.49]). The System 4 significantly overestimated torque across all 3 weight increments, and the System 3b overestimated torque over the moderate-torque increment. Conversion of raw voltage to torque values using the single-calibration-weight method is valid and comparable to a more complex multiweight calibration process; however, it is clear that

  12. Neutron induced radiation damage

    Williams, M.M.R.

    1977-01-01

    We derive a general expression for the number of displaced atoms of type j caused by a primary knock-on of type i. The Kinchin-Pease model is used, but considerably generalised to allow for realistic atomic potentials. Two cases are considered in detail: the single particle problem causing a cascade and the neutron initiated problem which leads to multiple subcascades. Numerical results have been obtained for a variety of scattering laws. An important conclusion is that neutron initiated damage is much more severe than atom-initiated damage and leads to the number of displaced atoms being a factor of (A+1) 2 /4A larger than the single primary knock-on theory predicts. A is the ratio of the atomic mass to the neutron mass. The importance of this result to the theory of neutron sputtering is explained. (orig.) [de

  13. Resveratrol Ameliorates Tau Hyperphosphorylation at Ser396 Site and Oxidative Damage in Rat Hippocampal Slices Exposed to Vanadate: Implication of ERK1/2 and GSK-3β Signaling Cascades.

    Jhang, Kyoung A; Park, Jin-Sun; Kim, Hee-Sun; Chong, Young Hae

    2017-11-08

    The objective of this study was to investigate the effect of resveratrol (a natural polyphenolic phytostilbene) on tau hyperphosphorylation and oxidative damage induced by sodium orthovanadate (Na 3 VO 4 ), the prevalent species of vanadium (vanadate), in rat hippocampal slices. Our results showed that resveratrol significantly inhibited Na 3 VO 4 -induced hyperphosphorylation of tau at the Ser396 (p-S396-tau) site, which is upregulated in the hippocampus of Alzheimer's disease (AD) brains and principally linked to AD-associated cognitive dysfunction. Subsequent mechanistic studies revealed that reduction of ERK1/2 activation was involved in the inhibitory effect of resveratrol by inhibiting the ERK1/2 pathway with SL327 mimicking the aforementioned effect of resveratrol. Moreover, resveratrol potently induced GSK-3β Ser9 phosphorylation and reduced Na 3 VO 4 -induced p-S396-tau levels, which were markedly replicated by pharmacologic inhibition of GSK-3β with LiCl. These results indicate that resveratrol could suppress Na 3 VO 4 -induced p-S396-tau levels via downregulating ERK1/2 and GSK-3β signaling cascades in rat hippocampal slices. In addition, resveratrol diminished the increased extracellular reactive oxygen species generation and hippocampal toxicity upon long-term exposure to Na 3 VO 4 or FeCl 2 . Our findings strongly support the notion that resveratrol may serve as a potential nutraceutical agent for AD.

  14. Radiation damage in DNA

    Lafleur, V.

    1978-01-01

    A number of experiments are described with the purpose to obtain a better insight in the chemical nature and the biological significance of radiation-induced damage in DNA, with some emphasis on the significance of alkali-labile sites. It is shown that not only reactions of OH radicals but also of H radicals introduce breaks and other inactivating damage in single-standed phiX174 DNA. It is found that phosphate buffer is very suitable for the study of the reactions of H radicals with DNA, as the H 2 PO 4 - ions convert the hydrated electrons into H radicals. The hydrated electron, which does react with DNA, does not cause a detectable inactivation. (Auth.)

  15. Updated synthesis of the knowledge about the impact on marine environment of the radioactive releases from Fukushima Dai-ichi damaged site - October 26, 2011; Synthese actualisee des connaissances relatives a l'impact sur le milieu marin des rejets radioactifs du site nucleaire accidente de Fukushima Dai-ichi - 26 octobre 2011

    NONE

    2011-10-26

    A strong radioactive contamination of the marine environment close to the damaged Fukushima Dai-ichi power plant has been observed since March 21. The high concentration of some nuclides ({sup 131}I, {sup 137}Cs, {sup 134}Cs, {sup 136}Cs, {sup 132}Te, {sup 132}I) comes from three possible sources: the liquid effluents from the damaged site, the atmospheric fallouts, and the weathering of contaminated soils. This information note presents and comments the most recent informations gathered by the French institute of radiation protection and nuclear safety (IRSN) since the previous information note from July 11 and devoted to the same topic. It presents the estimation of the relative contribution of each contamination source and the evolution with time of the marine contamination. The mapping of {sup 137}Cs concentrations in surface seawater allows to estimate the amount of total {sup 137}Cs in the marine environment and its evolution with time. {sup 137}Cs and {sup 134}Cs concentrations were measured both in samples of surface coastal sediments and in river fishes and seafood products (mainly fishes and molluscs). Results are reported in graphs showing their evolution with time. (J.S.)

  16. Hydrogeologic characterization and evolution of the 'excavation damaged zone' by statistical analyses of pressure signals: application to galleries excavated at the clay-stone sites of Mont Terri (Ga98) and Tournemire (Ga03)

    Fatmi, H.; Ababou, R.; Matray, J.M.; Joly, C.

    2010-01-01

    Document available in extended abstract form only. This paper presents methods of statistical analysis and interpretation of hydrogeological signals in clayey formations, e.g., pore water pressure and atmospheric pressure. The purpose of these analyses is to characterize the hydraulic behaviour of this type of formation in the case of a deep repository of Mid- Level/High-Level and Long-lived radioactive wastes, and to study the evolution of the geologic formation and its EDZ (Excavation Damaged Zone) during the excavation of galleries. We focus on galleries Ga98 and Ga03 in the sites of Mont Terri (Jura, Switzerland) and Tournemire (France, Aveyron), through data collected in the BPP- 1 and PH2 boreholes, respectively. The Mont Terri site, crossing the Aalenian Opalinus clay-stone, is an underground laboratory managed by an international consortium, namely the Mont Terri project (Switzerland). The Tournemire site, crossing the Toarcian clay-stone, is an Underground Research facility managed by IRSN (France). We have analysed pore water and atmospheric pressure signals at these sites, sometimes in correlation with other data. The methods of analysis are based on the theory of stationary random signals (correlation functions, Fourier spectra, transfer functions, envelopes), and on multi-resolution wavelet analysis (adapted to nonstationary and evolutionary signals). These methods are also combined with filtering techniques, and they can be used for single signals as well as pairs of signals (cross-analyses). The objective of this work is to exploit pressure measurements in selected boreholes from the two compacted clay sites, in order to: - evaluate phenomena affecting the measurements (earth tides, barometric pressures..); - estimate hydraulic properties (specific storage..) of the clay-stones prior to excavation works and compare them with those estimated by pulse or slug tests on shorter time scales; - analyze the effects of drift excavation on pore pressures

  17. Irradiation damage

    Howe, L.M

    2000-07-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization.

  18. Irradiation damage

    Howe, L.M.

    2000-01-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization

  19. JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells.

    Kiziltepe, Tanyel; Hideshima, Teru; Ishitsuka, Kenji; Ocio, Enrique M; Raje, Noopur; Catley, Laurence; Li, Chun-Qi; Trudel, Laura J; Yasui, Hiroshi; Vallet, Sonia; Kutok, Jeffery L; Chauhan, Dharminder; Mitsiades, Constantine S; Saavedra, Joseph E; Wogan, Gerald N; Keefer, Larry K; Shami, Paul J; Anderson, Kenneth C

    2007-07-15

    Here we investigated the cytotoxicity of JS-K, a prodrug designed to release nitric oxide (NO(*)) following reaction with glutathione S-transferases, in multiple myeloma (MM). JS-K showed significant cytotoxicity in both conventional therapy-sensitive and -resistant MM cell lines, as well as patient-derived MM cells. JS-K induced apoptosis in MM cells, which was associated with PARP, caspase-8, and caspase-9 cleavage; increased Fas/CD95 expression; Mcl-1 cleavage; and Bcl-2 phosphorylation, as well as cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G (EndoG) release. Moreover, JS-K overcame the survival advantages conferred by interleukin-6 (IL-6) and insulin-like growth factor 1 (IGF-1), or by adherence of MM cells to bone marrow stromal cells. Mechanistic studies revealed that JS-K-induced cytotoxicity was mediated via NO(*) in MM cells. Furthermore, JS-K induced DNA double-strand breaks (DSBs) and activated DNA damage responses, as evidenced by neutral comet assay, as well as H2AX, Chk2 and p53 phosphorylation. JS-K also activated c-Jun NH(2)-terminal kinase (JNK) in MM cells; conversely, inhibition of JNK markedly decreased JS-K-induced cytotoxicity. Importantly, bortezomib significantly enhanced JS-K-induced cytotoxicity. Finally, JS-K is well tolerated, inhibits tumor growth, and prolongs survival in a human MM xenograft mouse model. Taken together, these data provide the preclinical rationale for the clinical evaluation of JS-K to improve patient outcome in MM.

  20. Burn-up Credit Criticality Safety Benchmark Phase III-C. Nuclide Composition and Neutron Multiplication Factor of a Boiling Water Reactor Spent Fuel Assembly for Burn-up Credit and Criticality Control of Damaged Nuclear Fuel

    Suyama, K.; Uchida, Y.; Kashima, T.; Ito, T.; Miyaji, T.

    2016-01-01

    Criticality control of damaged nuclear fuel is one of the key issues in the decommissioning operation of the Fukushima Daiichi Nuclear Power Station accident. The average isotopic composition of spent nuclear fuel as a function of burn-up is required in order to evaluate criticality parameters of the mixture of damaged nuclear fuel with other materials. The NEA Expert Group on Burn-up Credit Criticality (EGBUC) has organised several international benchmarks to assess the accuracy of burn-up calculation methodologies. For BWR fuel, the Phase III-B benchmark, published in 2002, was a remarkable landmark that provided general information on the burn-up properties of BWR spent fuel based on the 8x8 type fuel assembly. Since the publication of the Phase III-B benchmark, all major nuclear data libraries have been revised; in Japan from JENDL-3.2 to JENDL-4, in Europe from JEF-2.2 to JEFF-3.1 and in the US from ENDF/B-VI to ENDF/B-VII.1. Burn-up calculation methodologies have been improved by adopting continuous-energy Monte Carlo codes and modern neutronics calculation methods. Considering the importance of the criticality control of damaged fuel in the Fukushima Daiichi Nuclear Power Station accident, a new international burn-up calculation benchmark for the 9 x 9 STEP-3 BWR fuel assemblies was organised to carry out the inter-comparison of the averaged isotopic composition in the interest of the burnup credit criticality safety community. Benchmark specifications were proposed and approved at the EGBUC meeting in September 2012 and distributed in October 2012. The deadline for submitting results was set at the end of February 2013. The basic model for the benchmark problem is an infinite two-dimensional array of BWR fuel assemblies consisting of a 9 x 9 fuel rod array with a water channel in the centre. The initial uranium enrichment of fuel rods without gadolinium is 4.9, 4.4, 3.9, 3.4 and 2.1 wt% and 3.4 wt% for the rods using gadolinium. The burn-up conditions are

  1. Role of the Checkpoint Clamp in DNA Damage Response

    Mihoko Kai

    2013-01-01

    Full Text Available DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. Coordination of these pathways requires tight regulation in order to prevent genomic instability. The checkpoint clamp complex consists of Rad9, Rad1 and Hus1 proteins, and is often called the 9-1-1 complex. This PCNA (proliferating cell nuclear antigen-like donut-shaped protein complex is a checkpoint sensor protein that is recruited to DNA damage sites during the early stage of the response, and is required for checkpoint activation. As PCNA is required for multiple pathways of DNA metabolism, the checkpoint clamp has also been implicated in direct roles in DNA repair, as well as in coordination of the pathways. Here we discuss roles of the checkpoint clamp in DNA damage response (DDR.

  2. Radiation damage to DNA: the effect of LET

    Ward, J F; Milligan, J R [California Univ., San Diego, La Jolla, CA (United States). School of Medicine

    1997-03-01

    Mechanisms whereby ionizing radiation induced damage are introduced into cellular DNA are discussed. The types of lesions induced are summarized and the rationale is presented which supports the statement that radiation induced singly damaged sites are biologically unimportant. The conclusion that multiply damaged sites are critical is discussed and the mechanisms whereby such lesions are formed are presented. Structures of multiply damaged sites are summarized and problems which they present to cellular repair systems are discussed. Lastly the effects of linear energy transfer on the complexity of multiply damaged sites are surveyed and the consequences of this increased complexity are considered in terms of cell survival and mutation. (author)

  3. Damaged Skylab

    1973-01-01

    The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows a crippled Skylab in orbit. The crew found their home in space to be in serious shape; the heat shield gone, one solar wing gone, and the other jammed. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

  4. Structural damage

    Gray, R.E.; Bruhn, R.W.

    1992-01-01

    Virtually all structures show some signs of distress due to deterioration of the building components, to changed loads, or to changed support conditions. Changed support conditions result from ground movements. In mining regions many cases of structural distress are attributed to mining without considering alternative causes. This is particularly true of coal mining since it occurs under extensive areas. Coal mining is estimated to have already undermined more than eight million acres and may eventually undermine 40 million acres in the United States. Other nonmetal and metal underground mines impact much smaller areas. Although it is sometimes difficult, even with careful study, to identify the actual cause of damage, persons responsible for underground coal mining should at least be aware of possible causes of building stress other than mine subsidence. This paper presents information on distress to structures and briefly reviews a number of causes of ground movements other than subsidence: Mass movements, dissolution, erosion, frost action, shrinking and swelling, yield into excavations and compressibility

  5. Radiation damage prediction system using damage function

    Tanaka, Yoshihisa; Mori, Seiji

    1979-01-01

    The irradiation damage analysis system using a damage function was investigated. This irradiation damage analysis system consists of the following three processes, the unfolding of a damage function, the calculation of the neutron flux spectrum of the object of damage analysis and the estimation of irradiation effect of the object of damage analysis. The damage function is calculated by applying the SAND-2 code. The ANISN and DOT3, 5 codes are used to calculate neutron flux. The neutron radiation and the allowable time of reactor operation can be estimated based on these calculations of the damage function and neutron flux. The flow diagram of the process of analyzing irradiation damage by a damage function and the flow diagram of SAND-2 code are presented, and the analytical code for estimating damage, which is determined with a damage function and a neutron spectrum, is explained. The application of the irradiation damage analysis system using a damage function was carried out to the core support structure of a fast breeder reactor for the damage estimation and the uncertainty evaluation. The fundamental analytical conditions and the analytical model for this work are presented, then the irradiation data for SUS304, the initial estimated values of a damage function, the error analysis for a damage function and the analytical results are explained concerning the computation of a damage function for 10% total elongation. Concerning the damage estimation of FBR core support structure, the standard and lower limiting values of damage, the permissible neutron flux and the allowable years of reactor operation are presented and were evaluated. (Nakai, Y.)

