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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Early election for Group 1, Phase II boilers. 76.8 Section 76.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1, Phase II boilers. (a) General...

  4. Emergency management in the early phase.

    PubMed

    Crick, M; McKenna, T; Buglova, E; Winkler, G; Martincic, R

    2004-01-01

    An overview of response management in the early phase of an emergency at a nuclear installation is provided from a systems approach. This starts with the recognition of response goals, and using detailed analyses of threats, past experience, international law and principles, a response strategy is developed. The process is illustrated for the case of severe accidents at pressurized water reactors (PWRs) and identifies the need for and nature of: emergency classification based on plant conditions, notification, radiological monitoring and assessment strategies, operational criteria for implementing protective action decisions and management of public information. From the strategy detailed, functional and infrastructure requirements can be defined. The paper also presents some reflections on the key differences between response to emergencies arising from accidents and those arising from deliberate acts; on the preparedness and response capabilities of States, highlighting areas where generic improvements are needed and how best to achieve that. PMID:15238649

  5. Topological phases protected by point group symmetry

    NASA Astrophysics Data System (ADS)

    Huang, Sheng-Jie; Song, Hao; Hermele, Michael

    There has been remarkable progress in the theoretical understanding of symmetry protected topological (SPT) phases. However, most theories focus on internal, or on-site, symmetries, even though spatial symmetries are important in solids. In this talk, we classify bosonic SPT phases protected by crystalline point group symmetry, which we dub point group SPT (pgSPT) phases. Our approach is based on a procedure to reduce a d-dimensional pgSPT phase to lower-dimensional SPT phases protected by internal symmetry. For three-dimensional pgSPT phases, this approach allows us to gain insight into non-trivial properties at symmetry preserving surfaces. In particular, we obtain toy models for the surfaces of certain pgSPT phases at which there is a symmetry preserving Z2 topological order with anomalous symmetry fractionalization. We also discuss connections between bosonic pgSPT phases and electronic topological crystalline insulators. This research is supported by the U.S. Department of Energy (DOE), Office of Science, Basic Energy Sciences (BES) under Award # DE-SC0014415.

  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. 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.

  8. Stroboscopic Symmetry-Protected Topological Phases

    NASA Astrophysics Data System (ADS)

    Santos, Luiz; Iadecola, Thomas; Chamon, Claudio

    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 talk, I 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. Phys. Rev. B 92, 125107 (2015); arXiv:1503.07871

  9. 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.

  10. The Early Phase of Spark Ignition

    NASA Astrophysics Data System (ADS)

    Pitt, Philip Lawrence

    In this dissertation, some practical ignition techniques are presented that show how some problems of lean-burn combustion can be overcome. Then, to shed light on the effects of the ignition techniques described, the focus shifts to the more specific problem of the early phase of spark ignition. Thermal models of ignition are reviewed. These models treat the energy provided by the electrical discharge as a point source, delivered infinitely fast and creating a spherically symmetric ignition kernel. The thesis challenges the basis of these thermal models by reviewing the work of many investigators who have clearly shown that the temporal characteristics of the discharge have a profound effect upon ignition. Photographic evidence of the early phase of ignition, as well as other evidence from the literature, is also presented. The evidence clearly demonstrates that the morphology of spark kernels in the early phase of development is toroidal, not spherical as suggested by thermal models. A new perspective for ignition, a fluid dynamic point of view, is described. The common ignition devices are then classified according to fluid dynamics. A model describing the behaviour of spark kernels is presented, which extends a previously established mixing model for plasma jets, to the realm of conventional axial discharges. Comparison of the model behaviour to some limited data is made. The model is modified by including the effect of heat addition from combustion, and ignition criteria are discussed.

  11. 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

  12. Protected boundary states in gapless topological phases

    NASA Astrophysics Data System (ADS)

    Matsuura, Shunji; Chang, Po-Yao; Schnyder, Andreas P.; Ryu, Shinsei

    2013-06-01

    We systematically study gapless topological phases of (semi-)metals and nodal superconductors described by Bloch and Bogoliubov-de Gennes Hamiltonians. Using K-theory, a classification of topologically stable Fermi surfaces in (semi-)metals and nodal lines in superconductors is derived. We discuss a generalized bulk-boundary correspondence that relates the topological features of the Fermi surfaces and superconducting nodal lines to the presence of protected zero-energy states at the boundary of the system. Depending on the case, the boundary states are either linearly dispersing (i.e. Dirac or Majorana states) or dispersionless, forming two-dimensional surface flat bands or one-dimensional arc surface states. We study examples of gapless topological phases in symmetry classes AIII and DIII, focusing in particular on nodal superconductors, such as nodal noncentrosymmetric superconductors. For some cases we explicitly compute the surface spectrum and examine the signatures of the topological boundary states in the surface density of states. We also discuss the robustness of the surface states against disorder.

