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Sample records for early phase protective

  1. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    NASA Astrophysics Data System (ADS)

    Race, Margaret; Conley, Catharine

    discussed by the study participants to date have set the agenda for additional work that will continue for at least another year, culminating in a final report that should be useful to current and new nations and partnerships in planning human missions beyond LEO. In addition, over the past two years, NASA has made progress in integrating planetary protection considerations into mission designs along with other important human, environmental and science needs. Details about planetary protection have also been incorporated into the latest Addendum of the Design Reference Architecture (DRA) for human missions to Mars. Other ongoing studies of Mars human mission architecture, technologies and operations have likewise been integrating PP requirements and guidelines into cross-cutting measures of various types. An important objective of all these studies is to proactively gather and communicate PP information to the broad community of planners, engineers and assorted partners who are facing the challenges of future human exploration missions. By analyzing ways to integrate PP provisions effectively into early mission phases in synergism with other needs, these projects and studies will help ensure that all institutions and organizations avoid releasing harmful contamination on bodies with biological potential, thereby ensuring protection of the Earth and astronauts throughout their missions and safeguarding the integrity of science exploration—all in compliance with the 1967 Outer Space Treaty.

  2. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    NASA Astrophysics Data System (ADS)

    Race, Margaret; Conley, Catharine

    yet been developed. Looking ahead, it is recognized that these planetary protection policies will apply to both governmental and non-governmental entities for the more than 100 countries that are signatories to the Outer SpaceTreaty. Fortunately, planetary protection controls for human missions are supportive of many other important mission needs, such as maximizing closed-loop and recycling capabilities to minimize mass required, minimizing exposure of humans to planetary materials for multiple health reasons, and minimizing contamination of planetary samples and environments during exploration and science activities. Currently, there is progress on a number of fronts in translating the basic COSPAR PP Principles and Implementation Guidelines into information that links with early engineering and process considerations. For example, an IAA Study Group on Planetary Protection and Human Missions is engaging robotic and human mission developers and scientists in exploring detailed technical, engineering and operational approaches by which planetary protection objectives can be accomplished for human missions in synergism with robotic exploration and in view of other constraints. This on-going study aims to highlight important information for the early stages of planning, and identify key research and technology development (R&TD) areas for further consideration and work. Such R&TD challenges provide opportunities for individuals, institutions and agencies of emerging countries to be involved in international exploration efforts. In January 2014, the study group presented an Interim Report to the IAA Heads of Agencies Summit in Washington DC. Subsequently, the group has continued to work on expanding the initial technical recommendations and findings, focusing especially on information useful to mission architects and designers as they integrate PP considerations in their varied plans-- scientific, commercial and otherwise. Already the findings and recommendations

  3. MAPKs and Hsc70 are critical to the protective effect of molecular hydrogen during the early phase of acute pancreatitis.

    PubMed

    Han, Bing; Zhou, Haoxin; Jia, Guang; Wang, Yongwei; Song, Zengfu; Wang, Gang; Pan, Shangha; Bai, Xuewei; Lv, Jiachen; Sun, Bei

    2016-02-01

    Molecular hydrogen (H2 ) has been proven to be an effective agent that can cure multiple organ diseases by reducing oxidative stress. Although the protective effect of hydrogen on acute pancreatitis (AP) has been confirmed, its molecular mechanism is still unclear. In this article, we aimed to investigate the changes in pancreatic cell protein expression associated with the protective effect of H2 against AP and attempted to uncover the molecular mechanism underlying this process. A proteomic analysis identified 73 differentially expressed proteins and generated the protein-protein interaction networks of these proteins. The results triggered our interest in mitogen-activated protein kinase (MAPK) and heat shock cognate 71 kDa protein (Hsc70). The subsequent in vitro experiments showed that H2 treatment inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK, and activated NF-κB and the expression of tumor necrosis factor α and interleukin-1β, while simultaneously preventing the translocation of phospho-ERK, phospho-JNK, and phospho-p38 from the cytoplasm to the nucleus. Furthermore, Hsc70 expression was upregulated by H2 administration. The animal experimental results were consistent with those of the in vitro experiments. In conclusion, H2 treatment can ameliorate the inflammatory response and reduce the expression of inflammatory mediators during the early phase of AP by inhibiting the MAPK pathways and increasing Hsc70 expression.

  4. NACUBO Report: Early and Phased Retirement.

    ERIC Educational Resources Information Center

    Covert-McGrath, Debra

    1984-01-01

    Information is provided on early and phased retirement plans of about 20 academic institutions. Eligibility requirements for participation in early retirement plans vary from campus to campus. Most plans have a requirement ranging from a minimum of 10 to 20 years of full-time (or part-time equivalent) service. There are basically two types of…

  5. Stroboscopic symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Iadecola, Thomas; Santos, Luiz H.; Chamon, Claudio

    2015-09-01

    Symmetry-protected topological (SPT) phases of matter have been the focus of many recent theoretical investigations, but controlled mechanisms for engineering them have so far been elusive. In this work, we demonstrate that by driving interacting spin systems periodically in time and tuning the available parameters, one can realize lattice models for bosonic SPT phases in the limit where the driving frequency is large. We provide concrete examples of this construction in one and two dimensions, and discuss signatures of these phases in stroboscopic measurements of local observables.

  6. Early phases of star formation

    NASA Astrophysics Data System (ADS)

    Bok, B. J.

    1981-04-01

    Five broad areas of potential star formation in our galaxy and the Magellanic Clouds are presented. The role of gravitational collapse in concentrating matter into eventual stars is examined briefly. The five areas of research are: (1) giant molecular clouds with dimensions of 50 to 100 parsecs and masses equivalent to 100,000 or more suns; (2) the proximity of an H II emission nebula with an embedded or attached cluster of association of O and B stars to a large molecular cloud; (3) the larger so-called globules, notably the roundish and often isolated dark nebulae called Barnard objects, of which 200 or so have been identified within 500 parsecs of the sun; (4) close passage or collisions between interstellar clouds; and (5) supernova explosions. The Large Magellanic Clouds are also examined as an example of an area of potential star formation without the protection of a cosmic dust cloud. Finally, the likelihood that many new stars might possess planets and perhaps even life is discussed.

  7. Early phases of LMC star clusters?

    NASA Technical Reports Server (NTRS)

    Kontizas, Evangelos; Michalitsianos, Andrew; Kontizas, Mary

    1991-01-01

    On the basis of optical and IUE observations we have investigated the possibility that some of the very young stellar systems of the LMC, such as SL360, may be regarded as globular clusters at the very early phases of their dynamical evolution after the gas cloud expulsion.

  8. Sprayable Phase Change Coating Thermal Protection Material

    NASA Technical Reports Server (NTRS)

    Richardson, Rod W.; Hayes, Paul W.; Kaul, Raj

    2005-01-01

    NASA has expressed a need for reusable, environmentally friendly, phase change coating that is capable of withstanding the heat loads that have historically required an ablative thermal insulation. The Space Shuttle Program currently relies on ablative materials for thermal protection. The problem with an ablative insulation is that, by design, the material ablates away, in fulfilling its function of cooling the underlying substrate, thus preventing the insulation from being reused from flight to flight. The present generation of environmentally friendly, sprayable, ablative thermal insulation (MCC-l); currently use on the Space Shuttle SRBs, is very close to being a reusable insulation system. In actual flight conditions, as confirmed by the post-flight inspections of the SRBs, very little of the material ablates. Multi-flight thermal insulation use has not been qualified for the Space Shuttle. The gap that would have to be overcome in order to implement a reusable Phase Change Coating (PCC) is not unmanageable. PCC could be applied robotically with a spray process utilizing phase change material as filler to yield material of even higher strength and reliability as compared to MCC-1. The PCC filled coatings have also demonstrated potential as cryogenic thermal coatings. In experimental thermal tests, a thin application of PCC has provided the same thermal protection as a much thicker and heavier application of a traditional ablative thermal insulation. In addition, tests have shown that the structural integrity of the coating has been maintained and phase change performance after several aero-thermal cycles was not affected. Experimental tests have also shown that, unlike traditional ablative thermal insulations, PCC would not require an environmental seal coat, which has historically been required to prevent moisture absorption by the thermal insulation, prevent environmental degradation, and to improve the optical and aerodynamic properties. In order to reduce

  9. Phase transitions in the early universe

    NASA Astrophysics Data System (ADS)

    Wainwright, Carroll L.

    I explore the theory and computation of early-Universe finite-temperature phase transitions involving scalar fields. I focus primarily on the electroweak phase transition, but some of the methods I develop are applicable to any scalar-field cosmological phase transition (such as the computation of the lifetime of zero-temperature metastable vacua). I begin by examining phase transition thermodynamics with many extra coupled degrees of freedom, finding that such transitions have the potential to produce large amounts of entropy and can significantly dilute the concentration of thermal relic species (e.g., dark matter). I then detail a novel algorithm for calculating instanton solutions with multiple dynamic scalar fields, and present a computational package which implements the algorithm and computes the finite-temperature phase structure. Next, I discuss theoretical and practical problems of gauge dependence in finite-temperature effective potentials, using the Abelian Higgs and Abelian Higgs plus singlet models to show the severity of the problem. Finally, I apply the aforementioned algorithm to the electroweak phase transition in the next-to-minimal supersymmetric standard model (NMSSM). My collaborators and I find viable regions of the NMSSM which contain a strongly first-order phase transition and large enough CP violation to support electroweak baryogenesis, evade electric dipole moment constraints, and provide a dark matter candidate which could produce the observed 130 GeV gamma-ray line observed in the galactic center by the Fermi Gamma-ray Space Telescope.

  10. Pharmacogenomics in early-phase clinical development

    PubMed Central

    Burt, Tal; Dhillon, Savita

    2015-01-01

    Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

  11. [Phase-directional management of protective plantations. I. Fundamentals].

    PubMed

    Jiang, Fengqi; Zhu, Jiaojun

    2002-10-01

    In order to ensure the higher effectiveness, more stability and sustainability of Protective plantations, the definition of phase-directional management (PDM) of protective plantations was brought forward on the basis of management researches and practices for protective plantations. The basics of PDM is protective maturity, which is defined as the time when the protective plantations attain to the state that the protective plantations can provide effective and complete protection to the objects needed to be protected. Protective maturity has two points, initial protective maturity age (IPMA), the age of protective maturity started, and terminal protective maturity age (TPMA), the age of protective maturity ended. Three management phases of protective plantation, i.e., prematurity phase, the period from sapling or establishment to initial protective maturity, protective maturity phase, the period of protective maturity lasting, and regeneration phase, the period during regeneration and before the establishment, are divided based on the fundamental of protective maturity. Directional management of protective plantation means that all of the management techniques in each phase are directed at the aim of protective maturity, i.e., protective maturity is the direction of management of protective forests, and protective maturity is the final objective for the management of protective forests. In order to sustain the protective maturity state, corresponding measures should be conducted in each phase, according to the classification of protective plantations. In pre-maturity phase, the purpose of managing is to accelerate the protective maturity, therefore, the measures such as weed clearing, soil cultivation, irrigation, fertilization, intercropping and branch cutting etc. should be conducted in protective plantations. In maturity phase, the aim of managing is to sustain the protective maturity, i.e., the techniques (tending and thinning) of controlling the structure of

  12. Symmetry-protected topological phases from decorated domain walls.

    PubMed

    Chen, Xie; Lu, Yuan-Ming; Vishwanath, Ashvin

    2014-03-26

    Symmetry-protected topological phases generalize the notion of topological insulators to strongly interacting systems of bosons or fermions. A sophisticated group cohomology approach has been used to classify bosonic symmetry-protected topological phases, which however does not transparently predict their properties. Here we provide a physical picture that leads to an intuitive understanding of a large class of symmetry-protected topological phases in d=1,2,3 dimensions. Such a picture allows us to construct explicit models for the symmetry-protected topological phases, write down ground state wave function and discover topological properties of symmetry defects both in the bulk and on the edge of the system. We consider symmetries that include a Z2 subgroup, which allows us to define domain walls. While the usual disordered phase is obtained by proliferating domain walls, we show that symmetry-protected topological phases are realized when these domain walls are decorated, that is, are themselves symmetry-protected topological phases in one lower dimension. This construction works both for unitary Z2 and anti-unitary time reversal symmetry.

  13. Symmetry-protected intermediate trivial phases in quantum spin chains

    NASA Astrophysics Data System (ADS)

    Kshetrimayum, Augustine; Tu, Hong-Hao; Orús, Román

    2016-06-01

    Symmetry-protected trivial (SPt) phases of matter are the product-state analog of symmetry-protected topological (SPT) phases. This means, SPt phases can be adiabatically connected to a product state by some path that preserves the protecting symmetry. Moreover, SPt and SPT phases can be adiabatically connected to each other when interaction terms that break the symmetries protecting the SPT order are added in the Hamiltonian. It is also known that spin-1 SPT phases in quantum spin chains can emerge as effective intermediate phases of spin-2 Hamiltonians. In this paper we show that a similar scenario is also valid for SPt phases. More precisely, we show that for a given spin-2 quantum chain, effective intermediate spin-1 SPt phases emerge in some regions of the phase diagram, these also being adiabatically connected to nontrivial intermediate SPT phases. We characterize the phase diagram of our model by studying quantities such as the entanglement entropy, symmetry-related order parameters, and 1-site fidelities. Our numerical analysis uses matrix product states and the infinite time evolving block decimation method to approximate ground states of the system in the thermodynamic limit. Moreover, we provide a field theory description of the possible quantum phase transitions between the SPt phases. Together with the numerical results, such a description shows that the transitions may be described by conformal field theories with central charge c =1 . Our results are in agreement with, and further generalize, those of Y. Fuji, F. Pollmann, and M. Oshikawa [Phys. Rev. Lett. 114, 177204 (2015), 10.1103/PhysRevLett.114.177204].

  14. Defects and degeneracies in supersymmetry protected phases

    NASA Astrophysics Data System (ADS)

    Fokkema, Thessa; Schoutens, Kareljan

    2015-08-01

    We analyse a class of 1D lattice models, known as \\text{M}k models, which are characterised by an order-k clustering of spin-less fermions and by N}=2 lattice supersymmetry. Our main result is the identification of a class of (bulk or edge) defects, that are in one-to-one correspondence with so-called spin fields in a corresponding {Z}k parafermion CFT. In the gapped regime, injecting such defects leads to ground-state degeneracies that are protected by the supersymmetry. The defects, which are closely analogous to quasi-holes over the fermonic Read-Rezayi quantum Hall states, display characteristic fusion rules, which are of Ising type for k = 2 and of Fibonacci type for k = 3.

  15. Immunization of pregnant women: Future of early infant protection

    PubMed Central

    Faucette, Azure N; Pawlitz, Michael D; Pei, Bo; Yao, Fayi; Chen, Kang

    2015-01-01

    Children in early infancy do not mount effective antibody responses to many vaccines against commons infectious pathogens, which results in a window of increased susceptibility or severity infections. In addition, vaccine-preventable infections are among the leading causes of morbidity in pregnant women. Immunization during pregnancy can generate maternal immune protection as well as elicit the production and transfer of antibodies cross the placenta and via breastfeeding to provide early infant protection. Several successful vaccines are now recommended to all pregnant women worldwide. However, significant gaps exist in our understanding of the efficacy and safety of other vaccines and in women with conditions associated with increased susceptible to high-risk pregnancies. Public acceptance of maternal immunization remained to be improved. Broader success of maternal immunization will rely on the integration of advances in basic science in vaccine design and evaluation and carefully planned clinical trials that are inclusive to pregnant women. PMID:26366844

  16. Predicting reading disability: early cognitive risk and protective factors.

    PubMed

    Eklund, Kenneth Mikael; Torppa, Minna; Lyytinen, Heikki

    2013-02-01

    This longitudinal study examined early cognitive risk and protective factors for Grade 2 reading disability (RD). We first examined the reading outcome of 198 children in four developmental cognitive subgroups that were identified in our previous analysis: dysfluent trajectory, declining trajectory, unexpected trajectory and typical trajectory. We found that RD was unevenly distributed among the subgroups, although children with RD were found in all subgroups. A majority of the children with RD had familial risk for dyslexia. Second, we examined in what respect children with similar early cognitive development but different RD outcome differ from each other in cognitive skills, task-focused behaviour and print exposure. The comparison of the groups with high cognitive risk but different RD outcome showed significant differences in phonological skills, in the amount of shared reading and in task-focused behaviour. Children who ended up with RD despite low early cognitive risk had poorer cognitive skills, more task avoidance and they were reading less than children without RD and low cognitive risk. In summary, lack of task avoidance seemed to act as a protective factor, which underlines the importance of keeping children interested in school work and reading. PMID:23297103

  17. Predicting reading disability: early cognitive risk and protective factors.

    PubMed

    Eklund, Kenneth Mikael; Torppa, Minna; Lyytinen, Heikki

    2013-02-01

    This longitudinal study examined early cognitive risk and protective factors for Grade 2 reading disability (RD). We first examined the reading outcome of 198 children in four developmental cognitive subgroups that were identified in our previous analysis: dysfluent trajectory, declining trajectory, unexpected trajectory and typical trajectory. We found that RD was unevenly distributed among the subgroups, although children with RD were found in all subgroups. A majority of the children with RD had familial risk for dyslexia. Second, we examined in what respect children with similar early cognitive development but different RD outcome differ from each other in cognitive skills, task-focused behaviour and print exposure. The comparison of the groups with high cognitive risk but different RD outcome showed significant differences in phonological skills, in the amount of shared reading and in task-focused behaviour. Children who ended up with RD despite low early cognitive risk had poorer cognitive skills, more task avoidance and they were reading less than children without RD and low cognitive risk. In summary, lack of task avoidance seemed to act as a protective factor, which underlines the importance of keeping children interested in school work and reading.

  18. Chandra Catches Early Phase of Cosmic Assembly

    NASA Astrophysics Data System (ADS)

    2004-08-01

    A NASA Chandra X-ray Observatory image has revealed a complex of several intergalactic hot gas clouds in the process of merging. The superb Chandra spatial resolution made it possible to distinguish individual galaxies from the massive clouds of hot gas. One of the clouds, which that envelops hundreds of galaxies, has an extraordinarily low concentration of iron atoms, indicating that it is in the very early stages of cluster evolution. "We may be seeing hot intergalactic gas in a relatively pristine state before it has been polluted by gas from galaxies," said Q. Daniel Wang of the University of Massachusetts in Amherst, and lead author on an upcoming Astrophysical Journal article describing the study. "This discovery should provide valuable insight into how the most massive structures in the universe are assembled." 3-Panel Image of Abell 2125, Its Core & Galaxy C153 3-Panel Image of Abell 2125, Its Core & Galaxy C153 The complex, known as Abell 2125,is about 3 billion light years from Earth, and is seen at a time about 11 billion years after the Big Bang, when many galaxy clusters are believed to have formed. The Chandra Abell 2125 image shows several huge elongated clouds of multimillion degree gas coming together from different directions. These hot gas clouds, each of which contains hundreds of galaxies, appear to be in the process of merging to form a single massive galaxy cluster. Chandra, Hubble Space Telescope, and Very Large Array radio telescope data show that several galaxies in the Abell 2125 core cluster are being stripped of their gas as they fall through surrounding high-pressure hot gas. This stripping process has enriched the core cluster's gas in heavy elements such as iron. Abell 2125's Core & Galaxy C153 Abell 2125's Core & Galaxy C153 The gas in the pristine cloud, which is still several million light years away from the core cluster, is conspicuous for its lack of iron atoms. This anemic cloud must be in a very early evolutionary stage. The

  19. Porous protective solid phase micro-extractor sheath

    DOEpatents

    Andresen, Brian D.; Randich, Erik

    2005-03-29

    A porous protective sheath for active extraction media used in solid phase microextraction (SPME). The sheath permits exposure of the media to the environment without the necessity of extending a fragile coated fiber from a protective tube or needle. Subsequently, the sheath can pierce and seal with GC-MS septums, allowing direct injection of samples into inlet ports of analytical equipment. Use of the porous protective sheath, within which the active extraction media is contained, mitigates the problems of: 1) fiber breakage while the fiber is extended during sampling, 2) active media coating loss caused by physical contact of the bare fiber with the sampling environment; and 3) coating slough-off during fiber extension and retraction operations caused by rubbing action between the fiber and protective needle or tube.

  20. Fluctuation-driven electroweak phase transition. [in early universe

    NASA Technical Reports Server (NTRS)

    Gleiser, Marcelo; Kolb, Edward W.

    1992-01-01

    We examine the dynamics of the electroweak phase transition in the early Universe. For Higgs masses in the range 46 less than or = M sub H less than or = 150 GeV and top quark masses less than 200 GeV, regions of symmetric and asymmetric vacuum coexist to below the critical temperature, with thermal equilibrium between the two phases maintained by fluctuations of both phases. We propose that the transition to the asymmetric vacuum is completed by percolation of these subcritical fluctuations. Our results are relevant to scenarios of baryogenesis that invoke a weakly first-order phase transition at the electroweak scale.

  1. Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates.

    PubMed

    Vohs, Jenifer L; Hummer, Tom A; Yung, Matthew G; Francis, Michael M; Lysaker, Paul H; Breier, Alan

    2015-01-01

    Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis.

  2. Abelian Floquet symmetry-protected topological phases in one dimension

    NASA Astrophysics Data System (ADS)

    Roy, Rahul; Harper, Fenner

    2016-09-01

    Time-dependent systems have recently been shown to support novel types of topological order that cannot be realized in static systems. In this paper we consider a range of time-dependent, interacting systems in one dimension that are protected by an Abelian symmetry group. We classify the distinct topological phases that can exist in this setting and find that they may be described by a bulk invariant associated with the unitary evolution of the closed system. In the open system, nontrivial phases correspond to the appearance of edge modes, which have signatures in the many-body quasienergy spectrum and which relate to the bulk invariant through a form of bulk-edge correspondence. We introduce simple models which realize nontrivial dynamical phases in a number of cases, and outline a loop construction that can be used to generate such phases more generally.

  3. Early phase of acute pancreatitis: Assessment and management

    PubMed Central

    Phillip, Veit; Steiner, Jörg M; Algül, Hana

    2014-01-01

    Acute pancreatitis (AP) is a potentially life-threatening disease with a wide spectrum of severity. The overall mortality of AP is approximately 5%. According to the revised Atlanta classification system, AP can be classified as mild, moderate, or severe. Severe AP often takes a clinical course with two phases, an early and a late phase, which should both be considered separately. In this review article, we first discuss general aspects of AP, including incidence, pathophysiology, etiology, and grading of severity, then focus on the assessment of patients with suspected AP, including diagnosis and risk stratification, followed by the management of AP during the early phase, with special emphasis on fluid therapy, pain management, nutrition, and antibiotic prophylaxis. PMID:25133018

  4. Horava-Lifshitz early universe phase transition beyond detailed balance

    NASA Astrophysics Data System (ADS)

    Kheyri, F.; Khodadi, M.; Sepangi, H. R.

    2013-01-01

    The early universe is believed to have undergone a QCD phase transition to hadrons at about 10 μs after the big bang. We study such a transition in the context of the non-detailed balance Horava-Lifshitz theory by investigating the effects of the dynamical coupling constant λ in a flat universe. The evolution of the relevant physical quantities, namely the energy density ρ, temperature T, scale factor a and the Hubble parameter H is investigated before, during and after the phase transition, assumed to be of first order. Also, in view of the recent lattice QCD simulations data, we study a cross-over phase transition of the early universe whose results are based on two different sets of lattice data.

  5. Beryllium and boron constraints on an early Galactic bright phase

    NASA Technical Reports Server (NTRS)

    Fields, Brian D.; Schramm, David N.; Truran, James W.

    1993-01-01

    The recent observations of Be and B in metal-deficient halo dwarfs are used to constrain a 'bright phase' of enhanced cosmic-ray flux in the early Galaxy. Assuming that this Be and B arises from cosmic-ray spallation in the early Galaxy, limits are placed on the intensity of the early (Population II) cosmic-ray flux relative to the present (Population I) flux. A simple estimate of bounds on the flux ratio is 1 - 40. This upper bound would restrict galaxies like our own from producing neutrino fluxes that would be detectable in any currently proposed detectors. It is found that the relative enhancement of the early flux varies inversely with the relative time of enhancement. It is noted that associated gamma-ray production via pp - pi sup 0 pp may be a significant contribution to the gamma-ray background above 100 MeV.

  6. Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy.

    PubMed

    Chen, Yung-Lung; Chung, Sheng-Ying; Chai, Han-Tan; Chen, Chih-Hung; Liu, Chu-Feng; Chen, Yi-Ling; Huang, Tien-Hung; Zhen, Yen-Yi; Sung, Pei-Hsun; Sun, Cheuk-Kwan; Chua, Sarah; Lu, Hung-I; Lee, Fan-Yen; Sheu, Jiunn-Jye; Yip, Hon-Kan

    2015-12-01

    This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.], and group 3 [carvedilol (15 mg/kg/d, from day 7 after DOX treatment for 28 days)], and euthanized by day 35 after DOX treatment. By day 35, the left ventricular ejection fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the left ventricular (LV) end-diastolic and LV end-systolic dimensions showed an opposite pattern to the LVEF among the three groups. The protein expressions of fibrotic (Smad3, TGF-β), apoptotic (BAX, cleaved caspase 3, PARP), DNA damage (γ-H2AX), oxidative stress (oxidized protein), mitochondrial damage (cytosolic cytochrome-C), heart failure (brain natriuretic peptide), and hypertrophic (β-MHC) biomarkers of the LV myocardium showed an opposite pattern to the LVEF among the three groups. The protein expressions of antifibrotic (BMP-2, Smad1/5), α-MHC, and phosphorylated-Akt showed an identical pattern to the LVEF among the three groups. The microscopic findings of fibrotic and collagen-deposition areas and the numbers of γ-H2AX(+) and 53BP1(+) cells in the LV myocardium exhibited an opposite pattern, whereas the numbers of endothelial cell (CD31(+), vWF(+)) markers showed an identical pattern to the LVEF among the three groups. Cardiac stem cell markers (C-kit(+) and Sca-1(+) cells) were significantly and progressively increased from group 1 to group 3. Additionally, the in vitro study showed carvedilol treatment significantly inhibited DOX-induced cardiomyoblast DNA (CD90/XRCC1(+), CD90/53BP1(+), and r-H2AX(+) cells) damage. Early carvedilol therapy protected against DOX-induced DNA damage and cardiomyopathy.

  7. Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy.

    PubMed

    Chen, Yung-Lung; Chung, Sheng-Ying; Chai, Han-Tan; Chen, Chih-Hung; Liu, Chu-Feng; Chen, Yi-Ling; Huang, Tien-Hung; Zhen, Yen-Yi; Sung, Pei-Hsun; Sun, Cheuk-Kwan; Chua, Sarah; Lu, Hung-I; Lee, Fan-Yen; Sheu, Jiunn-Jye; Yip, Hon-Kan

    2015-12-01

    This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.], and group 3 [carvedilol (15 mg/kg/d, from day 7 after DOX treatment for 28 days)], and euthanized by day 35 after DOX treatment. By day 35, the left ventricular ejection fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the left ventricular (LV) end-diastolic and LV end-systolic dimensions showed an opposite pattern to the LVEF among the three groups. The protein expressions of fibrotic (Smad3, TGF-β), apoptotic (BAX, cleaved caspase 3, PARP), DNA damage (γ-H2AX), oxidative stress (oxidized protein), mitochondrial damage (cytosolic cytochrome-C), heart failure (brain natriuretic peptide), and hypertrophic (β-MHC) biomarkers of the LV myocardium showed an opposite pattern to the LVEF among the three groups. The protein expressions of antifibrotic (BMP-2, Smad1/5), α-MHC, and phosphorylated-Akt showed an identical pattern to the LVEF among the three groups. The microscopic findings of fibrotic and collagen-deposition areas and the numbers of γ-H2AX(+) and 53BP1(+) cells in the LV myocardium exhibited an opposite pattern, whereas the numbers of endothelial cell (CD31(+), vWF(+)) markers showed an identical pattern to the LVEF among the three groups. Cardiac stem cell markers (C-kit(+) and Sca-1(+) cells) were significantly and progressively increased from group 1 to group 3. Additionally, the in vitro study showed carvedilol treatment significantly inhibited DOX-induced cardiomyoblast DNA (CD90/XRCC1(+), CD90/53BP1(+), and r-H2AX(+) cells) damage. Early carvedilol therapy protected against DOX-induced DNA damage and cardiomyopathy. PMID:26511374

  8. Early phase combined therapeutic management of acute ischaemic stroke.

    PubMed

    Bassi, P; Lattuada, P; Tonietti, S

    2005-05-01

    An adequate treatment of ischaemic stroke in the early phase (28-48 h) is the most important factor for a better outcome. Thrombolysis with rTPA (within 3 h) and oral ASA 300 mg/days are the first therapeutic misures. Continuous monitoring of cardiological and haemodinamic parameters allows early detection of cardiac disturbances. Treatment of hypertension, low haematic oxigenation, hyperglicaemia, seizures and hypertermia is basic to improve outcome. Pharmacological therapy is only one of the components of effective multidisciplinary integrated management of ischaemic stroke; we remind also the precocity of rehabilitation procedures and an accurate psychological assessment. PMID:15883687

  9. Gaia Science Alerts: Early Validation Phase Data from Gaia

    NASA Astrophysics Data System (ADS)

    Walton, Nicholas; Hodgkin, Simon; van Leeuwen, Floor

    2015-08-01

    The ESA Gaia satellite launched Dec 2013, and after successful completion of its in orbit commissioning in July 2014, begun routine operations, with the aim to accurately measure the astrometric and astrophysical properties of more than a billion stars in our Milky Way.As a significant by product of its observational scanning law, where each point on the sky is observed multiple times (~80 revisits on average) over the nominal 5 year mission, Gaia has significant utility in detecting new transients, both flux (e.g. Supernovae, Flare stars) and positional (e.g. Asteroids).We will present the current status of the Gaia Photometric Science Alerts (PSA) system that has been developed within the Gaia DPAC. The PSA pipeline provides a quick look analysis of the daily data stream from Gaia, and identifies new photometric alerts, from analysis of the object photometric and the low resolution spectro-photometric data. Via a set of filters, those identified as astrophysical in nature, are published to the community. The information provided currently includes positional and flux information.The Gaia Alerts working group has organised a significant early stage followup campaign, providing access to a wide variety of followup facilities. These have been used to provide classification spectra of the Gaia alert candidates, with the early phase data confirming that the alerts issued are indeed largely astrophysical transients, with only a small contamination rate.The presentation will address the early phase issues that have been addressed in localising and classifying alerts in the early phase of Gaia observations (for instance, how lack of early knowledge of the sky as seen by Gaia was mitigated by reference to external image data), and how the alert rate published by the PSA will ramp up towards the end of 2015, with the availability of more Gaia sky data.Information concerning the Gaia alerts system can be found at http://gaia.ac.uk/selected-gaia-science-alerts

  10. Phase structure of one-dimensional interacting Floquet systems. I. Abelian symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    von Keyserlingk, C. W.; Sondhi, S. L.

    2016-06-01

    Recent work suggests that a sharp definition of "phase of matter" can be given for some quantum systems out of equilibrium, first for many-body localized systems with time-independent Hamiltonians and more recently for periodically driven or Floquet localized systems. In this work, we propose a classification of the finite Abelian symmetry-protected phases of interacting Floquet localized systems in one dimension. We find that the different Floquet phases correspond to elements of ClG×AG , where ClG is the undriven interacting classification, and AG is a set of (twisted) one-dimensional representations corresponding to symmetry group G . We will address symmetry-broken phases in a subsequent paper C. W. von Keyserlingk and S. L. Sondhi, following paper, Phys. Rev. B 93, 245146 (2016), 10.1103/PhysRevB.93.245146.

  11. Topological color code and symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Yoshida, Beni

    2015-06-01

    We study (d -1 ) -dimensional excitations in the d -dimensional color code that are created by transversal application of the Rd phase operators on connected subregions of qubits. We find that such excitations are the superpositions of electric charges and can be characterized by the fixed-point wave functions of (d -1 ) -dimensional bosonic symmetry-protected topological (SPT) phases with (Z2) ⊗d symmetry. While these SPT excitations are localized on (d -1 ) -dimensional boundaries, their creation requires operations acting on all qubits inside the boundaries, reflecting the nontriviality of emerging SPT wave functions. Moreover, these SPT excitations can be physically realized as transparent gapped domain walls which exchange excitations in the color code. Namely, in the three-dimensional color code, the domain wall, associated with the transversal R3 operator, exchanges a magnetic flux and a composite of a magnetic flux and the looplike SPT excitation, revealing rich possibilities of boundaries in higher-dimensional TQFTs. We also find that magnetic fluxes and the looplike SPT excitations exhibit nontrivial three-loop braiding statistics in three dimensions as a result of the fact that the R3 phase operator belongs to the third level of the Clifford hierarchy. We believe that the connection between SPT excitations, fault-tolerant logical gates and gapped domain walls, established in this paper, can be generalized to a large class of topological quantum codes and TQFTs.

  12. First Order Phase Transitions in the Early Universe

    NASA Astrophysics Data System (ADS)

    Ferrera, Antonio

    1996-01-01

    First order phase transitions occur via nucleation of bubbles of the new phase (true vacuum) in the old phase (false vacuum). The technique most widely used to compute the probability of bubble nucleation in a field theory phase transition is based on instanton methods in the context of the semiclassical approximation. At zero temperature in 3+1 dimensions the nucleation rate is dominated by the O(4) symmetric instanton, a sphere of radius R, while at temperatures TggR^ {-1} the decay is dominated by a "cylindrical" (static) instanton with O(3) invariance. There has been discussion in the literature as to whether the transition between these two regimens would be first order (discontinuity in the first derivative of the nucleation rate at the transition temperature Tc), or second order (continuity of the first derivative, but discontinuity of the second derivative at Tc). In the first part of the thesis we obtain the finite temperature solutions corresponding to the quantum and the thermal regimes, and compute their action as a function of the temperature for different values of the wall thickness in a varphi^4 potential, as a toy model for a transition in the early universe. Our results indicate that only for the cases of very large wall thickness a second order transition takes place, while for all the other cases a first order transition occurs. We also study the 2+l and l+l dimensional cases in two condensed matter cases. In the second part of the thesis we study the collision process for vacuum bubbles expanding in a plasma. The effects of the plasma are simulated by introducing a damping term in the equations of motion for a U(1) global field. We find that Lorentz-contracted spherically symmetric domain walls adequately describe the overdamped motion of the bubbles in the thin wall approximation, and study the process of collision and phase equilibration both numerically and analytically. With an analytical model for the phase propagation in 1+1 dimensions

  13. Geometry defects in bosonic symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    You, Yizhi; You, Yi-Zhuang

    2016-06-01

    In this paper we focus on the interplay between geometry defects and topological properties in bosonic symmetry-protected topological (SPT) phases. We start from eight copies of 3D time-reversal (T ) invariant topological superconductors (TSC) on a crystal lattice. We melt the lattice by condensation of disclinations and therefore restore the rotation symmetry. Such a disclination condensation procedure confines the fermion and afterwards turns the system into a 3D boson topological liquid crystal (TCL). The low energy effective theory of this crystalline-liquid transition contains a topological term inherited from the geometry axion response in TSC. In addition, we investigate the interplay between dislocation and superfluid vortex on the surface of TCL. We demonstrate that the T and translation invariant surface state is a double [e T m T ] state with intrinsic surface topological order. We also look into the exotic behavior of dislocation in the 2D boson SPT state described by an O (4 ) nonlinear σ model (NL σ M ) with topological Θ term. By dressing the O (4 ) vector with spiral order and gauging the symmetry, the dislocation has mutual semion statistics with the gauge flux. Further reducing the O (4 )NL σ M to the Ising limit, we arrive at the Levin-Gu model with stripy modulation whose dislocation has nontrivial braiding statistics.

  14. Educational research visualizations: Scientific warrants in early-phase research

    NASA Astrophysics Data System (ADS)

    Zaritsky, Raul Alan

    This dissertation addresses the integration of advanced visualization methodologies into education in order to create appropriate new forms of research and thereby improving the diffusion and adoption of effective innovations. Beginning with an historical analysis of how meaning making via visualization systems has become an essential engine of science, and how today an appropriate visualization methodology for education can be created as an Educational Research Visualization exemplar. The research on the creation of an ERV provides details of the validation methods and technologies that converge to build this visualization methodology for education so as to create scientific warrants in research's early phases. These forms of visualization are truly scientific visualization methods for education, and use the filming methods of ethnography to create a video database resource.

  15. 17β-estradiol ameliorates oxygen-induced retinopathy in the early hyperoxic phase

    PubMed Central

    Zhang, Hongbing; Wang, Xiaodong; Xu, Kun; Wang, Yao; Wang, Yani; Liu, Xianning; Zhang, Xianjiao; Wang, Liang; Li, Xiaogang

    2016-01-01

    Retinopathy of prematurity (ROP) is a major and leading cause of blindness in premature infants. It has been realized that early treatment for ROP is important. However, all the early treatments of ROP are focusing on peripheral retinal ablation which does not surmount the limit of extinguishing retinal neovascularization and protecting the retinas of children with ROP from the injury of ablation. In this study, we investigated the morphological changes of retina and oxidative stress alterations in the early phase of oxygen-induced retinopathy (OIR) and tested the effects of 17β-estradiol (17β-E2) , a nonselective estrogen receptor (ER) agonist, on early phase OIR development. We found that large central capillary-free areas were induced in the retinas of pups exposed to hyperoxia on postnatal day 9 (P9) , whereas vascularization was almost complete in the retinas of pups exposed to normoxia at the same age. The concentrations of malondiadehyde (MDA) , an end-product of oxidative stress, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a major enzyme producing free radicals, as well as the activity of NADPH oxidase were significantly elevated in the retinas of pups exposed to hyperoxia on P9 and postnatal day 13 (P13) compared to those in age matched pups exposed to normoxia. Treatment with 17β-E2 decreased not only the percentage of the central capillary-free area to total retina area but also the concentrations of MDA and NADPH oxidase as well as the activity of NADPH oxidase in a dose-dependent manner in pups exposed to hyperoxia on p9 and P13. The concentration of VEGF was significantly decreased on P9 but increased on P14 in the retinas of pups exposed to hyperoxia, whereas it was significantly elevated on P9 but decreased on P14 in the retinas of pups treated with 17β-E2. The effect of 17β-E2 could be reversed by the co-treatment with ICI182780, a high affinity estrogen receptor antagonist, which suggested that 17β-E2 might exert its

  16. Early phase clinical trials to identify optimal dosing and safety

    PubMed Central

    Cook, Natalie; Hansen, Aaron R.; Siu, Lillian L.; Abdul Razak, Albiruni R.

    2014-01-01

    The purpose of early stage clinical trials is to determine the recommended dose and toxicity profile of an investigational agent or multi-drug combination. Molecularly targeted agents (MTAs) and immunotherapies have distinct toxicities from chemotherapies that are often not dose dependent and can lead to chronic and sometimes unpredictable side effects. Therefore utilizing a dose escalation method that has toxicity based endpoints may not be as appropriate for determination of recommended dose, and alternative parameters such as pharmacokinetic or pharmacodynamic outcomes are potentially appealing options. Approaches to enhance safety and optimize dosing include improved preclinical models and assessment, innovative model based design and dose escalation strategies, patient selection, the use of expansion cohorts and extended toxicity assessments. Tailoring the design of phase I trials by adopting new strategies to address the different properties of MTAs is required to enhance the development of these agents. This review will focus on the limitations to safety and dose determination that have occurred in the development of MTAs and immunotherapies. In addition, strategies are proposed to overcome these challenges to develop phase I trials that can more accurately define the recommended dose and identify adverse events. PMID:25160636

  17. Effectiveness of Child Protection Training for Pre-Service Early Childhood Educators

    ERIC Educational Resources Information Center

    McKee, Bronagh E.; Dillenburger, Karola

    2012-01-01

    International evidence confirms that early childhood educators can enter professional practice unprepared for child protection due to inadequate pre-service preparation. This paper makes an original contribution by using the Child Protection Questionnaire for Educators (CPQE) to examine the pre- and post-intervention child maltreatment and…

  18. Protective and Risk Factors Associated with Adolescent Boys' Early Sexual Debut and Risky Sexual Behaviors

    ERIC Educational Resources Information Center

    Lohman, Brenda J.; Billings, Amanda

    2008-01-01

    Protective and risk factors associated with rates of early sexual debut and risky sexual behaviors for a sample of low-income adolescent boys were examined using bioecological theory framed by a resiliency perspective. Protective processes examined include a close mother-son and father-son relationship, parental monitoring and family routines, as…

  19. Factor Structure and Invariance across Gender of the Devereux Early Childhood Assessment Protective Factor Scale

    ERIC Educational Resources Information Center

    Ogg, Julia A.; Brinkman, Tara M.; Dedrick, Robert F.; Carlson, John S.

    2010-01-01

    Early childhood social-emotional assessment has traditionally focused on risk factors or psychopathology, and has less frequently examined protective factors that may serve to promote positive developmental outcomes for children. To advance conceptual models that include protective factors as key explanatory constructs, there is a need for…

  20. A Bioecological Analysis of Risk and Protective Factors Associated With Early Sexual Intercourse of Young Adolescents

    PubMed Central

    Jordahl, Tina; Lohman, Brenda J.

    2009-01-01

    Microsystem risk and protective factors associated with early sexual intercourse among low-income adolescents were assessed using bioecological theory and a risk and resiliency framework. Waves 1 and 2 of Welfare, Children and Families: A Three-City Study were used (N=984, 10–14 years). Findings showed age, gender, race, two-parent households, separated households, households where the mother formed a union between waves, transitioning onto welfare between waves, and delinquency increased the odds that adolescents were sexually active. Protective factors for early sexual activity included maternal education and father involvement. Risk factors for early sexual debut were age, gender, race, two-parent households, separated households, and delinquency. A protective factor for early sexual debut was maternal education. Findings differed by gender, race, and race*gender. Policy implications include increasing social and human capital among low-income mothers to promote family stability and providing diversified sexual education programs due to gender differences. PMID:20161569

  1. Early Infection Following Arthroplasty – Are Patients Protected?

    PubMed Central

    Young, Simon W; Zhu, Mark; Ravi, Saiprasad; Luey, Chris

    2016-01-01

    Objective: Prophylactic antibiotics significantly reduce prosthetic joint infection (PJI) rates after hip and knee arthroplasty. However, the rise of antibiotic resistance has raised concern over the adequacy of conventional prophylaxis. This study aimed to identify organisms causing early PJI in hip and knee arthroplasties and their sensitivity to current prophylactic antibiotics. Method: We performed a multicentre audit of 4009 primary hip and knee arthroplasties (1852 hips and 2157 knees) at three tertiary referral hospitals. PJIs were identified according to the Infectious Diseases Society of America (IDSA) definition and all patients were followed for two years. For patients with confirmed PJIs, causative bacteria and their antibiotic sensitivities were identified. Results: Thirty-five PJI cases in total were identified in the follow-up period of two years, consisting of 13 hips and 22 knees. The overall definite prosthetic joint infection rate was 0.87% (0.7% for hips, 1.0% for knees). 51.4% of PJIs occurred within the first 6 weeks, 62.9% within the first 3 months and 82.9% during the first year. Ninety-six percent (96%) of patients were given cefazolin as prophylaxis. Thirty-four percent (34%) of patients were infected with Coagulase-negative staphylococci, which were the most common infective organisms. 91.7% of these organisms were resistant to cefazolin. Twenty-five percent (25%) of patients were infected with Staphylococcus aureus, 9.1% of which were methicillin resistant. Overall, 58% of organisms were resistant to cefazolin. Sixty percent (60%) of patients who were treated with cefazolin and had available sensitivities for infective organism(s) were infected with cefazolin-resistant organisms. Conclusions: The majority of bacteria causing early PJI are resistant to the antibiotic prophylaxis given at the time of surgery. Whilst all the organisms cultured were sensitive to vancomycin, concerns regarding antibiotic stewardship remain and there is

  2. Compliance in early-phase cancer clinical trials research.

    PubMed

    Kurzrock, Razelle; Stewart, David J

    2013-01-01

    Regulations and ethical principles require that investigators seek consent and that patients participate in experimental studies only under circumstances that minimize the possibility of undue pressure and/or enticements. In recent years, there has been a rapid rise in the monitoring requirements of early-phase trials accompanied by an increasing emphasis on assuring "investigator" compliance with the protocol. It is actually, however, the patient who must comply with the requirements of the study. If there is divergence from the protocol, investigators may be reported to regulatory bodies or agencies. Whereas the investigative community is expected to be vigilant about ensuring that patients participate in studies voluntarily and that their consent is procured without duress, it is also required to guarantee that complex protocols, which entail multiple procedures, be followed exactly by participants who suffer from the complications of advanced cancer. We explore the issue of compliance in a research environment in which investigators are subject to disciplinary action if they fail to ensure that patients adhere precisely to the intense monitoring mandates of a clinical trial.

  3. Mechanisms of the early phases of plant gravitropism

    NASA Technical Reports Server (NTRS)

    Kiss, J. Z.

    2000-01-01

    Gravitropism is directed growth of a plant or plant organ in response to gravity and can be divided into the following temporal sequence: perception, transduction, and response. This article is a review of the research on the early events of gravitropism (i.e., phenomena associated with the perception and transduction phases). The two major hypotheses for graviperception are the protoplast-pressure and starch-statolith models. While most researchers support the concept of statoliths, there are suggestions that plants have multiple mechanisms of perception. Evidence supports the hypothesis that the actin cytoskeleton is involved in graviperception/transduction, but the details of these mechanisms remain elusive. A number of recent developments, such as increased use of the molecular genetic approach, magnetophoresis, and laser ablation, have facilitated research in graviperception and have allowed for refinement of the current models. In addition, the entire continuum of acceleration forces from hypo- to hyper-gravity have been useful in studying perception mechanisms. Future interdisciplinary molecular approaches and the availability of sophisticated laboratories on the International Space Station should help to develop new insights into mechanisms of gravitropism in plants.

  4. Advanced worker protection system. Topical report, Phase I

    SciTech Connect

    Myers, J.

    1995-07-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D&D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D&D costs while providing appropriate protection to DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D&D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project will result in the development of an Advanced Worker Protection System (AWPS). The AWPS will be built around a life support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack will be combined with advanced protective garments, advanced liquid cooling garment, respirator, communications, and support equipment to provide improved worker protection, simplified system, maintenance, and dramatically improve worker productivity through longer duration work cycles.

  5. Early light-induced proteins protect Arabidopsis from photooxidative stress.

    PubMed

    Hutin, Claire; Nussaume, Laurent; Moise, Nicolae; Moya, Ismaël; Kloppstech, Klaus; Havaux, Michel

    2003-04-15

    The early light-induced proteins (ELIPs) belong to the multigenic family of light-harvesting complexes, which bind chlorophyll and absorb solar energy in green plants. ELIPs accumulate transiently in plants exposed to high light intensities. By using an Arabidopsis thaliana mutant (chaos) affected in the posttranslational targeting of light-harvesting complex-type proteins to the thylakoids, we succeeded in suppressing the rapid accumulation of ELIPs during high-light stress, resulting in leaf bleaching and extensive photooxidative damage. Constitutive expression of ELIP genes in chaos before light stress resulted in ELIP accumulation and restored the phototolerance of the plants to the wild-type level. Free chlorophyll, a generator of singlet oxygen in the light, was detected by chlorophyll fluorescence lifetime measurements in chaos leaves before the symptoms of oxidative stress appeared. Our findings indicate that ELIPs fulfill a photoprotective function that could involve either the binding of chlorophylls released during turnover of pigment-binding proteins or the stabilization of the proper assembly of those proteins during high-light stress. PMID:12676998

  6. Hidden-symmetry-protected topological phases on a one-dimensional lattice

    NASA Astrophysics Data System (ADS)

    Li, Linhu; Chen, Shu

    2015-02-01

    We demonstrate the existence of a topologically nontrivial phase in a one-dimensional fermionic lattice system subjected to synthetic gauge fields, which is beyond the standard Altland-Zirnbauer classification of topological insulators. The topological phase can be characterized by the presence of degenerate zero-mode edge states or a quantized Berry phase of the occupied Bloch band. By analyzing symmetries of the system, we identify that the topological phase and zero-mode edge states are protected by two hidden symmetries. An extended model with hidden symmetry breaking is also studied in order to reveal the effect of hidden symmetries on the symmetry-protected topological phase.

  7. Early post parturient changes in milk acute phase proteins.

    PubMed

    Thomas, Funmilola C; Waterston, Mary; Hastie, Peter; Haining, Hayley; Eckersall, P David

    2016-08-01

    The periparturient period is one of the most critical periods in the productive life of a dairy cow, and is the period when dairy cows are most susceptible to developing new intramammary infections (IMI) leading to mastitis. Acute phase proteins (APP) such as haptoglobin (Hp), mammary associated serum amyloid A3 (M-SAA3) and C-reactive protein (CRP) have been detected in milk during mastitis but their presence in colostrum and milk in the immediate postpartum period has had limited investigation. The hypothesis was tested that APP are a constituent of colostrum and milk during this period. Enzyme linked immunosorbent assays (ELISAs) were used to determine each APP's concentration in colostrum and milk collected daily from the first to tenth day following calving in 22 Holstein-Friesian dairy cows. Haptoglobin was assessed in individual quarters and composite milk samples while M-SAA3 and CRP concentration were determined in composite milk samples. Change in Hp in relation to the high abundance proteins during the transition from colostrum to milk were evaluated by 1 and 2 dimension electrophoresis and western blot. In 80% of the cows all APPs were detected in colostrum on the first day following parturition at moderately high levels but gradually decreased to minimal values in the milk by the 6th day after calving. The remaining cows (20%) showed different patterns in the daily milk APP concentrations and when an elevated level is detected could reflect the presence of IMI. Demonstration that APP are present in colostrum and milk following parturition but fall to low levels within 4 days means that elevated APP after this time could be biomarkers of post parturient mastitis allowing early intervention to reduce disease on dairy farms. PMID:27600971

  8. Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity.

    PubMed

    Garg, Meena; Thamotharan, Manikkavasagar; Dai, Yun; Thamotharan, Shanthie; Shin, Bo-Chul; Stout, David; Devaskar, Sherin U

    2012-06-01

    Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation-induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21) (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin sensitive, inactive, and exhibiting metabolic inflexibility (Vo(2)) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype. PMID:22461568

  9. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  10. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  11. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  12. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  13. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  14. 78 FR 8184 - DEEPWATER HORIZON Oil Spill; Final Phase II Early Restoration Plan and Environmental Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-05

    ... availability of the Phase II DERP/ER was published in the Federal Register on November 6, 2012. (77 FR 66626... DEEPWATER HORIZON Oil Spill; Final Phase II Early Restoration Plan and Environmental Review AGENCY: Interior... (OPA), the National Environmental Policy Act (NEPA), and the Framework Agreement for Early...

  15. Protecting HAZMAT personnel: A multi-phase process

    SciTech Connect

    Ziegler, P. )

    1993-03-01

    Protecting personnel during hazardous substance releases is a process requiring several integrated elements. Managers must ensure the proper training has occurred and the appropriate personal protective equipment is available. They also must have a thorough understanding of applicable regulations, a well-defined contingency planning program, a ready inventory of air monitoring equipment and provisions for outside assistance. Several regulations apply to an organization that could be responsible for an oil or hazardous substance spill. These have been issued by several regulatory agencies, primarily the US Environmental Protection Agency (EPA) and the Occupational Safety and Health Administration (OSHA). For treatment, storage and disposal facilities and both large and small quantity generators under the jurisdiction of the Resource Conservation and Recovery Act (RCRA), several rules detail emergency planning and training requirements. Title 2 of the Superfund Amendments and Reauthorization Act of 1986 (SARA) established requirements that apply to nearly all industries mainly for emergency incident and chemical use notification. The goal of its provisions, also known as the Emergency Planning and Community Right-to-Know Act (EPCRA), is to enable states and communities to improve chemical safety and better protect public health and the environment.

  16. Protection Against Hearing Loss in General Aviation Operations, Phase II

    NASA Technical Reports Server (NTRS)

    Parker, J. F., Jr.

    1972-01-01

    An inflight evaluation of four aural protectors is presented. The hearing protection devices studied were ear muffs, plastic ear plugs, rubber ear plugs, and wax ear plugs. It is concluded that ear plugs are satisfactory for providing adequate sound attenuation in general aviation aircraft. However, two problems were found in the use of ear plugs; comfort and interference with cabin communications.

  17. 76 FR 78016 - Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and Environmental Assessment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-15

    ....S. Fish and Wildlife Service, Interior Deepwater Horizon Oil Spill; Draft Phase I Early Restoration... Environmental Policy Act (NEPA), and the Framework Agreement for Early Restoration Addressing Injuries Resulting...) have prepared a Draft Early Restoration Plan and Environmental Assessment (DERP/EA) describing...

  18. Raising sun protection and early detection awareness among Florida high schoolers.

    PubMed

    Geller, Alan C; Shamban, Jill; O'Riordan, David L; Slygh, Carolyn; Kinney, John P; Rosenberg, Steven

    2005-01-01

    Changing adolescents' sun protection behaviors remains a challenge, and the need for effective interventions targeting this group is a priority, particularly in warmer climates where emphasis on appropriate sun protection remains a year-round concern. However, there has been little prospective research on the effect of school-based sun protection interventions, particularly on adolescents, especially teens aged 15 to 18. High school science students in Palm Beach County, Florida, received a seven-lesson sun protection and early detection curriculum preceded by pretests and followed with post-tests 6 months later. The main outcome measures were student knowledge and sun protection practices, including adherence to sunscreen recommendations. Of 344 students completing the baseline surveys, 184 students completed the postintervention questionnaire. Overall, there were significant improvements from baseline to follow-up for many of the knowledge questions. Greatest change scores were seen in the children's ability to correctly define the five rules of early detection of skin cancer (27-60%, p<0.001) with improved change scores by gender and race persisting after 6 months. No significant differences were found in reported use of sunscreen, hat wearing, or sunglasses, although there was a slight decrease in the reported use of always wearing sun protective clothing (p=0.03). In conclusion, in this study, a skin cancer prevention and detection curriculum integrated into high school biology, resulted in knowledge gains maintained at least 6 months after classroom teaching. For example, procedural knowledge (e.g., knowing ways to identify early malignant moles) obtained in this study improved in 6 months, and may lay the foundation for future behavioral change. Sun protection activities in the United States have met with many challenges and obstacles and thus, further work is needed to better understand what combination of knowledge-based information, activity

  19. Does Religious Involvement Protect against Early Drinking? A Behavior Genetic Approach

    ERIC Educational Resources Information Center

    Harden, K. Paige

    2010-01-01

    Background: Adolescent involvement in religious organizations has been hypothesized to protect against early age at first drink. However, the correlation between adolescent religiosity and later age at first drink may be confounded by environmental or genetic differences between families. This study tests whether, after controlling for shared…

  20. Family Risks and Protective Factors: Pathways to Early Head Start Toddlers' Social-Emotional Functioning

    ERIC Educational Resources Information Center

    Vick Whittaker, Jessica E.; Harden, Brenda Jones; See, Heather M.; Meisch, Allison D.; Westbrook, T'Pring R.

    2011-01-01

    Early Head Start children may be more likely to exhibit difficulties with social-emotional functioning due to the high-risk environments in which they live. However, positive parenting may serve as a protective factor against the influence of risk on children's outcomes. The current study examines the effects of contextual and proximal risks on…

  1. Impact shocked rocks as protective habitats on an anoxic early Earth

    NASA Astrophysics Data System (ADS)

    Bryce, Casey C.; Horneck, Gerda; Rabbow, Elke; Edwards, Howell G. M.

    2015-01-01

    On Earth, microorganisms living under intense ultraviolet (UV) radiation stress can adopt endolithic lifestyles, growing within cracks and pore spaces in rocks. Intense UV irradiation encountered by microbes leads to death and significant damage to biomolecules, which also severely diminishes the likelihood of detecting signatures of life. Here we show that porous rocks shocked by asteroid or comet impacts provide protection for phototrophs and their biomolecules during 22 months of UV radiation exposure outside the International Space Station. The UV spectrum used approximated the high-UV flux on the surface of planets lacking ozone shields such as the early Earth. These data provide a demonstration that endolithic habitats can provide a refugium from the worst-case UV radiation environments on young planets and an empirical refutation of the idea that early intense UV radiation fluxes would have prevented phototrophs without the ability to form microbial mats or produce UV protective pigments from colonizing the surface of early landmasses.

  2. An early warning and control system for urban, drinking water quality protection: China's experience.

    PubMed

    Hou, Dibo; Song, Xiaoxuan; Zhang, Guangxin; Zhang, Hongjian; Loaiciga, Hugo

    2013-07-01

    An event-driven, urban, drinking water quality early warning and control system (DEWS) is proposed to cope with China's urgent need for protecting its urban drinking water. The DEWS has a web service structure and provides users with water quality monitoring functions, water quality early warning functions, and water quality accident decision-making functions. The DEWS functionality is guided by the principles of control theory and risk assessment as applied to the feedback control of urban water supply systems. The DEWS has been deployed in several large Chinese cities and found to perform well insofar as water quality early warning and emergency decision-making is concerned. This paper describes a DEWS for urban water quality protection that has been developed in China.

  3. Selenol protecting groups in organic chemistry: special emphasis on selenocysteine Se-protection in solid phase peptide synthesis.

    PubMed

    Flemer, Stevenson

    2011-04-18

    The appearance of selenium in organic synthesis is relatively rare, and thus examples in the literature pertaining to the masking of its considerable reactivity are similarly uncommon. Greene's Protecting Groups in Organic Synthesis, the standard reference for the state of the art in this arena, offers no entries for selenium protective methodology, in stark comparison to its mention of the great variety of protecting groups germane to its chalcogen cousin sulfur. This scarcity of Se-protection methods makes it no less interesting and pertinent toward the construction of selenium-containing organic systems which do indeed require the iterative blocking and de-blocking of selenol functionalities. A selenium-containing system which is especially relevant is selenocysteine, as its use in Solid Phase Peptide Synthesis requires extensive protection of its selenol side chain. This review will attempt to summarize the current state of understanding with regard to selenium protection protocol in organic synthesis. Moreover, it will provide a special emphasis on selenocysteine side chain protection, comprising both the breadth of functionality used for this purpose as well as methods of deprotection.

  4. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits...

  5. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits...

  6. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits...

  7. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits...

  8. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits...

  9. Oxidation Protection of Uranium Nitride Fuel using Liquid Phase Sintering

    SciTech Connect

    Dr. Paul A. Lessing

    2012-03-01

    Two methods are proposed to increase the oxidation resistance of uranium nitride (UN) nuclear fuel. These paths are: (1) Addition of USi{sub x} (e.g. U3Si2) to UN nitride powder, followed by liquid phase sintering, and (2) 'alloying' UN nitride with various compounds (followed by densification via Spark Plasma Sintering or Liquid Phase Sintering) that will greatly increase oxidation resistance. The advantages (high thermal conductivity, very high melting point, and high density) of nitride fuel have long been recognized. The sodium cooled BR-10 reactor in Russia operated for 18 years on uranium nitride fuel (UN was used as the driver fuel for two core loads). However, the potential advantages (large power up-grade, increased cycle lengths, possible high burn-ups) as a Light Water Reactor (LWR) fuel are offset by uranium nitride's extremely low oxidation resistance (UN powders oxidize in air and UN pellets decompose in hot water). Innovative research is proposed to solve this problem and thereby provide an accident tolerant LWR fuel that would resist water leaks and high temperature steam oxidation/spalling during an accident. It is proposed that we investigate two methods to increase the oxidation resistance of UN: (1) Addition of USi{sub x} (e.g. U{sub 3}Si{sub 2}) to UN nitride powder, followed by liquid phase sintering, and (2) 'alloying' UN nitride with compounds (followed by densification via Spark Plasma Sintering) that will greatly increase oxidation resistance.

  10. Development and Evaluation of Gold-Centered Monolayer Protected Nanoparticle Stationary Phases for Gas Chromatography

    SciTech Connect

    Gross, Gwen M.; Grate, Jay W.; Synovec, Robert E.

    2004-12-10

    The current status for the development of novel open-tubular gas chromatography (GC) stationary phases consists of thin films of gold-centered monolayer protected nanoparticles (MPNs) is reported. Dodecanethiol MPNs, in which the monolayer is dodecanethiol linked to the gold nanoparticle, have shown great promise as a GC stationary phase with efficient columns having been produced in a variety of capillary i.d.'s with stationary phase film depths ranging from 10-60 nm, +/- 2 nm at a given film depth. Stationary phase operational parameters are discussed including maximum operating temperature, sample capacity, and stationary phase lifetime and robustness.

  11. Quantum Phase Transition and Protected Ideal Transport in a Kondo Chain.

    PubMed

    Tsvelik, A M; Yevtushenko, O M

    2015-11-20

    We study the low energy physics of a Kondo chain where electrons from a one-dimensional band interact with magnetic moments via an anisotropic exchange interaction. It is demonstrated that the anisotropy gives rise to two different phases which are separated by a quantum phase transition. In the phase with easy plane anisotropy, Z_{2} symmetry between sectors with different helicity of the electrons is broken. As a result, localization effects are suppressed and the dc transport acquires (partial) symmetry protection. This effect is similar to the protection of the edge transport in time-reversal invariant topological insulators. The phase with easy axis anisotropy corresponds to the Tomonaga-Luttinger liquid with a pronounced spin-charge separation. The slow charge density wave modes have no protection against localization.

  12. Quantum phase transition and protected ideal transport in a Kondo chain

    SciTech Connect

    Tsvelik, A. M.; Yevtushenko, O. M.

    2015-11-30

    We study the low energy physics of a Kondo chain where electrons from a one-dimensional band interact with magnetic moments via an anisotropic exchange interaction. It is demonstrated that the anisotropy gives rise to two different phases which are separated by a quantum phase transition. In the phase with easy plane anisotropy, Z2 symmetry between sectors with different helicity of the electrons is broken. As a result, localization effects are suppressed and the dc transport acquires (partial) symmetry protection. This effect is similar to the protection of the edge transport in time-reversal invariant topological insulators. The phase with easy axis anisotropy corresponds to the Tomonaga-Luttinger liquid with a pronounced spin-charge separation. The slow charge density wave modes have no protection against localizatioin.

  13. Quantum phase transition and protected ideal transport in a Kondo chain

    DOE PAGES

    Tsvelik, A. M.; Yevtushenko, O. M.

    2015-11-30

    We study the low energy physics of a Kondo chain where electrons from a one-dimensional band interact with magnetic moments via an anisotropic exchange interaction. It is demonstrated that the anisotropy gives rise to two different phases which are separated by a quantum phase transition. In the phase with easy plane anisotropy, Z2 symmetry between sectors with different helicity of the electrons is broken. As a result, localization effects are suppressed and the dc transport acquires (partial) symmetry protection. This effect is similar to the protection of the edge transport in time-reversal invariant topological insulators. The phase with easy axismore » anisotropy corresponds to the Tomonaga-Luttinger liquid with a pronounced spin-charge separation. The slow charge density wave modes have no protection against localizatioin.« less

  14. Stripe melting and a transition between weak and strong symmetry protected topological phases

    NASA Astrophysics Data System (ADS)

    You, Yizhi; You, Yi-Zhuang

    2016-05-01

    For a gapped disordered many-body system with both internal and translation symmetry, one can define the corresponding weak and strong symmetry protected topological (SPT) phases. A strong SPT phase is protected by the internal symmetry G only while a weak SPT phase, fabricated by alignment of a strong SPT state in a lower dimension, requires additional discrete translation symmetry protection. In this paper, we construct a phase transition between weak and strong SPT phase in a strongly interacting boson system. The starting point of our construction is the superconducting Dirac fermions with pair density wave (PDW) order in 2 d . We first demonstrate that the nodal line of the PDW contains a 1 d boson SPT phase. We further show that melting the PDW stripe and condensing the nodal line provoke the transition from weak to strong SPT phase in 2 d . The phase transition theory contains an O(4) nonlinear-σ model (NL σ M ) with topological Θ term emerging from the proliferation of domain walls bound to an SPT chain. A similar scheme also applies to weak-strong SPT transition in other dimensions and predicts possible phase transition from 2 d to 3 d topological order.

  15. 76 FR 9583 - Draft Guidance for Industry on Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-18

    ... guidance for industry entitled ``Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase Clinical Studies.'' The draft guidance is intended to assist the pharmaceutical industry and other investigators... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Clinical...

  16. Entropy production in the early-cosmology pionic phase

    NASA Astrophysics Data System (ADS)

    Dobado, Antonio; Llanes-Estrada, Felipe J.; Rodríguez Fernández, David

    2016-07-01

    We point out that in the early universe, for temperatures in the approximate interval 150-80 MeV (after the quark-gluon plasma), pions carried a large share of the entropy and supported the largest inhomogeneities. Its thermal conductivity (previously calculated) allows the characterization of entropy production due to equilibration (damping) of thermal fluctuations. Simple model distributions of thermal fluctuations are considered and the associated entropy production evaluated.

  17. 78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Availability AGENCY: Food and... Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products'' dated July 2013. The draft... assist in designing early-phase clinical trials of CGT products. DATES: Although you can comment on...

  18. 78 FR 69690 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Extension of Comment Period... entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular... assist in designing early-phase clinical trials of CGT products. In the notice, we requested comments...

  19. Early Childhood Technology Integrated Instructional System (EC-TIIS) Phase 1: A Final Report

    ERIC Educational Resources Information Center

    Hutinger, Patricia; Robinson, Linda; Schneider, Carol

    2004-01-01

    The Early Childhood Technology Integrated Instructional System (EC-TIIS), a Steppingstones of Technology Innovation Phase 1--Development project, was developed by the Center for Best Practices in Early Childhood (the Center) at Western Illinois University as an online instructional system. EC-TIIS' ultimate goal was to improve technology services…

  20. Determinants of Cancer Early Detection Behaviors:Application of Protection Motivation Theory

    PubMed Central

    Rahaei, Zohreh; Ghofranipour, Fazlollah; Morowatisharifabad, Mohammad Ali; Mohammadi, Eesa

    2015-01-01

    Background: Cancer is account for 13% of all deaths around the world and is the third cause of mortality in Iran. More than one third of these cases are pre-ventable and about 33% are curable with early detection. The aim of this study was to determine the predictors of cancer early detection (CED) behaviors applying Protection Motivation Theory (PMT). Methods: In this cross-sectional study, cluster sampling method was employed to recruit 260 individuals of above 20 years old in Yazd, Iran and a researcher designed questionnaire was completed through interviews for each of the respondents. PMT theoretical variables and CED behaviors were the basis of data collection procedure. Results: Participants acquired 64.47% of the protection motivation, 30.97% of the passive and 45.64% of the active behaviors‟ possible scores. Theory constructs predicted 19.8%, 15.6% and 9.6% of the variations for protection motivation, passive and active behavior respectively. Protection motivation was responsible for 3.6% of passive and 8% of active behaviors‟ variations. Conclusion: Considering the scarceness of CED behaviors and the applicability of PMT in predicting these behaviors, utilization of the PMT‟s constructs in any interventional programs to accelerate CED behaviors could be an alternate methodological choice in the cancer control initiatives. PMID:26290829

  1. Ultrastructure of Pseudomonas saccharophila at early and late log phase of growth.

    NASA Technical Reports Server (NTRS)

    Young, H. L.; Chao, F.-C.; Turnbill, C.; Philpott, D. E.

    1972-01-01

    Description of the fine structure of Pseudomonas saccarophila at the early log phase and the late log phase of growth, such as shown by electron microscopy with the aid of various techniques of preparation. The observations reported suggested that, under the experimental conditions applied, P. saccharophila multiplies by the method of constrictive division.

  2. Observable induced gravitational waves from an early matter phase

    SciTech Connect

    Alabidi, Laila; Sasaki, Misao; Kohri, Kazunori; Sendouda, Yuuiti E-mail: kohri@post.kek.jp E-mail: sendouda@cc.hirosaki-u.ac.jp

    2013-05-01

    Assuming that inflation is succeeded by a phase of matter domination, which corresponds to a low temperature of reheating T{sub r} < 10{sup 9}GeV, we evaluate the spectra of gravitational waves induced in the post-inflationary universe. We work with models of hilltop-inflation with an enhanced primordial scalar spectrum on small scales, which can potentially lead to the formation of primordial black holes. We find that a lower reheat temperature leads to the production of gravitational waves with energy densities within the ranges of both space and earth based gravitational wave detectors.

  3. Therapeutic inhibition of the early phase of complement activation.

    PubMed

    Roos, Anja; Ramwadhdoebé, Tamara H; Nauta, Alma J; Hack, C Erik; Daha, Mohamed R

    2002-09-01

    The complement system is a key component of innate immunity against invading pathogens. However, undesired activation of complement is involved in inflammation and associated tissue damage in a number of pathological conditions, such as ischemia/reperfusion injury, autoimmune diseases, and rejection of allo- and xenografts. During recent years, various therapeutically active complement inhibitors have been developed. In vivo studies using these inhibitors underscored the value of complement inhibition in the prevention of tissue damage. The currently available complement inhibitors mainly target the effector phase of the complement system that is common to all three activation pathways. Such a complete block of complement activation breaks the innate anti-microbial barrier, thereby increasing the risk for infection. Therefore, the development of potent complement inhibitors that interfere in the recognition phase of a specific complement activation pathway will generate important novel possibilities for treatment. The present review is focused on molecules that are able to inhibit the function of C1q and MBL, the recognition units of the classical pathway and the lectin pathway of complement, respectively. The potential value of these molecules for the development of therapeutically active complement inhibitors is discussed.