  6. Measurement of DNA adducts and strand breaks in dab (Limanda limanda) collected in the field: effects of biotic (age, sex) and abiotic (sampling site and period) factors on the extent of DNA damage

    Akcha, F.; Leday, G.; Pfohl-Leszkowicz, A

    2004-08-18

    In the Eastern English Channel, the potential application of the comet assay and post-labelling technique in dab was evaluated for genotoxicity monitoring of the marine environment. The effects of biotic (age, sex) and abiotic (sampling site and period) factors on the extent of DNA lesions were also studied. Female and male dab of two class of size (juvenile and adult) were collected by trawling in different sites in Seine Bay and Somme Bay during September 2001. Single-strand breaks and adducts were, respectively, measured in erythrocytes and the liver. Results obtained for the adult female were compared with those collected during a first cruise in March 2001 [Akcha et al., Mutat Res. 534 (1-2) (2003) 21]. Significant effects of sex and age were demonstrated on the level of strand breaks. Moreover, a significant interaction between age and sex was shown that might indicate the complex influence of other factors on the extent of DNA damage (i.e. reproduction status). In the adult dab, the level of breaks is higher in the male than in the female, whereas the opposite trend was observed for the juvenile. Whatever the sex, the number of DNA breaks is higher in the adult than in the juvenile. For the female dab, significant differences were observed with the comet assay between the Seine Bay and the Somme Bay in March but not in September. This may be due to seasonal variations in the formation of DNA lesions related to variations in lipid content and levels of biotransformation activities and/or to spawning cycles. The presence of genotoxic substances in the study areas was also confirmed by the detection of DNA adducts in each sample analysed. Whereas no effect was shown on the total level of adducts for the tested biotic and abiotic factors, qualitative differences in adduct profiles were observed for each of these factors. For the female dab, comparison of adduct profiles obtained in March and September with one generated by hepatic microsomal activation in dab of

  7. Ropizine concurrently enhances and inhibits [3H] dextromethorpan binding to different structures of the guinea pig brain: Autoradiographic evidence for multiple binding sites

    Canoll, P.D.; Smith, P.R.; and Musacchio, J.M.

    1990-01-01

    Ropizine produces a simultaneous enhancement and inhibition of [ 3 H] dextromethorphan (DM) high-affinity binding to different areas of the guinea pig brain. These results imply that there are two distinct types of high-affinity [ 3 H]DM binding sites, which are present in variable proportions in different brain structures. The ropizine-enhances [ 3 H]DM binding type was preferentially inhibited by (+)-pentazocine. This is consistent with the presumption that the (+)-pentazocine-sensitive site is identical with the common site for DM and 3-(-3-Hydroxphenyl)-N-(1-propyl)piperidine ((+)-3-PPP). The second binding type, which is inhibited by ropizine and is not so sensitive to (+)- pentazocine, has not been fully characterized. This study demonstrates that the biphasic effects to ropizine are due, at least in part, to the effects of ropizine on two different types of [ 3 H]DM binding sites. However, this study does not rule out that the common DM/(+)-3-PPP site also might be inhibited by higher concentrations of ropizine

  8. Comparison of glare in YAG-damaged intraocular lenses: injection-molded versus lathe-cut.

    Bath, P E; Dang, Y; Martin, W H

    1986-11-01

    A comparative analysis of YAG laser intraocular lens (IOL) damage was undertaken on injection-molded and lathe-cut IOLs. Damage sites were evaluated with polarized light. A consistent positive polarization was observed in the damage sites of lathe-cut IOLs. A consistent negative polarization was observed in the damage sites of injection-molded IOLs. The presence of positive polarization in IOL damage sites may be correlated with increased potential for glare. Results and clinical implications are discussed.

  9. Canonical A-to-I and C-to-U RNA editing is enriched at 3'UTRs and microRNA target sites in multiple mouse tissues.

    Tongjun Gu

    Full Text Available RNA editing is a process that modifies RNA nucleotides and changes the efficiency and fidelity of the central dogma. Enzymes that catalyze RNA editing are required for life, and defects in RNA editing are associated with many diseases. Recent advances in sequencing have enabled the genome-wide identification of RNA editing sites in mammalian transcriptomes. Here, we demonstrate that canonical RNA editing (A-to-I and C-to-U occurs in liver, white adipose, and bone tissues of the laboratory mouse, and we show that apparent non-canonical editing (all other possible base substitutions is an artifact of current high-throughput sequencing technology. Further, we report that high-confidence canonical RNA editing sites can cause non-synonymous amino acid changes and are significantly enriched in 3' UTRs, specifically at microRNA target sites, suggesting both regulatory and functional consequences for RNA editing.

  10. Sorption of trivalent lanthanides and actinides onto montmorillonite: Macroscopic, thermodynamic and structural evidence for ternary hydroxo and carbonato surface complexes on multiple sorption sites.

    Fernandes, M Marques; Scheinost, A C; Baeyens, B

    2016-08-01

    The credibility of long-term safety assessments of radioactive waste repositories may be greatly enhanced by a molecular level understanding of the sorption processes onto individual minerals present in the near- and far-fields. In this study we couple macroscopic sorption experiments to surface complexation modelling and spectroscopic investigations, including extended X-ray absorption fine structure (EXAFS) and time-resolved laser fluorescence spectroscopies (TRLFS), to elucidate the uptake mechanism of trivalent lanthanides and actinides (Ln/An(III)) by montmorillonite in the absence and presence of dissolved carbonate. Based on the experimental sorption isotherms for the carbonate-free system, the previously developed 2 site protolysis non electrostatic surface complexation and cation exchange (2SPNE SC/CE) model needed to be complemented with an additional surface complexation reaction onto weak sites. The fitting of sorption isotherms in the presence of carbonate required refinement of the previously published model by reducing the strong site capacity and by adding the formation of Ln/An(III)-carbonato complexes both on strong and weak sites. EXAFS spectra of selected Am samples and TRLFS spectra of selected Cm samples corroborate the model assumptions by showing the existence of different surface complexation sites and evidencing the formation of Ln/An(III) carbonate surface complexes. In the absence of carbonate and at low loadings, Ln/An(III) form strong inner-sphere complexes through binding to three Al(O,OH)6 octahedra, most likely by occupying vacant sites in the octahedral layers of montmorillonite, which are exposed on {010} and {110} edge faces. At higher loadings, Ln/An(III) binds to only one Al octahedron, forming a weaker, edge-sharing surface complex. In the presence of carbonate, we identified a ternary mono- or dicarbonato Ln/An(III) complex binding directly to one Al(O,OH)6 octahedron, revealing that type-A ternary complexes form with the one

  11. Equivalent damage of loads on pavements

    Prozzi, JA

    2009-05-26

    Full Text Available This report describes a new methodology for the determination of Equivalent Damage Factors (EDFs) of vehicles with multiple axle and wheel configurations on pavements. The basic premise of this new procedure is that "equivalent pavement response...

  12. Evolving Multiscale Deformation and Damage in Polycrystals

    McDowell, David

    2003-01-01

    ... near heterogeneities such as second phase particles or grain boundary triple points. Emphasis is placed on multiple length scale modeling of plastic deformation and damage for micro-, meso and macro-levels...

  13. The S-Layer Glycoprotein of the Crenarchaeote Sulfolobus acidocaldarius Is Glycosylated at Multiple Sites with Chitobiose-Linked N-Glycans

    Elham Peyfoon

    2010-01-01

    Full Text Available Glycosylation of the S-layer of the crenarchaea Sulfolobus acidocaldarius has been investigated using glycoproteomic methodologies. The mature protein is predicted to contain 31 N-glycosylation consensus sites with approximately one third being found in the C-terminal domain spanning residues L1004-Q1395. Since this domain is rich in Lys and Arg and therefore relatively tractable to glycoproteomic analysis, this study has focused on mapping its N-glycosylation. Our analysis identified nine of the 11 consensus sequence sites, and all were found to be glycosylated. This constitutes a remarkably high glycosylation density in the C-terminal domain averaging one site for each stretch of 30–40 residues. Each of the glycosylation sites observed was shown to be modified with a heterogeneous family of glycans, with the largest having a composition Glc1Man2GlcNAc2 plus 6-sulfoquinovose (QuiS, consistent with the tribranched hexasaccharide previously reported in the cytochrome b558/566 of S. acidocaldarius. S. acidocaldarius is the only archaeal species whose N-glycans are known to be linked via the chitobiose core disaccharide that characterises the N-linked glycans of Eukarya.

  14. Multiple autophosphorylation sites of the epidermal growth factor receptor are essential for receptor kinase activity and internalization. Contrasting significance of tyrosine 992 in the native and truncated receptors

    Sorkin, A; Helin, K; Waters, C M

    1992-01-01

    The role of epidermal growth factor (EGF) receptor autophosphorylation sites in the regulation of receptor functions has been studied using cells transfected with mutant EGF receptors. Simultaneous point mutation of 4 tyrosines (Y1068, Y1086, Y1148, Y1173) to phenylalanine, as well as removal of ...

  15. Multiple myeloma

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  16. Automated Damage Onset Analysis Techniques Applied to KDP Damage and the Zeus Small Area Damage Test Facility

    Sharp, R.; Runkel, M.

    1999-01-01

    Automated damage testing of KDP using LLNL's Zeus automated damage test system has allowed the statistics of KDP bulk damage to be investigated. Samples are now characterized by the cumulative damage probability curve, or S-curve, that is generated from hundreds of individual test sites per sample. A HeNe laser/PMT scatter diagnostic is used to determine the onset of damage at each test site. The nature of KDP bulk damage is such that each scatter signal may possess many different indicators of a damage event. Because of this, the determination of the initial onset for each scatter trace is not a straightforward affair and has required considerable manual analysis. The amount of testing required by crystal development for the National Ignition Facility (NIF) has made it impractical to continue analysis by hand. Because of this, we have developed and implemented algorithms for analyzing the scatter traces by computer. We discuss the signal cleaning algorithms and damage determination criteria that have lead to the successful implementation of a LabView based analysis code. For the typical R/1 damage data set, the program can find the correct damage onset in more than 80% of the cases, with the remaining 20% being left to operator determination. The potential time savings for data analysis is on the order of ∼ 100X over manual analysis and is expected to result in the savings of at least 400 man-hours over the next 3 years of NIF quality assurance testing

  17. Does Categorization Method Matter in Exploring Volume-Outcome Relation? A Multiple Categorization Methods Comparison in Coronary Artery Bypass Graft Surgery Surgical Site Infection.

    Yu, Tsung-Hsien; Tung, Yu-Chi; Chung, Kuo-Piao

    2015-08-01

    Volume-infection relation studies have been published for high-risk surgical procedures, although the conclusions remain controversial. Inconsistent results may be caused by inconsistent categorization methods, the definitions of service volume, and different statistical approaches. The purpose of this study was to examine whether a relation exists between provider volume and coronary artery bypass graft (CABG) surgical site infection (SSI) using different categorization methods. A population-based cross-sectional multi-level study was conducted. A total of 10,405 patients who received CABG surgery between 2006 and 2008 in Taiwan were recruited. The outcome of interest was surgical site infection for CABG surgery. The associations among several patient, surgeon, and hospital characteristics was examined. The definition of surgeons' and hospitals' service volume was the cumulative CABG service volumes in the previous year for each CABG operation and categorized by three types of approaches: Continuous, quartile, and k-means clustering. The results of multi-level mixed effects modeling showed that hospital volume had no association with SSI. Although the relation between surgeon volume and surgical site infection was negative, it was inconsistent among the different categorization methods. Categorization of service volume is an important issue in volume-infection study. The findings of the current study suggest that different categorization methods might influence the relation between volume and SSI. The selection of an optimal cutoff point should be taken into account for future research.

  18. Modelling multi-hazard hurricane damages on an urbanized coast with a Bayesian Network approach

    van Verseveld, H.C.W.; Van Dongeren, A. R.; Plant, Nathaniel G.; Jäger, W.S.; den Heijer, C.