  13. [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

  14. 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

  15. Protective factors in the development of early child conduct problems

    PubMed Central

    Vanderbilt-Adriance, Ella; Shaw, Daniel S.; Brennan, Lauretta M.; Dishion, Thomas J.; Gardner, Frances; Wilson, Melvin N.

    2014-01-01

    The present study utilized a resilience model to investigate child, family, and community protective factors in toddlerhood as they relate to low levels of conduct problems at age 5 in a sample of low income children at risk for early disruptive problem behavior. Child, family, and community factors were associated with lower levels of conduct problems at age 5. Child, family, and community protective factors also distinguished between children who remained below and above a clinical threshold for aggressive problems between age 2 and 5. Finally, each domain of protective factors made small but significant unique contributions to lower aggression at age 5. These results emphasize the importance of multivariate analysis of the ecology of development predicting child outcome, and suggest potential areas for intervention with children at high risk for conduct problems. PMID:25774071

  16. 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].

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. The immediate early gene of canine herpesvirus is transcribed through early and late phases.

    PubMed

    Miyoshi, Masahiro; Okazaki, Katsunori; Takiguchi, Mitsuyoshi; Kida, Hiroshi; Hashimoto, Akira

    2002-07-01

    The immediate early (IE) gene of canine herpesvirus (CHV), homologue of the infected cell protein 4 (ICP4) gene of herpes simplex virus 1, is transcribed as a 4.9kb mRNA during IE phase. The IE gene was further transcribed as a 4.8kb mRNA through early (E) and late (L) phases of productive infection. Transcription of the 4.8kb mRNA initiated from downstream of the TATA box in an intron which was spliced out during IE phase. The reverse transcription-polymerase chain reaction revealed that the IE promoter was turned off during L phase at a permissive temperature. We, thus, propose to redesignate the IE gene of CHV as CICP4 gene. PMID:12185320

  4. 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

  5. Management of the second phase of labour: perineum protection techniques.

    PubMed

    Laganà, A S; Burgio, M A; Retto, G; Pizzo, A; Granese, R; Sturlese, E; Ciancimino, L; Chiofalo, B; Retto, A; Triolo, O

    2015-06-01

    The obstetric experience alongside scientific evidences in literature indicate several management techniques during the expulsive period of labour to minimize obstetric complications. Among the various methods that can be used for the protection of the perineum during the expulsive phase, some are performed prepartum (perineum massage), while most are used during childbirth. Among the second group, progressively increasing importance is assumed by the manual techniques to protect the perineum (using the "hands-on" and "hands-off") and by episiotomy. These techniques, when used in accordance to the guidelines, may favour the reduction of adverse outcomes for both the mother and the newborn, both immediately after birth and after a longer time. The midwife should be aware of the evidences in literature so that a critical analysis of the available techniques can be made and put in action during the expulsive phase in order to protect the mother and the foetus from any unfavourable outcomes. Currently, clinical evidence in literature is directing obstetric and medical staff towards a careful analysis of the maternal-foetal parameters, in order to achieve a precise assessment of the risks factors of intrapartum and postpartum outcomes. Increasingly, there is the need for close collaboration between the midwife and medical staff to ensure proper personalized assistance based on the peculiar characteristics of the woman and the fetus. PMID:25909491

  6. Symmetry-protected topological phases in noninteracting fermion systems

    NASA Astrophysics Data System (ADS)

    Wen, Xiao-Gang

    2012-02-01

    Symmetry-protected topological (SPT) phases are gapped quantum phases with a certain symmetry, which can all be smoothly connected to the same trivial product state if we break the symmetry. For noninteracting fermion systems with time reversal (T̂), charge conjugation (Ĉ), and/or U(1) (N̂) symmetries, the total symmetry group can depend on the relations between those symmetry operations, such as T̂N̂T̂-1=N̂ or T̂N̂T̂-1=-N̂. As a result, the SPT phases of those fermion systems with different symmetry groups have different classifications. In this paper, we use Kitaev's K-theory approach to classify the gapped free-fermion phases for those possible symmetry groups. In particular, we can view the U(1) as a spin rotation. We find that superconductors with the Sz spin-rotation symmetry are classified by Z in even dimensions, while superconductors with the time reversal plus the Sz spin-rotation symmetries are classified by Z in odd dimensions. We show that all 10 classes of gapped free-fermion phases can be realized by electron systems with certain symmetries. We also point out that, to properly describe the symmetry of a fermionic system, we need to specify its full symmetry group that includes the fermion number parity transformation (-)N̂. The full symmetry group is actually a projective symmetry group.

  7. 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

  8. Cytokine expression during early and late phase of acute Puumala hantavirus infection

    PubMed Central

    2011-01-01

    Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

  9. 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.

  10. 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.