  4. Endogenous hydrogen sulfide mediates the cardioprotection induced by ischemic postconditioning in the early reperfusion phase

    PubMed Central

    HUANG, YI-E; TANG, ZHI-HAN; XIE, WEI; SHEN, XIN-TIAN; LIU, MI-HUA; PENG, XIANG-PING; ZHAO, ZHAN-ZHI; NIE, DE-BO; LIU, LU-SHAN; JIANG, ZHI-SHENG

    2012-01-01

    Hydrogen sulfide (H2S), produced by cystanthionine-γ-lysase (CSE) in the cardiovascular system, has been suggested to be the third gasotransmitter in addition to nitric oxide (NO) and carbon monoxide (CO). The present study aimed to investigate the role of H2S in ischemic postconditioning (IPO) during the early period of reperfusion. IPO with 6 episodes of 10 sec reperfusion followed by 6 episodes of 10 sec ischemia (IPO 2’) was administered when reperfusion was initiated. Cardiodynamics and the concentration of H2S were measured at 1, 2, 3, 4, 5, 10, 20, 30, 60, 90 and 120 min of reperfusion. Lactate dehydrogenase (LDH) levels and infarct size were determined at the end of the reperfusion. The concentration of H2S was stable during the whole experiment in the control group, whereas it reached a peak at the first minute of reperfusion in the ischemia-reperfusion (IR) group. The concentration of H2S at the first minute of reperfusion in the IPO 2’ group was higher compared to that of the IR group, which correlated with cardioprotection including improved heart contractile function and reduced infarct size and LDH levels. However, the above effects of IPO 2’ were attenuated by pre-treatment with blockade of endogenous H2S production with DL-propargylglycine for 20 min prior to global ischemia. Furthermore, we found that other forms of IPO, IPO commencing at 1 min after reperfusion (delayed IPO) or lasting only for 1 min (IPO 1’), failed to increase the concentration of H2S and protect the myocardium. We conclude that the peak of endogenous H2S in the early reperfusion phase is the key to cardioprotection induced by IPO. PMID:23226785

  5. The early phases of galaxy formation and evolution

    NASA Astrophysics Data System (ADS)

    Dickinson, Mark

    2016-05-01

    I review observations of galaxy formation and evolution from multiwavelength deep field surveys. These programs are designed to detect and study galaxies over a large range of cosmic history, with observations and many different wavelengths, each of which is important for measuring different physical processes at work in evolving galaxies. I begin with some background motivating interest in multiwavelength deep fields, and a short review of energetic processes that result in emission from galaxies in different wavelength/energy ranges. I then give a short summary of major observing facilities that are currently used for multiwavelength deep surveys, and then offer short descriptions of some of the major surveys that have produced much of the data used today by astronomers studying distant galaxy evolution. I continue with an overview of different methods that are commonly used to identify various types of galaxies at high redshift in deep field data sets. Then, for the remainder of the review, I focus on measurements of star formation rates and stellar masses in galaxies, and how they are used to evaluate the history of galaxy growth and evolution. I discuss the ways in which data at different wavelengths are used to infer star formation rates and stellar masses, concentrating on the complementarity of different techniques, as well as their limitations. I then discuss application of these methods for deriving the global history of star formation in the universe. These measurement now push back over more than 13 billion years of cosmic history and portray the rapid early growth of galaxies, and then the long, slow decline of star formation rates to the present era. I discuss recent results on the nature of star formation in galaxies at the peak epoch of galaxy growth, particularly around redshifts of 2, and their implications about the dominant physical processes that shaped the growth of most galaxies from the earliest times to the present day.

  6. Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress.

    PubMed

    Reuland, Danielle J; Khademi, Shadi; Castle, Christopher J; Irwin, David C; McCord, Joe M; Miller, Benjamin F; Hamilton, Karyn L

    2013-03-01

    Increased production of reactive oxygen species has been implicated in the pathogenesis of cardiovascular disease (CVD), and enhanced endogenous antioxidants have been proposed as a mechanism for regulating redox balance. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcriptional regulator of phase II antioxidant enzymes, and activation of Nrf2 has been suggested to be an important step in attenuating oxidative stress associated with CVD. A well-defined combination of five widely studied medicinal plants derived from botanical sources (Bacopa monniera, Silybum marianum (milk thistle), Withania somnifera (Ashwagandha), Camellia sinensis (green tea), and Curcuma longa (turmeric)) has been shown to activate Nrf2 and induce phase II enzymes through the antioxidant response element. The purpose of these experiments was to determine if treatment of cardiomyocytes with this phytochemical composition, marketed as Protandim, activates Nrf2, induces phase II detoxification enzymes, and protects cardiomyocytes from oxidant-induced apoptosis in a Nrf2-dependent manner. In cultured HL-1 cardiomyocytes, phytochemical treatment was associated with nuclear accumulation of Nrf2, significant induction of phase II enzymes, and concomitant protection against hydrogen peroxide-induced apoptosis. The protection against oxidant stress was abolished when Nrf2 was silenced by shRNA, suggesting that our phytochemical treatment worked through the Nrf2 pathway. Interestingly, phytochemical treatment was found to be a more robust activator of Nrf2 than oxidant treatment, supporting the use of the phytochemicals as a potential treatment to increase antioxidant defenses and protect heart cells against an oxidative challenge.

  7. Protection relay of phase-shifting device with thyristor switch for high voltage power transmission lines

    NASA Astrophysics Data System (ADS)

    Lachugin, V. F.; Panfilov, D. I.; Akhmetov, I. M.; Astashev, M. G.; Shevelev, A. V.

    2014-12-01

    Problems of functioning of differential current protection systems of phase shifting devices (PSD) with mechanically changed coefficient of transformation of shunt transformer are analyzed. Requirements for devices of protection of PSD with thyristor switch are formulated. Based on use of nonlinear models of series-wound and shunt transformers of PSD modes of operation of major protection during PSD, switching to zero load operation and to operation under load and during short circuit operation were studied for testing PSD with failures. Use of the principle of duplicating by devices of differential current protection (with realization of functions of breaking) of failures of separate pares of PSD with thyristor switch was substantiated. To ensure protection sensitivity to the shunt transformer winding short circuit, in particular, to a short circuit that is not implemented in the current differential protection for PSD with mechanical switch, the differential current protection reacting to the amount of primary ampere-turns of high-voltage and low-voltage winding of this transformer was designed. Studies have shown that the use of differential current cutoff instead of overcurrent protection for the shunt transformer wndings allows one to provide the sensitivity during thyristor failure with the formation of a short circuit. The results of simulation mode for the PSD with switch thyristor designed to be installed as switching point of Voskhod-Tatarskaya-Barabinsk 220 kV transmission line point out the efficiency of the developed solutions that ensure reliable functioning of the PSD.

  8. Radiation protection program for early detection of breast cancer in a mammography facility

    NASA Astrophysics Data System (ADS)

    Villagomez Casimiro, Mariana; Ruiz Trejo, Cesar; Espejo Fonseca, Ruby

    2014-11-01

    Mammography is the best tool for early detection of Breast Cancer. In this diagnostic radiology modality it is necessary to establish the criteria to ensure the proper use and operation of the equipment used to obtain mammographic images in order to contribute to the safe use of ionizing radiation. The aim of the work was to implement at FUCAM-AC the radiation protection program which must be established for patients and radiation workers according to Mexican standards [1-4]. To achieve this goal, radiation protection and quality control manuals were elaborated [5]. Furthermore, a quality control program (QCP) in the mammography systems (analog/digital), darkroom included, has been implemented. Daily sensitometry, non-variability of the image quality, visualizing artifacts, revision of the equipment mechanical stability, compression force and analysis of repetition studies are some of the QCP routine tests that must be performed by radiological technicians of this institution as a set of actions to ensure the protection of patients. Image quality and patients dose assessment were performed on 4 analog equipment installed in 2 mobile units. In relation to dose assessment, all equipment passed the acceptance criteria (<3 mGy per projection). The image quality test showed that most images (70%)- presented artifacts. A brief summary of the results of quality control tests applied to the equipment and film processor are presented. To maintain an adequate level of quality and safety at FUCAM-AC is necessary that the proposed radiation protection program in this work is applied.

  9. Radiation protection program for early detection of breast cancer in a mammography facility

    SciTech Connect

    Mariana, Villagomez Casimiro E-mail: cesar@fisica.unam.mx; Cesar, Ruiz Trejo E-mail: cesar@fisica.unam.mx; Ruby, Espejo Fonseca

    2014-11-07

    Mammography is the best tool for early detection of Breast Cancer. In this diagnostic radiology modality it is necessary to establish the criteria to ensure the proper use and operation of the equipment used to obtain mammographic images in order to contribute to the safe use of ionizing radiation. The aim of the work was to implement at FUCAM-AC the radiation protection program which must be established for patients and radiation workers according to Mexican standards [1–4]. To achieve this goal, radiation protection and quality control manuals were elaborated [5]. Furthermore, a quality control program (QCP) in the mammography systems (analog/digital), darkroom included, has been implemented. Daily sensitometry, non-variability of the image quality, visualizing artifacts, revision of the equipment mechanical stability, compression force and analysis of repetition studies are some of the QCP routine tests that must be performed by radiological technicians of this institution as a set of actions to ensure the protection of patients. Image quality and patients dose assessment were performed on 4 analog equipment installed in 2 mobile units. In relation to dose assessment, all equipment passed the acceptance criteria (<3 mGy per projection). The image quality test showed that most images (70%)– presented artifacts. A brief summary of the results of quality control tests applied to the equipment and film processor are presented. To maintain an adequate level of quality and safety at FUCAM-AC is necessary that the proposed radiation protection program in this work is applied.

  10. Early Expressed Clb Proteins Allow Accumulation of Mitotic Cyclin by Inactivating Proteolytic Machinery during S Phase

    PubMed Central

    Yeong, Foong May; Lim, Hong Hwa; Wang, Ya; Surana, Uttam

    2001-01-01

    Periodic accumulation and destruction of mitotic cyclins are important for the initiation and termination of M phase. It is known that both APCCdc20 and APCHct1 collaborate to destroy mitotic cyclins during M phase. Here we show that this relationship between anaphase-promoting complex (APC) and Clb proteins is reversed in S phase such that the early Clb kinases (Clb3, Clb4, and Clb5 kinases) inactivate APCHct1 to allow Clb2 accumulation. This alternating antagonism between APC and Clb proteins during S and M phases constitutes an oscillatory system that generates undulations in the levels of mitotic cyclins. PMID:11438663

  11. A matter of timing: early, not chronic phase intestinal nematode infection restrains control of a concurrent enteric protozoan infection.

    PubMed

    Rausch, Sebastian; Held, Josephin; Stange, Joerg; Lendner, Matthias; Hepworth, Matthew R; Klotz, Christian; Lucius, Richard; Pogonka, Thomas; Hartmann, Susanne

    2010-10-01

    Infections with parasitic worms are often long lasting and associated with modulated immune responses. We analyzed the influence of the nematode Heligmosomoides polygyrus bakeri dwelling in the small intestine on concurrent protozoan infection with Eimeria falciformis residing in the cecum. To dissect the effects of a nematode infection in the early versus chronic phase, we infected animals with E. falciformis 6 or 28 days post H. p. bakeri infection. Only a concurrent early nematode infection led to an increased replication of the protozoan parasite, whereas a chronic worm infection had no influence on the control of E. falciformis. Increased protozoan replication correlated with the reduced production of IFN-γ, IL-12/23, CCL4, CXCL9 and CXCL10, reduced migration of T cells and increased expression of Foxp3 at the site of protozoan infection. This was accompanied by a stronger nematode-specific Th2 response in gut-draining LN. Protection of mice against challenge infections with the protozoan parasite was not altered. Hence, the detrimental effect of a nematode infection on the control of a concurrent protozoan infection is transient and occurs only in the narrow time window of the early phase of infection.

  12. Possible realization of interacting symmetry-protected topological phases in topological crystalline insulators

    NASA Astrophysics Data System (ADS)

    Isobe, Hiroki; Fu, Liang

    2015-03-01

    The effects of electron-electron interaction in edge states of mirror-symmetry protected topological crystalline insulators (TCI's) are discussed. The analysis is performed by using bosonized Hamiltonian following the Tomonaga-Luttinger liquid theory. When two pairs of helical edge states exist, electron-electron interaction could gap out one edge mode, which is a possible realization of interacting symmetry-protected topological (SPT) phases. This type of SPT phase is closely related to a Luther-Emery liquid in spinful 1D system. We also propose a method of detecting the SPT phases by STM. The other focus of the study is the classification of SPT phases in mirror-symmetry protected TCI's. By adopting the Chern-Simons theory, we find that electron-electron interaction reduces the classification from Z to Z4. It means that the edge states can be gapped out when four pairs of edge states exist. In other cases, the edge modes cannot be fully gapped. Each of these states corresponds to a different SPT phase depending on the relevant interaction process.

  13. Visualizing a bosonic symmetry protected topological phase in an interacting fermion model

    NASA Astrophysics Data System (ADS)

    Wu, Han-Qing; He, Yuan-Yao; You, Yi-Zhuang; Yoshida, Tsuneya; Kawakami, Norio; Xu, Cenke; Meng, Zi Yang; Lu, Zhong-Yi

    2016-10-01

    Symmetry protected topological (SPT) phases in free fermion and interacting bosonic systems have been classified, but the physical phenomena of interacting fermionic SPT phases have not been fully explored. Here, employing large-scale quantum Monte Carlo simulation, we investigate the edge physics of a bilayer Kane-Mele-Hubbard model with zigzag ribbon geometry. Our unbiased numerical results show that the fermion edge modes are gapped out by interaction, while the bosonic edge modes remain gapless at the (1 +1 )d boundary, before the bulk quantum phase transition to a topologically trivial phase. Therefore, finite fermion gaps both in the bulk and on the edge, together with the robust gapless bosonic edge modes, prove that our system becomes an emergent bosonic SPT phase at low energy, which is directly observed in an interacting fermion lattice model.

  14. Detecting 2D symmetry-protected topological phases with the tensor-network method

    NASA Astrophysics Data System (ADS)

    Huang, Ching-Yu; Wei, Tzu-Chieh

    Symmetry-protected topological (SPT) phases exhibit nontrivial order if symmetry is respected but are adiabatically connected to the trivial product phase if symmetry is not respected. However, unlike the symmetry breaking phase, there is no local order parameter for SPT phases. Here we employ a tensor-network method to compute the topological invariants characterized by the simulated modular S and T matrices proposed by Hung and Wen to study a transition in a one-parameter family of wavefunctions which are Z2 symmetric. The studied wavefunctions are in some sense the SPT analog of Z2 topological states under a string tension. The numerically obtained S and T matrices are able to characterize the two different phases and identify the transition point.

  15. The Risk-Escalation Model: A Principled Design Strategy for Early-Phase Trials

    PubMed Central

    Hey, Spencer Phillips; Kimmelman, Jonathan

    2015-01-01

    Should first-in-human trials be designed to maximize the prospect of therapeutic benefit for volunteers, prioritize avoidance of unintended harms, or aim for some happy medium between the two? Perennial controversies surrounding initiation and design of early-phase trials hinge on how this question is resolved. In this paper, we build on the premise that the task of early-phase testing is to optimize various components of a potential therapy so that later, confirmatory trials have the maximal probability of informing drug development and clinical care. We then explore three strategies that investigators might use to manage trial risks while optimizing a therapy, using cell therapy for Amyotrophic Lateral Sclerosis (ALS) as an example. We argue that an iterative application of maximin strategies over successive cohorts and trials, which we call the “risk-escalation model,” establishes a moral principle that should guide decision-making in early-phase trials. PMID:25109092

  16. Modeling thermal insulation of firefighting protective clothing embedded with phase change material

    NASA Astrophysics Data System (ADS)

    Hu, Yin; Huang, Dongmei; Qi, Zhengkun; He, Song; Yang, Hui; Zhang, Heping

    2013-04-01

    Experiments and research on heat transport through firefighting protective clothing when exposed to high temperature or intensive radiation are significant. Phase change material (PCM) takes energy when changes from solid to liquid thus reducing heat transmission. A numerical simulation of heat protection of the firefighting protective clothing embedded with PCM was studied. We focused on the temperature variation by comparing different thicknesses and position conditions of PCM combined in the clothing, as well as the melting state of PCM and human irreversible burns through a simplified one-dimensional model. The results showed it was superior to place PCM between water and proof layer and inner layer, in addition, greater thickness increased protection time while might adding extra burden to the firefighter.

  17. Life history biology of early land plants: Deciphering the gametophyte phase

    PubMed Central

    Taylor, Thomas N.; Kerp, Hans; Hass, Hagen

    2005-01-01

    The ca. 400-million-year-old Rhynie chert biota represents a benchmark for studies of early terrestrial ecosystems. The exquisite preservation of the organisms documents an ancient biodiversity that also includes various levels of biological interaction. Absent from the picture until recently has been detailed information about the development of the gametophyte phase and the alternation of generations of the macroplants in this ecosystem. Here, we trace the development of the gametophyte phase of Aglaophyton, an early land plant with an unusual complement of structural and morphological characters. Mature gametophytes consist of a fleshy protocorm attached to the substrate by basal rhizoids; arising from the upper surface are one to several upright gametangiophores bearing multiple gametangia. Stomata are present on the upper surface of the protocorm and gametangiophore, and endomycorrhizal fungi extend throughout the gametophyte. Gametophytes are unisexual, producing either antheridiophores or archegoniophores. There is no evidence that gametophytes later become hermaphroditic. The sexual dimorphism of the Rhynie chert gametophytes is inconsistent with theoretical ideas about the haploid phase of early land plants. The gametophyte phase of early land plants can now be considered within an ecological and evolutionary framework that, in turn, can be used to develop hypotheses about some aspects of the population dynamics and growth of these early land plants. PMID:15809414

  18. The Relationship between Sun Protection Policy and Associated Practices in a National Sample of Early Childhood Services in Australia

    ERIC Educational Resources Information Center

    Ettridge, Kerry A.; Bowden, Jacqueline A.; Rayner, Joanne M.; Wilson, Carlene J.

    2011-01-01

    Limiting exposure to sunlight during childhood can significantly reduce the risk of skin cancer. This was the first national study to assess the sun protection policies and practices of early childhood services across Australia. It also examined the key predictors of services' sun protection practices. In 2007, 1017 respondents completed a…

  19. Using the Devereux Early Childhood Assessment to Identify Behavioral Risk and Protective Factors within a Head Start Population

    ERIC Educational Resources Information Center

    Brinkman, Tara M.; Wigent, Catherine A.; Tomac, Rachelle A.; Pham, Andy V.; Carlson, John S.

    2007-01-01

    The purpose of this study was to examine the prevalence of behavioral risk and protective factors among at-risk preschoolers. Parent-reported data ( N = 2,550) from the Devereux Early Childhood Assessment (DECA) indicated that Head Start preschoolers had significantly more behavior concerns and fewer protective factors than would be expected based…

  20. Baseline Survey of Sun-Protection Knowledge, Practices and Policy in Early Childhood Settings in Queensland, Australia

    ERIC Educational Resources Information Center

    Harrison, Simone L.; Saunders, V.; Nowak, M.

    2007-01-01

    Excessive exposure to sunlight during early childhood increases the risk of developing skin cancer. Self-administered questionnaires exploring sun-protection knowledge, practices and policy were mailed to the directors/co-ordinators/senior teachers of all known early childhood services in Queensland, Australia, in 2002 (n = 1383; 56.5% response).…

  1. A novel Fmoc-based anchorage for the synthesis of protected peptides on solid phase.

    PubMed

    Liu, Y Z; Ding, S H; Chu, J Y; Felix, A M

    1990-02-01

    A novel bifunctional compound, 9-(hydroxymethyl)-2-fluoreneacetic acid, was synthesized, coupled to benzhydrylamine-resin, and evaluated for its application to the solid phase synthesis of protected peptide fragments. Anchor-bond cleavage was achieved with 15% piperidine/DMF. A protected heptapeptide, Boc-Val-Val-Ser(Bzl)-His(Tos)-Phe-Asn-Lys-(Z)-OH, corresponding to the sequence (1-7) of rat-transforming growth factor-alpha, was synthesized using this new support with an overall yield of 46%.

  2. Implementing Effective Mission Systems Engineering Practices During Early Project Formulation Phases

    NASA Technical Reports Server (NTRS)

    Moton, Tryshanda

    2016-01-01

    Developing and implementing a plan for a NASA space mission can be a complicated process. The needs, goals, and objectives of any proposed mission or technology must be assessed early in the Project Life Cycle. The key to successful development of a space mission or flight project is the inclusion of systems engineering in early project formulation, namely during Pre-phase A, Phase A, and Phase B of the NASA Project Life Cycle. When a space mission or new technology is in pre-development, or "pre-Formulation", feasibility must be determined based on cost, schedule, and risk. Inclusion of system engineering during project formulation is key because in addition to assessing feasibility, design concepts are developed and alternatives to design concepts are evaluated. Lack of systems engineering involvement early in the project formulation can result in increased risks later in the implementation and operations phases of the project. One proven method for effective systems engineering practice during the pre-Formulation Phase is the use of a mission conceptual design or technology development laboratory, such as the Mission Design Lab (MDL) at NASA's Goddard Space Flight Center (GSFC). This paper will review the engineering process practiced routinely in the MDL for successful mission or project development during the pre-Formulation Phase.

  3. Gram staining of protected pulmonary specimens in the early diagnosis of ventilator-associated pneumonia.

    PubMed

    Mimoz, O; Karim, A; Mazoit, J X; Edouard, A; Leprince, S; Nordmann, P

    2000-11-01

    We evaluated prospectively the use of Gram staining of protected pulmonary specimens to allow the early diagnosis of ventilator-associated pneumonia (VAP), compared with the use of 60 bronchoscopic protected specimen brushes (PSB) and 126 blinded plugged telescopic catheters (PTC) obtained from 134 patients. Gram stains were from Cytospin slides; they were studied for the presence of microorganisms in 10 and 50 fields by two independent observers and classified according to their Gram stain morphology. Quantitative cultures were performed after serial dilution and plating on appropriate culture medium. A final diagnosis of VAP, based on a culture of > or = 10(3) c.f.u. ml-1, was established after 81 (44%) samplings. When 10 fields were analysed, a strong relationship was found between the presence of bacteria on Gram staining and the final diagnosis of VAP (for PSB and PTC respectively: sensitivity 74 and 81%, specificity 94 and 100%, positive predictive value 91 and 100%, negative predictive value 82 and 88%). The correlation was less when we compared the morphology of microorganisms observed on Gram staining with those of bacteria obtained from quantitative cultures (for PSB and PTC respectively: sensitivity 54 and 69%, specificity 86 and 89%, positive predictive value 72 and 78%, negative predictive value 74 and 84%). Increasing the number of fields read to 50 was associated with a slight decrease in specificity and positive predictive value of Gram staining, but with a small increase in its sensitivity and negative predictive value. The results obtained by the two observers were similar to each other for both numbers of fields analysed. Gram staining of protected pulmonary specimens performed on 10 fields predicted the presence of VAP and partially identified (using Gram stain morphology) the microorganisms growing at significant concentrations, and could help in the early choice of the treatment of VAP. Increasing the number of fields read or having the Gram

  4. Safeguards-by-Design: Early Integration of Physical Protection and Safeguardability into Design of Nuclear Facilities

    SciTech Connect

    T. Bjornard; R. Bean; S. DeMuth; P. Durst; M. Ehinger; M. Golay; D. Hebditch; J. Hockert; J. Morgan

    2009-09-01

    The application of a Safeguards-by-Design (SBD) process for new nuclear facilities has the potential to minimize proliferation and security risks as the use of nuclear energy expands worldwide. This paper defines a generic SBD process and its incorporation from early design phases into existing design / construction processes and develops a framework that can guide its institutionalization. SBD could be a basis for a new international norm and standard process for nuclear facility design. This work is part of the U.S. DOE’s Next Generation Safeguards Initiative (NGSI), and is jointly sponsored by the Offices of Non-proliferation and Nuclear Energy.

  5. Webcam Delivery of the Lidcombe Program for Early Stuttering: A Phase I Clinical Trial

    ERIC Educational Resources Information Center

    O'Brian, Sue; Smith, Kylie; Onslow, Mark

    2014-01-01

    Purpose: The Lidcombe Program is an operant treatment for early stuttering shown with meta-analysis to have a favorable odds ratio. However, many clients are unable to access the treatment because of distance and lifestyle factors. In this Phase I trial, we explored the potential efficacy, practicality, and viability of an Internet webcam Lidcombe…

  6. Histone modifications induced by MDV infection at early cytolytic and latency phases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Marek’s disease (MD) is a highly contagious, lymphomatous disease of chickens induced by a herpesvirus, Marek’s disease virus (MDV) that is the cause of major annual losses to the poultry industry. MD pathogenesis involves multiple stages including an early cytolytic phase and latency, a...

  7. Early weaning alters the acute phase immune response to an endotoxin challenge in beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research indicates that early weaning prior to shipment can reduce transportation-induced increases in acute phase proteins (APP), and can increase subsequent performance in the feedlot. These data suggest that the combination of weaning and transport stress may compromise the immune system...

  8. Early weaning alters the acute phase response to an endotoxin challenge in beef calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research indicates that early weaning prior to shipment can reduce transportation-induced increases in acute phase proteins (APP), and can increase subsequent performance in the feedlot. These data suggest that the combination of weaning and transport stress may compromise the immune system...

  9. Teachers' Beliefs on Foreign Language Teaching Practices in Early Phases of Primary Education: A Case Study

    ERIC Educational Resources Information Center

    Caner, Mustafa; Subasi, Gonca; Kara, Selma

    2010-01-01

    The purpose of the study was to examine whether teacher beliefs would play a role in their actual practices while teaching target language in early phases of primary education, principally, in kindergarten and first grades in a state school. As it is a very broad research area, the researchers exclusively analyzed teaching practices and teaching…

  10. Regulation of a ribonucleoside reductase during the early generative phase in Acetabularia.

    PubMed

    de Groot, E J; Schweiger, H G

    1985-02-01

    The activity of a ribonucleoside reductase was estimated during the life cycle of Acetabularia. During the early generative phase the enzyme activity was dramatically increased. Regulation of the ribonucleoside reductase was observed even in the absence of the nucleus. The increase in activity was inhibited by chloramphenicol but not by cycloheximide. These results indicate that the enzyme is translated on 70 S ribosomes.

  11. Fermionic Symmetry-Protected Topological Phase in a Two-Dimensional Hubbard Model

    NASA Astrophysics Data System (ADS)

    Chen, Cheng-Chien; Muechler, Lukas; Car, Roberto; Neupert, Titus; Maciejko, Joseph

    2016-08-01

    We study the two-dimensional (2D) Hubbard model using exact diagonalization for spin-1 /2 fermions on the triangular and honeycomb lattices decorated with a single hexagon per site. In certain parameter ranges, the Hubbard model maps to a quantum compass model on those lattices. On the triangular lattice, the compass model exhibits collinear stripe antiferromagnetism, implying d -density wave charge order in the original Hubbard model. On the honeycomb lattice, the compass model has a unique, quantum disordered ground state that transforms nontrivially under lattice reflection. The ground state of the Hubbard model on the decorated honeycomb lattice is thus a 2D fermionic symmetry-protected topological phase. This state—protected by time-reversal and reflection symmetries—cannot be connected adiabatically to a free-fermion topological phase.

  12. Fermionic Symmetry-Protected Topological Phase in a Two-Dimensional Hubbard Model.

    PubMed

    Chen, Cheng-Chien; Muechler, Lukas; Car, Roberto; Neupert, Titus; Maciejko, Joseph

    2016-08-26

    We study the two-dimensional (2D) Hubbard model using exact diagonalization for spin-1/2 fermions on the triangular and honeycomb lattices decorated with a single hexagon per site. In certain parameter ranges, the Hubbard model maps to a quantum compass model on those lattices. On the triangular lattice, the compass model exhibits collinear stripe antiferromagnetism, implying d-density wave charge order in the original Hubbard model. On the honeycomb lattice, the compass model has a unique, quantum disordered ground state that transforms nontrivially under lattice reflection. The ground state of the Hubbard model on the decorated honeycomb lattice is thus a 2D fermionic symmetry-protected topological phase. This state-protected by time-reversal and reflection symmetries-cannot be connected adiabatically to a free-fermion topological phase. PMID:27610869

  13. Archeological treasures protection based on early forest wildfire multi-band imaging detection system

    NASA Astrophysics Data System (ADS)

    Gouverneur, B.; Verstockt, S.; Pauwels, E.; Han, J.; de Zeeuw, P. M.; Vermeiren, J.

    2012-10-01

    Various visible and infrared cameras have been tested for the early detection of wildfires to protect archeological treasures. This analysis was possible thanks to the EU Firesense project (FP7-244088). Although visible cameras are low cost and give good results during daytime for smoke detection, they fall short under bad visibility conditions. In order to improve the fire detection probability and reduce the false alarms, several infrared bands are tested ranging from the NIR to the LWIR. The SWIR and the LWIR band are helpful to locate the fire through smoke if there is a direct Line Of Sight. The Emphasis is also put on the physical and the electro-optical system modeling for forest fire detection at short and longer ranges. The fusion in three bands (Visible, SWIR, LWIR) is discussed at the pixel level for image enhancement and for fire detection.

  14. Replacement of Ablators with Phase-Change Material for Thermal Protection of STS Elements

    NASA Technical Reports Server (NTRS)

    Kaul, Raj K.; Stuckey, Irvin; Munafo, Paul M. (Technical Monitor)

    2002-01-01

    As part of the research and development program to develop new Thermal Protection System (TPS) materials for aerospace applications at NASA's Marshall Space Flight Center (MSFC), an experimental study was conducted on a new concept for a non-ablative TPS material. Potential loss of TPS material and ablation by-products from the External Tank (ET) or Solid Rocket Booster (SRB) during Shuttle flight with the related Orbiter tile damage necessitates development of a non-ablative thermal protection system. The new Thermal Management Coating (TMC) consists of phase-change material encapsulated in micro spheres and a two-part resin system to adhere the coating to the structure material. The TMC uses a phase-change material to dissipate the heat produced during supersonic flight rather than an ablative material. This new material absorbs energy as it goes through a phase change during the heating portion of the flight profile and then the energy is slowly released as the phase-change material cools and returns to its solid state inside the micro spheres. The coating was subjected to different test conditions simulating design flight environments at the NASA/MSFC Improved Hot Gas Facility (IHGF) to study its performance.

  15. Phase I study of a topical skin protectant against chemical warfare agents.

    PubMed

    Eisenkraft, Arik; Krivoy, Amir; Vidan, Aviv; Robenshtok, Eyal; Hourvitz, Ariel; Dushnitsky, Tsvika; Markel, Gal

    2009-01-01

    Vesicants and some nerve agents penetrate exposed skin, mainly through the sensitive integration areas of the personal protective equipment. Therefore, improving dermal barrier with a topical agent should reduce the threat of exposure. A topical skin protectant lotion (IB1) was developed to improve protection against chemical warfare agents. Preclinical studies in several animal models have proven the protective efficacy of IB1. Here we present the results of a randomized placebo-controlled, double-blind phase I clinical study, performed with 34 healthy volunteers. The study tested the safety of repeated applications, including ruling out transdermal permeation of magnesium, which may lead to a dangerous blood magnesium level, since the lotion contains magnesium sulfate. Other objectives included detection of dermatological adverse effects, assessment of application convenience, and effect on daily activities. Importantly, no serious adverse effects were recorded and the lotion did not interfere with daily tasks. There were no significant differences in magnesium levels between the placebo and the study groups in any of the applications. No toxic levels of magnesium were found in either group. We conclude that IB1 is probably safe, easily self-applied, and does not cause any significant inconvenience. Therefore, IB1 can be considered as an adjunctive chemical, biological, and radio-nuclear (CBRN) protective aid to field soldiers.

  16. CRP at early follicular phase of menstrual cycle can cause misinterpretation for cardiovascular risk assessment

    PubMed Central

    Gursoy, Asli Yarci; Caglar, Gamze Sinem; Kiseli, Mine; Pabuccu, Emre; Candar, Tuba; Demirtas, Selda

    2015-01-01

    Objective C-reactive protein (CRP) is a well-known marker of inflammation and infection in clinical practice. This study is designed to evaluate CRP levels in different phases of menstrual cycle, which might end up with misleading conclusions especially when used for cardiovascular risk assessment. Methods Twenty-seven women were eligible for the cross-sectional study. Venous blood samples from each participant were collected twice during the menstrual cycle. The first sampling was held at 2nd to 5th days of the menstrual cycle for FSH, estradiol, CRP, and sedimentation, and the second was done at 21st to 24th days of the menstrual cycle for measurement of progesterone, CRP, and sedimentation values. Results CRP values were significantly higher in the early follicular phase compared to luteal phase (1.8 mg/L [0.3–7.67] vs. 0.7 mg/L [0.1–8.3], p < 0.001, respectively). In both phases of the menstrual cycle, sedimentation rate was similar (12.1 ± 6.7 vs. 12.3 ± 7.7; p = 0.717, respectively). Conclusions CRP levels in early follicular phase of the menstrual cycle (menstruation) are significantly higher than CRP levels in luteal phase of the same cycle. In reproductive age women, detection of CRP for cardiovascular risk assessment during menstruation might not be appropriate. PMID:26767119

  17. Analysis of short range entangled topological phases protected by time-reversal symmetry

    NASA Astrophysics Data System (ADS)

    Dick, Sebastian

    We discuss a short-range entangled topological phase in 3+1 dimensions that is protected by time-reversal symmetry. Two models are compared that realize this phase: The first is a construction developed by Chen, Gu, Liu and Wen, which encodes the system's topological properties in the representation of the symmetry group. The second theory uses a non-linear sigma model in which the distinct topological phases differ by the way the symmetry acts on the order parameter. Both theories have in common that the modeled phases are in one to one correspondence with the elements of the co-homology group Hd+1(Z2 T, UT(1)). In this work, we extend the Chen-Gu construction to 3+1 dimensional systems. Furthermore, we show that both models coincide with respect to their topological properties. This is proved by comparing spin-flip processes and their associated topological phase factors. We derive spin-flip operators on the surface of the (3+1)-dimensional Chen-Gu construction that commute with time-reversal symmetry. To implement spin-flip processes in the non-linear sigma model, we interpolate spin-configurations from a discrete, triangular lattice into the continuum. We proceed by analyzing the phases, generated by the theta-term, for spacetime configurations of the O(4) order parameter that correspond to these spin-flip processes.

  18. Application of Advanced Wide Area Early Warning Systems with Adaptive Protection

    SciTech Connect

    Blumstein, Carl; Cibulka, Lloyd; Thorp, James; Centeno, Virgilio; King, Roger; Reeves, Kari; Ashrafi, Frank; Madani, Vahid

    2014-09-30

    Recent blackouts of power systems in North America and throughout the world have shown how critical a reliable power system is to modern societies, and the enormous economic and societal damage a blackout can cause. It has been noted that unanticipated operation of protection systems can contribute to cascading phenomena and, ultimately, blackouts. This project developed and field-tested two methods of Adaptive Protection systems utilizing synchrophasor data. One method detects conditions of system stress that can lead to unintended relay operation, and initiates a supervisory signal to modify relay response in real time to avoid false trips. The second method detects the possibility of false trips of impedance relays as stable system swings “encroach” on the relays’ impedance zones, and produces an early warning so that relay engineers can re-evaluate relay settings. In addition, real-time synchrophasor data produced by this project was used to develop advanced visualization techniques for display of synchrophasor data to utility operators and engineers.

  19. Protection mechanism of early hyperbaric oxygen therapy in rats with permanent cerebral ischemia.

    PubMed

    Yu, Min; Xue, Yixue; Liang, Weidi; Zhang, Yupeng; Zhang, Zhiqiang

    2015-10-01

    [Purpose] The purpose of this study was to investigate whether early hyperbaric oxygen is useful in rats with permanent cerebral ischemia, and whether its mechanism relates to the inhibition of the tumor necrosis factor-alpha-protein kinase C-alpha pathway. [Subjects] Healthy, male Sprague-Dawley rats (N = 108) were the subjects. [Methods] After middle cerebral artery occlusion models were successfully made, rats were randomly divided into sham-operated, cerebral ischemia, and hyperbaric oxygen groups. At 4 and 12 hours after modeling, the volume of cerebral infarction was determined by triphenyltetrazolium chloride staining, and brain water content was measured using the dry and wet method. The expression of tumor necrosis factor-alpha and protein kinase C-alpha in the ischemic penumbra tissue was measured using Western blot analysis. [Results] The data showed that at 4 and 12 hours after modeling, cerebral infarct volume and brain water content decreased in the hyperbaric oxygen group, and expression of tumor necrosis factor-alpha and phospho-protein kinase C-alpha in the ischemic penumbra tissue also decreased. [Conclusion] Our study demonstrates that early hyperbaric oxygen therapy has protective effects on brain tissue after cerebral ischemia, possibly via inhibition of tumor necrosis factor-alpha and phospho-protein kinase C-alpha.

  20. Media representations of early human development: protecting, feeding and loving the developing brain.

    PubMed

    O'Connor, Cliodhna; Joffe, Helene

    2013-11-01

    The public profile of neurodevelopmental research has expanded in recent years. This paper applies social representations theory to explore how early brain development was represented in the UK print media in the first decade of the 21st century. A thematic analysis was performed on 505 newspaper articles published between 2000 and 2010 that discussed early brain development. Media coverage centred around concern with 'protecting' the prenatal brain (identifying threats to foetal neurodevelopment), 'feeding' the infant brain (indicating the patterns of nutrition that enhance brain development) and 'loving' the young child's brain (elucidating the developmental significance of emotionally nurturing family environments). The media focused almost exclusively on the role of parental action in promoting optimal neurodevelopment, rarely acknowledging wider structural, cultural or political means of supporting child development. The significance of parental care was intensified by deterministic interpretations of critical periods, which implied that inappropriate parental input would produce profound and enduring neurobiological impairments. Neurodevelopmental research was also used to promulgate normative judgements concerning the acceptability of certain gender roles and family contexts. The paper argues that media representations of neurodevelopment stress parental responsibility for shaping a child's future while relegating the contributions of genetic or wider societal factors, and examines the consequences of these representations for society and family life.

  1. Early Intervention for Alcohol Use Prevention and Vehicle Safety Skills: Evaluating the "Protecting You/Protecting Me" Curriculum

    ERIC Educational Resources Information Center

    Bohman, Thomas M.; Barker, Edward D.; Bell, Mary Lou; Lewis, Carol M.; Holleran, Lori; Pomeroy, Elizabeth

    2004-01-01

    The present study reports the evaluation results of the "Protecting You/Protecting Me" (PY/PM) alcohol use prevention and safety curriculum for third, fourth, and fifth graders when taught by high school peer leaders. The primary goal of the PY/PM prevention program, developed by Mothers Against Drunk Driving (MADD), is to prevent injury and death…

  2. Solid-phase synthesis of protected peptides using new cobalt(III) ammine linkers.

    PubMed

    Arbo, B E; Isied, S S

    1993-08-01

    Cobalt(III) ammine complexes of the type cis-[CoL4(4-AMB)O-AA-Boc](CF3SO3)2, where L4 = bisethylenediamine (en)2 or tetraammine (NH3)4, and 4-AMB = 4-(aminomethyl)benzoic acid, have been synthesized and used as linkers to polystyrene resins for solid-phase synthesis of protected peptides. Boc/t-Bu-protected [Leu5]enkephalin was assembled on the two different Co(III) resins, and then cleaved from the resins by reduction of the Co(III) center in 93-96% yield. HPLC-purified protected [Leu5]enkephalin was obtained in 67-69% overall yield and characterized by amino acid analysis and 1H NMR. Stepwise synthesis on the Co(en)2-resin was also used in the assembly of Boc-Asp(OcHex)-Arg(Mts)-Gly-Asp(OcHex)-Ala-Pro-Lys(2Cl-Z)-Gl y-OH, a sequence from collagen alpha 1 Type 1. The protected peptide was cleaved from the Co(III) resin in 74% yield, and the HPLC-purified nonapeptide was characterized by amino acid analysis, 1H NMR and liquid secondary-ion mass spectrometry (LSIMS). New routes are described for the synthesis of isomerically pure Co(III) anchor complexes. The Co(III) resins were found to be compatible with both the tert-butyloxycarbonyl (Boc) and the 9-fluorenylmethoxycarbonyl (Fmoc) N alpha-protecting group strategies used in solid-phase peptide synthesis.

  3. Protective effects of dexamethasone on early acute lung injury induced by oleic acid in rats

    PubMed Central

    Huang, Bin; Wang, Dao-Xin; Deng, Wang

    2014-01-01

    Objective: Whether alveolar edema could be cleared by alveolar epithelial is a key to the treatment and prognosis of ALI (acute lung injury). In this study, oleic acid(OA)-induced ALI model was established, the expression of α1 Na+/K+-ATPase (NKA) and β1 Na+/K+-ATPase were performed in vivo to investigate the mechanism of alveolar fluid clearance (AFC) in ALI and the effect of early low doses of dexamethasone on alveolar fluid clearance. Methods: In this study, Male rats were challenged by OA with or without dexamethasone (1 mg/kg, iv) post-treatment. Lung histopathology, blood gas, pulmonary vascular permeability, BALF IL-6, MPO and NKA activity of lung were examined. α1NKA and β1NKA mRNA and protein expression were detected. Results: The results indicated that compared with sham operated group, NKA activity, mRNA and protein expression of α1NKA and β1NKA were decreased in OA treated group, while wet/dry ratio, lung index, IL-6, and MPO activity were increased significantly. Pulmonary edema was obviously seen under light microscope. Those indexes were improved in dexamethasone treated group compared to OA treated group. Conclusion: The expression of NKA to decline for the lung injury is one important mechanism of pulmonary edema. Early low dose of dexamethasone treatment could suppress the expression of inflammatory mediators, improved lung epithelial-endothelial barrier permeability, increased the expressions of α1 NKA and β1 NKA mRNA, α1 NKA and β1 NKA protein level, stimulated NKA activity and decreased pulmonary edema. In conclusion, these observations suggest that early low dose of dexamethasone treatment has a protective effect on OA induced ALI. PMID:25663967

  4. Soluble ferric iron as an effective protective agent against UV radiation: Implications for early life

    NASA Astrophysics Data System (ADS)

    Gómez, Felipe; Aguilera, Angeles; Amils, Ricardo

    2007-11-01

    Some recent MER Rover Opportunity results on ancient sedimentary rocks from Mars describe sandstones originated from the chemical weathering of olivine basalts by acidic waters [Squyres, S.W., Knoll, A.H., 2005. Earth Planet. Sci. Lett. 240, 1-10]. The absence of protective components in early Mars atmosphere forced any possible primordial life forms to deal with high doses of UV radiation. A similar situation occurred on the primitive Earth during the development of early life in the Archean [Berkner, L.V., Marshall, L.C., 1965. J. Atmos. Sci. 22 (3), 225-261; Kasting, J.F., 1993. Science 259, 920-926]. It is known that some cellular and/or external components can shield organisms from damaging UV radiation or quench its toxic effects [Olson, J.M., Pierson, B.K., 1986. Photosynth. Res. 9, 251-259; García-Pichel, F., 1998. Origins Life Evol. B 28, 321-347; Cockell, C., Rettberg, P., Horneck, G., Scherer, K., Stokes, M.D., 2003. Polar Biol. 26, 62-69]. The effectiveness of iron minerals for UV protection has also been reported [Phoenix, V.R., Konhauser, K.O., Adams, D.G., Bottrell, S.H., 2001. Geology 29 (9), 823-826], but nothing is known about the effect of iron in solution. Here we demonstrate the protective effect of soluble ferric iron against UV radiation on acidophilic photosynthetic microorganisms. These results offer an interesting alternative means of protection for life on the surface of early Mars and Earth, especially in light of the geochemical conditions in which the sedimentary minerals, jarosite and goethite, recently reported by the MER missions, were formed [Squyres, S.W., Arvidson, R.E., Bell III, J.F., Brückner, J., Cabrol, N.A., Calvin, W., Carr, M.H., Christensen, P.R., Clark, B.C., Crumpler, L., Des Marais, D.J., d'Uston, C., Economou, T., Farmer, J., Farrand, W., Folkner, W., Golombek, M., Gorevan, S., Grant, J.A., Greeley, R., Grotzinger, J., Haskin, L., Herkenhoff, K.E., Hviid, S., Johnson, J., Klingelhöfer, G., Knoll, A.H., Landis, G

  5. Physical Environmental Adversity and the Protective Role of Maternal Monitoring in Relation to Early Child Conduct Problems.

    PubMed

    Supplee, Lauren H; Unikel, Emily B; Shaw, Daniel S

    2007-01-01

    Research on the development of externalizing behaviors during early childhood has focused on child and parenting factors. Fewer studies have investigated effects of aversive features of the micro-level physical environment, such as overcrowding and chaos in the home, and the macro-level environment, such as neighborhood quality. This study extends research on physical environmental factors by examining their association with children's early externalizing behaviors, and exploring how maternal monitoring may serve as a protective factor in such contexts. 120 male toddlers at high risk for developing early externalizing behaviors were followed from ages 2 to 5 years. Direct longitudinal associations were found for micro-level environmental factors beginning at age 2 and for neighborhood risk beginning at age 3. Maternal monitoring served as a protective factor for child externalizing behaviors in the context of neighborhood risk. Implications for prevention research and the development of early externalizing behaviors are discussed.

  6. Plasma sprayed manganese-cobalt spinel coatings: Process sensitivity on phase, electrical and protective performance

    NASA Astrophysics Data System (ADS)

    Han, Su Jung; Pala, Zdenek; Sampath, Sanjay

    2016-02-01

    Manganese cobalt spinel (Mn1.5Co1.5O4, MCO) coatings are prepared by the air plasma spray (APS) process to examine their efficacy in serving as protective coatings from Cr-poisoning of the cathode side in intermediate temperature-solid oxide fuel cells (IT-SOFCs). These complex oxides are susceptible to process induced stoichiometric and phase changes which affect their functional performance. To critically examine these effects, MCO coatings are produced with deliberate modifications to the spray process parameters to explore relationship among process conditions, microstructure and functional properties. The resultant interplay among particle thermal and kinetic energies are captured through process maps, which serve to characterize the parametric effects on properties. The results show significant changes to the chemistry and phase composition of the deposited material resulting from preferential evaporation of oxygen. Post deposition annealing recovers oxygen in the coatings and allows partial recovery of the spinel phase, which is confirmed through thermo-gravimetric analysis (TGA)/differential scanning calorimetry (DSC), X-ray Diffraction (XRD), and magnetic hysteresis measurements. In addition, coatings with high density after sintering show excellent electrical conductivity of 40 S cm-1 at 800 °C while simultaneously providing requisite protection characteristics against Cr-poisoning. This study provides a framework for optimal evaluation of MCO coatings in intermediate temperature SOFCs.

  7. Alcohol use among Hispanic early adolescents in the United States: an examination of behavioral risk and protective profiles.

    PubMed

    Salas-Wright, Christopher P; Hernandez, Lynn; Maynard, Brandy R; Saltzman, Leia Y; Vaughn, Michael G

    2014-06-01

    Few studies have examined the behavioral and protective correlates of alcohol use among young Hispanics. Using a national sample (N = 7,606), logistic regression and latent profile analysis (LPA) are employed to examine the relationships between alcohol use, psychosocial factors, and externalizing behavior among Hispanics during early adolescence. Early drinkers are more likely to report truancy, fighting, smoking, and drug use. LPA results revealed a three class solution. Classes identified included: psychosocial risk (41.11%), moderate protection (39.44%), and highly religious (19.44%). Alcohol use is clearly associated with externalizing behavior; however, an important degree of psychosocial and behavioral heterogeneity nevertheless exists.

  8. A Standardized Approach for the Early Restorative Phase After Esthetic Crown-Lengthening Surgery.

    PubMed

    Zucchelli, Giovanni; Mazzotti, Claudio; Monaco, Carlo

    2015-01-01

    The aim of the present case series article was to provide a standardized approach for the early restorative phase after a crown-lengthening surgical procedure. Different advantages can be ascribed to this approach: the clinician can prepare a definitive prosthetic finishing line in the supragingival location; the early postsurgical temporization allows the conditioning of soft tissues, especially the interdental papillae, during their maximum growing phase; and the clinician can choose the time for the definitive prosthetic rehabilitation in a patient-specific manner according to the individual potential and duration of the soft tissue rebound. In this study, this standardized approach was applied to the treatment of two esthetic cases requiring crown-lengthening procedures.

  9. The Role of Early-Phase Transmission in the Spread of Yersinia pestis

    PubMed Central

    EISEN, REBECCA J.; DENNIS, DAVID T.; GAGE, KENNETH L.

    2015-01-01

    Early-phase transmission (EPT) of Yersinia pestis by unblocked fleas is a well-documented, replicable phenomenon with poorly defined mechanisms. We review evidence demonstrating EPT and current knowledge on its biological and biomechanical processes. We discuss the importance of EPT in the epizootic spread of Y. pestis and its role in the maintenance of plague bacteria in nature. We further address the role of EPT in the epidemiology of plague. PMID:26336267

  10. Understanding the early cycling evolution behaviors for phase change memory application

    SciTech Connect

    Wang, Yuchan Chen, Yifeng Cai, Daolin; Cheng, Yan; Chen, Xiaogang; Wang, Yueqing; Xia, Mengjiao; Zhou, Mi; Li, Gezi; Zhang, Yiyun; Gao, Dan; Song, Zhitang; Feng, Gaoming

    2014-11-28

    The RESET current of T-shaped phase change memory cells with 35 nm heating electrodes has been studied to understand the behavior of early cycling evolution. Results show that the RESET current has been significantly reduced after the early cycling evolution (1st RESET) operation. Compared the transmission electron microscope images, it is found that the hexagonal Ge{sub 2}Sb{sub 2}Te{sub 5} (GST) crystal grains are changed into the grains with face centered cubic structure after the early cycling evolution operation, which is taken as the major reason for the reduced RESET current, confirmed by a two-dimensional finite analysis and ab initio calculations.

  11. Systemic and renal hemodynamic changes in the luteal phase of the menstrual cycle mimic early pregnancy.

    PubMed

    Chapman, A B; Zamudio, S; Woodmansee, W; Merouani, A; Osorio, F; Johnson, A; Moore, L G; Dahms, T; Coffin, C; Abraham, W T; Schrier, R W

    1997-11-01

    Blood pressure decreases during early pregnancy in association with a decrease in peripheral vascular resistance and increases in renal plasma flow and glomerular filtration rate. These early changes suggest a potential association with corpora lutea function. To determine whether peripheral vasodilation occurs following ovulation, we studied 16 healthy women in the midfollicular and midluteal phases of the menstrual cycle. A significant decrease in mean arterial pressure in the midluteal phase of the cycle (midfollicular of 81.7 +/- 2.0 vs. midluteal of 75.4 +/- 2.3 mmHg, P < 0.005) was found in association with a decrease in systemic vascular resistance and an increase in cardiac output. Renal plasma flow and glomerular filtration rate increased. Plasma renin activity and aldosterone concentration increased significantly in the luteal phase accompanied by a decrease in atrial natriuretic peptide concentration. Serum sodium, chloride, and bicarbonate concentrations and osmolarity also declined significantly in the midluteal phase of the menstrual cycle. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion increased in the luteal compared with the follicular phase, whereas no changes in urinary cGMP or NO2/NO3 excretion were found. Thus peripheral vasodilation occurs in the luteal phase of the normal menstrual cycle in association with an increase in renal plasma flow and filtration. Activation of the renin-angiotensin-aldosterone axis is found in the luteal phase of the menstrual cycle. These changes are accompanied by an increase in urinary cAMP excretion indicating potential vasodilating mediators responsible for the observed hemodynamic changes. PMID:9374841

  12. Muscle fiber conduction velocity in different gait phases of early and late-stage diabetic neuropathy.

    PubMed

    Suda, Eneida Yuri; Gomes, Aline A; Butugan, Marco Kenji; Sacco, Isabel C N

    2016-10-01

    We investigated the muscle fiber conduction velocity (MFCV) during gait phases of the lower limb muscles in individuals with various degrees of diabetic peripheral neuropathy (DPN). Forty-five patients were classified into severity degrees of DPN by a fuzzy model. The stages were absent (n=11), mild (n=14), moderate (n=11) and severe (n=9), with 10 matched healthy controls. While walking, all subjects had their sEMG (4 linear electrode arrays) recorded for tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL) and biceps femoris (BF). MFCV was calculated using a maximum likelihood algorithm with 30ms standard deviation Gaussian windows. In general, individuals in the earlier stages of DPN showed lower MFCV of TA, GM and BF, whilst individuals with severe DPN presented higher MFCV of the same muscles. We observed that mild patients already showed lower MFCV of TA at early stance and swing, and lower MFCV of BF at swing. All diabetic groups showed a markedly reduction in MFCV of VL, irrespective of DPN. Severe patients presented higher MFCV mainly in distal muscles, TA at early and swing phases and GM at propulsion and midstance. The absent group already showed MFCV of VL and GM reductions at the propulsion phase and of VL at early stance. Although MFCV changes were not as progressive as the DPN was, we clearly distinguished diabetic patients from controls, and severe patients from all others.

  13. Translational and Early Phase Strategies for Treatment Development: Report of ISCTM Autumn 2013 Symposium.

    PubMed

    Young, Jared W; Potter, William Z; Riley, Steve; Groeneveld, Geert J; Kinon, Bruce J; Egan, Mike F; Feltner, Douglas E

    2015-01-01

    For decades, there has been a distinct disconnect translating a compound's effects from basic neuroscience into clinical efficacy. This disconnect has not only been in terms of generating approved compounds, but also in rejecting targets. During the drug discovery process there are key points to be adhered to that would strengthen the likelihood of a compound being translated to the clinic. These points include 1) the importance of translational pharmacology whereby preclinical pharmacological data should predict clinical efficacy; 2) rigorous early phase drug evaluation to enhance early go/no-go decisionmaking; 3) using exposure response modeling to predict drug efficacy during proof-of-concept trials; 4) designing and conducting the appropriate proof-of-concept study; and 5) optimizing Phase II studies to set the stage for success in Phase III trials. These topics were covered in The International Society for CNS Clinical Trials and Methodology (ISCTM) Autumn 2013 meeting on the topic of translational and early development strategies and tools led by Drs. Potter and Feltner. This report comprises a review of those proceedings with a concluding summary to advance future clinical trials.

  14. Translational and Early Phase Strategies for Treatment Development: Report of ISCTM Autumn 2013 Symposium.

    PubMed

    Young, Jared W; Potter, William Z; Riley, Steve; Groeneveld, Geert J; Kinon, Bruce J; Egan, Mike F; Feltner, Douglas E

    2015-01-01

    For decades, there has been a distinct disconnect translating a compound's effects from basic neuroscience into clinical efficacy. This disconnect has not only been in terms of generating approved compounds, but also in rejecting targets. During the drug discovery process there are key points to be adhered to that would strengthen the likelihood of a compound being translated to the clinic. These points include 1) the importance of translational pharmacology whereby preclinical pharmacological data should predict clinical efficacy; 2) rigorous early phase drug evaluation to enhance early go/no-go decisionmaking; 3) using exposure response modeling to predict drug efficacy during proof-of-concept trials; 4) designing and conducting the appropriate proof-of-concept study; and 5) optimizing Phase II studies to set the stage for success in Phase III trials. These topics were covered in The International Society for CNS Clinical Trials and Methodology (ISCTM) Autumn 2013 meeting on the topic of translational and early development strategies and tools led by Drs. Potter and Feltner. This report comprises a review of those proceedings with a concluding summary to advance future clinical trials. PMID:25977839

  15. Muscle fiber conduction velocity in different gait phases of early and late-stage diabetic neuropathy.

    PubMed

    Suda, Eneida Yuri; Gomes, Aline A; Butugan, Marco Kenji; Sacco, Isabel C N

    2016-10-01

    We investigated the muscle fiber conduction velocity (MFCV) during gait phases of the lower limb muscles in individuals with various degrees of diabetic peripheral neuropathy (DPN). Forty-five patients were classified into severity degrees of DPN by a fuzzy model. The stages were absent (n=11), mild (n=14), moderate (n=11) and severe (n=9), with 10 matched healthy controls. While walking, all subjects had their sEMG (4 linear electrode arrays) recorded for tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL) and biceps femoris (BF). MFCV was calculated using a maximum likelihood algorithm with 30ms standard deviation Gaussian windows. In general, individuals in the earlier stages of DPN showed lower MFCV of TA, GM and BF, whilst individuals with severe DPN presented higher MFCV of the same muscles. We observed that mild patients already showed lower MFCV of TA at early stance and swing, and lower MFCV of BF at swing. All diabetic groups showed a markedly reduction in MFCV of VL, irrespective of DPN. Severe patients presented higher MFCV mainly in distal muscles, TA at early and swing phases and GM at propulsion and midstance. The absent group already showed MFCV of VL and GM reductions at the propulsion phase and of VL at early stance. Although MFCV changes were not as progressive as the DPN was, we clearly distinguished diabetic patients from controls, and severe patients from all others. PMID:27567140

  16. Resource quality of a symmetry-protected topologically ordered phase for quantum computation.

    PubMed

    Miller, Jacob; Miyake, Akimasa

    2015-03-27

    We investigate entanglement naturally present in the 1D topologically ordered phase protected with the on-site symmetry group of an octahedron as a potential resource for teleportation-based quantum computation. We show that, as long as certain characteristic lengths are finite, all its ground states have the capability to implement any unit-fidelity one-qubit gate operation asymptotically as a key computational building block. This feature is intrinsic to the entire phase, in that perfect gate fidelity coincides with perfect string order parameters under a state-insensitive renormalization procedure. Our approach may pave the way toward a novel program to classify quantum many-body systems based on their operational use for quantum information processing. PMID:25860730

  17. Kagome Chiral Spin Liquid as a Gauged U (1 ) Symmetry Protected Topological Phase

    NASA Astrophysics Data System (ADS)

    He, Yin-Chen; Bhattacharjee, Subhro; Pollmann, Frank; Moessner, R.

    2015-12-01

    While the existence of a chiral spin liquid (CSL) on a class of spin-1 /2 kagome antiferromagnets is by now well established numerically, a controlled theoretical path from the lattice model leading to a low-energy topological field theory is still lacking. This we provide via an explicit construction starting from reformulating a microscopic model for a CSL as a lattice gauge theory and deriving the low-energy form of its continuum limit. A crucial ingredient is the realization that the bosonic spinons of the gauge theory exhibit a U (1 ) symmetry protected topological (SPT) phase, which upon promoting its U (1 ) global symmetry to a local gauge structure ("gauging"), yields the CSL. We suggest that such an explicit lattice-based construction involving gauging of a SPT phase can be applied more generally to understand topological spin liquids.

  18. Kagome Chiral Spin Liquid as a Gauged U(1) Symmetry Protected Topological Phase.

    PubMed

    He, Yin-Chen; Bhattacharjee, Subhro; Pollmann, Frank; Moessner, R

    2015-12-31

    While the existence of a chiral spin liquid (CSL) on a class of spin-1/2 kagome antiferromagnets is by now well established numerically, a controlled theoretical path from the lattice model leading to a low-energy topological field theory is still lacking. This we provide via an explicit construction starting from reformulating a microscopic model for a CSL as a lattice gauge theory and deriving the low-energy form of its continuum limit. A crucial ingredient is the realization that the bosonic spinons of the gauge theory exhibit a U(1) symmetry protected topological (SPT) phase, which upon promoting its U(1) global symmetry to a local gauge structure ("gauging"), yields the CSL. We suggest that such an explicit lattice-based construction involving gauging of a SPT phase can be applied more generally to understand topological spin liquids.

  19. Protein Export Marks the Early Phase of Gametocytogenesis of the Human Malaria Parasite Plasmodium falciparum*

    PubMed Central

    Silvestrini, Francesco; Lasonder, Edwin; Olivieri, Anna; Camarda, Grazia; van Schaijk, Ben; Sanchez, Massimo; Younis Younis, Sumera; Sauerwein, Robert; Alano, Pietro

    2010-01-01

    Despite over a century of study of malaria parasites, parts of the Plasmodium falciparum life cycle remain virtually unknown. One of these is the early gametocyte stage, a round shaped cell morphologically similar to an asexual trophozoite in which major cellular transformations ensure subsequent development of the elongated gametocyte. We developed a protocol to obtain for the first time highly purified preparations of early gametocytes using a transgenic line expressing a green fluorescent protein from the onset of gametocytogenesis. We determined the cellular proteome (1427 proteins) of this parasite stage by high accuracy tandem mass spectrometry and newly determined the proteomes of asexual trophozoites and mature gametocytes, identifying altogether 1090 previously undetected parasite proteins. Quantitative label-free comparative proteomics analysis determined enriched protein clusters for the three parasite developmental stages. Gene set enrichment analysis on the 251 proteins enriched in the early gametocyte proteome revealed that proteins putatively exported and involved in erythrocyte remodeling are the most overrepresented protein set in these stages. One-tenth of the early gametocyte-enriched proteome is constituted of putatively exported proteins, here named PfGEXPs (P. falciparum gametocyte-exported proteins). N-terminal processing and N-acetylation at a conserved leucine residue within the Plasmodium export element pentamotif were detected by mass spectrometry for three such proteins in the early but not in the mature gametocyte sample, further supporting a specific role in protein export in early gametocytogenesis. Previous reports and results of our experiments confirm that the three proteins are indeed exported in the erythrocyte cytoplasm. This work indicates that protein export profoundly marks early sexual differentiation in P. falciparum, probably contributing to host cell remodeling in this phase of the life cycle, and that gametocyte

  20. Systems approach to tamper protection

    SciTech Connect

    Myre, W. C.; Eaton, M. J.

    1980-01-01

    Tamper-protection is a fundamental requirement of effective containment and surveillance systems. Cost effective designs require that the tamper protection requirements be considered early in the design phase and at the system level. A discussion of tamper protection alternatives as well as an illustrative example system is presented.

  1. Inhibition of protein kinase B activity induces cell cycle arrest and apoptosis during early G₁ phase in CHO cells.

    PubMed

    van Opstal, Angélique; Bijvelt, José; van Donselaar, Elly; Humbel, Bruno M; Boonstra, Johannes

    2012-04-01

    Inhibition of PKB (protein kinase B) activity using a highly selective PKB inhibitor resulted in inhibition of cell cycle progression only if cells were in early G1 phase at the time of addition of the inhibitor, as demonstrated by time-lapse cinematography. Addition of the inhibitor during mitosis up to 2 h after mitosis resulted in arrest of the cells in early G1 phase, as deduced from the expression of cyclins D and A and incorporation of thymidine. After 24 h of cell cycle arrest, cells expressed the cleaved caspase-3, a central mediator of apoptosis. These results demonstrate that PKB activity in early G1 phase is required to prevent the induction of apoptosis. Using antibodies, it was demonstrated that active PKB translocates to the nucleus during early G1 phase, while an even distribution of PKB was observed through cytoplasm and nucleus during the end of G1 phase. PMID:22251027

  2. The evolution of the interstellar medium in elliptical galaxies. I - The early wind phase

    NASA Technical Reports Server (NTRS)

    David, L. P.; Forman, W.; Jones, C.

    1990-01-01

    The evolving mass loss rates from type I and II SNe, stellar winds, and PN and the associated evolution of the mass-averaged temperature of the stellar ejecta are calculated. At early times, the mass-averaged temperature of the ejecta is found to be much greater than the central escape temperature from even very luminous elliptical galaxies due to the high frequency of type II SNe. The amount of oxygen and iron that can be injected into the intracluster medium from type II SN-driven winds in elliptical galaxies is calculated and the results are compared with observations. The gas ejected during this early wind phase is very hot and can heat the cluster gas to temperatures greater than that produced by gravitational heating alone. Two numerical simulations concerning the evolution of the ISM in an elliptical galaxy model with L(B) = 10 to the 11th solar are presented which confirm the existence of an early type II SN-driven wind phase and reproduce the observed X-ray properties of bright elliptical galaxies in the present epoch.

  3. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

    PubMed

    Kawakami, Kohsaku

    2009-09-01

    Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

  4. Efficient runner safety assessment during early design phase and root cause analysis

    NASA Astrophysics Data System (ADS)

    Liang, Q. W.; Lais, S.; Gentner, C.; Braun, O.

    2012-11-01

    Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for

  5. Human exposure to early morning Anopheles funestus biting behavior and personal protection provided by long-lasting insecticidal nets.

    PubMed

    Moiroux, Nicolas; Damien, Georgia B; Egrot, Marc; Djenontin, Armel; Chandre, Fabrice; Corbel, Vincent; Killeen, Gerry F; Pennetier, Cédric

    2014-01-01

    A shift towards early morning biting behavior of the major malaria vector Anopheles funestus have been observed in two villages in south Benin following distribution of long-lasting insecticidal nets (LLINs), but the impact of these changes on the personal protection efficacy of LLINs was not evaluated. Data from human and An. funestus behavioral surveys were used to measure the human exposure to An. funestus bites through previously described mathematical models. We estimated the personal protection efficacy provided by LLINs and the proportions of exposure to bite occurring indoors and/or in the early morning. Average personal protection provided by using of LLIN was high (≥80% of the total exposure to bite), but for LLIN users, a large part of remaining exposure occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoué) and/or in the early morning (38.5% in Tokoli-V and 69.4% in Lokohoué). This study highlights the crucial role of LLIN use and the possible need to develop new vector control strategies targeting malaria vectors with outdoor and early morning biting behavior. This multidisciplinary approach that supplements entomology with social science and mathematical modeling illustrates just how important it is to assess where and when humans are actually exposed to malaria vectors before vector control program managers, policy-makers and funders conclude what entomological observations imply.

  6. Extinct radioactivities - A three-phase mixing model. [for early solar system abundances

    NASA Technical Reports Server (NTRS)

    Clayton, D. D.

    1983-01-01

    A new class of models is advanced for interpreting the relationship of radioactive abundances in the early solar system to their average concentration in the interstellar medium. The model assumes that fresh radioactivities are ejected from supernovae into the hot interstellar medium, and that the time scales for changes of phase into molecular clouds determine how much survives for formation therein of the solar system. A more realistic and physically motivated understanding of the low observed concentrations of I-129, Pu-244, and Pd-107 may result.

  7. The Impact of Early Design Phase Risk Identification Biases on Space System Project Performance

    NASA Technical Reports Server (NTRS)

    Reeves, John D., Jr.; Eveleigh, Tim; Holzer, Thomas; Sarkani, Shahryar

    2012-01-01

    Risk identification during the early design phases of complex systems is commonly implemented but often fails to result in the identification of events and circumstances that truly challenge project performance. Inefficiencies in cost and schedule estimation are usually held accountable for cost and schedule overruns, but the true root cause is often the realization of programmatic risks. A deeper understanding of frequent risk identification trends and biases pervasive during space system design and development is needed, for it would lead to improved execution of existing identification processes and methods.

  8. A tale of two timescales: Mixing, mass generation, and phase transitions in the early universe

    NASA Astrophysics Data System (ADS)

    Dienes, Keith R.; Kost, Jeff; Thomas, Brooks

    2016-02-01

    Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically—such as during cosmological mass-generating phase transitions—the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this paper, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system—often by many orders of magnitude—but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "reoverdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings.

  9. Bending the curve: force health protection during the insertion phase of the Ebola outbreak response.

    PubMed

    Bailey, Mark S; Beaton, K; Bowley, D; Eardley, W; Hunt, P; Johnson, S; Round, J; Tarmey, N T; Williams, A

    2016-06-01

    After >10 years of enduring operations in Iraq and Afghanistan, Defence Strategic Direction is returning to a contingency posture. As the first post-Afghanistan operation, in September 2014, a UK Joint Inter-Agency Task Force deployed to Sierra Leone in response to the Ebola virus disease (EVD) epidemic in West Africa. The aims were expanding treatment capacity, assisting with training and supporting host nation resilience. The insertion phase of this deployment created a unique set of challenges for force health protection. In addition to the considerable risk of tropical disease and trauma, deployed personnel faced the risks of working in an EVD epidemic. This report explores how deployed medical assets overcame the difficulties of mounting a short-notice contingent operation in a region of the world with inherent major climatic and health challenges. PMID:26036821

  10. Characteristics of the early flight phase in the Olympic ski jumping competition.

    PubMed

    Virmavirta, Mikko; Isolehto, Juha; Komi, Paavo; Brüggemann, Gert-Peter; Müller, Erich; Schwameder, Hermann

    2005-11-01

    Early flight phase (approximately 40 m) of the athletes participating in the final round of the individual large hill ski jumping competition in Salt Lake City Olympics was filmed with two high-speed pan & tilt video cameras. The results showed that jumpers' steady flight position was almost completed within 0.5s. The most significant correlation with the length of the jump was found in the angle between the skis and body (r=.714, p.001 at 1.1s after the take-off). This particular phase seemed to be important because the ski angle of attack was also related to the jumping distance at the same phase. Although the more upright ski position relative to flight path resulted in longer jumping distance, the winner of the competition had significantly lower ski position as compared to the other good jumpers. This may be due to the high altitude (>2000 m) of the ski jumping stadium in this competition. Because of the low air density, the aerodynamic forces were also low and this probably caused less skillful jumpers to lean too much forward at this phase. Maintenance of speed seemed to be emphasized in this particular competition.

  11. Topological quantum field theory of three-dimensional bosonic Abelian-symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Ye, Peng; Gu, Zheng-Cheng

    2016-05-01

    Symmetry-protected topological phases (SPT) are short-range entangled gapped states protected by global symmetry. Nontrivial SPT phases cannot be adiabatically connected to the trivial disordered state (or atomic insulator) as long as certain global symmetry G is unbroken. At low energies, most of the two-dimensional SPTs with Abelian symmetry can be described by topological quantum field theory (TQFT) of the multicomponent Chern-Simons type. However, in contrast to the fractional quantum Hall effect where TQFT can give rise to interesting bulk anyons, TQFT for SPTs only supports trivial bulk excitations. The essential question in TQFT descriptions for SPTs is to understand how the global symmetry is implemented in the partition function. In this paper, we systematically study TQFT of three-dimensional SPTs with unitary Abelian symmetry (e.g., ZN1×ZN2×... ). In addition to the usual multicomponent B F topological term at level-1, we find that there are new topological terms with quantized coefficients (e.g., a1∧a2∧d a2 and a1∧a2∧a3∧a4 ) in TQFT actions, where a1,a2,... are 1-form U(1) gauge fields. These additional topological terms cannot be adiabatically turned off as long as G is unbroken. By investigating symmetry transformations for the TQFT partition function, we end up with the classification of SPTs that is consistent with the well-known group cohomology approach. We also discuss how to gauge the global symmetry and possible TQFT descriptions of Dijkgraaf-Witten gauge theory.

  12. Entanglement Spectra of Gapped One-dimensional Field Theories and Symmetry-Protected Topological Phases

    NASA Astrophysics Data System (ADS)

    Cho, Gil Young; Shiozaki, Ken; Ludwig, Andreas; Ryu, Shinsei

    We discuss the entanglement spectrum(ES) of (1+1)d gapped Lorentz invariant field theories in the vicinity of a conformal field theory (CFT). In particular, for a gapped theory obtained by perturbing a CFT in infinite space by relevant perturbations, we show that the low-lying ES for the half-line is equal to the physical spectrum of the gapless CFT defined on a finite interval of length L = log (ξ / a) , which is the spectrum of a boundary CFT. Here ξ is the correlation length, a a microscopic lattice scale, and our result applies in the ''scaling limit'' where ξ >> a . A similar property has been known to hold for Baxter's Corner Transfer Matrices of a class of very special, namely integrable lattice models, for the entire ES and independent of the scaling limit. In contrast, our result applies to completely general gapped Lorentz invariant theories in the scaling limit, without the requirement of integrability, for the low-lying ES. As a consequence, while on a finite interval of length 2 R the physical spectrum of the gapped theory is known to undergo a dramatic reorganization as 2 R crosses ξ, the bipartite ES remains unchanged up to an overall scale. We apply these to (1+1)d symmetry-protected topological phases and symmetry-protected degeneracy of ES.

  13. c-Cbl-mediated degradation of TRAIL receptors is responsible for the development of the early phase of TRAIL resistance

    PubMed Central

    Song, Jae J.; Szczepanski, Miroslaw Jerzy; Kim, So Young; Kim, Joo-Hang; An, Jee Young; Kwon, Yong Tae; Alcala, Marco A.; Bartlett, David L.; Lee, Yong J.