    2015-01-01

    Hurricane flood impacts to residential buildings in coastal zones are caused by a number of hazards, such as inundation, overflow currents, erosion, and wave attack. However, traditional hurricane damage models typically make use of stage-damage functions, where the stage is related to flooding depth only. Moreover, these models are deterministic and do not consider the large amount of uncertainty associated with both the processes themselves and with the predictions. This uncertainty becomes increasingly important when multiple hazards (flooding, wave attack, erosion, etc.) are considered simultaneously. This paper focusses on establishing relationships between observed damage and multiple hazard indicators in order to make better probabilistic predictions. The concept consists of (1) determining Local Hazard Indicators (LHIs) from a hindcasted storm with use of a nearshore morphodynamic model, XBeach, and (2) coupling these LHIs and building characteristics to the observed damages. We chose a Bayesian Network approach in order to make this coupling and used the LHIs ‘Inundation depth’, ‘Flow velocity’, ‘Wave attack’, and ‘Scour depth’ to represent flooding, current, wave impacts, and erosion related hazards.The coupled hazard model was tested against four thousand damage observations from a case site at the Rockaway Peninsula, NY, that was impacted by Hurricane Sandy in late October, 2012. The model was able to accurately distinguish ‘Minor damage’ from all other outcomes 95% of the time and could distinguish areas that were affected by the storm, but not severely damaged, 68% of the time. For the most heavily damaged buildings (‘Major Damage’ and ‘Destroyed’), projections of the expected damage underestimated the observed damage. The model demonstrated that including multiple hazards doubled the prediction skill, with Log-Likelihood Ratio test (a measure of improved accuracy and reduction in uncertainty) scores between 0.02 and 0

  19. Chemical characterization and source identification of PM2.5 at multiple sites in the Beijing-Tianjin-Hebei region, China

    Huang, Xiaojuan; Liu, Zirui; Liu, Jingyun; Hu, Bo; Wen, Tianxue; Tang, Guiqian; Zhang, Junke; Wu, Fangkun; Ji, Dongsheng; Wang, Lili; Wang, Yuesi

    2017-11-01

    The simultaneous observation and analysis of atmospheric fine particles (PM2.5) on a regional scale is an important approach to develop control strategies for haze pollution. In this study, samples of filtered PM2.5 were collected simultaneously at three urban sites (Beijing, Tianjin, and Shijiazhuang) and at a regional background site (Xinglong) in the Beijing-Tianjin-Hebei (BTH) region from June 2014 to April 2015. The PM2.5 at the four sites was mainly comprised of organic matter, secondary inorganic ions, and mineral dust. Positive matrix factorization (PMF) demonstrated that, on an annual basis, secondary inorganic aerosol was the largest PM2.5 source in this region, accounting for 29.2-40.5 % of the PM2.5 mass at the urban sites; the second-largest PM2.5 source was motor vehicle exhaust, particularly in Beijing (24.9 %), whereas coal combustion was also a large source in Tianjin (12.4 %) and Shijiazhuang (15.5 %), with particular dominance in winter. Secondary inorganic aerosol plays a vital role in the haze process, with the exception of the spring haze in Shijiazhuang and Tianjin, for which the dust source was crucial. In addition to secondary transformations, local direct emissions (coal combustion and motor vehicle exhaust) significantly contribute to the winter haze at the urban sites. Moreover, with the aggravation of haze pollution, the OC / EC mass ratio of PM2.5 decreased considerably and the nitrate-rich secondary aerosol increased during all four seasons in Beijing, both of which indicate that local motor vehicle emissions significantly contribute to the severe haze episodes in Beijing. To assess the impacts of regional transport on haze pollution, the PMF results were further processed with backward-trajectory cluster analysis, revealing that haze pollution usually occurred when air masses originating from polluted industrial regions in the south prevailed and is characterized by high PM2.5 loadings with considerable contributions from secondary

  20. Chemical characterization and source identification of PM2.5 at multiple sites in the Beijing–Tianjin–Hebei region, China

    X. Huang

    2017-11-01

    Full Text Available The simultaneous observation and analysis of atmospheric fine particles (PM2.5 on a regional scale is an important approach to develop control strategies for haze pollution. In this study, samples of filtered PM2.5 were collected simultaneously at three urban sites (Beijing, Tianjin, and Shijiazhuang and at a regional background site (Xinglong in the Beijing–Tianjin–Hebei (BTH region from June 2014 to April 2015. The PM2.5 at the four sites was mainly comprised of organic matter, secondary inorganic ions, and mineral dust. Positive matrix factorization (PMF demonstrated that, on an annual basis, secondary inorganic aerosol was the largest PM2.5 source in this region, accounting for 29.2–40.5 % of the PM2.5 mass at the urban sites; the second-largest PM2.5 source was motor vehicle exhaust, particularly in Beijing (24.9 %, whereas coal combustion was also a large source in Tianjin (12.4 % and Shijiazhuang (15.5 %, with particular dominance in winter. Secondary inorganic aerosol plays a vital role in the haze process, with the exception of the spring haze in Shijiazhuang and Tianjin, for which the dust source was crucial. In addition to secondary transformations, local direct emissions (coal combustion and motor vehicle exhaust significantly contribute to the winter haze at the urban sites. Moreover, with the aggravation of haze pollution, the OC ∕ EC mass ratio of PM2.5 decreased considerably and the nitrate-rich secondary aerosol increased during all four seasons in Beijing, both of which indicate that local motor vehicle emissions significantly contribute to the severe haze episodes in Beijing. To assess the impacts of regional transport on haze pollution, the PMF results were further processed with backward-trajectory cluster analysis, revealing that haze pollution usually occurred when air masses originating from polluted industrial regions in the south prevailed and is characterized by high PM2.5 loadings with considerable

  1. Radiation-induced normal tissue damage: implications for radiotherapy

    Prasanna, Pataje G.

    2014-01-01

    Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

  2. Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage.

    Hill, Sarah J; Mordes, Daniel A; Cameron, Lisa A; Neuberg, Donna S; Landini, Serena; Eggan, Kevin; Livingston, David M

    2016-11-29

    Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron dysfunction disease that leads to paralysis and death. There is currently no established molecular pathogenesis pathway. Multiple proteins involved in RNA processing are linked to ALS, including FUS and TDP43, and we propose a disease mechanism in which loss of function of at least one of these proteins leads to an accumulation of transcription-associated DNA damage contributing to motor neuron cell death and progressive neurological symptoms. In support of this hypothesis, we find that FUS or TDP43 depletion leads to increased sensitivity to a transcription-arresting agent due to increased DNA damage. Thus, these proteins normally contribute to the prevention or repair of transcription-associated DNA damage. In addition, both FUS and TDP43 colocalize with active RNA polymerase II at sites of DNA damage along with the DNA damage repair protein, BRCA1, and FUS and TDP43 participate in the prevention or repair of R loop-associated DNA damage, a manifestation of aberrant transcription and/or RNA processing. Gaining a better understanding of the role(s) that FUS and TDP43 play in transcription-associated DNA damage could shed light on the mechanisms underlying ALS pathogenesis.

  3. Repair of Clustered Damage and DNA Polymerase Iota.

    Belousova, E A; Lavrik, O I

    2015-08-01

    Multiple DNA lesions occurring within one or two turns of the DNA helix known as clustered damage are a source of double-stranded DNA breaks, which represent a serious threat to the cells. Repair of clustered lesions is accomplished in several steps. If a clustered lesion contains oxidized bases, an individual DNA lesion is repaired by the base excision repair (BER) mechanism involving a specialized DNA polymerase after excising DNA damage. Here, we investigated DNA synthesis catalyzed by DNA polymerase iota using damaged DNA templates. Two types of DNA substrates were used as model DNAs: partial DNA duplexes containing breaks of different length, and DNA duplexes containing 5-formyluracil (5-foU) and uracil as a precursor of apurinic/apyrimidinic sites (AP) in opposite DNA strands. For the first time, we showed that DNA polymerase iota is able to catalyze DNA synthesis using partial DNA duplexes having breaks of different length as substrates. In addition, we found that DNA polymerase iota could catalyze DNA synthesis during repair of clustered damage via the BER system by using both undamaged and 5-foU-containing templates. We found that hPCNA (human proliferating cell nuclear antigen) increased efficacy of DNA synthesis catalyzed by DNA polymerase iota.

  4. Discovery of multiple interacting partners of gankyrin, a proteasomal chaperone and an oncoprotein--evidence for a common hot spot site at the interface and its functional relevance.

    Nanaware, Padma P; Ramteke, Manoj P; Somavarapu, Arun K; Venkatraman, Prasanna

    2014-07-01

    Gankyrin, a non-ATPase component of the proteasome and a chaperone of proteasome assembly, is also an oncoprotein. Gankyrin regulates a variety of oncogenic signaling pathways in cancer cells and accelerates degradation of tumor suppressor proteins p53 and Rb. Therefore gankyrin may be a unique hub integrating signaling networks with the degradation pathway. To identify new interactions that may be crucial in consolidating its role as an oncogenic hub, crystal structure of gankyrin-proteasome ATPase complex was used to predict novel interacting partners. EEVD, a four amino acid linear sequence seems a hot spot site at this interface. By searching for EEVD in exposed regions of human proteins in PDB database, we predicted 34 novel interactions. Eight proteins were tested and seven of them were found to interact with gankyrin. Affinity of four interactions is high enough for endogenous detection. Others require gankyrin overexpression in HEK 293 cells or occur endogenously in breast cancer cell line- MDA-MB-435, reflecting lower affinity or presence of a deregulated network. Mutagenesis and peptide inhibition confirm that EEVD is the common hot spot site at these interfaces and therefore a potential polypharmacological drug target. In MDA-MB-231 cells in which the endogenous CLIC1 is silenced, trans-expression of Wt protein (CLIC1_EEVD) and not the hot spot site mutant (CLIC1_AAVA) resulted in significant rescue of the migratory potential. Our approach can be extended to identify novel functionally relevant protein-protein interactions, in expansion of oncogenic networks and in identifying potential therapeutic targets. © 2013 Wiley Periodicals, Inc.

  5. Direct and indirect effects of multiple stressors on stream invertebrates across watershed, reach and site scales: A structural equation modelling better informing on hydromorphological impacts.

    Villeneuve, B; Piffady, J; Valette, L; Souchon, Y; Usseglio-Polatera, P

    2018-01-15

    The purpose of our approach was to take into account the nested spatial scales driving stream functioning in the description of pressures/ecological status links by analysing the results of a hierarchical model. The development of this model has allowed us to answer the following questions: Does the consideration of the indirect links between anthropogenic pressures and stream ecological status modify the hierarchy of pressure types impacting benthic invertebrates? Do the different nested scales play different roles in the anthropogenic pressures/ecological status relationship? Does this model lead to better understanding of the specific role of hydromorphology in the evaluation of stream ecological status? To achieve that goal, we used the Partial Least Square (PLS) path modelling method to develop a structural model linking variables describing (i) land use and hydromorphological alterations at the watershed scale, (ii) hydromorphological alterations at the reach scale, (iii) nutrients-organic matter contamination levels at the site scale, and (iv) substrate characteristics at the sampling site scale, to explain variation in values of a macroinvertebrate-based multimetric index: the French I 2 M 2 . We have highlighted the importance of land use effects exerted on both hydromorphological and chemical characteristics of streams observed at finer scales and their subsequent indirect impact on stream ecological status. Hydromorphological alterations have an effect on the substrate mosaic structure and on the concentrations of nutrients and organic matter at site scale. This result implies that stream hydromorphology can have a major indirect effect on macroinvertebrate assemblages and that the hierarchy of impacts of anthropogenic pressures on stream ecological status generally described in the literature - often determining strategic restoration priorities - has to be re-examined. Finally, the effects of nutrients and organic matter on macroinvertebrate assemblages

  6. Attenuation-difference radar tomography: results of a multiple-plane experiment at the U.S. Geological Survey Fractured-Rock Research Site, Mirror Lake, New Hampshire

    Lane, J.W.; Day-Lewis, F. D.; Harris, J.M.; Haeni, F.P.; Gorelick, S.M.

    2000-01-01

    Attenuation-difference, borehole-radar tomography was used to monitor a series of sodium chloride tracer injection tests conducted within the FSE, wellfield at the U.S. Geological Survey Fractured-Rock Hydrology Research Site in Grafton County, New Hampshire, USA. Borehole-radar tomography surveys were conducted using the sequential-scanning and injection method in three boreholes that form a triangular prism of adjoining tomographic image planes. Results indicate that time-lapse tomography methods provide high-resolution images of tracer distribution in permeable zones.

  7. Multiple phosphorylation sites at the C-terminus regulate nuclear import of HCMV DNA polymerase processivity factor ppUL44

    Alvisi, Gualtiero; Marin, Oriano; Pari, Gregory; Mancini, Manuela; Avanzi, Simone; Loregian, Arianna; Jans, David A.; Ripalti, Alessandro

    2011-01-01

    The processivity factor of human cytomegalovirus DNA polymerase, phosphoprotein ppUL44, is essential for viral replication. During viral infection ppUL44 is phosphorylated by the viral kinase pUL97, but neither the target residues on ppUL44 nor the effect of phosphorylation on ppUL44's activity are known. We report here that ppUL44 is phosphorylated when transiently expressed in mammalian cells and coimmunoprecipitates with cellular kinases. Of three potential phosphorylation sites (S413, S415, S418) located upstream of ppUL44's nuclear localization signal (NLS) and one (T427) within the NLS itself, protein kinase CK2 (CK2) specifically phosphorylates S413, to trigger a cascade of phosphorylation of S418 and S415 by CK1 and CK2, respectively. Negative charge at the CK2/CK1 target serine residues facilitates optimal nuclear accumulation of ppUL44, whereas negative charge on T427, a potential cyclin-dependent 1 phosphorylation site, strongly decreases nuclear accumulation. Thus, nuclear transport of ppUL44 is finely tuned during viral infection through complex phosphorylation events.

  8. Multiple Hfq-Crc target sites are required to impose catabolite repression on (methyl)phenol metabolism in Pseudomonas putida CF600.