  11. Phase Relationship between Alternans of Early and Late Phases of Ventricular Action Potentials

    PubMed Central

    Jing, Linyuan; Agarwal, Anuj; Chourasia, Sonam; Patwardhan, Abhijit

    2012-01-01

    Background: Alternans of early phase and of duration of action potential (AP) critically affect dispersion of refractoriness through their influence on conduction and repolarization. We investigated the phase relationship between the two alternans and its effect on conduction. Methods and Results: Transmembrane potentials recorded from ventricles of eight swine and three canines during paced activation intervals of ≤300 ms were used to quantify alternans of maximum rate of depolarization (|dv/dt|max) and of action potential duration (APD). Incidence of APD alternans was 62 and 76% in swine and canines. Alternans of APD was frequently accompanied with alternans of |dv/dt|max. Of these, 4 and 26% were out of phase in swine and canines, i.e., low |dv/dt|max preceded long APD. Computer simulations show that out of phase alternans attenuate variation of wavelength and thus minimize formation of spatially discordant alternans. Conclusion: The spontaneous switching of phase relationship between alternans of depolarization and repolarization suggests that mechanisms underlying these alternans may operate independent of each other. The phase between these alternans can critically impact spatial dispersion of refractoriness and thus stability of conduction, with the in phase relation promoting transition from concord to discord while out of phase preventing formation of discord. PMID:22701104

  12. 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…

  13. 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…

  14. 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…

  15. Investigation of condensed and early stage gas phase hypergolic reactions

    NASA Astrophysics Data System (ADS)

    Dennis, Jacob Daniel

    hypergolic liquid propellant combination of MMH and RFNA or pure nitric acid. The first and most important effort focuses on furthering the understanding of condensed phase reactions between MMH and nitric acid. To accomplish this goal diluted MMH and nitric acid were studied in a Fourier transform infrared spectrometer. By tracking the generation or destruction of specific chemical species in the reacting fluid we can measure the reaction progress as a function of reactant concentration and temperature. This work provides the propulsion community with a quantitative global condensed phase reaction rate equation for MMH/nitric acid. The second effort focuses on improving understanding the recently proposed gas phase hypergolic reaction mechanisms using a streak camera based ultraviolet and visible spectrometer. The time resolution on the streak camera system allows for detailed investigation of the pre-ignition and early stage gas phase species present during the reaction between MMH and RFNA.

  16. 17β-estradiol ameliorates oxygen-induced retinopathy in the early hyperoxic phase.

    PubMed

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

    2015-02-20

    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 effect

  17. Phase-Synchronization Early Epileptic Seizure Detector VLSI Architecture.

    PubMed

    Abdelhalim, K; Smolyakov, V; Genov, R

    2011-10-01

    A low-power VLSI processor architecture that computes in real time the magnitude and phase-synchronization of two input neural signals is presented. The processor is a part of an envisioned closed-loop implantable microsystem for adaptive neural stimulation. The architecture uses three CORDIC processing cores that require shift-and-add operations but no multiplication. The 10-bit processor synthesized and prototyped in a standard 1.2 V 0.13 μm CMOS technology utilizes 41,000 logic gates. It dissipates 3.6 μW per input pair, and provides 1.7 kS/s per-channel throughput when clocked at 2.5 MHz. The power scales linearly with the number of input channels or the sampling rate. The efficacy of the processor in early epileptic seizure detection is validated on human intracranial EEG data. PMID:23852175

  18. Probing early-universe phase transitions with CMB spectral distortions

    NASA Astrophysics Data System (ADS)

    Amin, Mustafa A.; Grin, Daniel

    2014-10-01

    Global, symmetry-breaking phase transitions in the early universe can generate scaling seed networks which lead to metric perturbations. The acoustic waves in the photon-baryon plasma sourced by these metric perturbations, when Silk damped, generate spectral distortions of the cosmic microwave background (CMB). In this work, the chemical potential distortion (μ ) due to scaling seed networks is computed and the accompanying Compton y -type distortion is estimated. The specific model of choice is the O (N ) nonlinear σ -model for N ≫1 , but the results remain the same order of magnitude for other scaling seeds. If CMB anisotropy constraints to the O (N ) model are saturated, the resulting chemical potential distortion μ ≲2 ×1 0-9 .

  19. 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.