    2010-01-01

    We previously reported two modes of development of acquired TRAIL resistance: early phase and late phase [1]. In these studies, we observed that greater Akt activity and the expression of Bcl-xL were related mainly to the late phase of acquired TRAIL resistance. Recently we became aware of a possible mechanism of early phase TRAIL resistance development through internalization and degradation of TRAIL receptors (DR4 and DR5). Our current studies demonstrate that TRAIL receptors rapidly diminish at the membrane as well as the cytoplasm within four hours after TRAIL exposure, but recover completely after one or two days. Our studies also reveal that Cbl, a ubiquitously expressed cytoplasmic adaptor protein, is responsible for the rapid degradation of TRAIL receptors; Cbl binds to them and induces mono-ubiquitination of these receptors concurrent with their degeneration soon after TRAIL exposure, creating the early phase of acquired TRAIL resistance. PMID:19932172

  14. 78 FR 73555 - Deepwater Horizon Oil Spill; Draft Programmatic and Phase III Early Restoration Plan and Draft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ... announced in the May 6, 2013 Federal Register notice (78 FR 26319), and the document now proposes these 28... Deepwater Horizon Oil Spill; Draft Programmatic and Phase III Early Restoration Plan and Draft Early Restoration Programmatic Environmental Impact Statement AGENCY: Interior. ACTION: Notice of...

  15. Early Childhood Settings in 15 Countries: What Are Their Structural Characteristics? The IEA Preprimary Project, Phase 2.

    ERIC Educational Resources Information Center

    Olmsted, Patricia P., Ed.; Montie, Jeanne, Ed.

    This is the second of four monographs reporting the findings of Phase 2 of the International Association for the Evaluation of Educational Achievement (IEA) Preprimary Project, which presents data on the physical characteristics of children's early childhood settings. Early childhood settings were documented in the following 15 countries: (1)…

  16. Left-turn phase: permissive, protected, or both? A quasi-experimental design in New York City.

    PubMed

    Chen, Li; Chen, Cynthia; Ewing, Reid

    2015-03-01

    The practice of left-turn phasing selection (permissive, protected-only, or both) varies from one locality to another. The literature evidence on this issue is equally mixed and insufficient. In this study, we evaluate the safety impacts of changing left-turn signal phasing from permissive to protected/permissive or protected-only at 68 intersections in New York City using a rigorous quasi-experimental design accompanied with regression modeling. Changes in police reported crashes including total crashes, multiple-vehicle crashes, left-turn crashes, pedestrian crashes and bicyclist crashes were compared between before period and after period for the treatment group and comparison group by means of negative binomial regression using a Generalized Estimating Equations (GEE) technique. Confounding factors such as the built environment characteristics that were not controlled in comparison group selection are accounted for by this approach. The results show that the change of permissive left-turn signal phasing to protected/permissive or protected-only signal phasing does not result in a significant reduction in intersection crashes. Though the protected-only signal phasing does reduce the left-turn crashes and pedestrian crashes, this reduction was offset by a possible increase in over-taking crashes. These results suggest that left-turn phasing should not be treated as a universal solution that is always better than the permissive control for left-turn vehicles. The selection and implementation of left-turn signal phasing needs to be done carefully, considering potential trade-offs between safety and delay, and many other factors such as geometry, traffic flows and operations. PMID:25626164

  17. Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials

    PubMed Central

    Ang, Joo Ern; Kaye, Stan; Banerji, Udai

    2012-01-01

    Anti-cancer clinical drug development is currently costly and slow with a high attrition rate. There is thus an urgent and unmet need to integrate pharmacodynamic biomarkers into early phase clinical trials in the framework provided by the “pharmacologic audit trail” in order to overcome this challenge. This review discusses the rationale, advantages and disadvantages, as well as the practical considerations of various tissue-based approaches to perform pharmacodynamic studies in early phase oncology clinical trials using case histories of molecular targeting agents such as PI3K, m-TOR, HSP90, HDAC and PARP inhibitors. These approaches include the use of normal “surrogate” tissues such as peripheral blood mononuclear cells, platelet-rich plasma, plucked hair follicles, skin biopsies, plasma-based endocrine assays, proteomics, metabolomics and circulating endothelial cells. In addition, the review discusses the use of neoplastic tissues including tumor biopsies, circulating tumor DNA and tumor cells and metabolomic approaches. The utilization of these tissues and technology platforms to study biomarkers will help accelerate the development of molecularly targeted agents for the treatment of cancer. PMID:22974395

  18. Optimal adaptive two-stage designs for early phase II clinical trials.

    PubMed

    Shan, Guogen; Wilding, Gregory E; Hutson, Alan D; Gerstenberger, Shawn

    2016-04-15

    Simon's optimal two-stage design has been widely used in early phase clinical trials for Oncology and AIDS studies with binary endpoints. With this approach, the second-stage sample size is fixed when the trial passes the first stage with sufficient activity. Adaptive designs, such as those due to Banerjee and Tsiatis (2006) and Englert and Kieser (2013), are flexible in the sense that the second-stage sample size depends on the response from the first stage, and these designs are often seen to reduce the expected sample size under the null hypothesis as compared with Simon's approach. An unappealing trait of the existing designs is that they are not associated with a second-stage sample size, which is a non-increasing function of the first-stage response rate. In this paper, an efficient intelligent process, the branch-and-bound algorithm, is used in extensively searching for the optimal adaptive design with the smallest expected sample size under the null, while the type I and II error rates are maintained and the aforementioned monotonicity characteristic is respected. The proposed optimal design is observed to have smaller expected sample sizes compared to Simon's optimal design, and the maximum total sample size of the proposed adaptive design is very close to that from Simon's method. The proposed optimal adaptive two-stage design is recommended for use in practice to improve the flexibility and efficiency of early phase therapeutic development. PMID:26526165

  19. Population genomic analyses of early-phase Atlantic Salmon (Salmo salar) domestication/captive breeding

    PubMed Central

    Mäkinen, Hannu; Vasemägi, Anti; McGinnity, Philip; Cross, Tom F; Primmer, Craig R

    2015-01-01

    Domestication can have adverse genetic consequences, which may reduce the fitness of individuals once released back into the wild. Many wild Atlantic salmon (Salmo salarL.) populations are threatened by anthropogenic influences, and they are supplemented with captively bred fish. The Atlantic salmon is also widely used in selective breeding programs to increase the mean trait values for desired phenotypic traits. We analyzed a genomewide set of SNPs in three domesticated Atlantic salmon strains and their wild conspecifics to identify loci underlying domestication. The genetic differentiation between domesticated strains and wild populations was low (FST < 0.03), and domesticated strains harbored similar levels of genetic diversity compared to their wild conspecifics. Only a few loci showed footprints of selection, and these loci were located in different linkage groups among the different wild population/hatchery strain comparisons. Simulated scenarios indicated that differentiation in quantitative trait loci exceeded that in neutral markers during the early phases of divergence only when the difference in the phenotypic optimum between populations was large. This study indicates that detecting selection using standard approaches in the early phases of domestication might be challenging unless selection is strong and the traits under selection show simple inheritance patterns. PMID:25667605

  20. The early phase of /see symbol/ production development in adult Japanese learners of English.

    PubMed

    Saito, Kazuya; Munro, Murray J

    2014-12-01

    Although previous research indicates that Japanese speakers' second language (L2) perception and production of English /see symbol/ may improve with increased L2 experience, relatively little is known about the fine phonetic details of their /see symbol/ productions, especially during the early phase of L2 speech learning. This cross-sectional study examined acoustic properties of word-initial /see symbol/ from 60 Japanese learners with a length of residence of between one month and one year in Canada. Their performance was compared to that of 15 native speakers of English and 15 low-proficiency Japanese learners of English. Formant frequencies (F2 and F3) and F1 transition durations were evaluated under three task conditions--word reading, sentence reading, and timed picture description. Learners with as little as two to three months of residence demonstrated target-like F2 frequencies. In addition, increased LOR was predictive of more target-like transition durations. Although the learners showed some improvement in F3 as a function of LOR, they did so mainly at a controlled level of speech production. The findings suggest that during the early phase of L2 segmental development, production accuracy is task-dependent and is influenced by the availability of L1 phonetic cues for redeployment in L2.

  1. Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells.

    PubMed

    Imamura, O; Fujita, K; Shimamoto, A; Tanabe, H; Takeda, S; Furuichi, Y; Matsumoto, T

    2001-03-01

    Bloom syndrome (BS) is a recessive human genetic disorder characterized by short stature, immunodeficiency and an elevated risk of malignancy. The gene mutated in BS, BLM, encodes a RecQ-type DNA helicase. BS cells have mutator phenotypes such as hyper-recombination, chromosome instability and an increased frequency of sister chromatid exchange (SCE). To define the primary role of BLM, we generated BLM(-/-) mutants of the chicken B-cell line DT40. In addition to characteristics of BLM(-/-) cells reported previously by the other group, they are hypersensitive to genotoxic agents such as etoposide, bleomycin and 4-nitroquinoline-1-oxide and irradiation with the short wave length of UV (UVC) light, whereas they exhibit normal sensitivity to X-ray irradiation and hydroxyurea. UVC irradiation to BLM(-/-) cells during G(1) to early S phase caused chromosomal instability such as chromatid breaks and chromosomal quadriradials, leading to eventual cell death. These results suggest that BLM is involved in surveillance of base abnormalities in genomic DNA that may be encountered by replication forks in early S phase. Such surveillance would maintain genomic stability in vertebrate cells, resulting in the prevention of cellular tumorigenesis. PMID:11313858

  2. Establishing proof of mechanism: Assessing target modulation in early-phase clinical trials.

    PubMed

    Kummar, Shivaani; Do, Khanh; Coyne, Geraldine O'Sullivan; Chen, Alice; Ji, Jiuping; Rubinstein, Larry; Doroshow, James H

    2016-08-01

    Since modulation of the putative target and the observed anti-tumor effects form the basis for the clinical development of a molecularly targeted therapy, early-phase clinical trials should be designed to demonstrate proof-of-mechanism in tissues of interest. In addition to establishing safety and the maximum tolerated dose, first-in-human clinical trials should be designed to demonstrate target modulation, define the proposed mechanism of action, and evaluate pharmacokinetic-pharmacodynamic relationships of a new anti-cancer agent. Assessing target modulation in paired tumor biopsies in patients with solid tumors presents multiple challenges, including procedural issues such as patient safety, ethical considerations, and logistics of sample handling and processing. In addition, the availability of qualified biomarker assay technologies, resources to conduct such studies, and real-time analysis of samples to detect inter-species differences that may affect the determination of optimal sampling time points must be taken into account. This article provides a discussion of the challenges that confront the practical application of pharmacodynamic studies in early-phase clinical trials of anti-cancer agents. PMID:27663476

  3. Integration of mass spectrometry into early-phase discovery and development of central nervous system agents.

    PubMed

    Prokai, L; Zharikova, A; Janáky, T; Li, X; Braddy, A C; Perjési, P; Matveeva, L; Powell, D H; Prokai-Tatrai, K

    2001-11-01

    The early-phase discovery and development of useful central nervous system (CNS) agents present ample opportunities to exploit mass spectrometry and provide detailed compound/mixture characterization, or to make the process faster and/or more economic. Neuropeptide FF antagonists and centrally active thyrotropin-releasing hormone analogues were used as specific examples in this work. We evaluated the characterization of focused libraries of peptide derivatives by electrospray ionization, tandem mass spectrometry and liquid chromatography/tandem mass spectrometry on a quadrupole ion trap and nanoelectrospray on a Fourier transform ion cyclotron resonance mass spectrometer. Immobilized artificial-membrane chromatography was employed as a model to predict/rank new agents against lead compounds for their potential to reach the central nervous system in pharmacologically significant amounts. Measuring brain concentrations in rodents after the intravenous administration of test compounds was used as an in vivo approach, and we took advantage of microdialysis sampling that furnished samples without interfering tissue matrix and afforded the estimation of extracellular concentrations in a localized part of the brain. Overall, making atmospheric-pressure ionization mass spectrometry an integral part of the process has played a major role in increasing throughput, selectivity, specificity and detection sensitivity and thereby providing useful information about the extent or mechanism of transport and metabolic activation/inactivation in early-phase discovery and development of CNS agents.

  4. Bona fide interaction-driven topological phase transition in correlated symmetry-protected topological states

    NASA Astrophysics Data System (ADS)

    He, Yuan-Yao; Wu, Han-Qing; You, Yi-Zhuang; Xu, Cenke; Meng, Zi Yang; Lu, Zhong-Yi

    2016-03-01

    It is expected that the interplay between nontrivial band topology and strong electron correlation will lead to very rich physics. Thus a controlled study of the competition between topology and correlation is of great interest. Here, employing large-scale quantum Monte Carlo simulations, we provide a concrete example of the Kane-Mele-Hubbard model on an AA-stacking bilayer honeycomb lattice with interlayer antiferromagnetic interaction. Our simulation identified several different phases: a quantum spin Hall insulator (QSH), an x y -plane antiferromagnetic Mott insulator, and an interlayer dimer-singlet insulator. Most importantly, a bona fide topological phase transition between the QSH and the dimer-singlet insulators, purely driven by the interlayer antiferromagnetic interaction, is found. At the transition, the spin and charge gap of the system close while the single-particle excitations remain gapped, which means that this transition has no mean-field analog and it can be viewed as a transition between bosonic symmetry-protected topological (SPT) states. At one special point, this transition is described by a (2 +1 )d O (4 ) nonlinear sigma model with exact S O (4 ) symmetry and a topological term at exactly Θ =π . The relevance of this work towards more general interacting SPT states is discussed.

  5. Enabling Parametric Optimal Ascent Trajectory Modeling During Early Phases of Design

    NASA Technical Reports Server (NTRS)

    Holt, James B.; Dees, Patrick D.; Diaz, Manuel J.

    2015-01-01

    During the early phases of engineering design, the costs committed are high, costs incurred are low, and the design freedom is high. It is well documented that decisions made in these early design phases drive the entire design's life cycle. In a traditional paradigm, key design decisions are made when little is known about the design. As the design matures, design changes become more difficult -- in both cost and schedule -- to enact. Indeed, the current capability-based paradigm that has emerged because of the constrained economic environment calls for the infusion of knowledge acquired during later design phases into earlier design phases, i.e. bring knowledge acquired during preliminary and detailed design into pre-conceptual and conceptual design. An area of critical importance to launch vehicle design is the optimization of its ascent trajectory, as the optimal trajectory will be able to take full advantage of the launch vehicle's capability to deliver a maximum amount of payload into orbit. Hence, the optimal ascent trajectory plays an important role in the vehicle's affordability posture as the need for more economically viable access to space solutions are needed in today's constrained economic environment. The problem of ascent trajectory optimization is not a new one. There are several programs that are widely used in industry that allows trajectory analysts to, based on detailed vehicle and insertion orbit parameters, determine the optimal ascent trajectory. Yet, little information is known about the launch vehicle early in the design phase - information that is required of many different disciplines in order to successfully optimize the ascent trajectory. Thus, the current paradigm of optimizing ascent trajectories involves generating point solutions for every change in a vehicle's design parameters. This is often a very tedious, manual, and time-consuming task for the analysts. Moreover, the trajectory design space is highly non-linear and multi

  6. Fault instability on a finite and planar fault related to early phase of nucleation

    NASA Astrophysics Data System (ADS)

    Mitsui, Yuta; Hirahara, Kazuro

    2011-06-01

    We numerically investigate the early phase of nucleation on a planar fault with the rate- and state-dependent friction law, loaded externally by steady slip, to clarify its relation to fault instability. We define Rn as the invasion distance of the inward creep to characterize that phase. For a circular fault, the dependence of Rn on the dimensionless parameters lb, lb-a, and lRA (all of these are proportional to the rigidity and the characteristic distance of the state evolution L and inversely proportional to the normal stress and the fault radius) can be compiled. We found that Rn is proportional to lb (both aging law and slip law of the state evolution) and lb-a (aging law). In the case of the aging law only, there are two regimes (ordinary events and slow events) separated by the value of lRA. The regimes have different trend lines, although we could not measure Rn for the case of lRA < 0.35 because of breaking of the mirror symmetry of instability along the loading direction. Rn in the slow event regime is smaller. Moreover, we investigated the effect of fault shape and found that a model with a long radius along the mode 2 direction has similar parameter dependence to circular faults, but a model with a long radius along the mode 3 direction has different ones. Our results imply that we can qualitatively estimate the fault instability parameters from the early phase of nucleation, although further research is necessary to enable application to actual faults.

  7. The progamic phase of an early-divergent angiosperm, Annona cherimola (Annonaceae)

    PubMed Central

    Lora, J.; Hormaza, J. I.; Herrero, M.

    2010-01-01

    Background and Aims Recent studies of reproductive biology in ancient angiosperm lineages are beginning to shed light on the early evolution of flowering plants, but comparative studies are restricted by fragmented and meagre species representation in these angiosperm clades. In the present study, the progamic phase, from pollination to fertilization, is characterized in Annona cherimola, which is a member of the Annonaceae, the largest extant family among early-divergent angiosperms. Beside interest due to its phylogenetic position, this species is also an ancient crop with a clear niche for expansion in subtropical climates. Methods The kinetics of the reproductive process was established following controlled pollinations and sequential fixation. Gynoecium anatomy, pollen tube pathway, embryo sac and early post-fertilization events were characterized histochemically. Key Results A plesiomorphic gynoecium with a semi-open carpel shows a continuous secretory papillar surface along the carpel margins, which run from the stigma down to the obturator in the ovary. The pollen grains germinate in the stigma and compete in the stigma-style interface to reach the narrow secretory area that lines the margins of the semi-open stylar canal and is able to host just one to three pollen tubes. The embryo sac has eight nuclei and is well provisioned with large starch grains that are used during early cellular endosperm development. Conclusions A plesiomorphic simple gynoecium hosts a simple pollen–pistil interaction, based on a support–control system of pollen tube growth. Support is provided through basipetal secretory activity in the cells that line the pollen tube pathway. Spatial constraints, favouring pollen tube competition, are mediated by a dramatic reduction in the secretory surface available for pollen tube growth at the stigma–style interface. This extramural pollen tube competition contrasts with the intrastylar competition predominant in more recently derived

  8. SURVIVAL OF INTERSTELLAR MOLECULES TO PRESTELLAR DENSE CORE COLLAPSE AND EARLY PHASES OF DISK FORMATION

    SciTech Connect

    Hincelin, U.; Wakelam, V.; Hersant, F.; Guilloteau, S.; Commerçon, B.

    2013-09-20

    An outstanding question of astrobiology is the link between the chemical composition of planets, comets, and other solar system bodies and the molecules formed in the interstellar medium. Understanding the chemical and physical evolution of the matter leading to the formation of protoplanetary disks is an important step for this. We provide some new clues to this long-standing problem using three-dimensional chemical simulations of the early phases of disk formation: we interfaced the full gas-grain chemical model Nautilus with the radiation-magnetohydrodynamic model RAMSES, for different configurations and intensities of the magnetic field. Our results show that the chemical content (gas and ices) is globally conserved during the collapsing process, from the parent molecular cloud to the young disk surrounding the first Larson core. A qualitative comparison with cometary composition suggests that comets are constituted of different phases, some molecules being direct tracers of interstellar chemistry, while others, including complex molecules, seem to have been formed in disks, where higher densities and temperatures allow for an active grain surface chemistry. The latter phase, and its connection with the formation of the first Larson core, remains to be modeled.

  9. Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Gharagozloo, Marjan; Mahmoud, Shaimaa; Gris, Denis

    2016-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized with MOG35–55 plus complete Freund's adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO congeners. Together, the present study supports a role for mMCP-4 in the early inflammatory phases of the disease in a mouse model of MS. PMID:27610007

  10. Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis.

    PubMed

    Desbiens, Louisane; Lapointe, Catherine; Gharagozloo, Marjan; Mahmoud, Shaimaa; Pejler, Gunnar; Gris, Denis; D'Orléans-Juste, Pedro

    2016-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized with MOG35-55 plus complete Freund's adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO congeners. Together, the present study supports a role for mMCP-4 in the early inflammatory phases of the disease in a mouse model of MS. PMID:27610007

  11. Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Gharagozloo, Marjan; Mahmoud, Shaimaa; Gris, Denis

    2016-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized with MOG35–55 plus complete Freund's adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO congeners. Together, the present study supports a role for mMCP-4 in the early inflammatory phases of the disease in a mouse model of MS.

  12. Correlation between the spin Hall angle and the structural phases of early 5d transition metals

    SciTech Connect

    Liu, Jun; Ohkubo, Tadakatsu; Mitani, Seiji; Hono, Kazuhiro; Hayashi, Masamitsu

    2015-12-07

    We have studied the relationship between the structure and the spin Hall angle of the early 5d transition metals in X/CoFeB/MgO (X = Hf, Ta, W, and Re) heterostructures. Spin Hall magnetoresistance (SMR) is used to characterize the spin Hall angle of the heavy metals. Transmission electron microscopy images show that all underlayers are amorphous-like when their thicknesses are small, however, crystalline phases emerge as the thickness is increased for certain elements. We find that the heavy metal layer thickness dependence of the SMR reflects these changes in structure. The largest spin Hall angle |θ{sub SH}| of Hf, Ta, W, and Re (∼0.11, 0.10, 0.23, and 0.07, respectively) is found when the dominant phase is amorphous-like. We find that the amorphous-like phase not only possesses large resistivity but also exhibits sizeable spin Hall conductivity, which both contribute to the emergence of the large spin Hall angle.

  13. Multi-stability of circadian phase wave within early postnatal suprachiasmatic nucleus

    PubMed Central

    Jeong, Byeongha; Hong, Jin Hee; Kim, Hyun; Choe, Han Kyoung; Kim, Kyungjin; Lee, Kyoung J.

    2016-01-01

    The suprachiasmatic nucleus (SCN) is a group of cells that functions as a biological master clock. In different SCN cells, oscillations of biochemical markers such as the expression-level of clock genes, are not synchronized but instead form slow circadian phase waves propagating over the whole cell population spatio-temporal struc- ture is a fixed property set by the anatomy of a given SCN. Here, we show that this is not the case in early postnatal SCN. Earlier studies presumed that their Based on bioluminescence imaging experiments with Per2-Luciferase mice SCN cultures which guided computer simulations of a realistic model of the SCN, we demonstrate that the wave is not unique but can be in various modes including phase- coherent oscillation, crescent-shaped wave, and most notably, a rotating pinwheel wave that conceptually resembles a wall clock with a rotating hand. Furthermore, mode transitions can be induced by a pulse of 38.5 °C temperature perturbation. Importantly, the waves support a significantly different period, suggesting that neither a spatially-fixed phase ordering nor a specialized pacemaker having a fixed period exist in these studied SCNs. These results lead to new important questions of what the observed multi-stability means for the proper function of an SCN and its arrhythmia. PMID:26891917

  14. Insights into Long-Lasting Protection Induced by RTS,S/AS02A Malaria Vaccine: Further Results from a Phase IIb Trial in Mozambican Children

    PubMed Central

    Guinovart, Caterina; Aponte, John J.; Sacarlal, Jahit; Aide, Pedro; Leach, Amanda; Bassat, Quique; Macete, Eusébio; Dobaño, Carlota; Lievens, Marc; Loucq, Christian; Ballou, W. Ripley; Cohen, Joe; Alonso, Pedro L.

    2009-01-01

    Background The pre-erythrocytic malaria vaccine RTS,S/AS02A has shown to confer protection against clinical malaria for at least 21 months in a trial in Mozambican children. Efficacy varied between different endpoints, such as parasitaemia or clinical malaria; however the underlying mechanisms that determine efficacy and its duration remain unknown. We performed a new, exploratory analysis to explore differences in the duration of protection among participants to better understand the protection afforded by RTS,S. Methodology/Principal Findings The study was a Phase IIb double-blind, randomized controlled trial in 2022 children aged 1 to 4 years. The trial was designed with two cohorts to estimate vaccine efficacy against two different endpoints: clinical malaria (cohort 1) and infection (cohort 2). Participants were randomly allocated to receive three doses of RTS,S/AS02A or control vaccines. We did a retrospective, unplanned sub-analysis of cohort 2 data using information collected for safety through the health facility-based passive case detection system. Vaccine efficacy against clinical malaria was estimated over the first six-month surveillance period (double-blind phase) and over the following 12 months (single-blind phase), and analysis was per-protocol. Adjusted vaccine efficacy against first clinical malaria episodes in cohort 2 was of 35.4% (95% CI 4.5–56.3; p = 0.029) over the double-blind phase and of 9.0% (−30.6–36.6; p = 0.609) during the single-blind phase. Conclusions/Significance Contrary to observations in cohort 1, where efficacy against clinical malaria did not wane over time, in cohort 2 the efficacy decreases with time. We hypothesize that this reduced duration of protection is a result of the early diagnosis and treatment of infections in cohort 2 participants, preventing sufficient exposure to asexual-stage antigens. On the other hand, the long-term protection against clinical disease observed in cohort 1 may be a consequence

  15. Phase noise reveals early category-specific modulation of the event-related potentials

    PubMed Central

    Németh, Kornél; Kovács, Petra; Vakli, Pál; Kovács, Gyula; Zimmer, Márta

    2014-01-01

    Previous studies have found that the amplitude of the early event-related potential (ERP) components evoked by faces, such as N170 and P2, changes systematically as a function of noise added to the stimuli. This change has been linked to an increased perceptual processing demand and to enhanced difficulty in perceptual decision making about faces. However, to date it has not yet been tested whether noise manipulation affects the neural correlates of decisions about face and non-face stimuli similarly. To this end, we measured the ERPs for faces and cars at three different phase noise levels. Subjects performed the same two-alternative age-discrimination task on stimuli chosen from young–old morphing continua that were created from faces as well as cars and were calibrated to lead to similar performances at each noise-level. Adding phase noise to the stimuli reduced performance and enhanced response latency for the two categories to the same extent. Parallel to that, phase noise reduced the amplitude and prolonged the latency of the face-specific N170 component. The amplitude of the P1 showed category-specific noise dependence: it was enhanced over the right hemisphere for cars and over the left hemisphere for faces as a result of adding phase noise to the stimuli, but remained stable across noise levels for cars over the left and for faces over the right hemisphere. Moreover, noise modulation altered the category-selectivity of the N170, while the P2 ERP component, typically associated with task decision difficulty, was larger for the more noisy stimuli regardless of stimulus category. Our results suggest that the category-specificity of noise-induced modulations of ERP responses starts at around 100 ms post-stimulus. PMID:24795689

  16. Early effector cells survive the contraction phase in malaria infection and generate both central and effector memory T cells.

    PubMed

    Opata, Michael M; Carpio, Victor H; Ibitokou, Samad A; Dillon, Brian E; Obiero, Joshua M; Stephens, Robin

    2015-06-01

    CD4 T cells orchestrate immunity against blood-stage malaria. However, a major challenge in designing vaccines to the disease is poor understanding of the requirements for the generation of protective memory T cells (Tmem) from responding effector T cells (Teff) in chronic parasite infection. In this study, we use a transgenic mouse model with T cells specific for the merozoite surface protein (MSP)-1 of Plasmodium chabaudi to show that activated T cells generate three distinct Teff subsets with progressive activation phenotypes. The earliest observed Teff subsets (CD127(-)CD62L(hi)CD27(+)) are less divided than CD62L(lo) Teff and express memory genes. Intermediate (CD62L(lo)CD27(+)) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62L(lo)CD27(-)) late effector cells have a terminal Teff phenotype (PD-1(+), Fas(hi), AnnexinV(+)). We show that although IL-2 promotes expansion, it actually slows terminal effector differentiation. Using adoptive transfer, we show that only early Teff survive the contraction phase and generate the terminal late Teff subsets, whereas in uninfected recipients, they become both central and effector Tmem. Furthermore, we show that progression toward full Teff activation is promoted by increased duration of infection, which in the long-term promotes Tem differentiation. Therefore, we have defined markers of progressive activation of CD4 Teff at the peak of malaria infection, including a subset that survives the contraction phase to make Tmem, and show that Ag and cytokine levels during CD4 T cell expansion influence the proportion of activated cells that can survive contraction and generate memory in malaria infection.

  17. Early effector cells survive the contraction phase in malaria infection and generate both central and effector memory T cells.

    PubMed

    Opata, Michael M; Carpio, Victor H; Ibitokou, Samad A; Dillon, Brian E; Obiero, Joshua M; Stephens, Robin

    2015-06-01

    CD4 T cells orchestrate immunity against blood-stage malaria. However, a major challenge in designing vaccines to the disease is poor understanding of the requirements for the generation of protective memory T cells (Tmem) from responding effector T cells (Teff) in chronic parasite infection. In this study, we use a transgenic mouse model with T cells specific for the merozoite surface protein (MSP)-1 of Plasmodium chabaudi to show that activated T cells generate three distinct Teff subsets with progressive activation phenotypes. The earliest observed Teff subsets (CD127(-)CD62L(hi)CD27(+)) are less divided than CD62L(lo) Teff and express memory genes. Intermediate (CD62L(lo)CD27(+)) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62L(lo)CD27(-)) late effector cells have a terminal Teff phenotype (PD-1(+), Fas(hi), AnnexinV(+)). We show that although IL-2 promotes expansion, it actually slows terminal effector differentiation. Using adoptive transfer, we show that only early Teff survive the contraction phase and generate the terminal late Teff subsets, whereas in uninfected recipients, they become both central and effector Tmem. Furthermore, we show that progression toward full Teff activation is promoted by increased duration of infection, which in the long-term promotes Tem differentiation. Therefore, we have defined markers of progressive activation of CD4 Teff at the peak of malaria infection, including a subset that survives the contraction phase to make Tmem, and show that Ag and cytokine levels during CD4 T cell expansion influence the proportion of activated cells that can survive contraction and generate memory in malaria infection. PMID:25911759

  18. Secondary structures of short peptide chains in the gas phase: Double resonance spectroscopy of protected dipeptides

    NASA Astrophysics Data System (ADS)

    Chin, Wutharath; Dognon, Jean-Pierre; Canuel, Clélia; Piuzzi, François; Dimicoli, Iliana; Mons, Michel; Compagnon, Isabelle; von Helden, Gert; Meijer, Gerard

    2005-02-01

    The conformational structure of short peptide chains in the gas phase is studied by laser spectroscopy of a series of protected dipeptides, Ac-Xxx-Phe-NH2, Xxx=Gly, Ala, and Val. The combination of laser desorption with supersonic expansion enables us to vaporize the peptide molecules and cool them internally; IR/UV double resonance spectroscopy in comparison to density functional theory calculations on Ac-Gly-Phe-NH2 permits us to identify and characterize the conformers populated in the supersonic expansion. Two main conformations, corresponding to secondary structures of proteins, are found to compete in the present experiments. One is composed of a doubly γ-fold corresponding to the 27 ribbon structure. Topologically, this motif is very close to a β-strand backbone conformation. The second conformation observed is the β-turn, responsible for the chain reversal in proteins. It is characterized by a relatively weak hydrogen bond linking remote NH and CO groups of the molecule and leading to a ten-membered ring. The present gas phase experiment illustrates the intrinsic folding properties of the peptide chain and the robustness of the β-turn structure, even in the absence of a solvent. The β-turn population is found to vary significantly with the residues within the sequence; the Ac-Val-Phe-NH2 peptide, with its two bulky side chains, exhibits the largest β-turn population. This suggests that the intrinsic stabilities of the 27 ribbon and the β-turn are very similar and that weakly polar interactions occurring between side chains can be a decisive factor capable of controlling the secondary structure.

  19. Lyman horizons in the early phases of the epoch of reionization

    NASA Astrophysics Data System (ADS)

    Vonlanthen, P.; Semelin, B.

    2011-12-01

    It has been shown that the radial profile of the Lyman-α flux around light sources emitting in the Lyman band during the early phases of the epoch of reionization is characterized by a series of step-like discontinuities. This property originates in the fact that the neutral intergalactic medium is optically thick at the frequencies of all the Lyman-series lines. We show that, through unsaturated Wouthuysen-Field coupling, these spherical discontinuities are also present in the redshifted 21 cm signal of neutral hydrogen. We use realistic 3D numerical simulations with full radiative transfer calculation in the first five Lyman lines in order to study the properties of these discontinuities and the possibility for detection with the future Square Kilometre Array. Although challenging, these observations could provide a diagnostic tool to disentangle the cosmological signal and residuals from imperfect foreground removal.

  20. HISPASAT launch and early operations phases: Computation and monitoring of geostationary satellite positioning

    NASA Technical Reports Server (NTRS)

    Brousse, Pascal; Desprairies, Arnaud

    1993-01-01

    Since 1974, CNES, the French National Space Agency, has been involved in the geostationary launch and early operations phases (LEOP) of moving satellites from a transfer orbit delivered by a launcher to a geostationary point. During the operations and their preparation, the Flight Dynamics Center (FDC), part of CNES LEOP facilities, is in charge of the space mechanics aspects. What is noteworthy about the Spanish HISPASAT satellite positioning is that all the operations were performed on the customer's premises, and consequently the FDC was duplicated in Madrid, Spain. The first part of this paper is the FDC presentation: its role, its hardware configuration, and its space dynamics ground control system called MERCATOR. The second part of this paper details the preparation used by the FDC for the HISPASAT mission: hardware and software installation in Madrid, integration with the other entities, and technical and operational qualifications. The third part gives results concerning flight dynamics aspects and operational activities.

  1. Prognostic implications of cardiac scintigraphic parameters obtained in the early phase of acute myocardial infarction

    SciTech Connect

    Suzuki, A.; Matsushima, H.; Satoh, A.; Hayashi, H.; Sotobata, I.

    1988-06-01

    A cohort of 76 patients with acute myocardial infarction was studied with infarct-avid scan, radionuclide ventriculography, and thallium-201 myocardial perfusion scintigraphy. Infarct area, left ventricular ejection fraction, and defect score were calculated as radionuclide indices of the extent of myocardial infarction. The correlation was studied between these indices and cardiac events (death, congestive heart failure, postinfarction angina, and recurrence of myocardial infarction) in the first postinfarction year. High-risk patients (nonsurvivors and patients who developed heart failure) had a larger infarct area, a lower left ventricular ejection fraction, and a larger defect score than the others. Univariate linear discriminant analysis was done to determine the optimal threshold of these parameters for distinguishing high-risk patients from others. Radionuclide parameters obtained in the early phase of acute myocardial infarction were useful for detecting both patients with grave complications and those with poor late prognosis during a mean follow-up period of 2.6 years.

  2. Precision Medicine for Molecularly Targeted Agents and Immunotherapies in Early-Phase Clinical Trials

    PubMed Central

    Lopez, Juanita; Harris, Sam; Roda, Desam; Yap, Timothy A

    2015-01-01

    Precision medicine in oncology promises the matching of genomic, molecular, and clinical data with underlying mechanisms of a range of novel anticancer therapeutics to develop more rational and effective antitumor strategies in a timely manner. However, despite the remarkable progress made in the understanding of novel drivers of different oncogenic processes, success rates for the approval of oncology drugs remain low with substantial fiscal consequences. In this article, we focus on how recent rapid innovations in technology have brought greater clarity to the biological and clinical complexities of different cancers and advanced the development of molecularly targeted agents and immunotherapies in clinical trials. We discuss the key challenges of identifying and validating predictive biomarkers of response and resistance using both tumor and surrogate tissues, as well as the hurdles associated with intratumor heterogeneity. Finally, we outline evolving strategies employed in early-phase trial designs that incorporate omics-based technologies. PMID:26609214

  3. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    PubMed Central

    Xu, Jintao; Eastman, Alison J.; Flaczyk, Adam; Neal, Lori M.; Zhao, Guolei; Carolan, Jacob; Malachowski, Antoni N.; Stolberg, Valerie R.; Yosri, Mohammed; Chensue, Stephen W.; Curtis, Jeffrey L.; Osterholzer, John J.

    2016-01-01

    ABSTRACT Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance. PMID:27406560

  4. No increased risk of early revision during the implementation phase of new cup designs

    PubMed Central

    Björk, Mathias; Nemes, Szilard; Rolfson, Ola; Jolbäck, Per; Kärrholm, Johan

    2016-01-01

    Background and purpose — In Sweden, less than 5% of patients who undergo total hip arthroplasty (THA) have revision. Younger patients have an increased risk of revision. New prosthetic designs are being introduced in order to improve outcomes further. We investigated whether the introductory phase of new cup designs would increase the revision rate. Patients and methods — All THAs and first-time cup revisions performed from 1993 through 2011 were identified in the Swedish Hip Arthroplasty Register. The 15 types of cups used in more than 500 operations and inserted in more than 50 cases in each hospital (n = 52,903) were selected. All cups were given an order number, based on the order in which the cup had been inserted at each hospital. The influence of order number on the risk of revision was analyzed in a regression model, which was adjusted for potentially confounding demographic and surgical data. Revision within 2 years for all reasons (n = 940) was used as primary endpoint. Changes in the risk of revision based on the order number were analyzed using a spline. Results — The order number of the cup had no influence on the risk of early revision (p ≥ 0.7). Categorizing the order number using cutoff values obtained from the splines did not result in any statistically significant changes in risk of revision (p ≥ 0.2). Interpretation — We did not find any increased risk of early revision during the implementation phase of new cup designs. This finding is unexpected, and partly conflicts with data from other registries. The structured and stepwise introduction of new prosthesis designs, facilitated by the annual feedback from the Swedish Hip Arthroplasty Register, may partly explain this discrepancy. PMID:27168095

  5. The early phases of the Type Iax supernova SN 2011ay

    NASA Astrophysics Data System (ADS)

    Szalai, Tamás; Vinkó, József; Sárneczky, Krisztián; Takáts, Katalin; Benkő, József M.; Kelemen, János; Kuli, Zoltán; Silverman, Jeffrey M.; Marion, G. Howie; Wheeler, J. Craig

    2015-10-01

    We present a detailed study of the early phases of the peculiar supernova (SN) 2011ay based on BVRI photometry obtained at Konkoly Observatory, Hungary, and optical spectra taken with the Hobby-Eberly Telescope at McDonald Observatory, Texas. The spectral analysis carried out with SYN++ and SYNAPPS confirms that SN 2011ay belongs to the recently defined class of SNe Iax, which is also supported by the properties of its light and colour curves. The estimated photospheric temperature around maximum light, Tphot ˜ 8000 K, is lower than in most SNe Ia, which results in the appearance of strong Fe II features in the spectra of SN 2011ay, even during the early phases. We also show that strong blending with metal features (those of Ti II, Fe II, Co II) makes the direct analysis of the broad spectral features very difficult, and this may be true for all SNe Iax. We find two alternative spectrum models that both describe the observed spectra adequately, but their photospheric velocities differ by at least ˜3000 km s-1. The quasi-bolometric light curve of SN 2011ay has been assembled by integrating the ultraviolet-optical spectral energy distributions. Fitting a modified Arnett model to Lbol(t), the moment of explosion and other physical parameters, i.e. the rise time to maximum, the 56Ni mass and the total ejecta mass are estimated as trise ˜ 14 ± 1 d, MNi ˜ 0.22 ± 0.01 M⊙ and Mej ˜ 0.8 M⊙, respectively.

  6. Alteration in Endometrial Proteins during Early- and Mid-Secretory Phases of the Cycle in Women with Unexplained Infertility

    PubMed Central

    Manohar, Murli; Khan, Huma; Sirohi, Vijay Kumar; Das, Vinita; Agarwal, Anjoo; Pandey, Amita; Siddiqui, Waseem Ahmad; Dwivedi, Anila

    2014-01-01

    Background Compromised receptivity of the endometrium is a major cause of unexplained infertility, implantation failure and subclinical pregnancy loss. In order to investigate the changes in endometrial protein profile as a cause of unexplained infertility, the current study was undertaken to analyze the differentially expressed proteins of endometrium from early-secretory (LH+2) to mid-secretory phase (LH+7), in women with unexplained infertility. Methods 2-D gel electrophoresis was performed to analyze the proteomic changes between early- (n = 8) and mid-secretory (n = 8) phase endometrium of women with unexplained infertility. The differentially expressed protein spots were identified by LC-MS analysis and validated by immunoblotting and immuno-histochemical analysis in early- (n = 4) and mid-secretory (n = 4) phase endometrium of infertile women. Validated proteins were also analyzed in early- (n = 4) and mid-secretory (n = 4) phase endometrium of fertile women. Results Nine proteins were found to be differentially expressed between early- and mid- secretory phases of endometrium of infertile women. The expression of Ras-related protein Rap-1b, Protein disulfide isomerase A3, Apolipoprotein-A1 (Apo-A1), Cofilin-1 and RAN GTP-binding nuclear protein (Ran) were found to be significantly increased, whereas, Tubulin polymerization promoting protein family member 3, Superoxide dismutase [Cu-Zn], Sorcin, and Proteasome subunit alpha type-5 were significantly decreased in mid- secretory phase endometrium of infertile women as compared to early-secretory phase endometrium of infertile women. Validation of 4 proteins viz. Sorcin, Cofilin-1, Apo-A1 and Ran were performed in separate endometrial biopsy samples from infertile women. The up-regulated expression of Sorcin and down-regulated expression of Cofilin-1 and Apolipoprotein-A1, were observed in mid-secretory phase as compared to early-secretory phase in case of fertile women. Conclusions De

  7. Ikaros is degraded by proteasome-dependent mechanism in the early phase of apoptosis induction

    SciTech Connect

    He, Li-Cai; Xu, Han-Zhang; Gu, Zhi-Min; Liu, Chuan-Xu; Chen, Guo-Qiang; Wang, Yue-Fei; Wen, Dong-Hua; Wu, Ying-Li

    2011-03-18

    Research highlights: {yields} Chemotherapeutic drugs or UV treatment reduces Ikaros prior to caspase-3 activation. {yields} Etoposide treatment does not alter the mRNA but shortens the half-life of Ikaros. {yields} MG132 or epoxomicin but not calpeptin inhibits etoposide-induced Ikaros degradation. {yields} Overexpression of Ikaros accelerates etoposide-induced apoptosis in NB4 cells. -- Abstract: Ikaros is an important transcription factor involved in the development and differentiation of hematopoietic cells. In this work, we found that chemotherapeutic drugs or ultraviolet radiation (UV) treatment could reduce the expression of full-length Ikaros (IK1) protein in less than 3 h in leukemic NB4, Kasumi-1 and Jurkat cells, prior to the activation of caspase-3. Etoposide treatment could not alter the mRNA level of IK1 but it could shorten the half-life of IK1. Co-treatment with the proteasome inhibitor MG132 or epoxomicin but not calpain inhibitor calpeptin inhibited etoposide-induced Ikaros downregulation. Overexpression of IK1 could accelerate etoposide-induced apoptosis in NB4 cells, as evidenced by the increase of Annexin V positive cells and the more early activation of caspase 3. To our knowledge, this is the first report to show that upon chemotherapy drugs or UV treatment, IK1 could be degraded via the proteasome system in the early phase of apoptosis induction. These data might shed new insight on the role of IK1 in apoptosis and the post-translational regulation of IK1.

  8. REMIR: The REM infrared camera to follow up the early phases of GRBs afterglows

    NASA Astrophysics Data System (ADS)

    Calzoletti, L.; Melandri, A.; Testa, V.; Antonelli, L. A.; Vitali, F.; D'Alessio, F.; di Paola, A.; Zerbi, F. M.; Chincarini, G.; Cunniffe, R.; Jordan, B.; Rodonò, M.; Conconi, P.; Covino, S.; Cutispoto, G.; Molinari, E.; Tosti, G.; Ross/Rem Team

    2005-07-01

    REMIR is a near-infrared camera, covering the 0.95-2.3 μm range with 5 filters (z,J,H,Ks and H2), mounted at one of the Nasmyth foci of the REM (Rapid Eye Mount) telescope. REM is a fully robotic fast-slewing 60 cm telescope, primarily designed to follow-up the early phases of the afterglow of GRBs detected by dedicated instruments onboard satellites (like SWIFT, a satellite entirely dedicated to GRBs science launched the 12 November 2004). Moreover REM hosts a slitless spectrograph covering the range 0.45-0.95 μm, with 30 sample points and with the possibility to perform broad-band V,R,I photometry (ROSS, REM Optical Slitless Spectrograph). The main task of REMIR is to perform realtime NIR observations of GRBs detected by gamma-ray monitors onboard satellites, looking for any possible infrared transient source. As soon as a transient source is detected in the IR images, larger telescopes are promptly alerted to perform early spectroscopy of the afterglow. All the above operations are performed in a fully automatic way and without any human supervision. We present the results of on-site tests that have been done to characterize the REMIR camera and the performances of the dedicated reduction pipeline AQuA (Automatic Quick Analysis), suited for fast transients detection.

  9. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    PubMed Central

    2012-01-01

    Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs) and thromboxane A2 (TXA2). The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA) sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2) after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187) induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells. PMID:22439792

  10. Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats.

    PubMed

    Ahn, Hyo-Jin; An, Beum-Soo; Jung, Eui-Man; Yang, Hyun; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-09-01

    Parabens are widely used as anti-microbial agents in the cosmetic and pharmaceutical industries. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In the present study, 55 female pups were given daily subcutaneous injections of methyl-, propyl-, and butyl-paraben or 17beta-estradiol (E2) during neonatal Day 1-7. The ovaries were excised on postnatal Day 8, then fixed and stained with hematoxylin and eosin for histological analysis. The follicles were counted and classified as being in the primordial, early primary, or primary stages. The number of primordial follicles increased while early primary follicles decreased at the high doses of propyl- and butyl-paraben. The levels of anti-Mullerian hormone (AMH) and Foxl2 mRNA increased by propyl- and butyl-parabens whereas kit ligand/stem cell factor (KITL) expression was up regulated only by butyl-paraben. The mRNA levels of StAR and Cyp11a1 were significantly decreased after treatment with methyl-, propyl-, and butyl-parabens. Consistent with its use as a positive control, E2 regulated the expression of KITL, StAR, and Cyp11a1 genes, but surprisingly did not affect AMH and Foxl2 levels. Thus, E2 and parabens had different effects on the regulation of folliculogenic and steroidogenic genes, demonstrating the estrogenic and nonestrogenic properties of parabens in the ovary. Taken together, our data show that parabens stimulated AMH mRNA expression and consequently inhibited the early phase of folliculogenesis in the ovaries of neonatal female rat. The levels of steroidogenic enzymes, indicators of follicle differentiation, appeared to be regulated by parabens through inhibition of their transcriptional repressor, Foxl2.

  11. Global anomalies on the surface of fermionic symmetry-protected topological phases in (3+1) dimensions

    NASA Astrophysics Data System (ADS)

    Hsieh, Chang-Tse; Cho, Gil Young; Ryu, Shinsei

    2016-02-01

    Quantum anomalies, breakdown of classical symmetries by quantum effects, provide a sharp definition of symmetry protected topological phases. In particular, they can diagnose interaction effects on the noninteracting classification of fermionic symmetry protected topological phases. In this paper, we identify quantum anomalies in two kinds of (3+1)d fermionic symmetry protected topological phases: (i) topological insulators protected by CP (charge conjugation × reflection) and electromagnetic U (1 ) symmetries, and (ii) topological superconductors protected by reflection symmetry. For the first example, which is related to, by CPT-theorem, time-reversal symmetric topological insulators, we show that the CP-projected partition function of the surface theory is not invariant under large U (1 ) gauge transformations, but picks up an anomalous sign, signaling a Z2 topological classification. Similarly, for the second example, which is related to, by CPT-theorem, class DIII topological superconductors, we discuss the invariance/noninvariance of the partition function of the surface theory, defined on the three-torus and its descendants generated by the orientifold projection, under large diffeomorphisms (coordinate transformations). The connection to the collapse of the noninteracting classification by an integer (Z ) to Z16, in the presence of interactions, is discussed.

  12. SUMOylation of Rb enhances its binding with CDK2 and phosphorylation at early G1 phase.

    PubMed

    Meng, Fengxi; Qian, Jiang; Yue, Han; Li, Xiaofeng; Xue, Kang

    2016-07-01

    Retinoblastoma protein (Rb) is a prototypical tumor suppressor that is vital to the negative regulation of the cell cycle and tumor progression. Hypo-phosphorylated Rb is associated with G0/G1 arrest by suppressing E2F transcription factor activity, whereas Rb hyper-phosphorylation allows E2F release and cell cycle progression from G0/G1 to S phase. However, the factors that regulate cyclin-dependent protein kinase (CDK)-dependent hyper-phosphorylation of Rb during the cell cycle remain obscure. In this study, we show that throughout the cell cycle, Rb is specifically small ubiquitin-like modifier (SUMO)ylated at early G1 phase. SUMOylation of Rb stimulates its phosphorylation level by recruiting a SUMO-interaction motif (SIM)-containing kinase CDK2, leading to Rb hyper-phosphorylation and E2F-1 release. In contrast, a SUMO-deficient Rb mutant results in reduced SUMOylation and phosphorylation, weakened CDK2 binding, and attenuated E2F-1 sequestration. Furthermore, we reveal that Rb SUMOylation is required for cell proliferation. Therefore, our study describes a novel mechanism that regulates Rb phosphorylation during cell cycle progression. PMID:27163259

  13. SUMOylation of Rb enhances its binding with CDK2 and phosphorylation at early G1 phase

    PubMed Central

    Meng, Fengxi; Qian, Jiang; Yue, Han; Li, Xiaofeng; Xue, Kang

    2016-01-01

    ABSTRACT Retinoblastoma protein (Rb) is a prototypical tumor suppressor that is vital to the negative regulation of the cell cycle and tumor progression. Hypo-phosphorylated Rb is associated with G0/G1 arrest by suppressing E2F transcription factor activity, whereas Rb hyper-phosphorylation allows E2F release and cell cycle progression from G0/G1 to S phase. However, the factors that regulate cyclin-dependent protein kinase (CDK)-dependent hyper-phosphorylation of Rb during the cell cycle remain obscure. In this study, we show that throughout the cell cycle, Rb is specifically small ubiquitin-like modifier (SUMO)ylated at early G1 phase. SUMOylation of Rb stimulates its phosphorylation level by recruiting a SUMO-interaction motif (SIM)-containing kinase CDK2, leading to Rb hyper-phosphorylation and E2F-1 release. In contrast, a SUMO-deficient Rb mutant results in reduced SUMOylation and phosphorylation, weakened CDK2 binding, and attenuated E2F-1 sequestration. Furthermore, we reveal that Rb SUMOylation is required for cell proliferation. Therefore, our study describes a novel mechanism that regulates Rb phosphorylation during cell cycle progression. PMID:27163259

  14. Early Tumor Development Captured Through Nondestructive, High Resolution Differential Phase Contrast X-ray Imaging

    PubMed Central

    Beheshti, A.; Pinzer, B. R.; McDonald, J. T.; Stampanoni, M.; Hlatky, L.

    2014-01-01

    Although a considerable amount is known about molecular dysregulations in later stages of tumor progression, much less is known about the regulated processes supporting initial tumor growth. Insight into such processes can provide a fuller understanding of carcinogenesis, with implications for cancer treatment and risk assessment. Work from our laboratory suggests that organized substructure emerges during tumor formation. The goal here was to examine the feasibility of using state-of-the-art differential phase contrast X-ray imaging to investigate density differentials that evolve during early tumor development. To this end the beamline for TOmographic Microscopy and Coherent rAdiology experimenTs (TOMCAT) at the Swiss Light Source was used to examine the time-dependent assembly of substructure in developing tumors. Differential phase contrast (DPC) imaging based on grating interferometry as implemented with TOMCAT, offers sensitivity to density differentials within soft tissues and a unique combination of high resolution coupled with a large field of view that permits the accommodation of larger tissue sizes (1 cm in diameter), difficult with other imaging modalities. PMID:24125488

  15. Early Steroid-Induced Osteonecrosis of Rabbit Femoral Head and Panax notoginseng Saponins: Mechanism and Protective Effects

    PubMed Central

    Qiang, Hui; Liu, Huitong; Ling, Ming; Wang, Kunzheng; Zhang, Chen

    2015-01-01

    Background. This study was aimed at investigating the pathogenesis of oxidative stress in steroid-induced avascular necrosis of the femoral head (SANFH) and at exploring the mechanism and protective effects of Panax notoginseng saponins (PNS) on early SANFH. Methods. 80 adult New Zealand rabbits were randomly divided into control group, model group, and PNS group. In model group, equine serum was injected into auricular vein; then methylprednisolone was injected into gluteus. In PNS group, PNS was applied for 14 consecutive days before methylprednisolone management. At different time points, serum and femoral heads were prepared for T-AOC, SOD, GSH-PX, ·OH, and MDA determination. Two weeks after steroid management, all femoral heads were assessed with MRI and HE staining. Results. Typical early osteonecrosis symptoms were observed in model group. Our results showed that PNS could significantly ameliorate the decrease of T-AOC level, improve SOD and GSH-PX activity, suppress ·OH ability, and augment MDA level. Besides, PNS improved MRI and pathological changes of the femoral head, markedly reducing the incidence of osteonecrosis. Conclusion. Based on our research, we found oxidative stress played a positive role in the occurrence of SANFH where reactive oxygen species was the direct cause. PNS could protect rabbits against early steroid-induced osteonecrosis of femoral head by its antioxidative effect. PMID:25866538

  16. Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth – Three Phases in Early Lactation and Progressive Individual Differences

    PubMed Central

    Zhang, Tong; Zhang, Rong; Zhang, Liang; Zhang, Zhihe; Hou, Rong; Wang, Hairui; Loeffler, I. Kati; Watson, David G.; Kennedy, Malcolm W.

    2015-01-01

    Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1–6 (Phase 1), days 7–20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth. PMID:26630345

  17. Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth--Three Phases in Early Lactation and Progressive Individual Differences.

    PubMed

    Zhang, Tong; Zhang, Rong; Zhang, Liang; Zhang, Zhihe; Hou, Rong; Wang, Hairui; Loeffler, I Kati; Watson, David G; Kennedy, Malcolm W

    2015-01-01

    Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1-6 (Phase 1), days 7-20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth.

  18. Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth--Three Phases in Early Lactation and Progressive Individual Differences.

    PubMed

    Zhang, Tong; Zhang, Rong; Zhang, Liang; Zhang, Zhihe; Hou, Rong; Wang, Hairui; Loeffler, I Kati; Watson, David G; Kennedy, Malcolm W

    2015-01-01

    Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1-6 (Phase 1), days 7-20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth. PMID:26630345

  19. Project fires. Volume 2: Protective ensemble performance standards, phase 1B

    NASA Astrophysics Data System (ADS)

    Abeles, F. J.

    1980-05-01

    The design of the prototype protective ensemble was finalized. Prototype ensembles were fabricated and then subjected to a series of qualification tests which were based upon the protective ensemble performance standards PEPS requirements. Engineering drawings and purchase specifications were prepared for the new protective ensemble.

  20. Project FIRES [Firefighters' Integrated Response Equipment System]. Volume 2: Protective Ensemble Performance Standards, Phase 1B

    NASA Technical Reports Server (NTRS)

    Abeles, F. J.

    1980-01-01

    The design of the prototype protective ensemble was finalized. Prototype ensembles were fabricated and then subjected to a series of qualification tests which were based upon the protective ensemble performance standards PEPS requirements. Engineering drawings and purchase specifications were prepared for the new protective ensemble.

  1. Relation between progesterone concentrations during the early luteal phase and follicular dynamics in goats.

    PubMed

    Menchaca, Alejo; Rubianes, Edgardo

    2002-03-15

    We studied the relationship between progesterone (P4) concentrations early in the estrus cycle and follicular dynamics in dairy goats. We used seven untreated goats (control group) and six progesterone treated goats (P group) with a controlled internal drug release device from Days 0 to 5 (Day 0: day of ovulation). We performed daily ultrasonograph during the interovulatory interval to determine ovarian change and took daily blood samples to determine serum estradiol 17beta (E2) and P4 concentrations by RIA. We divided the control goats into 3- (n = 4) and 4-wave goats (n = 3), according to the number of follicular waves recorded during the ovulatory cycle. Mean progesterone concentrations between Days I and 5 were higher and mean estradiol concentrations between Days 3 and 5 were lower in 4-wave goats (P4: 3.8+/-0.2 ng/ml; E2: 1.6+/-0.2 pg/ml) than in 3-wave goats (P4: 2.0+/-0.5 ng/ml, P < 0.05; E2: 4.4+/-0.9 pg/ml, P < 0.05). Wave 2 emerged earlier in 4-wave (Day 4.2+/-0.3) than in 3-wave goats (Day 7.3+/-0.3, P < 0.05). Three out of six of the progesterone-treated goats had short cycles (mean 8.0+/-0.0 days) and ovulated from Wave 1. The other three goats had shorter cycles (mean 18.3+/-0.3 days) than the control group (20.0+/-0.2 days; P < 0.05), although they were within the normal range of control cycles (shortened cycles). In the three treated goats with shortened cycles (two with four waves, one with three waves), mean progesterone concentrations between Days I and 5 were higher (4.7+/-0.6 ng/ml) than in the 3-wave control goats. In these goats, Wave 2 emerged at Day 4.3+/-0.3, similar to the time observed in 4-wave goats but earlier (P < or = 0.05) than in 3-wave control goats. Overall results confirm a relationship between the progesterone levels and the follicular wave turnover during the early luteal phase in the goat. Higher progesterone concentrations may accelerate follicular turnover probably by an early decline of the negative feedback action of

  2. Decreased cellular permeability to H2O2 protects Saccharomyces cerevisiae cells in stationary phase against oxidative stress.

    PubMed

    Sousa-Lopes, A; Antunes, F; Cyrne, L; Marinho, H S

    2004-12-01

    The higher resistance of stationary-phase Saccharomyces cerevisiae to H2O2 when compared with exponential phase is well characterized, but the molecular mechanisms underlying it remain mostly unknown. By applying the steady-state H2O2-delivery model, we show that (a) cellular permeability to H2O2 is five times lower in stationary--than in exponential phase; (b) cell survival to H2O2 correlates with H2O2 cellular gradients for a variety of cells; and, (c) cells in stationary phase are predicted to be more susceptible to intracellular H2O2 than in exponential phase. In conclusion, limiting H2O2 diffusion into cells is a key protective mechanism against extracellular H2O2.

  3. The role of meniscal tissue in joint protection in early osteoarthritis.

    PubMed

    Verdonk, Rene; Madry, Henning; Shabshin, Nogah; Dirisamer, Florian; Peretti, Giuseppe M; Pujol, Nicolas; Spalding, Tim; Verdonk, Peter; Seil, Romain; Condello, Vincenzo; Di Matteo, Berardo; Zellner, Johannes; Angele, Peter

    2016-06-01

    It is widely accepted that partial meniscectomy leads to early onset of osteoarthritis (OA). A strong correlation exists between the amount and location of the resected meniscus and the development of degenerative changes in the knee. On the other hand, osteoarthritic changes of the joint alter the structural and functional integrity of meniscal tissue. These alterations might additionally compromise the limited healing capacity of the meniscus. In young, active patients without cartilage damage, meniscus therapy including partial meniscectomy, meniscus suture, and meniscus replacement has proven beneficial effects in long-term studies. Even in an early osteoarthritic milieu, there is a relevant regenerative potential of the meniscus and the surrounding cartilage. This potential should be taken into account, and meniscal surgery can be performed with the correct timing and the proper indication even in the presence of early OA.

  4. Peer Victimization among Young Children with Disabilities: Early Risk and Protective Factors

    ERIC Educational Resources Information Center

    Son, Esther; Peterson, N. Andrew; Pottick, Kathleen J.; Zippay, Allison; Parish, Susan L.; Lohrmann, Sharon

    2014-01-01

    The purpose of this study was to examine the risk and protective factors of peer victimization among young children with disabilities. This study analyzed data from the Pre-Elementary Education Longitudinal Study (n =1,130) to test a path model that included child, family, and school characteristics at Year 1 and peer-relation difficulties and…

  5. Adolescents' Sexually Transmitted Disease Protective Attitudes Predict Sexually Transmitted Disease Acquisition in Early Adulthood

    ERIC Educational Resources Information Center

    Crosby, Richard A.; Danner, Fred

    2008-01-01

    Background: Estimates suggest that about 48% of nearly 19 million cases of sexually transmitted diseases (STDs) occurring annually in the United States are acquired by persons aged 15-24 years. The purpose of this study was to test the hypothesis that adolescents' attitudes about protecting themselves from STDs predict their laboratory-confirmed…

  6. Can Socially Adept Friends Protect Peer-Victimized Early Adolescents against Lower Academic Competence?

    ERIC Educational Resources Information Center

    Tu, Kelly M.; Erath, Stephen A.; Flanagan, Kelly S.

    2012-01-01

    The present study examined indices of friends' social adjustment (prosocial skills and social anxiety) that may protect against or exacerbate vulnerability to lower academic competence in the context of peer victimization during middle school (N=320). Peer victimization was assessed with peer nominations, social anxiety was measured with self…

  7. Online Biomonitoring and Early Warning Systems for Protection of Water Sources

    EPA Science Inventory

    The ability to perform real time biomonitoring of behavioral responses and stress levels experienced by fish is important as it could be used for assessing source water toxicity as a first line of defense to protect and encourage recreational use of waterbodies. This paper propos...

  8. Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation.

    PubMed

    Nordling, Sofia; Hong, Jaan; Fromell, Karin; Edin, Fredrik; Brännström, Johan; Larsson, Rolf; Nilsson, Bo; Magnusson, Peetra U

    2015-06-01

    Ischaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and in whole organ transplantation. Activation of the endothelial cells and shedding of the protective vascular glycocalyx during IRI increase the risk of innate immune activation, cell infiltration and severe thrombus formation, promoting damage to the tissue. Here, we present a novel one-step strategy to protect the vasculature by immobilisation of a unique multi-arm heparin conjugate to the endothelium. Applying a new in vitro blood endothelial cell chamber model, the heparin conjugate was found to bind not only to primary human endothelial cells but also directly to the collagen to which the cells adhered. Incubation of hypoxic endothelial cells with freshly drawn human blood in the blood chambers elicited coagulation activation reflected by thrombin anti-thrombin formation and binding of platelets and neutrophils. Immobilisation of the heparin conjugate to the hypoxic endothelial cells created a protective coating, leading to a significant reduction of the recruitment of blood cells and coagulation activation compared to untreated hypoxic endothelial cells. This novel approach of immobilising multi-arm heparin conjugates on the endothelial cells and collagen of the basement membrane ensures to protect the endothelium against IRI in thrombotic disorders and in transplantation.

  9. Parent/Student Risk and Protective Factors in Understanding Early Adolescent's Body Mass Index

    ERIC Educational Resources Information Center

    Fitzpatrick, Kevin M.; Willis, Don

    2016-01-01

    This article's aim is to examine correlates of middle school students' body mass index (BMI). Little research simultaneously has considered both child and parent correlates in predicting child's BMI; we examine the interrelationships between middle school students and their parent's risks and protective factors and their impact on the child's BMI.…

  10. Early and moderate sensory stimulation exerts a protective effect on perilesion representations of somatosensory cortex after focal ischemic damage.

    PubMed

    Xerri, Christian; Zennou-Azogui, Yoh'i

    2014-01-01

    Previous studies have shown that intensive training within an early critical time window after focal cortical ischemia increases the area of damaged tissue and is detrimental to behavioral recovery. We postulated that moderate stimulation initiated soon after the lesion could have protective effects on peri-infarct cortical somatotopic representations. Therefore, we have assessed the effects of mild cutaneous stimulation delivered in an attention-demanding behavioral context on the functional organization of the perilesion somatosensory cortex using high-density electrophysiological mapping. We compared the effects of 6-day training initiated on the 3rd day postlesion (early training; ET) to those of same-duration training started on the 8th day (delayed training; DT). Our findings confirm previous work showing that the absence of training aggravates representational loss in the perilesion zone. In addition, ET was found to be sufficient to limit expansion of the ischemic lesion and reduce tissue loss, and substantially maintain the neuronal responsiveness to tactile stimulation, thereby preserving somatotopic map arrangement in the peri-infarct cortical territories. By contrast, DT did not prevent tissue loss and only partially reinstated lost representations in a use-dependent manner within the spared peri-infarct cortical area. This study differentiates the effects of early versus delayed training on perilesion tissue and cortical map reorganization, and underscores the neuroprotective influence of mild rehabilitative stimulation on neuronal response properties in the peri-infarct cortex during an early critical period. PMID:24914807

  11. Kindergarten Disruptive Behaviors, Protective Factors, and Educational Achievement by Early Adulthood

    ERIC Educational Resources Information Center

    Vitaro, Frank; Brendgen, Mara; Larose, Simon; Trembaly, Richard E.

    2005-01-01

    This study examined whether 2 aspects of disruptive behaviors (i.e., hyperactivity-inattention and aggressiveness-opposition) observed in kindergarten predict noncompletion of high school by early adulthood. Also investigated was whether other personal characteristics such as anxiety or prosociality as well as parent child-rearing attitudes and…

  12. Protective and Compensatory Factors Mitigating the Influence of Deviant Friends on Delinquent Behaviours during Early Adolescence

    ERIC Educational Resources Information Center

    Fergusson, David M.; Vitaro, Frank; Wanner, Brigitte; Brendgen, Mara

    2007-01-01

    This study examined factors that could moderate or compensate the link between exposure to deviant friends and delinquent behaviours in a sample of 265 early adolescents. The putative moderating or compensatory factors referred to the behavioural domain (i.e. novelty seeking, harm avoidance), the biological domain (i.e. physical maturation), the…

  13. ["Epistemic Negotiations" and the Pluralism of the Radiation Protection Regime: The Determination of Radiation Protection Standards for the General Population in the Early Years After World War II].

    PubMed

    Higuchi, Toshihiro

    2015-10-01

    Radiation protection standards for the general population have constituted one of the most controversial subjects in the history of atomic energy uses. This paper reexamines the process in which the first such standards evolved in the early postwar period. While the existing literature has emphasized a "collusion" between the standard-setters and users, the paper seeks to examine the horizontal relationship among the standard-setters. It first examines a series of expert consultations between the United States and the United Kingdom. Representing a different configuration of power and interest, the two failed to agree on the assessment of genetic damage and cancer induction whose occurrence might have no threshold and therefore be dependent on the population size. This stalemate prevented the International Commission on Radiological Protection (ICRP), established in 1950, from formulating separate guidelines for the general public. Situations radically changed when the Bikini incident in 1954 led to the creation of more scientific panels. One such panel under the U.S. Academy of Sciences enabled the geneticists to bridge their internal divide, unanimously naming 100 mSv as the genetically permissible dose for the general population. Not to be outdone, ICRP publicized its own guidelines for the same purpose. The case examined in this paper shows that the standard-setting process is best understood as a series of "epistemic negotiations" among and within the standard-setters, whose agendas were determined from the outset but whose outcomes were not.

  14. EARLY PHASE OBSERVATIONS OF EXTREMELY LUMINOUS TYPE Ia SUPERNOVA 2009dc

    SciTech Connect

    Yamanaka, M.; Arai, A.; Chiyonobu, S.; Fukazawa, Y.; Ikejiri, Y.; Itoh, R.; Komatsu, T.; Miyamoto, H.; Kawabata, K. S.; Kinugasa, K.; Hashimoto, O.; Honda, S.; Tanaka, M.; Imada, A.; Kuroda, D.; Maeda, K.; Nomoto, K.; Kamata, Y.; Kawai, N.; Konishi, K.

    2009-12-20

    We present early phase observations in optical and near-infrared wavelengths for the extremely luminous Type Ia supernova (SN Ia) 2009dc. The decline rate of the light curve is DELTAm{sub 15}(B) = 0.65 +- 0.03, which is one of the slowest among SNe Ia. The peak V-band absolute magnitude is estimated to be M{sub V} = -19.90 +- 0.15 mag if no host extinction is assumed. It reaches M{sub V} = -20.19 +- 0.19 mag if we assume the host extinction of A{sub V} = 0.29 mag. SN 2009dc belongs to the most luminous class of SNe Ia, like SNe 2003fg and 2006gz. Our JHK{sub s} -band photometry shows that this SN is also one of the most luminous SNe Ia in near-infrared wavelengths. We estimate the ejected {sup 56}Ni mass of 1.2 +- 0.3 M{sub sun} for the no host extinction case (and of 1.6 +- 0.4 M{sub sun} for the host extinction of A{sub V} = 0.29 mag). The C II lambda6580 absorption line remains visible until a week after the maximum brightness, in contrast to its early disappearance in SN 2006gz. The line velocity of Si II lambda6355 is about 8000 km s{sup -1} around the maximum, being considerably slower than that of SN 2006gz. The velocity of the C II line is similar to or slightly less than that of the Si II line around the maximum. The presence of the carbon line suggests that the thick unburned C+O layer remains after the explosion. Spectropolarimetric observations by Tanaka et al. indicate that the explosion is nearly spherical. These observational facts suggest that SN 2009dc is a super-Chandrasekhar mass SN Ia.

  15. Prolonged QT interval at onset of acute myocardial infarction in predicting early phase ventricular tachycardia

    SciTech Connect

    Taylor, G.J.; Crampton, R.S.; Gibson, R.S.; Stebbins, P.T.; Waldman, M.T.; Beller, G.A.

    1981-07-01

    The prospectively assessed time course of changes in ventricular repolarization during acute myocardial infarction (AMI) is reported in 32 patients admitted 2.0 +/- 1.8 (SD) hours after AMI onset. The initial corrected QT interval (QTc) upon hospitalization was longer in the 14 patients developing ventricular tachycardia (VT) within the first 48 hours as compared to QTc in the eight patients with frequent ventricular premature beats (VPBs) and to QTc in the 10 patients with infrequent VPBs. By the fifth day after AMI onset, the QTc shortened significantly only in the VT group, suggesting a greater initial abnormality of repolarization in these patients. All 32 patients had coronary angiography, radionuclide ventriculography, and myocardial perfusion scintigraphy before hospital discharge. Significant discriminating factors related to early phase VT in AMI included initially longer QT and QTc intervals, faster heart rate, higher peak serum levels of creatine kinase, acute anterior infarction, angiographically documented proximal stenosis of the left anterior descending coronary artery, and scintigraphic evidence of hypoperfusion of the interventricular septum. Prior infarction, angina pectoris, hypertension, multivessel coronary artery disease, and depressed left ventricular ejection fraction did not provide discrimination among the three different ventricular arrhythmia AMI groups. Researchers conclude that (1) the QT interval is frequently prolonged early in AMI, (2) the initial transiently prolonged ventricular repolarization facilitates and predicts complex ventricular tachyarrhythmias within the first 48 hours of AMI, (3) jeopardized blood supply to the interventricular septum frequently coexists, and (4) therapeutic enhancement of rapid recovery of the ventricular repolarization process merits investigation for prevention of VT in AMI.

  16. Potent induction of cellular antioxidants and phase 2 enzymes by resveratrol in cardiomyocytes: protection against oxidative and electrophilic injury.