    Wirebrand, Lisa; Madhushani, Anjana W K; Irie, Yasuhiko; Shingler, Victoria

    2018-01-01

    The dmp-system encoded on the IncP-2 pVI150 plasmid of Pseudomonas putida CF600 confers the ability to assimilate (methyl)phenols. Regulation of the dmp-genes is subject to sophisticated control, which includes global regulatory input to subvert expression of the pathway in the presence of preferred carbon sources. Previously we have shown that in P. putida, translational inhibition exerted by the carbon repression control protein Crc operates hand-in-hand with the RNA chaperon protein Hfq to reduce translation of the DmpR regulator of the Dmp-pathway. Here, we show that Crc and Hfq co-target four additional sites to form riboprotein complexes within the proximity of the translational initiation sites of genes encoding the first two steps of the Dmp-pathway to mediate two-layered control in the face of selection of preferred substrates. Furthermore, we present evidence that Crc plays a hitherto unsuspected role in maintaining the pVI150 plasmid within a bacterial population, which has implications for (methyl)phenol degradation and a wide variety of other physiological processes encoded by the IncP-2 group of Pseudomonas-specific mega-plasmids. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  9. Laser damage in optical components: metrology, statistical and photo-induced analysis of precursor centres; Endommagement laser dans les composants optiques: metrologie, analyse statistique et photo-induite des sites initiateurs

    Gallais, L

    2002-11-15

    This thesis deals with laser damage phenomena for nanosecond pulses, in optical components such as glasses, dielectric and metallic thin films. Firstly, a work is done on the laser damage metrology, in order to obtain accurate and reliable measurement of laser-induced damage probabilities, with a rigorous control of test parameters. Then, with the use of a specific model, we find densities of laser damage precursors in the case of bulk glasses (few tens by (100{mu}m){sup 3}) and in the case of glass surfaces (one precursor by {mu}m{sup 3}). Our analysis is associated to morphology studies by Atomic Force Microscope to discuss about precursor nature and damage process. Influence of wavelength (from 355 to 1064 nm) and cumulated shots is also studied. Simulations are performed to study initiation mechanisms on these inclusions. This work gives an estimation of complex index and size of the precursor, which permits to discuss about possible detection by non-destructive tools. (author)

  10. Multiple [3H]imipramine binding sites in brains of male and female Fawn-Hooded and Long-Evans rats

    Ieni, J.R.; Zukin, S.R.; Praag, H.M. van; Tobach, E.; Barr, G.A.

    1985-01-01

    Comparisons of high- and low-affinity [ 3 H]imipramine binding to whole brain homogenates from adult male and female rats of the Fawn-Hooded and Long-Evans strains were performed. Most strikingly, no significant differences were observed between the two strains in any of the binding parameters, indicating that brain [ 3 H]imipramine binding sites, which may be related to the serotonergic uptake process, appear normal in a strain of rats with serotonin platelet storage pool disease. However, a significant sex difference in high- but not low-affinity whole brain [ 3 H]imipramine Bsub(max) values was observed, with females of both strains having higher densities than males. (Auth.)

  11. Pain at multiple body sites and health-related quality of life in older adults: results from the North Staffordshire Osteoarthritis Project.

    Lacey, Rosie J; Belcher, John; Rathod, Trishna; Wilkie, Ross; Thomas, Elaine; McBeth, John

    2014-11-01

    Number of pain sites (NPS) is a potentially important marker of health-related quality of life (HRQoL) but remains unexplored in older people. This cross-sectional study investigated whether, in older people including the oldest old, NPS was independently associated with poorer mental and physical HRQoL and if the association was moderated by age. A postal questionnaire sent to a population sample of adults aged ≥50 years in North Staffordshire, UK, included the 12-item Short Form Health Survey (SF-12) mental component summary (MCS) and physical component summary (PCS), a blank body pain manikin, socio-demographic, health behaviour and morbidity questions. Participants shaded sites of pain lasting ≥1 day in the past 4 weeks on the manikin. OA consultation data were obtained for participants consenting to medical records review. A total of 13 986 individuals (adjusted response 70.6%) completed a questionnaire, of which 12 408 provided complete pain data. The median NPS reported was 4 [interquartile range (IQR) 0-8]. General linear models showed that an increasing NPS was significantly associated with poorer MCS (β = -0.43, 95% CI -0.46, -0.40) and PCS (β = -0.87, 95% CI -0.90, -0.84). Adjustment for covariates attenuated the associations but they remained significant ( β = -0.28, 95% CI -0.31, -0.24; PCS: β = -0.63, 95% CI -0.66, -0.59). The association between NPS and MCS or PCS was moderated by age, but the strongest associations were not in the oldest old. NPS appears to be a potentially modifiable target for improving physical and mental HRQoL in older people. Future analyses should investigate the influence of NPS on HRQoL over time in older people. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  12. Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites

    Pothof, F.; Bonini, L.; Lanzilotto, M.; Livi, A.; Fogassi, L.; Orban, G. A.; Paul, O.; Ruther, P.

    2016-08-01

    Objective. Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. Approach. Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 μm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. Main results. Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. Significance. With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the

  13. ALMA OBSERVATIONS OF A HIGH-DENSITY CORE IN TAURUS: DYNAMICAL GAS INTERACTION AT THE POSSIBLE SITE OF A MULTIPLE STAR FORMATION

    Tokuda, Kazuki; Onishi, Toshikazu [Department of Physical Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531 (Japan); Saigo, Kazuya; Kawamura, Akiko [National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan); Fukui, Yasuo; Inutsuka, Shu-ichiro; Tachihara, Kengo [Department of Physics, Nagoya University, Chikusa-ku, Nagoya 464-8602 (Japan); Matsumoto, Tomoaki [Faculty of Humanity and Environment, Hosei University, Fujimi, Chiyoda-ku, Tokyo 102-8160 (Japan); Machida, Masahiro N. [Department of Earth and Planetary Sciences, Kyushu University, Fukuoka 812-8581 (Japan); Tomida, Kengo, E-mail: s_k.tokuda@p.s.osakafu-u.ac.jp [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States)

    2014-07-01

    Starless dense cores eventually collapse dynamically, forming protostars inside them, and the physical properties of the cores determine the nature of the forming protostars. We report ALMA observations of dust continuum emission and molecular rotational lines toward MC27 or L1521F, which is considered to be very close to the first protostellar core phase. We found a few starless high-density cores, one of which has a very high density of ∼10{sup 7} cm{sup –3}, within a region of several hundred AU around a very low-luminosity protostar detected by Spitzer. A very compact bipolar outflow with a dynamical timescale of a few hundred years was found toward the protostar. The molecular line observation shows several cores with an arc-like structure, possibly due to the dynamical gas interaction. These complex structures revealed in the present observations suggest that the initial condition of star formation is highly dynamical in nature, which is considered to be a key factor in understanding fundamental issues of star formation such as the formation of multiple stars and the origin of the initial mass function of stars.

  14. ATP-dependent chromatin remodeling in the DNA-damage response

    Lans Hannes

    2012-01-01

    Full Text Available Abstract The integrity of DNA is continuously challenged by metabolism-derived and environmental genotoxic agents that cause a variety of DNA lesions, including base alterations and breaks. DNA damage interferes with vital processes such as transcription and replication, and if not repaired properly, can ultimately lead to premature aging and cancer. Multiple DNA pathways signaling for DNA repair and DNA damage collectively safeguard the integrity of DNA. Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response. Chromatin influences access to DNA, and often serves as a docking or signaling site for repair and signaling proteins. Its structure can be adapted by post-translational histone modifications and nucleosome remodeling, catalyzed by the activity of ATP-dependent chromatin-remodeling complexes. In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response. In this review, we summarize the current knowledge on the involvement of ATP-dependent chromatin remodeling in three major DNA repair pathways: nucleotide excision repair, homologous recombination, and non-homologous end-joining. This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response. Moreover, several complexes seem to have multiple functions, and are implicated in various mechanistically distinct repair pathways.

  15. Role of multiple phosphorylation sites in the COOH-terminal tail of aquaporin-2 for water transport: evidence against channel gating

    Moeller, Hanne B; Macaulay, Nanna; Knepper, Mark A

    2009-01-01

    demonstrated that lack of phosphorylation at S256, S261, S264, or S269 had no effect on AQP2 unit water transport. Similarly, no effect on AQP2 unit water transport was observed for the 264D and 269D forms, indicating that phosphorylation of the COOH-terminal tail of AQP2 is not involved in gating......Arginine vasopressin (AVP)-regulated phosphorylation of the water channel aquaporin-2 (AQP2) at serine 256 (S256) is essential for its accumulation in the apical plasma membrane of collecting duct principal cells. In this study, we examined the role of additional AVP-regulated phosphorylation sites...... in the COOH-terminal tail of AQP2 on protein function. When expressed in Xenopus laevis oocytes, prevention of AQP2 phosphorylation at S256A (S256A-AQP2) reduced osmotic water permeability threefold compared with wild-type (WT) AQP2-injected oocytes. In contrast, prevention of AQP2 single phosphorylation at S...

  16. DNA damage by Auger emitters

    Martin, R.F.; d'Cunha, Glenn; Gibbs, Richard; Murray, Vincent; Pardee, Marshall; Allen, B.J.

    1988-01-01

    125 I atoms can be introduced at specific locations along a defined DNA target molecule, either by site-directed incorporation of an 125 I-labelled deoxynucleotide or by binding of an 125 I-labelled sequence-selective DNA ligand. After allowing accumulation of 125 I decay-induced damage to the DNA, application of DNA sequencing techniques enables positions of strand breaks to be located relative to the site of decay, at a resolution corresponding to the distance between adjacent nucleotides [0.34 nm]. Thus, DNA provides a molecular framework to analyse the extent of damage following [averaged] individual decay events. Results can be compared with energy deposition data generated by computer-simulation methods developed by Charlton et al. The DNA sequencing technique also provides information about the chemical nature of the termini of the DNA chains produced following Auger decay-induced damage. In addition to reviewing the application of this approach to the analysis of 125 I decay induced DNA damage, some more recent results obtained by using 67 Ga are also presented. (author)

  17. Code verification and Y2K testing, calibration, testing, and installation of the radionuclide assay system-photon (RAS-P) at multiple sites for the Savannah River Site

    Hodge, C.A.

    2000-01-01

    The Radionuclide Assay System - Photon (RAS-P) is a near-field, transmission-corrected assay system developed for measurement of the actinide content of relatively homogeneous waste generated by facility operations. It is intended for use by facility operations personnel, and has features to enhance its usefulness and efficiency. These include multinuclide assay capability, automatic (off-shift) collection of background and straight-through transmission source data, enforcement of measurement control requirements, Go-NoGo or Assay modes, password protection, and reporting of total fissile gram equivalent values. System hardware consists of a shielded high-resolution germanium detector, a turntable, a shielded transmission source and shutter assembly, and a desktop computer and laser printer mounted on a compact frame. RAS-P was designed to assay the contents of cylindrical containers up to 30 inches diameter by 32 inches high, boxes up to 30 inches diagonal by 32 inches high, and HE PA filters up to 2 x 2 x 1 feet. Prior to installation at the Savannah River Site (SRS), code validation, system performance, and assurance against Y2K effects all were confirmed. Code validation was accomplished using spreadsheet calculations that were independent of the original code to calculate intermediate and final result produced by RAS-P. System testing was performed by repeated operation of the instrument under all required circumstances. Y2K testing was performed simultaneously with code validation following a protocol prescribed by the SRS Y2K subcommittee that required assays with dates varying throughout the expected useful life of the RAS-P, particularly those bracketing Y2K boundaries. Performance history has been compiled demonstrating reliability (system availability), diversability (the ability to alter assay parameters and obtain results quickly), and measurement control characteristics

  18. DNA Damage Signals and Space Radiation Risk

    Cucinotta, Francis A.

    2011-01-01

    Space radiation is comprised of high-energy and charge (HZE) nuclei and protons. The initial DNA damage from HZE nuclei is qualitatively different from X-rays or gamma rays due to the clustering of damage sites which increases their complexity. Clustering of DNA damage occurs on several scales. First there is clustering of single strand breaks (SSB), double strand breaks (DSB), and base damage within a few to several hundred base pairs (bp). A second form of damage clustering occurs on the scale of a few kbp where several DSB?s may be induced by single HZE nuclei. These forms of damage clusters do not occur at low to moderate doses of X-rays or gamma rays thus presenting new challenges to DNA repair systems. We review current knowledge of differences that occur in DNA repair pathways for different types of radiation and possible relationships to mutations, chromosomal aberrations and cancer risks.

  19. A Detached Protostellar Disk around a ˜0.2 M ⊙ Protostar in a Possible Site of a Multiple Star Formation in a Dynamical Environment in Taurus

    Tokuda, Kazuki; Onishi, Toshikazu; Saigo, Kazuya; Hosokawa, Takashi; Matsumoto, Tomoaki; Inutsuka, Shu-ichiro; Machida, Masahiro N.; Tomida, Kengo; Kunitomo, Masanobu; Kawamura, Akiko; Fukui, Yasuo; Tachihara, Kengo

    2017-11-01

    We report ALMA observations in 0.87 mm continuum and 12CO (J = 3-2) toward a very low-luminosity (<0.1 L ⊙) protostar, which is deeply embedded in one of the densest cores, MC27/L1521F, in Taurus with an indication of multiple star formation in a highly dynamical environment. The beam size corresponds to ˜20 au, and we have clearly detected blueshifted/redshifted gas in 12CO associated with the protostar. The spatial/velocity distributions of the gas show there is a rotating disk with a size scale of ˜10 au, a disk mass of ˜10-4 M ⊙, and a central stellar mass of ˜0.2 M ⊙. The observed disk seems to be detached from the surrounding dense gas, although it is still embedded at the center of the core whose density is ˜106 cm-3. The current low-outflow activity and the very low luminosity indicate that the mass accretion rate onto the protostar is extremely low in spite of a very early stage of star formation. We may be witnessing the final stage of the formation of ˜0.2 M ⊙ protostar. However, we cannot explain the observed low luminosity with the standard pre-main-sequence evolutionary track unless we assume cold accretion with an extremely small initial radius of the protostar (˜0.65 {R}⊙ ). These facts may challenge our current understanding of the low mass star formation, in particular the mass accretion process onto the protostar and the circumstellar disk.