  20. 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

  1. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial

    PubMed Central

    Donskih, Roman; Jones, C. Michael; Nixon, Allen; Vidal, Maria J.; Nakov, Roumen; Singh, Pritibha; Schaffar, Gregor; Gascón, Pere; Harbeck, Nadia

    2016-01-01

    Background. Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy. Methods. A total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) on day 1 of each cycle, for six or more cycles. Pegfilgrastim (LA-EP2006 or reference) was given subcutaneously (6 mg in 0.6 mL) on day 2 of each cycle. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with an absolute neutrophil count <0.5 × 109/L), with equivalence confirmed if 90% and 95% confidence intervals (CIs) were within a 1-day margin. Results. Baseline characteristics were well balanced. DSN was equivalent between groups at mean ± SD 1.36 ± 1.13 (LA-EP2006, n = 155) and 1.19 ± 0.98 (reference, n = 153) in cycle 1. With a treatment difference (reference minus LA-EP2006) of −0.16 days (90% CI −0.36 to 0.04; 95% CI −0.40 to 0.08), LA-EP2006 was equivalent to reference pegfilgrastim. Secondary efficacy parameters were similar between groups during cycle 1 and across cycles. Safety profiles were also similar between groups. No neutralizing antibodies against pegfilgrastim, filgrastim, or polyethylene glycol were detected. Conclusion. LA-EP2006 and reference pegfilgrastim were therapeutically equivalent and comparable regarding efficacy and safety in the prevention of neutropenia in patients with early-stage breast cancer receiving TAC. Implications for Practice: The

  2. 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

  3. Early family regularity protects against later disruptive behavior.

    PubMed

    Rijlaarsdam, Jolien; Tiemeier, Henning; Ringoot, Ank P; Ivanova, Masha Y; Jaddoe, Vincent W V; Verhulst, Frank C; Roza, Sabine J

    2016-07-01

    Infants' temperamental anger or frustration reactions are highly stable, but are also influenced by maturation and experience. It is yet unclear why some infants high in anger or frustration reactions develop disruptive behavior problems whereas others do not. We examined family regularity, conceptualized as the consistency of mealtime and bedtime routines, as a protective factor against the development of oppositional and aggressive behavior. This study used prospectively collected data from 3136 families participating in the Generation R Study. Infant anger or frustration reactions and family regularity were reported by mothers when children were ages 6 months and 2-4 years, respectively. Multiple informants (parents, teachers, and children) and methods (questionnaire and interview) were used in the assessment of children's oppositional and aggressive behavior at age 6. Higher levels of family regularity were associated with lower levels of child aggression independent of temperamental anger or frustration reactions (β = -0.05, p = 0.003). The association between child oppositional behavior and temperamental anger or frustration reactions was moderated by family regularity and child gender (β = 0.11, p = 0.046): family regularity reduced the risk for oppositional behavior among those boys who showed anger or frustration reactions in infancy. In conclusion, family regularity reduced the risk for child aggression and showed a gender-specific protective effect against child oppositional behavior associated with anger or frustration reactions. Families that ensured regularity of mealtime and bedtime routines buffered their infant sons high in anger or frustration reactions from developing oppositional behavior. PMID:26589300

  4. 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

  5. 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... Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits supplying power to portable or mobile three-phase alternating equipment shall contain: (1) Either a direct...

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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…

  11. 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…

  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, 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...

  14. 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...

  15. 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...

  16. Protective Effect of Surgery Against Early Subtalar Arthrodesis in Displaced Intra-articular Calcaneal Fractures

    PubMed Central

    Liu, Yueju; Li, Zhi; Li, Heng; Zhang, Yingze; Wang, Pengcheng

    2015-01-01

    Abstract The aim of this study is to determine whether surgery offers protection against early subtalar arthrodesis in displaced intraarticular calcaneal fractures. Systematic review and meta-analysis: searches of electronic databases 1980 to August 2014, checking of reference lists, hand searching of journals, and contact with experts. Randomized controlled trials (RCTs) in which surgical treatment was compared with nonsurgical treatment of displaced intra-articular calcaneal fractures from 1980 to 2014. The modified Jadad scale was used for trial quality and effective data were pooled for meta-analysis. Study results related to early subtalar arthrodesis were extracted and risk assessment was combined with surgical treatment and nonsurgical treatment. The primary analysis included 4 studies and 966 participants. The estimated overall risk ratio was 4.40 (95% confidence interval 2.67–7.39), indicating the incidence of early subtalar arthrodesis in nonsurgical group is 4.4 times the surgical group. The results showed that surgical treatment was superior to nonsurgical treatment in protection against early subtalar arthrodesis in displaced intra-articular calcaneal fractures (Z = 5.600, P < 0.001). Surgery offers protection against early subtalar arthrodesis in displaced intra-articular calcaneal fractures. PMID:26559281

  17. 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.

  18. 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.

  19. 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.