    PubMed

    Cao, Zhuoxiao; Li, Yunbo

    2004-04-01

    Resveratrol is known to be protective against oxidative cardiovascular disorders. However, the underlying mechanisms remain unclear. This study was undertaken to determine if resveratrol could increase endogenous antioxidants and phase 2 enzymes in cardiomyocytes, and if such increased cellular defenses could provide protection against oxidative and electrophilic cell injury. Incubation of cardiac H9C2 cells with low micromolar resveratrol resulted in a significant induction of a scope of cellular antioxidants and phase 2 enzymes in a concentration- and/or time-dependent fashion. To investigate the protective effects of the resveratrol-induced cellular defenses on oxidative and electrophilic cell injury, H9C2 cells were first incubated with resveratrol, and then exposed to xanthine oxidase (XO)/xanthine, 4-hydroxy-2-nonenal or doxorubicin. We observed that resveratrol pretreatment afforded a marked protection against the above agent-mediated cytotoxicity in H9C2 cells. Moreover, the resveratrol pretreatment led to a great reduction in XO/xanthine-induced intracellular accumulation of ROS. Taken together, this study demonstrates that resveratrol induces antioxidants and phase 2 enzymes in cardiomyocytes, which is accompanied by increased resistance to oxidative and electrophilic cell injury.

  17. p27 kip1 haplo-insufficiency improves cardiac function in early-stages of myocardial infarction by protecting myocardium and increasing angiogenesis by promoting IKK activation.

    PubMed

    Zhou, Ningtian; Fu, Yuxuan; Wang, Yunle; Chen, Pengsheng; Meng, Haoyu; Guo, Shouyu; Zhang, Min; Yang, Zhijian; Ge, Yingbin

    2014-08-07

    p27(kip1) (p27) is widely known as a potent cell cycle inhibitor in several organs, especially in the heart. However, its role has not been fully defined during the early phase of myocardial infarction (MI). In this study, we investigated the relationships between p27, vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) and NF-κB in post-MI cardiac function repair both in vivo and in the hypoxia/ischemia-induced rat myocardiocyte model. In vivo, haplo-insufficiency of p27 improved cardiac function, diminished the infarct zone, protected myocardiocytes and increased angiogenesis by enhancing the production of VEGF/HGF. In vitro, the presence of conditioned medium from hypoxia/ischemia-induced p27 knockdown myocardiocytes reduced the injury caused by hypoxia/ischemia in myocardiocytes, and this effect was reversed by VEGF/HGF neutralizing antibodies, consistent with the cardioprotection being due to VEGF/HGF secretion. We also observed that p27 bound to IKK and that p27 haplo-insufficiency promoted IKK/p65 activation both in vivo and in vitro, thereby inducing the NF-κB downstream regulator, VEGF/HGF. Furthermore, IKKi and IKK inhibitor negated the effect of VEGF/HGF. Therefore, we conclude that p27 haplo-insufficiency protects against heart injury by VEGF/HGF mediated cardioprotection and increased angiogenesis through promoting IKK activation.

  18. Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss

    PubMed Central

    Jukic, Anne Marie; Calafat, Antonia M.; McConnaughey, D. Robert; Longnecker, Matthew P.; Hoppin, Jane A.; Weinberg, Clarice R.; Wilcox, Allen J.; Baird, Donna D.; Calafat, Antonia M.; McConnaughey, D. Robert; Longnecker, Matthew P.; Hoppin, Jane A.; Weinberg, Clarice R.; Wilcox, Allen J.; Baird, Donna D.

    2015-01-01

    Background Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss. Objectives We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy. Methods Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss. Results Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: –0.5 days (95% CI: –0.9, –0.1), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: –0.8 days (95% CI: –1.2, –0.4), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.02), p = 0.001]. Conclusions BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle–specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5-oxohexyl) phthalate] and ΣDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies. Citation Jukic

  19. Phase Retrieval from Modulus Using Homeomorphic Signal Processing and the Complex Cepstrum: An Algorithm for Lightning Protection Systems

    SciTech Connect

    Clark, G A

    2004-06-08

    In general, the Phase Retrieval from Modulus problem is very difficult. In this report, we solve the difficult, but somewhat more tractable case in which we constrain the solution to a minimum phase reconstruction. We exploit the real-and imaginary part sufficiency properties of the Fourier and Hilbert Transforms of causal sequences to develop an algorithm for reconstructing spectral phase given only spectral modulus. The algorithm uses homeomorphic signal processing methods with the complex cepstrum. The formal problem of interest is: Given measurements of only the modulus {vert_bar}H(k){vert_bar} (no phase) of the Discrete Fourier Transform (DFT) of a real, finite-length, stable, causal time domain signal h(n), compute a minimum phase reconstruction {cflx h}(n) of the signal. Then compute the phase of {cflx h}(n) using a DFT, and exploit the result as an estimate of the phase of h(n). The development of the algorithm is quite involved, but the final algorithm and its implementation are very simple. This work was motivated by a Phase Retrieval from Modulus Problem that arose in LLNL Defense Sciences Engineering Division (DSED) projects in lightning protection for buildings. The measurements are limited to modulus-only spectra from a spectrum analyzer. However, it is desired to perform system identification on the building to compute impulse responses and transfer functions that describe the amount of lightning energy that will be transferred from the outside of the building to the inside. This calculation requires knowledge of the entire signals (both modulus and phase). The algorithm and software described in this report are proposed as an approach to phase retrieval that can be used for programmatic needs. This report presents a brief tutorial description of the mathematical problem and the derivation of the phase retrieval algorithm. The efficacy of the theory is demonstrated using simulated signals that meet the assumptions of the algorithm. We see that for

  20. TLR 9 involvement in early protection induced by immunization with rPb27 against Paracoccidioidomycosis.

    PubMed

    Morais, Elis Araujo; Chame, Daniela Ferreira; Melo, Eliza Mathias; de Carvalho Oliveira, Junnia Alvarenga; de Paula, Ana Cláudia Chagas; Peixoto, Andiara Cardoso; da Silva Santos, Lílian; Gomes, Dawidson Assis; Russo, Remo Castro; de Goes, Alfredo Miranda

    2016-02-01

    Paracoccidioidomycosis is caused by fungi of the Paracoccidioides genus and constitutes the most prevalent deep mycosis in Latin America. Toll-like receptors promote immune response against infectious agents. Recently, it was reported that TLR9 is crucial for mice survival during the first 48 h of P. brasiliensis infection. In this study, we used CPG oligodeoxynucleotide motif as an adjuvant with and without rPb27 to immunize mice against Paracoccidioidomycosis. CPG adjuvant induced differential recruitment of lymphocytes in the inflammatory process and a lower recruitment of neutrophils. In addition, CPG induced the production of pro-inflammatory cytokines such as IL-1β, TNF-α, IL-6 and IL-12; increased phagocytic ability and microbicidal activity by macrophages; and induced differential production of lgG2a and lgG2b, subtypes of Ig. Knockout mice for TLR9 and IL-12 showed higher fungal loads and rates of mortality compared to control mice after 30 days of infection. The association between CPG and rPb27 induced a high level of protection against Paracoccidioidomycosis after the first 30 days of infection but not at 60 days. Our findings demonstrate that TLR 9 plays a role in the protection induced by immunization with rPb27 and confirms the importance of TLR9 in the initial protection against Paracoccidioidomycosis. PMID:26597327

  1. Alkaline Phosphatase Protects Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

    PubMed Central

    Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C.

    2015-01-01

    Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women. PMID:25910276

  2. Early childhood healthy and obese weight status: potentially protective benefits of breastfeeding and delaying solid foods.

    PubMed

    Moss, Brian G; Yeaton, William H

    2014-07-01

    The aim of this study was to assess the relationship between breastfeeding and postponing introduction to solid food (SF) on children's obesity and healthy weight status (WS), at 2 and 4 years. Drawing upon a nationally representative sample of children from the Early Childhood Longitudinal Study-Birth Cohort, we estimated the magnitude of the relationship between children's WS and early feeding practices. Contingency tables and multinomial logistic regression were used to analyze obese and healthy WS for breastfed and never breastfed children and examine three timing categories for SF introduction. With both percentages and odds, breastfeeding and delaying introduction to SF until 4 months were associated with lower obesity rates and higher, healthy WS rates (typically 5-10%). Analyses of feeding practice combinations revealed that when children were not breastfed, obesity odds decreased when SF introduction was postponed until 4 months. Obesity odds were further reduced when SF delay was combined with breastfeeding. Consistent increases in healthy WS were also observed. Benefits were stable across both follow-up periods. Breastfeeding and delaying complementary foods yielded consistently and substantially lower likelihood of obesity and greater probability of healthy WS. Health policies targeting early feeding practices represent promising interventions to decrease preschool obesity and promote healthy WS. PMID:24057991

  3. A Little Inflation in the Early Universe at the QCD Phase Transition

    SciTech Connect

    Boeckel, Tillmann; Schaffner-Bielich, Juergen

    2010-07-23

    We explore a scenario that allows for a strong first order phase transition of QCD at a non-negligible baryon number in the early Universe and its possible observable consequences. The main assumption is a quasistable QCD-vacuum state that leads to a short period of inflation, consequently diluting the net baryon to photon ratio to today's observed value. A strong mechanism for baryogenesis is needed to start out with a baryon asymmetry of order unity, e.g., as provided by Affleck-Dine baryogenesis. The cosmological implications are direct effects on primordial density fluctuations up to dark matter mass scales of M{sub max{approx}}1-10M{sub {center_dot},} change in the spectral slope up to M{sub max{approx}}10{sup 6}-10{sup 8}M{sub {center_dot},} production of strong primordial magnetic fields and a gravitational wave spectrum with present day peak strain amplitude of up to h{sub c}({nu}{sub peak}){approx}5x10{sup -15} around {nu}{sub peak{approx}}4x10{sup -8} Hz.

  4. A little inflation in the early universe at the QCD phase transition.

    PubMed

    Boeckel, Tillmann; Schaffner-Bielich, Jürgen

    2010-07-23

    We explore a scenario that allows for a strong first order phase transition of QCD at a non-negligible baryon number in the early Universe and its possible observable consequences. The main assumption is a quasistable QCD-vacuum state that leads to a short period of inflation, consequently diluting the net baryon to photon ratio to today's observed value. A strong mechanism for baryogenesis is needed to start out with a baryon asymmetry of order unity, e.g., as provided by Affleck-Dine baryogenesis. The cosmological implications are direct effects on primordial density fluctuations up to dark matter mass scales of M{max}∼1-10M{⊙}, change in the spectral slope up to M{max}∼10{6}-10{8}M{⊙}, production of strong primordial magnetic fields and a gravitational wave spectrum with present day peak strain amplitude of up to h{c}(ν{peak})∼5×10{-15} around ν{peak}∼4×10{-8}  Hz.

  5. 2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

    PubMed

    2015-12-01

    The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors.

  6. Macrophage function in murine allogeneic bone marrow radiation chimeras in the early phase after transplantation

    SciTech Connect

    Roesler, J.; Baccarini, M.; Vogt, B.; Lohmann-Matthes, M.L. )

    1989-08-01

    We tested several of the functions of macrophages (M phi) in the early phase after allogeneic bone marrow transfer to get information about this important aspect of the nonspecific immune system in the T-cell-deficient recipient. On days 3-5 after transfer, the number of M phi was reduced in the spleen, liver, lungs, and peritoneal cavity (Pe). The phagocytosis of sheep red blood cells (SRBC) by these M phi was normal or even enhanced, as in the case of Pe-M phi. Already on days 8-12 after transfer, the number of M phi in spleen and liver exceeded that of controls, whereas the number was still reduced in lungs and Pe. We examined their ability to kill P815 tumor cells, to produce tumor necrosis factor-alpha (TNF alpha), to phagocytose SRBC, to produce reactive oxygen intermediates (ROI) in vitro and to kill Listeria monocytogenes in vivo. Most functions were normal and often even enhanced, depending on the organ origin, but the ability of Pe-M phi to produce ROI was reduced. Proliferative response to macrophage colony-stimulating factor (M-CSF) and killing of YAC-1 tumor cells revealed a high frequency of macrophage precursor cells in the spleen and liver and a high natural killer (NK) activity in the liver. Altogether, enhanced nonspecific immune function, especially preactivated M phi, may enable chimeras to survive attacks by opportunistic pathogens.

  7. Distribution of CCS and HC3N in L1147, an Early Phase Dark Cloud

    NASA Astrophysics Data System (ADS)

    Suzuki, Taiki; Ohishi, Masatoshi; Hirota, Tomoya

    2014-06-01

    We used the Nobeyama 45 m radio telescope to reveal spatial distributions of CCS and HC3N in L1147, one of the carbon-chain producing region (CCPR) candidates, where carbon-chain molecules are dominant rather than NH3. We found that three cores (two CCS cores and one HC3N core), which are away from a very low luminosity object (a source that may turn into a sub-stellar mass brown dwarf), exist along the NE-SW filament traced by the 850 μm dust continuum. The column densities of CCS are 3-7 × 1012 cm-2 and those of HC3N are 2-6 × 1012 cm-2, respectively, much lower than those previously reported toward other CCPRs. We also found that two CCS peaks are displaced from the peaks of HC3N. In order to interpret such interleaved distributions, we conducted chemical reaction network simulations and found that slightly different gas densities could lead to large variation of the CCS-to-HC3N ratio in the early phase of dark cloud evolution. Such a chemical "variation" may be seen in other CCPRs. Finally, we were able to confirm that the L1147 filament can be regarded as a CCPR.

  8. Pretend play and development in early childhood (with implications for the oedipal phase).

    PubMed

    Gilmore, Karen

    2011-12-01

    Pretend play reflects both the unique mental organization and the developmental challenges of early to middle childhood, with a trajectory that parallels the monumental transformation of the toddler to the school-age child. Despite evidence for various forms of playing throughout the life cycle, the flowering of symbolic play in this phase is specific, essential, and typically transient in terms of its dominance in the life of the child. It reflects the simultaneous emergence, processing, and integration of the remarkable developmental advances occurring during this period, most especially the capacity to symbolize, in the service of the exponentially expanded psychosexual/social/emotional force field implied in the contemporary use of the term oedipus complex. Moreover, it constitutes a particular mental organization and ego state, with idiosyncratic mentation, affect regulation, and relationship to inner and outer experience, that accompanies the child's gradual orientation to consensual reality. Subsequent access to some form of this state varies widely among individuals but is rarely fully comparable. PMID:22080503

  9. Experimental infection with Toxocara cati in pigs: migratory pattern and pathological response in early phase.

    PubMed

    Sommerfelt, Irma Estela; Duchene, Adriana; Daprato, Betina; Lopez, Clara María; Cardillo, Natalia; Franco, Aníbal Juan

    2014-01-01

    Experimental inoculations of approximately 100,000 infective Toxocara cati larval eggs were done in twelve pigs. The T. cati eggs used for inoculation were collected from cat's feces. Another group of three pigs served as an uninfected control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days post-inoculation (dpi). Tissue samples were taken for digestion and histopathology changes in early phase. The number of larvae recovered from the lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae of T. cati were present in the lymph nodes of the small and large intestine at seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other studied tissues, no larvae or less than one larva per gram was detected. The pathological response observed in the liver and lungs at seven and 14 dpi, showed white spots on the liver surface and areas of consolidation were observed in the lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi. In the liver we observed periportal and perilobular hepatitis. The lymph nodes of the intestines displayed eosinophil lymphadenitis with reactive centers containing parasitic forms in some of them. The granulomatous reaction was not observed in any tissues. The role of the other examined tissues had less significance. The relevance of this parasite as an etiological agent that leads to disease in paratenic hosts is evident.

  10. Temporal Genetic Dynamics of an Invasive Species, Frankliniella occidentalis (Pergande), in an Early Phase of Establishment

    PubMed Central

    Yang, Xian-Ming; Lou, Heng; Sun, Jing-Tao; Zhu, Yi-Ming; Xue, Xiao-Feng; Hong, Xiao-Yue

    2015-01-01

    Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using mitochondrial and microsatellite markers. This study was conducted in eight localities from four climate regions in China, where F. occidentalis was introduced in the year 2000 and had lower genetic diversity than its native populations. We also tested the level of genetic differentiation in these introduced populations. The genetic diversity of the samples at different years in the same locality was not significantly different from each other in most localities. FST and STRUCTURE analysis also showed that most temporal population comparisons from the same sites were not significantly differentiated. Our results showed that the invasive populations of F. occidentalis in China can maintain temporal stability in genetic composition at an early phase of establishment despite having lower genetic diversity than in their native range. PMID:26138760

  11. Formation of the Photosynthetic Electron Transport System during the Early Phase of Greening in Barley Leaves

    PubMed Central

    Ohashi, Kazuko; Tanaka, Ayumi; Tsuji, Hideo

    1989-01-01

    The development of photochemical activity in isolated plastids during the early phase of greening of 5-day-old etiolated barley seedlings was studied and related to the appearance of chlorophyll-protein complexes. Photochemical activities of PSI (DCIPH2 → MV) and PSII (H2O → DCIP, DPC → DCIP) appeared at 1 and 1.5 hours after the onset of illumination, respectively. However, PSI + PSII activity (H2O → MV, H2O → NADP) appeared at 4 hours. The functional plastoquinone pool was noticed, at the latest, from 4 hours. Chloroplast preparations from seedlings of 1 h of greening showed O2 uptake upon illumination in the absence of MV (−MV activity). This activity peaked at 2 hours of greening, then fell to zero by 6 hours. In contrast to the −MV activity, MV-Hill activity began to increase at 2 hours. Although PSI activity appeared at 1 hour, it failed to reduce ferredoxin until 2 hours. NADP began to be photoreduced at 4 hours in accordance with the appearance of the ferredoxin:NADP reductase activity. After formation of PSI and PSII, electron transport systems between them and between PSI and NADP developed in coordination with each other. Thus, the whole electron transport from water to NADP began to operate at 4 hours. PMID:16667034

  12. Encephalic hemodynamic phases in subarachnoid hemorrhage: how to improve the protective effect in patient prognoses

    PubMed Central

    de Lima Oliveira, Marcelo; de Azevedo, Daniel Silva; de Azevedo, Milena Krajnyk; de Carvalho Nogueira, Ricardo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

    2015-01-01

    Subarachnoid hemorrhage is frequently associated with poor prognoses. Three different hemodynamic phases were identified during subarachnoid hemorrhage: oligemia, hyperemia, and vasospasm. Each phase is associated with brain metabolic changes. In this review, we correlated the hemodynamic phases with brain metabolism and potential treatment options in the hopes of improving patient prognoses. PMID:26109948

  13. Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

    PubMed Central

    2013-01-01

    Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into

  14. Masks as Self-Study. Challenging and Sustaining Teachers' Personal and Professional Personae in Early-Mid Career Life Phases

    ERIC Educational Resources Information Center

    Leitch, Ruth

    2010-01-01

    Drawing on previous research identifying how teachers' capacities to sustain their effectiveness in different phases of their professional lives are affected positively and/or negatively by their sense of identity, this paper illuminates three early-mid career teachers' self-study inquiries, centring on mask work. The creative development of…

  15. Removal efficiency of vapour/particulate phase PAHs by using alternative protective respirators in PAHs exposure workers.

    PubMed

    Chen, Hsiu-Ling; Yang, Chien-Hung; Lin, Ming-Hsiu

    2012-06-15

    Due to the high heat environment in foundry industries, it is difficult for foundry workers to wear masks during their workday. Thus, how to prevent inhaling vapour or the particulate phase of polycyclic aromatic hydrocarbons (PAHs) is important for occupational hazard management. The present study assesses the characteristics of PAHs emission in foundry and plastic industries to evaluate the removal efficiencies of PAHs while workers use alternative personal protective equipment. The highest 1-hydroxypyrene (1-OHP) level was found for workers who used a cotton-fabric face mask (1.19 μg/g creatinine) and activated-carbon face mask (1.16 μg/g creatinine), compared to a lower level in workers who wore a surgical face mask (0.27 μg/g creatinine) and a N95 respirator (0.51 μg/g creatinine). The urinary 1-OHP in end-of-shift samples correlated to the airborne vapour phase Bapeq, but not for the particulate phase Bapeq in the foundry industry. This is probably because workers wore personal protective equipment that only removed the particulate phase PAH. The current study suggests that future work focus on developing an appropriate and comfortable respirator with high removal efficiency for ultrafine particulates and vapour phase PAHs simultaneously in PAH work environments. PMID:22525483

  16. River Protection Project Integrated safety management system phase II verification report, volumes I and II - 8/19/99

    SciTech Connect

    SHOOP, D.S.

    1999-09-10

    The Department of Energy policy (DOE P 450.4) is that safety is integrated into all aspects of the management and operations of its facilities. In simple and straightforward terms, the Department will ''Do work safely.'' The purpose of this River Protection Project (RPP) Integrated Safety Management System (ISMS) Phase II Verification was to determine whether ISMS programs and processes are implemented within RFP to accomplish the goal of ''Do work safely.'' The goal of an implemented ISMS is to have a single integrated system that includes Environment, Safety, and Health (ES&H) requirements in the work planning and execution processes to ensure the protection of the worker, public, environment, and federal property over the RPP life cycle. The ISMS is comprised of the (1) described functions, components, processes, and interfaces (system map or blueprint) and (2) personnel who are executing those assigned roles and responsibilities to manage and control the ISMS. Therefore, this review evaluated both the ''paper'' and ''people'' aspects of the ISMS to ensure that the system is implemented within RPP. Richland Operations Office (RL) conducted an ISMS Phase I Verification of the TWRS from September 28-October 9, 1998. The resulting verification report recommended that TWRS-RL and the contractor proceed with Phase II of ISMS verification given that the concerns identified from the Phase I verification review are incorporated into the Phase II implementation plan.

  17. Cognitive and Neuroplasticity Mechanisms by Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia

    PubMed Central

    Silverstein, Steven M.; Wang, Yushi; Keane, Brian P.

    2013-01-01

    Several authors have noted that there are no reported cases of people with schizophrenia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E) blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted individuals. We next discuss: (1) the role of neuroplasticity in driving these cognitive changes in C/E blindness; (2) evidence that C/E blindness does not confer protective effects against other mental disorders; and (3) evidence that other forms of C/E sensory loss (e.g., deafness) do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself. PMID:23349646

  18. Similarity of risk and protective behaviors among African-American pre- and early adolescent members of naturally occurring friendship groups.

    PubMed

    Fang, X; Stanton, B; Li, X; Romer, D; Galbraith, J; Feigelman, S

    1996-01-01

    To determine whether self-reported risk and protective behaviors, expectations, and attitudes are more similar among African-American early adolescents within a community-based friendship group than across groups, a cross-sectional study was conducted among 382 African-American youth 9 through 15 years of age forming 76 community-based groups of 3 through 10 same-gender friends. Each member of the friendship group reported his/her own past involvement in nine risk behaviors (sexual intercourse, substance abuse, drug-trafficking, and other delinquent activities) and two protective behaviors (high academic performance and regular church attendance) and their expectations and feelings regarding several of these behaviors. Intraclass correlation coefficients were calculated overall and by gender and age. Members were generally more similar within friendship groups than across groups with regard to several risk behaviors and expectations including sexual intercourse and drug-trafficking. Particularly striking was the similarity among members of "junior" friendship groups (e.g., median age of youth < 11 years) of both risk and protective behaviors and expectations. The finding of enhanced similarity of risk behaviors and expectations among members within groups suggests that intervention delivery through community-based friendship groups may be a useful approach for risk prevention efforts targeting pre-adolescent African-American youth living in low-income settings. PMID:8982522

  19. Neddylation is required for herpes simplex virus type I (HSV-1)-induced early phase interferon-beta production

    PubMed Central

    Zhang, Xueying; Ye, Zhenjie; Pei, Yujun; Qiu, Guihua; Wang, Qingyang; Xu, Yunlu; Shen, Beifen; Zhang, Jiyan

    2016-01-01

    Type I interferons such as interferon-beta (IFN-β) play essential roles in the host innate immune response to herpes simplex virus type I (HSV-1) infection. The transcription of type I interferon genes is controlled by nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF) family members including IRF3. NF-κB activation depends on the phosphorylation of inhibitor of κB (IκB), which triggers its ubiqitination and degradation. It has been reported that neddylation inhibition by a pharmacological agent MLN4924 potently suppresses lipopolysaccharide (LPS)-induced proinflammatory cytokine production with the accumulation of phosphorylated IκBα. However, the role of neddylation in type I interferon expression remains unknown. Here, we report that neddylation inhibition with MLN4924 or upon UBA3 deficiency led to accumulation of phosphorylated IκBα, impaired IκBα degradation, and impaired NF-κB nuclear translocation in the early phase of HSV-1 infection even though phosphorylation and nuclear translocation of IRF3 were not affected. The blockade of NF-κB nuclear translocation by neddylation inhibition becomes less efficient at the later time points of HSV-1 infection. Consequently, HSV-1-induced early phase IFN-β production significantly decreased upon MLN4924 treatment and UBA3 deficiency. NF-κB inhibitor JSH-23 mimicked the effects of neddylation inhibition in the early phase of HSV-1 infection. Moreover, the effects of neddylation inhibition on HSV-1-induced early phase IFN-β production diminished in the presence of NF-κB inhibitor JSH-23. Thus, neddylation contributes to HSV-1-induced early phase IFN-β production through, at least partially, promoting NF-κB activation. PMID:27593482

  20. Neddylation is required for herpes simplex virus type I (HSV-1)-induced early phase interferon-beta production.

    PubMed

    Zhang, Xueying; Ye, Zhenjie; Pei, Yujun; Qiu, Guihua; Wang, Qingyang; Xu, Yunlu; Shen, Beifen; Zhang, Jiyan

    2016-09-01

    Type I interferons such as interferon-beta (IFN-β) play essential roles in the host innate immune response to herpes simplex virus type I (HSV-1) infection. The transcription of type I interferon genes is controlled by nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF) family members including IRF3. NF-κB activation depends on the phosphorylation of inhibitor of κB (IκB), which triggers its ubiqitination and degradation. It has been reported that neddylation inhibition by a pharmacological agent MLN4924 potently suppresses lipopolysaccharide (LPS)-induced proinflammatory cytokine production with the accumulation of phosphorylated IκBα. However, the role of neddylation in type I interferon expression remains unknown. Here, we report that neddylation inhibition with MLN4924 or upon UBA3 deficiency led to accumulation of phosphorylated IκBα, impaired IκBα degradation, and impaired NF-κB nuclear translocation in the early phase of HSV-1 infection even though phosphorylation and nuclear translocation of IRF3 were not affected. The blockade of NF-κB nuclear translocation by neddylation inhibition becomes less efficient at the later time points of HSV-1 infection. Consequently, HSV-1-induced early phase IFN-β production significantly decreased upon MLN4924 treatment and UBA3 deficiency. NF-κB inhibitor JSH-23 mimicked the effects of neddylation inhibition in the early phase of HSV-1 infection. Moreover, the effects of neddylation inhibition on HSV-1-induced early phase IFN-β production diminished in the presence of NF-κB inhibitor JSH-23. Thus, neddylation contributes to HSV-1-induced early phase IFN-β production through, at least partially, promoting NF-κB activation. PMID:27593482

  1. Early weaning alters the acute-phase reaction to an endotoxin challenge in beef calves.

    PubMed

    Carroll, J A; Arthington, J D; Chase, C C

    2009-12-01

    Previous research indicates that early weaning before shipment can reduce transportation-induced increases in acute-phase proteins (APP) and can increase feedlot performance in beef calves. These data suggest that the combination of weaning and transport stress may compromise the immune system of calves, thus hindering subsequent performance and health. Therefore, our objective was to determine if the innate immune response of early weaned calves (EW; 80 d of age) differed from normal-weaned calves (NW; 250 d of age) in response to an endotoxin challenge. Eighteen Brahman x Angus calves (8 and 10 EW and NW, respectively; 233 +/- 5 kg of BW) were used. Calves were maintained on pasture with supplement and then moved into individual pens for 1 wk of acclimation before the start of the study. Calves were fitted with an indwelling jugular catheter 1 d before LPS challenge (0 h; 1.0 microg/kg of BW, intravenously). Blood samples were collected at 30-min intervals from -2 to 8 h. Serum samples were stored at -80 degrees C until analyzed for cortisol, tumor necrosis factor-alpha (TNF), IL-1 beta, IL-6, interferon-gamma (IFN), ceruloplasmin, and haptoglobin. Whereas LPS increased serum cortisol (P or= 0.15) was observed. A weaning age x time interaction (P

  2. Overview of the U.S. Environmental Protection Agency's Hazardous Air Pollutant Early Reduction Program.

    PubMed

    Laznow, J; Daniel, J

    1992-01-01

    Under provision of the Clean Air Act Amendments of 1990 Title III, the EPA has proposed a regulation (Early Reduction Program) to allow a six-year compliance extension from Maximum Achievable Control Technology (MACT) standards for sources that voluntarily reduce emissions of Hazardous Air Pollutants (HAPs) by 90 percent or more (95 percent or more for particulates) from a base year of 1987 or later. The emission reduction must be made before the applicable MACT standard is proposed for the source category or be subject to an enforceable commitment to achieve the reduction by January 1, 1994 for sources subject to MACT standards prior to 1994. The primary purpose of this program is to encourage reduction of HAPs emissions sooner than otherwise required. Industry would be allowed additional time in evaluating emission reduction options and developing more cost-effective compliance strategies, although, under strict guidelines to ensure actual, significant and verifiable emission reductions occur.

  3. Sildenafil Augments Early Protective Transcriptional Changes After Ischemia In Mouse Myocardium

    PubMed Central

    Vidavalur, Ramesh; Penumathsa, Suresh Varma; Thirunavukkarasu, Mahesh; Zhan, Lijun; Krueger, Winfried; Maulik, Nilanjana

    2009-01-01

    Recently, targeting cyclic-GMP specific phosphodiesterase-5 (PDE5) has attracted much interest in several cardiopulmonary diseases, in particular myocardial ischemia (MI). Although multiple mechanisms were postulated for these beneficial effects at cellular level, early transcriptional changes were unknown. The aim of present study was to examine gene expression profiles in response to MI after 24h of ischemia in murine model and compare transcriptional modulation by sildenafil, a popular phosphodiesterase 5 (PDE5) inhibitor. Mice were divided into four groups: Control sham (C), Sildenafil sham (S), Control MI (CMI) and Sildenafil MI (SMI). Sildenafil was given at a dose of 0.7 mg/kg intraperitoneally 30 minutes before LAD occlusion. cDNA microarray analysis of peri-infarct tissue was done using a custom cloneset and employing a looped dye swap design. Replicate signals were median averaged and normalized using LOWESS algorithm. R/MAANOVA analysis was used and false discovery rate corrected permutation p-values < 0.005 were employed as significance thresholds. 156 genes were identified as significantly regulated demonstrating fold difference >1.5 in atleast one of the four groups. 52 genes were significantly upregulated in SMI compared to CMI. For a randomly chosen subset of genes (9), microarray data were confirmed through real time RT-PCR. The differentially expressed genes could be classified into following groups based on their function: Phosphorylation/dephosphorylation, Apoptosis, differentiation, ATP binding. Our results suggest that sildenafil treatment might regulate early genetic reprogramming strategy for preservation of the ischemic myocardium. PMID:19013509

  4. Project FIRES. Volume 4: Prototype Protective Ensemble Qualification Test Report, Phase 1B

    NASA Technical Reports Server (NTRS)

    Abeles, F. J.

    1980-01-01

    The qualification testing of a prototype firefighter's protective ensemble is documented. Included are descriptions of the design requirements, the testing methods, and the test apparatus. The tests include measurements of individual subsystem characteristics in areas relating to both physical testing, such as heat, flame, impact penetration and human factors testing, such as dexterity, grip, and mobility. Also, measurements related to both physical and human factors testing of the complete ensemble, such as water protection, metabolic expenditures, and compatibility are considered.

  5. Proliferation during early phases of bronchiolar repair in neonatal rabbits following lung injury by 4-ipomeanol.

    PubMed

    Smiley-Jewell, Suzette M; Plopper, Charles G

    2003-10-01

    Nonciliated bronchiolar (Clara cells) are progenitor cells during development. During differentiation, they are more susceptible to injury by environmental toxicants metabolized by the cytochrome P450 monooxygenase system, and injury results in altered bronchiolar repair and development. Squamous cells and abnormal cuboidal epithelium persist into early adulthood. The hypothesis tested in this study was that the failure of bronchiolar epithelium to repair normally in neonates following injury is due to an inhibition of proliferation. A model of differential repair in rabbit kits was used. Proliferation was followed for 1 week post injury in rabbit kits treated with a single dose of the P450-mediated cytotoxicant 4-ipomeanol (IPO) at 7 days old (repair abnormal) and compared to rabbits treated with a single dose of IPO at 21 days old (repair normal). Proliferation was measured by the nuclear incorporation of 5-chloro-2'-deoxyuridine (CldU) within epithelium at the target site (terminal bronchiole). The repair pattern between the two age groups was histologically defined. There was no difference in the CldU labeling index during the week of repair between the two age groups, even though the bronchiolar epithelium did not return to normal in the animals treated at 7 days old. In summary, proliferation (through S-phase) is not inhibited during repair in neonatal rabbits treated with IPO at 7 days old compared to animals treated at 21 days old, and we conclude that other factors may be responsible for the altered repair in the young neonates injured by a P450-mediated cytotoxicant. PMID:14554104

  6. Early-phase dental students' motivations and expectations concerning the study and profession of dentistry.

    PubMed

    Lalloo, R; Ayo-Yusuf, O A; Yengopal, V

    2008-05-01

    This study investigated the career choice and aspirations of early phase dental students in the four dental schools in South Africa, namely the University of the Western Cape (UWC), University of the Witwatersrand (Wits), University of Limpopo (Medunsa) and University of Pretoria (UP). Willing participants completed a self-administered questionnaire (n=184). Motivations for entering a dentistry programme were similar across race and university, with wanting a secure job most often stated as an important factor. For a third of respondents, dentistry was not a first choice. Amongst the White students, it was a first choice for 82% compared with 59% amongst Black Africans. Expected income five-years after graduation also differed significantly across race and university, with White and UP students expecting to earn considerably higher than the others. About 36% of students were concerned about the levels of personal debt related to studying, with the White and Asian students less concerned. Those who expected lower levels of income from the profession were more concerned about personal debts. Most students planned to enter general dental practice (GDP) after community service, almost all White and Wits students expressed this intention, compared with only 35% of Black Africans and 39% of Medunsa students. Orthodontics and Maxillofacial & Oral Surgery were the most popular specialities of choice. The professional attribute "Has a friendly manner and good relationship with patients" was ranked high most often. In conclusion, career advice may not need to be tailored differently for the different racial groups. There is however a need for further investigations on how to address the concerns of financial security which may be realised by the practice of dentistry, and in particular the racial disparities observed in expectations of the profession. This study further highlights the need for government financial assistance for students from under-represented groups.

  7. Intraoperative Radiotherapy in Early-Stage Breast Cancer: Results of the Montpellier Phase II Trial

    SciTech Connect

    Lemanski, Claire; Azria, David; Gourgon-Bourgade, Sophie; Gutowski, Marian; Rouanet, Phillippe; Saint-Aubert, Bernard; Ailleres, Norbert; Fenoglietto, Pascal; Dubois, Jean-Bernard

    2010-03-01

    Purpose: We recently presented the intraoperative radiotherapy (IORT) technique given as a reliable alternative to conventional boost radiation after breast-conserving surgery. The low crude numbers of recurrence in elderly patients led us to investigate the feasibility and the efficacy of this procedure as a sole treatment. Methods and Materials: We included 94 patients older than 65 years in this phase II trial. Among them, 42 patients presented with all the inclusion criteria, i.e., stages pT0 to pT1 and pN0, ductal invasive unifocal carcinoma, and tumor-free margin of >2 mm. IORT was delivered using a dedicated linear accelerator. One 21-Gy fraction was prescribed and specified at the 90% isodose, using electrons. In vivo dosimetry was performed for all patients. The primary endpoint was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, and specific and overall rates of survival. Results: The median follow-up was 30 months (range, 12-49 months), and median age was 72 years (range, 66-80 years). The median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Endpoints for all but one patient corresponded to acceptable quality index criteria. Pretreatment quality-of-life scores were maximal, and no significant decrease was observed during follow-up. Cosmesis was good to excellent at 6 months. Two patients experienced recurrence but underwent salvage mastectomy. Conclusion: Our results confirm that exclusive partial-breast IORT is feasible for treating early-stage breast cancer in the elderly. IORT may be considered an alternative treatment for a selected population and offers a safe one-step treatment.

  8. Wildlife Protection, Mitigation, and Enhancement Planning Phase II, Dworshak Reservoir, Final Report.

    SciTech Connect

    Hansen, H. Jerome; Martin, Robert C.

    1989-11-01

    The Pacific Northwest Electric Power Planning and Conservation Act of 1980 directed that measures be implemented to protect, mitigate, and enhance fish and wildlife to the extent affected by development and operation of hydropower projects on the Columbia River System. This Act created the Northwest Power Planning Council, which in turn developed the Columbia River Basin Fish and Wildlife Program. This program established a four-part process: wildlife mitigation status reports; wildlife impact assessments; wildlife protection, mitigation, and enhancement plans; and implementation of protection, mitigation, and enhancement projects. This mitigation plan for the Dworshak Reservoir Hydroelectric Facility was developed to fulfill requirements of Sections 1003(b)(2) and (3) of the Columbia River Basin Fish and Wildlife Program. Specific objectives of wildlife protection, mitigation, and enhancement planning for Dworshak Reservoir included: quantify net impacts to target wildlife species affected by hydroelectric development and operation of Dworshak Dam and Reservoir; develop protection, mitigation, and enhancement goals and objectives for the target wildlife species; recommend protection, mitigation, and enhancement actions for the target wildlife species; and coordination of project activities. 46 refs., 4 figs., 31 tabs.

  9. Endothelial gaps and adherent leukocytes in allergen-induced early- and late-phase plasma leakage in rat airways.

    PubMed

    Baluk, P; Bolton, P; Hirata, A; Thurston, G; McDonald, D M

    1998-06-01

    Exposure of sensitized individuals to antigen can induce allergic responses in the respiratory tract, manifested by early and late phases of vasodilatation, plasma leakage, leukocyte influx, and bronchoconstriction. Similar responses can occur in the skin, eye, and gastrointestinal tract. The early-phase response involves mast cell mediators and the late-phase response is leukocyte dependent, but the mechanism of leakage is not understood. We sought to identify the leaky blood vessels, to determine whether these vessels contained endothelial gaps, and to analyze the relationship of the gaps to adherent leukocytes, using biotinylated lectins or silver nitrate to stain the cells in situ and Monastral blue as a tracer to quantify plasma leakage. Most of the leakage occurred in postcapillary venules (< 40-microns diameter), whereas most of the leukocyte migration (predominantly neutrophils) occurred in collecting venules. Capillaries and arterioles did not leak. Endothelial gaps were found in the leaky venules, both by silver nitrate staining and by scanning electron microscopy, and 94% of the gaps were distinct from sites of leukocyte adhesion or migration. We conclude that endothelial gaps contribute to both early and late phases of plasma leakage induced by antigen, but most leakage occurs upstream to sites of leukocyte adhesion. PMID:9626051

  10. Role of apolipoprotein E4 in protecting children against early childhood diarrhea outcomes and implications for later development

    PubMed Central

    Oriá, Reinaldo B.; Patrick, Peter D.; Blackman, James A.; Lima, Aldo A.M.; Guerrant, Richard L.

    2014-01-01

    Summary Our group and others have reported a series of studies showing that heavy burdens of diarrheal diseases in the formative first two years of life in children in urban shantytowns have profound consequences of impaired physical and cognitive development lasting into later childhood and schooling. Based on these previous studies showing that apolipoprotein E4 (APOE4) is relatively common in favela children, we review recent data suggesting a protective role for the APOE4 allele in the cognitive and physical development of children with heavy burdens of diarrhea in early childhood. Despite being a marker for cognitive decline with Alzheimer's and cardiovascular diseases later in life, APOE4 appears to be important for cognitive development under the stress of heavy diarrhea. The reviewed findings provide a potential explanation for the survival advantage in evolution of the thrifty APOE4 allele and raise questions about its implications for human development under life-style changes and environmental challenges. PMID:17098371

  11. Relevance of Foxp3⁺ regulatory T cells for early and late phases of murine sepsis.

    PubMed

    Tatura, Roman; Zeschnigk, Michael; Hansen, Wiebke; Steinmann, Joerg; Vidigal, Pedrina Goncalves; Hutzler, Marina; Pastille, Eva; Westendorf, Astrid M; Buer, Jan; Kehrmann, Jan

    2015-09-01

    The role of Foxp3(+) regulatory T (Treg) cells in the course of the early hyper-inflammatory and subsequent hypo-inflammatory phases of sepsis is ambiguous. Whereas Nrp1 expression has been reported to discriminate natural Treg cells from induced Treg cells, the Treg cell stability depends on the methylation status of foxp3-TSDR. To specifically evaluate the role of Foxp3(+) Treg cells in the early and late phases of sepsis, we induced sepsis by caecal ligation and puncture and subsequent Pseudomonas aeruginosa lung infection in a DEREG (DEpletion of REGulatory T cells) mouse model. We found an increase of Foxp3(+) Treg cells to all CD4(+) T cells during murine sepsis. Using a new methylation-sensitive quantitative RT-PCR method and deep amplicon sequencing, we demonstrated that natural (Nrp1(+) Foxp3(+) ) Treg cells and most induced (Nrp1(-) Foxp3(+) ) Treg cells are stable and exhibit unmethylated foxp3-TSDR, and that both Treg populations are functionally suppressive in healthy and septic mice. DEREG mice depleted of Foxp3(+) Treg cells exhibit higher disease scores, mortality rates and interleukin-6 expression levels than do non-depleted DEREG mice in early-phase sepsis, a finding indicating that Foxp3(+) Treg cells limit the hyper-inflammatory response and accelerate recovery. Treg cell depletion before secondary infection with P. aeruginosa 1 week after caecal ligation and puncture does not influence cytokine levels or the course of secondary infection. However, a moderate Treg cell recurrence, which we observed in DEREG mice during secondary infection, may interfere with these results. In summary, Treg cells contribute to a positive outcome after early-phase sepsis, but the data do not support a significant role of Treg cells in immune paralysis during late-phase sepsis. PMID:26059660

  12. Early indicators of survival following exposure to mustard gas: Protective role of 25(OH)D.

    PubMed

    Das, Lopa M; Binko, Amy M; Traylor, Zachary P; Duesler, Lori R; Dynda, Scott M; Debanne, Sara; Lu, Kurt Q

    2016-04-25

    The use of sulfur mustard (SM) as a chemical weapon for warfare has once again assumed center stage, endangering civilian and the military safety. SM causes rapid local skin vesication and late-onset systemic toxicity. Most studies on SM rely on obtaining tissue and blood for characterizing burn pathogenesis and assessment of systemic pathology, respectively. However the present study focuses on developing a non-invasive method to predict mortality from high dose skin SM exposure. We demonstrate that exposure to SM leads to a dose dependent increase in wound area size on the dorsal surface of mice that is accompanied by a progressive loss in body weight loss, blood cytopenia, bone marrow destruction, and death. Thus our model utilizes local skin destruction and systemic outcome measures as variables to predict mortality in a novel skin-based model of tissue injury. Based on our recent work using vitamin D (25(OH)D) as an intervention to treat toxicity from SM-related compounds, we explored the use of 25(OH)D in mitigating the toxic effects of SM. Here we show that 25(OH)D offers protection against SM and is the first known demonstration of an intervention that prevents SM-induced mortality. Furthermore, 25(OH)D represents a safe, novel, and readily translatable potential countermeasure following mass toxic exposure. PMID:26940683

  13. The microbiome in early life: self-completion and microbiota protection as health priorities.

    PubMed

    Dietert, Rodney R

    2014-08-01

    This minireview considers the benefits of refocusing attention away from treating the patient as a mammalian human to managing the complete patient: a majority microbial superorganism. Under the "completed self" model for formation of the human-microbial superorganism, the single, most pivotal sign in distinguishing a life course of health versus that filled with disease is self-completion (i.e., seeding of the minority mammalian human by the majority microbial portion of the symbiont). From a disease prevention perspective, microbial seeding at birth and subsequent nurturing of the microbiota are significant steps to reduce the risk of both noncommunicable diseases (e.g., type 1 diabetes) and certain infectious diseases. Management of the microbiome during pregnancy, birth, and shortly thereafter appears to be the most significant critical window for healthy superorganism formation. However, the bolus for microbiota seeding at birth and the nurturing process are subject to environmental influences and disruption, such as exposure to toxic chemicals and drugs, infections, and other physical and psychological stressors. Additionally, childhood and adult corrective measures, such as fecal transplantation and administration of prebiotics and probiotics, while potentially useful, may have limitations that are yet to be fully defined. This minireview considers (1) basic features of management of the microbiome to facilitate self-completion, (2) protection of the microbiota from environmental hazards, and (3) the benefits of using a superorganism focus for health management beginning with pregnancy and extending throughout childhood and adult life.

  14. Protective effect of yacon leaves decoction against early nephropathy in experimental diabetic rats.

    PubMed

    Honoré, Stella M; Cabrera, Wilfredo M; Genta, Susana B; Sánchez, Sara S

    2012-05-01

    Nephropathy is the most common cause of morbidity and mortality in diabetic patients. Prevention of this complication has a major relevance. Smallanthus sonchifolius (yacon) leaves have been shown to ameliorate hyperglycemia in streptozotocin-induced diabetic rats. We examined the beneficial effects of yacon leaves decoction on diabetic nephropathy and explored the possible underlying action mechanism. Streptozotocin-diabetic rats were orally administered 10% yacon leaves water decoction (70mg dry extract/kg body weight) once a day for 4weeks. Biochemical parameters in blood and urine were analyzed and immunohistochemistry staining, western immunoblotting and qRT-PCR were assessed. Yacon decoction significantly decreased high blood glucose level in diabetic rats and improved insulin production. Diabetic-dependent alterations in urinary albumin excretion, creatinine clearance, kidney hypertrophy and basement membrane thickening were attenuated by yacon decoction. These findings were associated with a marked decrease in TGF-β1/Smad2/3 signaling. The expression of molecular markers of diabetic nephropathy such as collagen IV, laminin-1, fibronectin and collagen III were also diminished in the yacon-treated group compared to control diabetic group. These results suggest that yacon leaves decoction is a protective agent against renal damage in diabetic nephropathy, whose action can be mediated by TGF-β/Smads signals. PMID:22406203

  15. Environmental enrichment protects the retina from early diabetic damage in adult rats.

    PubMed

    Dorfman, Damián; Aranda, Marcos L; González Fleitas, María Florencia; Chianelli, Mónica S; Fernandez, Diego C; Sande, Pablo H; Rosenstein, Ruth E

    2014-01-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Available treatments are not completely effective. We analyzed the effect of environmental enrichment on retinal damage induced by experimental diabetes in adult Wistar rats. Diabetes was induced by an intraperitoneal injection of streptozotocin. Three days after vehicle or streptozotocin injection, animals were housed in enriched environment or remained in a standard environment. Retinal function (electroretinogram, and oscillatory potentials), retinal morphology, blood-retinal barrier integrity, synaptophysin, astrocyte and Müller cell glial fibrillary acidic protein, vascular endothelial growth factor, tumor necrosis factor-α, and brain-derived neurotrophic factor levels, as well as lipid peroxidation were assessed in retina from diabetic animals housed in standard or enriched environment. Environmental enrichment preserved scotopic electroretinogram a-wave, b-wave and oscillatory potential amplitude, avoided albumin-Evan's blue leakage, prevented the decrease in retinal synaptophysin and astrocyte glial fibrillary acidic protein levels, the increase in Müller cell glial fibrillary acidic protein, vascular endothelial growth factor and tumor necrosis factor-α levels, as well as oxidative stress induced by diabetes. In addition, enriched environment prevented the decrease in retinal brain-derived neurotrophic factor levels induced by experimental diabetes. When environmental enrichment started 7 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that enriched environment could attenuate the early diabetic damage in the retina from adult rats.

  16. Consumer of concern early entry program (C-CEEP): protecting against the biological suicidal warfare host

    NASA Astrophysics Data System (ADS)

    Fish, Janet D.

    2014-05-01

    Man has used poisons for assassination purposes ever since the dawn of civilization, not only against individual enemies but also occasionally against armies. According to (Frischknecht, 2003)11 article on the History of Biological Warfare, during the past century, more than 500 million people died of infectious diseases. Several tens of thousands of these deaths were due to the deliberate release of pathogens or toxins. Two international treaties outlawed biological weapons in 1925 and 1972, but they have largely failed to stop countries from conducting offensive weapons research and large-scale production of biological weapons. Before the 20th century, biological warfare took on three main forms: (1) deliberate poisoning of food and water with infectious material, (2) use of microorganisms or toxins in some form of weapon system, and (3) use of biologically inoculated fabrics (Dire, 2013)8. This action plan is aimed at the recognition of the lack of current processes in place under an unidentified lead agency to detect, identify, track, and contain biological agents that can enter into the United States through a human host. This action plan program has been identified as the Consumer of Concern Early Entry Program or a simpler title is C-CEEP.

  17. Environmental Enrichment Protects the Retina from Early Diabetic Damage in Adult Rats

    PubMed Central

    Dorfman, Damián; Aranda, Marcos L.; González Fleitas, María Florencia; Chianelli, Mónica S.; Fernandez, Diego C.; Sande, Pablo H.; Rosenstein, Ruth E.

    2014-01-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Available treatments are not completely effective. We analyzed the effect of environmental enrichment on retinal damage induced by experimental diabetes in adult Wistar rats. Diabetes was induced by an intraperitoneal injection of streptozotocin. Three days after vehicle or streptozotocin injection, animals were housed in enriched environment or remained in a standard environment. Retinal function (electroretinogram, and oscillatory potentials), retinal morphology, blood-retinal barrier integrity, synaptophysin, astrocyte and Müller cell glial fibrillary acidic protein, vascular endothelial growth factor, tumor necrosis factor-α, and brain-derived neurotrophic factor levels, as well as lipid peroxidation were assessed in retina from diabetic animals housed in standard or enriched environment. Environmental enrichment preserved scotopic electroretinogram a-wave, b-wave and oscillatory potential amplitude, avoided albumin-Evan's blue leakage, prevented the decrease in retinal synaptophysin and astrocyte glial fibrillary acidic protein levels, the increase in Müller cell glial fibrillary acidic protein, vascular endothelial growth factor and tumor necrosis factor-α levels, as well as oxidative stress induced by diabetes. In addition, enriched environment prevented the decrease in retinal brain-derived neurotrophic factor levels induced by experimental diabetes. When environmental enrichment started 7 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that enriched environment could attenuate the early diabetic damage in the retina from adult rats. PMID:25004165

  18. Enriched Environment Protects the Optic Nerve from Early Diabetes-Induced Damage in Adult Rats

    PubMed Central

    Dorfman, Damián; Aranda, Marcos L.; Rosenstein, Ruth E.

    2015-01-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Axoglial alterations of the distal (close to the chiasm) optic nerve (ON) could be the first structural change of the visual pathway in streptozotocin (STZ)-induced diabetes in rats. We analyzed the effect of environmental enrichment on axoglial alterations of the ON provoked by experimental diabetes. For this purpose, three days after vehicle or STZ injection, animals were housed in enriched environment (EE) or remained in a standard environment (SE) for 6 weeks. Anterograde transport, retinal morphology, optic nerve axons (toluidine blue staining and phosphorylated neurofilament heavy immunoreactivity), microglia/macrophages (ionized calcium binding adaptor molecule 1 (Iba-1) immunoreactivity), astrocyte reactivity (glial fibrillary acid protein-immunostaining), myelin (myelin basic protein immunoreactivity), ultrastructure, and brain derived neurotrophic factor (BDNF) levels were assessed in non-diabetic and diabetic animals housed in SE or EE. No differences in retinal morphology or retinal ganglion cell number were observed among groups. EE housing which did not affect the STZ-induced weight loss and hyperglycemia, prevented a decrease in the anterograde transport from the retina to the superior colliculus, ON axon number, and phosphorylated neurofilament heavy immunoreactivity. Moreover, EE housing prevented an increase in Iba-1 immunoreactivity, and astrocyte reactivity, as well as ultrastructural myelin alterations in the ON distal portion at early stages of diabetes. In addition, EE housing avoided a decrease in BDNF levels induced by experimental diabetes. These results suggest that EE induced neuroprotection in the diabetic visual pathway. PMID:26312758

  19. Lipoic acid protects against reperfusion injury in the early stages of cerebral ischemia.

    PubMed

    Connell, Barry J; Saleh, Monique; Khan, Bobby V; Saleh, Tarek M

    2011-02-23

    Lipoic acid (LA) is a known antioxidant currently used as a therapy in patients with vascular and metabolic disorders. We tested the hypothesis that lipoic acid is protective against the cell death observed following stroke. Lipoic acid was administered 30minutes prior to, or immediately following removal of sutures used to occlude the middle cerebral artery (MCA) in male Sprague-Dawley rats. Following removal of the sutures, the MCA territory was allowed to undergo 5.5hrs of reperfusion. This ischemia/reperfusion (I/R) resulted in a focal infarct restricted to the prefrontal cortex (24±3mm(3)). Pretreatment with LA 30minutes prior to occlusion resulted in a dose-dependent reduction in infarct volume. This reduction in infarct volume was not observed when the LA was administered immediately prior to reperfusion (30minutes post-occlusion). To investigate a potential hemodynamic mechanism for this LA-induced neuroprotection, blood pressure, heart rate and baroreceptor reflex sensitivity (BRS) were measured. Intravenous administration of LA did not result in any significant changes in any of these parameters compared to saline-treated rats. Similarly, there was no significant contribution of systemic nitric oxide or alteration in cerebral perfusion measured following pretreatment with lipoic acid or during the course of occlusion and reperfusion compared with saline-treated rats. Western blot analysis of tissue from the ischemic cortex showed an increase in protein expression of superoxide dismutase (SOD2), but not SOD1, in LA pretreated rats. This suggests a potential mechanism of action contributing to the LA-induced neuroprotection observed. Furthermore, the data in the present investigation suggest the potential use of LA pretreatment as a neuroprotectant in stroke patients. PMID:21172313

  20. River Protection Project Integrated safety management system phase II verification review plan - 7/29/99

    SciTech Connect

    SHOOP, D.S.

    1999-09-10

    The purpose of this review is to verify the implementation status of the Integrated Safety Management System (ISMS) for the River Protection Project (RPP) facilities managed by Fluor Daniel Hanford, Inc. (FDH) and operated by Lockheed Martin Hanford Company (LMHC). This review will also ascertain whether within RPP facilities and operations the work planning and execution processes are in place and functioning to effectively protect the health and safety of the workers, public, environment, and federal property over the RPP life cycle. The RPP ISMS should support the Hanford Strategic Plan (DOERL-96-92) to safely clean up and manage the site's legacy waste and deploy science and technology while incorporating the ISMS central theme to ''Do work safely'' and protect human health and the environment.

  1. Ischemic conditioning protects the rat retina in an experimental model of early type 2 diabetes.

    PubMed

    Salido, Ezequiel M; Dorfman, Damián; Bordone, Melina; Chianelli, Mónica S; Sarmiento, María Inés Keller; Aranda, Marcos; Rosenstein, Ruth E

    2013-02-01

    Diabetic retinopathy is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages, and provokes significant retinal alterations. We investigated the effect of ischemic conditioning on retinal changes induced by the moderate metabolic derangement. For this purpose, adult male Wistar rats received a control diet or 30% sucrose in the drinking water, and 3 weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25mg/kg). Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 weeks after vehicle or STZ injection and was weekly repeated in one eye, while control eyes were submitted to a sham procedure. Fasting and postprandial glycemia, and glucose, and insulin tolerance tests were analyzed. At 12 weeks of treatment, animals which received a sucrose-enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Brief ischemia pulses in one eye and a sham procedure in the contralateral eye did not affect glucose metabolism in control or diabetic rats. Ischemic pulses reduced the decrease in the electroretinogram a-wave, b-wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic protein, and vascular endothelial growth factor levels observed in diabetic animals. In addition, ischemic conditioning prevented the decrease in retinal catalase activity induced by T2DM. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies to treat diabetic retinopathy associated with T2DM. PMID:23153579

  2. Iodine Deficiency Induces a Thyroid Stimulating Hormone-Independent Early Phase of Microvascular Reshaping in the Thyroid

    PubMed Central

    Gérard, Anne-Catherine; Poncin, Sylvie; Caetano, Bertrand; Sonveaux, Pierre; Audinot, Jean-Nicolas; Feron, Olivier; Colin, Ides M.; Soncin, Fabrice

    2008-01-01

    Expansion of the thyroid microvasculature is the earliest event during goiter formation, always occurring before thyrocyte proliferation; however, the precise mechanisms governing this physiological angiogenesis are not well understood. Using reverse transcriptase-polymerase chain reaction and immunohistochemistry to measure gene expression and laser Doppler to measure blood flow in an animal model of goitrogenesis, we show that thyroid angiogenesis occurred into two successive phases. The first phase lasted a week and involved vascular activation; this process was thyroid-stimulating hormone (TSH)-independent and was directly triggered by expression of vascular endothelial growth factor (VEGF) by thyrocytes as soon as the intracellular iodine content decreased. This early reaction was followed by an increase in thyroid blood flow and endothelial cell proliferation, both of which were mediated by VEGF and inhibited by VEGF-blocking antibodies. The second, angiogenic, phase was TSH-dependent and was activated as TSH levels increased. This phase involved substantial up-regulation of the major proangiogenic factors VEGF-A, fibroblast growth factor-2, angiopoietin 1, and NG2 as well as their receptors Flk-1/VEGFR2, Flt-1/VEGFR1, and Tie-2. In conclusion, goiter-associated angiogenesis promotes thyroid adaptation to iodine deficiency. Specifically, as soon as the iodine supply is limited, thyrocytes produce proangiogenic signals that elicit early TSH-independent microvascular activation; if iodine deficiency persists, TSH plasma levels increase, triggering the second angiogenic phase that supports thyrocyte proliferation. PMID:18276786

  3. Beyond Cahn-Hilliard-Cook ordering theory: early time behavior of spatial-symmetry-breaking phase transition kinetics.

    PubMed

    Barros, Kipton; Dominguez, Rachele; Klein, W

    2009-04-01

    We extend the early time ordering theory of Cahn, Hilliard, and Cook (CHC) so that our generalized theory applies to solid-to-solid transitions. Our theory involves spatial-symmetry breaking (the initial phase contains a symmetry not present in the final phase). The predictions of our generalization differ from those of the CHC theory in two important ways: exponential growth does not begin immediately following the quench and the objects that grow exponentially are not necessarily Fourier modes. Our theory is consistent with simulation results for the long-range antiferromagnetic Ising model. PMID:19518282

  4. Conditioned Medium from Early-Outgrowth Bone Marrow Cells Is Retinal Protective in Experimental Model of Diabetes.

    PubMed

    Duarte, Diego A; Papadimitriou, Alexandros; Gilbert, Richard E; Thai, Kerri; Zhang, Yanling; Rosales, Mariana A B; Lopes de Faria, José B; Lopes de Faria, Jacqueline M

    2016-01-01

    Bone marrow-derived cells were demonstrated to improve organ function, but the lack of cell retention within injured organs suggests that the protective effects are due to factors released by the cells. Herein, we tested cell therapy using early outgrowth cells (EOCs) or their conditioned media (CM) to protect the retina of diabetic animal models (type 1 and type 2) and assessed the mechanisms by in vitro study. Control and diabetic (db/db) mice (8 weeks of age) were randomized to receive a unique intravenous injection of 5×105EOCs or 0.25 ml thrice weekly tail-vein injections of 10x concentrated CM and Wystar Kyoto rats rendered diabetic were randomized to receive 0.50 ml thrice weekly tail-vein injections of 10x concentrated CM. Four weeks later, the animals were euthanized and the eyes were enucleated. Rat retinal Müller cells (rMCs) were exposed for 24 h to high glucose (HG), combined or not with EOC-conditioned medium (EOC-CM) from db/m EOC cultures. Diabetic animals showed increase in diabetic retinopathy (DR) and oxidative damage markers; the treatment with EOCs or CM infusions significantly reduced this damage and re-established the retinal function. In rMCs exposed to diabetic milieu conditions (HG), the presence of EOC-CM reduced reactive oxygen species production by modulating the NADPH-oxidase 4 system, thus upregulating SIRT1 activity and deacetylating Lys-310-p65-NFκB, decreasing GFAP and VEGF expressions. The antioxidant capacity of EOC-CM led to the prevention of carbonylation and nitrosylation posttranslational modifications on the SIRT1 molecule, preserving its activity. The pivotal role of SIRT1 on the mode of action of EOCs or their CM was also demonstrated on diabetic retina. These findings suggest that EOCs are effective as a form of systemic delivery for preventing the early molecular markers of DR and its conditioned medium is equally protective revealing a novel possibility for cell-free therapy for the treatment of DR. PMID:26836609

  5. Conditioned Medium from Early-Outgrowth Bone Marrow Cells Is Retinal Protective in Experimental Model of Diabetes

    PubMed Central

    Duarte, Diego A.; Papadimitriou, Alexandros; Gilbert, Richard E.; Thai, Kerri; Zhang, Yanling; Rosales, Mariana A. B.; Lopes de Faria, José B.; Lopes de Faria, Jacqueline M.

    2016-01-01

    Bone marrow-derived cells were demonstrated to improve organ function, but the lack of cell retention within injured organs suggests that the protective effects are due to factors released by the cells. Herein, we tested cell therapy using early outgrowth cells (EOCs) or their conditioned media (CM) to protect the retina of diabetic animal models (type 1 and type 2) and assessed the mechanisms by in vitro study. Control and diabetic (db/db) mice (8 weeks of age) were randomized to receive a unique intravenous injection of 5×105EOCs or 0.25 ml thrice weekly tail-vein injections of 10x concentrated CM and Wystar Kyoto rats rendered diabetic were randomized to receive 0.50 ml thrice weekly tail-vein injections of 10x concentrated CM. Four weeks later, the animals were euthanized and the eyes were enucleated. Rat retinal Müller cells (rMCs) were exposed for 24 h to high glucose (HG), combined or not with EOC-conditioned medium (EOC-CM) from db/m EOC cultures. Diabetic animals showed increase in diabetic retinopathy (DR) and oxidative damage markers; the treatment with EOCs or CM infusions significantly reduced this damage and re-established the retinal function. In rMCs exposed to diabetic milieu conditions (HG), the presence of EOC-CM reduced reactive oxygen species production by modulating the NADPH-oxidase 4 system, thus upregulating SIRT1 activity and deacetylating Lys-310-p65-NFκB, decreasing GFAP and VEGF expressions. The antioxidant capacity of EOC-CM led to the prevention of carbonylation and nitrosylation posttranslational modifications on the SIRT1 molecule, preserving its activity. The pivotal role of SIRT1 on the mode of action of EOCs or their CM was also demonstrated on diabetic retina. These findings suggest that EOCs are effective as a form of systemic delivery for preventing the early molecular markers of DR and its conditioned medium is equally protective revealing a novel possibility for cell-free therapy for the treatment of DR. PMID:26836609

  6. Degradation phase of apoptosis during the early stages of human metanephros development.

    PubMed

    Wagner, Filip; Erdösová, Bela; Kylarová, Dana

    2004-12-01

    Apoptosis as a vital process is necessary for human intrauterine development. Not only the induction and course of apoptosis, but engulfment of the apoptotic cells (bodies) were the centre of our interest. Macrophages were detected in the early stages of human intrauterine development and the role of macrophages in the clearance of apoptotic cells in the early stages of human metanephros development was confirmed.

  7. Definition of technology development missions for early space stations. Large space structures, phase 2, midterm review

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The large space structures technology development missions to be performed on an early manned space station was studied and defined and the resources needed and the design implications to an early space station to carry out these large space structures technology development missions were determined. Emphasis is being placed on more detail in mission designs and space station resource requirements.

  8. Is It Possible to Maintain Consciousness and Spontaneous Ventilation with Chest Compression in the Early Phase of Cardiac Arrest?

    PubMed Central

    Oksar, Menekse; Turhanoglu, Selim

    2016-01-01

    Chest compression is important in cardiopulmonary resuscitation. However, life support algorithms do not specify when chest compression should be initiated in patients with persistent spontaneous normal breathing in the early phase after cardiac arrest. Here we describe the case of a 69-year-old man who underwent femoral bypass surgery and was extubated at the end of the procedure. After extubation, the patient's breathing pattern and respiratory rate were normal. The patient subsequently developed ventricular fibrillation, evident on two monitors. Because defibrillation was ineffective, chest compression was initiated even though the patient had spontaneous normal breathing and defensive motor reflexes, which were continued throughout resuscitation. He regained consciousness and underwent tracheal extubation without neurological sequelae on postoperative day 1. This case highlights the necessity of chest compression in the early phase of cardiac arrest. PMID:26981288

  9. Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide

    PubMed Central

    Turalba, Angela V; Pasquale, Louis R

    2014-01-01

    Objective To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. Design Retrospective comparative case series. Participants Forty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA. Methods A retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery. Main outcome measures Primary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures. Results Five out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2±4.6 in TA cases versus [vs] 14.7±5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8±1.3 in TA cases vs 1.6±1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13% in the TA group vs 16% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group. Conclusions Subtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery. PMID:25050061

  10. The early break-up phase of the South Atlantic - magnetic anomalies, volcanism and kinematics

    NASA Astrophysics Data System (ADS)

    Koopmann, H.; Schreckenberger, B.; Franke, D.; Becker, K.; Schnabel, M.

    2013-12-01

    The South Atlantic has been generally recognized as a prime example for continental break-up with accompanying volcanic activity reflected today in massive seaward dipping reflector sequences (SDRS) in reflection as well as high velocity lower crust in refraction seismic data. The early history of the South Atlantic passive margin evolution is investigated in the view of interlaced magnetic anomalies related to seafloor spreading lineations and anomalies caused by seaward-dipping reflector sequences (SDRS). As the Atlantic opened from South to North, the magma-poor segments of the southernmost South Atlantic are also the oldest segments of the Ocean. Therefore, the magma-poor segments on the conjugated margins must be considered crucial in the understanding of the initial phase of spreading and rifting concluding in the opening of the South Atlantic. The interpretation of pre-M5n lineations define timing of the termination of excess breakup related volcanic activity and the transition to 'normal' seafloor spreading. Termination of magnetic anomalies within SDR wedges point towards a scissor-like succession in volcanic activity from south to north, following the opening of the South Atlantic. Reflection, refraction seismic and potential field data show that while the two conjugated margins share much of their structural features such as segmentation and abundant volcanism, they are by no means perfectly symmetrical. This is for example shown in shelf width, strength of the magnetic anomalies or orientation of break-up related sedimentary basins. From our data, we suggest changes in spreading and later rifting direction to be the cause of for these asymmetries. This directional change is also suggested to be responsible for the change in margin character from magma-poor to volcanic rather than solely a spontaneous change in crustal melt-generation. New models for the magnetic response of SDRS reveal a high variability within the wedges on either side of the Atlantic

  11. Preserved endothelium-dependent dilatation of the coronary microvasculature at the early phase of diabetes mellitus despite the increased oxidative stress and depressed cardiac mechanical function ex vivo

    PubMed Central

    2013-01-01

    Background There has been accumulating evidence associating diabetes mellitus and cardiovascular dysfunctions. However, most of the studies are focused on the late stages of diabetes and on the function of large arteries. This study aimed at characterizing the effects of the early phase of diabetes mellitus on the cardiac and vascular function with focus on the intact coronary microvasculature and the oxidative stress involved. Materials and methods Zucker diabetic fatty rats and their lean littermates fed with standard diet A04 (Safe) were studied at the 11th week of age. Biochemical parameters such as glucose, insulin and triglycerides levels as well as their oxidative stress status were measured. Their hearts were perfused ex vivo according to Langendorff and their cardiac activity and coronary microvascular reactivity were evaluated. Results Zucker fatty rats already exhibited a diabetic state at this age as demonstrated by the elevated levels of plasma glucose, insulin, glycated hemoglobin and triglycerides. The ex vivo perfusion of their hearts revealed a decreased cardiac mechanical function and coronary flow. This was accompanied by an increase in the overall oxidative stress of the organs. However, estimation of the active form of endothelial nitric oxide synthase and coronary reactivity indicated a preserved function of the coronary microvessels at this phase of the disease. Diabetes affected also the cardiac membrane phospholipid fatty acid composition by increasing the arachidonic acid and n-3 polyunsaturated fatty acids levels. Conclusions The presence of diabetes, even at its beginning, significantly increased the overall oxidative stress of the organs resulting to decreased cardiac mechanical activity ex vivo. However, adaptations were adopted at this early phase of the disease regarding the preserved coronary microvascular reactivity and the associated cardiac phospholipid composition in order to provide a certain protection to the heart. PMID

  12. Developmental associations between adolescent change in depressive symptoms and menstrual-cycle-phase-specific negative affect during early adulthood.

    PubMed

    Kiesner, Jeff; Poulin, François

    2012-10-01

    The causal factors associated with increases in depressive symptoms among adolescent girls remain an area of theoretical debate, and the limited research considering a hormonal influence has provided mixed results. The goal of the present study was to test a set of longitudinal associations, that, if found, would provide support for a hormonal contribution to these changes. Specifically, this study tested the hypotheses that changes in depressive symptoms among adolescent girls would be associated with phase-specific symptoms of the menstrual cycle during early adulthood; that these associations would differ across three phases of the menstrual cycle; and that the pattern of associations would differ for changes in depressive symptoms during early- and late-adolescence. The sample consisted of 47 women with longitudinal data from 12 to 21 years old (approximately 91% European Canadian, 4% Middle Eastern Canadian, 2% Haitian Canadian, and 2% Asian Canadian). Consistent with expectations, results showed that early-adolescent increases in depressive symptoms were negatively associated with menstrual-phase negative affect, and positively associated with mid-cycle negative affect, but not associated with premenstrual negative affect; whereas late-adolescent change in depressive symptoms was only associated with depressive symptoms at 20-21 years. Thus, early-adolescent changes in depressive symptoms are longitudinally associated with later mood change across the menstrual cycle, suggesting a common underlying cause, which is hypothesized to be hormonal. Moreover, results suggest that, with respect to variables that are involved in affective development, important differences exist between early- and late-adolescence. The discussion considers menstrual-cycle-related symptoms (e.g., dysmenorrhea) during adolescence, and the need to study their effects on development. It is suggested that focused intervention and prevention efforts may be indicated to interrupt negative

  13. Rhodopsin and Melanopsin Contributions to the Early Redilation Phase of the Post-Illumination Pupil Response (PIPR)

    PubMed Central

    Adhikari, Prakash; Feigl, Beatrix; Zele, Andrew J.