  20. Climate change and spring frost damages for sweet cherries in Germany

    Chmielewski, Frank-M.; Götz, Klaus-P.; Weber, Katharina C.; Moryson, Susanne

    2018-02-01

    Spring frost can be a limiting factor in sweet cherry ( Prunus avium L.) production. Rising temperatures in spring force the development of buds, whereby their vulnerability to freezing temperatures continuously increases. With the beginning of blossom, flowers can resist only light frosts without any significant damage. In this study, we investigated the risk of spring frost damages during cherry blossom for historical and future climate conditions at two different sites in NE (Berlin) and SW Germany (Geisenheim). Two phenological models, developed on the basis of phenological observations at the experimental sweet cherry orchard in Berlin-Dahlem and validated for endodormancy release and for warmer climate conditions (already published), were used to calculate the beginning of cherry blossom in Geisenheim, 1951-2015 (external model validation). Afterwards, on the basis of a statistical regionalisation model WETTREG (RCP 8.5), the frequency of frost during cherry blossom was calculated at both sites for historical (1971-2000) and future climate conditions (2011-2100). From these data, we derived the final flower damage, defined as the percentage of frozen flowers due to single or multiple frost events during blossom. The results showed that rising temperatures in this century can premature the beginning of cherry blossom up to 17 days at both sites, independent of the used phenological model. The frequency and strength of frost was characterised by a high temporal and local variability. For both sites, no significant increase in frost frequency and frost damage during blossom was found. In Geisenheim, frost damages significantly decreased from the middle of the twenty-first century. This study additionally emphasises the importance of reliable phenological models which not only work for current but also for changed climate conditions and at different sites. The date of endodormancy release should always be a known parameter in chilling/forcing models.

  1. Optimal Siting and Sizing of Multiple DG Units for the Enhancement of Voltage Profile and Loss Minimization in Transmission Systems Using Nature Inspired Algorithms

    Ambika Ramamoorthy

    2016-01-01

    Full Text Available Power grid becomes smarter nowadays along with technological development. The benefits of smart grid can be enhanced through the integration of renewable energy sources. In this paper, several studies have been made to reconfigure a conventional network into a smart grid. Amongst all the renewable sources, solar power takes the prominent position due to its availability in abundance. Proposed methodology presented in this paper is aimed at minimizing network power losses and at improving the voltage stability within the frame work of system operation and security constraints in a transmission system. Locations and capacities of DGs have a significant impact on the system losses in a transmission system. In this paper, combined nature inspired algorithms are presented for optimal location and sizing of DGs. This paper proposes a two-step optimization technique in order to integrate DG. In a first step, the best size of DG is determined through PSO metaheuristics and the results obtained through PSO is tested for reverse power flow by negative load approach to find possible bus locations. Then, optimal location is found by Loss Sensitivity Factor (LSF and weak (WK bus methods and the results are compared. In a second step, optimal sizing of DGs is determined by PSO, GSA, and hybrid PSOGSA algorithms. Apart from optimal sizing and siting of DGs, different scenarios with number of DGs (3, 4, and 5 and PQ capacities of DGs (P alone, Q alone, and  P and Q both are also analyzed and the results are analyzed in this paper. A detailed performance analysis is carried out on IEEE 30-bus system to demonstrate the effectiveness of the proposed methodology.

  2. Flow cytometric evaluation of peripheral blood and bone marrow and fine-needle aspirate samples from multiple sites in dogs with multicentric lymphoma.

    Joetzke, Alexa E; Eberle, Nina; Nolte, Ingo; Mischke, Reinhard; Simon, Daniela

    2012-06-01

    To determine whether the extent of disease in dogs with lymphoma can be assessed via flow cytometry and to evaluate the suitability of fine-needle aspirates from the liver and spleen of dogs for flow cytometric examination. 44 dogs with multicentric B-cell (n = 35) or T-cell lymphoma (9) and 5 healthy control dogs. Procedures-Peripheral blood and bone marrow samples and fine-needle aspirates of lymph node, liver, and spleen were examined via flow cytometry. Logarithmically transformed T-cell-to-B-cell percentage ratio (log[T:B]) values were calculated. Thresholds defined by use of log(T:B) values of samples from control dogs were used to determine extranodal lymphoma involvement in lymphoma-affected dogs; results were compared with cytologic findings. 12 of 245 (5%) samples (9 liver, 1 spleen, and 2 bone marrow) had insufficient cellularity for flow cytometric evaluation. Mean log(T:B) values of samples from dogs with B-cell lymphoma were significantly lower than those of samples from the same site in dogs with T-cell lymphoma and in control dogs. In dogs with T-cell lymphoma, the log(T:B) of lymph node, bone marrow, and spleen samples was significantly higher than in control dogs. Of 165 samples assessed for extranodal lymphoma involvement, 116 (70%) tested positive via flow cytometric analysis; results agreed with cytologic findings in 133 of 161 (83%) samples evaluated via both methods. Results suggested that flow cytometry may aid in detection of extranodal lymphoma involvement in dogs, but further research is needed. Most fine-needle aspirates of liver and spleen were suitable for flow cytometric evaluation.

  3. Optimal Siting and Sizing of Multiple DG Units for the Enhancement of Voltage Profile and Loss Minimization in Transmission Systems Using Nature Inspired Algorithms.

    Ramamoorthy, Ambika; Ramachandran, Rajeswari

    2016-01-01

    Power grid becomes smarter nowadays along with technological development. The benefits of smart grid can be enhanced through the integration of renewable energy sources. In this paper, several studies have been made to reconfigure a conventional network into a smart grid. Amongst all the renewable sources, solar power takes the prominent position due to its availability in abundance. Proposed methodology presented in this paper is aimed at minimizing network power losses and at improving the voltage stability within the frame work of system operation and security constraints in a transmission system. Locations and capacities of DGs have a significant impact on the system losses in a transmission system. In this paper, combined nature inspired algorithms are presented for optimal location and sizing of DGs. This paper proposes a two-step optimization technique in order to integrate DG. In a first step, the best size of DG is determined through PSO metaheuristics and the results obtained through PSO is tested for reverse power flow by negative load approach to find possible bus locations. Then, optimal location is found by Loss Sensitivity Factor (LSF) and weak (WK) bus methods and the results are compared. In a second step, optimal sizing of DGs is determined by PSO, GSA, and hybrid PSOGSA algorithms. Apart from optimal sizing and siting of DGs, different scenarios with number of DGs (3, 4, and 5) and PQ capacities of DGs (P alone, Q alone, and P and Q both) are also analyzed and the results are analyzed in this paper. A detailed performance analysis is carried out on IEEE 30-bus system to demonstrate the effectiveness of the proposed methodology.

  4. Dramatic variability of the carbonate system at a temperate coastal ocean site (Beaufort, North Carolina, USA is regulated by physical and biogeochemical processes on multiple timescales.

    Zackary I Johnson

    Full Text Available Increasing atmospheric carbon dioxide (CO2 from anthropogenic sources is acidifying marine environments resulting in potentially dramatic consequences for the physical, chemical and biological functioning of these ecosystems. If current trends continue, mean ocean pH is expected to decrease by ~0.2 units over the next ~50 years. Yet, there is also substantial temporal variability in pH and other carbon system parameters in the ocean resulting in regions that already experience change that exceeds long-term projected trends in pH. This points to short-term dynamics as an important layer of complexity on top of long-term trends. Thus, in order to predict future climate change impacts, there is a critical need to characterize the natural range and dynamics of the marine carbonate system and the mechanisms responsible for observed variability. Here, we present pH and dissolved inorganic carbon (DIC at time intervals spanning 1 hour to >1 year from a dynamic, coastal, temperate marine system (Beaufort Inlet, Beaufort NC USA to characterize the carbonate system at multiple time scales. Daily and seasonal variation of the carbonate system is largely driven by temperature, alkalinity and the balance between primary production and respiration, but high frequency change (hours to days is further influenced by water mass movement (e.g. tides and stochastic events (e.g. storms. Both annual (~0.3 units and diurnal (~0.1 units variability in coastal ocean acidity are similar in magnitude to 50 year projections of ocean acidity associated with increasing atmospheric CO2. The environmental variables driving these changes highlight the importance of characterizing the complete carbonate system rather than just pH. Short-term dynamics of ocean carbon parameters may already exert significant pressure on some coastal marine ecosystems with implications for ecology, biogeochemistry and evolution and this shorter term variability layers additive effects and

  5. The potential impact of green agendas on historic river landscapes: Numerical modelling of multiple weir removal in the Derwent Valley Mills world heritage site, UK

    Howard, A. J.; Coulthard, T. J.; Knight, D.

    2017-09-01

    The exploitation of river systems for power and navigation has commonly been achieved through the installation of a variety of in-channel obstacles of which weirs in Britain are amongst the most common. In the UK, the historic value of many of these features is recognised by planning designations and protection more commonly associated with historic buildings and other major monuments. Their construction, particularly in the north and west of Britain, has often been associated with industries such as textiles, chemicals, and mining, which have polluted waterways with heavy metals and other contaminants. The construction of weirs altered local channel gradients resulting in sedimentation upstream with the potential as well for elevated levels of contamination in sediments deposited there. For centuries these weirs have remained largely undisturbed, but as a result of the growth in hydropower and the drive to improve water quality under the European Union's Water Framework Directive, these structures are under increasing pressure to be modified or removed altogether. At present, weir modifications appear to be considered largely on an individual basis, with little focus on the wider impacts this might have on valley floor environments. Using a numerical modelling approach, this paper simulates the removal of major weirs along a 24-km stretch of the river Derwent, Derbyshire, UK, designated as a UNESCO World Heritage Site. The results suggest that although removal would not result in significant changes to the valley morphology, localised erosion would occur upstream of structures as the river readjusts its base level to new boundary conditions. Modelling indicates that sediment would also be evacuated away from the study area. In the context of the Derwent valley, this raises the potential for the remobilisation of contaminants (legacy sediments) within the wider floodplain system, which could have detrimental, long-term health and environmental implications for the

  6. Capturing Snapshots of APE1 Processing DNA Damage

    Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; Dyrkheeva, Nadezhda S.; Wilson, Samuel H.

    2015-01-01

    DNA apurinic-apyrimidinic (AP) sites are prevalent non-coding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive due in part to limited structural information. We report multiple high-resolution human APE1:DNA structures that divulge novel features of the APE1 reaction, including the metal binding site, nucleophile, and arginine clamps that mediate product release. We also report APE1:DNA structures with a T:G mismatch 5′ to the AP-site, representing a clustered lesion occurring in methylated CpG dinucleotides. These reveal that APE1 molds the T:G mismatch into a unique Watson-Crick like geometry that distorts the active site reducing incision. These snapshots provide mechanistic clarity for APE1, while affording a rational framework to manipulate biological responses to DNA damage. PMID:26458045

  7. Radiation damage of nonmetallic solids

    Goland, A.N.

    1975-01-01

    A review of data and information on radiation damage in nonmetallic solids is presented. Discussions are included on defects in nonmetals, radiation damage processes in nonmetals, electronic damage processes, physical damage processes, atomic displacement, photochemical damage processes, and ion implantation

  8. Black bear damage to northwestern conifers in California: a review

    Kenneth O. Fulgham; Dennis Hosack

    2017-01-01

    A total of 789 black bear damaged trees were investigate over a multi-year period on 14 different study sites chosen on lands of four participating timber companies. The sites ranged from 30 to 50 years of age. Four different conifer species were found to have black bear damage: coastal redwood (Sequoia sempervirens (D. Don) Endl.), Douglas-fir (...

  9. Categorization skills and recall in brain damaged children: a multiple case study Habilidades de categorização e recordação em crianças com lesões cerebrais: um estudo de casos multiplos

    Claudia Berlim de Mello

    2009-09-01

    Full Text Available During development, children become capable of categorically associating stimuli and of using these relationships for memory recall. Brain damage in childhood can interfere with this development. This study investigated categorical association of stimuli and recall in four children with brain damages. The etiology, topography and timing of the lesions were diverse. Tasks included naming and immediate recall of 30 perceptually and semantically related figures, free sorting, delayed recall, and cued recall of the same material. Traditional neuropsychological tests were also employed. Two children with brain damage sustained in middle childhood relied on perceptual rather than on categorical associations in making associations between figures and showed deficits in delayed or cued recall, in contrast to those with perinatal lesions. One child exhibited normal performance in recall despite categorical association deficits. The present results suggest that brain damaged children show deficits in categorization and recall that are not usually identified in traditional neuropsychological tests.No desenvolvimento, as crianças tornam-se capazes de associar estímulos em categorias e de se beneficiar dessas associações para sua recordação posterior. Lesões cerebrais na infância podem interferir nesse desenvolvimento. Neste estudo, essas habilidades foram avaliadas em crianças com lesões cerebrais. A etiologia, topografia e época de instalação da lesão variaram. As tarefas incluíram: nomeação e recordação imediata de 30 figuras relacionadas perceptual e semanticamente; associação livre; recordação tardia e recordação com pistas. Testes neuropsicológicos tradicionais também foram usados. Duas crianças com lesões adquiridas na fase escolar associaram as figuras baseadas em relações perceptivas e não categóricas e apresentaram déficits de recordação tardia e com pistas, ao contrario das outras duas com lesões perinatais

  10. Femoral nerve damage (image)

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  11. Ozone Damages to Mediterranean Crops: Physiological Responses

    Albino Maggio

    2008-03-01

    Full Text Available In this brief review we analyzed some aspects of tropospheric ozone damages to crop plants. Specifically, we addressed this issue to Mediterranean environments, where plant response to multiple stresses may either exacerbate or counteract deleterious ozone effects. After discussing the adequacy of current models to predict ozone damages to Mediterranean crops, we present a few examples of physiological responses to drought and salinity stress that generally overlap with seasonal ozone peaks in Southern Italy. The co-existence of multiple stresses is then analyzed in terms of stomatal vs. non-stomatal control of ozone damages. Recent results on osmoprotectant feeding experiments, as a non-invasive strategy to uncouple stomatal vs. non stomatal contribution to ozone protection, are also presented. In the final section, we discuss critical needs in ozone research and the great potential of plant model systems to unravel multiple stress responses in agricultural crops.