  20. Simple uncertainty propagation for early design phase aircraft sizing

    NASA Astrophysics Data System (ADS)

    Lenz, Annelise

    Many designers and systems analysts are aware of the uncertainty inherent in their aircraft sizing studies; however, few incorporate methods to address and quantify this uncertainty. Many aircraft design studies use semi-empirical predictors based on a historical database and contain uncertainty -- a portion of which can be measured and quantified. In cases where historical information is not available, surrogate models built from higher-fidelity analyses often provide predictors for design studies where the computational cost of directly using the high-fidelity analyses is prohibitive. These surrogate models contain uncertainty, some of which is quantifiable. However, rather than quantifying this uncertainty, many designers merely include a safety factor or design margin in the constraints to account for the variability between the predicted and actual results. This can become problematic if a designer does not estimate the amount of variability correctly, which then can result in either an "over-designed" or "under-designed" aircraft. "Under-designed" and some "over-designed" aircraft will likely require design changes late in the process and will ultimately require more time and money to create; other "over-designed" aircraft concepts may not require design changes, but could end up being more costly than necessary. Including and propagating uncertainty early in the design phase so designers can quantify some of the errors in the predictors could help mitigate the extent of this additional cost. The method proposed here seeks to provide a systematic approach for characterizing a portion of the uncertainties that designers are aware of and propagating it throughout the design process in a procedure that is easy to understand and implement. Using Monte Carlo simulations that sample from quantified distributions will allow a systems analyst to use a carpet plot-like approach to make statements like: "The aircraft is 'P'% likely to weigh 'X' lbs or less, given the

  1. 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.

  2. Development of orthogonally protected hypusine for solid-phase peptide synthesis.

    PubMed

    Song, Aimin; Tom, Jeffrey; Yu, Zhiyong; Pham, Victoria; Tan, Dajin; Zhang, Dengxiong; Fang, Guoyong; Yu, Tao; Deshayes, Kurt

    2015-04-01

    An orthogonally protected hypusine reagent was developed for solid-phase synthesis of hypusinated peptides using the Fmoc/t-Bu protection strategy. The reagent was synthesized in an overall yield of 27% after seven steps from Cbz-Lys-OBzl and (R)-3-hydroxypyrrolidin-2-one. The side-chain protecting groups (Boc and t-Bu) are fully compatible with standard Fmoc chemistry and can be readily removed during the peptide cleavage step. The utility of the reagent was demonstrated by solid-phase synthesis of hypusinated peptides. PMID:25769022

  3. Protection of reinforcement with corrosion inhibitors, phase 1. Final report

    SciTech Connect

    Allyn, M.; Frantz, G.C.; Stephens, J.E.

    1998-11-01

    Costs due to corrosion in reinforcement in concrete caused by deicing salts has been estimated at up to $1 billion per year in the US alone. For most situations, corrosion inhibiting admixtures offer significant advantages over other protection methods to delay initiation of corrosion for the service life of the structure. Two new prototype corrosion inhibiting chemicals were evaluated and compared with two commercial corrosion inhibiting admixtures as well as with a typical air-entrained control concrete. Corrosion testing consisted of weekly wetting (with salt solution) and drying cycles applied to slab type specimens and to both 2-inch and 3-inch diameter lollipop specimens. Some lollipop specimens were also `pre-cracked` prior to corrosion testing. Linear polarization techniques measured corrosion rates. Reinforcing bar were removed and visually examined at completion of testing. Other concrete material test results included compression strength, freeze-thaw resistance, and absorption.

  4. Dual role of chloroquine in liver ischemia reperfusion injury: reduction of liver damage in early phase, but aggravation in late phase.

    PubMed

    Fang, H; Liu, A; Dahmen, U; Dirsch, O

    2013-01-01

    The anti-malaria drug chloroquine is well known as autophagy inhibitor. Chloroquine has also been used as anti-inflammatory drugs to treat inflammatory diseases. We hypothesized that chloroquine could have a dual effect in liver ischemia/reperfusion (I/R) injury: chloroquine on the one hand could protect the liver against I/R injury via inhibition of inflammatory response, but on the other hand could aggravate liver I/R injury through inhibition of autophagy. Rats (n=6 per group) were pre-treated with chloroquine (60 mg/kg, i.p.) 1 h before warm ischemia, and they were continuously subjected to a daily chloroquine injection for up to 2 days. Rats were killed 0.5, 6, 24 and 48 h after reperfusion. At the early phase (i.e., 0-6 h after reperfusion), chloroquine treatment ameliorated liver I/R injury, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory cytokines and fewer histopathologic changes. In contrast, chloroquine worsened liver injury at the late phase of reperfusion (i.e., 24-48 h after reperfusion). The mechanism of protective action of chloroquine appeared to involve its ability to modulate mitogen-activated protein kinase activation, reduce high-mobility group box 1 release and inflammatory cytokines production, whereas chloroquine worsened liver injury via inhibition of autophagy and induction of hepatic apoptosis at the late phase. In conclusion, chloroquine prevents ischemic liver damage at the early phase, but aggravates liver damage at the late phase in liver I/R injury. This dual role of chloroquine should be considered when using chloroquine as an inhibitor of inflammation or autophagy in I/R injury. PMID:23807223