    2016-01-01

    Melanopsin expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) entirely control the post-illumination pupil response (PIPR) from 6 s post-stimulus to the plateau during redilation after light offset. However, the photoreceptor contributions to the early redilation phase of the PIPR (< 6 s post-stimulus) have not been reported. Here, we evaluated the photoreceptor contributions to the early phase PIPR (0.6 s to 5.0 s) by measuring the spectral sensitivity of the criterion PIPR amplitude in response to 1 s light pulses at five narrowband stimulus wavelengths (409, 464, 508, 531 and 592 nm). The retinal irradiance producing a criterion PIPR was normalised to the peak and fitted by either a single photopigment nomogram or the combined melanopsin and rhodopsin spectral nomograms with the +L+M cone photopic luminous efficiency (Vλ) function. We show that the PIPR spectral sensitivity at times ≥ 1.7 s after light offset is best described by the melanopsin nomogram. At times < 1.7 s, the peak PIPR sensitivity shifts to longer wavelengths (range: 482 to 498 nm) and is best described by the combined photoreceptor nomogram, with major contributions from melanopsin and rhodopsin. This first report of melanopsin and rhodopsin contributions to the early phase PIPR is in line with the electrophysiological findings of ipRGC and rod signalling after the cessation of light stimuli and provides a cut-off time for isolating photoreceptor specific function in healthy and diseased eyes. PMID:27548480

  14. Office of River Protection Integrated Safety Management System Phase 1 Verification Corrective Action Plan

    SciTech Connect

    CLARK, D.L.

    1999-08-09

    The purpose of this Corrective Action Plan is to demonstrate the OW planned and/or completed actions to implement ISMS as well as prepare for the RPP ISMS Phase II Verification scheduled for August, 1999. This Plan collates implied or explicit ORP actions identified in several key ISMS documents and aligns those actions and responsibilities perceived necessary to appropriately disposition all ISM Phase II preparation activities specific to the ORP. The objective will be to complete or disposition the corrective actions prior to the commencement of the ISMS Phase II Verification. Improvement products/tasks not slated for completion prior to the RPP Phase II verification will be incorporated as corrective actions into the Strategic System Execution Plan (SSEP) Gap Analysis. Many of the business and management systems that were reviewed in the ISMS Phase I verification are being modified to support the ORP transition and are being assessed through the SSEP. The actions and processes identified in the SSEP will support the development of the ORP and continued ISMS implementation as committed to be complete by end of FY-2000.

  15. Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia.

    PubMed

    Pereira, Priscila Cristina; Pernomian, Larissa; Côco, Hariane; Gomes, Mayara Santos; Franco, João José; Marchi, Kátia Colombo; Hipólito, Ulisses Vilela; Uyemura, Sergio Akira; Tirapelli, Carlos Renato; de Oliveira, Ana Maria

    2016-06-15

    Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/l to 1.0µmol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5µmol/l) and VAS2870 (Nox-4 inhibitor, 5µmol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions. PMID:27063446

  16. Tissue responses to low protracted doses of high let radiations or photons - Early and late damage relevant to radio-protective countermeasures

    NASA Technical Reports Server (NTRS)

    Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

    1989-01-01

    Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

  17. Replication initiation and elongation fork rates within a differentially expressed human multicopy locus in early S phase.

    PubMed Central

    Scott, R S; Truong, K Y; Vos, J M

    1997-01-01

    Replication of the 400 copies of the 43 kb human ribosomal RNA (rDNA) locus spans most of the S phase. To examine the basis for the unusual pattern of rDNA replication, a sensitive strategy was developed to map origins of DNA replication and measure apparent rates of fork progression within a chromosomal locus. This technique, termed differential intragenomic replication timing, revealed that initiation within the actively transcribed rDNA occurred in early S within a 10.7 kb region spanning the promoter and 5' external transcribed spacer. Forks emanating from this early bidirectional origin progressed at an apparent slow rate with the sense and anti-sense forks moving at 0.32 and 0.23 kb/min. Using a photochemical-based technique, the chromatin status of the rDNA repeats was assayed throughout the S phase. Approximately 85% of the rDNA repeats were in a transcriptionally active chromatin structure at the start of S phase. A progressive decrease in the transcription state of the rDNA loci was observed, reaching a minimum between 3 and 6 h in mid S phase. Altogether, the data suggest a link between RNA polymerase I mediated transcription and site-specific initiation of DNA replication within the rDNA multicopy locus. PMID:9358159

  18. The Wnt Receptor Ryk Reduces Neuronal and Cell Survival Capacity by Repressing FOXO Activity During the Early Phases of Mutant Huntingtin Pathogenicity

    PubMed Central

    Tourette, Cendrine; Farina, Francesca; Vazquez-Manrique, Rafael P.; Orfila, Anne-Marie; Voisin, Jessica; Hernandez, Sonia; Offner, Nicolas; Parker, J. Alex; Menet, Sophie; Kim, Jinho; Lyu, Jungmok; Choi, Si Ho; Cormier, Kerry; Edgerly, Christina K.; Bordiuk, Olivia L.; Smith, Karen; Louise, Anne; Halford, Michael; Stacker, Steven; Vert, Jean-Philippe; Ferrante, Robert J.; Lu, Wange; Neri, Christian

    2014-01-01

    The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD). Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT) in several models of Huntington's disease (HD). Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD. PMID:24960609

  19. The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity.

    PubMed

    Tourette, Cendrine; Farina, Francesca; Vazquez-Manrique, Rafael P; Orfila, Anne-Marie; Voisin, Jessica; Hernandez, Sonia; Offner, Nicolas; Parker, J Alex; Menet, Sophie; Kim, Jinho; Lyu, Jungmok; Choi, Si Ho; Cormier, Kerry; Edgerly, Christina K; Bordiuk, Olivia L; Smith, Karen; Louise, Anne; Halford, Michael; Stacker, Steven; Vert, Jean-Philippe; Ferrante, Robert J; Lu, Wange; Neri, Christian

    2014-06-01

    The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD). Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT) in several models of Huntington's disease (HD). Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.

  20. Phytochrome-mediated germination and early development in spores of Dryopteris filix-mas L.: phase-specific and non phase-specific inhibition by staurosporine

    NASA Technical Reports Server (NTRS)

    Haas, C. J.; Scheuerlein, R.; Roux, S. J.

    1991-01-01

    The alkaloid staurosporine, currently known as the most potent inhibitor of protein kinase C, PKC, was tested for its ability to inhibit phytochrome-mediated spore germination in Dryopteris filix-mas L., evaluated by the induction of chlorophyll synthesis. Approximately half-maximal inhibition was obtained at a concentration of 10(-5) M. This effect of staurosporine was phase-specific and was found during the same period in which the presence of extracellular calcium is necessary for realization of the light signal. Furthermore, the ability of staurosporine to prevent progression of a germinated spore into early gametophyte development, evaluated by the accumulation of chlorophyll, was examined. Again, staurosporine (10(-5) M) significantly diminished chlorophyll accumulation, determined quantitatively in vivo by single-cell measurements, in a non-phase specific way. The fact that the phase-specific inhibitory effect of staurosporine in preventing germination was coincident with the phase-specific requirement of Ca2+ suggests that both Ca2+ and staurosporine affect the same step in the signal-transduction chain. A phosphorylation event catalysed by PKC or any Ca2+ -dependent protein kinase is proposed as the target of staurosporine and Ca2+.

  1. Quantum phase transitions between bosonic symmetry-protected topological states without sign problem: Nonlinear sigma model with a topological term

    NASA Astrophysics Data System (ADS)

    You, Yi-Zhuang; Bi, Zhen; Mao, Dan; Xu, Cenke

    2016-03-01

    We propose a series of simple two-dimensional (2D) lattice interacting fermion models that we demonstrate at low energy describe bosonic symmetry-protected topological (SPT) states and quantum phase transitions between them. This is because due to interaction, the fermions are gapped both at the boundary of the SPT states and at the bulk quantum phase transition, thus these models at low energy can be described completely by bosonic degrees of freedom. We show that the bulk of these models is described by a Sp (N ) principal chiral model with a topological Θ term, whose boundary is described by a Sp (N ) principal chiral model with a Wess-Zumino-Witten term at level 1. The quantum phase transition between SPT states in the bulk is tuned by a particular interaction term, which corresponds to tuning Θ in the field theory, and the phase transition occurs at Θ =π . The simplest version of these models with N =1 is equivalent to the familiar O(4) nonlinear sigma model (NLSM) with a topological term, whose boundary is a (1 +1 )D conformal field theory with central charge c =1 . After breaking the O(4) symmetry to its subgroups, this model can be viewed as bosonic SPT states with U(1), or Z2 symmetries, etc. All of these fermion models, including the bulk quantum phase transitions, can be simulated with the determinant quantum Monte Carlo method without the sign problem. Recent numerical results strongly suggest that the quantum disordered phase of the O(4) NLSM with precisely Θ =π is a stable (2 +1 )D conformal field theory with gapless bosonic modes.

  2. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever.

    PubMed

    Cui, Liang; Lee, Yie Hou; Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R

    2016-04-01

    Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism-serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved

  3. Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis.

    PubMed

    Oezcueruemez-Porsch, M; Kunz, D; Hardt, P D; Fadgyas, T; Kress, O; Schulz, H U; Schnell-Kretschmer, H; Temme, H; Westphal, S; Luley, C; Kloer, H U

    1998-08-01

    Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been suggested as a model for acute pancreatitis (AP), which allows evaluation of early alterations in the time course of the disease. The influence of the clinical course on procalcitonin (PCT), serum amyloid A (SAA), and several proinflammatory and inhibitory cytokines was evaluated in patients with AP following ERCP. Blood samples were prospectively collected from patients undergoing ERCP. The incidence of ERCP-induced pancreatic damage, defined as abdominal complaints, a threefold increase of serum lipase, and elevation of CRP from <10 to >20 mg/liter was 12.8% (12/94). Only mild clinical courses of acute pancreatitis were observed. PCT significantly increased in subjects with post-ERCP pancreatitis after 24 hr. However, PCT levels did not exceed 0.5 ng/ml in any patient. Interleukin-1 receptor antagonist (IL-1RA) began to differ from baseline 2 hr after ERCP, followed by interleukin-6 (IL-6, 6 hr), solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII, 24 hr) and SAA (24 hr). Interleukin 10 (IL-10) showed marked interindividual variations with no obvious peak. Among all parameters evaluated, only peak values of IL-6 and IL-10 showed significant correlations with the reported pain score (r2 = 0.62/0.78), degree of ampullar irritation (r2 = NS/0.87), and the duration of ERCP (r2 = 0.58/0.76). No correlation was found with the volume of the injected contrast agent. We conclude that IL-10 and IL-6 appear to be useful to monitor patients after ERCP. The absence of any PCT elevation in the present study is in accordance with the clinical course of the patients who suffered from mild pancreatic damage without systemic or infectious complications.

  4. Protective effects of resveratrol on the inhibition of hippocampal neurogenesis induced by ethanol during early postnatal life.

    PubMed

    Xu, Le; Yang, Yang; Gao, Lixiong; Zhao, Jinghui; Cai, Yulong; Huang, Jing; Jing, Sheng; Bao, Xiaohang; Wang, Ying; Gao, Junwei; Xu, Haiwei; Fan, Xiaotang

    2015-07-01

    Ethanol (EtOH) exposure during early postnatal life triggers obvious neurotoxic effects on the developing hippocampus and results in long-term effects on hippocampal neurogenesis. Resveratrol (RSV) has been demonstrated to exert potential neuroprotective effects by promoting hippocampal neurogenesis. However, the effects of RSV on the EtOH-mediated impairment of hippocampal neurogenesis remain undetermined. Thus, mice were pretreated with RSV and were later exposed to EtOH to evaluate its protective effects on EtOH-mediated toxicity during hippocampal development. The results indicated that a brief exposure of EtOH on postnatal day 7 resulted in a significant impairment in hippocampal neurogenesis and a depletion of hippocampal neural precursor cells (NPCs). This effect was attenuated by pretreatment with RSV. Furthermore, EtOH exposure resulted in a reduction in spine density on the granular neurons of the dentate gyrus (DG), and the spines exhibited a less mature morphological phenotype characterized by a higher proportion of stubby spines and a lower proportion of mushroom spines. However, RSV treatment effectively reversed these responses. We further confirmed that RSV treatment reversed the EtOH-induced down-regulation of hippocampal pERK and Hes1 protein levels, which may be related to the proliferation and maintenance of NPCs. Furthermore, EtOH exposure in the C17.2 NPCs also diminished cell proliferation and activated apoptosis, which could be reversed by pretreatment of RSV. Overall, our results suggest that RSV pretreatment protects against EtOH-induced defects in neurogenesis in postnatal mice and may thus play a critical role in preventing EtOH-mediated toxicity in the developing hippocampus.

  5. Early Terminal Complement Blockade and C6 Deficiency Are Protective in Enterohemorrhagic Escherichia coli-Infected Mice.

    PubMed

    Arvidsson, Ida; Rebetz, Johan; Loos, Sebastian; Herthelius, Maria; Kristoffersson, Ann-Charlotte; Englund, Elisabet; Chromek, Milan; Karpman, Diana

    2016-08-15

    Complement activation occurs during enterohemorrhagic Escherichia coli (EHEC) infection and may exacerbate renal manifestations. In this study, we show glomerular C5b-9 deposits in the renal biopsy of a child with EHEC-associated hemolytic uremic syndrome. The role of the terminal complement complex, and its blockade as a therapeutic modality, was investigated in a mouse model of E. coli O157:H7 infection. BALB/c mice were treated with monoclonal anti-C5 i.p. on day 3 or 6 after intragastric inoculation and monitored for clinical signs of disease and weight loss for 14 d. All infected untreated mice (15 of 15) or those treated with an irrelevant Ab (8 of 8) developed severe illness. In contrast, only few infected mice treated with anti-C5 on day 3 developed symptoms (three of eight, p < 0.01 compared with mice treated with the irrelevant Ab on day 3) whereas most mice treated with anti-C5 on day 6 developed symptoms (six of eight). C6-deficient C57BL/6 mice were also inoculated with E. coli O157:H7 and only 1 of 14 developed disease, whereas 10 of 16 wild-type mice developed weight loss and severe disease (p < 0.01). Complement activation via the terminal pathway is thus involved in the development of disease in murine EHEC infection. Early blockade of the terminal complement pathway, before the development of symptoms, was largely protective, whereas late blockade was not. Likewise, lack of C6, and thereby deficient terminal complement complex, was protective in murine E. coli O157:H7 infection. PMID:27421478

  6. Refurbishment cost study of the thermal protection system of a space shuttle vehicle, phase 2

    NASA Technical Reports Server (NTRS)

    Haas, D. W.

    1972-01-01

    The labor costs and techniques associated with the refurbishment and maintenance of representative thermal protection system (TPS) components and their attachment concepts suitable for space shuttle application are defined, characterized, and evaluated from the results of an experimental test program. This program consisted of designing selected TPS concepts, fabricating and assembling test hardware, and performing a time and motion study of specific maintenance functions of the test hardware on a full-scale- mockup. Labor requirements and refurbishment techniques, as they relate to the maintenance functions of inspection, repair, removal, and replacement were identified.

  7. Pain relief induces dopamine release in the rat nucleus accumbens during the early but not late phase of neuropathic pain.

    PubMed

    Kato, Takahiro; Ide, Soichiro; Minami, Masabumi

    2016-08-26

    Comorbidity of chronic pain and depression has long been recognized in the clinic, and preclinical studies have reported depression-like behaviors in animal models of chronic pain. These findings suggest a common neuronal basis for chronic pain and depression. The neuronal pathway from the ventral tegmental area to the nucleus accumbens (NAc) is critical in the mesolimbic dopamine (DA) reward circuit, and dysfunction of this pathway has been implicated in depression. Although time-dependent development of depression-related behaviors has been reported in chronic pain animals, time-dependent functional changes in this pathway remain to be examined. To address this issue, we examined the effects of two types of rewards, pain relief by intrathecal injection of pregabalin (100μg in 10μL phosphate buffered saline) and 30% sucrose solution intake, on intra-NAc DA release in rats subjected to spinal nerve ligation (SNL). Specifically, the effects were investigated during the early (17-20days after ligation) and late (31-34days after ligation) phases of neuropathic pain. Pain relief increased the intra-NAc DA levels in the SNL rats during the early but not late phase of neuropathic pain. Intake of the sucrose solution increased the intra-NAc DA levels both in the SNL and sham animals during the early phase of neuropathic pain, while it induced DA release in the sham but not SNL animals during the late phase. These results suggest that dysfunction of the mesolimbic DA reward circuit develops in a time-dependent manner. Mesolimbic DA reward circuit dysfunction might be a common neuronal mechanism underlying chronic pain and depression, and a potential target for novel analgesic and antidepressant medications. PMID:27369326

  8. Cosmological QCD phase transition in steady non-equilibrium dissipative Hořava–Lifshitz early universe

    SciTech Connect

    Khodadi, M. Sepangi, H.R.

    2014-07-15

    We study the phase transition from quark–gluon plasma to hadrons in the early universe in the context of non-equilibrium thermodynamics. According to the standard model of cosmology, a phase transition associated with chiral symmetry breaking after the electro-weak transition has occurred when the universe was about 1–10 μs old. We focus attention on such a phase transition in the presence of a viscous relativistic cosmological background fluid in the framework of non-detailed balance Hořava–Lifshitz cosmology within an effective model of QCD. We consider a flat Friedmann–Robertson–Walker universe filled with a non-causal and a causal bulk viscous cosmological fluid respectively and investigate the effects of the running coupling constants of Hořava–Lifshitz gravity, λ, on the evolution of the physical quantities relevant to a description of the early universe, namely, the temperature T, scale factor a, deceleration parameter q and dimensionless ratio of the bulk viscosity coefficient to entropy density (ξ)/s . We assume that the bulk viscosity cosmological background fluid obeys the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively. -- Highlights: •In this paper we have studied quark–hadron phase transition in the early universe in the context of the Hořava–Lifshitz model. •We use a flat FRW universe with the bulk viscosity cosmological background fluid obeying the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively.

  9. Supported liquid membrane-protected molecularly imprinted beads for micro-solid phase extraction of sulfonamides in environmental waters.

    PubMed

    Díaz-Álvarez, M; Barahona, F; Turiel, E; Martín-Esteban, A

    2014-08-29

    In this work, molecularly imprinted polymer (MIP) beads have been prepared and evaluated for the development of a supported liquid membrane-protected micro-solid phase extraction method for the analysis of sulfonamides (SAs) in aqueous samples. The performance of MIP beads was firstly evaluated in cartridges by conventional solid-phase extraction for the simultaneous analysis of SAs. Afterward, beads were packed into a polypropylene hollow fiber protected by an organic solvent immobilized in the pores of the capillary wall. During the process, the analytes were extracted from the aqueous sample to the immobilized organic solvent and then selectively retained by the MIP beads located inside the capillary. The effect of various experimental parameters as sample pH, time and stirring-rate among others, were studied for the establishment of optimum rebinding conditions. Relative recoveries for all sulfonamides tested in river and reservoir water samples by the proposed method using 100mL water sample spiked with 50μg L-1 of each sulfonamide were within 70-120%, with a relative standard deviation (RSD) <10% (n=3). The detection limits (LODs) were within 0.2-3μgL(-1), depending upon the sulfonamide and the type of water used.

  10. The Validation of Vapor Phase Hydrogen Peroxide Microbial Reduction for Planetary Protection and a Proposed Vacuum Process Specification

    NASA Technical Reports Server (NTRS)

    Chung, Shirley; Barengoltz, Jack; Kern, Roger; Koukol, Robert; Cash, Howard

    2006-01-01

    The Jet Propulsion Laboratory, in conjunction with the NASA Planetary Protection Officer, has selected the vapor phase hydrogen peroxide sterilization process for continued development as a NASA approved sterilization technique for spacecraft subsystems and systems. The goal is to include this technique, with an appropriate specification, in NPR 8020.12C as a low temperature complementary technique to the dry heat sterilization process.To meet microbial reduction requirements for all Mars in-situ life detection and sample return missions, various planetary spacecraft subsystems will have to be exposed to a qualified sterilization process. This process could be the elevated temperature dry heat sterilization process (115 C for 40 hours) which was used to sterilize the Viking lander spacecraft. However, with utilization of such elements as highly sophisticated electronics and sensors in modern spacecraft, this process presents significant materials challenges and is thus an undesirable bioburden reduction method to design engineers. The objective of this work is to introduce vapor hydrogen peroxide (VHP) as an alternative to dry heat microbial reduction to meet planetary protection requirements.The VHP process is widely used by the medical industry to sterilize surgical instruments and biomedical devices, but high doses of VHP may degrade the performance of flight hardware, or compromise material properties. Our goal for this study was to determine the minimum VHP process conditions to achieve microbial reduction levels acceptable for planetary protection.

  11. Cyclin CYB-3 controls both S-phase and mitosis and is asymmetrically distributed in the early C. elegans embryo.

    PubMed

    Michael, W Matthew

    2016-09-01

    In early C. elegans embryos the timing of cell division is both invariant and developmentally regulated, yet how the cell cycle is controlled in the embryo and how cell cycle timing impacts early development remain important, unanswered questions. Here, I focus on the cyclin B3 ortholog CYB-3, and show that this cyclin has the unusual property of controlling both the timely progression through S-phase and mitotic entry, suggesting that CYB-3 is both an S-phase-promoting and mitosis-promoting factor. Furthermore, I find that CYB-3 is asymmetrically distributed in the two-cell embryo, such that the somatic precursor AB cell contains ∼2.5-fold more CYB-3 than its sister cell, the germline progenitor P1 CYB-3 is not only physically limited in P1 but also functionally limited, and this asymmetry is controlled by the par polarity network. These findings highlight the importance of the CYB-3 B3-type cyclin in cell cycle regulation in the early embryo and suggest that CYB-3 asymmetry helps establish the well-documented cell cycle asynchrony that occurs during cell division within the P-lineage. PMID:27578178

  12. Cyclin CYB-3 controls both S-phase and mitosis and is asymmetrically distributed in the early C. elegans embryo.

    PubMed

    Michael, W Matthew

    2016-09-01

    In early C. elegans embryos the timing of cell division is both invariant and developmentally regulated, yet how the cell cycle is controlled in the embryo and how cell cycle timing impacts early development remain important, unanswered questions. Here, I focus on the cyclin B3 ortholog CYB-3, and show that this cyclin has the unusual property of controlling both the timely progression through S-phase and mitotic entry, suggesting that CYB-3 is both an S-phase-promoting and mitosis-promoting factor. Furthermore, I find that CYB-3 is asymmetrically distributed in the two-cell embryo, such that the somatic precursor AB cell contains ∼2.5-fold more CYB-3 than its sister cell, the germline progenitor P1 CYB-3 is not only physically limited in P1 but also functionally limited, and this asymmetry is controlled by the par polarity network. These findings highlight the importance of the CYB-3 B3-type cyclin in cell cycle regulation in the early embryo and suggest that CYB-3 asymmetry helps establish the well-documented cell cycle asynchrony that occurs during cell division within the P-lineage.

  13. Catastrophic shifts in ecosystems: spatial early warnings and management procedures (Inspired in the physics of phase transitions)

    NASA Astrophysics Data System (ADS)

    Fort, H.; Mazzeo, N.; Scheffer, M.; van Nes, E.

    2010-09-01

    Ecosystems are complex systems which can respond to gradual changes of their conditions by a sudden shift to a contrasting regime or alternative stable state (ASS). Predicting such critical points before they are reached is extremely difficult and providing early warnings is fundamental to design management protocols for ecosystems. Here we study different spatial versions of popular ecological models which are known to exhibit ASS. The spatial heterogeneity is introduced by a local parameter varying from cell to cell in a regular lattice. Transport of biomass among cells occurs by simple diffusion. We investigate whether different quantities from statistical mechanics -like the variance, the two-point correlation function and the patchiness-may serve as early warnings of catastrophic phase transitions between the ASS. In particular, we find that the patch-size distribution follows a power law when the system is close to the catastrophic transition. We also provide links between spatial and temporal indicators and analyze how the interplay between diffusion and spatial heterogeneity may affect the earliness of each of the observables. Finally, we comment on similarities and differences between these catastrophic shifts and paradigmatic thermodynamic phase transitions like the liquid-vapor change of state for a fluid like water.

  14. Species-driven phases and increasing structure in early-successional plant communities.

    PubMed

    Zaplata, Markus K; Winter, Susanne; Fischer, Anton; Kollmann, Johannes; Ulrich, Werner

    2013-01-01

    Successional phases describe changes in ecological communities that proceed in steps rather than continuously. Despite their importance for the understanding of ecosystem development, there still exists no reliable definition of phases and no quantitative measure of phase transitions. In order to obtain these data, we investigated primary succession in an artificial catchment (6 ha) in eastern Germany over a period of 6 years. The data set consists of records of plant species and their cover values, and initial substrate properties, both from plots in a regular grid (20 m × 20 m) suitable for spatial data analysis. Community assembly was studied by analyses of species co-occurrence and nestedness. Additionally, we correlated lognormal and log series distributions of species abundance to each community. We here introduce a new general method for detection of successional phases based on the degree of transient spatial homogeneity in the study system. Spatially coherent vegetation patterns revealed nonoverlapping partitions within this sequence of primary succession and were characterized as two distinct ecological phases. Patterns of species co-occurrence were increasingly less random, and hence the importance of demographic stochasticity and neutral community assembly decreased during the study period. Our findings highlight the spatial dimension of successional phases and quantify the degree of change between these steps. They are an element for advancing a more reliable terminology of ecological successions.

  15. Myocardial protection of early extracorporeal membrane oxygenation (ECMO) support for acute myocardial infarction with cardiogenic shock in pigs.

    PubMed

    Zhu, Gang-jie; Sun, Li-na; Li, Xing-hai; Wang, Ning-fu; Wu, Hong-hai; Yuan, Chen-xing; Li, Qiao-qiao; Xu, Peng; Ren, Ya-qi; Mao, Bao-gen

    2015-09-01

    The aim of this study was to explore myocardial protection of early extracorporeal membrane oxygenation (ECMO) support for acute myocardial infarction with cardiogenic shock in pigs. 24 male pigs (34.6 ± 1.3 kg) were randomly divided into three groups-control group, drug therapy group, and ECMO group. Myocardial infarction model was created in drug therapy group and ECMO group by ligating coronary artery. When cardiogenic shock occurred, drugs were given in drug therapy group and ECMO began to work in ECMO group. The pigs were killed 24 h after cardiogenic shock. Compared with in drug therapy group, left ventricular end-diastolic pressure in ECMO group decreased significantly 6 h after ligation (P < 0.05). At the end of the experiments, LV - dp/dt among three groups was significantly different, drug therapy group < ECMO group < control group. There was no difference in LV + dp/dt between drug therapy group and ECMO group. Compared with drug group, myocardial infarct size of ECMO group did not reduce significantly, but myocardial enzyme and troponin-I decreased significantly. Compared with drug therapy, ECMO improves left ventricular diastolic function, and may improve systolic function. ECMO cannot reduce myocardial infarct size without revascularization, but may have positive effects on ischemic areas by avoiding further injuring.

  16. W Phase Inversion and Tsunami Inundation Modeling for Tsunami Early Warning: Case Study for the 2011 Tohoku Event

    NASA Astrophysics Data System (ADS)

    Gusman, Aditya Riadi; Tanioka, Yuichiro

    2014-07-01

    Centroid moment tensor solutions for the 2011 Tohoku earthquake are determined by W phase inversions using 5 and 10 min data recorded by the Full Range Seismograph Network of Japan (F-net). By a scaling relation of moment magnitude to rupture area and an assumption of rigidity of 4 × 1010 N m-2, simple rectangular earthquake fault models are estimated from the solutions. Tsunami inundations in the Sendai Plain, Minamisanriku, Rikuzentakata, and Taro are simulated using the estimated fault models. Then the simulated tsunami inundation area and heights are compared with the observations. Even the simulated tsunami heights and inundations from the W phase solution that used only 5 min data are considerably similar to the observations. The results are improved when using 10 min of W phase data. These show that the W phase solutions are reliable to be used for tsunami inundation modeling. Furthermore, the technique that combines W phase inversion and tsunami inundation modeling can produce results that have sufficient accuracy for tsunami early warning purposes.

  17. Detecting and identifying two-dimensional symmetry-protected topological, symmetry-breaking, and intrinsic topological phases with modular matrices via tensor-network methods

    NASA Astrophysics Data System (ADS)

    Huang, Ching-Yu; Wei, Tzu-Chieh

    2016-04-01

    Symmetry-protected topological (SPT) phases exhibit nontrivial order if symmetry is respected but are adiabatically connected to the trivial product phase if symmetry is not respected. However, unlike the symmetry-breaking phase, there is no local order parameter for SPT phases. Here we employ a tensor-network method to compute the topological invariants characterized by the simulated modular S and T matrices to study transitions in a few families of two-dimensional (2D) wave functions which are ZN (N =2 and3 ) symmetric. We find that in addition to the topologically ordered phases, the modular matrices can be used to identify nontrivial SPT phases and detect transitions between different SPT phases as well as between symmetric and symmetry-breaking phases. Therefore modular matrices can be used to characterize various types of gapped phases in a unifying way.

  18. Cosmological QCD phase transition in steady non-equilibrium dissipative Hořava-Lifshitz early universe

    NASA Astrophysics Data System (ADS)

    Khodadi, M.; Sepangi, H. R.

    2014-07-01

    We study the phase transition from quark-gluon plasma to hadrons in the early universe in the context of non-equilibrium thermodynamics. According to the standard model of cosmology, a phase transition associated with chiral symmetry breaking after the electro-weak transition has occurred when the universe was about 1-10 μs old. We focus attention on such a phase transition in the presence of a viscous relativistic cosmological background fluid in the framework of non-detailed balance Hořava-Lifshitz cosmology within an effective model of QCD. We consider a flat Friedmann-Robertson-Walker universe filled with a non-causal and a causal bulk viscous cosmological fluid respectively and investigate the effects of the running coupling constants of Hořava-Lifshitz gravity, λ, on the evolution of the physical quantities relevant to a description of the early universe, namely, the temperature T, scale factor a, deceleration parameter q and dimensionless ratio of the bulk viscosity coefficient to entropy density ξ/s. We assume that the bulk viscosity cosmological background fluid obeys the evolution equation of the steady truncated (Eckart) and full version of the Israel-Stewart fluid, respectively.

  19. Late-phase expression of a murine cytomegalovirus immediate-early antigen recognized by cytolytic T lymphocytes.

    PubMed Central

    Reddehase, M J; Fibi, M R; Keil, G M; Koszinowski, U H

    1986-01-01

    The cloned murine cytolytic T-lymphocyte line IE1-IL and several sublines detect a murine cytomegalovirus immediate-early (IE) membrane determinant in conjunction with Ld class I major histocompatibility glycoprotein. The lines retained cytolytic activity, strict antigen specificity, and self-restriction even when adapted to long-term, antigen-independent growth in the presence of interleukin-2 only (M. J. Reddehase, H.-J. Bühring, and U. H. Koszinowski, J. Virol. 57:408-412). These attributes allowed us to use IE1-IL as a stable, monospecific probe for tracing the expression of the IE membrane antigen throughout the viral replication cycle. Presentation of the antigen at the cell membrane proved to be most effective when expression of IE genes in infected mouse embryo fibroblasts was selectively enhanced by consecutive cycloheximide-actinomycin D treatment, whereas without enhancement high numbers of IE1-IL cytolytic T lymphocytes were required to demonstrate the antigen in the IE phase. In the early phase of infection when IE genes were no longer transcribed, cytolysis was not observed, although IE proteins were detectable in the nuclei of the infected cells. Without application of inhibitors IE membrane antigen expression was most prominent during the late phase of infection. Reinitiation of transcription from the genomic region encoding the major IE protein (pp89) and de novo synthesis of pp89 correlated with this reexpression of the IE membrane antigen. Images PMID:2431160

  20. Geometry of reduced density matrices for symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Chen, Ji-Yao; Ji, Zhengfeng; Liu, Zheng-Xin; Shen, Yi; Zeng, Bei

    2016-01-01

    In this paper, we study the geometry of reduced density matrices for states with symmetry-protected topological (SPT) order. We observe ruled surface structures on the boundary of the convex set of low-dimensional projections of the reduced density matrices. In order to signal the SPT order using ruled surfaces, it is important that we add a symmetry-breaking term to the boundary of the system—no ruled surface emerges in systems without a boundary or when we add a symmetry-breaking term representing a thermodynamic quantity. Although the ruled surfaces only appear in the thermodynamic limit where the ground-state degeneracy is exact, we analyze the precision of our numerical algorithm and show that a finite-system calculation suffices to reveal the ruled surface structures.

  1. Wave functions of symmetry-protected topological phases from conformal field theories

    NASA Astrophysics Data System (ADS)

    Scaffidi, Thomas; Ringel, Zohar

    2016-03-01

    We propose a method for analyzing two-dimensional symmetry-protected topological (SPT) wave functions using a correspondence with conformal field theories (CFTs) and integrable lattice models. This method generalizes the CFT approach for the fractional quantum Hall effect wherein the wave-function amplitude is written as a many-operator correlator in the CFT. Adopting a bottom-up approach, we start from various known microscopic wave functions of SPTs with discrete symmetries and show how the CFT description emerges at large scale, thereby revealing a deep connection between group cocycles and critical, sometimes integrable, models. We show that the CFT describing the bulk wave function is often also the one describing the entanglement spectrum, but not always. Using a plasma analogy, we also prove the existence of hidden quasi-long-range order for a large class of SPTs. Finally, we show how response to symmetry fluxes is easily described in terms of the CFT.

  2. Cuyahoga County Early Childhood Initiative Evaluation: Phase I Final Report and Executive Summary.

    ERIC Educational Resources Information Center

    Coulton, Claudia

    Responding to the need for a universal and comprehensive approach for supporting all families with children from birth through age 5, the Early Childhood Initiative (ECI) was launched by a broad-based coalition of public and private partners brought together by the Cuyahoga County government in Ohio. This report describes the history of ECI,…

  3. A Phase II Trial of Telehealth Delivery of the Lidcombe Program of Early Stuttering Intervention

    ERIC Educational Resources Information Center

    Lewis, Christine; Packman, Ann; Onslow, Mark; Simpson, Judy M.; Jones, Mark

    2008-01-01

    Purpose: The aims of this study were to evaluate the efficacy of telehealth delivery of the Lidcombe Program of Early Stuttering Intervention, compared with a control group, and to determine the number of children who could be regarded as "responders." Method: A speech-language pathologist provided telehealth delivery of the Lidcombe Program…

  4. The Relationship between Jewish Early Childhood Education and Family Jewish Practices: Phase II.

    ERIC Educational Resources Information Center

    Ravid, Ruth; Ginsburg, Marvell

    The purpose of this study was to investigate changes in the practices of Jewish families which occurred after the first enrollment of a child in a Jewish Early Childhood Center operated by the Board of Jewish Education of Metropolitan Chicago. Participants included 109 families who completed survey questionnaires at the beginning and end of the…

  5. Which System Variables Carry Robust Early Signs of Upcoming Phase Transition? An Ecological Example

    PubMed Central

    Negahbani, Ehsan; Steyn-Ross, D. Alistair; Steyn-Ross, Moira L.; Aguirre, Luis A.

    2016-01-01

    Growth of critical fluctuations prior to catastrophic state transition is generally regarded as a universal phenomenon, providing a valuable early warning signal in dynamical systems. Using an ecological fisheries model of three populations (juvenile prey J, adult prey A and predator P), a recent study has reported silent early warning signals obtained from P and A populations prior to saddle-node (SN) bifurcation, and thus concluded that early warning signals are not universal. By performing a full eigenvalue analysis of the same system we demonstrate that while J and P populations undergo SN bifurcation, A does not jump to a new state, so it is not expected to carry early warning signs. In contrast with the previous study, we capture a significant increase in the noise-induced fluctuations in the P population, but only on close approach to the bifurcation point; it is not clear why the P variance initially shows a decaying trend. Here we resolve this puzzle using observability measures from control theory. By computing the observability coefficient for the system from the recordings of each population considered one at a time, we are able to quantify their ability to describe changing internal dynamics. We demonstrate that precursor fluctuations are best observed using only the J variable, and also P variable if close to transition. Using observability analysis we are able to describe why a poorly observable variable (P) has poor forecasting capabilities although a full eigenvalue analysis shows that this variable undergoes a bifurcation. We conclude that observability analysis provides complementary information to identify the variables carrying early-warning signs about impending state transition. PMID:27631984

  6. Which System Variables Carry Robust Early Signs of Upcoming Phase Transition? An Ecological Example.

    PubMed

    Negahbani, Ehsan; Steyn-Ross, D Alistair; Steyn-Ross, Moira L; Aguirre, Luis A

    2016-01-01

    Growth of critical fluctuations prior to catastrophic state transition is generally regarded as a universal phenomenon, providing a valuable early warning signal in dynamical systems. Using an ecological fisheries model of three populations (juvenile prey J, adult prey A and predator P), a recent study has reported silent early warning signals obtained from P and A populations prior to saddle-node (SN) bifurcation, and thus concluded that early warning signals are not universal. By performing a full eigenvalue analysis of the same system we demonstrate that while J and P populations undergo SN bifurcation, A does not jump to a new state, so it is not expected to carry early warning signs. In contrast with the previous study, we capture a significant increase in the noise-induced fluctuations in the P population, but only on close approach to the bifurcation point; it is not clear why the P variance initially shows a decaying trend. Here we resolve this puzzle using observability measures from control theory. By computing the observability coefficient for the system from the recordings of each population considered one at a time, we are able to quantify their ability to describe changing internal dynamics. We demonstrate that precursor fluctuations are best observed using only the J variable, and also P variable if close to transition. Using observability analysis we are able to describe why a poorly observable variable (P) has poor forecasting capabilities although a full eigenvalue analysis shows that this variable undergoes a bifurcation. We conclude that observability analysis provides complementary information to identify the variables carrying early-warning signs about impending state transition. PMID:27631984

  7. Early Origins of Child Obesity: Bridging Disciplines and Phases of Development - September 30–October 1, 2010

    PubMed Central

    Christoffel, Katherine Kaufer; Wang, Xiaobin; Binns, Helen J.

    2012-01-01

    This report summarizes a conference: “Early Origins of Child Obesity: Bridging Disciplines and Phases of Development”, held in Chicago on September 30–October 1, 2010. The conference was funded in part by the National Institutes of Health and the Williams Heart Foundation, to achieve the conference objective: forging a next-step research agenda related to the early origins of childhood obesity. This research agenda was to include working with an array of factors (from genetic determinants to societal ones) along a continuum from prenatal life to age 7, with an emphasis on how the developing child deals with the challenges presented by his/her environment (prenatal, parental, nutritional, etc.). The conference offered a unique opportunity to facilitate communication and planning of future work among a variety of researchers whose work separately addresses different periods in early life. Over the span of two days, speakers addressed existing, critical research topics within each of the most-studied age ranges. On the final day, workshops fostered the discussion needed to identify the highest priority research topics related to linking varied early factor domains. These are presented for use in planning future research and research funding. PMID:23443002

  8. PLASMA HEATING IN THE VERY EARLY AND DECAY PHASES OF SOLAR FLARES

    SciTech Connect

    Falewicz, R.; Rudawy, P.; Siarkowski, M. E-mail: rudawy@astro.uni.wroc.pl

    2011-05-20

    In this paper, we analyze the energy budgets of two single-loop solar flares under the assumption that non-thermal electrons (NTEs) are the only source of plasma heating during all phases of both events. The flares were observed by RHESSI and GOES on 2002 September 20 and 2002 March 17, respectively. For both investigated flares we derived the energy fluxes contained in NTE beams from the RHESSI observational data constrained by observed GOES light curves. We showed that energy delivered by NTEs was fully sufficient to fulfill the energy budgets of the plasma during the pre-heating and impulsive phases of both flares as well as during the decay phase of one of them. We concluded that in the case of the investigated flares there was no need to use any additional ad hoc heating mechanisms other than heating by NTEs.

  9. Enhanced resistance against Listeria monocytogenes at an early phase of primary infection in pregnant mice: activation of macrophages during pregnancy.

    PubMed Central

    Watanabe, Y; Mitsuyama, M; Sano, M; Nakano, H; Nomoto, K

    1986-01-01

    We investigated the pregnancy-induced changes in macrophage activity which are important in the expression of host defense against infections. Several macrophage functions were examined by using Listeria monocytogenes. In pregnant mice, prolonged survival and enhanced in vivo elimination of bacteria were observed in the early phase of primary infection. Functions of peritoneal macrophages, including in vitro phagocytosis intracellular killing, glucose consumption, generation of superoxide anion, and intracellular beta-glucuronidase activity were shown to be enhanced in pregnant mice. These findings indicate that pregnancy enhances macrophage functions qualitatively. Possible mechanisms for this enhancement and the significance of macrophage activation for pregnant hosts are discussed. PMID:3011673

  10. The influence of surface microchemistry in protective film formation on multi-phase magnesium alloys

    NASA Astrophysics Data System (ADS)

    Gray-Munro, J. E.; Luan, B.; Huntington, L.

    2008-02-01

    The high strength:weight ratio of magnesium alloys makes them an ideal metal for automotive and aerospace applications where weight reduction is of significant concern. Unfortunately, magnesium alloys are highly susceptible to corrosion particularly in salt-spray conditions. This has limited their use in the automotive and aerospace industries, where exposure to harsh service conditions is unavoidable. The simplest way to avoid corrosion is to coat the magnesium-based substrate by a process such as electroless plating, which is a low-cost, non line of sight process. Magnesium is classified as a difficult to plate metal due to its high reactivity. This means that in the presence of air magnesium very quickly forms a passive oxide layer that must be removed prior to plating. Furthermore, high aluminium content alloys are especially difficult to plate due to the formation of intermetallic species at the grain boundaries, resulting in a non-uniform surface potential across the substrate and thereby further complicating the plating process. The objective of this study is to understand how the magnesium alloy microstructure influences the surface chemistry of the alloy during both pretreatment and immersion copper coating of the substrate. A combination of scanning electron microscopy, energy dispersive spectroscopy and scanning Auger microscopy has been used to study the surface chemistry at the various stages of the coating process. Our results indicate that the surface chemistry of the alloy is different on the aluminum rich β phase of the material compared to the magnesium matrix which leads to preferential deposition of the metal on the aluminum rich phase of the alloy.

  11. Identification of a protective protein from stationary-phase exoproteome of Brucella abortus.

    PubMed

    Jain, Shikha; Kumar, Subodh; Dohre, Sudhir; Afley, Prachiti; Sengupta, Nabonita; Alam, Syed I

    2014-02-01

    Brucellosis is a worldwide zoonotic disease. No Brucella vaccine is available for use in humans, and existing animal vaccines have limitations. To search the putative vaccine candidates, we studied the exoproteome of Brucella abortus NCTC 10093 using 2-DE-MS approach. Twenty-six proteins were identified using MALDI-TOF/TOF tandem mass spectrometry. Outer membrane protein 25, d-galactose periplasmic-binding protein, oligopeptide ABC transporter protein and isopropylmalate synthase were found to be the most abundant proteins. Most proteins (6, 23%) were predicted to be involved in amino acid transport and metabolism followed by carbohydrate transport and metabolism (4, 15%). Outer membrane protein 25, Omp2b porin and one hypothetical protein were predicted as outer membrane proteins. In addition, Omp28, Omp31 and one ribosomal protein (L9) were also identified. The ribosomal protein L9 was produced as a recombinant protein and was studied in mouse model for vaccine potential. It was found to be immunogenic in terms of generating serum antibody response and release of IFN-γ from mice spleen cells. Recombinant L9-immunized mice were protected against challenge with virulent B. abortus strain 544, suggesting usefulness of ribosomal protein L9 as a good vaccine candidate against brucellosis.

  12. Theory of supersymmetry ``protected'' topological phases of isostatic lattices and highly frustrated magnets

    NASA Astrophysics Data System (ADS)

    Lawler, Michael

    I generalize the theory of phonon topological band structures of isostatic lattices to highly frustrated antiferromagnets. I achieve this with a discovery of a many-body supersymmetry (SUSY) in the phonon problem of balls and springs which also applies to geometrically frustrated magnets. The Witten index of the SUSY model, when restricted to the single body problem (meaningful for linearized phonons), is then shown to be the Calladine-Kane-Lubensky index of mechanical structures that forms the cornerstone of the phonon topological band structure theory. ``Spontaneous supersymmetry breaking'' is then identified as the need to gap all modes in the bulk to create the topological state. The many-body SUSY formulation shows that the topology is not restricted to a band structure problem but extends to systems of coupled bosons and fermions that are in principle also realizable in solid state systems. The analogus supersymmetry of the magnon problem turns out to be particularly useful for highly frustrated magnets with the kagome family of antiferromagnets an analog of topological isostatic lattices. Thus, a solid state realization of the theory of phonon topological band structure may be found in highly frustrated magnets. However, our results show that this topology is protected not

  13. Neuroendocrine activation and markers of early reperfusion in the acute phase of myocardial infarction.

    PubMed

    Ray, S G; Morton, J J; Dargie, H J

    1993-12-01

    Potentially harmful stimulation of the neuroendocrine axis occurs in the early hours of myocardial infarction. It has been suggested that this acute neuroendocrine response might be attenuated by early therapeutic reperfusion. To test this hypothesis we measured plasma concentrations of atrial natriuretic factor (ANF), renin, adrenaline (ADR) and noradrenaline (NADR) on admission and at 1 h and 4 h in 32 patients undergoing streptokinase treatment within 6 h of myocardial infarction. Fractional changes (FC) in hormone levels were calculated: e.g. ANFO-ANF4/ANFO. Resolution of ST segment elevation at 4 h was the primary measure of reperfusion. Sixteen patients showed ST segment resolution. There was no difference in hormone levels at baseline between reperfused and non-reperfused patients. Fractional changes in ANF, renin and ADR were similar in both groups. NADR fell from admission to 4 h in reperfused patients but rose in non-reperfused (FC 0.28 vs -0.10; P = 0.054). There was no difference in the changes in pulse rate or blood pressure from admission to 4 h between the two groups. Thus there is no evidence that early reperfusion acutely alters the release of ANF, renin or ADR to myocardial infarction. Although plasma NADR tended to fall acutely in reperfused patients this was not accompanied by other markers of sympathetic withdrawal.

  14. Early molecular changes in Alzheimer disease: can we catch the disease in its presymptomatic phase?

    PubMed

    Wirz, Kerstin T S; Keitel, Stella; Swaab, Dick F; Verhaagen, Joost; Bossers, Koen

    2014-01-01

    Alzheimer disease (AD) is the most common form of dementia and characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles consisting of hyperphosphorylated tau, atrophy, and progressive neurodegeneration. While the familial, early onset form of AD is known to be caused by specific mutations in genes encoding presenilin 1, presenilin 2, or amyloid-β protein precursor, the underlying mechanisms leading to the development of sporadic AD are still not known. The major risk factors are, however, aging and APOE ε4. Here we review the latest evidence for the involvement of malfunctioning insulin signaling, dysfunction of mitochondria-associated membranes, cerebrovascular changes, increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic dysfunction in early stages of AD. We focus on whether the changes in these processes precede or succeed the earliest symptoms in AD patients, i.e., minimal cognitive impairment. Since changes in Aβ processing are probably a key event in AD we also highlight the relationship of the above mentioned processes with the formation, secretion, aggregation, and toxicity of Aβ. Based on our literature findings we propose a model in which insulin dysfunction, pathological cerebrovascular changes, dysfunction of mitochondria-associated membranes, and/or synaptic changes are likely to interact with each other, thereby initiating and facilitating the development of AD pathology by accelerating the production and deposition of Aβ. Increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic loss follow these events, but still occur very early in AD.

  15. 77 FR 58301 - Final Requirements-Race to the Top-Early Learning Challenge; Phase 2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ... Register on June 20, 2012 (77 FR 36958). The NPR contained background information and our reasons for... applications, published in the Federal Register on August 26, 2011 (76 FR 53564), apply to the Phase 2 RTT-ELC... 2011 RTT-ELC competition, published in the Federal Register on August 26, 2011 (76 FR 53564) and...

  16. Phase-based x-ray scattering—A possible method to detect cancer cells in a very early stage

    SciTech Connect

    Feye-Treimer, U. Treimer, W.

    2014-05-15

    Purpose: This theoretical work contains a detailed investigation of the potential and sensitivity of phase-based x-ray scattering for cancer detection in biopsies if cancer is in a very early stage of development. Methods: Cancer cells in their early stage of development differ from healthy ones mainly due to their faster growing cell nuclei and the enlargement of their densities. This growth is accompanied by an altered nucleus–plasma relation for the benefit of the cell nuclei, that changes the physical properties especially the index of refraction of the cell and the one of the cell nuclei. Interaction of radiation with matter is known to be highly sensitive to small changes of the index of refraction of matter; therefore a detection of such changes of volume and density of cell nuclei by means of high angular resolved phase-based scattering of x rays might provide a technique to distinguish malignant cells from healthy ones ifthe cell–cell nucleus system is considered as a coherent phase shifting object. Then one can observe from a thin biopsy which represents a monolayer of cells (no multiple scattering) that phase-based x-ray scattering curves from healthy cells differ from those of cancer cells in their early stage of development. Results: Detailed calculations of x-ray scattering patterns from healthy and cancer cell nuclei yield graphs and numbers with which one can distinguish healthy cells from cancer ones, taking into account that both kinds of cells occur in a tissue within a range of size and density. One important result is the role and the influence of the (lateral) coherence width of the radiation on the scattering curves and the sensitivity of phase-based scattering for cancer detection. A major result is that a larger coherence width yields a larger sensitivity for cancer detection. Further import results are calculated limits for critical sizes and densities of cell nuclei in order to attribute the investigated tissue to be healthy or

  17. Early and protective microglial activation in Alzheimer's disease: a prospective study using 18F-DPA-714 PET imaging.

    PubMed

    Hamelin, Lorraine; Lagarde, Julien; Dorothée, Guillaume; Leroy, Claire; Labit, Mickael; Comley, Robert A; de Souza, Leonardo Cruz; Corne, Helene; Dauphinot, Luce; Bertoux, Maxime; Dubois, Bruno; Gervais, Philippe; Colliot, Olivier; Potier, Marie Claude; Bottlaender, Michel; Sarazin, Marie

    2016-04-01

    scores and grey matter volume, as well as with Pittsburgh compound B binding. Amyloidosis controls displayed higher translocator protein-binding than controls, especially in the frontal cortex. We found higher translocator protein-binding in slow decliners than fast decliners, with no difference in Pittsburgh compound B binding. Microglial activation appears at the prodromal and possibly at the preclinical stage of Alzheimer's disease, and seems to play a protective role in the clinical progression of the disease at these early stages. The extent of microglial activation appears to differ between patients, and could explain the overlap in translocator protein binding values between patients with Alzheimer's disease and amyloidosis controls.

  18. Discrete spin structures and commuting projector models for two-dimensional fermionic symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Tarantino, Nicolas; Fidkowski, Lukasz

    2016-09-01

    We construct exactly solved commuting projector Hamiltonian lattice models for all known (2+1)-dimensional (2+1D) fermionic symmetry protected topological phases (SPTs) with on-site unitary symmetry group Gf=G ×Z2f , where G is finite and Z2f is the fermion parity symmetry. In particular, our models transcend the class of group supercohomology models, which realize some, but not all, fermionic SPTs in 2+1D. A natural ingredient in our construction is a discrete form of the spin structure of the 2D spatial surface M on which our model is defined, namely a "Kasteleyn" orientation of a certain graph associated with the lattice. As a special case, our construction yields commuting projector models for all eight members of the Z8 classification of 2D fermionic SPTs with G =Z2 .

  19. Topiramate attenuates early brain injury following subarachnoid haemorrhage in rats via duplex protection against inflammation and neuronal cell death.

    PubMed

    Tian, Yong; Guo, Song-Xue; Li, Jian-Ru; Du, Hang-Gen; Wang, Chao-Hui; Zhang, Jian-Min; Wu, Qun

    2015-10-01

    Early brain injury (EBI) following aneurysmal subarachnoid haemorrhage (SAH) insults contributes to the poor prognosis and high mortality observed in SAH patients. Topiramate (TPM) is a novel, broad-spectrum, antiepileptic drug with a reported protective effect against several brain injuries. The current study aimed to investigate the potential of TPM for neuroprotection against EBI after SAH and the possible dose-dependency of this effect. An endovascular perforation SAH model was established in rats, and TPM was administered by intraperitoneal injection after surgery at three different doses (20mg/kg, 40mg/kg, and 80mg/kg). The animals' neurological scores and brain water content were evaluated, and ELISA, Western blotting and immunostaining assays were conducted to assess the effect of TPM. The results revealed that TPM lowers the elevated levels of myeloperoxidase and proinflammatory mediators observed after SAH in a dose-related fashion, and the nuclear factor-kappa B (NF-κB) signalling pathway is the target of neuroinflammation regulation. In addition, TPM ameliorated SAH-induced cortical neuronal apoptosis by influencing Bax, Bcl-2 and cleaved caspase-3 protein expression, and the effect of TPM was enhanced in a dose-dependent manner. Various dosages of TPM also upregulated the protein expression of the γ-aminobutyric acid (GABA)-ergic signalling molecules, GABAA receptor (GABAAR) α1, GABAAR γ2, and K(+)-Cl(-) co-transporter 2 (KCC2) together and downregulated Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1) expression. Thus, TPM may be an effective neuroprotectant in EBI after SAH by regulating neuroinflammation and neuronal cell death.

  20. Topiramate attenuates early brain injury following subarachnoid haemorrhage in rats via duplex protection against inflammation and neuronal cell death.

    PubMed

    Tian, Yong; Guo, Song-Xue; Li, Jian-Ru; Du, Hang-Gen; Wang, Chao-Hui; Zhang, Jian-Min; Wu, Qun

    2015-10-01

    Early brain injury (EBI) following aneurysmal subarachnoid haemorrhage (SAH) insults contributes to the poor prognosis and high mortality observed in SAH patients. Topiramate (TPM) is a novel, broad-spectrum, antiepileptic drug with a reported protective effect against several brain injuries. The current study aimed to investigate the potential of TPM for neuroprotection against EBI after SAH and the possible dose-dependency of this effect. An endovascular perforation SAH model was established in rats, and TPM was administered by intraperitoneal injection after surgery at three different doses (20mg/kg, 40mg/kg, and 80mg/kg). The animals' neurological scores and brain water content were evaluated, and ELISA, Western blotting and immunostaining assays were conducted to assess the effect of TPM. The results revealed that TPM lowers the elevated levels of myeloperoxidase and proinflammatory mediators observed after SAH in a dose-related fashion, and the nuclear factor-kappa B (NF-κB) signalling pathway is the target of neuroinflammation regulation. In addition, TPM ameliorated SAH-induced cortical neuronal apoptosis by influencing Bax, Bcl-2 and cleaved caspase-3 protein expression, and the effect of TPM was enhanced in a dose-dependent manner. Various dosages of TPM also upregulated the protein expression of the γ-aminobutyric acid (GABA)-ergic signalling molecules, GABAA receptor (GABAAR) α1, GABAAR γ2, and K(+)-Cl(-) co-transporter 2 (KCC2) together and downregulated Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1) expression. Thus, TPM may be an effective neuroprotectant in EBI after SAH by regulating neuroinflammation and neuronal cell death. PMID:26086367

  1. Protective role of propofol on the kidney during early unilateral ureteral obstruction through inhibition of epithelial-mesenchymal transition

    PubMed Central

    Song, Li; Shi, Sen; Jiang, Wei; Liu, Xueru; He, Yanzheng

    2016-01-01

    Unilateral ureteral obstruction (UUO) induces functional and pathological changes in the obstructed kidney. Inducible nitric oxide synthase (iNOS) expression is high inearly UUO mouse kidney, which is accompanied with fibrosis. Propofol has preventive effects against renal injury by downregulating iNOS expression in UUO mouse models. However, the role of propofol in kidney fibrosis progression has not been reported. We explored the therapeutic potential and possible mechanisms of action of propofol in kidney fibrosis using a UUO mouse model. Herein, mice anesthetized with propofol or sevoflurane underwent UUO induction. Serum and kidney sections were collected 5 and 28 days post-operation for histological, morphometric, immunofluorescence, microRNA analyses; quantitative PCR and western blotting. In vivo, the effect and mechanism of propofol on epithelial-mesenchymal transition (EMT), transforming growth factor β (TGF-β) signaling and miR-155 levels were detected in cultured HK-2 cells. We found that propofol significantly suppressed UUO-induced kidney fibrosis, which was associated with TGF-β/Smad3 signaling, EMT, and iNOS-NO production. MiR-155 levels were higher in UUO mouse kidneys; compared with sevoflurane, propofol suppressed miR-155 levels. However, in late UUO, propofol could not prevent kidney fibrosis or suppress EMT and miR-155. The in vitro results showed that propofol suppressed TGF-β1-induced EMT by regulating miR-155 levels. As a conclusion, in early UUO mice, propofol may inhibit TGF-β1 expression and NO-iNOS production, consequently inhibiting EMT and kidney fibrosis by regulating miR-155 levels, and might be a new protective agent against kidney injury during surgery and in therapy to prevent kidney fibrosis. PMID:27158339

  2. Proline accumulation protects Saccharomyces cerevisiae cells in stationary phase from ethanol stress by reducing reactive oxygen species levels.

    PubMed

    Takagi, Hiroshi; Taguchi, Junpei; Kaino, Tomohiro

    2016-08-01

    During fermentation processes, Saccharomyces cerevisiae cells are exposed to multiple stresses, including a high concentration of ethanol that represents toxicity through intracellular reactive oxygen species (ROS) generation. We previously reported that proline protected yeast cells from damage caused by various stresses, such as freezing and ethanol. As an anti-oxidant, proline is suggested to scavenge intracellular ROS. In this study, we examined the role of intracellular proline during ethanol treatment in S. cerevisiae strains that accumulate different concentrations of proline. When cultured in YPD medium, there was a significant accumulation of proline in the put1 mutant strain, which is deficient in proline oxidase, in the stationary phase. Expression of the mutant PRO1 gene, which encodes the γ-glutamyl kinase variant (Asp154Asn or Ile150Thr) with desensitization to feedback inhibition by proline in the put1 mutant strain, showed a prominent increase in proline content as compared with that of the wild-type strain. The oxidation level was clearly increased in wild-type cells after exposure to ethanol, indicating that the generation of ROS occurred. Interestingly, proline accumulation significantly reduces the ROS level and increases the survival rate of yeast cells in the stationary phase under ethanol stress conditions. However, there was not a clear correlation between proline content and survival rate in yeast cells. An appropriate level of intracellular proline in yeast might be important for its stress-protective effect. Hence, the engineering of proline metabolism could be promising for breeding stress-tolerant industrial yeast strains. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26833688

  3. Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer.

    PubMed

    Panis, Carolina; Pizzatti, Luciana; Bufalo, Aedra Carla; Herrera, Ana Cristina; Victorino, Vanessa Jacob; Cecchini, Rubens; Abdelhay, Eliana

    2016-03-01

    Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1β, IL-12, TGF-β1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment.

  4. Stress and stressors of the early phases of the Persian Gulf War

    PubMed Central

    Gifford, Robert K; Ursano, Robert J; Stuart, John A; Engel, Charles C

    2006-01-01

    Soldiers who deployed to Saudi Arabia in support of Operation Desert Shield were exposed to a wide variety of stressors. These stressors from the pre-combat phase of the deployment undoubtedly affect the current health of Gulf War veterans, but the exact mechanisms and linkages are not known. This article examines the nature of those stressors and possible effects on later health of veterans. PMID:16687263

  5. Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase.

    PubMed

    van Overbeek, Megan; de Lange, Titia

    2006-07-11

    Human chromosome ends are protected by shelterin, an abundant six-subunit protein complex that binds specifically to the telomeric-repeat sequences, regulates telomere length, and ensures that chromosome ends do not elicit a DNA-damage response (reviewed in). Using mass spectrometry of proteins associated with the shelterin component Rap1, we identified an SMN1/PSO2 nuclease family member that is closely related to Artemis. We refer to this protein as Apollo and report that Apollo has the ability to localize to telomeres through an interaction with the shelterin component TRF2. Although its low abundance at telomeres indicates that Apollo is not a core component of shelterin, Apollo knockdown with RNAi resulted in senescence and the activation of a DNA-damage signal at telomeres as evidenced by telomere-dysfunction-induced foci (TIFs). The TIFs occurred primarily in S phase, suggesting that Apollo contributes to a processing step associated with the replication of chromosome ends. Furthermore, some of the metaphase chromosomes showed two telomeric signals at single-chromatid ends, suggesting an aberrant telomere structure. We propose that the Artemis-like nuclease Apollo is a shelterin accessory factor required for the protection of telomeres during or after their replication.

  6. Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase.

    PubMed

    Buganim, Yosef; Faddah, Dina A; Cheng, Albert W; Itskovich, Elena; Markoulaki, Styliani; Ganz, Kibibi; Klemm, Sandy L; van Oudenaarden, Alexander; Jaenisch, Rudolf

    2012-09-14

    During cellular reprogramming, only a small fraction of cells become induced pluripotent stem cells (iPSCs). Previous analyses of gene expression during reprogramming were based on populations of cells, impeding single-cell level identification of reprogramming events. We utilized two gene expression technologies to profile 48 genes in single cells at various stages during the reprogramming process. Analysis of early stages revealed considerable variation in gene expression between cells in contrast to late stages. Expression of Esrrb, Utf1, Lin28, and Dppa2 is a better predictor for cells to progress into iPSCs than expression of the previously suggested reprogramming markers Fbxo15, Fgf4, and Oct4. Stochastic gene expression early in reprogramming is followed by a late hierarchical phase with Sox2 being the upstream factor in a gene expression hierarchy. Finally, downstream factors derived from the late phase, which do not include Oct4, Sox2, Klf4, c-Myc, and Nanog, can activate the pluripotency circuitry. PMID:22980981

  7. Single-cell gene expression analyses of cellular reprogramming reveal a stochastic early and hierarchic late phase

    PubMed Central

    Buganim, Yosef; Faddah, Dina A.; Cheng, Albert W.; Itskovich, Elena; Markoulaki, Styliani; Ganz, Kibibi; Klemm, Sandy L.; van Oudenaarden, Alexander; Jaenisch, Rudolf

    2012-01-01

    During cellular reprogramming only a small fraction of cells become induced pluripotent stem cells (iPSCs). Previous analyses of gene expression during reprogramming were based on populations of cells, impeding single-cell level identification of reprogramming events. We utilized two gene expression technologies to profile 48 genes in single cells at various stages during the reprogramming process. Analysis of early stages revealed considerable variation in gene expression between cells in contrast to late stages. Expression of Esrrb, Utf1, Lin28, and Dppa2 is a better predictor for cells to progress into iPSCs than expression of Fbxo15, Fgf4, and Oct4 previously suggested to be reprogramming markers. Stochastic gene expression early in reprogramming is followed by a late hierarchical phase with Sox2 being the upstream factor in a gene expression hierarchy. Finally, downstream factors derived from the late phase, which do not include Oct4, Sox2, Klf4, c-Myc and Nanog, can activate the pluripotency circuitry. PMID:22980981

  8. [Increased urinary sodium excretion in the early phase of aneurysmal subarachnoid hemorrhage as a predictor of cerebral salt wasting syndrome].

    PubMed

    Nakagawa, Ichiro; Kurokawa, Shinichiro; Takayama, Katsutoshi; Wada, Takeshi; Nakase, Hiroyuki

    2009-12-01

    Cerebral salt wasting syndrome (CSWS) in patients with aneurysmal subarachnoid hemorrhage (SAH) is considered to correlate with delayed ischemic neurological deficits (DIND) induced by cerebral vasospasm; however, its exact mechanism is still not well-known. The purpose of the present study is to evaluate the relationship between hyponatremia caused by CSWS and the increase of the urinary sodium excretion in early phase following SAH. Fifty-four patients with SAH were divided into 2 groups, normonatremia group and hyponatremia group which suffered hyponatremia after SAH. The hyponatremia group comprise 14 patients (26%) in whom the hyponatremia developed of the SAH. In this group, the serum level of sodium significantly decreased 7 days after SAH and then gradually normalised. Further, excretion of sodium in the urine tended to increase 3 days after SAH and significantly increased 7 days after SAH. In conclusion, the increased urinary sodium excretion in the early phase of SAH would serve as a predictive factor for CSWS after SAH. We consider that it is important to start sodium and fluid supplementation and inhibit natriuresis by fludrocortisone acetate administration before hyponatremia occurs in order to prevention delayed ischemic neurological deficits in SAH patients.

  9. Hyperhomocysteinemia, a Biochemical Tool for Differentiating Ischemic and Nonischemic Central Retinal Vein Occlusion during the Early Acute Phase

    PubMed Central

    Mukherjee, Somnath; Ghosh, Sambuddha; Mukherjee, Suman; Dutta, Jayanta; Datta, Himadri; Das, Harendra Nath

    2015-01-01

    Purpose The purpose of the study was to differentiate ischemic central retinal vein occlusion (CRVO) from nonischemic CRVO during the early acute phase using plasma homocysteine as a biochemical marker. Methods Fasting plasma homocysteine, serum vitamin B12, and folate levels were measured in 108 consecutive unilateral elderly adult (age >50 years) ischemic CRVO patients in the absence of local and systemic disease and compared with a total of 144 age and sex matched nonischemic CRVO patients and 120 age and sex matched healthy control subjects. Results Homocysteine level was significantly increased in the patients with ischemic CRVO in comparison with nonischemic CRVO patients (p = 0.009) and also in comparison with control subjects (p < 0.001). Analysis also showed that hyperhomocysteinemia was associated with increased incidence of ischemic CRVO (odds ratio, 18) than that for nonischemic CRVO (odds ratio, 4.5). Serum vitamin B12 and folate levels were significantly lower (p < 0.001) in CRVO patients compared to the control but were not significantly different between nonischemic and ischemic CRVO patients (p > 0.1). Conclusions Hyperhomocysteinemia can be regarded as useful in differentiating nonischemic and ischemic CRVO during the early acute phase in absence of local and systemic disease in the elderly adult (age >50 years) population. PMID:25829824

  10. Design and conduct of early-phase radiotherapy trials with targeted therapeutics: lessons from the PRAVO experience.

    PubMed

    Ree, Anne Hansen; Hollywood, Donal

    2013-07-01

    New strategies to facilitate the improvement of physical and integrated biological optimization of high-precision treatment protocols are an important priority for modern radiation oncology. From a clinical perspective, as knowledge accumulates from molecular radiobiology, there is a complex and exciting opportunity to investigate novel approaches to rational patient treatment stratification based on actionable tumor targets, together with the appropriate design of next-generation early-phase radiotherapy trials utilizing targeted therapeutics, to formally evaluate relevant clinical and biomarker endpoints. A unique aspect in the development pathway of systemic agents with presumed radiosensitizing activity will also be the need for special attention on patient eligibility and the rigorous definition of radiation dose-volume relationships and potential dose-limiting toxicities. Based on recent experience from systematically investigating histone deacetylase inhibitors as radiosensitizing agents, from initial studies in preclinical tumor models through the conduct of a phase I clinical study to evaluate tumor activity of the targeted agent as well as patient safety and tumor response to the combined treatment modality, this communication will summarize principles relating to early clinical evaluation of combining radiotherapy and targeted therapeutics.

  11. Overexpression of α1-protease Inhibitor and Galectin-1 in Radiation-induced Early Phase of Pulmonary Fibrosis

    PubMed Central

    Im, Hee-Soon; Kim, Hyung-Doo; Song, Jie-Young; Han, Youngsoo; Lee, Do-Youn; Kim, Chan-Wha

    2006-01-01

    Purpose Radiation-induced pulmonary fibrosis (RIF) is a significant complication of radiotherapy for lung cancer. Despite the large number of studies, the molecular mechanisms of RIF are poorly understood. Therefore, the complex protein expression pattern in RIF was characterized by identifying the proteins with an altered expression level after thorax irradiation using two-dimensional electrophoresis (2-DE) and mass spectrometry. Materials and Methods A mouse model of RIF was used to examine the alteration of the lung proteome because of availability of murine data related to human cases and the abundance of murine fibrotic lung samples. A mouse model of RIF was induced in radiosensitive C57BL/6 mice. Twenty-one weeks after 25 Gy irradiation, hematoxylin-eosin staining and hydroxyproline assay confirmed the early-phase pulmonary fibrosis. Results Lung samples from the irradiated and age-matched control mice were used to generate 16 high quality 2-DE gels containing approximately 1,000 spots. Of the 31 significantly up- or down-regulated protein spots, 17 were identified by MALDI-TOF/MS. Conclusions Two important upregulated proteins were found, the α1-protease inhibitor and galectin-1, which might be used as potential markers for the early phase of RIF. PMID:19771266

  12. Adenoviral protein VII packages intracellular viral DNA throughout the early phase of infection.

    PubMed Central

    Chatterjee, P K; Vayda, M E; Flint, S J

    1986-01-01

    The proteins associated with parental, adenoviral DNA in productively-infected HeLa cells have been examined both directly and indirectly. HeLa cells infected with 32P-labelled Ad2 were irradiated with u.v. light at various points in the infectious cycle. Following degradation of the DNA, nuclear proteins carrying cross-linked nucleotides, or oligonucleotides, were distinguished from virion phosphoproteins by the resistance of their 32P radioactivity to 1 M NaOH. The major core protein of the virion, protein VII, was found to be associated with viral DNA throughout infection, even when cells were infected at a multiplicity of 0.14. Micrococcal nuclease digestion of intranuclear viral DNA 4 h after infection liberated two nucleoprotein particles containing viral DNA, neither of which co-migrated with HeLa cell mononucleosomes. These results indicate that core protein VII remains associated with parental adenoviral DNA during productive infections. The observation that protein VII can be cross-linked to DNA in cells infected at very low multiplicity, together with the results of a comparison of proteins cross-linkable to viral DNA in cells infected by wild-type virus and a non-infectious mutant containing the precursor to protein VII, suggest that nucleoproteins comprising viral DNA and protein VII must be the templates for expression of pre-early and early viral genes. Images Fig. 1. Fig. 3. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:3743550

  13. CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation

    PubMed Central

    López-Pacheco, C.; Soldevila, G.; Du Pont, G.; Hernández-Pando, R.