  12. Ozone Damages to Mediterranean Crops: Physiological Responses

    Massimo Fagnano

    2011-02-01

    Full Text Available In this brief review we analyzed some aspects of tropospheric ozone damages to crop plants. Specifically, we addressed this issue to Mediterranean environments, where plant response to multiple stresses may either exacerbate or counteract deleterious ozone effects. After discussing the adequacy of current models to predict ozone damages to Mediterranean crops, we present a few examples of physiological responses to drought and salinity stress that generally overlap with seasonal ozone peaks in Southern Italy. The co-existence of multiple stresses is then analyzed in terms of stomatal vs. non-stomatal control of ozone damages. Recent results on osmoprotectant feeding experiments, as a non-invasive strategy to uncouple stomatal vs. non stomatal contribution to ozone protection, are also presented. In the final section, we discuss critical needs in ozone research and the great potential of plant model systems to unravel multiple stress responses in agricultural crops.

  13. Deltoid contracture: a case with multiple muscle contractures.

    Chen, Hsin-Chang; Huang, Tung-Fu; Chou, Po-Hsin; Chen, Tain-Hsiung

    2008-11-01

    Deltoid contracture is relatively uncommon. The literature consists primarily of case reports and few articles on large case series. The pathogenesis has been well studied. Muscle contractures can occur in the deltoid, biceps, triceps, gluteus and quadriceps muscles; however, cases of multiple muscle contractures are rare. We reported a patient with multiple contractures of the bilateral deltoid, bilateral gluteus, and bilateral quadriceps muscles, who had received repeated intramuscular injections during childhood and adulthood. The radiographic, including magnetic resonance imaging (MRI), features of the bone and joint abnormalities are presented. Some literatures reported that damage to the structures of the body due to intramuscular injection is related to the site of injection, age of the patient, and the volume, pH, chemical composition, and diffusional capacity of the injectate. Our patient had muscular contracture induced by needle injection regardless of her age, medication and injection site.

  14. Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

    Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

  15. Drug-Induced Liver Injury by Glatiramer Acetate Used for Treatment of Multiple Sclerosis

    Attila Onmez

    2013-12-01

    Full Text Available Glatiramer acetate (GA, Copaxone is an approved drug for the treatment of relapsing–remitting multiple sclerosis. Most common side effects observed with GA are local injection site reactions, which can include pain, swelling, or redness. However, systemic adverse event such as hepatotoxicity related to GA is rarely seen. In this report, we present a case of GA-induced toxic hepatitis associated with cholestatic and hepatocellular damage.

  16. Radiation damage to histones

    Mee, L.K.; Adelstein, S.J.

    1985-01-01

    The damage to histones irradiated in isolation is being elaborated to aid the identification of the crosslinking sites in radiation-induced DNA-histone adducts. Histones are being examined by amino acid analysis to determine the destruction of residues and by polyacrylamide gel electrophoresis to delineate changes in conformation. For the slightly lysine-rich histone, H2A, a specific attack on selective residues has been established, the aromatic residues, tyrosine and phenylalanine, and the heterocyclic residue, histidine, being significantly destroyed. In addition, a significant increase in aspartic acid was found; this may represent a radiation product from scission of the ring in the histidine residues. The similarity of the effects on residues in nitrous oxide-saturated and nitrogen-saturated solutions suggests that OH . and e/sub aq//sup -/ are equally efficient and selective in their attack. On gel electrophoresis degradation of the histone H2A was found to be greatest for irradiations in nitrous oxide-saturated solutions, suggesting CH . is the most effective radical for producing changes in conformation; O/sub 2//sup -/ was essentially ineffective. Other histones are being examined for changes in amino acid composition, conformation, and for the formation of radiation products

  17. Special technology with high safety-related standards for the repair of the wellhead damage of a gas filled cavern at storage site Stassfurt; Spezialtechnologie mit hohen Sicherheitsvorkehrungen zur Beseitigung des Bohrlochkopfschadens einer Gaskaverne des Kavernenspeichers Stassfurt

    Walden, S.; Klafki, M. [ESK-Erdgasspeicher Kalle GmbH, Freiberg (Germany)

    2008-11-15

    For the completion of the cavern Stassfurt S 106 which was leached by the so called ''solution mining under gas'' technology, the leaching strings 6 5/8''-4 1/2'' should be pulled out by using a snubbing unit. Due to an unexpected damage at the wellhead, the job could not be realized as projected. Therefore the snubbing work was stopped. For solving the technical damage different repair concepts were investigated, for example partial flooding of the cavern with brine or water, sealing of wellhead components by freezing or cutting of the lower leaching string section and setting plugs afterwards. All concepts had been evaluated concerning feasibility and risks. The most favourable technology was selected on the basis of a comparison of pros and cons and was planned for realization according to a detailed working programme. The specialized contractors as well as the fire brigade have guaranteed the required safety measures. The essential planning and working steps will be described as well as the acquired experiences will be explained in the following section. Finally, it can be stated that all jobs were realized according to the projected programme and all involved persons perfectly worked with the special technologies. (orig.)

  18. Forest decline: Verification of phytohormones and secondary plant constituents (especially flavonoids and sesquiterpenes) in healthy and damaged needles from a natural site (Wank) with a defined pollutant load and defined infectious diseases (continuation). Final report. Waldschaeden: Nachweis von Phytohormonen und sekundaeren Pflanzenstoffen (vor allem Flavonoiden und Sesquiterpenen) in gesunden und geschaedigten Nadeln vom natuerlichen Standort (Wank), bei definierter Schadstoffbelastung und definierten Infektionskrankheiten (Fortsetzung). Abschlussbericht

    Ziegler, H; Kraus, M; Deigele, C

    1992-03-01

    The aim of the project was to study the formation and accumulation of the phytohormone abscisic acid and soluble phenolic compounds and terpenes in spruce and fir needles with a view to various parameters (season, needle age, degree of damage, distribution within the tree crown, and site altitude), in the Wank forest under field conditions. For the extraction and clean-up of abscisic acid (ABA) a method by Doerffling was modified, and for its quantitative analysis ELISA, HPLC, GC with flame ionization and GC with electron capturing detector were tested and the latter chosen. In individual trees needles from the crown top had increased ABA content; needle age and degree of damage had no significant effect; the year curve showed a maximum in May/June and a minimum in August/September. As regards some soluble phenolic compounds, young needles, unlike older ones, have a year curve; the concentrations of some SPCs increase with altitude above mean sea level (ultraviolet radiation protection function, ozone effect possible but not confirmed), while the concentrations of some monoterpenes go down. Young needles (of cloned spruces) have no day curve for monoterpenes, but their concentration increases where water is scarce. The degree of damage (chlorotic needles, loss of needles) and SPC, monoterpene and sesquiterpene levels are not associated. (orig.)

  19. Theory of inner product vector and its application to multi-location damage detection

    Wang Le; Yang Zhichun; Zhang Muyu; Waters, T P

    2011-01-01

    Structural damage detection methods using time domain vibration responses have shown appeal in recent years. In previous papers by the authors, the inner product vector (IPV) was proposed as a damage detection algorithm which uses cross correlation functions between vibration responses under white noise excitation or band pass white noise excitation. The proposed algorithm was verified by some simulative and experimental examples featuring a single damage location. However, damage at multiple locations was not considered. Therefore, this paper extends the application of IPV-based structural damage detection to the problem of multiple damage locations. Firstly, the theory of the IPV and its implementation in a damage detection context is reviewed. Then, two strategies for detecting multiple damages utilizing IPV are proposed. Finally, a damage detection experiment of a honeycomb sandwich composite beam is adopted to illustrate the feasibility and effectiveness of the IPV-based damage detection method.

  20. Importance of secondary damage in downer cows.

    Poulton, P J; Vizard, A L; Anderson, G A; Pyman, M F

    2016-05-01

    To investigate the relative importance in downer cows of the primary cause of recumbency in comparison with secondary complications. Downer dairy cows were monitored during their recumbency under field conditions in South Gippsland, Victoria, Australia. The cause of the original recumbency of the 218 cows was determined and secondary damage, status on day 7 and final outcome were recorded. Some type of secondary damage was found in 183/218 (84%) cows, of which 173/218 (79%) had damage deemed to be clinically important. By day 7, 52 (24%) had recovered and 69 (32%) eventually recovered. Of the 149 (68%) cows that were euthanased or died, 23 (15%) were deemed to have been lost solely from the primary cause, 107 (72%) from secondary damage and 19 (13%) from a combination of both. There was no difference in recovery among the five broad groups of causes of primary recumbency. Secondary damage was very common and presented in a large variety of ways, with many cows having multiple types of secondary damage concurrently. For most cows the secondary damage was more important than the initial primary damage in determining their fate. © 2016 Australian Veterinary Association.

  1. Treatment of Multiple Sclerosis

    Bošnjak-Pašić, Marija; Vidrih, Branka; Miškov, Snježana; Demarin, Vida

    2009-01-01

    Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system, characterized by multifocal inflammatory destruction of myelin, axonal damage and loss of oligodendrocytes. The disease is carried through two stages: inflammatory and degenerative. The most common form of disease in approximately 85% of the cases is RRMS (relapsing-remitting form). The treatment of MS is divided into: treatment of the acute phase of illness, prevention of new relapses and di...

  2. Midkine and multiple sclerosis

    Takeuchi, Hideyuki

    2014-01-01

    Multiple sclerosis (MS) is an autoimmune neurological disease characterized by inflammatory demyelination with subsequent neuronal damage in the CNS. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have been thought as autoreactive Th1 and Th17 cell-mediated diseases. CD4+CD25+FoxP3+ regulatory T-cell (Treg) plays a pivotal role in autoimmune tolerance, and tolerogenic dendritic cells (DCreg) drive the development of inducible Treg cells. Thus, a dysfunction in the d...

  3. Comparison of serum markers for muscle damage, surgical blood loss, postoperative recovery, and surgical site pain after extreme lateral interbody fusion with percutaneous pedicle screws or traditional open posterior lumbar interbody fusion.

    Ohba, Tetsuro; Ebata, Shigeto; Haro, Hirotaka

    2017-10-16

    The benefits of extreme lateral interbody fusion (XLIF) as a minimally invasive lumbar spinal fusion treatment for lumbar degenerative spondylolisthesis have been unclear. We sought to evaluate the invasiveness and tolerability of XLIF with percutaneous pedicle screws (PPS) compared with traditional open posterior lumbar interbody fusion (PLIF). Fifty-six consecutive patients underwent open PLIF and 46 consecutive patients underwent single-staged treatment with XLIF with posterior PPS fixation for degenerative lumbar spondylolisthesis, and were followed up for a minimum of 1 year. We analyzed postoperative serum makers for muscle damage and inflammation, postoperative surgical pain, and performance status. A Roland-Morris Disability Questionnaire (RDQ) and Oswestry Disability Index (ODI) were obtained at the time of hospital admission and 1 year after surgery. Intraoperative blood loss (51 ± 41 ml in the XLIF/PPS group and 206 ± 191 ml in the PLIF group), postoperative WBC counts and serum CRP levels in the XLIF/PPS group were significantly lower than in the PLIF group. Postoperative serum CK levels were significantly lower in the XLIF/PPS group on postoperative days 4 and 7. Postoperative recovery of performance was significantly greater in the XLIF/PPS group than in the PLIF group from postoperative days 2 to 7. ODI and visual analog scale (VAS) score (lumbar) 1 year after surgery were significantly lower in the XLIF/PPS group compared with the PLIF group. The XLIF/PPS procedure is advantageous to minimize blood loss and muscle damage, with consequent earlier recovery of daily activities and reduced incidence of low back pain after surgery than with the open PLIF procedure.

  4. Delayed chromosomal instability induced by DNA damage

    Morgan, W.F.; Marder, B.A.; Day, J.P.

    1994-01-01

    Cellular exposure to DNA damaging agents rapidly results in a dose dependent increase in chromosomal breakage and gross structural chromosomal rearrangements. Over recent years, evidence has been accumulating indicating genomic instability can manifest multiple generations after cellular exposure to physical and chemical DNA damaging agents. Genomic instability manifests in the progeny of surviving cells, and has been implicated in mutation, gene application, cellular transformation, and cell killing. To investigate chromosome instability following DNA damage, we have used fluorescence in situ hybridization to detect chromosomal rearrangements in a human/hamster somatic hybrid cell line following exposure to ionizing radiation. Delayed chromosomal instability was detected when multiple populations of uniquely arranged metaphases were observed in clonal isolates raised from single cells surviving X-irradiation many generations after exposure. At higher radiation doses, chromosomal instability was observed in a relatively high frequency of surviving clones and, in general, those clones showed delayed chromosome instability also showed reduced survival as measured by colony forming ability

  5. Chemokines and Chemokine Receptors in Multiple Sclerosis

    Wenjing Cheng

    2014-01-01

    Full Text Available Multiple sclerosis is an autoimmune disease with classical traits of demyelination, axonal damage, and neurodegeneration. The migration of autoimmune T cells and macrophages from blood to central nervous system as well as the destruction of blood brain barrier are thought to be the major processes in the development of this disease. Chemokines, which are small peptide mediators, can attract pathogenic cells to the sites of inflammation. Each helper T cell subset expresses different chemokine receptors so as to exert their different functions in the pathogenesis of MS. Recently published results have shown that the levels of some chemokines and chemokine receptors are increased in blood and cerebrospinal fluid of MS patients. This review describes the advanced researches on the role of chemokines and chemokine receptors in the development of MS and discusses the potential therapy of this disease targeting the chemokine network.

  6. Repair of abasic sites in DNA

    Dianov, Grigory L.; Sleeth, Kate M.; Dianova, Irina I.; Allinson, Sarah L

    2003-10-29

    Repair of both normal and reduced AP sites is activated by AP endonuclease, which recognizes and cleaves a phosphodiester bond 5' to the AP site. For a short period of time an incised AP site is occupied by poly(ADP-ribose) polymerase and then DNA polymerase {beta} adds one nucleotide into the repair gap and simultaneously removes the 5'-sugar phosphate. Finally, the DNA ligase III/XRCC1 complex accomplishes repair by sealing disrupted DNA ends. However, long-patch BER pathway, which is involved in the removal of reduced abasic sites, requires further DNA synthesis resulting in strand displacement and the generation of a damage-containing flap that is later removed by the flap endonuclease. Strand-displacement DNA synthesis is accomplished by DNA polymerase {delta}/{epsilon} and DNA ligase I restores DNA integrity. DNA synthesis by DNA polymerase {delta}/{epsilon} is dependent on proliferating cell nuclear antigen, which also stimulates the DNA ligase I and flap endonuclease. These repair events are supported by multiple protein-protein interactions.