  5. 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

  6. Protection induced by early stage vaccination with pandemic influenza virus-like particles.

    PubMed

    Lee, Gi-Ja; Quan, Fu-Shi

    2016-07-19

    The 2009 worldwide influenza pandemic emphasized the need for new approaches to develop emergency vaccines. In this study, a virus-like particle vaccine comprised of hemagglutinin (HA) and M1 from the pandemic influenza virus A/California/04/09 were used and its ability to induce protective immunity during the early stage of vaccination was assessed in a mouse model. A single intramuscular vaccination with virus-like particles (VLPs) provided protection on days 4 and 7 post-vaccination against lethal virus challenge with only moderate body weight loss. VLP vaccination induced significantly higher IgG antibody responses and high hemagglutinin inhibition (HAI) titers on day 4 post-vaccination. A predominant IgG2a antibody response and viral neutralizing antibodies were induced on day 7. These immune responses were closely correlated with protection. Lung virus titers decreased significantly on day 7 compared to those on day 4 post-vaccination. The lung virus titer on day 4 post-vaccination also decreased significantly compared to that of the naïve control. These results demonstrate that VLP vaccination confers effective protection during the early stage after vaccination in a mouse model. PMID:27317263

  7. 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.

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

    DOE PAGESBeta

    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

  9. 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.

  10. 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.

  11. Topological phases protected by reflection symmetry and cross-cap states

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

    Twisting symmetries provides an efficient method to diagnose symmetry-protected topological (SPT) phases. In this paper, edge theories of (2+1)-dimensional topological phases protected by reflection as well as other symmetries are studied by twisting reflection symmetry, which effectively puts the edge theories on an unoriented space-time, such as the Klein bottle. A key technical step taken in this paper is the use of the so-called cross-cap states, which encode entirely the unoriented nature of space-time, and can be obtained by rearranging the space-time geometry and exchanging the role of space and time coordinates. When the system is in a nontrivial SPT phase, we find that the corresponding cross-cap state is noninvariant under the action of the symmetries of the SPT phase, but acquires an anomalous phase. This anomalous phase, with a proper definition of a reference state, on which symmetry acts trivially, reproduces the known classification of (2+1)-dimensional bosonic and fermionic SPT phases protected by reflection symmetry, including in particular the Z8 classification of topological crystalline superconductors protected by reflection and time-reversal symmetries.

  12. 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…

  13. Relaxin Peptide Hormones Are Protective During the Early Stages of Ischemic Stroke in Male Rats

    PubMed Central

    Willcox, Jordan M.; Alibhai, Faisal J.; Connell, Barry J.; Saleh, Tarek M.; Wilson, Brian C.; Summerlee, Alastair J. S.

    2015-01-01

    The pregnancy hormone relaxin protects tissue from ischemic damage. The ability of relaxin-3, a relaxin paralog, to do so has not been explored. The cerebral expression levels of these peptides and their receptors make them logical targets for study in the ischemic brain. We assessed relaxin peptide-mediated protection, relative relaxin family peptide receptor (RXFP) involvement, and protective mechanisms. Sprague-Dawley rats receiving permanent (pMCAO) or transient middle cerebral artery occlusions (tMCAO) were treated with relaxin peptides, and brains were collected for infarct analysis. Activation of the endothelial nitric oxide synthase pathway was evaluated as a potential protective mechanism. Primary cortical rat astrocytes were exposed to oxygen glucose deprivation and treated with relaxin peptides, and viability was examined. Receptor involvement was explored using RXFP3 antagonist or agonist treatment and real-time PCR. Relaxin and relaxin-3 reduced infarct size after pMCAO. Both peptides activated endothelial nitric oxide synthase. Because relaxin-3 has not previously been associated with this pathway and displays promiscuous RXFP binding, we explored the receptor contribution. Expression of rxfp1 was greater than that of rxfp3 in rat brain, although peptide binding at either receptor resulted in similar overall protection after pMCAO. Only RXFP3 activation reduced infarct size after tMCAO. In astrocytes, rxfp3 gene expression was greater than that of rxfp1. Selective activation of RXFP3 maintained astrocyte viability after oxygen glucose deprivation. Relaxin peptides are protective during the early stages of ischemic stroke. Differential responses among treatments and models suggest that RXFP1 and RXFP3 initiate different protective mechanisms. This preliminary work is a pivotal first step in identifying the clinical implications of relaxin peptides in ischemic stroke. PMID:25456068

  14. Relaxin peptide hormones are protective during the early stages of ischemic stroke in male rats.

    PubMed

    Bergeron, Lindsay H; Willcox, Jordan M; Alibhai, Faisal J; Connell, Barry J; Saleh, Tarek M; Wilson, Brian C; Summerlee, Alastair J S