    2016-01-01

    Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes. Moreover, in challenged CCR9-deficient mice, cell recruitment was impaired at peribronchial and perivenular levels. OVA-administration in CCR9-deficient mice leads to a less inflammatory cell recruitment, which modifies the expression of IL-10, CCL11, and CCL25 at 24 hours after OVA challenge. In contrast, the secretion of IL-4 and IL-5 was not affected in CCR9-deficient mice compared to WT mice. These results demonstrate for the first time that CCR9 and CCL25 expressions are induced in the early stages of airway inflammation and they have an important role modulating eosinophils and lymphocytes recruitment at the first stages of inflammatory process, suggesting that they might be a potential target to regulate inflammation in asthma. PMID:27795621

  14. Solid Waste Processing: An Essential Technology for the Early Phases of Mars Exploration and Colonization

    NASA Technical Reports Server (NTRS)

    Wignarajah, Kanapathipillai; Pisharody, Suresh; Fisher, John; Flynn, Michael; Kliss, Mark (Technical Monitor)

    1997-01-01

    Terraforming of Mars is the long-term goal of colonization of Mars. However, this process is likely to be a very slow process and conservative estimates involving a synergic, technocentric approach estimate that it may take around 10,000 years before the planet can be parallel to that of Earth and where humans can live in open systems. Hence, any early missions will require the presence of a closed life support system where all wastes, both solids and liquids, will need to be recycled or where all consumables will need to be supplied. The economics of both are often a matter of speculation and conjecture, but some attempt is made here to evaluate the choice. If a choice is made to completely resupply and eject the waste mass, a number of unknown issues are at hand. On the other hand, processing of the wastes, will enable predictability and reliability of the ecosystem. Solid wastes though smaller in volume and mass than the liquid wastes contains more than 90% of the essential elements required by humans and plants. Further, if left unprocessed they present a serious risk to human health. This paper presents the use of well established technology in processing solid wastes, ensuring that the biogeochemical cycles of ecosystems are maintained, reliability of the closed life support system maintained and the establishment of the early processes necessary for the permanent presence of humans on Mars.

  15. Hypokalemia during the early phase of refeeding in patients with cancer

    PubMed Central

    Grasso, Simona; Ferro, Yvelise; Migliaccio, Valeria; Mazza, Elisa; Rotundo, Stefania; Pujia, Arturo; Montalcini, Tiziana

    2013-01-01

    OBJECTIVE: Refeeding syndrome occurs in patients with severe malnutrition when refeeding begins after a long period of starvation. This syndrome increases the risk of clinical complications and mortality. Hypophosphatemia is considered the primary characteristic of the syndrome. The aim of our study was to investigate the presence of other electrolyte alterations in patients with cancer during the early stage of refeeding. METHODS: In this observational study, we enrolled 34 patients with cancer of the upper aerodigestive tract receiving upfront radiotherapy who were also enrolled in a nutrition program. A caloric intake assessment, anthropometric measurements and biochemical laboratory tests were performed. RESULTS: Significant weight loss (∼20%) was found in these patients. In the patients receiving artificial nutrition, we found lower levels of potassium and total protein compared with those who were fed orally (p = 0.03 for potassium and 0.02 for protein, respectively). Patients on enteral tube feeding had a higher caloric intake compared with those who were fed orally (25±5 kcal/kg/day vs. 10±2 kcal/kg/day). CONCLUSION: Hypokalemia, like hypophosphatemia, could be a complication associated with refeeding in patients with cancer. Hypokalemia was present in the early stages of high-calorie refeeding. PMID:24270952

  16. Effects of intensive gait-oriented physiotherapy during early acute phase of stroke.

    PubMed

    Peurala, Sinikka H; Airaksinen, Olavi; Jäkälä, Pekka; Tarkka, Ina M; Sivenius, Juhani

    2007-01-01

    We assessed the effects and strenuousness of intensive gait-oriented inpatient rehabilitation initiated very early after stroke. Therapy content and interrater reliability of the assessments were also analyzed. Of 22 patients, 19 (average 8.0 d poststroke) completed the study. Before rehabilitation, 13 patients were unable to walk or needed two assistants to walk and 6 patients needed one assistant. Patients spent a daily maximum of 1 h therapy time to obtain 20 min of walking. Additional physiotherapy was also provided during the 3 wk therapy period. Seven structured motor tests were recorded before and after rehabilitation and at 6 months postrehabilitation, and perceived exertion was followed during physiotherapy. After rehabilitation, 16 patients could walk unassisted and 3 needed one assistant to walk. Mean +/- standard deviation exercise walking distance was 10,784 +/- 4,446 m and exercise was ranked as slightly strenuous. After 3 wk, the patients' 10 m walking time, ankle spasticity, lower-limb muscle force, and motor scale scores improved (p < 0.05). The early intensive rehabilitation was well tolerated and only three patients dropped out. Improved motor abilities were seen in all stroke patients.

  17. Review of hardware cost estimation methods, models and tools applied to early phases of space mission planning

    NASA Astrophysics Data System (ADS)

    Trivailo, O.; Sippel, M.; Şekercioğlu, Y. A.

    2012-08-01

    The primary purpose of this paper is to review currently existing cost estimation methods, models, tools and resources applicable to the space sector. While key space sector methods are outlined, a specific focus is placed on hardware cost estimation on a system level, particularly for early mission phases during which specifications and requirements are not yet crystallised, and information is limited. For the space industry, cost engineering within the systems engineering framework is an integral discipline. The cost of any space program now constitutes a stringent design criterion, which must be considered and carefully controlled during the entire program life cycle. A first step to any program budget is a representative cost estimate which usually hinges on a particular estimation approach, or methodology. Therefore appropriate selection of specific cost models, methods and tools is paramount, a difficult task given the highly variable nature, scope as well as scientific and technical requirements applicable to each program. Numerous methods, models and tools exist. However new ways are needed to address very early, pre-Phase 0 cost estimation during the initial program research and establishment phase when system specifications are limited, but the available research budget needs to be established and defined. Due to their specificity, for vehicles such as reusable launchers with a manned capability, a lack of historical data implies that using either the classic heuristic approach such as parametric cost estimation based on underlying CERs, or the analogy approach, is therefore, by definition, limited. This review identifies prominent cost estimation models applied to the space sector, and their underlying cost driving parameters and factors. Strengths, weaknesses, and suitability to specific mission types and classes are also highlighted. Current approaches which strategically amalgamate various cost estimation strategies both for formulation and validation

  18. The stationary-phase morphogene bolA from Escherichia coli is induced by stress during early stages of growth.

    PubMed

    Santos, J M; Freire, P; Vicente, M; Arraiano, C M

    1999-05-01

    The Escherichia coli morphogene bolA causes round morphology when overexpressed. The expression of bolA is mainly regulated by a sigmas-dependent gearbox promoter bolA1p. Such regulation results in increased relative levels of expression at slow growth rates, as seen with those attained at the onset of stationary phase. We demonstrate that bolA1p is also induced during early logarithmic growth in response to several forms of stress, and that this induction can be partially sigmas independent. Sudden carbon starvation results in a 17-fold increase in mRNA levels derived from bolA1p 1 h after stress imposition. Increased osmolarity results in a more than 20-fold increase after the same period. Considerable increases in bolA1p mRNA levels were also detected as a result of heat shock, acidic stress and oxidative stress, which has been shown to inhibit sigmas translation. The orders of magnitude of bolA1p induction in log phase due to sudden starvation, osmotic shock and oxidative stress surpass the levels reached in stationary phase. Under sudden carbon starvation and osmotic shock, the cells changed their morphology, resembling those cells in which bolA is overexpressed in stationary phase. Increased expression and morphological changes due to sudden carbon starvation and osmotic shock still occur when sigmaS is not present in a rpoS- background. The results show that expression of bolA is not confined to stationary phase, but it can also play an important role in general stress response. We propose that bolA1p stress induction overrides the normal regulation imposed by growth rate, which is strictly the result of sigmaS-directed transcription.

  19. Does a phase transition in the early universe produce the conditions needed for inflation\\?

    NASA Astrophysics Data System (ADS)

    Mazenko, Gene F.; Unruh, William G.; Wald, Robert M.

    1985-01-01

    In the standard ``new inflationary scenario,'' it is assumed that when the Higgs field φ is cooled below its phase-transition temperature Tc it is found in a metastable state which has negligible kinetic and spatial-derivative energy but has large, positive potential energy V0. Hence, in this picture, the stress-energy tensor of φ is of the form Tab=-V0gab and remains of this form until the state becomes unstable and ``rolls down the hill'' to its true minimum at φ=φc. With this stress-energy tensor Einstein's equation for a Robertson-Walker model predicts expansion of the universe on an exponential time scale, i.e., inflation. We argue here that, at least in many possible models this standard picture of the behavior of φ as it is cooled to Tc and below is wrong. Rather than be ``supercooled'' to a state with φ~=0 locally, the field should rapidly form domains with φ near +/-φc. The dynamics of the phase transition is governed by the growth and coalescence of these domains, not by a ``roll down the hill'' of the spatially averaged value of φ. Furthermore, the stress-energy tensor of φ does not take the form needed to produce inflation. Our arguments are based mainly on physical reasoning, but they are supported by the known behavior of certain condensed-matter systems. We believe that our description of dynamical behavior near the phase transition is applicable to a wide class of field-theory models considered in inflation-in particular, to models where φ is not coupled to other fields and Coleman-Weinberg gauge-coupled models with g2~1-although precise criteria for the applicability of our arguments have not been obtained.

  20. Early signs, diagnosis and therapeutics of the prodromal phase of schizophrenia and related psychotic disorders

    PubMed Central

    Larson, Molly K; Walker, Elaine F; Compton, Michael T

    2010-01-01

    During recent decades, interest in the prevention of mental illnesses has increased. Improved diagnostic tools, the advent of atypical antipsychotic medications and the development of phase-specific psychosocial treatments have made intervention research in people at ultra-high risk for developing schizophrenia or a related psychotic disorder possible. Preliminary data suggest that low doses of atypical antipsychotic medications augmented by psychosocial treatments may delay the onset of psychosis in some individuals. Findings support further research for the establishment of best-practice standards. PMID:20662758

  1. Deoxycytidine monophosphate deaminase in Acetabularia: properties and regulation in the early generative phase.

    PubMed

    Bannwarth, H; Ikehara, N; Schweiger, H G

    1982-06-01

    The occurrence of a dCMP deaminase in Acetabularia mediterranea has been demonstrated. The enzyme which is found in a particulate fraction is substantially stimulated by the addition of dCTP. The activity of the enzyme is increased at the beginning of the generative phase in nucleate as well as in anucleate cells. This regulation is due to de novo synthesis of the enzyme. By means of inhibitor studies, it has been shown that the enzyme is translated on 70S ribosomes of and coced for in cell organelles.

  2. Differential roles of p38-MAPK and JNKs in mediating early protection or apoptosis in the hyperthermic perfused amphibian heart.

    PubMed

    Gaitanaki, Catherine; Mastri, Michalis; Aggeli, Ioanna-Katerina S; Beis, Isidoros

    2008-08-01

    In the present study the activation of p38 mitogen-activated protein kinase (p38-MAPK) and c-Jun N-terminal kinases (JNKs) by hyperthermia was investigated in the isolated perfused Rana ridibunda heart. Hyperthermia (42 degrees C) was found to profoundly stimulate p38-MAPK phosphorylation within 0.5 h, with maximal values being attained at 1 h [4.503(+/-0.577)-fold relative to control, P<0.01]. JNKs were also activated under these conditions in a sustained manner for at least 4 h [2.641(+/-0.217)-fold relative to control, P<0.01]. Regarding their substrates, heat shock protein 27 (Hsp27) was maximally phosphorylated at 1 h [2.261(+/-0.327)-fold relative to control, P<0.01] and c-Jun at a later phase [3 h: 5.367(+/-0.081)-fold relative to control, P<0.001]. Hyperthermia-induced p38-MAPK activation was found to be dependent on the Na+/H+ exchanger 1 (NHE1) and was also suppressed by catalase (Cat) and superoxide dismutase (SOD), implicating the generation of reactive oxygen species (ROS). ROS were also implicated in the activation of JNKs by hyperthermia, with the Na+/K+-ATPase acting as a mediator of this effect at an early stage and the NHE1 getting involved at a later time point. Finally, JNKs were found to be the principal mediators of the apoptosis induced under hyperthermic conditions, as their inhibition abolished poly(ADP-ribose) polymerase (PARP) cleavage after 4 h at 42 degrees C. Overall, to our knowledge, this study highlights for the first time the variable mediators implicated in the transduction of the hyperthermic signal in the isolated perfused heart of an ectotherm and deciphers a potential salutary effect of p38-MAPK as well as the fundamental role of JNKs in the induced apoptosis.

  3. Translation Repressors, an RNA Helicase, and Developmental Cues Control RNP Phase Transitions during Early Development

    PubMed Central

    Hubstenberger, Arnaud; Noble, Scott L.; Cameron, Cristiana; Evans, Thomas C.

    2013-01-01

    SUMMARY Like membranous organelles, large-scale coassembly of macromolecules can organize functions in cells. Ribonucleoproteins (RNPs) can form liquid or solid aggregates, but control and consequences of these RNP states in living, developing tissue are poorly understood. Here, we show that regulated RNP factor interactions drive transitions among diffuse, semiliquid, or solid states to modulate RNP sorting and exchange in the Caenorhabditis elegans oocyte cytoplasm. Translation repressors induce an intrinsic capacity of RNP components to coassemble into either large semiliquids or solid lattices, whereas a conserved RNA helicase prevents polymerization into nondynamic solids. Developmental cues dramatically alter both fluidity and sorting within large RNP assemblies, inducing a transition from RNP segregation in quiescent oocytes to dynamic exchange in the early embryo. Therefore, large-scale organization of gene expression extends to the cytoplasm, where regulation of supramolecular states imparts specific patterns of RNP dynamics. PMID:24176641

  4. Nanodomains in Early and Later Phases of FcεRI Signaling

    PubMed Central

    Holowka, David; Baird, Barbara

    2014-01-01

    Our long term efforts to elucidate receptor-mediated signaling in immune cells, particularly transmembrane signaling initiated by the receptor (FcεRI) for immunoglobulin E (IgE) in mast cells, led us unavoidably to contemplate the role of the heterogeneous plasma membrane. Our early investigations with fluorescence microscopy revealed co-redistribution of certain lipids and signaling components with antigen-crosslinked IgE-FcεRI and pointed to participation of ordered membrane domains in the signaling process. With a focus on this function, we have worked along with others to develop diverse and increasingly sophisticated tools to analyze the complexity of membrane structure that facilitates regulation and targeting of signaling events. This essay describes how initial membrane interactions of clustered IgE-FcεRI lead to downstream cellular responses and how biochemical information integrated with nanoscale resolution spectroscopy and imaging is providing mechanistic insights at the level of molecular complexes. PMID:25658351

  5. Studies of high temperature ternary phases in mixed-metal-rich early transition metal sulfide and phosphide systems

    SciTech Connect

    Marking, G.A.

    1994-01-04

    Investigations of ternary mixed early transition metal-rich sulfide and phosphide systems resulted in the discovery of new structures and new phases. A new series of Zr and Hf - group V transition metal - sulfur K-phases was synthesized and crystallographically characterized. When the group V transition metal was Nb or Ta, the unit cell volume was larger than any previously reported K-phase. The presence of adventitious oxygen was determined in two K-phases through a combination of neutron scattering and X-ray diffraction experiments. A compound Hf{sub 10}Ta{sub 3}S{sub 3} was found to crystallize in a new-structure type similar to the known gamma brasses. This structure is unique in that it is the only reported {open_quotes}stuffed{close_quotes} gamma-brass type structure. The metal components, Hf and Ta, are larger in size and more electropositive than the metals found in normal gamma brasses (e.g. Cu and Zn) and because of the larger metallic radii, sulfur can be incorporated into the structure where it plays an integral role in stabilizing this phase relative to others. X-ray single-crystal, X-ray powder and neutron powder refinements were performed on this structure. A new structure was found in the ternary Nb-Zr-P system which has characteristics in common with many known early transition metal-rich sulfides, selenides, and phosphides. This structure has the simplest known interconnection of the basic building blocks known for this structural class. Anomalous scattering was a powerful tool for differentiating between Zr and Nb when using Mo K{alpha} X-radiation. The compounds ZrNbP and HfNbP formed in the space group Prima with the simple Co{sub 2}Si structure which is among the most common structures found for crystalline solid materials. Solid solution compounds in the Ta-Nb-P, Ta-Zr-P, Nb-Zr-P, Hf-Nb-P, and Hf-Zr-S systems were crystallographically characterized. The structural information corroborated ideas about bonding in metal-rich compounds.

  6. Mechanisms underlying the early phase of spike frequency adaptation in mouse spinal motoneurones.

    PubMed

    Miles, G B; Dai, Y; Brownstone, R M

    2005-07-15

    Spike frequency adaptation (SFA) is a fundamental property of repetitive firing in motoneurones (MNs). Early SFA (occurring over several hundred milliseconds) is thought to be important in the initiation of muscular contraction. To date the mechanisms underlying SFA in spinal MNs remain unclear. In the present study, we used both whole-cell patch-clamp recordings of MNs in lumbar spinal cord slices prepared from motor functionally mature mice and computer modelling of spinal MNs to investigate the mechanisms underlying SFA. Pharmacological blocking agents applied during whole-cell recordings in current-clamp mode demonstrated that the medium AHP conductance (apamin), BK-type Ca2+ -dependent K+ channels (iberiotoxin), voltage-activated Ca2+ channels (CdCl2), M-current (linopirdine) and persistent Na+ currents (riluzole) are all unnecessary for SFA. Measurements of Na+ channel availability including action potential amplitude, action potential threshold and maximum depolarization rate of the action potential were found to correlate with instantaneous firing frequency suggesting that the availability of fast, inactivating Na+ channels is involved in SFA. Characterization of this Na+ conductance in voltage-clamp mode demonstrated that it undergoes slow inactivation with a time course similar to that of SFA. When experimentally measured parameters for the fast, inactivating Na+ conductance (including slow inactivation) were incorporated into a MN model, SFA could be faithfully reproduced. The removal of slow inactivation from this model was sufficient to remove SFA. These data indicate that slow inactivation of the fast, inactivating Na+ conductance is likely to be the key mechanism underlying early SFA in spinal MNs.

  7. Effects of TORC1 Inhibition during the Early and Established Phases of Polycystic Kidney Disease

    PubMed Central

    Ta, Michelle H. T.; Schwensen, Kristina G.; Foster, Sheryl; Korgaonkar, Mayuresh; Ozimek-Kulik, Justyna E.; Phillips, Jacqueline K.; Peduto, Anthony; Rangan, Gopala K.

    2016-01-01

    The disease-modifying effects of target of rapamycin complex 1 (TORC1) inhibitors during different stages of polycystic kidney disease (PKD) are not well defined. In this study, male Lewis Polycystic Kidney Disease (LPK) rats (a genetic ortholog of human NPHP9, phenotypically characterised by diffuse distal nephron cystic growth) and Lewis controls received either vehicle (V) or sirolimus (S, 0.2 mg/kg by intraperitoneal injection 5 days per week) during the early (postnatal weeks 3 to 10) or late stages of disease (weeks 10 to 20). In early-stage disease, sirolimus reduced kidney enlargement (by 63%), slowed the rate of increase in total kidney volume (TKV) in serial MRI by 78.2% (LPK+V: 132.3±59.7 vs. LPK+S: 28.8±12.0% per week) but only partly reduced the percentage renal cyst area (by 19%) and did not affect the decline in endogenous creatinine clearance (CrCl) in LPK rats. In late-stage disease, sirolimus reduced kidney enlargement (by 22%) and the rate of increase in TKV by 71.8% (LPK+V: 13.1±6.6 vs. LPK+S: 3.7±3.7% per week) but the percentage renal cyst area was unaltered, and the CrCl only marginally better. Sirolimus reduced renal TORC1 activation but not TORC2, NF-κB DNA binding activity, CCL2 or TNFα expression, and abnormalities in cilia ultrastructure, hypertension and cardiac disease were also not improved. Thus, the relative treatment efficacy of TORC1 inhibition on kidney enlargement was consistent at all disease stages, but the absolute effect was determined by the timing of drug initiation. Furthermore, cystic microarchitecture, renal function and cardiac disease remain abnormal with TORC1 inhibition, indicating that additional approaches to normalise cellular dedifferentiation, inflammation and hypertension are required to completely arrest the progression of PKDs. PMID:27723777

  8. Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer.

    PubMed

    Panis, Carolina; Pizzatti, Luciana; Bufalo, Aedra Carla; Herrera, Ana Cristina; Victorino, Vanessa Jacob; Cecchini, Rubens; Abdelhay, Eliana

    2016-03-01

    Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1β, IL-12, TGF-β1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment. PMID:26472721

  9. Leptogenesis in the symmetric phase of the early universe: Baryon asymmetry and hypermagnetic helicity evolution

    SciTech Connect

    Semikoz, V. B. Smirnov, A. Yu.

    2015-02-15

    We investigate the evolution of the baryon asymmetry of the Universe (BAU) in its symmetric phase before the electroweak phase transition (EWPT) induced by leptogenesis in the hypermagnetic field of an arbitrary structure and with a maximum hypermagnetic helicity density. The novelty of this work is that the BAU has been calculated for a continuous hypermagnetic helicity spectrum. The observed BAU B{sub obs} = 10{sup −10} that can be in large-scale hypermagnetic fields satisfying the wave number inequality k ≤ k{sub max} grows with increasing k{sub max}. We will also show that the initial right-handed electron asymmetry ξ{sub eR}(η{sub 0}) used in our leptogenesis model as a free parameter cannot take too large values, ξ{sub eR}(η{sub 0}) = 10{sup −4}, because this leads to a negative BAU by the EWPT time. In contrast, a sufficiently small initial right-handed electron asymmetry, ξ{sub eR}(η{sub 0}), provides its further growth and the corresponding BAU growth from zero to some positive value, including the observed B{sub obs} = 10{sup −10}.

  10. The scaffold protein Nde1 safeguards the brain genome during S phase of early neural progenitor differentiation

    PubMed Central

    Houlihan, Shauna L; Feng, Yuanyi

    2014-01-01

    Successfully completing the S phase of each cell cycle ensures genome integrity. Impediment of DNA replication can lead to DNA damage and genomic disorders. In this study, we show a novel function for NDE1, whose mutations cause brain developmental disorders, in safeguarding the genome through S phase during early steps of neural progenitor fate restrictive differentiation. Nde1 mutant neural progenitors showed catastrophic DNA double strand breaks concurrent with the DNA replication. This evoked DNA damage responses, led to the activation of p53-dependent apoptosis, and resulted in the reduction of neurons in cortical layer II/III. We discovered a nuclear pool of Nde1, identified the interaction of Nde1 with cohesin and its associated chromatin remodeler, and showed that stalled DNA replication in Nde1 mutants specifically occurred in mid-late S phase at heterochromatin domains. These findings suggest that NDE1-mediated heterochromatin replication is indispensible for neuronal differentiation, and that the loss of NDE1 function may lead to genomic neurological disorders. DOI: http://dx.doi.org/10.7554/eLife.03297.001 PMID:25245017

  11. Electron-phonon coupling and structural phase transitions in early transition metal oxides and chalcogenides

    NASA Astrophysics Data System (ADS)

    Farley, Katie Elizabeth

    Pronounced nonlinear variation of electrical transport characteristics as a function of applied voltage, temperature, magnetic field, strain, or photo-excitation is usually underpinned by electronic instabilities that originate from the complex interplay of spin, orbital, and lattice degrees of freedom. This dissertation focuses on two canonical materials that show pronounced discontinuities in their temperature-dependent resistivity as a result of electron---phonon and electron---electron correlations: orthorhombic TaS3 and monoclinic VO2. Strong electron-phonon interactions in transition metal oxides and chalcogenides results in interesting structural and electronic phase transitions. The properties of the material can be changed drastically in response to external stimuli such as temperature, voltage, or light. Understanding the influence these interactions have on the electronic structure and ultimately transport characteristics is of utmost importance in order to take these materials from a fundamental aspect to prospective applications such as low-energy interconnects, steep-slope transistors, and synaptic neural networks. This dissertation describes synthetic routes to nanoscale TaS3 and VO2, develops mechanistic understanding of their electronic instabilities, and in the case of the latter system explores modulation of the electronic and structural phase transition via the incorporation of substitutional dopant atoms. We start in chapter 2 with a detailed study of the synthesis and electronic transport properties of TaS3, which undergoes a Peierls' distortion to form a charge density wave. Scaling this material down to the nanometer-sized regime allows for interrogation of single or discrete phase coherent domains. Using electrical transport and broad band noise measurements, the dynamics of pinning/depinning of the charge density wave is investigated. Chapter 3 provides a novel synthetic approach to produce high-edge-density MoS2 nanorods. MoS2 is a

  12. Mechanistic insight into the Brust-Schiffrin two-phase method for organochalcogenate-protected metal nanoparticles

    NASA Astrophysics Data System (ADS)

    Lopez Jimenez, Francisco

    The primary objective of this thesis research was to explore the mechanism of the Brust---Schiffrin two--phase method, which has been widely used for preparing the thiolate--protected metal nanoparticles with the core diameter less than 5nm; to synthesize and characterize the ligand--protected gold nanoparticles using dialkyl ditelluride with different alkyl chain length as ligand precursor; and to develop a new synthetic route for obtaining ultra--small (< 2 nm) gold nanoparticels covered by tellurium-anchoring ligands. Since the Brust---Schiffrin two--phase method was first reported in 1994, many groups have tried to identify the precursors of metal ions prior to the addition of NaBH4. The widely accepted assumption has been that the addition of thiol reduces Au(III) to Au(I) and forms [AuSR] n--like polymers. Recently Lennox and coworkers have demonstrated that the metal precursor before the addition of the reductant is TOA metal(I) halide complex [TOA][MX2], and not [MSR]n--like polymers. Our Raman spectroscopic investigations showed that, in a typical BSM synthesis, no metal(M)---sulfur(S) bonds were formed after thiol addition. These observations provide independent spectroscopic confirmation of the recent work by Lennox and co--workers. On the basis of Raman, NMR, and surface plasmon resonance characterizations, we found that before the formation of any metal-chalcogen bonds, metal nucleation centers/NPs were first formed inside the inverse micelles of the tetrabutylammonium bromide in the organic solvent, where the metal ions were reduced by NaBH4. The ensuing formation of the metal---chalcogen bonds between the naked metal NPs inside the micelles and the organochalcogen ligands in the organic solvent is the mechanism by which the further growth of the metal core can be controlled. This proposed mechanism has been further examined in the formation of Ag and Cu nanoparticles. This new mechanistic understanding enabled the design of some specifically targeted

  13. PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos.

    PubMed

    Nakamura, Toshinobu; Liu, Yu-Jung; Nakashima, Hiroyuki; Umehara, Hiroki; Inoue, Kimiko; Matoba, Shogo; Tachibana, Makoto; Ogura, Atsuo; Shinkai, Yoichi; Nakano, Toru

    2012-06-03

    The modification of DNA by 5-methylcytosine (5mC) has essential roles in cell differentiation and development through epigenetic gene regulation. 5mC can be converted to another modified base, 5-hydroxymethylcytosine (5hmC), by the tet methylcytosine dioxygenase (Tet) family of enzymes. Notably, the balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment. We have previously reported that the maternal factor PGC7 (also known as Dppa3, Stella) is required for the maintenance of DNA methylation in early embryogenesis, and protects 5mC from conversion to 5hmC in the maternal genome. Here we show that PGC7 protects 5mC from Tet3-mediated conversion to 5hmC by binding to maternal chromatin containing dimethylated histone H3 lysine 9 (H3K9me2) in mice. In addition, imprinted loci that are marked with H3K9me2 in mature sperm are protected by PGC7 binding in early embryogenesis. This type of regulatory mechanism could be involved in DNA modifications in somatic cells as well as in early embryos.

  14. In situ observations of soil minerals and organic matter in the early phases of prescribed fires

    NASA Astrophysics Data System (ADS)

    Kavouras, Ilias G.; Nikolich, George; Etyemezian, Vic; Dubois, David W.; King, James; Shafer, David

    2012-06-01

    We examined the chemical composition of aerosol samples collected during a prescribed fire at a Great Basin Desert site in the context of samples collected from controlled combustion of vegetation clippings from the same site and resuspension of soil samples obtained prior to and after the burn event. We observed a distinct difference in the composition of organic carbon resuspended soil dust after the burn, reflecting changes caused by the heating of the soil. The relative abundances of minerals and organic carbon fractions in aerosols collected during the first period of the burn were identical to those measured in soil dust. For aerosol samples collected for the remaining two periods of the burn event, the profiles of both minerals and organic carbon matched quite well those observed for vegetation combustion. Reconstruction of aerosol samples collected during the burn event showed that vegetation combustion dominated emissions but mineral soil dust may account for about 10% of PM10emissions (reconstructed) during the early stages of the fire. A large fraction of emissions during the first two hours was also unaccounted mainly because of the insufficient conversion of organic carbon to organic mass. The abundance of heavier non-volatile organics in soil dust suggested the presence of humic/fulvic acids that exhibit higher OM-to-OC ratios and thus, account for a proportion of the unaccounted emissions. These findings indicated that soil dust may be released into the air during a fire event, probably due to the enhanced turbulent mixing near the burn front.

  15. Stable isotope evidence for an amphibious phase in early proboscidean evolution

    PubMed Central

    Liu, Alexander G. S. C.; Seiffert, Erik R.; Simons, Elwyn L.

    2008-01-01

    The order Proboscidea includes extant elephants and their extinct relatives and is closely related to the aquatic sirenians (manatees and dugongs) and terrestrial hyracoids (hyraxes). Some analyses of embryological, morphological, and paleontological data suggest that proboscideans and sirenians shared an aquatic or semiaquatic common ancestor, but independent tests of this hypothesis have proven elusive. Here we test the hypothesis of an aquatic ancestry for advanced proboscideans by measuring δ18O in tooth enamel of two late Eocene proboscidean genera, Barytherium and Moeritherium, which are sister taxa of Oligocene-to-Recent proboscideans. The combination of low δ18O values and low δ18O standard deviations in Barytherium and Moeritherium matches the isotopic pattern seen in aquatic and semiaquatic mammals, and differs from that of terrestrial mammals. δ13C values of these early proboscideans suggest that both genera are likely to have consumed freshwater plants, although a component of C3 terrestrial vegetation cannot be ruled out. The simplest explanation for the combined evidence from isotopes, dental functional morphology, and depositional environments is that Barytherium and Moeritherium were at least semiaquatic and lived in freshwater swamp or riverine environments, where they grazed on freshwater vegetation. These results lend new support to the hypothesis that Oligocene-to-Recent proboscideans are derived from amphibious ancestors. PMID:18413605

  16. Metabolite Modulation in Human Plasma in the Early Phase of Acclimatization to Hypobaric Hypoxia

    PubMed Central

    Liao, Wen-Ting; Liu, Bao; Chen, Jian; Cui, Jian-Hua; Gao, Yi-Xing; Liu, Fu-Yu; Xu, Gang; Sun, Bing-Da; Zhang, Er-Long; Yuan, Zhi-Bin; Zhang, Gang; Gao, Yu-Qi

    2016-01-01

    The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia. We explored a plasma metabolomics approach to detect alterations induced by the exposure of subjects to high altitude. Plasma samples were collected from 60 subjects both on plain and at high altitude (5300 m). Metabolite profiling was performed by gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) in conjunction with univariate and multivariate statistical analyses. ELISA assays were further employed to measure the levels of several relevant enzymes together with perturbed metabolic pathways. The results showed that hypobaric hypoxia caused significant and comprehensive metabolic changes, as represented by significant changes of 44 metabolites and 4 relevant enzymes. Using MetaboAnalyst 3.0, it was found that several key metabolic pathways were acutely perturbed. In addition, 5 differentially expressed metabolites in pre-exposure samples from the acute mountain sickness-susceptible (AMS-S) group compared with those from the AMS-resistant (AMS-R) group are identified, which warrant further validation as potential predictive biomarkers for AMS-S individuals. These results provide new insights for further understanding the pathophysiological mechanism of early acclimatization to hypobaric hypoxia and other diseases correlated to tissue hypoxia. PMID:26940428

  17. Stable isotope evidence for an amphibious phase in early proboscidean evolution.

    PubMed

    Liu, Alexander G S C; Seiffert, Erik R; Simons, Elwyn L

    2008-04-15

    The order Proboscidea includes extant elephants and their extinct relatives and is closely related to the aquatic sirenians (manatees and dugongs) and terrestrial hyracoids (hyraxes). Some analyses of embryological, morphological, and paleontological data suggest that proboscideans and sirenians shared an aquatic or semiaquatic common ancestor, but independent tests of this hypothesis have proven elusive. Here we test the hypothesis of an aquatic ancestry for advanced proboscideans by measuring delta(18)O in tooth enamel of two late Eocene proboscidean genera, Barytherium and Moeritherium, which are sister taxa of Oligocene-to-Recent proboscideans. The combination of low delta(18)O values and low delta(18)O standard deviations in Barytherium and Moeritherium matches the isotopic pattern seen in aquatic and semiaquatic mammals, and differs from that of terrestrial mammals. delta(13)C values of these early proboscideans suggest that both genera are likely to have consumed freshwater plants, although a component of C(3) terrestrial vegetation cannot be ruled out. The simplest explanation for the combined evidence from isotopes, dental functional morphology, and depositional environments is that Barytherium and Moeritherium were at least semiaquatic and lived in freshwater swamp or riverine environments, where they grazed on freshwater vegetation. These results lend new support to the hypothesis that Oligocene-to-Recent proboscideans are derived from amphibious ancestors.

  18. Tea bag filter paper as a novel protective membrane for micro-solid phase extraction of butachlor in aqueous samples.

    PubMed

    Pelden, Tshering; Thammaknet, Chongdee; Thavarungkul, Panote; Kanatharana, Proespichaya

    2014-01-01

    An innovative, cost-effective, simple, and environmental friendly tea bag filter paper protected micro-solid phase extraction (μ-SPE) technique was developed for the first time with the aim to miniaturize and minimize the use of organic solvents for the extraction and determination of butachlor in aqueous samples. The μ-SPE device was produced by packing 3.0 mg of an easily synthesized new sorbent, hydroxyl-functionalized polypyrrole (OH-PPY), inside a small tea bag filter paper sachet (1.0 cm × 0.5 cm) that served as a protective envelope. Both the extraction and desorption procedures were facilitated by sonication. Due to the high porosity and the fast water absorption of the tea bag filter paper, the analyte could easily diffuse through and enhance the interaction with the sorbent. Under the optimized conditions for the GC-ECD and the μ-SPE, the limit of detection (S/N ≥ 3) was 2.0 μg L(-1) while the limit of quantitation (S/N ≥ 10) was 10.0 μg L(-1). The recoveries of the butachlor spiked at 0.050, 0.10, and 0.50 μg mL(-1) ranged from 77.9 ± 3.0 to 112.5 ± 2.9%. The proposed method was successfully applied for the determination of butachlor in water samples from paddy cultivation sites. The levels found were from non-detectable to 24.71 ± 0.37 μg L(-1).

  19. Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial

    PubMed Central

    2015-01-01

    Summary Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0.10. The study is registered at ClinicalTrials.gov, number NCT01280123. Findings 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4.42 (95% CI 2.55–6.28) for 15 mg pioglitazone, 5.13 (95% CI 3.17–7.08) for 45 mg pioglitazone, and 6.25 (95% CI 4.35–8.15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was −1.83 (80% CI −3.56 to −0.10) and the null hypothesis could not be rejected (p=0.19). The mean difference between the 45 mg and placebo

  20. Factors associated with a positive attitude towards change among employees during the early phase of a downsizing process.

    PubMed

    Svensen, Erling; Neset, Gunnar; Eriksen, Hege R

    2007-04-01

    Most research on organizational changes in working life, including downsizing, focuses on the negative attitudes and negative consequences of the change. The aim of this study was to evaluate if the employee's previous learning experience and characteristics of the working environment were associated with positive attitudes towards organizational change. The 467 employees (73.5% males) working in a global oil company in the early phases of a downsizing process were asked to answer a questionnaire with demographic variables, perception of the working environment, and attitude to change (93% response rate). Corporate social responsibility (CSR), involvement and participation, team leadership and team effectiveness were important factors related to positive attitudes towards organizational change. Non-leaders and older employees were positive to change. We conclude that employees' perceptions of their psychosocial working environment, in particular the CSR, were highly related to their attitude to organizational change. PMID:17430368

  1. Factors associated with a positive attitude towards change among employees during the early phase of a downsizing process.

    PubMed

    Svensen, Erling; Neset, Gunnar; Eriksen, Hege R

    2007-04-01

    Most research on organizational changes in working life, including downsizing, focuses on the negative attitudes and negative consequences of the change. The aim of this study was to evaluate if the employee's previous learning experience and characteristics of the working environment were associated with positive attitudes towards organizational change. The 467 employees (73.5% males) working in a global oil company in the early phases of a downsizing process were asked to answer a questionnaire with demographic variables, perception of the working environment, and attitude to change (93% response rate). Corporate social responsibility (CSR), involvement and participation, team leadership and team effectiveness were important factors related to positive attitudes towards organizational change. Non-leaders and older employees were positive to change. We conclude that employees' perceptions of their psychosocial working environment, in particular the CSR, were highly related to their attitude to organizational change.

  2. Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division

    SciTech Connect

    Nakanishi, Akira; Han, Xiangzi; Saito, Hiroko; Taguchi, Keiko; Ohta, Yoshiyasu; Imajoh-Ohmi, Shinobu; Miki, Yoshio; E-mail: miki.mgen@mri.tmd.ac.jp

    2007-03-30

    BRCA2 is responsible for familial breast and ovarian cancer, and its gene product is linked to DNA repair and transcriptional regulation. The BRCA2 protein exists mainly in the nucleus. Here, we show that BRCA2 has a centrosomal localization signal (CLS), localizes also to centrosomes during S and early M phases, and may regulate duplication and separation of the centrosomes. Green fluorescent protein (GFP) fused to the CLS peptides from BRCA2 (GFP-CLS) localizes to centrosomes and prevents endogenous BRCA2 from localizing to centrosomes. In addition, expression of GFP-CLS in cells leads to the abnormal duplication and positioning of centrosomes, resulting in the generation of multinuclear cells. These results thus implicate BRCA2 in the regulation of the centrosome cycle, and provide new insight into the aneuploid nature of many breast cancers.

  3. Efficacy of continuous epidural analgesia and the implications for patient care in the early postoperative phase.

    PubMed

    Slack, J F; Faut-Callahan, M

    1990-06-01

    Management of postoperative pain has been shown to be inadequately controlled, and, in fact, can have significant deleterious effects on a patient's early postoperative recovery. Continuous epidural analgesia has recently been used to control postoperative pain. This mode of analgesia controls postoperative pain without the delays inherent in the PRN administration of systemic narcotics. This was a multidisciplinary, prospective, randomized, double-blind study of various epidural analgesic agents in 53 thoracic and 81 abdominal surgery patients. The focus of the study was to identify the benefits and problems of continuous epidural analgesia for postoperative pain management and the implications for the nursing care of the patients. Evaluation of the effectiveness of the analgesia was based on the following measures: (1) pain measured at regular intervals in the 72-hour period with a visual analog; (2) pain as measured after 72 hours with the word descriptor section of the McGill Pain Questionnaire; (3) amount of supplemental systemic narcotic analgesic needed; (4) recovery of ambulatory and respiratory function, including ability to perform coughing and deep-breathing exercises; (5) occurrence of adverse effects; and (6) the type and distribution of nursing care problems associated with continuous epidural infusions. The results of this study showed that the level of pain relief and recovery of postoperative function was superior to that provided by the more widely used (PRN) systemic administration of narcotics. With the exception of the report of back pain by patients receiving the normal saline epidural solution, complications did not occur in a significantly greater proportion when using the epidural route. Although some nursing care problems were identified, patients who received epidural analgesia were able to be cared for on general care units with no adverse effects reported. PMID:2285719

  4. Global Warming Potential from early phase decomposition of soil organic matter amendments

    NASA Astrophysics Data System (ADS)

    Mayer, A.; Silver, W. L.

    2015-12-01

    Organic matter amendments to soil are widely used as a method of enhancing nutrient availability for crops or grassland. Amendments such as composted manure or greenwaste also have the co-benefits of potentially increasing soil carbon (C) stocks (DeLonge et al., 2013) and diverting organic waste from landfills or manure lagoons. However, application of organic matter amendments can also stimulate emissions of greenhouse gases (GHGs). In this study we determined how the chemical quality of organic matter amendments affected soil C and N content and GHG emissions during early stage decomposition. California grassland soils were amended with six different amendments of varying C and N content including three composts and three feedstocks (goat and horse bedding and cattle manure). Amendments and soils were incubated in the laboratory for 7 weeks; GHG fluxes were measured weekly. The three feedstocks emitted significantly more GHGs than the composted materials. With the exception of cow manure, N content of the amendment was linearly correlated with global warming potential emitted (R2= 0.66, P <0.0001). C:N ratios were not a significant predictor of GHG emissions. Cow manure stimulated a net loss of C (or C equivalents) in the mineral soil, as expected. However, greenwaste compost also surprisingly resulted in net C losses, while goat bedding, horse bedding, and the other compost were either C neutral or a slight net C sink at the end of the incubation. Ongoing analyses are examining the fate of the C incorporated from the amendment to the soil as occluded or free light fraction, as well as N mineralization rates. Our data suggest that N content of organic matter amendments is a good predictor of initial GHG emissions. The study also indicates that composting greenwaste with N-rich bedding and manure can result in lower GHG emissions and C sequestration compared to the individual uncomposted components.

  5. Adolescents' views on war and peace in the early phases of the Iraq conflict.

    PubMed

    Garatti, Marinella; Rudnitski, Rose A

    2007-01-01

    Adolescents' views of war and peace were assessed among 209 children aged 10-14 who attended a parochial school or its after-school religious program located in a predominantly middle-class, suburban area within commuting distance of New York City. Findings were compared to those of youth surveyed during other armed conflicts, specifically the Vietnam War, the first Persian Gulf War, and the U.S. military involvement in Latin America. The study took place in early fall 2003, and results were interpreted in light of the social climate and complex realities of post 9/11 in New York State, the Catholic Church's initial opposition to the Iraq conflict, and popular opinion. In spite of differences between the Iraq War and other conflicts, findings are remarkably similar. Although the present group is highly preoccupied with terrorism and nuclear war, even in a time of war, participants show concern for what they perceived as affecting their lives directly, rather than with conventional war. While they believe that President Bush was honest about the war in Iraq and right in sending troops, they do not glorify war. On a theoretical level, they overwhelmingly believe that wars are bad and the majority is optimistic that world peace is possible, though they realize that wars are difficult to prevent, believe that they are sometimes needed, and will occur in the future. Unlike the Catholic group surveyed by Tolley during the Vietnam War, however, participants are not as ready to die for their country, although findings show that, overall, like past groups, more boys tend to be pro-war than are girls and participants' views tend to reflect contemporary public opinions.

  6. Experimental investigation of the dissolution of fractures. From early stage instability to phase diagram

    NASA Astrophysics Data System (ADS)

    Osselin, Florian; Budek, Agnieszka; Cybulski, Olgierd; Kondratiuk, Pawel; Garstecki, Piotr; Szymczak, Piotr

    2016-04-01

    Dissolution of natural rocks is a fundamental geological process and a key part of landscape formation and weathering processes. Moreover, in current hot topics like Carbon Capture and Storage or Enhanced Oil Recovery, mastering dissolution of the host rock is fundamental for the efficiency and the security of the operation. The basic principles of dissolution are well-known and the theory of the reactive infiltration instability has been extensively studied. However, the experimental aspect has proved very challenging because of the strong dependence of the outcome with pore network, chemical composition, flow rate... In this study we are trying to tackle this issue by using a very simple and efficient device consisting of a chip of pure gypsum inserted between two polycarbonate plates and subjected to a constant flow rate of pure water. Thanks to this device, we are able to control all parameters such as flow rate, fracture aperture, roughness of the walls... but also to observe in situ the progression of the dissolution thanks to the transparency of the polycarbonate which is impossible with 3D rocks. We have been using this experimental set-up to explore and investigate all aspects of the dissolution in a fracture, such as initial instability and phase diagram of different dissolution patterns, and to compare it with theory and simulations, yielding very good agreement and interesting feedbacks on the coupling between flow and chemistry in geological media

  7. Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results.

    PubMed Central

    Waugh, W. H.; Daeschner, C. W.; Files, B. A.; McConnell, M. E.; Strandjord, S. E.

    2001-01-01

    L-Arginine may be a conditionally essential amino acid in children and adolescents with sickle cell disease, particularly as required substrate in the arginine-nitric oxide pathway for endogenous nitrovasodilation and vasoprotection. Vasoprotection by arginine is mediated partly by nitric oxide-induced inhibition of endothelial damage and inhibition of adhesion and activation of leukocytes. Activated leukocytes may trigger many of the complications, including vasoocclusive events and intimal hyperplasias. High blood leukocyte counts during steady states in the absence of infection are significant laboratory risk factors for adverse complications. L-Citrulline as precursor amino acid was given orally twice daily in daily doses of approximately 0.1 g/kg in a pilot Phase II clinical trial during steady states in four homozygous sickle cell disease subjects and one sickle cell-hemoglobin C disease patient (ages 10-18). There soon resulted dramatic improvements in symptoms of well-being, raised plasma arginine levels, and reductions in high total leukocyte and high segmented neutrophil counts toward or to within normal limits. Continued L-citrulline supplementation in compliant subjects continued to lessen symptomatology, to maintain plasma arginine concentrations greater than control levels, and to maintain nearly normal total leukocyte and neutrophil counts. Side effects or toxicity from citrulline were not experienced. Oral L-citrulline may portend very useful for palliative therapy in sickle cell disease. Placebo-controlled, long-term trials are now indicated. PMID:11688916

  8. Early-phase Development of Cancer Prevention Agents, Challenges and Opportunities

    PubMed Central

    Perloff, Marjorie; Steele, Vernon E.

    2013-01-01

    Chemoprevention is the administration of agents (drugs, biologics, dietary supplements, or nutrients) to reduce the risk of developing cancer or prevent the recurrence of cancer. The National Cancer Institute, Division of Cancer Prevention (NCI, DCP) is a major sponsor of cancer preventive preclinical and clinical research. As such, it has developed a comprehensive drug development program specifically designed to meet the requirements needed for cancer preventive drugs to achieve initial regulatory approval. Clinical development of cancer prevention agents presents unique challenges not encountered with most cancer therapeutic agents. To meet these challenges, NCI, DCP has implemented new approaches and programs, including Phase 0 clinical trial designs and microdose studies. In addition, the PREVENT Cancer Program was recently implemented by NCI, DCP to offer a formalized structure for moving drugs forward in the prevention pipeline using a continue/not continue decision process. Likewise, DCP has implemented a clinical trials Consortium to further develop these agents. These and other approaches will be discussed in this commentary. PMID:23466485

  9. Morphology and Dynamics of Jets of Comet 67P Churyumov-Gerasimenko: Early Phase Development

    NASA Astrophysics Data System (ADS)

    Lin, Zhong-Yi; Ip, Wing-Huen; Lai, Ian-Lin; Lee, Jui-Chi; Pajola, Maurizio; Lara, Luisa; Gutierrez, Pedro; Rodrigo, Rafael; Bodewits, Dennis; A'Hearn, Mike; Vincent, Jean-Baptiste; Agarwal, Jessica; Keller, Uwe; Mottola, Stefano; Bertini, Ivano; Lowry, Stephen; Rozek, Agata; Liao, Ying; Rosetta Osiris Coi Team

    2015-04-01

    The scientific camera, OSIRIS (Optical, Spectroscopic, and Infrared Remote Imaging System), onboard the Rosetta spacecraft comprises a Narrow Angle Camera (NAC) for nucleus surface and dust studies and a Wide Angle Camera (WAC) for the wide field of dust and gas coma investigations. The dynamical behavior of jets in the dust coma continuously monitored by using dust filters from the arrival at the comet (August 2014) throughout the mapping phase (Oct. 2014) is described here. The analysis will cover the study of the time variability of jets, the source regions of these jets, the excess brightness of jets relative to the averaged coma brightness, and the brightness distribution of dust jets along the projected distance. The jets detected between August and September originated mostly from the neck region (Hapi). Morphological changes appeared over a time scale of several days in September. The brightness slope of the dust jets is much steeper than the background coma. This might be related to the sublimation or fragmentation of the emitted dust grains. Inter-comparison with results from other experiments will be necessary to understand the difference between the dust emitted from Hapi and those from the head and the body of the nucleus surface. The physical properties of the Hapi jets will be compared to dust jets (and their source regions) to emerge as comet 67P moves around the perihelion.

  10. Operational limits on WEST inertial divertor sector during the early phase experiment

    NASA Astrophysics Data System (ADS)

    Firdaouss, M.; Corre, Y.; Languille, P.; Greuner, H.; Autissier, E.; Desgranges, C.; Guilhem, D.; Gunn, J. P.; Lipa, M.; Missirlian, M.; Pascal, J.-Y.; Pocheau, C.; Richou, M.; Tsitrone, E.

    2016-02-01

    The primary goal of the WEST project is to be a test bed to characterize the fatigue and lifetime of ITER-like W divertor components subjected to relevant thermal loads. During the first phase of exploitation (S2 2016), these components (W monoblock plasma facing unit—W-PFU) will be installed in conjunction with graphite components (G-PFU). Since the G-PFU will not be actively cooled, it is necessary to ensure the expected pulse duration allows the W-PFU to reach its steady state without overheating the G-PFU assembly structure or the embedded stainless-steel diagnostics. High heat flux tests were performed at the GLADIS facility to assess the thermal behavior of the G-PFU. Some operational limits based on plasma parameters were determined. It was found that it is possible to operate at an injected power such that the maximal incident heat flux on the lower divertor is 10 MW m-2 for the required pulse length.

  11. Insulin modulates cytokine release and selectin expression in the early phase of allergic airway inflammation in diabetic rats

    PubMed Central

    2010-01-01

    Background Clinical and experimental data suggest that the inflammatory response is impaired in diabetics and can be modulated by insulin. The present study was undertaken to investigate the role of insulin on the early phase of allergic airway inflammation. Methods Diabetic male Wistar rats (alloxan, 42 mg/Kg, i.v., 10 days) and controls were sensitized by s.c. injection of ovalbumin (OA) in aluminium hydroxide 14 days before OA (1 mg/0.4 mL) or saline intratracheal challenge. The following analyses were performed 6 hours thereafter: a) quantification of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage fluid (BALF) by Enzyme-Linked Immunosorbent Assay, b) expression of E- and P- selectins on lung vessels by immunohistochemistry, and c) inflammatory cell infiltration into the airways and lung parenchyma. NPH insulin (4 IU, s.c.) was given i.v. 2 hours before antigen challenge. Results Diabetic rats exhibited significant reduction in the BALF concentrations of IL-1β (30%) and TNF-α (45%), and in the lung expression of P-selectin (30%) compared to non-diabetic animals. This was accompanied by reduced number of neutrophils into the airways and around bronchi and blood vessels. There were no differences in the CINC-1 levels in BALF, and E-selectin expression. Treatment of diabetic rats with NPH insulin, 2 hours before antigen challenge, restored the reduced levels of IL-1β, TNF-α and P-selectin, and neutrophil migration. Conclusion Data presented suggest that insulin modulates the production/release of TNF-α and IL-1β, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction. PMID:20667094

  12. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    PubMed

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers.

  13. The Silicon and Calcium High-velocity Features in Type Ia Supernovae from Early to Maximum Phases

    NASA Astrophysics Data System (ADS)

    Zhao, Xulin; Wang, Xiaofeng; Maeda, Keiichi; Sai, Hanna; Zhang, Tianmeng; Zhang, Jujia; Huang, Fang; Rui, Liming; Zhou, Qi; Mo, Jun

    2015-09-01

    The high-velocity features (HVFs) in optical spectra of type Ia supernovae (SNe Ia) are examined with a large sample including very early-time spectra (e.g., t < -7 days). Multiple Gaussian fits are applied to examine the HVFs and their evolutions, using constraints on expansion velocities for the same species (i.e., Si ii 5972 and Si ii 6355). We find that strong HVFs tend to appear in SNe Ia with smaller decline rates (e.g., Δm15(B) ≲ 1.4 {mag}), clarifying that the finding by Childress et al. for the Ca-HVFs in near-maximum-light spectra applies both to the Si-HVFs and Ca-HVFs in the earlier phase. The Si-HVFs seem to be more common in rapidly expanding SNe Ia, which is different from the earlier result that Ca-HVFs are associated with SNe Ia that have slower Si ii 6355 velocities at maximum light (i.e., VSimax). Moreover, SNe Ia with both stronger HVFs at early phases and larger VSimax are found to have noticeably redder B-V colors and to occur preferentially in the inner regions of their host galaxies, while those with stronger HVFs but smaller VSimax show opposite tendencies, suggesting that these two subclasses have different explosion environments and their HVFs may have different origins. We further examine the relationships between the absorption features of Si ii 6355 and Ca ii IR lines, and find that their photospheric components are well correlated in velocity and strength but that the corresponding HVFs show larger scatter. These results cannot be explained with ionization and/or thermal processes alone, and different mechanisms are required for the creation of HVF-forming regions in SNe Ia.

  14. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    PubMed

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. PMID:26711734

  15. The genetic basis of strain-dependent differences in the early phase of radiation injury in mouse lung

    SciTech Connect

    Franko, A.J.; Sharplin, J.; Ward, W.F.; Hinz, J.M. )

    1991-06-01

    Substantial differences between mouse strains have been reported in the lesions present in the lung during the early phase of radiation injury. Some strains show only classical pneumonitis, while other strains develop substantial fibrosis and hyaline membranes which contribute appreciably to respiratory insufficiency, in addition to pneumonitis. Other strains are intermediate between these extremes. These differences correlate with intrinsic differences in activities of lung plasminogen activator and angiotensin converting enzyme. The genetic basis of these differences was assessed by examining histologically the early reaction in lungs of seven murine hybrids available commercially after whole-thorax irradiation. Crosses between fibrosing and nonfibrosing parents were uniformly nonfibrosing, and crosses between fibrosing and intermediate parents were uniformly intermediate. No evidence of sex linkage was seen. Thus the phenotype in which fibrosis is found is controlled by autosomal recessive determinants. Strains prone to radiation-induced pulmonary fibrosis and hyaline membranes exhibited intrinsically lower activities of lung plasminogen activator and angiotensin converting enzyme than either the nonfibrosing strains or the nonfibrosing hybrid crosses. The median time of death of the hybrids was genetically determined primarily by the longest-lived parent regardless of the types of lesions expressed.

  16. Early to middle Miocene vegetation history of Antarctica supports eccentricity-paced warming intervals during the Antarctic icehouse phase

    NASA Astrophysics Data System (ADS)

    Griener, Kathryn W.; Warny, Sophie; Askin, Rosemary; Acton, Gary

    2015-04-01

    Recent palynological evidence from the upper section (< 664 mbsf) of the Miocene ANDRILL 2A (AND-2A) core in the Ross Sea indicated a brief warm period during the Mid Miocene Climatic Optimum (MMCO), during Antarctica's icehouse phase. The nature of other Miocene climate fluctuations in Antarctica remains poorly resolved. Here, we present new palynological data from the lower section of the AND-2A core (> 664 mbsf) that reveal additional intervals of increased palynomorph abundance and diversity during the Antarctic early to middle Miocene. This evidence is consistent with a relatively dynamic early Miocene Antarctic icehouse climate with intervals of increased temperature and moisture, prior to the MMCO. Comparison with previous AND-2A studies indicates that periods of increased palynomorph abundance in the lower stratigraphic section largely coincide with ice sheet minima, distal ice conditions, and the presence of freshwater (i.e. increased precipitation, meltwater run-off, and freshwater ponds). Decreases in plant productivity mostly coincide with increased glaciation, decreased freshwater, and ice-proximal conditions during the Antarctic Miocene. Comparing the palynological data with other AND-2A data and global climate proxies (e.g., pCO2, δ18O, relative sea level, Milankovitch cycles) helps to resolve questions regarding the driving forces behind climate and vegetation change. We found that palynomorph assemblages reflecting generally warmer conditions are largely associated with 400-kyr eccentricity maxima, while assemblages indicative of colder conditions coincide with 400-kyr eccentricity minima. These data are consistent with other findings that indicate the early to middle Miocene climate was eccentricity-paced.

  17. Experimental model for the study of the effects of platelet-rich plasma on the early phases of muscle healing

    PubMed Central

    Borrione, Paolo; Grasso, Loredana; Chierto, Elena; Geuna, Stefano; Racca, Silvia; Abbadessa, Giuliana; Ronchi, Giulia; Faiola, Fabio; Di Gianfrancesco, Alessia; Pigozzi, Fabio

    2014-01-01

    Background There is abundant evidence suggesting that growth factors may play a key role in the healing process, especially in the early stages of inflammation. Despite the reported clinical successes with the use of growth factors there is still a lack of knowledge on the biological mechanism underlying the activity of platelet-rich plasma during the process of muscle healing. The aim of this study was to analyse the early effects of platelet- rich plasma in an easily reproducible animal model. Materials and methods Wistar male adult rats (n =102) were used in this study. The muscle lesion was created with a scalpel in the flexor sublimis muscles. Platelet-rich plasma was applied immediately after surgery. Treated, untreated and contralateral muscles were analysed by morphological evaluation and western blot assay. Results Leucocyte infiltration was significantly greater in muscles treated with platelet-rich plasma than in both untreated and contralateral muscles. The latter showed greater leucocyte infiltration when compared to the untreated muscles. Platelet-rich plasma treatment also modified the cellular composition of the leucocyte infiltration leading to increased expression of CD3, CD8, CD19 and CD68 and to decreased CD4 antigen expression in both platelet-rich plasma treated and contralateral muscles. Blood vessel density and blood vessel diameters were not statistically significantly different between the three groups analysed. Discussion The results of this study showed that treatment with platelet-rich plasma magnified the physiological early inflammatory response following a muscle injury, modifying the pattern of cellular recruitment. Local platelet-rich plasma treatment may exert a direct or, more plausibly, indirect systemic effect on healing processes, at least in the earliest inflammatory phase. PMID:23867182

  18. Tracking the Distribution of 26Al and 60Fe during the Early Phases of Star and Disk Evolution

    NASA Astrophysics Data System (ADS)

    Kuffmeier, Michael; Frostholm Mogensen, Troels; Haugbølle, Troels; Bizzarro, Martin; Nordlund, Åke

    2016-07-01

    The short-lived 26Al and 60Fe radionuclides are synthesized and expelled into the interstellar medium by core-collapse supernova events. The solar system’s first solids, calcium-aluminum refractory inclusions (CAIs), contain evidence for the former presence of the 26 Al nuclide defining the canonical 26Al/27 Al ratio of ˜ 5× {10}-5. A different class of objects temporally related to canonical CAIs are CAIs with fractionation and unidentified nuclear effects (FUN CAIs), which record a low initial 26Al/27Al of 10-6. The contrasting level of 26Al between these objects is often interpreted as reflecting the admixing of the 26Al nuclides during the early formative phase of the Sun. We use giant molecular cloud scale adaptive mesh-refinement numerical simulations to trace the abundance of 26Al and 60Fe in star-forming gas during the early stages of accretion of individual low-mass protostars. We find that the 26Al/27Al and 60Fe/56Fe ratios of accreting gas within a vicinity of 1000 au of the stars follow the predicted decay curves of the initial abundances at the time of star formation without evidence of spatial or temporal heterogeneities for the first 100 kyr of star formation. Therefore, the observed differences in 26Al/27Al ratios between FUN and canonical CAIs are likely not caused by admixing of supernova material during the early evolution of the proto-Sun. Selective thermal processing of dust grains is a more viable scenario to account for the heterogeneity in 26Al/27Al ratios at the time of solar system formation.

  19. Chemical characterization of the early evolutionary phases of high-mass star-forming regions

    NASA Astrophysics Data System (ADS)

    Gerner, Thomas

    2014-10-01

    The formation of high-mass stars is a very complex process and up to date no comprehensive theory about it exists. This thesis studies the early stages of high-mass star-forming regions and employs astrochemistry as a tool to probe their different physical conditions. We split the evolutionary sequence into four observationally motivated stages that are based on a classification proposed in the literature. The sequence is characterized by an increase of the temperatures and densities that strongly influences the chemistry in the different stages. We observed a sample of 59 high-mass star-forming regions that cover the whole sequence and statistically characterized the chemical compositions of the different stages. We determined average column densities of 18 different molecular species and found generally increasing abundances with stage. We fitted them for each stage with a 1D model, such that the result of the best fit to the previous stage was used as new input for the following. This is a unique approach and allowed us to infer physical properties like the temperature and density structure and yielded a typical chemical lifetime for the high-mass star-formation process of 1e5 years. The 18 analyzed molecular species also included four deuterated molecules whose chemistry is particularly sensitive to thermal history and thus is a promising tool to infer chemical ages. We found decreasing trends of the D/H ratios with evolutionary stage for 3 of the 4 molecular species and that the D/H ratio depends more on the fraction of warm and cold gas than on the total amount of gas. That indicates different chemical pathways for the different molecules and confirms the potential use of deuterated species as chemical age indicators. In addition, we mapped a low-mass star forming region in order to study the cosmic ray ionization rate, which is an important parameter in chemical models. While in chemical models it is commonly fixed, we found that it ! strongly varies with

  20. Effects of a beetroot juice with high neobetanin content on the early-phase insulin response in healthy volunteers.

    PubMed

    Wootton-Beard, Peter C; Brandt, Kirsten; Fell, David; Warner, Sarah; Ryan, Lisa

    2014-01-01

    Produce rich in phytochemicals may alter postprandial glucose and insulin responses by interacting with the pathways that regulate glucose uptake and insulin secretion in humans. The aims of the present study were to assess the phytochemical constituents of red beetroot juice and to measure the postprandial glucose and insulin responses elicited by either 225 ml beetroot juice (BEET), a control beverage matched for macronutrient content (MCON) or a glucose beverage in healthy adults. Beetroot juice was a particularly rich source of betalain degradation compounds. The orange/yellow pigment neobetanin was measured in particularly high quantities (providing 1·3 g in the 225 ml). A total of sixteen healthy individuals were recruited, and consumed the test meals in a controlled single-blind cross-over design. Results revealed a significant lowering of the postprandial insulin response in the early phase (0-60 min) (P < 0·05) and a significantly lower glucose response in the 0-30 min phase (P < 0·05) in the BEET treatment compared with MCON. Betalains, polyphenols and dietary nitrate found in the beetroot juice may each contribute to the observed differences in the postprandial insulin concentration. PMID:25191617

  1. The - interaction: A study of early stages of phase separation in a Fe-20%Cr-6%Al-0.5%Ti alloy

    SciTech Connect

    Capdevila, C.; Miller, Michael K; Russell, Kaye F; Chao, J.; Lopez, F

    2011-01-01

    The temporal evolution of the microstructure resulting from phase separation into Fe-rich ({alpha}), Cr-rich ({alpha}{prime}), and Fe(Ti,Al) ({beta}{prime}) phases of a Fe-20Cr-6Al-0.5Ti alloy has been analyzed by thermoelectric power measurements (TEP). The early stages of decomposition and the evolution of the three-dimensional microstructure have been analyzed by atom probe tomography (APT). The roles of Cr, Al, and Ti during the decomposition process have been investigated in terms of solute partitioning between the phases. Analysis of proximity histograms revealed that significant Al and Ti partitioning occurs, which is consistent with theoretical calculations. The results indicate that as the {alpha}-{alpha}{prime} phase separation proceeds, Al and Ti are rejected into the {alpha} phase, which causes the {beta}{prime} phase to nucleate on the surface of the {alpha}{prime} phase.

  2. Determination of haloacetic acids in swimming pool waters by membrane-protected micro-solid phase extraction.

    PubMed

    Nsubuga, Hakimu; Basheer, Chanbasha

    2013-11-01

    In this study, a simple and efficient extraction method for determining haloacetic acids (HAAs) in swimming pool waters has been developed. HAAs are toxic organic pollutants of disinfection origin most commonly detected in swimming pool and drinking waters at trace level concentrations. For the first time, a highly efficient sorbent was developed using rice husk and used for micro-solid phase extraction (μ-SPE) technique. To increase the extraction capability of rice husk silica, iron oxide was incorporated via sol-gel process. In μ-SPE device, the novel sorbent was packed and used for extraction of HAAs prior to analysis using ultra performance liquid chromatography-ultraviolet detection (UPLC-UV). Various extraction parameters were optimized to improve the extraction efficiency of μ-SPE. Under optimum conditions, linearity (coefficient of determination, r(2)≥0.991 over the concentration range of 1-150 μg/L), detection limits in the range of 0.001-0.092 μg/L, mean recoveries up to 110% with corresponding relative standard deviations of 2-7% (n=3) had been obtained. Finally, the method was applied to swimming pool water to evaluate its feasibility. The mean concentrations for HAAs from the pool waters were in the range of 6.8 and 48.6 μg/L which are far below the standard values set by United States Environmental Protection Agency. PMID:24075018

  3. An association between low-dose hyper-radiosensitivity and the early G2-phase checkpoint in normal fibroblasts of cancer patients.

    PubMed

    Słonina, Dorota; Gasińska, Anna; Biesaga, Beata; Janecka, Anna; Kabat, Damian

    2016-03-01

    In our previous study, low-dose hyper-radiosensitivity (HRS) effect was demonstrated for normal fibroblasts (asynchronous and G2-phase enriched) of 4 of the 25 cancer patients investigated. For the rest of patients, HRS was not defined in either of the 2 fibroblast populations. Thus, the study indicated that G2-phase enrichment had no influence on HRS identification. The conclusion contradicts that reported for human tumor cells, and suggests different mechanism of HRS in normal human cells. In the present paper we report, for the first time, the activity of early G2-phase checkpoint after low-dose irradiation in normal fibroblasts of these 4 HRS-positive patients and 4 HRS-negative patients and answer the question regarding the role of this checkpoint in normal human cells. The response of the early G2-phase checkpoint was determined by assessment of the progression of irradiated cells into mitosis using the mitotic marker, phosphorylated histone H3. We found evident differences in the activity of the early G2-phase checkpoint between HRS-positive and HRS-negative fibroblasts. In HRS-positive fibroblasts the checkpoint was not triggered and DNA damage was not recognized after doses lower than 0.2Gy resulting in HRS response. On the contrary, in HRS-negative fibroblasts the early G2-phase checkpoint was activated regardless of the dose in the range 0.1-2Gy. In conclusion, although cell cycle phase has no effect on the presence of HRS effect in normal human fibroblasts, the data reported here indicate that HRS response in these cells is associated with the functioning of early G2-phase checkpoint in a threshold-dose dependent manner, similarly as it takes place in most of human tumor and other cells. PMID:26725161

  4. Ring current activity during the early Bz<0 phase of the January 1997 magnetic cloud

    NASA Astrophysics Data System (ADS)

    Jordanova, V. K.; Torbert, R. B.; Thorne, R. M.; Collin, H. L.; Roeder, J. L.; Foster, J. C.

    1999-11-01

    The passage at Earth of the January 10-11, 1997, magnetic cloud induced a storm of moderate geomagnetic activity with Dst index reaching minimum values of about -83 nT. We study ring current formation during the early Bz negative phase of this magnetic cloud, using energetic particle data from three instruments on the Polar spacecraft and geosynchronous plasma data from the LANL spacecraft. We use our kinetic drift-loss model to simulate the evolution of ring current H+, He+, and O+ ion distributions and associated aeronomical effects during this period. The results from two Volland-Stern type magnetospheric electric field model formulations are compared: (1) Kp-dependent and (2) interplanetary magnetic field (IMF) dependent. We demonstrate that while both electric field models reproduce well the main trends of ring current formation and decay during the storm, the IMF-dependent model reproduces the rapidity of the main storm growth phase and its strength better. Comparing model results during the main phase of the storm with HYDRA, TIMAS, and CAMMICE data we find that the model reproduces very well the ring current distributions near dawn. The formation of the nose event, i.e., the rise of the 10-30 keV energy particles near dusk due to abruptly increased convection is, however, overestimated by the model. We compute plasmaspheric heating through Coulomb collisions as the storm evolves and find that maximum heating occurs initially on the nightside near L~3.5 and subsequently moves earthward to L~2.75, in agreement with Millstone Hill radar observations of midlatitude electron temperature enhancement on January 10. However, the magnitude of the energy transferred to plasmaspheric electrons through Coulomb collisions appears to be not sufficient to yield the observed elevated electron temperature at ~0830 UT, suggesting that additional energy sources should be considered during this event.

  5. HSP70.1 AND -70.3 ARE REQUIRED FOR LATE-PHASE PROTECTION INDUCED BY ISCHEMIC PRECONDITIONING OF MOUSE HEARTS

    EPA Science Inventory

    Heat-Shock Proteins 70.1 and 70.3 Are Required for Late-phase Protection
    Induced by Ischemic Preconditioning of the Mouse Heart
    Craig R. Hampton 1 , Akira Shimamoto 1 , Christine L. Rothnie 1 , Jeaneatte Griscavage-Ennis 1 ,
    Albert Chong 1 , David J. Dix 2 , Edward D. Ve...

  6. The Use of Fermented Soybean Meals during Early Phase Affects Subsequent Growth and Physiological Response in Broiler Chicks

    PubMed Central

    Kim, S. K.; Kim, T. H.; Lee, S. K.; Chang, K. H.; Cho, S. J.; Lee, K. W.; An, B. K.

    2016-01-01

    The objectives of this experiment was to evaluate the subsequent growth and organ weights, blood profiles and cecal microbiota of broiler chicks fed pre-starter diets containing fermented soybean meal products during early phase. A total of nine hundred 1-d-old chicks were randomly assigned into six groups with six replicates of 25 chicks each. The chicks were fed control pre-starter diet with dehulled soybean meal (SBM) or one of five experimental diets containing fermented SBM products (Bacillus fermented SBM [BF-SBM], yeast by product and Bacillus fermented SBM [YBF-SBM]; Lactobacillus fermented SBM 1 [LF-SBM 1]; Lactobacillus fermented SBM 2 [LF-SBM 2]) or soy protein concentrate (SPC) for 7 d after hatching, followed by 4 wk feeding of commercial diets without fermented SBMs or SPC. The fermented SBMs and SPC were substituted at the expense of dehulled SBM at 3% level on fresh weight basis. The body weight (BW) during the starter period was not affected by dietary treatments, but BW at 14 d onwards was significantly higher (p<0.05) in chicks that had been fed BF-SBM and YBF-SBM during the early phase compared with the control group. The feed intake during grower and finisher phases was not affected (p>0.05) by dietary treatments. During total rearing period, the daily weight gains in six groups were 52.0 (control), 57.7 (BF-SBM), 58.5 (YBF-SBM), 52.0 (LF-SBM 1), 56.7 (LF-SBM 2), and 53.3 g/d (SPC), respectively. The daily weight gain in chicks fed diet containing BF-SBM, YBF-SBM, and LF-SBM 2 were significantly higher values (p<0.001) than that of the control group. Chicks fed BF-SBM, YBF-SBM, and LF-SBM 2 had significantly lower (p<0.01) feed conversion ratio compared with the control group. There were no significant differences in the relative weight of various organs and blood profiles among groups. Cecal microbiota was altered by dietary treatments. At 35 d, chicks fed on the pre-starter diets containing BF-SBM and YBF-SBM had significantly increased (p<0

  7. The Use of Fermented Soybean Meals during Early Phase Affects Subsequent Growth and Physiological Response in Broiler Chicks.