  7. Multiple sclerosis

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  8. Radiation damage to mushrooms

    Sattler, P.W.

    1986-01-01

    This document contains newspaper cuttings and correspondence with various ministries in Hessen on the subject of radiation damage to mushrooms from the Odenwald area. The reader is given, amongst other things, detailed information on radiation damage to different types of mushroom in 1986. (MG) [de

  9. Animal damage to birch

    James S. Jordan; Francis M. Rushmore

    1969-01-01

    A relatively few animal species are responsible for most of the reported damage to the birches. White-tailed deer, yellow-bellied sapsuckers, porcupines, moose, and hares are the major animals involved. We will review reports of damage, discuss the underlying causes, and describe possible methods of control. For example, heavy deer browsing that eliminates birch...

  10. Animal damage management handbook.

    Hugh C. Black

    1994-01-01

    This handbook treats animal damage management (ADM) in the West in relation to forest, range, and recreation resources; predator management is not addressed. It provides a comprehensive reference of safe, effective, and practical methods for managing animal damage on National Forest System lands. Supporting information is included in references after each chapter and...

  11. Nuclear damage - civil liability

    Simoes, A.C.

    1980-01-01

    An analysis is made of the civil liability for nuclear damage since there is a need to adjust the existing rules to the new situations created. The conventions that set up the new disciplining rules not considered in the common law for the liability of nuclear damage are also mentioned. (A.L.) [pt

  12. DNA damage and autophagy

    Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely; Panayiotidis, Mihalis I.; Franco, Rodrigo

    2011-01-01

    Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.

  13. Molecular models for DNA damaged by photoreaction

    Pearlman, D.A.; Holbrook, S.R.; Pirkle, D.H.; Kim, S.H.

    1985-01-01

    Structural models of a DNA molecule containing a radiation-induced psoralen cross-link and of a DNA containing a thymine photodimer were constructed by applying energy-minimization techniques and model-building procedures to data from x-ray crystallographic studies. The helical axes of the models show substantial kinking and unwinding at the sites of the damage, which may have long-range as well as local effects arising from the concomitant changes in the supercoiling and overall structure of the DNA. The damaged areas may also serve as recognition sites for repair enzymes. These results should help in understanding the biologic effects of radiation-induced damage on cells

  14. 127 REMEDIES FOR ENVIRONMENTAL DAMAGE UNDER THE ...

    Fr. Ikenga

    continuing to dump waste at the site; and (iii) of mandamus to direct the Dar Es ..... Act 2007, from failure of a person with or without lawful authority to exercise the care .... exemplary damages), to punish the defendant for particularly obnoxious ...

  15. Improving Flood Damage Assessment Models in Italy

    Amadio, M.; Mysiak, J.; Carrera, L.; Koks, E.

    2015-12-01

    The use of Stage-Damage Curve (SDC) models is prevalent in ex-ante assessments of flood risk. To assess the potential damage of a flood event, SDCs describe a relation between water depth and the associated potential economic damage over land use. This relation is normally developed and calibrated through site-specific analysis based on ex-post damage observations. In some cases (e.g. Italy) SDCs are transferred from other countries, undermining the accuracy and reliability of simulation results. Against this background, we developed a refined SDC model for Northern Italy, underpinned by damage compensation records from a recent flood event. Our analysis considers both damage to physical assets and production losses from business interruptions. While the first is calculated based on land use information, production losses are measured through the spatial distribution of Gross Value Added (GVA). An additional component of the model assesses crop-specific agricultural losses as a function of flood seasonality. Our results show an overestimation of asset damage from non-calibrated SDC values up to a factor of 4.5 for tested land use categories. Furthermore, we estimate that production losses amount to around 6 per cent of the annual GVA. Also, maximum yield losses are less than a half of the amount predicted by the standard SDC methods.

  16. Natural resource damage assessments: The second generation

    Luthi, R.; Burlington, L.; Reinharz, E.; Shutler, S.

    1993-01-01

    The Damage Assessment Regulations Team (DART), Office of General Counsel, National Oceanic and Atmospheric Administration (NOAA), has focused on developing natural resource damage assessment regulations for oil pollution in navigable waters. These procedures may lower the transaction costs of assessments, encourage joint cooperative assessments, simplify most assessments and provide technical guidance for conducting assessments. DART is developing regulations for the assessment of damages due to injuries related to oil spills under the Oil pollution Act of 1990. These regulations will involve coordination, restoration and economic valuation. NOAA encourages federal, state, tribal and foreign trustees, to develop prespill plans. Coordination with response agencies assures protection of important natural resources. The regulations provide an open record, which becomes the basis for judicial review. Various methods being developed to assess damages for injuries to natural resources include: compensation formulas for spills under 50,000 gallons of oil, the Type A model, expedited damage assessment (EDA) procedures, and comprehensive damage assessment (CDA) procedures which can be used for spills of various sizes. These procedures provide trustees with a choice for assessing natural resource damages to each oil spill. NOAA is emphasizing the importance of restoration. Restoration plans will define project goals and objectives, establish procedures and methods for site restoration, and define the approach based on sound science. Finally, numerous economic methods are identified to calculate the lost or diminished use as passive use of the affected resources

  17. Metabolite Damage and Metabolite Damage Control in Plants

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  18. Distribution patterns of postmortem damage in human mitochondrial DNA

    Gilbert, M Thomas P; Willerslev, Eske; Hansen, Anders J

    2002-01-01

    1 (HVR1) and cytochrome oxidase subunit III genes. A comparison of damaged sites within and between the regions reveals that damage hotspots exist and that, in the HVR1, these correlate with sites known to have high in vivo mutation rates. Conversely, HVR1 subregions with known structural function......, such as MT5, have lower in vivo mutation rates and lower postmortem-damage rates. The postmortem data also identify a possible functional subregion of the HVR1, termed "low-diversity 1," through the lack of sequence damage. The amount of postmortem damage observed in mitochondrial coding regions...... was significantly lower than in the HVR1, and, although hotspots were noted, these did not correlate with codon position. Finally, a simple method for the identification of incorrect archaeological haplogroup designations is introduced, on the basis of the observed spectrum of postmortem damage....

  19. Laser induced damage threshold on metallic surfaces during laser cleaning

    Labuschagne, K

    2005-07-01

    Full Text Available laser paint removal. Laser induced damage on 316L stainless steel was studied, with the target subjected to single and multiple pulse irradiations using a Q-switched Nd:YAG, with fluences between 0.15 and 11.8 J/cm2. Several different damage morphologies...

  20. DNA damage and polyploidization.

    Chow, Jeremy; Poon, Randy Y C

    2010-01-01

    A growing body of evidence indicates that polyploidization triggers chromosomal instability and contributes to tumorigenesis. DNA damage is increasingly being recognized for its roles in promoting polyploidization. Although elegant mechanisms known as the DNA damage checkpoints are responsible for halting the cell cycle after DNA damage, agents that uncouple the checkpoints can induce unscheduled entry into mitosis. Likewise, defects of the checkpoints in several disorders permit mitotic entry even in the presence of DNA damage. Forcing cells with damaged DNA into mitosis causes severe chromosome segregation defects, including lagging chromosomes, chromosomal fragments and chromosomal bridges. The presence of these lesions in the cleavage plane is believed to abort cytokinesis. It is postulated that if cytokinesis failure is coupled with defects of the p53-dependent postmitotic checkpoint pathway, cells can enter S phase and become polyploids. Progress in the past several years has unraveled some of the underlying principles of these pathways and underscored the important role of DNA damage in polyploidization. Furthermore, polyploidization per se may also be an important determinant of sensitivity to DNA damage, thereby may offer an opportunity for novel therapies.

  1. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

    Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

    2017-01-01

    Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  2. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach

    Mario Stampanoni Bassi

    2017-12-01

    Full Text Available Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS, structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the “clinico-radiological paradox.” The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  3. Structural damage detection using higher-order finite elements and a scanning laser vibrometer

    Jin, Si

    Deflection Shapes (ODSs) measured by the scanning laser vibrometer. The BED method decomposes an ODS into central and boundary solutions by using a sliding-window least-squares fitting technique. Because boundary solutions are non-zero only at damage sites as well as structural boundaries, they can reveal damage locations. Three signal processing methods are developed for use in the BED method: (1) processing 1-D ODSs (i.e., beams) using a sliding-window curve-fitting technique, (2) processing 2-D ODSs (i.e., plates) using a sliding-window surface-fitting technique, and (3) processing 2-D ODSs using a sliding-window curve-fitting technique. Experiments are performed on isotropic beams and plates with different types of damage. At a damage location on a beam, results show that the boundary solution of slope changes sign, the boundary solution of displacement peaks up or dimples down, the fitting error peaks up, and second and third spatial derivatives show sudden changes. For plates, results show that sensitive damage detection parameters are boundary solutions and parameters related to bending moments and shear forces because they show significant sign changes or peaks at damage locations. All the results show that the BED method is more sensitive than other dynamics-based methods using curvatures and/or strain energies. Moreover, because the BED method works without using any structural models or historical data and it provides multiple damage detection parameters for users to ensure the identified damage locations, it is a reliable method and is applicable to actual structures.

  4. Seasonal and Inter-annual Phenological Varibility is Greatest in Low-Arctic and Wet Sites Across the North Slope of Alaska as Observed from Multiple Remote Sensing Platforms

    Vargas, S. A., Jr.; Andresen, C. G.; May, J. L.; Oberbauer, S. F.; Hollister, R. D.; Tweedie, C. E.

    2017-12-01

    The Arctic is experiencing among the most dramatic impacts from climate variability on the planet. Arctic plant phenology has been identified as an ideal indicator of climate change impacts and provides great insight into seasonal and inter-annual vegetative trends and their responses to such changes. Traditionally, phenology has been quantified using satellite-based systems and plot-level observations but each approach presents limitations especially in high latitude regions. Mid-scale systems (e.g. automated sensor platforms and trams) have shown to provide alternative, and in most cases, cheaper solutions with comparable results to those acquired traditionally. This study contributes to the US Arctic Observing Network (AON) and assesses the effectiveness of using digital images acquired from pheno-cams, a kite aerial photography (KAP) system, and plot-level images (PLI) in their capacity to assess phenological variability (e.g. snow melt, greening and end-of-season) for dominant vegetation communities present at two sites in both Utqiagvik and Atqasuk, Alaska, namely the Mobile Instrumented Sensor Platform (MISP) and the Circum-arctic Active Layer Monitoring (CALM) grids. RGB indices (e.g. GEI and %G) acquired from these methods were compared to the normalized difference vegetation index (NDVI) calculated from multispectral ground-based reflectance measurements, which has been identified and used as a proxy of primary productivity across multiple ecosystems including the Arctic. The 5 years of growing season data collected generally resulted with stronger Pearson's correlations between indices located in plots containing higher soil moisture versus those that were drier. Future studies will extend platform inter-comparison to the satellite level by scaling trends to MODIS land surface products. Trends documented thus far, however, suggest that the long-term changes in satellite NDVI for these study areas, could be a direct response from wet tundra landscapes.

  5. LSD and Genetic Damage

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  6. Diabetes and nerve damage

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  7. Detection of laser damage by Raman microscopy

    Fauchet, P.M.; Campbell, I.H.; Adar, F.

    1988-01-01

    The authors demonstrate that Raman miroscopy is a sensitive and quantitative tool to detect and characterize laser-induced damage in solids. After damage is induced with single or multiple high power laser pulses, a Raman microprobe maps the surface of the sample with one micron spatial resolution. By performing accurate measurements of the Stokes line, the authors have been able to measure stress, strain and crystallinity in various samples which had been exposed to high intensity pulses. These results are compared to those obtained using conventional tools such as Nomarski microscopy. Major advantages of Raman microscopy include sensitivity to subtle structural modifications and the fact that it gives quantitative measurements

  8. Picosecond laser damage of fused silica at 355 nm

    Meng Xiangjie; Liu Hongjie; Wang Fang; Zhang Zhen; An Xinyou; Huang Jin; Jiang Xiaodong; Wu Weidong; Ren Weiyi

    2013-01-01

    This paper studies the initiated damage threshold, the damage morphology and the subsequent damage growth on fused silica's input-surface and exit-surface under picosecond laser irradiation at 355 nm. Defects induced fluorescence on surface of the optical component is observed. The results demonstrate a significant dependence of the initiated damage on pulse duration and surface defects, and that of the damage growth on self-focusing, sub-surface defects. The damage-threshold is 3.98 J/cm 2 of input surface and 2.91 J/cm 2 of exit surface. The damage morphologies are quite different between input surface and exit surface. Slow growth behavior appears for the diameter of exit-surface and linear growth one for the depth of exit-surface in the lateral side of damage site with the increase of shot number. Defects have changed obviously compared with nanosecond laser damage in the damage area. Several main reasons such as electric intensification and self-focusing for the observed initiated damage and damage growth behavior are discussed. (authors)

  9. Laser-Induced Damage Growth on Larger-Aperture Fused Silica Optical Components at 351 nm

    Wan-Qing, Huang; Wei, Han; Fang, Wang; Yong, Xiang; Fu-Quan, Li; Bin, Feng; Feng, Jing; Xiao-Feng, Wei; Wan-Guo, Zheng; Xiao-Min, Zhang

    2009-01-01

    Laser-induced damage is a key lifetime limiter for optics in high-power laser facility. Damage initiation and growth under 351 nm high-fluence laser irradiation are observed on larger-aperture fused silica optics. The input surface of one fused silica component is damaged most severely and an explanation is presented. Obscurations and the area of a scratch on it are found to grow exponentially with the shot number. The area of damage site grows linearly. Micrographs of damage sites support the micro-explosion damage model which could be used to qualitatively explain the phenomena

  10. Radiation damage in He implanted silicon at high temperature using multi-energies

    David, M L; Oliviero, E; Denanot, M F; Beaufort, M F; Declemy, A; Blanchard, C; Gerasimenko, N N; Barbot, J F

    2002-01-01

    He sup + ions were implanted at 800 deg. C into (1 0 0) silicon with multiple energies and selected fluences to get a number of displacement per atom constant in a large plateau. The ion-related defects have been mainly studied by transmission electron microscopy. Both the amount and the microstructure of defects have been found to be strongly dependent on the order of implants. Faceted cavities are only observed where damage overlapping occurs. The first implant provides thus nucleation sites for cavities. The generation of these sites is less efficient when using increasing energies because of damage recovery; fewer cavities are observed. Concurrently interstitial-type defects, left brace 1 1 3 right brace agglomerates, are formed. The observed state of growth of these left brace 1 1 3 right brace defects (rod-like and ribbon-like defects) is dependent on the implantation energy order but in any cases, no dislocation loops are observed even in the deepest damage region.