    2015-02-01

    The pregnancy hormone relaxin protects tissue from ischemic damage. The ability of relaxin-3, a relaxin paralog, to do so has not been explored. The cerebral expression levels of these peptides and their receptors make them logical targets for study in the ischemic brain. We assessed relaxin peptide-mediated protection, relative relaxin family peptide receptor (RXFP) involvement, and protective mechanisms. Sprague-Dawley rats receiving permanent (pMCAO) or transient middle cerebral artery occlusions (tMCAO) were treated with relaxin peptides, and brains were collected for infarct analysis. Activation of the endothelial nitric oxide synthase pathway was evaluated as a potential protective mechanism. Primary cortical rat astrocytes were exposed to oxygen glucose deprivation and treated with relaxin peptides, and viability was examined. Receptor involvement was explored using RXFP3 antagonist or agonist treatment and real-time PCR. Relaxin and relaxin-3 reduced infarct size after pMCAO. Both peptides activated endothelial nitric oxide synthase. Because relaxin-3 has not previously been associated with this pathway and displays promiscuous RXFP binding, we explored the receptor contribution. Expression of rxfp1 was greater than that of rxfp3 in rat brain, although peptide binding at either receptor resulted in similar overall protection after pMCAO. Only RXFP3 activation reduced infarct size after tMCAO. In astrocytes, rxfp3 gene expression was greater than that of rxfp1. Selective activation of RXFP3 maintained astrocyte viability after oxygen glucose deprivation. Relaxin peptides are protective during the early stages of ischemic stroke. Differential responses among treatments and models suggest that RXFP1 and RXFP3 initiate different protective mechanisms. This preliminary work is a pivotal first step in identifying the clinical implications of relaxin peptides in ischemic stroke. PMID:25456068

  15. 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.

  16. 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.

  17. Tsunami: psychosocial aspects of Andaman and Nicobar islands. Assessments and intervention in the early phase.

    PubMed

    Math, Suresh Bada; Girimaji, Satish Chandra; Benegal, Vivek; Uday Kumar, G S; Hamza, Ameer; Nagaraja, D

    2006-06-01

    The aim of this paper is to describe the activities and observations of the team from National Institute of Mental Health and Neuro Sciences (NIMHANS) Bangalore, India in the Andaman and Nicobar Islands during the early phase of the Tsunami disaster in January and February 2005. The activities comprised mental health consultation at camps, community sensitization, mental health services to the students and children, teachers orientation sessions and training of non-governmental organization [NGO] functionaries. Initial assessment reveals 5-8% of the population were suffering from significant mental health problems following the early phase of the disaster. This may increase in the aftermath of the early relief phase. Psychiatric morbidity is expected be around 25-30% in the disillusionment phase. High resilience was seen in the joint family system of tribal Nicobarese during early phase of disaster. In developing countries like India, limited availability of mental health professionals and poor knowledge about disaster mental health among the medical and para-medical staff, may lead to poor psychosocial rehabilitation of the survivors. To respond to a high magnitude natural disaster like a tsunami, the disaster mental health team must be able to understand the local culture, traditions, language, belief systems and local livelihood patterns. They also need to integrate with the network of various governmental and non-governmental organizations to cater to the needs of the survivors. Hence the presence of a disaster mental health team is definitely required during the early phase of the disaster in developing countries. PMID:16753660

  18. 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.

  19. 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.

  20. Solid-phase synthesis of oligoribonucleotides using 9-fluorenylmethoxycarbonyl (Fmoc) for 5'-hydroxyl protection.

    PubMed Central

    Lehmann, C; Xu, Y Z; Christodoulou, C; Tan, Z K; Gait, M J

    1989-01-01

    Efficient solid-phase synthesis of a series of oligoribonucleotides of up to 20 residues is described that utilises the 9-fluorenylmethoxycarbonyl group (Fmoc) for 5'-protection and 4-methoxytetrahydropyran-4-yl (Mthp) for 2'-protection of ribonucleotide monomers and a phosphoramidite coupling procedure. The Fmoc group is removed after each coupling step by treatment with 0.1M DBU in acetonitrile. Oligoribonucleotides are isolated in 2'-protected form in good yield and shown to be readily and efficiently deprotected by mild acidic treatment. PMID:2717397

  1. 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.