    PubMed

    Kim, S K; Kim, T H; Lee, S K; Chang, K H; Cho, S J; Lee, K W; An, B K

    2016-09-01

    The objectives of this experiment was to evaluate the subsequent growth and organ weights, blood profiles and cecal microbiota of broiler chicks fed pre-starter diets containing fermented soybean meal products during early phase. A total of nine hundred 1-d-old chicks were randomly assigned into six groups with six replicates of 25 chicks each. The chicks were fed control pre-starter diet with dehulled soybean meal (SBM) or one of five experimental diets containing fermented SBM products (Bacillus fermented SBM [BF-SBM], yeast by product and Bacillus fermented SBM [YBF-SBM]; Lactobacillus fermented SBM 1 [LF-SBM 1]; Lactobacillus fermented SBM 2 [LF-SBM 2]) or soy protein concentrate (SPC) for 7 d after hatching, followed by 4 wk feeding of commercial diets without fermented SBMs or SPC. The fermented SBMs and SPC were substituted at the expense of dehulled SBM at 3% level on fresh weight basis. The body weight (BW) during the starter period was not affected by dietary treatments, but BW at 14 d onwards was significantly higher (p<0.05) in chicks that had been fed BF-SBM and YBF-SBM during the early phase compared with the control group. The feed intake during grower and finisher phases was not affected (p>0.05) by dietary treatments. During total rearing period, the daily weight gains in six groups were 52.0 (control), 57.7 (BF-SBM), 58.5 (YBF-SBM), 52.0 (LF-SBM 1), 56.7 (LF-SBM 2), and 53.3 g/d (SPC), respectively. The daily weight gain in chicks fed diet containing BF-SBM, YBF-SBM, and LF-SBM 2 were significantly higher values (p<0.001) than that of the control group. Chicks fed BF-SBM, YBF-SBM, and LF-SBM 2 had significantly lower (p<0.01) feed conversion ratio compared with the control group. There were no significant differences in the relative weight of various organs and blood profiles among groups. Cecal microbiota was altered by dietary treatments. At 35 d, chicks fed on the pre-starter diets containing BF-SBM and YBF-SBM had significantly increased (p<0

  8. Challenge of pigs with classical swine fever viruses after C-strain vaccination reveals remarkably rapid protection and insights into early immunity.

    PubMed

    Graham, Simon P; Everett, Helen E; Haines, Felicity J; Johns, Helen L; Sosan, Olubukola A; Salguero, Francisco J; Clifford, Derek J; Steinbach, Falko; Drew, Trevor W; Crooke, Helen R

    2012-01-01

    Pre-emptive culling is becoming increasingly questioned as a means of controlling animal diseases, including classical swine fever (CSF). This has prompted discussions on the use of emergency vaccination to control future CSF outbreaks in domestic pigs. Despite a long history of safe use in endemic areas, there is a paucity of data on aspects important to emergency strategies, such as how rapidly CSFV vaccines would protect against transmission, and if this protection is equivalent for all viral genotypes, including highly divergent genotype 3 strains. To evaluate these questions, pigs were vaccinated with the Riemser® C-strain vaccine at 1, 3 and 5 days prior to challenge with genotype 2.1 and 3.3 challenge strains. The vaccine provided equivalent protection against clinical disease caused by for the two challenge strains and, as expected, protection was complete at 5 days post-vaccination. Substantial protection was achieved after 3 days, which was sufficient to prevent transmission of the 3.3 strain to animals in direct contact. Even by one day post-vaccination approximately half the animals were partially protected, and were able to control the infection, indicating that a reduction of the infectious potential is achieved very rapidly after vaccination. There was a close temporal correlation between T cell IFN-γ responses and protection. Interestingly, compared to responses of animals challenged 5 days after vaccination, challenge of animals 3 or 1 days post-vaccination resulted in impaired vaccine-induced T cell responses. This, together with the failure to detect a T cell IFN-γ response in unprotected and unvaccinated animals, indicates that virulent CSFV can inhibit the potent antiviral host defences primed by C-strain in the early period post vaccination.

  9. Challenge of Pigs with Classical Swine Fever Viruses after C-Strain Vaccination Reveals Remarkably Rapid Protection and Insights into Early Immunity

    PubMed Central

    Haines, Felicity J.; Johns, Helen L.; Sosan, Olubukola A.; Salguero, Francisco J.; Clifford, Derek J.; Steinbach, Falko; Drew, Trevor W.; Crooke, Helen R.

    2012-01-01

    Pre-emptive culling is becoming increasingly questioned as a means of controlling animal diseases, including classical swine fever (CSF). This has prompted discussions on the use of emergency vaccination to control future CSF outbreaks in domestic pigs. Despite a long history of safe use in endemic areas, there is a paucity of data on aspects important to emergency strategies, such as how rapidly CSFV vaccines would protect against transmission, and if this protection is equivalent for all viral genotypes, including highly divergent genotype 3 strains. To evaluate these questions, pigs were vaccinated with the Riemser® C-strain vaccine at 1, 3 and 5 days prior to challenge with genotype 2.1 and 3.3 challenge strains. The vaccine provided equivalent protection against clinical disease caused by for the two challenge strains and, as expected, protection was complete at 5 days post-vaccination. Substantial protection was achieved after 3 days, which was sufficient to prevent transmission of the 3.3 strain to animals in direct contact. Even by one day post-vaccination approximately half the animals were partially protected, and were able to control the infection, indicating that a reduction of the infectious potential is achieved very rapidly after vaccination. There was a close temporal correlation between T cell IFN-γ responses and protection. Interestingly, compared to responses of animals challenged 5 days after vaccination, challenge of animals 3 or 1 days post-vaccination resulted in impaired vaccine-induced T cell responses. This, together with the failure to detect a T cell IFN-γ response in unprotected and unvaccinated animals, indicates that virulent CSFV can inhibit the potent antiviral host defences primed by C-strain in the early period post vaccination. PMID:22235283

  10. Early protection in sheep against intratypic heterologous challenge with serotype O foot-and-mouth disease virus using high-potency, emergency vaccine.

    PubMed

    Horsington, Jacquelyn; Zhang, Zhidong; Bittner, Hilary; Hole, Kate; Singanallur, Nagendrakumar B; Alexandersen, Soren; Vosloo, Wilna

    2015-01-01

    In 2009-2011, spread of a serotype O foot-and-mouth disease virus (FMDV) belonging to the South East Asia topotype led to the culling of over 3.5 million cattle and pigs in Japan and Korea. The O1 Manisa vaccine (belonging to the Middle East-South Asian topotype) was used at high potency in Korea to limit the expansion of the outbreak. However, no data are available on the spread of this virus or the efficacy of the O1 Manisa vaccine against this virus in sheep. In this study, the early protection afforded with a high potency (>6 PD50) FMD O1 Manisa vaccine against challenge with the O/SKR/2010 virus was tested in sheep. Sheep (n=8) were vaccinated 4 days prior to continuous direct-contact challenge with donor sheep. Donor sheep were infected with FMDV O/SKR/2010 by coronary band inoculation 24h prior to contact with the vaccinated animals, or unvaccinated controls (n=4). Three of the four control sheep became infected, two clinically. All eight O1 Manisa vaccinated sheep were protected from clinical disease. None had detectable antibodies to FMDV non-structural proteins (3ABC), no virus was isolated from nasal swabs, saliva or oro-pharyngeal fluid and none became carriers. Using this model of challenge, sheep were protected against infection as early as 4 days post vaccination.

  11. EARLY-PHASE PHOTOMETRY AND SPECTROSCOPY OF TRANSITIONAL TYPE Ia SN 2012ht: DIRECT CONSTRAINT ON THE RISE TIME

    SciTech Connect

    Yamanaka, Masayuki; Nogami, Daisaku; Maeda, Keiichi; Kawabata, Miho; Masumoto, Kazunari; Matsumoto, Katsura; Tanaka, Masaomi; Takaki, Katsutoshi; Ueno, Issei; Itoh, Ryosuke; Kawabata, Koji S.; Moritani, Yuki; Akitaya, Hiroshi; Yoshida, Michitoshi; Arai, Akira; Honda, Satoshi; Nishiyama, Koichi; Kabashima, Fujio

    2014-02-20

    We report photometric and spectroscopic observations of the nearby Type Ia Supernova (SN Ia) 2012ht from –15.8 days to +49.1 days after B-band maximum. The decline rate of the light curve is Δm {sub 15}(B) = 1.39 ± 0.05 mag, which is intermediate between normal and subluminous SNe Ia, and similar to that of the ''transitional'' Type Ia SN 2004eo. The spectral line profiles also closely resemble those of SN 2004eo. We were able to observe SN 2012ht at a very early phase, when it was still rising and was about three magnitudes fainter than at the peak. The rise time to the B-band maximum is estimated to be 17.6 ± 0.5 days and the time of the explosion is MJD 56277.98 ± 0.13. SN 2012ht is the first transitional SN Ia whose rise time is directly measured without using light curve templates, and the fifth SN Ia overall. This rise time is consistent with those of the other four SNe within the measurement error, even including the extremely early detection of SN 2013dy. The rising part of the light curve can be fitted by a quadratic function, and shows no sign of a shock-heating component due to the interaction of the ejecta with a companion star. The rise time is significantly longer than that inferred for subluminous SNe such as SN 1991bg, which suggests that a progenitor and/or explosion mechanism of transitional SNe Ia are more similar to normal SNe Ia rather than to subluminous SNe Ia.

  12. Caspr3-Deficient Mice Exhibit Low Motor Learning during the Early Phase of the Accelerated Rotarod Task

    PubMed Central

    Hirata, Haruna; Takahashi, Aki; Shimoda, Yasushi; Koide, Tsuyoshi

    2016-01-01

    Caspr3 (Contactin-associated protein-like 3, Cntnap3) is a neural cell adhesion molecule belonging to the Caspr family. We have recently shown that Caspr3 is expressed abundantly between the first and second postnatal weeks in the mouse basal ganglia, including the striatum, external segment of the globus pallidus, subthalamic nucleus, and substantia nigra. However, its physiological role remains largely unknown. In this study, we conducted a series of behavioral analyses on Capsr3-knockout (KO) mice and equivalent wild-type (WT) mice to investigate the role of Caspr3 in brain function. No significant differences were observed in most behavioral traits between Caspr3-KO and WT mice, but we found that Caspr3-KO mice performed poorly during the early phase of the accelerated rotarod task in which latency to falling off a rod rotating with increasing velocity was examined. In the late phase, the performance of the Caspr3-KO mice caught up to the level of WT mice, suggesting that the deletion of Caspr3 caused a delay in motor learning. We then examined changes in neural activity after training on the accelerated rotarod by conducting immunohistochemistry using antibody to c-Fos, an indirect marker for neuronal activity. Experience of the accelerated rotarod task caused increases in the number of c-Fos-positive cells in the dorsal striatum, cerebellum, and motor cortex in both Caspr3-KO and WT mice, but the number of c-Fos-positive cells was significantly lower in the dorsal striatum of Caspr3-KO mice than in that of WT mice. The expression of c-Fos in the ventral striatum of Caspr3-KO and WT mice was not altered by the training. Our findings suggest that reduced activation of neural cells in the dorsal striatum in Caspr3-KO mice leads to a decline in motor learning in the accelerated rotarod task. PMID:26807827

  13. Early Murine Cytomegalovirus (MCMV) Infection Induces Liver Natural Killer (NK) Cell Inflammation and Protection Through Macrophage Inflammatory Protein 1α (MIP-1α)–dependent Pathways

    PubMed Central

    Salazar-Mather, Thais P.; Orange, Jordan S.; Biron, Christine A.

    1998-01-01

    Natural killer (NK) cells mediate defense against early murine cytomegalovirus (MCMV) infections in liver. The chemokine, macrophage inflammatory protein 1α (MIP-1α), can promote inflammatory responses. Our studies evaluated contributions of NK cells to early MCMV-induced liver inflammation and MIP-1α requirements for inflammation and delivery of antiviral defenses. NK cells were shown to be responsible for focal inflammation, and to be induced to migrate at high levels, in MCMV-infected livers. MIP-1α gene expression was elevated at coinciding times, and mice deficient in MIP-1α function were dramatically inhibited in both inflammatory and protective liver responses. The results precisely define MIP-1α–dependent steps required to achieve NK cell inflammation during, and mechanisms promoting defense against, viral infections in tissues. PMID:9419206

  14. Bullying in Early Adolescence and Antisocial Behavior and Depression Six Years Later: What Are the Protective Factors?

    ERIC Educational Resources Information Center

    Vassallo, Suzanne; Edwards, Ben; Renda, Jennifer; Olsson, Craig A.

    2014-01-01

    This study identified factors that protected (a) adolescent bullies from becoming antisocial young adults, and (b) adolescent victims of bullying from subsequent depression. Data were drawn from the Australian Temperament Project, a population birth cohort study that has followed participants since 1983. Systematic examination of potential risk…

  15. Physical Environmental Adversity and the Protective Role of Maternal Monitoring in Relation to Early Child Conduct Problems

    ERIC Educational Resources Information Center

    Supplee, Lauren H.; Unikel, Emily B.; Shaw, Daniel S.

    2007-01-01

    Research on the development of externalizing behaviors during early childhood has focused on child and parenting factors. Fewer studies have investigated effects of aversive features of the micro-level physical environment, such as overcrowding and chaos in the home, and the macro-level environment, such as neighborhood quality. This study extends…

  16. SunSmart: Evaluation of a Pilot School-Based Sun Protection Intervention in Hispanic Early Adolescents

    ERIC Educational Resources Information Center

    Miller, K. A.; Langholz, B. M.; Ly, T.; Harris, S. C.; Richardson, J. L.; Peng, D. H.; Cockburn, M. G.

    2015-01-01

    The incidence of melanoma is rising among Hispanic populations in the United States. The purpose of this study is to evaluate the impact of a pilot sun safety educational intervention conducted from 2006 to 2012 on Hispanic early adolescents in a high ultraviolet environment. Nineteen schools with high Hispanic enrollment were recruited from urban…

  17. Convenient Synthesis of Acetonide Protected 3,4-Dihydroxyphenylalanine (DOPA) for Fmoc Solid-Phase Peptide Synthesis

    PubMed Central

    Liu, Zhongqiang; Hu, Bi-huang; Messersmith, Phillip B.

    2008-01-01

    We report a facile approach to the synthesis of acetonide and Fmoc protected 3,4-dihydroxyphenylalanine (DOPA), Fmoc-DOPA(acetonide)-OH. By protecting the amino group of DOPA with a phthaloyl group and the carboxyl group as a methyl ester, acetonide protection of the catechol of DOPA derivative was realized in the presence of p-toluenesulfonic acid. Following removal of protecting groups, the intermediate was converted to Fmoc-DOPA(acetonide)-OH, which was successfully incorporated into a short DOPA-containing peptide, derived from marine tubeworm cement proteins Pc1 and Pc2. PMID:19759805

  18. An investigation of low ergonomics risk awareness, among staffs at early product development phase in Malaysia automotive industries

    NASA Astrophysics Data System (ADS)

    Aziz, Fazilah Abdul; Razali, Noraini; Najmiyah Jaafar, Nur

    2016-02-01

    Currently there are many automotive companies still unable to effectively prevent consequences of poor ergonomics in their manufacturing processes. This study purpose is to determine the surrounding factors that influence low ergonomics risk awareness among staffs at early product development phase in Malaysia automotive industry. In this study there are four variables, low ergonomic risk awareness, inappropriate method and tools, tight development schedule and lack of management support. The survey data were gathered from 245 respondents of local automotive companies in Malaysia. The data was analysed through multiple regression and moderated regression using the IBM SPSS software. Study results revealed that low ergonomic risk awareness has influenced by inappropriate method and tool, and tight development schedule. There were positive linear relationships between low ergonomic risk awareness and inappropriate method and tools, and tight development schedule. The more inappropriate method and tools applied; the lower their ergonomic risk awareness. The more tight development schedule is the lower ergonomic risk awareness. The relationship between low ergonomic risk awareness and inappropriate method and tools depends on staff's age, and education level. Furthermore the relationship between low ergonomic risk awareness and tight development schedule depends on staff's working experience and number of project involvement. The main contribution of this paper was identified the number of factors of low ergonomics risk awareness and offers better understanding on ergonomics among researchers and automotive manufacturer's employees during product development process.

  19. Organization and development of the mineral phase during early ontogenesis of the bony fin rays of the trout Oncorhynchus mykiss.

    PubMed

    Landis, W J; Géraudie, J

    1990-12-01

    Characterization of mineral deposition has been studied by electron optical methods during early ontogenesis of lepidotrichia, the bony fin rays, of the trout Oncorhynchus mykiss (the former Salmo gairdneri). The fin rays consist of an extracellular granular ground substance containing in part a network of collagen fibrils within the basal lamella of the fin dermoepidermal interface. Growth of individual rays proceeds in a proximodistal direction. The mineral phase appears as electron-dense needle or plate-like particles and is associated with the collagenous matrix. On analysis of progressively maturing tissue, the mineral was characterized as a poorly crystalline hydroxyapatite with Ca/P molar ratios in the range of 1.0-1.4, corresponding to distal and proximal areas, respectively. With selected-area electron diffraction and dark field imaging of lepidotrichia, the mineral particles were found to be about 3-10 nm thick and 12-20 nm in length (along their crystallographic c-axes), possibly aggregated into larger crystals 35-40 nm long observed with bright field microscopy. No definitive relation was found between either the c- or a,b-axes images of the crystals and the periodic structure of collagen, which forms the framework for mineral deposition in this and in other vertebrate calcifying tissues. PMID:2285157

  20. Enzymatic characterization of germination-specific cysteine protease-1 expressed transiently in cotyledons during the early phase of germination.

    PubMed

    Tsuji, Akihiko; Tsukamoto, Kana; Iwamoto, Keiko; Ito, Yuka; Yuasa, Keizo

    2013-01-01

    Papain-like cysteine protease activity that shows a unique transient expression profile in cotyledons of daikon radish during germination was detected. The enzyme showed a distinct elution pattern on DEAE-cellulose compared with cathepsin B-like and Responsive to dessication-21 cysteine protease. Although this activity was not detected in seed prior to imbibition, the activity increased markedly and reached a maximum at 2 days after imbibition and then decreased rapidly and completely disappeared after 5 days. Using cystatin-Sepharose, the 26 kDa cysteine protease (DRCP26) was isolated from cotyledons at 2 days after imbibition. The deduced amino acid sequence from the cDNA nucleotide sequence indicated that DRCP26 is an orthologue of Arabidopsis unidentified protein, germination-specific cysteine protease-1, belonging to the C1 family of cysteine protease predicted from genetic information. In an effort to characterize the enzymatic properties of DRCP26, the enzyme was purified to homogeneity from cotyledons at 48 h after imbibition. The best synthetic substrate for the enzyme was carbobenzoxy-Phe-Arg-4-methylcoumaryl-7-amide. All model peptides were digested to small peptides by the enzyme, suggesting that DRCP26 possesses broad cleavage specificity. These results indicated that DRCP26 plays a role in the mobilization of storage proteins in the early phase of seed germination.

  1. Distribution of CCS and HC{sub 3}N in L1147, an early phase dark cloud

    SciTech Connect

    Suzuki, Taiki; Ohishi, Masatoshi; Hirota, Tomoya

    2014-06-20

    We used the Nobeyama 45 m radio telescope to reveal spatial distributions of CCS and HC{sub 3}N in L1147, one of the carbon-chain producing region (CCPR) candidates, where carbon-chain molecules are dominant rather than NH{sub 3}. We found that three cores (two CCS cores and one HC{sub 3}N core), which are away from a very low luminosity object (a source that may turn into a sub-stellar mass brown dwarf), exist along the NE-SW filament traced by the 850 μm dust continuum. The column densities of CCS are 3-7 × 10{sup 12} cm{sup –2} and those of HC{sub 3}N are 2-6 × 10{sup 12} cm{sup –2}, respectively, much lower than those previously reported toward other CCPRs. We also found that two CCS peaks are displaced from the peaks of HC{sub 3}N. In order to interpret such interleaved distributions, we conducted chemical reaction network simulations and found that slightly different gas densities could lead to large variation of the CCS-to-HC{sub 3}N ratio in the early phase of dark cloud evolution. Such a chemical 'variation' may be seen in other CCPRs. Finally, we were able to confirm that the L1147 filament can be regarded as a CCPR.

  2. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib

    PubMed Central

    Saglio, Giuseppe; Kantarjian, Hagop M.; Guilhot, François; Niederwieser, Dietger; Rosti, Gianantonio; Nakaseko, Chiaki; De Souza, Carmino Antonio; Kalaycio, Matt E.; Meier, Stephan; Fan, Xiaolin; Menssen, Hans D.; Larson, Richard A.; Hochhaus, Andreas

    2014-01-01

    We explored the impact of early molecular response (EMR; BCR-ABL ≤10% on the international scale [BCR-ABLIS] at 3 or 6 months) on outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with nilotinib or imatinib based on 4 years of follow up in Evaluating Nilotinib Efficacy and Safety in Clinical Trials—Newly Diagnosed Patients. Patients (n = 846) received nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, or imatinib 400 mg once daily. At 3 months, more patients had EMR failure (ie, BCR-ABLIS >10%) on imatinib (33%) than on nilotinib (9%-11%); similarly at 6 months, 16% of patients in the imatinib arm vs 3% and 7% in the nilotinib arms had EMR failure. In all arms, EMR failure was associated with lower rates of molecular response, an increased risk of progression, and lower overall survival compared with EMR achievement. We also analyzed patient and treatment characteristics associated with EMR and found distinct patterns in the nilotinib arms vs the imatinib arm. High Sokal risk score was associated with a high rate of EMR failure on imatinib, but not on nilotinib. In contrast, reduced dose intensity and dose interruptions were strongly associated with EMR failure in nilotinib-treated, but not imatinib-treated, patients. This study is registered at www.clinicaltrials.gov as #NCT00471497. PMID:24335106

  3. Presence of Citrullinated Histone H3-Positive Neutrophils in Microscopic Polyangiitis from the Early Phase: An Autopsy Proven Case.

    PubMed

    Matsuda, Yoko; Hamayasu, Hideki; Seki, Atsuko; Nonaka, Keisuke; Wang, Tan; Matsumoto, Takumi; Hamano, Yoshitomo; Sumikura, Hiroyuki; Kumasaka, Toshio; Murayama, Shigeo; Ishizu, Akihiko; Shimizu, Akira; Sugihara, Takahiko; Arai, Tomio

    2016-08-01

    A 76-year-old man was admitted with general fatigue, weight loss, fever, headache, renal failure, and a high serum level of myeloperoxidase-antineutrophil cytoplasmic antibody. Biopsy revealed citrullinated histone H3 (citH3)-positive neutrophils adherent to the temporal artery endothelium. Three days after completing pulse steroid therapy, he suffered from a sudden disturbance of consciousness and died. On autopsy, the kidneys showed the most severe vasculitis with dense infiltration of citH3-positive neutrophils. The lungs showed intra-alveolar hemorrhage due to capillaritis. Severe brain hemorrhage was found in the left frontal lobe and putamen with uncal herniation. No vasculitis or thrombi was observed in the brain. The right dura mater was thickened due to fibrosis and inflammation. In conclusion, autopsy revealed systemic vasculitis with infiltration of abundant citH3-positive neutrophils, suggesting that the neutrophil extracellular trap formation and citH3 might play important roles in the early phases and development of microscopic polyangiitis. PMID:27427341

  4. Effects of prior treatment with simvastatin on skeletal muscle structure and mitochondrial enzyme activities during early phases of sepsis.

    PubMed

    Ozkok, Elif; Yorulmaz, Hatice; Ates, Gulten; Serdaroglu-Oflazer, Piraye; Tamer, Ayse Sule

    2014-01-01

    We investigated the effects of the early phase of sepsis and prior treatment of Simvastatin on muscle structure and mitochondrial enzymes treated with lipopolysaccharide (LPS) in rats. We divided rats into control, LPS, simvastatin, simvastatin + LPS groups. Mitochondrial citrate synthase, complex I, II, I + III, II + III, cytochrome c oxidase (COX) activities were measured. Muscle tissue was stained using modified Gomori trichrome (MGT), succinic dehydrogenase (SDH) and cytochrome oxidase (COX). In all treated groups, complex I and citrate synthase activities were higher than in the controls. In the control and LPS groups, COX activity was increased when compared with simvastatins'. Complex II, II-III activities were higher in the LPS group than in the control group. Complex I-III activities were higher in the Simvastatin and Simvastatin + LPS groups than in the control and LPS groups (P < 0.05). Myopathic changes with LPS group were observed in MGT stained sections. Our findings showed improvements in the alterations of enzyme activities and muscle myofibrils after treating rats with LPS that had received a prior dose of simvastatin.

  5. Estrus synchronization and conception rate after a progesterone releasing intravaginal device (PRID) treatment from the early luteal phase in heifers.

    PubMed

    Kuroiwa, Takenobu; Ishibashi, Ai; Fukuda, Masaharu; Kim, Seungjoon; Tanaka, Tomomi; Kamomae, Hideo

    2005-10-01

    The objective of the present study was to evaluate estrus synchronization and conception rate after progesterone releasing intravaginal device (PRID) treatment from the early luteal phase in the presence or absence of estradiol benzoate (EB) in heifers. Heifers (n=11) were assigned randomly to two treatments; insertion of a PRID containing 1.55 g progesterone with a capsule attached including 10 mg EB (P+EB; n=6) and the PRID withdrawn the EB capsule (P-EB; n=5). The PRID was inserted into the vagina on Day 2 of the estrous cycle (Day 0 was the day of ovulation) and was left for 12 days. The proportion of heifers exhibiting standing estrus within 3 days after PRID removal was 83.3% (5/6) for the P+EB group, and 80.0% (4/5) for the P-EB group, respectively. Conception rate by artificial insemination on synchronized estrus was 80.0% (4/5) in the P+EB group, and 100% (4/4) in the P-EB treatment group, respectively. These results suggest that a PRID treatment from 2 days after ovulation for 12 days in the presence or absence of EB has an effect on the synchronization of estrus and produces a beneficial conception rate in heifers.

  6. The Solar and Heliospheric Observatory (SOHO) Mission: An Overview of Flight Dynamics Support of the Early Mission Phase

    NASA Technical Reports Server (NTRS)

    Short, R.; Behuncik, J.

    1996-01-01

    The SOHO spacecraft was successfully launched by an Atlas 2AS from the Eastern Range on December 2, 1995. After a short time in a nearly circular parking orbit, the spacecraft was placed by the Centaur upper stage on a transfer trajectory to the L1 libration point where it was inserted into a class 1 Halo orbit. The nominal mission lifetime is two years which will be spent collecting data from the Sun using a complement of twelve instruments. An overview of the early phases of Flight Dynamics Facility support of the mission is given. Maneuvers required for the mission are discussed, and an evaluation of these maneuvers is given with the attendent effects on the resultant orbit. Thruster performance is presented as well as real time monitoring of thruster activity during maneuvers. Attitude areas presented are the star identification process and role angle determination, momentum management, operating constraints on the star tracker, and guide star switching. A brief description of the two Heads Up displays is given.

  7. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib.

    PubMed

    Hughes, Timothy P; Saglio, Giuseppe; Kantarjian, Hagop M; Guilhot, François; Niederwieser, Dietger; Rosti, Gianantonio; Nakaseko, Chiaki; De Souza, Carmino Antonio; Kalaycio, Matt E; Meier, Stephan; Fan, Xiaolin; Menssen, Hans D; Larson, Richard A; Hochhaus, Andreas

    2014-02-27

    We explored the impact of early molecular response (EMR; BCR-ABL ≤10% on the international scale [BCR-ABL(IS)] at 3 or 6 months) on outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with nilotinib or imatinib based on 4 years of follow up in Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients. Patients (n = 846) received nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, or imatinib 400 mg once daily. At 3 months, more patients had EMR failure (ie, BCR-ABL(IS) >10%) on imatinib (33%) than on nilotinib (9%-11%); similarly at 6 months, 16% of patients in the imatinib arm vs 3% and 7% in the nilotinib arms had EMR failure. In all arms, EMR failure was associated with lower rates of molecular response, an increased risk of progression, and lower overall survival compared with EMR achievement. We also analyzed patient and treatment characteristics associated with EMR and found distinct patterns in the nilotinib arms vs the imatinib arm. High Sokal risk score was associated with a high rate of EMR failure on imatinib, but not on nilotinib. In contrast, reduced dose intensity and dose interruptions were strongly associated with EMR failure in nilotinib-treated, but not imatinib-treated, patients. This study is registered at www.clinicaltrials.gov as #NCT00471497.

  8. A central role for the mast cell in early phase vasculitis in the Brown Norway rat model of vasculitis: a histological study

    PubMed Central

    Vinen, Catherine S; Turner, David R; Oliveira, David B G

    2004-01-01

    Administration of mercuric chloride (HgCl2) to Brown Norway rats causes Th2-dominated autoimmunity with raised immunoglobulin E concentrations and gut vasculitis, both of which are T-cell dependent, peak at 14 days after starting HgCl2 and then spontaneously resolve. If animals are re-challenged with HgCl2 6 weeks after initial exposure, they are resistant to autoimmunity, developing only attenuated disease. Recently, a separate phase of early caecal vasculitis was described beginning 24 h after initiating HgCl2 and prior to caecal entry of T cells. Previous work suggested this early vasculitis was αβ T-cell independent and implied a role for mast cells. We further tested this hypothesis by performing a histological study during the first 93 h following HgCl2 challenge defining the precise relationship between gut mast cell degranulation and appearing caecal vasculitis. We also studied whether early caecal vasculitis enters a resistant phase upon re-challenge with HgCl2. We show a direct correlation between mast cell degranulation and early caecal vasculitis following initial HgCl2 challenge. We demonstrate resistance to re-challenge in this phase of injury, with results at re-challenge also showing a correlation between mast cell degranulation and early caecal injury. PMID:15255970

  9. Psychotropic and Anticonvulsant Drug Usage in Early Childhood Special Education Programs I. Phase One: A Preliminary Report: Prevalence, Attitude, Training, and Problems.

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.

    As part of a three phase study designed to survey the teachers and parents of children receiving psychotropic and anticonvulsant drugs, 208 teachers of preschool special education children on medication were mailed questionnaires. The Early Childhood Medication Questionnaire used in the survey included items relating to teacher, program, and…

  10. Migration as a turning point in food habits: the early phase of dietary acculturation among women from South Asian, African, and Middle Eastern Countries living in Norway.

    PubMed

    Terragni, Laura; Garnweidner, Lisa M; Pettersen, Kjell Sverre; Mosdøl, Annhild

    2014-01-01

    This article explores the early phase of dietary acculturation after migration. South Asian, African and Middle Eastern women (N = 21) living in Norway were interviewed about their early experiences with food in a new context. The findings pointed to abrupt changes in food habits in the first period after migration. To various degrees, women reported unfamiliarity with foods in shops, uncertainty about meal formats and food preparation and fear of eating food prohibited by their religion. Their food consumption tended to be restricted to food items perceived as familiar or safe. Our findings indicate that the first period after migration represents a specific phase in the process of dietary acculturation. Early initiatives aimed at enhancing confidence in food and familiarity with the new food culture are recommended.

  11. Peer acceptance protects global self-esteem from negative effects of low closeness to parents during adolescence and early adulthood.

    PubMed

    Birkeland, Marianne Skogbrott; Breivik, Kyrre; Wold, Bente

    2014-01-01

    Having a distant relationship with parents seems to increase the risk of developing a more negative global self-esteem. This article describes a longitudinal study of 1,090 Norwegian adolescents from the age of 13-23 (54 % males) that explored whether peer acceptance can act as a moderator and protect global self-esteem against the negative effects of experiencing low closeness in relationships with parents. A quadratic latent growth curve for global self-esteem with closeness to parents and peer acceptance as time-varying covariates was modeled, taking partial measurement invariance in global self-esteem into account. Peer acceptance was found to have a general protective effect on global self-esteem for all adolescents. In addition, at most ages, peer acceptance was found to have a protective-stabilizing effect on the relationship between closeness to parents and global self-esteem. This indicates that peer acceptance can be an especially valuable source of global self-esteem when closeness to parents is low. PMID:23435859

  12. Peer acceptance protects global self-esteem from negative effects of low closeness to parents during adolescence and early adulthood.

    PubMed

    Birkeland, Marianne Skogbrott; Breivik, Kyrre; Wold, Bente

    2014-01-01

    Having a distant relationship with parents seems to increase the risk of developing a more negative global self-esteem. This article describes a longitudinal study of 1,090 Norwegian adolescents from the age of 13-23 (54 % males) that explored whether peer acceptance can act as a moderator and protect global self-esteem against the negative effects of experiencing low closeness in relationships with parents. A quadratic latent growth curve for global self-esteem with closeness to parents and peer acceptance as time-varying covariates was modeled, taking partial measurement invariance in global self-esteem into account. Peer acceptance was found to have a general protective effect on global self-esteem for all adolescents. In addition, at most ages, peer acceptance was found to have a protective-stabilizing effect on the relationship between closeness to parents and global self-esteem. This indicates that peer acceptance can be an especially valuable source of global self-esteem when closeness to parents is low.

  13. Water availability influences morphology, mycorrhizal associations, PSII efficiency and polyamine metabolism at early growth phase of Scots pine seedlings.

    PubMed

    Muilu-Mäkelä, Riina; Vuosku, Jaana; Läärä, Esa; Saarinen, Markku; Heiskanen, Juha; Häggman, Hely; Sarjala, Tytti

    2015-03-01

    Scots pine (Pinus sylvestris L.) is adapted to various soil types with diverse water availabilities. However, Scots pine seedlings are vulnerable to abiotic stress during the early growth, when they may be exposed to both dry and wet conditions. Here, we focused on the above and below ground coping strategies of Scots pine seedlings under controlled wet, optimal and dry soil conditions by investigating morphological traits including seedling biomass, number of root tips, proportion of mycorrhizal root tips and brown needles. In addition, we studied metabolic and physiological responses including gene expression involved in biosynthesis and catabolism of polyamines (PA), PSII efficiency and the expression of the catalase (CAT) late-embryogenesis abundant protein (LEA), pyruvate decarboxylase (PDC), glutamate-cysteine ligase (GCL) and glutathione synthetase (GS) genes. We found that seedlings invested in shoots by maintaining stable shoot water content and high PSII efficiency under drought stress. Free and soluble conjugated putrescine (Put) accumulated in needles under drought stress, suggesting the role of Put in protection of photosynthesizing tissues. However, the expression of the PA biosynthesis genes, arginine decarboxylase (ADC), spermidine synthase (SPDS) and thermospermine synthase (ACL5) was not affected under drought stress whereas catabolizing genes diamino oxidase (DAO) and polyamine oxidase (PAO) were down-regulated in shoots. The morphology of the roots was affected by peat water content. Furthermore, both drought stress and water excess restricted the seedling ability to sustain a symbiotic relationship. The consistent pattern of endogenous PAs seems to be advantageous to the Scots pine seedlings also under stress conditions. PMID:25666263

  14. Changes of hippocampal beta-alanine and citrulline levels are paralleling early and late phase of retrieval in the Morris Water Maze.

    PubMed

    Sase, Ajinkya; Dahanayaka, Sudath; Höger, Harald; Wu, Guoyao; Lubec, Gert

    2013-07-15

    Although a series of amino acids (AA) have been associated with spatial memory formation, there is limited information on concentrations of beta-alanine and citrulline in rodent brains. Given the importance of AA metabolism in cognitive functions it was the aim of the study to determine hippocampal levels of beta-alanine and citrulline in rats during two different phases of memory retrieval in a spatial memory paradigm. Ten rats were used per group and the first group was trained and sacrificed five min, the second six hours following retrieval in the Morris Water Maze (MWM) and the third and fourth group were untrained, yoked controls. Hippocampi were taken and free AA were determined using a well-established HPLC protocol. Beta-alanine and citrulline levels were higher in trained rat hippocampi, during both, early and late phase of memory retrieval. Taurine, methionine, cysteine, lysine and ornithine levels were higher in yoked rats at the late phase while tyrosine was higher in yoked rats during the early phase. There were no significant correlations between time spent in the target quadrant and any of the AA levels. Herein, an AA pattern, different between yoked and trained animals at early and late phase of memory retrieval is shown, indicating probable involvement of different AA pathways in animals trained and untrained in the MWM. The results may be useful for the interpretation of previous studies and the design of future experiments to identify amino acids as possible targets for modulating spatial memory.

  15. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations

    PubMed Central

    2014-01-01

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen. PMID:24589193

  16. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.

    PubMed

    Marchandeau, Stéphane; Pontier, Dominique; Guitton, Jean-Sébastien; Letty, Jérôme; Fouchet, David; Aubineau, Jacky; Berger, Francis; Léonard, Yves; Roobrouck, Alain; Gelfi, Jacqueline; Peralta, Brigitte; Bertagnoli, Stéphane

    2014-03-04

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.

  17. Differential signaling circuits in regulation of ultraviolet C light-induced early- and late-phase activation of NF-κB.

    PubMed

    Wu, Shiyong; Tong, Lingying

    2010-01-01

    Ultraviolet C light (UVC) induces nuclear factor-kappa B (NF-κB) activation via a complex network. In the early phase (4-12 h) of irradiation, NF-κB activation is accompanied with IκBα reduction via a translation inhibition pathway. In the late phase of UVC-induced NF-κB activation (16-24 h), the IκBα depletion is a combined result of regulation at both transcriptional and translational levels. However, the NF-κB activation appears to be independent of the level of IκBα. In this review, we will discuss the multiple signaling circuits that regulate NF-κB activation during the early and late phases of UVC irradiation. PMID:20553411

  18. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial

    PubMed Central

    Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John MS; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

    2009-01-01

    Summary Background Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. Methods In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2 at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m2 at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m2 at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. Findings All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0·95, 95% CI 0·85–1·08; p=0·44). 75·6% (95% CI 73·7–77·5) of patients in the experimental group and 74·3% (72·3–76·2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0·0001); the most frequent events were neutropenia (937 events vs 797 events

  19. Noninvasive early detection of anthracycline-induced cardiotoxicity in patients with hematologic malignancies using the phased tracking method.

    PubMed

    Saito, Yoshiko; Susukida, Ikuko; Uzuka, Yoshiro; Kanai, Hiroshi

    2016-09-01

    Anthracyclines are among the most effective and widely used anticancer drugs; however, their use is limited by serious cardiotoxicity. Early detection is necessary to prevent the high mortality rate associated with heart failure (HF). We evaluated cardiac function in 142 patients using conventional echocardiography and the phased tracking method (PTM), which was measured using the minute vibration and the rapid motion components, neither of which is recognized in standard M-mode nor in tissue Doppler imaging. For systolic function comparison, we compared left ventricular ejection fraction (LVEF) in conventional echocardiography with the average velocity of ventricular septum myocytes (Vave ) in the PTM. The Vave of 12 healthy volunteers was 1.5 (m/s)/m or more. At baseline of 99 patients, there was a positive correlation between LVEF and Vave in all patients. There were no significant differences in baseline cardiac function between patients with and without HF. There was a negative correlation between the cumulative anthracycline dose and LVEF or Vave among all patients. We determined that Vave 1.5 (m/s)/m was equivalent to LVEF 60%, 1.25 (m/s)/m to 55%, and 1.0 (m/s)/m to 50%. During the follow-up period, there was a pathological decrease in LVEF (<55%) and Vave (<1.25 m/s/m) in patients with HF; decreases in Vave were detected significantly earlier than those in LVEF (P < 0.001). When Vave declined to 1.5 (m/s)/m or less, careful continuous observation and cardiac examination was required. When Vave further declined to 1.0 (m/s)/m or lower, chemotherapy was postponed or discontinued; thus, serious drug-induced cardiomyopathy was avoided in patients who did not relapse. The PTM was superior to echocardiography for early, noninvasive detection and intermediate-term monitoring of left ventricle systolic function associated with anthracycline chemotherapy, among patients with hematologic malignancies. The PTM was an effective laboratory procedure to avoid the

  20. Phagosomal Acidification Prevents Macrophage Inflammatory Cytokine Production to Malaria, and Dendritic Cells Are the Major Source at the Early Stages of Infection: IMPLICATION FOR MALARIA PROTECTIVE IMMUNITY DEVELOPMENT.

    PubMed

    Wu, Xianzhu; Gowda, Nagaraj M; Gowda, D Channe

    2015-09-18

    Inflammatory cytokines produced at the early stages of malaria infection contribute to shaping protective immunity and pathophysiology. To gain mechanistic insight into these processes, it is important to understand the cellular origin of cytokines because both cytokine input and cytokine-producing cells play key roles. Here, we determined cytokine responses by monocytes, macrophages, and dendritic cells (DCs) to purified Plasmodium falciparum and Plasmodium berghei ANKA, and by spleen macrophages and DCs from Plasmodium yoelii 17NXL-infected and P. berghei ANKA-infected mice. The results demonstrate that monocytes and macrophages do not produce inflammatory cytokines to malaria parasites and that DCs are the primary source early in infection, and DC subsets differentially produce cytokines. Importantly, blocking of phagosomal acidification by inhibiting vacuolar-type H(+)-ATPase enabled macrophages to elicit cytokine responses. Because cytokine responses to malaria parasites are mediated primarily through endosomal Toll-like receptors, our data indicate that the inability of macrophages to produce cytokines is due to the phagosomal acidification that disrupts endosomal ligand-receptor engagement. Macrophages efficiently produced cytokines to LPS upon simultaneously internalizing parasites and to heat-killed Escherichia coli, demonstrating that phagosomal acidification affects endosomal receptor-mediated, but not cell surface receptor-mediated, recognition of Toll-like receptor agonists. Enabling monocytes/macrophages to elicit immune responses to parasites by blocking endosomal acidification can be a novel strategy for the effective development of protective immunity to malaria. The results have important implications for enhancing the efficacy of a whole parasite-based malaria vaccine and for designing strategies for the development of protective immunity to pathogens that induce immune responses primarily through endosomal receptors.

  1. Mild hypothermia protects against early brain injury in rats following subarachnoid hemorrhage via the TrkB/ERK/CREB signaling pathway.

    PubMed

    Lv, Ou; Zhou, Fenggang; Zheng, Yongri; Li, Qingsong; Wang, Jianjiao; Zhu, Yulan

    2016-10-01

    Subarachnoid hemorrhage (SAH) is a severe neurological disease, which is associated with a significant number of cases of premature mortality and disability worldwide. Mild hypothermia (MH) has been proposed as a potential therapeutic strategy to reduce neuronal injury following SAH. The present study aimed to investigate the mechanisms of MH's protective role in the process of SAH. The present study demonstrated that MH was able to protect against early brain injury in a rat model of SAH. Treating SAH rats with MH reduced the release of reactive oxygen species and prevented activation of apoptotic cascades. Furthermore, the protective effects of MH were shown to be mediated by enhanced activity of the tropomyosin receptor kinase B/extracellular signal‑regulated kinases/cAMP response element binding protein (TrkB/ERK/CREB) pathway. Inhibition of TrkB/ERK/CREB activity using a small molecule inhibitor largely abolished the beneficial effects of MH in SAH rats. These results outline an endogenous mechanism underlying the neuroprotective effects of MH in SAH. PMID:27600366

  2. Comet 67P: surface temperature maps as derived by Rosetta/VIRTIS in the early Mapping phase

    NASA Astrophysics Data System (ADS)

    Tosi, Federico; Capria, Maria Teresa; Capaccioni, Fabrizio; Filacchione, Gianrico; De Sanctis, Maria Cristina; Erard, Stéphane; Leyrat, Cedric; Bockelee-Morvan, Dominique; Kuehrt, Ekkehard

    2014-11-01

    We show spatially-resolved temperature maps of comet 67P/Churyumov-Gerasimenko, main target of the ESA Rosetta spacecraft, as obtained from infrared hyperspectral images acquired by the VIRTIS imaging spectrometer onboard the Rosetta Orbiter in the early Mapping phase carried out in August 2014.VIRTIS infrared spectra in the range longward of about 4 μm are affected by the thermal emission of the comet, hence the measured radiance in that spectral region can be used to determine surface temperatures and spectral emissivities by means of temperature-retrieval algorithms.The VIRTIS instrument onboard Rosetta is not sensitive to physical temperatures on the nightside of the comet, where the signal is considerably low. Typically, ~170 K is the minimum temperature that allows one to retrieve surface temperatures while preserving small formal errors (<1 K on retrieved temperatures). On the other hand, for a given local solar time (LST), the maximum temperature depends on the solar incidence angle and on surface properties such as thermal inertia and albedo.Here we show surface temperature maps of comet 67P at a spatial resolution of 20-25 m/px, and under variable phase angles, illumination conditions, and heliocentric distances (spanning the range from 3.62 to 3.45 AU). We focus both on regional maps and on peculiar sites of interest seen at the local scale, with a special emphasis on the expected location of the landing site.The availability of spatially-resolved, accurate temperature observations, significantly spaced out in local solar time, provides clues to the physical structure of specific surface units, which complements the mineralogical investigation based on imaging spectroscopy data collected at shorter wavelengths.AcknowledgementsThis work is supported by the Italian Space Agency (ASI), ASI-INAF Contract n. I/024/12/0. We acknowledge funding from the French Space Agency (CNES) and the German Aerospace Center (DLR). Support of the Rosetta and VIRTIS Science

  3. Protective Vaccination against Blood-Stage Malaria of Plasmodium chabaudi: Differential Gene Expression in the Liver of Balb/c Mice toward the End of Crisis Phase.

    PubMed

    Al-Quraishy, Saleh A; Dkhil, Mohamed A; Abdel-Baki, Abdel-Azeem A; Delic, Denis; Wunderlich, Frank

    2016-01-01

    Protective vaccination induces self-healing of otherwise fatal blood-stage malaria of Plasmodium chabaudi in female Balb/c mice. To trace processes critically involved in self-healing, the liver, an effector against blood-stage malaria, is analyzed for possible changes of its transcriptome in vaccination-protected in comparison to non-protected mice toward the end of the crisis phase. Gene expression microarray analyses reveal that vaccination does not affect constitutive expression of mRNA and lincRNA. However, malaria induces significant (p < 0.01) differences in hepatic gene and lincRNA expression in vaccination-protected vs. non-vaccinated mice toward the end of crisis phase. In vaccination-protected mice, infections induce up-regulations of 276 genes and 40 lincRNAs and down-regulations of 200 genes and 43 lincRNAs, respectively, by >3-fold as compared to the corresponding constitutive expressions. Massive up-regulations, partly by >100-fold, are found for genes as RhD, Add2, Ank1, Ermap, and Slc4a, which encode proteins of erythrocytic surface membranes, and as Gata1 and Gfi1b, which encode transcription factors involved in erythrocytic development. Also, Cldn13 previously predicted to be expressed on erythroblast surfaces is up-regulated by >200-fold, though claudins are known as main constituents of tight junctions acting as paracellular barriers between epithelial cells. Other genes are up-regulated by <100- and >10-fold, which can be subgrouped in genes encoding proteins known to be involved in mitosis, in cell cycle regulation, and in DNA repair. Our data suggest that protective vaccination enables the liver to respond to P. chabaudi infections with accelerated regeneration and extramedullary erythropoiesis during crisis, which contributes to survival of otherwise lethal blood-stage malaria. PMID:27471498

  4. Protective Vaccination against Blood-Stage Malaria of Plasmodium chabaudi: Differential Gene Expression in the Liver of Balb/c Mice toward the End of Crisis Phase.

    PubMed

    Al-Quraishy, Saleh A; Dkhil, Mohamed A; Abdel-Baki, Abdel-Azeem A; Delic, Denis; Wunderlich, Frank

    2016-01-01

    Protective vaccination induces self-healing of otherwise fatal blood-stage malaria of Plasmodium chabaudi in female Balb/c mice. To trace processes critically involved in self-healing, the liver, an effector against blood-stage malaria, is analyzed for possible changes of its transcriptome in vaccination-protected in comparison to non-protected mice toward the end of the crisis phase. Gene expression microarray analyses reveal that vaccination does not affect constitutive expression of mRNA and lincRNA. However, malaria induces significant (p < 0.01) differences in hepatic gene and lincRNA expression in vaccination-protected vs. non-vaccinated mice toward the end of crisis phase. In vaccination-protected mice, infections induce up-regulations of 276 genes and 40 lincRNAs and down-regulations of 200 genes and 43 lincRNAs, respectively, by >3-fold as compared to the corresponding constitutive expressions. Massive up-regulations, partly by >100-fold, are found for genes as RhD, Add2, Ank1, Ermap, and Slc4a, which encode proteins of erythrocytic surface membranes, and as Gata1 and Gfi1b, which encode transcription factors involved in erythrocytic development. Also, Cldn13 previously predicted to be expressed on erythroblast surfaces is up-regulated by >200-fold, though claudins are known as main constituents of tight junctions acting as paracellular barriers between epithelial cells. Other genes are up-regulated by <100- and >10-fold, which can be subgrouped in genes encoding proteins known to be involved in mitosis, in cell cycle regulation, and in DNA repair. Our data suggest that protective vaccination enables the liver to respond to P. chabaudi infections with accelerated regeneration and extramedullary erythropoiesis during crisis, which contributes to survival of otherwise lethal blood-stage malaria.

  5. Protective Vaccination against Blood-Stage Malaria of Plasmodium chabaudi: Differential Gene Expression in the Liver of Balb/c Mice toward the End of Crisis Phase

    PubMed Central

    Al-Quraishy, Saleh A.; Dkhil, Mohamed A.; Abdel-Baki, Abdel-Azeem A.; Delic, Denis; Wunderlich, Frank

    2016-01-01

    Protective vaccination induces self-healing of otherwise fatal blood-stage malaria of Plasmodium chabaudi in female Balb/c mice. To trace processes critically involved in self-healing, the liver, an effector against blood-stage malaria, is analyzed for possible changes of its transcriptome in vaccination-protected in comparison to non-protected mice toward the end of the crisis phase. Gene expression microarray analyses reveal that vaccination does not affect constitutive expression of mRNA and lincRNA. However, malaria induces significant (p < 0.01) differences in hepatic gene and lincRNA expression in vaccination-protected vs. non-vaccinated mice toward the end of crisis phase. In vaccination-protected mice, infections induce up-regulations of 276 genes and 40 lincRNAs and down-regulations of 200 genes and 43 lincRNAs, respectively, by >3-fold as compared to the corresponding constitutive expressions. Massive up-regulations, partly by >100-fold, are found for genes as RhD, Add2, Ank1, Ermap, and Slc4a, which encode proteins of erythrocytic surface membranes, and as Gata1 and Gfi1b, which encode transcription factors involved in erythrocytic development. Also, Cldn13 previously predicted to be expressed on erythroblast surfaces is up-regulated by >200-fold, though claudins are known as main constituents of tight junctions acting as paracellular barriers between epithelial cells. Other genes are up-regulated by <100- and >10-fold, which can be subgrouped in genes encoding proteins known to be involved in mitosis, in cell cycle regulation, and in DNA repair. Our data suggest that protective vaccination enables the liver to respond to P. chabaudi infections with accelerated regeneration and extramedullary erythropoiesis during crisis, which contributes to survival of otherwise lethal blood-stage malaria. PMID:27471498

  6. Conceptual Design of Simulation Models in an Early Development Phase of Lunar Spacecraft Simulator Using SMP2 Standard

    NASA Astrophysics Data System (ADS)

    Lee, Hoon Hee; Koo, Cheol Hea; Moon, Sung Tae; Han, Sang Hyuck; Ju, Gwang Hyeok

    2013-08-01

    The conceptual study for Korean lunar orbiter/lander prototype has been performed in Korea Aerospace Research Institute (KARI). Across diverse space programs around European countries, a variety of simulation application has been developed using SMP2 (Simulation Modelling Platform) standard related to portability and reuse of simulation models by various model users. KARI has not only first-hand experience of a development of SMP compatible simulation environment but also an ongoing study to apply the SMP2 development process of simulation model to a simulator development project for lunar missions. KARI has tried to extend the coverage of the development domain based on SMP2 standard across the whole simulation model life-cycle from software design to its validation through a lunar exploration project. Figure. 1 shows a snapshot from a visualization tool for the simulation of lunar lander motion. In reality, a demonstrator prototype on the right-hand side of image was made and tested in 2012. In an early phase of simulator development prior to a kick-off start in the near future, targeted hardware to be modelled has been investigated and indentified at the end of 2012. The architectural breakdown of the lunar simulator at system level was performed and the architecture with a hierarchical tree of models from the system to parts at lower level has been established. Finally, SMP Documents such as Catalogue, Assembly, Schedule and so on were converted using a XML(eXtensible Mark-up Language) converter. To obtain benefits of the suggested approaches and design mechanisms in SMP2 standard as far as possible, the object-oriented and component-based design concepts were strictly chosen throughout a whole model development process.

  7. Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

    SciTech Connect

    McGarry, Ronald C. . E-mail: rmcgarry@iupui.edu; Papiez, Lech; Williams, Mark; Whitford, Tia; Timmerman, Robert D.

    2005-11-15

    Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy), but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.

  8. Proteomic Insights into the Protective Mechanisms of an In Vitro Oxidative Stress Model of Early Stage Parkinson’s Disease

    PubMed Central

    Bauereis, Brian; Haskins, William E.; LeBaron, Richard G.; Renthal, Robert

    2010-01-01

    Previous studies in Parkinson's disease (PD) models suggest that early events along the path to neurodegeneration involve activation of the ubiquitin-proteasome system (UPS), endoplasmic reticulum-associated degradation (ERAD), and the unfolded protein response (UPR) pathways, in both the sporadic and familial forms of the disease, and thus ER stress may be a common feature. Furthermore, impairments in protein degradation have been linked to oxidative stress as well as pathways associated with ER stress. We hypothesize that oxidative stress is a primary initiator in a multi-factorial cascade driving dopaminergic (DA) neurons towards death in the early stages of the disease. We now report results from proteomic analysis of a rotenone-induced oxidative stress model of PD in the human neuroblastoma cell line, SH-SY5Y. Cells were exposed to sub-micromolar concentrations of rotenone for 48 hours prior to whole cell protein extraction and shotgun proteomic analysis. Evidence for activation of the UPR comes from our observation of up-regulated Binding immunoglobulin Protein (BiP), heat shock proteins, and foldases. We also observed up-regulation of proteins that contribute to the degradation of misfolded or unfolded proteins controlled by the UPS and ERAD pathways. Activation of the UPR may allow neurons to maintain protein homeostasis in the cytosol and ER despite an increase in reactive oxygen species due to oxidative stress, and activation of the UPS and ERAD may further augment clean-up and quality control in the cell. PMID:21056633

  9. Project FIRES - Firefighters Integrated Response Equipment System. Volume 3: Protective Ensemble Design and Procurement Specification, Phase 1B

    NASA Technical Reports Server (NTRS)

    Abeles, F. J.

    1980-01-01

    Each of the subsystems comprising the protective ensemble for firefighters is described. These include: (1) the garment system which includes turnout gear, helmets, faceshields, coats, pants, gloves, and boots; (2) the self-contained breathing system; (3) the lighting system; and (4) the communication system. The design selection rationale is discussed and the drawings used to fabricate the prototype ensemble are provided. The specifications presented were developed using the requirements and test method of the protective ensemble standard. Approximate retail prices are listed.

  10. Design and evaluation of improved barrier fabrics for protection against toxic aerosols and biological agents. Phase 2. Final report, January 1993-December 1994

    SciTech Connect

    Hersh, S.P.; Tucker, P.A.

    1995-05-01

    The ultimate objective of this research is to develop semipermeable barrier fabrics which provide better protection for chemical protective clothing applications. In order to understand the relationship between the aerosol particle penetration and the structure of barrier fabrics, the research activities in Phase I focused on measuring the transmission of aerosols through test fabrics, determining the penetration mechanisms, and evaluating the pore size distributions in the fabrics. Based on the knowledge gained in Phase I, a set of 32 fabrics was designed, fabricated, and evaluated in Phase II using a 2-level, 7-factor, statistical design. Five additional outer fabrics and a carbon foam liner supplied by the U.S. Army Natick RDE Center (Natick) were evaluated to provide further insights into the effect of dual layers of fabrics and their relative orientations on aerosol penetration. The results of this research have been described in a Doctoral Dissertation by Dr. Surinder M. Maini (based on the 32 statistically designed fabrics) 1 and in a Master of Science thesis by Ms. Amelia Tosti 2 (on the fabrics supplied by Natick) in accordance with the research proposal. Abstracts of these two documents are presented in Section 2.0. The rest of this report describes the work and results conducted during Phase II. pg14. JMD.

  11. The replication timing program of the Chinese hamster β-globin locus is established coincident with its repositioning near peripheral heterochromatin in early G1 phase

    PubMed Central

    Li, Feng; Chen, Jianhua; Izumi, Masako; Butler, Mark C.; Keezer, Susan M.; Gilbert, David M.

    2001-01-01

    We have examined the dynamics of nuclear repositioning and the establishment of a replication timing program for the actively transcribed dihydrofolate reductase (DHFR) locus and the silent β-globin gene locus in Chinese hamster ovary cells. The DHFR locus was internally localized and replicated early, whereas the β-globin locus was localized adjacent to the nuclear periphery and replicated during the middle of S phase, coincident with replication of peripheral heterochromatin. Nuclei were prepared from cells synchronized at various times during early G1 phase and stimulated to enter S phase by introduction into Xenopus egg extracts, and the timing of DHFR and β-globin replication was evaluated in vitro. With nuclei isolated 1 h after mitosis, neither locus was preferentially replicated before the other. However, with nuclei isolated 2 or 3 h after mitosis, there was a strong preference for replication of DHFR before β-globin. Measurements of the distance of DHFR and β-globin to the nuclear periphery revealed that the repositioning of the β-globin locus adjacent to peripheral heterochromatin also took place between 1 and 2 h after mitosis. These results suggest that the CHO β-globin locus acquires the replication timing program of peripheral heterochromatin upon association with the peripheral subnuclear compartment during early G1 phase. PMID:11470818

  12. Zinc might protect oxidative changes in the retina and pancreas at the early stage of diabetic rats

    SciTech Connect

    Moustafa, Sohair A. . E-mail: Sohabdulla@hotmail.com

    2004-12-01

    It is well documented that oxidative stress is a basic mechanism behind the development of diabetic retinopathy (DR). The current study was undertaken to elucidate the possible role of zinc as an antioxidant and a biological membrane stabilizer in the protection against (DR). Male Wistar rats weighing 250 {+-} 50 g were made diabetic by injection with a single ip dose of alloxan (100 mg/kg). Another group of rats was simultaneously treated with alloxan (100 mg/kg) and a single ip dose of zinc chloride (ZnCl{sub 2}) (5 mg/kg). Blood and tissue samples were collected at 24, 48, and 72 h post-treatment in both groups. Diabetic state was confirmed by the determination of plasma glucose levels (significantly elevated at any time of the experiment when compared with controls receiving vehicle). Plasma insulin was significantly increased 24 h after treatment in both alloxan and alloxan plus ZnCl{sub 2}-treated groups, and then decreased markedly 48 and 72 h post treatment in both groups. Alloxan treatment depleted both retinal and liver glutathione contents. The decrease in retinal and liver GSH in alloxan-treated rats was accompanied with a sustained increase in their thiobarbituric acid (TBA) content. Simultaneous treatment of rats with alloxan and ZnCl{sub 2} blunted the sustained increment in plasma glucose induced by alloxan. The combined administration of alloxan and zinc reversed the depleting effect on retinal and hepatic GSH in alloxan-treated rats and reduced the elevations in TBA content of both retinas and livers. At variance with many other antioxidants the current results clearly indicate the beneficial effects of Zn in both controlling hyperglycemia and the protection of the retina against oxidative stress in diabetes which may help set a new direction toward the development of effective treatments of DR.

  13. Freedom to divorce or protection of marriage? The divorce laws in Denmark, Norway, and Sweden in the early twentieth century.

    PubMed

    Le Bouteillec, Nathalie; Bersbo, Zara; Festy, Patrick

    2011-01-01

    In the period 1909-1927, new laws concerning divorce and marriage were enacted by the Scandinavian countries. Both at the time and more recently, these laws were considered as "liberal" as they promoted greater freedom to divorce based on individuality and gender equality. In this article, the authors first analyze the changes in these Family laws in the early twentieth century. Then, the authors study the effect of these laws on divorce and marriage patterns. As these laws did not modify the trend in divorce rates, the authors ask why this was the case. The authors' conclusions are that the laws were more concerned with preserving the sanctity of marriage and maintaining social order than with promoting individual freedom and gender equality.

  14. What promotes secure attachment in early adoption? The protective roles of infants' temperament and adoptive parents' attachment.

    PubMed

    Lionetti, Francesca

    2014-01-01

    Life before adoption is characterized by the lack of sensitive and stable caregiving, putting infants at risk for non-secure attachment patterns. What leads to adoptees' attachment security in their adoptive families has not been conclusively determined. We investigated the roles of children's temperament and adoptive parents' attachment on adoptees' attachment security. The variables were studied in a sample of 30 early-placed adoptees (age at adoption placement M = 5.37 months, SD = 4.43) and their adoptive mothers and fathers. Attachment patterns were investigated by means of the Strange Situation Procedure and the Adult Attachment Interview, and temperament via the Infant Behavior Questionnaire. Results showed that mothers' secure attachment, but not fathers' attachment or adoptees' temperament, increased the chance of secure attachment in adoptees. Temperament moderated the mother-child attachment match.

  15. Transition and protective agency of early childhood learning behaviors as portents of later school attendance and adjustment.

    PubMed

    McDermott, Paul A; Rikoon, Samuel H; Fantuzzo, John W

    2016-02-01

    This article reports on the study of differential change trajectories for early childhood learning behaviors as they relate to future classroom adjustment and school attendance. A large sample (N=2152) of Head Start children was followed through prekindergarten, kindergarten, and 1st grade. Classroom learning behaviors were assessed twice each year by teachers who observed gradual declines in Competence Motivation and Attentional Persistence as children transitioned through schooling. Cross-classified multilevel growth models revealed distinct transitional pathways for future adjustment versus maladjustment and sporadic versus chronic absenteeism. Generalized multilevel logistic modeling and receiver operating characteristic curve analyses showed that teachers' earliest assessments were substantially predictive of eventual good classroom adjustment and school attendance, with increasing accuracy for prediction of future sociobehavioral adjustment as time progressed. PMID:26790703

  16. Hippocampal injury-induced cognitive and mood dysfunction, altered neurogenesis, and epilepsy: can early neural stem cell grafting intervention provide protection?

    PubMed

    Shetty, Ashok K

    2014-09-01

    Damage to the hippocampus can occur through many causes including head trauma, ischemia, stroke, status epilepticus, and Alzheimer's disease. Certain changes such as increased levels of neurogenesis and elevated concentrations of multiple neurotrophic factors that ensue in the acute phase after injury seem beneficial for restraining hippocampal dysfunction. However, many alterations that arise in the intermediate to chronic phase after injury such as abnormal migration of newly born neurons, aberrant synaptic reorganization, progressive loss of inhibitory gamma-amino butyric acid positive interneurons including those expressing reelin, greatly declined neurogenesis, and sustained inflammation are detrimental. Consequently, the net effect of postinjury plasticity in the hippocampus remains inadequate for promoting significant functional recovery. Hence, ideal therapeutic interventions ought to be efficient for restraining these detrimental changes in order to block the propensity of most hippocampal injuries to evolve into learning deficits, memory dysfunction, depression, and temporal lobe epilepsy. Neural stem cell (NSC) grafting into the hippocampus early after injury appears alluring from this perspective because several recent studies have demonstrated the therapeutic value of this intervention, especially for preventing/easing memory dysfunction, depression, and temporal lobe epilepsy development in the chronic phase after injury. These beneficial effects of NSC grafting appeared to be mediated through considerable modulation of aberrant hippocampal postinjury plasticity with additions of new inhibitory gamma-amino butyric acid positive interneurons and astrocytes secreting a variety of neurotrophic factors and anticonvulsant proteins. This review presents advancements made in NSC grafting therapy for treating hippocampal injury in animal models of excitotoxic injury, traumatic brain injury, Alzheimer's disease, and status epilepticus; potential mechanisms of

  17. Dynamic shifts in corticostriatal expression patterns of the immediate early genes Homer 1a and Zif268 during early and late phases of instrumental training.

    PubMed

    Hernandez, Pepe J; Schiltz, Craig A; Kelley, Ann E

    2006-01-01

    Adaptive motor actions require prior knowledge of instrumental contingencies. With practice, these actions can become highly automatic in nature. However, the molecular and anatomical substrates mediating these related forms of learning are not understood. In the present study, we used in situ hybridization to measure the mRNA levels of two immediate early genes (IEGs) in an instrumental paradigm where rats learned to lever-press for food. We report that after three training sessions, Homer 1a and Zif268 (an effector and regulatory IEG, respectively) were significantly induced within an extensive corticostriatal network relative to untrained controls. With extended training (23 sessions), however, a shift in the expression patterns of the two genes was evident. Expression of Homer 1a (official symbol Homer1) decreased significantly in frontal and cingulate cortices, whereas striatal expression was generally maintained. Interestingly, Homer 1a expression markedly increased with extensive training in the ventrolateral region of the striatum (VLS) relative to early learners, suggesting that plasticity in the VLS is required for the efficient production of the learned behavior or in habit formation. Zif268 (official symbol Egr1) expression generally decreased with extensive training; however, these changes were not significant. These results demonstrate for the first time, on a molecular level, a dynamic shift in the contribution of corticostriatal systems mediating the early acquisition and consolidation of goal-directed responses to those engaged after extensive training. PMID:17015857

  18. Early identification of mental health needs for children in care: a therapeutic assessment programme for statutory clients of child protection.

    PubMed

    Milburn, Nicole L; Lynch, Marell; Jackson, Jennifer

    2008-01-01

    Infants, children and young people enter out of home care in distressing circumstances. They have often suffered traumatic experiences and have had their primary relationships disrupted. They and their families and carers have specific mental health needs at this time but few have attended a mental health service. A systematic comprehensive therapeutic assessment approach is described for all child protection clients who entered out-of-home care for the first time in one calendar year. The work of the programme is described using both case study and assessment findings. More than 60 per cent of participants met criteria for a major psychiatric diagnosis, with Post Traumatic Stress and Adjustment Disorders being the most common diagnostic categories. Nearly three-quarters of participants over the age of 5 years scored in the borderline or abnormal range on the Strengths and Difficulties Questionnaire (SDQ; Goodman, 1997). There was an over-representation of infants less than 1 year of age and adolescents in the cohort, representing particular developmental challenges. The findings are discussed within the context of specific mental health service delivery to this vulnerable population of maltreated infants, children and young people.

  19. Early Phase Clinical Trials with Human Immunodeficiency Virus-1 and Malaria Vectored Vaccines in The Gambia: Frontline Challenges in Study Design and Implementation

    PubMed Central

    Afolabi, Muhammed O.; Adetifa, Jane U.; Imoukhuede, Egeruan B.; Viebig, Nicola K.; Kampmann, Beate; Bojang, Kalifa

    2014-01-01

    Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings. PMID:24615122

  20. Klotho deficiency is an early biomarker of renal ischemia–reperfusion injury and its replacement is protective

    PubMed Central

    Hu, Ming-Chang; Shi, Mingjun; Zhang, Jianning; Quiñones, Henry; Kuro-o, Makoto; Moe, Orson W.

    2011-01-01

    Klotho is an antiaging substance with pleiotropic actions including regulation of mineral metabolism. It is highly expressed in the kidney and is present in the circulation and urine but its role in acute kidney injury (AKI) is unknown. We found that ischemia–reperfusion injury (IRI) in rodents reduced Klotho in the kidneys, urine, and blood, all of which were restored upon recovery. Reduction in kidney and plasma Klotho levels were earlier than that of neutrophil gelatinase-associated lipocalin (NGAL), a known biomarker of kidney injury. Patients with AKI were found to have drastic reductions in urinary Klotho. To examine whether Klotho has a pathogenic role, we induced IRI in mice with different endogenous Klotho levels ranging from heterozygous Klotho haploinsufficient, to wild-type (WT), to transgenic mice overexpressing Klotho. Klotho levels in AKI were lower in haploinsufficient and higher in transgenic compared with WT mice. The haploinsufficient mice had more extensive functional and histological alterations compared with WT mice, whereas these changes were milder in overexpressing transgenic mice, implying that Klotho is renoprotective. Rats with AKI given recombinant Klotho had higher Klotho protein, less kidney damage, and lower NGAL than rats with AKI given vehicle. Hence, AKI is a state of acute reversible Klotho deficiency, low Klotho exacerbates kidney injury and its restoration attenuates renal damage and promotes recovery from AKI. Thus, endogenous Klotho not only serves as an early biomarker for AKI but also functions as a renoprotective factor with therapeutic potential. PMID:20861825

  1. Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury.

    PubMed

    Papa, Simonetta; Caron, Ilaria; Erba, Eugenio; Panini, Nicolò; De Paola, Massimiliano; Mariani, Alessandro; Colombo, Claudio; Ferrari, Raffaele; Pozzer, Diego; Zanier, Elisa R; Pischiutta, Francesca; Lucchetti, Jacopo; Bassi, Andrea; Valentini, Gianluca; Simonutti, Giulio; Rossi, Filippo; Moscatelli, Davide; Forloni, Gianluigi; Veglianese, Pietro

    2016-01-01

    Many efforts have been performed in order to understand the role of recruited macrophages in the progression of spinal cord injury (SCI). Different studies revealed a pleiotropic effect played by these cells associated to distinct phenotypes (M1 and M2), showing a predictable spatial and temporal distribution in the injured site after SCI. Differently, the role of activated microglia in injury progression has been poorly investigated, mainly because of the challenges to target and selectively modulate them in situ. A delivery nanovector tool (poly-ε-caprolactone-based nanoparticles) able to selectively treat/target microglia has been developed and used here to clarify the temporal and spatial involvement of the pro-inflammatory response associated to microglial cells in SCI. We show that a treatment with nanoparticles loaded with minocycline, the latter a well-known anti-inflammatory drug, when administered acutely in a SCI mouse model is able to efficiently modulate the resident microglial cells reducing the pro-inflammatory response, maintaining a pro-regenerative milieu and ameliorating the behavioral outcome up to 63 days post injury. Furthermore, by using this selective delivery tool we demonstrate a mechanistic link between early microglia activation and M1 macrophages recruitment to the injured site via CCL2 chemokine, revealing a detrimental contribution of pro-inflammatory macrophages to injury progression after SCI.

  2. Occupant Protection Project

    NASA Technical Reports Server (NTRS)

    Bopp, Genie; Somers, Jeff; Granderson, Brad; Gernhardt, Mike; Currie, Nancy; Lawrence, Chuck

    2010-01-01

    Topics include occupant protection overview with a focus on crew protection during dynamic phases of flight; occupant protection collaboration; modeling occupant protection; occupant protection considerations; project approach encompassing analysis tools, injury criteria, and testing program development; injury criteria update methodology, unique effects of pressure suits and other factors; and a summary.