  11. Determination on Damage Mechanism of the Planet Gear of Heavy Vehicle Final Drive

    Ramdan, RD; Setiawan, R.; Sasmita, F.; Suratman, R.; Taufiqulloh

    2018-02-01

    The works focus on the investigation of damage mechanism of fractured in the form of spalling of the planet gears from the final drive assembly of 160-ton heavy vehicles. The objective of this work is to clearly understand the mechanism of damage. The work is the first stage of the on-going research on the remaining life estimation of such gears. The understanding of the damage mechanism is critical in order to provide accurate estimate of the gear’s remaining life with observed initial damage. The analysis was performed based on the metallurgy laboratory works, including visual observation, macro-micro fractography by optical stereo and optical microscope and micro-vickers hardness test. From visual observation it was observed pitting that form lining defect at common position, which is at gear flank position. From spalling sample it was observed ratchet mark at the boundary between macro pitting and the edge of fractured parts. Further observation on the cross-section of the samples by optical microscope confirm that initial micro pitting occur without spalling of the case hardened surface. Spalling occur when pitting achieve certain critical size, and occur at multiple initiation site of crack propagation. From the present research it was concluded that pitting was resulted due to repeated contact fatigue. In addition, development of micro to macro pitting as well as spalling occur at certain direction towards the top of the gear teeth.

  12. Multiple sclerosis

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  13. Multiple intracranial hydatid cysts: MR findings

    Pumar, J.; Alvarez, M.; Leira, R.; Prieto, J.M.; Arrojo, L.; Pereira, J.; Vidal, J.

    1992-01-01

    Multiple intracranial hydatid cysts are uncommon and usually localized in the supratentorial compartment. We report a case studied by CT and MR of multiple intracranial hydatid cysts scattered in various anatomic sites: supratentorial, infratentorial and also intraventricular. (orig.)

  14. Damage instability and Earthquake nucleation

    Ionescu, I. R.; Gomez, Q.; Campillo, M.; Jia, X.

    2017-12-01

    Earthquake nucleation (initiation) is usually associated to the loss of the stability of the geological structure under a slip-weakening friction acting on the fault. The key parameters involved in the stability of the fault are the stress drop, the critical slip distance but also the elastic stiffness of the surrounding materials (rocks). We want to explore here how the nucleation phenomena are correlated to the material softening during damage accumulation by dynamic and/or quasi-static processes. Since damage models are describing micro-cracks growth, which is generally an unstable phenomenon, it is natural to expect some loss of stability on the associated micro-mechanics based models. If the model accurately captures the material behavior, then this can be due to the unstable nature of the brittle material itself. We obtained stability criteria at the microscopic scale, which are related to a large class of damage models. We show that for a given continuous strain history the quasi-static or dynamic problems are instable or ill-posed (multiplicity of material responses) and whatever the selection rule is adopted, shocks (time discontinuities) will occur. We show that the quasi-static equilibria chosen by the "perfect delay convention" is always stable. These stability criteria are used to analyze how NIC (Non Interacting Crack) effective elasticity associated to "self similar growth" model work in some special configurations (one family of micro-cracks in mode I, II and III and in plane strain or plain stress). In each case we determine a critical crack density parameter and critical micro-crack radius (length) which distinguish between stable and unstable behaviors. This critical crack density depends only on the chosen configuration and on the Poisson ratio.

  15. Development of the autoinflammatory disease damage index (ADDI)

    Ter Haar, Nienke M; Annink, Kim V; Al-Mayouf, Sulaiman M

    2017-01-01

    enrollers of patients in the Eurofever Registry and 9 experts from the Americas participated in multiple rounds of online surveys to select items and definitions. Further, 22 (parents of) patients rated damage items and suggested new items. A consensus meeting was held to refine the items and definitions....../amyloidosis, developmental, serosal, neurological, ears, ocular and musculoskeletal damage. The categories renal/amyloidosis and neurological damage were assigned the highest number of points, serosal damage the lowest number of points. The involvement of (parents of) patients resulted in the inclusion of, for example...

  16. Radiation damage in lithium orthosilicate

    Noda, K.; Nakazawa, T.; Ishii, Y.; Fukai, K.; Watanabe, H. (Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment); Matsui, H.; Vollath, D.

    1993-11-01

    Radiation damage in lithium orthosilicate (Li[sub 4]SiO[sub 4]) and Al-doped Li[sub 4]SiO[sub 4] (Li[sub 3.7]Al[sub 0.1]SiO[sub 4]) irradiated with oxygen ions was studied with ionic conductivity measurements, Raman spectroscopy, Fourier transform infrared photo-acoustic spectroscopy (FT-IR PAS) and transmission electron microscopy. It was seen from the ionic conductivity measurements that lithium-ion vacancies were introduced as irradiation defects for Li-ions sites in both materials due to the irradiation. By the Raman spectroscopy, oxygen atoms in SiO[sub 4] tetrahedra were considered to be preferentially displaced due to the irradiation for Li[sub 4]SiO[sub 4], although only a decrease of the number of SiO[sub 4] tetrahedra occurred for Li[sub 3.7]Al[sub 0.1]SiO[sub 4] by displacement of both silicon and oxygen atoms. Decomposition of SiO[sub 4] tetrahedra and formation of some new phases having Si-O-Si and Si-O bonds were found to take place for both Li[sub 4]SiO[sub 4] and Li[sub 3.7]Al[sub 0.1]SiO[sub 4] by FT-IR PAS. In the electron microscopy, damage microstructure consisting of many voids or cavities and amorphization were observed for Li[sub 4]SiO[sub 4] irradiated with oxygen ions. The recovery behavior of radiation damage mentioned above was also investigated. (author).

  17. SIRT participates at DNA damage response

    Yun, Mi Yong; Joeng, Jae Min; Lee, Kee Ho [Korea Cancer Center Hospital, Seoul (Korea, Republic of); Park, Gil Hong [College of Medicine, Korea University, Seoul (Korea, Republic of)

    2009-05-15

    Sir2 maintains genomic stability in multiple ways in yeast. As a NAD{sup +}-dependent histone deacetylase, Sir2 has been reported to control chromatin silencing. In both budding yeast and Drosophila, overexpression of Sir2 extends life span. Previous reports have also demonstrated that Sir2 participate at DNA damage repair. A protein complex containing Sir2 has been reported to translocate to DNA double-strand breaks. Following DNA damage response, SIRT1 deacetylates p53 protein and attenuates its ability as a transcription factor. Consequently, SIRT1 over-expression increases cell survival under DNA damage inducing conditions. These previous observations mean a possibility that signals generated during the process of DNA repair are delivered through SIRT1 to acetylated p53. We present herein functional evidence for the involvement of SIRT1 in DNA repair response to radiation. In addition, this modulation of DNA repair activity may be connected to deacetylation of MRN proteins.

  18. Multiple homicides.

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  19. Site decontamination

    Bicker, A.E.

    1981-01-01

    Among the several DOE sites that have been radiologically decontaminated under the auspices of the Nevada Operations Office are three whose physical characteristics are unique. These are the Tatum Dome Test Site (TDTS) near Hattiesburg, Mississippi; a location of mountainous terrain (Pahute Mesa) on the Nevada Test Site; and the GNOME site near Carlsbad, New Mexico. In each case the contamination, the terrain, and the climate conditions were different. This presentation includes a brief description of each site, the methods used to perform radiological surveys, the logistics required to support the decontamination (including health physics and sample analysis), and the specific techniques used to reduce or remove the contamination

  20. Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

    Chen, J.; van de Geijn, J.; Goffman, T. (ROB, DCT, NCI, NIH, Bethesda, Maryland 20892 (US))

    1991-05-01

    In the conventional linear--quadratic model of single-dose response, the {alpha} and {beta} terms reflect lethal damage created {ital during} the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD.

  1. Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

    Chen, J.; van de Geijn, J.; Goffman, T.

    1991-01-01

    In the conventional linear--quadratic model of single-dose response, the α and β terms reflect lethal damage created during the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with ''unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD

  2. Coal transportation road damage

    Burtraw, D.; Harrison, K.; Pawlowski, J.A.

    1994-01-01

    Heavy trucks are primarily responsible for pavement damage to the nation's highways. In this paper we evaluate the pavement damage caused by coal trucks. We analyze the chief source of pavement damage (vehicle weight per axle, not total vehicle weight) and the chief cost involved (the periodic overlay that is required when a road's surface becomes worn). This analysis is presented in two stages. In the first section we present a synopsis of current economic theory including simple versions of the formulas that can be: used to calculate costs of pavement wear. In the second section we apply this theory to a specific example proximate to the reference environment for the Fuel Cycle Study in New Mexico in order to provide a numerical measure of the magnitude of the costs

  3. Natural resource damage assessment

    Seddelmeyer, J.

    1991-01-01

    The assessment and collection of natural resource damages from petroleum and chemical companies unfortunate enough to have injured publicly owned natural resources is perhaps the most rapidly expanding area of environmental liability. The idea of recovering for injury to publicly owned natural resources is an extension of traditional common law tort concepts under which a person who negligently injures another or his property is called upon to compensate the injured party. Normally, once liability has been established, it is a fairly straightforward matter to calculate the various elements of loss, such as the cost to repair or replace damaged property, or medical expenses, and lost income. More difficult questions, such as the amount to be awarded for pain and suffering or emotional distress, are left to the jury, although courts limit the circumstances in which the jury is permitted to award such damages

  4. Lattice damage caused by the irradiation of diamond

    Campbell, B; Mainwood, A; Newton, M; Davies, G

    2002-01-01

    Diamond is perceived to be radiation-hard, but the damage caused to the diamond is not well understood. The intrinsic defects (vacancies and interstitials) which are created by radiation damage are immobile at room temperature in diamond, unlike in silicon. Therefore, once the mechanisms of damage are understood for one type and energy of the particle, the dose and energy dependence of irradiation by other particles at a range of energies can be extrapolated. When a crystal is irradiated, the generation rates of vacancies and self-interstitials are generally determined by optical or electron paramagnetic resonance (EPR) spectroscopy experiments carried out after the irradiation has stopped. However, as the irradiation proceeds some of the carbon atoms displaced from their lattice sites may relax back into the vacant site, and the damage event will not be observed in the later measurement. In this paper, the mechanisms for radiation damage by charged particles in particular electrons and photons are investigat...

  5. Multiple myeloma.

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  6. Multiple mononeuropathy

    ... with multiple mononeuropathy are prone to new nerve injuries at pressure points such as the knees and elbows. They should avoid putting pressure on these areas, for example, by not leaning on the elbows, crossing the knees, ...

  7. Site organization and site arrangement

    Boissonnet, B.; Macqueron, J.F.

    1976-01-01

    The present paper deals with criteria for the choice of a production unit or power plant site, the organization and development of a site in terms of its particular characteristics and takes into account personnel considerations in site organizations as well as the problem of integrating the architecture into the environment. (RW) [de

  8. Radiation damage in A-15 materials: EXAFS studies

    Knapp, G.S.; Kampwirth, R.T.; Georgopoulos, P.; Brown, B.S.

    1980-01-01

    EXAFS measurements are useful in determining the local atomic environment of a particular element in a solid. Since there has been some controversy about the nature of the defects produced in A-15 materials by radiation damage, such studies were carried out on some A-15 compounds, V 3 Ga which was damaged by neutrons, as well as Nb 3 Ge damaged by 2.5 MeV a particles. In the V 3 Ga sample, site exchange disorder seems to be the most important result of the neutron damage with less than 20% of the vanadium atoms on wrong sites. However, in the Nb 3 Ge samples in addition to site exchange disorder, an unusual splitting of the first near-neighbor distance between the Ge and Nb is found. This splitting, approximately 0.2 A, may explain the large Debye Waller factors observed by Burbank et al

  9. Albumin and multiple sclerosis.

    LeVine, Steven M

    2016-04-12

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth.

  10. Feral burro populations: Distribution and damage assessment

    Tiller, B.L.

    1997-12-01

    This report was prepared to document (1) regional use of the National Training Center (NTC), Fort Irwin, CA, by burros, (2)influence of available water sources for burro use, (3) burro-related damage at several NTC sensitive habitat areas, and (4) management recommendations. All work described in this report was conducted in 1996 and 1997. Roadside transects were conducted and mapped using Geographical Positioning Systems/Geographical Information Systems (GPS/GIS) to indirectly measure relative abundance of feral burros (scat per mile) and to examine the spatial relationship of burro use to permanent or semi-permanent water sources that exist on the NTC. The authors also surveyed several permanent springs for burro-related damage and mapped the impact areas using GPS/GIS to quantify the extent of damage and to provide guidance on size and extent of burro exclosures in those areas. Photographs of the spring sites were also archived and permanent photo points were established for long-term monitoring of feral burro damage areas. In addition, aquatic invertebrate data collected during another spring site study were summarized and discussed in relation to burro-related impacts on the NTC`s sensitive habitats. Several water-quality parameters were also obtained from each spring, including temperature, dissolved oxygen,