  3. Piceatannol, Natural Polyphenolic Stilbene, Inhibits Adipogenesis via Modulation of Mitotic Clonal Expansion and Insulin Receptor-dependent Insulin Signaling in Early Phase of Differentiation*

    PubMed Central

    Kwon, Jung Yeon; Seo, Sang Gwon; Heo, Yong-Seok; Yue, Shuhua; Cheng, Ji-Xin; Lee, Ki Won; Kim, Kee-Hong

    2012-01-01

    Piceatannol, a natural stilbene, is an analog and a metabolite of resveratrol. Despite a well documented health benefit of resveratrol in intervention of the development of obesity, the role of piceatannol in the development of adipose tissue and related diseases is unknown. Here, we sought to determine the function of piceatannol in adipogenesis and elucidate the underlying mechanism. We show that piceatannol inhibits adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner at noncytotoxic concentrations. This anti-adipogenic property of piceatannol was largely limited to the early event of adipogenesis. In the early phase of adipogenesis, piceatannol-treated preadipocytes displayed a delayed cell cycle entry into G2/M phase at 24 h after initiation of adipogenesis. Furthermore, the piceatannol-suppressed mitotic clonal expansion was accompanied by reduced activation of the insulin-signaling pathway. Piceatannol dose-dependently inhibited differentiation mixture-induced phosphorylation of insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/Akt pathway in the early phase of adipogenesis. Moreover, we showed that piceatannol is an inhibitor of IR kinase activity and phosphatidylinositol 3-kinase (PI3K). Our kinetics study of IR further identified a Km value for ATP of 57.8 μm and a Ki value for piceatannol of 28.9 μm. We also showed that piceatannol directly binds to IR and inhibits IR kinase activity in a mixed noncompetitive manner to ATP, through which piceatannol appears to inhibit adipogenesis. Taken together, our study reveals an anti-adipogenic function of piceatannol and highlights IR and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis. PMID:22298784

  4. 30 CFR 75.901 - Protection of low- and medium-voltage three-phase circuits used underground.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... diesel engine powering the electrical generator must be approved under 30 CFR part 7, subpart E. (2) A...) specified in 30 CFR part 18, appendix I, table 9, Specifications for Cables Longer than 500 Feet. (7... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Protection of low- and medium-voltage...

  5. 30 CFR 75.901 - Protection of low- and medium-voltage three-phase circuits used underground.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... diesel engine powering the electrical generator must be approved under 30 CFR part 7, subpart E. (2) A...) specified in 30 CFR part 18, appendix I, table 9, Specifications for Cables Longer than 500 Feet. (7... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Protection of low- and medium-voltage...

  6. Liquid-phase synthesis of bridged peptides using olefin metathesis of a protected peptide with a long aliphatic chain anchor.

    PubMed

    Aihara, Keisuke; Komiya, Chiaki; Shigenaga, Akira; Inokuma, Tsubasa; Takahashi, Daisuke; Otaka, Akira

    2015-02-01

    Bridged peptides including stapled peptides are attractive tools for regulating protein-protein interactions (PPIs). An effective synthetic methodology in a heterogeneous system for the preparation of these peptides using olefin metathesis and hydrogenation of protected peptides with a long aliphatic chain anchor is reported. PMID:25629979

  7. Liquid-phase synthesis of bridged peptides using olefin metathesis of a protected peptide with a long aliphatic chain anchor.

    PubMed

    Aihara, Keisuke; Komiya, Chiaki; Shigenaga, Akira; Inokuma, Tsubasa; Takahashi, Daisuke; Otaka, Akira

    2015-02-01

    Bridged peptides including stapled peptides are attractive tools for regulating protein-protein interactions (PPIs). An effective synthetic methodology in a heterogeneous system for the preparation of these peptides using olefin metathesis and hydrogenation of protected peptides with a long aliphatic chain anchor is reported.

  8. Peripheral therapeutic ultrasound stimulation alters the distribution of spinal C-fos immunoreactivity induced by early or late phase of inflammation.

    PubMed

    Hsieh, Yueh-Ling

    2008-03-01

    The purpose of this investigation was to examine the central modulated effects of therapeutic ultrasound (US) on neuronal activity in the spinal cord on early and late phases of inflammation. In this study, induction of c-Fos protein, which reflects neuronal activation (particularly inflammatory nociception), was investigated in the lumbar spinal cord with immunohistochemistry. Inflammatory monoarthritis was induced in 20 male Wistar rats (weighing 250-300 g) via intra-articular injection of complete Freund's adjuvant (CFA) into the tibiotarsal joint. Two phases of arthritis, early phase (18 h after adjuvant injection) and late phase (7 d after adjuvant injection), were studied in the rats. Pulsed-mode US (1 MHz, the spatial average temporal average intensity [I(SATA)] = 0.5 W/cm(2), 50% duty cycle) was applied for 5 min. The effects of US and sham treatments against these phases of arthritis were demonstrated by spinal c-Fos-like immunoreactivity (c-Fos-LI). All data were evaluated statistically with the paired t-test or analysis of variance with Bonferroni corrections. c-Fos-LI neurons were abundant (average 264.2 +/- 11.9) in the L3 and L4 neurons of the spinal cord in areas ipsilateral to the CFA-induced arthritic leg in the early phase, but few were present (average 40.4 +/- 4.5) in the late phase in sham-treated animals. Bonferroni corrections to the alpha level were used to check the group differences in spinal c-Fos expression, and significance was reached when p < 0.025. In the early inflammatory phase, US treatment significantly suppressed the increased number of c-Fos-LI neurons associated with CFA-induced arthritis in superficial laminae, nucleus proprius, deep laminae and ventral horn of the spinal cord. However, during the late inflammatory phase, US significantly triggered c-Fos expression in most laminae, particularly in the nucleus proprius, deep laminae and ventral horn of the spinal cord. The results of our study suggest that administration of US

  9. A hypomorphic mutation reveals a stringent requirement for the ATM checkpoint protein in telomere protection during early cell division in Drosophila.

    PubMed

    Morciano, Patrizia; Zhang, Yi; Cenci, Giovanni; Rong, Yikang S

    2013-06-01

    Using Drosophila as a model system, we identified a stringent requirement for the conserved function of Ataxia Telangiectasia Mutated (ATM) in telomere protection during early embryonic development. Animals homozygous for a hypomorphic mutation in atm develop normally with minimal telomere dysfunction. However, mutant females produce inviable embryos that succumb to mitotic failure caused by covalent fusions of telomeric DNA. Interestingly, although the atm mutation encodes a premature stop codon, it must not have eliminated the production of the mutant protein, and the mutant protein retains kinase activity upon DNA damage. Moreover, although the embryonic phenotype of this mutation resembles that of hypomorphic mutations in the MRN complex, the function of MRN appears normal in the atm embryos. In contrast, there is a prominent reduction of the level of HipHop, an essential member of the Drosophila capping complex. How ATM functions in telomere protection remains poorly understood. The amenability of Drosophila embryos to molecular and biochemical investigations ensures that this newly identified mutation will facilitate future studies of ATM in telomere maintenance. PMID:23604076

  10. A Hypomorphic Mutation Reveals a Stringent Requirement for the ATM Checkpoint Protein in Telomere Protection During Early Cell Division in Drosophila

    PubMed Central

    Morciano, Patrizia; Zhang, Yi; Cenci, Giovanni; Rong, Yikang S.

    2013-01-01

    Using Drosophila as a model system, we identified a stringent requirement for the conserved function of Ataxia Telangiectasia Mutated (ATM) in telomere protection during early embryonic development. Animals homozygous for a hypomorphic mutation in atm develop normally with minimal telomere dysfunction. However, mutant females produce inviable embryos that succumb to mitotic failure caused by covalent fusions of telomeric DNA. Interestingly, although the atm mutation encodes a premature stop codon, it must not have eliminated the production of the mutant protein, and the mutant protein retains kinase activity upon DNA damage. Moreover, although the embryonic phenotype of this mutation resembles that of hypomorphic mutations in the MRN complex, the function of MRN appears normal in the atm embryos. In contrast, there is a prominent reduction of the level of HipHop, an essential member of the Drosophila capping complex. How ATM functions in telomere protection remains poorly understood. The amenability of Drosophila embryos to molecular and biochemical investigations ensures that this newly identified mutation will facilitate future studies of ATM in telomere maintenance. PMID:23604076

  11. A hypomorphic mutation reveals a stringent requirement for the ATM checkpoint protein in telomere protection during early cell division in Drosophila.

    PubMed

    Morciano, Patrizia; Zhang, Yi; Cenci, Giovanni; Rong, Yikang S

    2013-06-21

    Using Drosophila as a model system, we identified a stringent requirement for the conserved function of Ataxia Telangiectasia Mutated (ATM) in telomere protection during early embryonic development. Animals homozygous for a hypomorphic mutation in atm develop normally with minimal telomere dysfunction. However, mutant females produce inviable embryos that succumb to mitotic failure caused by covalent fusions of telomeric DNA. Interestingly, although the atm mutation encodes a premature stop codon, it must not have eliminated the production of the mutant protein, and the mutant protein retains kinase activity upon DNA damage. Moreover, although the embryonic phenotype of this mutation resembles that of hypomorphic mutations in the MRN complex, the function of MRN appears normal in the atm embryos. In contrast, there is a prominent reduction of the level of HipHop, an essential member of the Drosophila capping complex. How ATM functions in telomere protection remains poorly understood. The amenability of Drosophila embryos to molecular and biochemical investigations ensures that this newly identified mutation will facilitate future studies of ATM in telomere maintenance.

  12. Recurrent surgical site infection of the spine diagnosed by dual (18)F-NaF-bone PET/CT with early-phase scan.

    PubMed

    Shim, Jai-Joon; Lee, Jeong Won; Jeon, Min Hyok; Lee, Sang Mi

    2016-09-01

    We report a case of a 31-year-old man who showed recurrently elevated level of the serum inflammatory marker C-reactive protein (CRP) after spinal operation. He underwent (18)F-flurodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and dual (18)F-sodium-fluoride ((18)F-NaF) PET/CT with an additional early-phase scan to find a hidden inflammation focus. Only mildly increased (18)F-FDG was found at the surgical site of T11 spine on (18)F-FDG PET/CT. In contrast, dual (18)F-NaF bone PET/CT with early-phase scan demonstrated focal active inflammation at the surgical site of T11 spine. After a revision operation of the T11 spine, serum CRP level decreased to the normal range without any symptom or sign of inflammation. Inflammatory focus in the surgical site of the spine can be detected with using dual (18)F-NaF bone PET/CT scan with early-phase scan.

  13. Early enriched environment exposure protects spatial memory and accelerates amyloid plaque formation in APP(Swe)/PS1(L166P) mice.

    PubMed

    Montarolo, Francesca; Parolisi, Roberta; Hoxha, Eriola; Boda, Enrica; Tempia, Filippo

    2013-01-01

    Enriched environment exposure improves several aspects of cognitive performance in Alzheimer's disease patients and in animal models and, although the role of amyloid plaques is questionable, several studies also assessed their response to enriched environment, with contrasting results. Here we report that rearing APP(Swe)/PS1(L166P) mice in an enriched environment since birth rescued the spatial memory impairment otherwise present at 6 months of age. At the same time, the exposure to the enriched environment caused a transient acceleration of plaque formation, while there was no effect on intracellular staining with the 6E10 antibody, which recognizes β-amyloid, full length amyloid precursor protein and its C-terminal fragments. The anticipation of plaque formation required exposure during early development, suggesting an action within critical periods for circuits formation. On the other hand, chronic neuronal activity suppression by tetrodotoxin decreased the number of plaques without affecting intracellular amyloid. These results indicate that enriched environment exposure since early life has a protective effect on cognitive deterioration although transiently accelerates amyloid deposition. In addition, the effects of the enriched environment might be due to increased neuronal activity, because plaques were reduced by suppression of electrical signaling by tetrodotoxin.

  14. Quantitative single serum-dilution liquid phase competitive blocking ELISA for the assessment of herd immunity and expected protection against foot-and-mouth disease virus in vaccinated cattle.

    PubMed

    Robiolo, Blanca; La Torre, José; Duffy, Sergio; Leon, Emilio; Seki, Cristina; Torres, Adriana; Mattion, Nora

    2010-06-01

    A single serum-dilution liquid phase ELISA (slpELISA) was standardized to be used for serological evaluation of herd immunity against foot-and-mouth disease. The absorbance value at a dilution 1:64 of each serum sample was interpolated in a standard curve by plotting the antibody titers of six control sera determined by end point dilution liquid phase ELISA (lpELISA), against the absorbance values for the same control sera at 1:64 dilutions. A straight line was obtained by linear regression analysis (r>0.90) in the titer range of 1.40-2.40. The reliability of the antibody titers was confirmed by the simultaneous titration of 60 cattle sera by slpELISA and lpELISA, which showed an acceptable correlation (R(2)>0.87) for viral strains A24/Cruzeiro, A/Argentina/01, O1/Campos and C3/Indaial. Titers obtained by both methods were not significantly different (p>0.05), thus confirming that slpELISA could be used successfully to replace the conventional serial dilution ELISA for the assessment of protection status of cattle in epidemiological studies. In addition, this quantitative slpELISA provides an adequate method for monitoring the effectiveness of vaccination campaigns and is also suitable for the assessment of seroconversion of naive animals during early stages of infection.

  15. Quantitative single serum-dilution liquid phase competitive blocking ELISA for the assessment of herd immunity and expected protection against foot-and-mouth disease virus in vaccinated cattle.

    PubMed

    Robiolo, Blanca; La Torre, José; Duffy, Sergio; Leon, Emilio; Seki, Cristina; Torres, Adriana; Mattion, Nora

    2010-06-01

    A single serum-dilution liquid phase ELISA (slpELISA) was standardized to be used for serological evaluation of herd immunity against foot-and-mouth disease. The absorbance value at a dilution 1:64 of each serum sample was interpolated in a standard curve by plotting the antibody titers of six control sera determined by end point dilution liquid phase ELISA (lpELISA), against the absorbance values for the same control sera at 1:64 dilutions. A straight line was obtained by linear regression analysis (r>0.90) in the titer range of 1.40-2.40. The reliability of the antibody titers was confirmed by the simultaneous titration of 60 cattle sera by slpELISA and lpELISA, which showed an acceptable correlation (R(2)>0.87) for viral strains A24/Cruzeiro, A/Argentina/01, O1/Campos and C3/Indaial. Titers obtained by both methods were not significantly different (p>0.05), thus confirming that slpELISA could be used successfully to replace the conventional serial dilution ELISA for the assessment of protection status of cattle in epidemiological studies. In addition, this quantitative slpELISA provides an adequate method for monitoring the effectiveness of vaccination campaigns and is also suitable for the assessment of seroconversion of naive animals during early stages of infection. PMID:20170683

  16. An evaluation of fish early life stage tests for predicting reproductive and longer-term toxicity from plant protection product active substances.

    PubMed

    Wheeler, James R; Maynard, Samuel K; Crane, Mark

    2014-08-01

    The chronic toxicity of chemicals to fish is routinely assessed by using fish early life stage (ELS) test results. Fish full life cycle (FLC) tests are generally required only when toxicity, bioaccumulation, and persistence triggers are met or when there is a suspicion of potential endocrine-disrupting properties. This regulatory approach is based on a relationship between the results of fish ELS and FLC studies first established more than 35 yrs ago. Recently, this relationship has been challenged by some regulatory authorities, and it has been recommended that more substances should undergo FLC testing. In addition, a project proposal has been submitted to the Organisation for Economic Cooperation and Development (OECD) to develop a fish partial life cycle (PLC) test including a reproductive assessment. Both FLC and PLC tests are animal- and resource-intensive and technically challenging and should therefore be undertaken only if there is clear evidence that they are necessary for coming to a regulatory decision. The present study reports on an analysis of a database of paired fish ELS and FLC endpoints for plant protection product active substances from European Union draft assessment reports and the US Environmental Protection Agency Office of Pesticide Programs Pesticide Ecotoxicity Database. Analysis of this database shows a clear relationship between ELS and FLC responses, with similar median sensitivity across substances when no-observed-effect concentrations (NOECs) are compared. There was also no indication that classification of a substance as a mammalian reproductive toxicant leads to more sensitive effects in fish FLC tests than in ELS tests. Indeed, the response of the ELS tests was generally more sensitive than the most sensitive reproduction NOEC from a FLC test. This analysis indicates that current testing strategies and guidelines are fit for purpose and that there is no need for fish full or partial life cycle tests for most plant protection

  17. An evaluation of fish early life stage tests for predicting reproductive and longer-term toxicity from plant protection product active substances.

    PubMed

    Wheeler, James R; Maynard, Samuel K; Crane, Mark

    2014-08-01

    The chronic toxicity of chemicals to fish is routinely assessed by using fish early life stage (ELS) test results. Fish full life cycle (FLC) tests are generally required only when toxicity, bioaccumulation, and persistence triggers are met or when there is a suspicion of potential endocrine-disrupting properties. This regulatory approach is based on a relationship between the results of fish ELS and FLC studies first established more than 35 yrs ago. Recently, this relationship has been challenged by some regulatory authorities, and it has been recommended that more substances should undergo FLC testing. In addition, a project proposal has been submitted to the Organisation for Economic Cooperation and Development (OECD) to develop a fish partial life cycle (PLC) test including a reproductive assessment. Both FLC and PLC tests are animal- and resource-intensive and technically challenging and should therefore be undertaken only if there is clear evidence that they are necessary for coming to a regulatory decision. The present study reports on an analysis of a database of paired fish ELS and FLC endpoints for plant protection product active substances from European Union draft assessment reports and the US Environmental Protection Agency Office of Pesticide Programs Pesticide Ecotoxicity Database. Analysis of this database shows a clear relationship between ELS and FLC responses, with similar median sensitivity across substances when no-observed-effect concentrations (NOECs) are compared. There was also no indication that classification of a substance as a mammalian reproductive toxicant leads to more sensitive effects in fish FLC tests than in ELS tests. Indeed, the response of the ELS tests was generally more sensitive than the most sensitive reproduction NOEC from a FLC test. This analysis indicates that current testing strategies and guidelines are fit for purpose and that there is no need for fish full or partial life cycle tests for most plant protection

  18. Early administration of nifedipine protects against angiotensin II-induced cardiomyocyte hypertrophy through regulating CaMKII-SERCA2a pathway and apoptosis in rat cardiomyocytes.

    PubMed

    Luo, Ji; Zhang, Wei-dong; Du, Yi-meng

    2016-04-01

    The calcium channel blocker (CCB), nifedipine, is a more effective treatment for early- than late-stage cardiac hypertrophy. We investigated the effects of early- and late-stage nifedipine administration on calcium homeostasis, CaMKII (Ca(2+) /calmodulin-dependent protein kinase II) activity and apoptosis of cardiomyocytes under hypertrophic stimulation with angiotensin II (AngII). Primary rat cardiomyocytes were divided into five treatment groups: AK, AngII plus the CaMKII inhibitor, KN-93; AN-1 (early-stage), AngII plus nifedipine × 48 h; AN-2 (late-stage), AngII × 48 h, then AngII plus nifedipine × 48 h; C, untreated; and A, AngII × 48 h. The t1/2β [time required for intracellular Ca(2+) concentration ([Ca(2+) ]i) to decline to one half of the peak value] decreased; however, CaMKII and SERCA2a (sarcoplasmic reticulum Ca(2+) -ATPase 2a) activities increased in the AN-1 group compared with the AK group. In the AN-2 group compared with the AN-1 group, CaMKII activity, t1/2α [time required for [Ca(2+) ]i to increase from the bottom to one half of peak value], t1/2β, and apoptosis increased. These results indicate that the timing of CCB administration affects the calcium concentration and apoptosis of hypertrophic cardiomyocytes through the CaMKII-SERCA2a signalling pathway, thereby influencing the drug's protective activity against cardiomyocyte hypertrophy. PMID:26968727

  19. A new combination of protecting groups and links for encoded synthetic libraries suited for consecutive tests on the solid phase and in solution.

    PubMed

    Felder, E R; Heizmann, G; Matthews, I T; Rink, H; Spieser, E

    1996-02-01

    A strategy for high-throughput evaluation of combinatorial compound libraries is reported, which circumvents the necessity to test complex mixtures. The method is based on a new combination of protecting groups, solid-phase linker and tags. The bulk of the library first undergoes a binding assay with the components grafted on beads. A selection of beads carrying strong ligands is stripped from the labelled target and distributed into microvessels. The ligands are cleaved and rinsed into microeluates. Subsequently, a more detailed characterization with a functional assay in solution determines the best performers, which are identified through the peptidic tag left behind on the corresponding mother bead. PMID:9237199

  20. Cooperation between Epstein-Barr virus immune evasion proteins spreads protection from CD8+ T cell recognition across all three phases of the lytic cycle.

    PubMed

    Quinn, Laura L; Zuo, Jianmin; Abbott, Rachel J M; Shannon-Lowe, Claire; Tierney, Rosemary J; Hislop, Andrew D; Rowe, Martin

    2014-08-01

    CD8+ T cell responses to Epstein-Barr virus (EBV) lytic cycle expressed antigens display a hierarchy of immunodominance, in which responses to epitopes of immediate-early (IE) and some early (E) antigens are more frequently observed than responses to epitopes of late (L) expressed antigens. It has been proposed that this hierarchy, which correlates with the phase-specific efficiency of antigen presentation, may be due to the influence of viral immune-evasion genes. At least three EBV-encoded genes, BNLF2a, BGLF5 and BILF1, have the potential to inhibit processing and presentation of CD8+ T cell epitopes. Here we examined the relative contribution of these genes to modulation of CD8+ T cell recognition of EBV lytic antigens expressed at different phases of the replication cycle in EBV-transformed B-cells (LCLs) which spontaneously reactivate lytic cycle. Selective shRNA-mediated knockdown of BNLF2a expression led to more efficient recognition of immediate-early (IE)- and early (E)-derived epitopes by CD8+ T cells, while knock down of BILF1 increased recognition of epitopes from E and late (L)-expressed antigens. Contrary to what might have been predicted from previous ectopic expression studies in EBV-negative model cell lines, the shRNA-mediated inhibition of BGLF5 expression in LCLs showed only modest, if any, increase in recognition of epitopes expressed in any phase of lytic cycle. These data indicate that whilst BNLF2a interferes with antigen presentation with diminishing efficiency as lytic cycle progresses (IE>E>L), interference by BILF1 increases with progression through lytic cycle (IEphase-specific effects that provide mechanistic insight into

  1. Sigma S-Dependent Antioxidant Defense Protects Stationary-Phase Escherichia coli against the Bactericidal Antibiotic Gentamicin

    PubMed Central

    Wang, Jing-Hung; Singh, Rachna; Benoit, Michael; Keyhan, Mimi; Sylvester, Matthew; Hsieh, Michael; Thathireddy, Anuradha; Hsieh, Yi-Ju

    2014-01-01

    Stationary-phase bacteria are important in disease. The σs-regulated general stress response helps them become resistant to disinfectants, but the role of σs in bacterial antibiotic resistance has not been elucidated. Loss of σs rendered stationary-phase Escherichia coli more sensitive to the bactericidal antibiotic gentamicin (Gm), and proteomic analysis suggested involvement of a weakened antioxidant defense. Use of the psfiA genetic reporter, 3′-(p-hydroxyphenyl) fluorescein (HPF) dye, and Amplex Red showed that Gm generated more reactive oxygen species (ROS) in the mutant. HPF measurements can be distorted by cell elongation, but Gm did not affect stationary-phase cell dimensions. Coadministration of the antioxidant N-acetyl cysteine (NAC) decreased drug lethality particularly in the mutant, as did Gm treatment under anaerobic conditions that prevent ROS formation. Greater oxidative stress, due to insufficient quenching of endogenous ROS and/or respiration-linked electron leakage, therefore contributed to the greater sensitivity of the mutant; infection by a uropathogenic strain in mice showed this to be the case also in vivo. Disruption of antioxidant defense by eliminating the quencher proteins, SodA/SodB and KatE/SodA, or the pentose phosphate pathway proteins, Zwf/Gnd and TalA, which provide NADPH for ROS decomposition, also generated greater oxidative stress and killing by Gm. Thus, besides its established mode of action, Gm also kills stationary-phase bacteria by generating oxidative stress, and targeting the antioxidant defense of E. coli can enhance its efficacy. Relevant aspects of the current controversy on the role of ROS in killing by bactericidal drugs of exponential-phase bacteria, which represent a different physiological state, are discussed. PMID:25070093

  2. Sigma S-dependent antioxidant defense protects stationary-phase Escherichia coli against the bactericidal antibiotic gentamicin.

    PubMed

    Wang, Jing-Hung; Singh, Rachna; Benoit, Michael; Keyhan, Mimi; Sylvester, Matthew; Hsieh, Michael; Thathireddy, Anuradha; Hsieh, Yi-Ju; Matin, A C

    2014-10-01

    Stationary-phase bacteria are important in disease. The σ(s)-regulated general stress response helps them become resistant to disinfectants, but the role of σ(s) in bacterial antibiotic resistance has not been elucidated. Loss of σ(s) rendered stationary-phase Escherichia coli more sensitive to the bactericidal antibiotic gentamicin (Gm), and proteomic analysis suggested involvement of a weakened antioxidant defense. Use of the psfiA genetic reporter, 3'-(p-hydroxyphenyl) fluorescein (HPF) dye, and Amplex Red showed that Gm generated more reactive oxygen species (ROS) in the mutant. HPF measurements can be distorted by cell elongation, but Gm did not affect stationary-phase cell dimensions. Coadministration of the antioxidant N-acetyl cysteine (NAC) decreased drug lethality particularly in the mutant, as did Gm treatment under anaerobic conditions that prevent ROS formation. Greater oxidative stress, due to insufficient quenching of endogenous ROS and/or respiration-linked electron leakage, therefore contributed to the greater sensitivity of the mutant; infection by a uropathogenic strain in mice showed this to be the case also in vivo. Disruption of antioxidant defense by eliminating the quencher proteins, SodA/SodB and KatE/SodA, or the pentose phosphate pathway proteins, Zwf/Gnd and TalA, which provide NADPH for ROS decomposition, also generated greater oxidative stress and killing by Gm. Thus, besides its established mode of action, Gm also kills stationary-phase bacteria by generating oxidative stress, and targeting the antioxidant defense of E. coli can enhance its efficacy. Relevant aspects of the current controversy on the role of ROS in killing by bactericidal drugs of exponential-phase bacteria, which represent a different physiological state, are discussed. PMID:25070093

  3. Protective effect of N-acetylcysteine against DNA damage and S-phase arrest induced by ochratoxin A in human embryonic kidney cells (HEK-293).

    PubMed

    Yang, Qian; Shi, Lei; Huang, Kunlun; Xu, Wentao

    2014-08-01

    N-acetylcysteine (NAC) has recently gained particular interest as a beneficial antioxidant. This study investigated the protective effects of NAC against ochratoxin A (OTA)-induced DNA damage and S-phase arrest in human embryonic kidney cells (HEK-293). OTA exposure results in nephrotoxicity, hepatotoxicity as well as immunotoxicity; and, in the present study, the toxicity of OTA toward HEK-293 cells was explored by analyzing the involvement of the oxidative pathway. It was found that OTA treatment led to oxidative damage; meanwhile, OTA treatment induced significant DNA damage and S-phase arrest by down-regulating cyclin A2, cyclin E1, and CDK2 expression. However, NAC pretreatment alleviated OTA-induced ROS overproduction, the loss of mitochondrial membrane potential (ΔΨm), and the decrease in superoxide dismutase (SOD) activity. NAC pretreatment was also discovered to attenuate OTA-induced DNA damage using the comet assay and by determining the expression of γ-H2AX. In addition, NAC pretreatment partly ameliorated OTA-induced S-phase arrest by preventing the down-regulation of cyclin A2, cyclin E1 and CDK2 expression in HEK-293 cells. All of these results demonstrated that oxidative damage was involved in OTA-induced DNA damage and cell cycle arrest in HEK-293 cells. Therefore, NAC has the potential to reverse the DNA damage and S-phase arrest induced by OTA.

  4. Annual Report for Hybrid Plasma Reactor/Filter for Transportable Collective Protection Systems—Phase 1B

    SciTech Connect

    Josephson, Gary B.; Tonkyn, Russell G.; Rappe, Kenneth G.; Frye, John G.

    2009-06-01

    Annual report covering the development of a hybrid nonthermal plasma single-pass filtration system for collective protection. This report covers NTP destruction testing on a high priority Toxic Industrial Material and an surrogate for a sulfur containing chemical agent (e.g. mustard), Effects of catalysts in the nonthermal plasma and catalyst poisoning by the sulfur are presented. Also presented are proof-of-principle data for utilizing ozone created in the NTP as a beneficial reactant to destroy adsorbed contaminants in-situ. Catalysts to decompose the ozone within the adsorbent bed are necessary to convert the adsorber into an ozone reactor.

  5. Imaging the morphological change of tissue structure during the early phase of esophageal tumor progression using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Kang, Deyong; Xu, Meifang; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2012-12-01

    Esophageal cancer is a common malignancy with a very poor prognosis. Successful strategies for primary prevention and early detection are critically needed to control this disease. Multiphoton microscopy (MPM) is becoming a novel optical tool of choice for imaging tissue architecture and cellular morphology by two-photon excited fluorescence. In this study, we used MPM to image microstructure of human normal esophagus, carcinoma in situ (CIS), and early invasive carcinoma in order to establish the morphological features to differentiate these tissues. The diagnostic features such as the appearance of cancerous cells, the significant loss of stroma, the absence of the basement membrane were extracted to distinguish between normal and cancerous esophagus tissue. These results correlated well with the paired histological findings. With the advancement of clinically miniaturized MPM and the multi-photon probe, combining MPM with standard endoscopy will therefore allow us to make a real-time in vivo diagnosis of early esophageal cancer at the cellular level.

  6. Gravitational waves from first order phase transitions as a probe of an early matter domination era and its inverse problem

    NASA Astrophysics Data System (ADS)

    Barenboim, Gabriela; Park, Wan-Il

    2016-08-01

    We investigate the gravitational wave background from a first order phase transition in a matter-dominated universe, and show that it has a unique feature from which important information about the properties of the phase transition and thermal history of the universe can be easily extracted. Also, we discuss the inverse problem of such a gravitational wave background in view of the degeneracy among macroscopic parameters governing the signal.

  7. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)

    PubMed Central

    Jabbour, Elias; Saglio, Giuseppe; Steegmann, Juan Luis; Shah, Neil P.; Boqué, Concepción; Chuah, Charles; Pavlovsky, Carolina; Mayer, Jiří; Cortes, Jorge; Baccarani, Michele; Kim, Dong-Wook; Bradley-Garelik, M. Brigid; Mohamed, Hesham; Wildgust, Mark; Hochhaus, Andreas

    2014-01-01

    This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP) in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients trial with a minimum follow-up of 3 years. Patients with newly diagnosed CML-CP were randomized to receive 100 mg dasatinib (n = 259) or 400 mg imatinib (n = 260) once daily. The retrospective landmark analysis included patients evaluable at the relevant time point (3, 6, or 12 months). Median time to complete cytogenetic response was 3 vs 6 months with dasatinib vs imatinib. At 3 and 6 months, the proportion of patients with BCR-ABL transcript levels ≤10% was higher in the dasatinib arm. Deeper responses at 3, 6, and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival and overall survival in both arms. First-line dasatinib resulted in faster and deeper responses compared with imatinib. The achievement of an early molecular response was predictive of improved progression-free survival and overall survival, supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors. This study was registered at www.clinicaltrials.gov as NCT00481247. PMID:24311723

  8. Efficient natural defense mechanisms against Listeria monocytogenes in T and B cell-deficient allogeneic bone marrow radiation chimeras. Preactivated macrophages are the main effector cells in an early phase after bone marrow transfer

    SciTech Connect

    Roesler, J.; Groettrup, E.B.; Baccarini, M.; Lohmann-Mattes, M.L. )

    1989-09-01

    Radiation chimeras in the early phase after bone marrow transplantation are a good model to study the efficiency of the body's nonspecific defense system represented by macrophages (M phi), polymorphonuclear cells (PMN), and NK cells. These cell types are present in large numbers in spleen and liver at that time, whereas the specific immune system represented by T and B cells is functionally deficient. We previously reported enhanced activities in vitro of M phi (and PMN) from recipient animals in an early phase after allogeneic bone marrow transfer. We here demonstrate that these activities result in enhanced spontaneous resistance against Listeria monocytogenes in vivo: CFU of L. monocytogenes in spleen and liver 48 h after infection were about 1 or 2 to 4 log steps less than in untreated control mice of donor or host haplotype. This enhanced resistance decreased over the 4-mo period after marrow transfer. Preactivated M phi were identified as the most important effector cells. Isolated from spleen and peritoneal cavity, they performed enhanced killing of phagocytosed Listeria. Such preactivated M phi occurred in recipient animals after transfer of allogeneic but not of syngeneic bone marrow. The precise mechanism of M phi activation in the allogeneic radiation chimera in the complete absence of any detectable T cell function is not clear at present. However, these preactivated M phi display an important protective effect against L. monocytogenes: chimeras could eliminate Listeria without acquisition of positive delayed-type sensitivity when infected with 10(3) bacteria. An inoculum of 5 . 10(3) L. monocytogenes resulted either in prolonged survival compared with normal mice of the recipient haplotype or in definitive survival accompanied by a positive delayed-type sensitivity.

  9. Astaxanthin protects ARPE-19 cells from oxidative stress via upregulation of Nrf2-regulated phase II enzymes through activation of PI3K/Akt

    PubMed Central

    Li, Zhongrui; Dong, Xin; Liu, Hongling; Chen, Xi; Shi, Huanqi; Fan, Yan; Hou, Dingshan

    2013-01-01

    Purpose Oxidative stress on retinal pigment epithelial (RPE) cells is thought to play a crucial role in the development and progression of age-related macular degeneration. Astaxanthin (AST) is a carotenoid that shows significant antioxidant properties. This study was designed to investigate the protective effect of AST on ARPE-19 cells against oxidative stress and the possible underlying mechanism. Methods ARPE-19 cells exposed to different doses of H2O2 were incubated with various concentrations of AST and cell viability subsequently detected with the (4-[3-[4-iodophenyl]-2–4(4-nitrophenyl)-2H-5- tetrazolio-1,3-benzene disulfonate]; WST-1) assay. The apoptosis rate and intracellular levels of reactive oxygen species (ROS) were measured with flow cytometry. NAD(P)H quinine oxidoreductase 1 (NQO1), hemeoxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC) expression were examined with real-time PCR and western blotting. The nuclear localization of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein and the expression levels of cleaved caspase-3 and protein kinase B proteins were evaluated with western blotting. Results AST clearly reduced H2O2-induced cell viability loss, cell apoptosis, and intracellular generation of ROS. Furthermore, treatment with AST activated the Nrf2-ARE pathway by inducing Nrf2 nuclear localization. Consequently, Phase II enzymes NQO1, HO-1, GCLM, and GCLC mRNA and proteins were increased. AST inhibited expression of H2O2-induced cleaved caspase-3 protein. Activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway was involved in the protective effect of AST on the ARPE-19 cells. Conclusions AST protected ARPE-19 cells against H2O2-induced oxidative stress via Nrf2-mediated upregulation of the expression of Phase II enzymes involving the PI3K/Akt pathway. PMID:23901249

  10. SU-E-I-91: Quantitative Assessment of Early Hepatocellular Carcinoma and Cavernous Hemangioma of Live Using In-Line Phase-Contrast X-Ray Imaging

    SciTech Connect

    Duan, J

    2015-06-15

    Purpose: To investigate the potential utility of in-line phase-contrast imaging (ILPCI) technique with synchrotron radiation in detecting early hepatocellular carcinoma and cavernous hemangioma of live using in vitro model system. Methods: Without contrast agents, three typical early hepatocellular carcinoma specimens and three typical cavernous hemangioma of live specimens were imaged using ILPCI. To quantitatively discriminate early hepatocellular carcinoma tissues and cavernous hemangioma tissues, the projection images texture feature based on gray level co-occurrence matrix (GLCM) were extracted. The texture parameters of energy, inertia, entropy, correlation, sum average, sum entropy, difference average, difference entropy and inverse difference moment, were obtained respectively. Results: In the ILPCI planar images of early hepatocellular carcinoma specimens, vessel trees were clearly visualized on the micrometer scale. Obvious distortion deformation was presented, and the vessel mostly appeared as a ‘dry stick’. Liver textures appeared not regularly. In the ILPCI planar images of cavernous hemangioma of live specimens, typical vessels had not been found compared with the early hepatocellular carcinoma planar images. The planar images of cavernous hemangioma of live specimens clearly displayed the dilated hepatic sinusoids with the diameter of less than 100 microns, but all of them were overlapped with each other. The texture parameters of energy, inertia, entropy, correlation, sum average, sum entropy, and difference average, showed a statistically significant between the two types specimens image (P<0.01), except the texture parameters of difference entropy and inverse difference moment(P>0.01). Conclusion: The results indicate that there are obvious changes in morphological levels including vessel structures and liver textures. The study proves that this imaging technique has a potential value in evaluating early hepatocellular carcinoma and cavernous

  11. 77 FR 7174 - Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ...), United States Department of the Interior (DOI), published a notice in the Federal Register (76 FR 78016... Restoration Plan and Environmental Assessment AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of... (OPA), the National Environmental Policy Act (NEPA), and the Framework Agreement for Early...

  12. Evaluation of acid-labile S-protecting groups to prevent Cys racemization in Fmoc solid-phase peptide synthesis

    PubMed Central

    Hibino, Hajime; Miki, Yasuyoshi; Nishiuchi, Yuji

    2014-01-01

    Phosphonium and uronium salt-based reagents enable efficient and effective coupling reactions and are indispensable in peptide chemistry, especially in machine-assisted SPPS. However, after the activating and coupling steps with these reagents in the presence of tertiary amines, Fmoc derivatives of Cys are known to be considerably racemized during their incorporation. To avoid this side reaction, a coupling method mediated by phosphonium/uronium reagents with a weaker base, such as 2,4,6-trimethylpyridine, than the ordinarily used DIEA or that by carbodiimide has been recommended. However, these methods are appreciably inferior to the standard protocol applied for SPPS, that is, a 1 min preactivation procedure of coupling with phosphonium or uronium reagents/DIEA in DMF, in terms of coupling efficiency, and also the former method cannot reduce racemization of Cys(Trt) to an acceptable level (<1.0%) even when the preactivation procedure is omitted. Here, the 4,4′-dimethoxydiphenylmethyl and 4-methoxybenzyloxymethyl groups were demonstrated to be acid-labile S-protecting groups that can suppress racemization of Cys to an acceptable level (<1.0%) when the respective Fmoc derivatives are incorporated via the standard SPPS protocol of phosphonium or uronium reagents with the aid of DIEA in DMF. Furthermore, these protecting groups significantly reduced the rate of racemization compared to the Trt group even in the case of microwave-assisted SPPS performed at a high temperature. © 2013 The Authors. European Peptide Society published by John Wiley & Sons, Ltd. PMID:24357151

  13. Inflammatory cytokines imbalance in the very early phase of acute coronary syndrome: correlations with angiographic findings and in-hospital events.

    PubMed

    Brunetti, Natale Daniele; Munno, Irene; Pellegrino, Pier Luigi; Ruggero, Vincenzo; Correale, Michele; De Gennaro, Luisa; Cuculo, Andrea; Campanale, Erasmo Giulio; Di Biase, Matteo

    2011-02-01

    The aim of this study is to investigate the release of some inflammatory cytokines (Cks) during the very early phase (first 24 h) of acute coronary syndrome (ACS). Twenty-six consecutive subjects admitted to coronary care unit with ACS underwent serial blood sampling in order to evaluate concentrations of interleukin (IL)-2, IL-10, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Blood samples were taken within 6 h after onset of chest pain (T₀), at 12 h (T₁), and at 24 h (T₂). Patients were thus divided into four groups comparing pro-inflammatory Ck release (IL-2, TNF-α, and IFN-γ) and anti-inflammatory activity (IL-10). Clinical features, risk factors, incidence of adverse events, and coronary angiography findings were compared with Ck activation. Ck levels were significantly increased if compared with baseline. Subjects with marked inflammatory response showed a higher incidence of left anterior descending coronary disease (IL-2, p < 0.001; TNF-α and IFN-γ, p < 0.05) and more often incurred early complications (IL-2, p < 0.05; IFN-γ, p < 0.001). A correlation was detectable between IL-18 levels and myocardial enzyme release (creatine kinase, r = 0.47; lactate dehydrogenase, r = 0.54; troponin I, r = 0.58; p < 0.05). TNF-α levels were associated with a worse prognosis at follow-up (Log rank, p < 0.05). A Ck activation characterizes the early phase of ACS. Early inflammatory reaction seems to correlate with coronary disease and adverse events.

  14. The Protective Role of Resilience in Attenuating Emotional Distress and Aggression Associated with Early-life Stress in Young Enlisted Military Service Candidates

    PubMed Central

    Kim, Joohan; Choi, Kang; Jon, Duk-In; Hong, Hyun Ju; Hong, Narei; Lee, Eunjeong

    2015-01-01

    Early life stress (ELS) may induce long-lasting psychological complications in adulthood. The protective role of resilience against the development of psychopathology is also important. The purpose of this study was to investigate the relationships among ELS, resilience, depression, anxiety, and aggression in young adults. Four hundred sixty-one army inductees gave written informed consent and participated in this study. We assessed psychopathology using the Korea Military Personality Test, ELS using the Childhood Abuse Experience Scale, and resilience with the resilience scale. Analyses of variance, correlation analyses, and hierarchical multiple linear regression analyses were conducted for statistical analyses. The regression model explained 35.8%, 41.0%, and 23.3% of the total variance in the depression, anxiety, and aggression indices, respectively. We can find that even though ELS experience is positively associated with depression, anxiety, and aggression, resilience may have significant attenuating effect against the ELS effect on severity of these psychopathologies. Emotion regulation showed the most beneficial effect among resilience factors on reducing severity of psychopathologies. To improve mental health for young adults, ELS assessment and resilience enhancement program should be considered. PMID:26539013

  15. The Protective Role of Resilience in Attenuating Emotional Distress and Aggression Associated with Early-life Stress in Young Enlisted Military Service Candidates.

    PubMed

    Kim, Joohan; Seok, Jeong-Ho; Choi, Kang; Jon, Duk-In; Hong, Hyun Ju; Hong, Narei; Lee, Eunjeong

    2015-11-01

    Early life stress (ELS) may induce long-lasting psychological complications in adulthood. The protective role of resilience against the development of psychopathology is also important. The purpose of this study was to investigate the relationships among ELS, resilience, depression, anxiety, and aggression in young adults. Four hundred sixty-one army inductees gave written informed consent and participated in this study. We assessed psychopathology using the Korea Military Personality Test, ELS using the Childhood Abuse Experience Scale, and resilience with the resilience scale. Analyses of variance, correlation analyses, and hierarchical multiple linear regression analyses were conducted for statistical analyses. The regression model explained 35.8%, 41.0%, and 23.3% of the total variance in the depression, anxiety, and aggression indices, respectively. We can find that even though ELS experience is positively associated with depression, anxiety, and aggression, resilience may have significant attenuating effect against the ELS effect on severity of these psychopathologies. Emotion regulation showed the most beneficial effect among resilience factors on reducing severity of psychopathologies. To improve mental health for young adults, ELS assessment and resilience enhancement program should be considered.

  16. [EFFICACY AND SECURITY OF A CONVENTIONAL PROCEDURE OF PLASMAPHERESIS IN COMPLEX OF TREATMENT OF NONBILIARY ACUTE PANCREATITIS IN EARLY PHASE OF THE DISEASE].

    PubMed

    Mishalov, V G; Markulan, L Yu; Matveyev, R M

    2016-02-01

    Abstract Efficacy and security of a plasmapheresis procedure in complex of treatment of nonbiliary acute pancreatitis in early phase of the disease were established, basing on the treatment results analysis in 48 patients. The plasmapheresis results were estimated in accordance to changes revealed in the intoxication leukocytic index (ILI), a general protein (GP) content, general calcium (GC) in the blood plasm and of the activated partial thrombin time (APTHT). Application of plasmapheresis in patients, suffering purulent pancreatitis in the enzymal phase, have guaranteed a staged reduction of ILI by (34.86 ± 1.27)%, the APTHT enhancement from (35.15 ± 0.37) to (52.01 ± 0.62) sec, a trustworthy lowering of the GP by (4.35 ± 0.02) g/L at average and of GC in a blood plasmby (10.45 ± 0.38)%. PMID:27244915

  17. Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study)

    PubMed Central

    Quintela-Fandino, M; Urruticoechea, A; Guerra, J; Gil, M; Gonzalez-Martin, A; Marquez, R; Hernandez-Agudo, E; Rodriguez-Martin, C; Gil-Martin, M; Bratos, R; Escudero, M J; Vlassak, S; Hilberg, F; Colomer, R

    2014-01-01

    Introduction: Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer. Methods: Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method). Results: The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide. The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose intensity was ∼100%. The pathologic complete response was 50%. Conclusions: The combination allows the delivery of full-dose intensity, while efficacy seems promising. PMID:25058346

  18. ET-1 deletion from endothelial cells protects the kidney during the extension phase of ischemia/reperfusion injury

    SciTech Connect

    Arfian, Nur; Emoto, Noriaki; Vignon-Zellweger, Nicolas; Nakayama, Kazuhiko; Yagi, Keiko; Hirata, Ken-ichi

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Ischemia/reperfusion injury (IRI) induced increased endothelin-1 (ET-1) expression. Black-Right-Pointing-Pointer IRI was accompanied by tubular injury and remodeling of renal arteries. Black-Right-Pointing-Pointer IRI increased oxidative stress and inflammation. Black-Right-Pointing-Pointer Genetic suppression of ET-1 in endothelial cells attenuates IRI in the kidney. Black-Right-Pointing-Pointer The mechanisms include the inhibition of oxidative stress and inflammation. -- Abstract: Background: The prognosis of patients after acute kidney injury (AKI) is poor and treatment is limited. AKI is mainly caused by renal ischemia/reperfusion injury (IRI). During the extension phase of IRI, endothelial damage may participate in ischemia and inflammation. Endothelin-1 (ET-1) which is mostly secreted by endothelial cells is an important actor of IRI, particularly through its strong vasoconstrictive properties. We aimed to analyze the specific role of ET-1 from the endothelial cells in AKI. Methods: We used mice lacking ET-1 in the vascular endothelial cells (VEETKO). We induced IRI in VEETKO mice and wild type controls by clamping both kidneys for 30 min. Sham operated mice were used as controls. Mice were sacrificed one day after IRI in order to investigate the extension phase of IRI. Kidney function was assessed based on serum creatinine concentration. Levels of expression of ET-1, its receptor ET{sub A}, protein kinase C, eNOS, E-Cadherin and inflammation markers were evaluated by real time PCR or western blot. Tubular injury was scored on periodic acid Schiff stained kidney preparations. Lumen and wall area of small intrarenal arteries were measured on kidney slices stained for alpha smooth muscle cell actin. Oxidative stress, macrophage infiltration and cell proliferation was evaluated on slices stained for 8-hydroxy-2 Prime -deoxyguanosine, F4/80 and PCNA, respectively. Results: IRI induced kidney failure and increased ET-1 and

  19. Asymmetric fluorination of α-branched cyclohexanones enabled by a combination of chiral anion phase-transfer catalysis and enamine catalysis using protected amino acids.

    PubMed

    Yang, Xiaoyu; Phipps, Robert J; Toste, F Dean

    2014-04-01

    We report a study involving the successful merger of two separate chiral catalytic cycles: a chiral anion phase-transfer catalysis cycle to activate Selectfluor and an enamine activation cycle, using a protected amino acid as organocatalyst. We have demonstrated the viability of this approach with the direct asymmetric fluorination of α-substituted cyclohexanones to generate quaternary fluorine-containing stereocenters. With these two chiral catalytic cycles operating together in a matched sense, high enantioselectivites can be achieved, and we envisage that this dual catalysis method has the potential to be more broadly applicable, given the breadth of enamine catalysis. It also represents a rare example of chiral enamine catalysis operating successfully on α-branched ketones, substrates commonly inert to this activation mode.

  20. Supported liquid membrane-protected molecularly imprinted beads for the solid phase micro-extraction of triazines from environmental waters.

    PubMed

    Turiel, E; Díaz-Álvarez, M; Martín-Esteban, A

    2016-02-01

    In this work, a novel methodology based on the combination of MIP technology with micro solid-phase extraction in a hollow fibre device for the trace enrichment and cleanup of triazines in environmental waters is described. All parameters affecting both migration of triazines from samples to the lumen of the fibre and rebinding into MIP sites have been carefully optimized. Final conditions included, addition of 20% NaCl to the sample to produce salting-out effect, extraction of analytes during 45min with orbital stirring at 750rpm, and then washing the fibre with toluene during 5min to allow selective recognition of triazines before elution in HPLC inserts containing 450μL of a methanol/acetic acid mixture (95/5, v/v). Under optimum conditions, quantitative recoveries for simazine, cyanazine, atrazine, propazine and terbutylazine, were achieved both in surface, ground and tap water samples, with relative standard deviations lower than 10.6%, and limits of detection in the low ngL(-1) concentration level. PMID:26777780

  1. Supported liquid membrane-protected molecularly imprinted beads for the solid phase micro-extraction of triazines from environmental waters.

    PubMed

    Turiel, E; Díaz-Álvarez, M; Martín-Esteban, A

    2016-02-01

    In this work, a novel methodology based on the combination of MIP technology with micro solid-phase extraction in a hollow fibre device for the trace enrichment and cleanup of triazines in environmental waters is described. All parameters affecting both migration of triazines from samples to the lumen of the fibre and rebinding into MIP sites have been carefully optimized. Final conditions included, addition of 20% NaCl to the sample to produce salting-out effect, extraction of analytes during 45min with orbital stirring at 750rpm, and then washing the fibre with toluene during 5min to allow selective recognition of triazines before elution in HPLC inserts containing 450μL of a methanol/acetic acid mixture (95/5, v/v). Under optimum conditions, quantitative recoveries for simazine, cyanazine, atrazine, propazine and terbutylazine, were achieved both in surface, ground and tap water samples, with relative standard deviations lower than 10.6%, and limits of detection in the low ngL(-1) concentration level.

  2. S phase entry causes homocysteine-induced death while ataxia telangiectasia and Rad3 related protein functions anti-apoptotically to protect neurons

    PubMed Central

    Ye, Weizhen

    2010-01-01

    A major phenotype seen in neurodegenerative disorders is the selective loss of neurons due to apoptotic death and evidence suggests that inappropriate re-activation of cell cycle proteins in post-mitotic neurons may be responsible. To investigate whether reactivation of the G1 cell cycle proteins and S phase entry was linked with apoptosis, we examined homocysteine-induced neuronal cell death in a rat cortical neuron tissue culture system. Hyperhomocysteinaemia is a physiological risk factor for a variety of neurodegenerative diseases, including Alzheimer’s disease. We found that in response to homocysteine treatment, cyclin D1, and cyclin-dependent kinases 4 and 2 translocated to the nucleus, and p27 levels decreased. Both cyclin-dependent kinases 4 and 2 regained catalytic activity, the G1 gatekeeper retinoblastoma protein was phosphorylated and DNA synthesis was detected, suggesting transit into S phase. Double-labelling immunofluorescence showed a 95% co-localization of anti-bromodeoxyuridine labelling with apoptotic markers, demonstrating that those cells that entered S phase eventually died. Neurons could be protected from homocysteine-induced death by methods that inhibited G1 phase progression, including down-regulation of cyclin D1 expression, inhibition of cyclin-dependent kinases 4 or 2 activity by small molecule inhibitors, or use of the c-Abl kinase inhibitor, Gleevec™, which blocked cyclin D and cyclin-dependent kinase 4 nuclear translocation. However, blocking cell cycle progression post G1, using DNA replication inhibitors, did not prevent apoptosis, suggesting that death was not preventable post the G1-S phase checkpoint. While homocysteine treatment caused DNA damage and activated the DNA damage response, its mechanism of action was distinct from that of more traditional DNA damaging agents, such as camptothecin, as it was p53-independent. Likewise, inhibition of the DNA damage sensors, ataxia-telangiectasia mutant and ataxia telangiectasia

  3. Fibrinogen level deteriorates before other routine coagulation parameters and massive transfusion in the early phase of severe trauma: a retrospective observational study.

    PubMed

    Hayakawa, Mineji; Gando, Satoshi; Ono, Yuichi; Wada, Takeshi; Yanagida, Yuichiro; Sawamura, Atsushi

    2015-02-01

    In trauma, hemostatic functions should be maintained appropriately to prevent massive bleeding. This study elucidated the time-dependent changes in platelet count and coagulation variables, and the effects of disseminated intravascular coagulation (DIC) on these changes during the early phase of trauma. Trauma patients with an injury severity score ≥16 were enrolled. The critical levels of platelet count and coagulation variables were defined according to recent trauma guidelines. Massive transfusion was defined as >10 units red cell concentrate. The time from arrival at the emergency department to reaching the critical levels and meeting the criteria for massive transfusion were evaluated. Eighty trauma patients were enrolled; 35 were diagnosed with DIC on arrival. Among all patients, fibrinogen levels reached the critical level earliest among routine coagulation parameters; other routine coagulation parameters deteriorated after the patients met the criteria for massive transfusion. Routine coagulation parameters reached their critical levels earlier in DIC patients than patients without DIC. Massive transfusion was performed more frequently in DIC patients, who met the criteria earlier. During the early phase of trauma, fibrinogen levels deteriorate earlier than other routine coagulation parameters, especially in DIC patients.

  4. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

    PubMed Central

    Pustylnyak, Vladimir O.; Lisachev, Pavel D.; Shtark, Mark B.

    2015-01-01

    Gene expression plays an important role in the mechanisms of long-term potentiation (LTP), which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC) tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity. PMID:25767724

  5. Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

    NASA Astrophysics Data System (ADS)

    Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

    in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for γ rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

  6. Nanoscale studies of the early stages of phase separation in model nickel-aluminum-chromium-X superalloys

    NASA Astrophysics Data System (ADS)

    Booth-Morrison, Christopher

    The phase separation of model Ni-Al-Cr-X alloys is studied at the nanoscale employing atom-probe tomography (APT), electron microscopy and first-principles calculations. A comparison of the kinetic pathways resulting from the formation of coherent gamma'-precipitates in two Ni-Al-Cr alloys, Ni-7.5 Al-8.5 Cr and Ni-5.2 Al-14.2 Cr at.%, with similar gamma'-precipitate volume fractions at 873 K, is performed. The morphologies of the gamma'-precipitates of the alloys are similar, though the degrees of gamma'-precipitate coagulation and coalescence differ. Quantification within the framework of classical nucleation theory reveals that differences in the chemical driving forces for phase decomposition result in differences in the nucleation behavior of the two alloys. The temporal evolution of the gamma'-precipitate average radii and the gamma-matrix supersaturations follow the predictions of classical coarsening models. The compositional trajectories of the gamma-matrix phases of the alloys are found to follow approximately the equilibrium tie-lines, while the trajectories of the gamma'-precipitates do not, resulting in significant differences in the partitioning ratios of the solute elements. Phase separation in a Ni-6.5 Al-9.5 Cr at.% alloy aged at 873 K occurs in four distinct regimes: (i) quasi-stationary-state gamma' (L12)-precipitate nucleation; (ii) concomitant precipitate nucleation, growth, and coagulation and coalescence; (iii) concurrent growth and coarsening, wherein coarsening occurs via both gamma'-precipitate coagulation and coalescence and by the classical evaporation-condensation mechanism; and (iv) quasi-stationary-state coarsening of gamma'-precipitates, once the equilibrium volume fraction of precipitates is achieved. The predictions of classical nucleation and growth models are not validated experimentally, likely due to the complexity of the atomistic kinetic pathways involved in precipitation. During coarsening, the temporal evolution of the gamma

  7. Secondary structures of Val-Phe and Val-Tyr(Me) peptide chains in the gas phase: effect of the nature of the protecting groups

    NASA Astrophysics Data System (ADS)

    Chin, Wutharath; Dognon, Jean-Pierre; Piuzzi, François; Dimicoli, Iliana; Mons, Michel

    Recent experimental gas-phase studies of very similar peptide chain models (Ac-Val-Tyr(Me)-NHMe and Ac-Val-Phe-NH2) have led to different assignments for the secondary structures adopted: β-strand and β-turn, respectively. We present a discussion of the possible causes for such different behaviour in the light of quantum chemistry calculations. The consistent set of data presently obtained (relative energies and IR calculated spectra) leads us to propose the same structural assignment for the experimentally observed Val-Tyr(Me) and Val-Phe peptide chains, i.e. a β-turn conformation. In addition, calculations also suggest that the nature of the chemical protection on the C-terminal (-NHMe vs. -NH2) of the chain model does not affect its conformational preference, nor its structure or its energetics, which suggests the less simple, but more informative, -NH2-protected models for the determination of the intrinsic structural properties of a peptide chain.

  8. Memory signals from the thalamus: early thalamocortical phase synchronization entrains gamma oscillations during long-term memory retrieval.

    PubMed

    Staudigl, Tobias; Zaehle, Tino; Voges, Jürgen; Hanslmayr, Simon; Esslinger, Christine; Hinrichs, Hermann; Schmitt, Friedhelm C; Heinze, Hans-Jochen; Richardson-Klavehn, Alan

    2012-12-01

    The thalamus is believed to be a key node in human memory networks, however, very little is known about its real-time functional role. Here we examined the dynamics of thalamocortical communication during long-term episodic memory retrieval in two experiments. In experiment 1, intrathalamic and surface EEG was recorded in an epileptic patient implanted with depth electrodes for brain stimulation therapy. In a recognition memory test, early (300-500 ms) stimulus-linked oscillatory synchrony between mediodorsal thalamic and frontal surface electrodes at beta frequency (20 Hz) was enhanced for correctly remembered old compared to correctly rejected new items. Directionality measures (Granger causality) indicated that the thalamus was the sender, and the neocortex the receiver, of this beta signal, which also modulated the power of neocortical gamma (55-80 Hz) oscillations (cross-frequency coupling). Experiment 2 validated the cross-frequency coupling effects in a healthy participant sample. Confirming the findings from experiment 1, significantly increased cross-frequency coupling was found over frontal scalp electrodes during successful recognition. Extending anatomical knowledge on thalamic connectivity with frontal neocortex, these results suggest that the thalamus sends an early memory signal to frontal regions, triggering further memory search processes.

  9. Planetary Protection Progress of Hayabusa2 and Its Piggyback PROCYON: Launch, Earth Swingby and Outbound Cruising Phases

    NASA Astrophysics Data System (ADS)

    Yano, Hajime; Yoshikawa, Makoto; Sarli, Bruno; Ozaki, Naoya; Funase, Ryu; Tsuda, Yuichi; Chujo, Toshihiro; Ariu, Kaito

    2016-07-01

    Hayabusa-2 is Japan's second asteroid sample return mission which was successfully launched into the planned Earth departure trajectory with the H-IIA rocket on December 3rd, 2014, together with a group of its interplanetary piggyback micro- spacecraft, including the PROCYON(Proximate Object Close flYby with Optical Navigation)spacecraft, the world's first 50 kg-class deep space micro-spacecraft developed by the University of Tokyo and the Japan Aerospace Exploration Agency. The Hayabusa-2 spacecraft will go to Rug, a C-type NEO, and attempt surface investigations with daughter rovers (MINERVA-II series and MASCOT), artificial impact cratering experiment (SCI) and both surface and sub-surface sampling (Sampler) in 2018-2019 and plans to return to the Earth in December 2020. The PROCYON mission objective was to demonstrate a micro-spacecraft bus technology for deep space exploration and proximity flyby to asteroids performing optical measurements. Both of the above missions were fully evaluated by the COSPAR Planetary Protection Panel at the dedicated COSPAR colloquium and scientific assembly in 2014 and the COSPAR PPP has endorsed the Category-2 for their outbound trajectories and the non-restricted Earth return for the inbound trajectory of Hayabusa-2. As a part of the fulfillments of the Category-2 classification, both spacecraft must be compliant with the COSPAR PPP requirements of non-impact probability to Mars since they would have enough energy to reach and beyond the orbit of Mars, due to the Earth swing-by and ion engine operations for their outbound cruising. As for the Hayabusa-2 spacecraft, it successfully performed its Earth gravity assist in December 2015, resulting on accurate orbit determination for the post-swing-by orbit to be ready to restart the ion engine operation. Thus the non-impact probability to Mars did not change from the estimate given by Chujo, et al. (2015). As for the PROCYON spacecraft after the completion of the bus system

  10. Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

    PubMed Central

    Boer, R H de; Smith, I E; Pastorino, U; O'Brien, M E R; Ramage, F; Ashley, S; Goldstraw, P

    1999-01-01

    Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaign PMID:10188899

  11. Design Tools for Cost-Effective Implementation of Planetary Protection Requirements

    NASA Technical Reports Server (NTRS)

    Hamlin, Louise; Belz, Andrea; Evans, Michael; Kastner, Jason; Satter, Celeste; Spry, Andy

    2006-01-01

    Since the Viking missions to Mars in the 1970s, accounting for the costs associated with planetary protection implementation has not been done systematically during early project formulation phases, leading to unanticipated costs during subsequent implementation phases of flight projects. The simultaneous development of more stringent planetary protection requirements, resulting from new knowledge about the limits of life on Earth, together with current plans to conduct life-detection experiments on a number of different solar system target bodies motivates a systematic approach to integrating planetary protection requirements and mission design. A current development effort at NASA's Jet Propulsion Laboratory is aimed at integrating planetary protection requirements more fully into the early phases of mission architecture formulation and at developing tools to more rigorously predict associated cost and schedule impacts of architecture options chosen to meet planetary protection requirements.

  12. Altered Phase-Relationship between Peripheral Oscillators and Environmental Time in Cry1 or Cry2 Deficient Mouse Models for Early and Late Chronotypes

    PubMed Central

    Destici, Eugin; Jacobs, Edwin H.; Tamanini, Filippo; Loos, Maarten; van der Horst, Gijsbertus T. J.; Oklejewicz, Małgorzata

    2013-01-01

    The mammalian circadian system is composed of a light-entrainable central clock in the suprachiasmatic nuclei (SCN) of the brain and peripheral clocks in virtually any other tissue. It allows the organism to optimally adjust metabolic, physiological and behavioral functions to the physiological needs it will have at specific time of the day. According to the resonance theory, such rhythms are only advantageous to an organism when in tune with the environment, which is illustrated by the adverse health effects originating from chronic circadian disruption by jetlag and shift work. Using short-period Cry1 and long-period Cry2 deficient mice as models for morningness and eveningness, respectively, we explored the effect of chronotype on the phase relationship between the central SCN clock and peripheral clocks in other organs. Whereas the behavioral activity patterns and circadian gene expression in the SCN of light-entrained Cry1-/- and Cry2-/- mice largely overlapped with that of wild type mice, expression of clock and clock controlled genes in liver, kidney, small intestine, and skin was shown to be markedly phase-advanced or phase-delayed, respectively. Likewise, circadian rhythms in urinary corticosterone were shown to display a significantly altered phase relationship similar to that of gene expression in peripheral tissues. We show that the daily dissonance between peripheral clocks and the environment did not affect the lifespan of Cry1-/- or Cry2-/- mice. Nonetheless, the phase-shifted peripheral clocks in light-entrained mice with morningness and eveningness-like phenotypes may have implications for personalized preventive and therapeutic (i.e. chronomodulation-based) health care for people with early and late chronotypes. PMID:24386234

  13. Apatite Chemistry in a Felsic Magmatic System From the El Teniente District (Chile) as Monitor of an Early, Single-phase, Cl and S-rich Magmatic Volatile Phase Evolution.

    NASA Astrophysics Data System (ADS)

    Hernandez, L. B.; Rabbia, O. M.

    2009-05-01

    Apatite (Ap) is a ubiquitous accessory mineral phase in igneous rocks, that can incorporate several geochemically important elements among which are volatiles as Cl, H2O, S, As, F. Furthermore, as Ap starts to crystallize early in felsic magmas, and continue through a wide temperature range, it can potentially be used to monitor the evolution of magmatic volatiles in porphyry copper systems. In this work, we have studied magmatic Ap from Late Miocene dacitic porphyries spatially and temporally associated to the Cu-(Mo) La Huifa- La Negra prospect (4 km NE from the giant El Teniente porphyry copper deposit, Chile). These felsic rocks formed from hydrous magmas as indicated by early crystallized Hb (before Bt). Al-Hb geobarometer indicates that phenocrysts formed at ˜2 Kb, while fine grained groundmass suggests a depressurization. Ap is present as small (˜10-50 microns) subhedral to euhedral prisms included in Fe-Ti oxides, plagioclase, amphibole and biotite phenocrysts (IAp), and as bigger (up to ˜300 microns) isolated microphenocrysts (MAp), indicating crystallization throughout magmatic evolution. About 300 EPM analyses of Cl, F and SO3 have been performed on Ap in different textural positions. Only Ap included in anhydrous phases (mostly Pl and oxides) and unaltered grains from the groundmass were used to evaluate volatile evolution. Calculated apatite saturation temperature following Piccoli and Candela (1994) indicates that they started to crystallize ˜900°C. The most outstanding chemical feature of the studied Ap is their high Cl (up to 4.52 wt%) and SO3 (up to 0.98 wt%) contents, being highest in IAp. Cl/F and Cl/OH strongly decrease from ApI to MAp within all studied samples varying in SiO2 content from 66.3 to 69.7 wt%. They display a continuous and well defined trend. This variation is controlled mainly by Cl decrease and F increase, meanwhile OH remains roughly constant. SO3 in Ap varies from 0.98wt% in IAp to below detection limit (0.02 wt% SO3) in

  14. YB-1 immunization combined with regulatory T-cell depletion induces specific T-cell responses that protect against neuroblastoma in the early stage.

    PubMed

    Zheng, Jin; Liu, Ping; Yang, Xiaofeng

    2012-12-01

    Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy. Currently, no effective clinical treatments are available for advanced neuroblastoma. In a previous study, we screened Y Box protein 1 (YB-1) as a potential neuroblastoma-associated antigen from sera of AGN2a-immunized mice by serological analysis of recombinant cDNA expression libraries technique. The aim of this study is to explore if YB-1 immunization in the context of Treg depletion could induce protective immune response against the neuroblastoma in mice. YB-1 was expressed and purified by pET-15b prokaryotic expression system. It was demonstrated that anti-YB-1 CD8(+) T-cell responses could be induced by AGN2a immunization, and the strongest CD8(+) T-cell responses against AGN2a were induced by YB-1-immunized mice in the context of Treg depletion compared with YB-1 only immunization group and control group. Importantly, the survival rate of mice treated with YB-1 immunization combined with Treg depletion was 80% when challenged by 1 × 10(4) AGN2a cells, significantly higher than that of mice immunized with YB-1 alone (P < 0.01). Furthermore, T-cell adoptive therapy showed that the neuroblastoma growth was inhibited when T cells or splenic cells from YB-1-immunized mice with Treg depletion were transferred to AGN2a bearing mice. Both CD4(+) and CD8(+) T cells were involved in the anti-neuroblastoma responses induced by YB-1 immunization combined with Treg depletion. These results indicated that YB-1 immunization combined with Treg depletion could induce specific T-cell responses against neuroblastoma and could be a potential strategy for the prevention and treatment of neuroblastoma in the early stage.

  15. Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats.

    PubMed

    Mitsuhashi, Junko; Morikawa, Shunichi; Shimizu, Kazuhiko; Ezaki, Taichi; Yasuda, Yoshiko; Hori, Sadao

    2013-01-01

    A single intravitreal injection of erythropoietin (EPO) (50 ng/eye) or phosphate-buffered saline was administered to 5-week-old Sprague-Dawley rats at the onset of diabetes mellitus (DM) to determine and evaluate the protective effect of EPO on retinal microvessels. DM was induced by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Morphological changes in microvessels in flat retinal preparations were evaluated during the subsequent 4 weeks by three-dimensional imaging of all blood vessels stained with fluorescein isothiocyanate-conjugated tomato lectin, following immunofluorescence techniques. No marked differences were observed in the shape or density of retinal vessels and the number of retinal capillary branches of the four groups [control, EPO, DM, and DM/EPO] up to 4 weeks after STZ administration. We also observed unique type IV collagen-positive filamentous structures that lacked both cellular elements and blood circulation (lectin-/type IV+ acellular strands), suggesting regressed vessel remnants. The lectin-/type IV+ acellular strands were detected soon after the onset of DM in the diabetic rats, and the number of these structures increased in the DM group (P < 0.01). A single intravitreal injection of EPO caused a significant reduction in the number of lectin-/type IV+ acellular strands to levels observed in the control group. However, the lectin-/type IV+ acellular strands were observed in the central area of the retina near the optic disc in all four groups. Intravitreal injection of EPO resulted in downregulation of the EPO receptor, vascular endothelial growth factor (VEGF), and VEGF receptor at 4 weeks. We conclude that EPO may play a primary role against the progression of diabetic retinopathy by reducing blood vessel degeneration at a very early disease stage. PMID:23178551

  16. Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group

    PubMed Central

    Cervantes, Francisco; López-Garrido, Pilar; Montero, María-Isabel; Jonte, Fermín; Martínez, Jesús; Hernández-Boluda, Juan-Carlos; Calbacho, María; Sureda, Anna; Pérez-Rus, Gloria; Nieto, José B.; Pérez-López, Cristina; Román-Gómez, José; González, Marcos; Pereira, Arturo; Colomer, Dolors

    2010-01-01

    Background Despite the favorable results of imatinib front line in chronic-phase chronic myeloid leukemia there is room for improvement. Design and Methods Early intervention during imatinib therapy was undertaken in 210 adults with chronic-phase chronic myeloid leukemia less than three months from diagnosis (Sokal high risk: 16%). Patients received imatinib 400 mg/day. At three months, dose was increased if complete hematologic response was not achieved. At six months, patients in complete cytogenetic response were kept on 400 mg and the remainder randomized to higher imatinib dose or 400 mg plus interferon-alfa. At 18 months, randomized patients were switched to a 2nd generation tyrosine kinase inhibitor if not in complete cytogenetic response and imatinib dose increased in non-randomized patients not in major molecular response. Results Seventy-two percent of patients started imatinib within one month from diagnosis. Median follow-up is 50.5 (range: 1.2–78) months. At three months 4 patients did not have complete hematologic response; at six months 73.8% were in complete cytogenetic response; among the remainder, 9 could not be randomized (toxicity or consent withdrawal), 17 were assigned to high imatinib dose, and 15 to 400 mg + interferon-alpha. The low number of randomized patients precluded comparison between the two arms. Cumulative response at three years was: complete hematologic response 98.6%, complete cytogenetic response 90% and major molecular response 82%. On an intention-to-treat basis, complete cytogenetic response was 78.8% at 18 months. At five years, survival was 97.5%, survival free from accelerated/blastic phase 94.3%, failure free survival 82.5%, and event free survival (including permanent imatinib discontinuation) 71.5%. Concl