  2. Symmetry-protected topological phases and transition in a frustrated spin-1/2 XXZ chain

    NASA Astrophysics Data System (ADS)

    Ueda, Hiroshi; Onoda, Shigeki

    2014-12-01

    A frustrated spin-1/2 XXZ zigzag chain relevant to Rb2Cu2Mo3O12 is revisited in the light of symmetry-protected topological (SPT) phases. Using a density-matrix renormalization group method for infinite systems, we identify projective representations for four distinct time-reversal invariant SPT phases; two parity-symmetric dimer phases near the Heisenberg and XX limits and two parity-broken vector-chiral (VC) dimer phases in between. A small bond alternation in the nearest-neighbor ferromagnetic exchange coupling induces a direct SPT transition between the two distinct VC dimer phases. It is also found numerically that two Berezinskii-Kosterlitz-Thouless transitions, which occur from the gapless to the two distinct gapped VC phases in the case of δ =0 , meet each other in the case of δ >0 at a Gaussian criticality of the same Tomonaga-Luttinger parameter value as in the SU(2)-symmetric case.

  3. 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…

  4. 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).…

  5. [Advocacy and early discharge under the new system of hospitalization for medical care and protection].

    PubMed

    Otsuka, Atsuko

    2014-01-01

    The Act on Mental Health and Welfare for the Mentally Disabled was partially amended during the 183rd ordinary session of the Diet, on June 13, 2013. The revision abolished the system of guardianship that had long imposed conflicting roles on families of people with mental disorders. Various issues and concerns remain, however, including the requirement that consent for hospitalization be provided by a family member. Many people who need involuntary hospitalization find themselves in situations where it is difficult to continue living in the community. At the time of hospital admission, along with a medical examination, it is necessary to assess the patient's support system in the community and ascertain whether "hospitalization for medical care and protection" is, in fact, the only option. When hospitalization for medical care and protection is determined to be unavoidable, treatment and planning focused on early discharge and the patient's return to life in the community should be initiated immediately after hospitalization. Actual patient outcomes clearly indicate that early discharge is often the result when medical institutions collaborate and network with multidisciplinary teams and community support workers immediately after hospitalization. It is hoped that the amended law will have a practical impact that will result in similar outcomes throughout the nation in the future. At the same' time, it is crucial to expand staffing in medical institutions, foster a culture of team treatment, and promote the creation of better community mental health systems that include housing, social resources, and family support. PMID:24864564

  6. 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.

  7. Baseline survey of sun-protection knowledge, practices and policy in early childhood settings in Queensland, Australia.

    PubMed

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

    2007-04-01

    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/coordinators/senior teachers of all known early childhood services in Queensland, Australia, in 2002 (n = 1383; 56.5% response). Most (73.7%) services had a written sun-protection policy (SPP). However, 40.6% of pre-schools and kindergartens had not developed a written SPP. Most directors had moderate knowledge about sun-protection (median score: 7/12 [IQR 6, 8]), but few understood the UV index, the sun-protection factor rating for sunscreens or the association between childhood sun-exposure, mole development and melanoma. Pre-school teachers had lower knowledge scores than directors of long day care centers and other services (P = 0.0005). Staff members reportedly wore sun-protective hats, clothing and sunglasses more often than children. However, sunscreen use was higher among children than staff. Directors' knowledge scores predicted reported hat, clothing, sunscreen and shade utilization among children. Remoteness impacted negatively on director's knowledge (P = 0.043) and written SPP development (P = 0.0005). Higher composite sun-protection scores were reported for children and staff from services with written sun-protection policies. SPP development and increased sun-protection knowledge of directors may improve reported sun-protective behaviors of children and staff of early childhood services. PMID:16880216

  8. 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

  9. Protection from cancer and early diagnosis applications in Izmir, Turkey: a pilot study.

    PubMed

    Sirin, Ahsen; Atan, Senay Unsal; Tasci, Emel

    2006-01-01

    Research was planned as a descriptive and cross-sectional study in order to explore knowledge and practices of individuals residing in the Bornova District about protection from and early diagnosis of cancer. The individuals residing in the Bornova District in Izmir constituted the population of research. A total of 195 persons, who were selected by convenience sampling method, participated in the study. Results show that 89.2% of the individuals knew what cancer was, 50.3% were alcohol consumers, 45.6% knew the relationship between cancer and being overweight, and 41.5% were exercising regularly. Of the individuals enrolled, 75.4% knew that some ingredients in ready-made foods contain substances causing cancer, but only 10.8% paid attention to the ingredients while buying a food, and 26.7% did not pay any attention at all. Of the women, 53.9% knew how to do breast self-examination and 29.2% thought that to have pap smear performed regularly was essential for protection from cancer. Although 14.2% of the men knew how to do testis examination, 76.4% did not know the importance of testis examination. A statistically significant correlation was found between the research participants who knew what cancer was and those who knew the signs of cancer (chi2 = 8.077, SD = 1, P = .004 < .05). The levels of knowledge and practices related to protection from and early diagnosis of cancer among the individuals enrolled in the research were not sufficient. PMID:16783120

  10. 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.

  11. 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

  12. 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.

  13. 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.

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

    NASA Astrophysics Data System (ADS)

    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

    2014-11-01

    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 Ge2Sb2Te5 (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.

  15. 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

    ... Deepwater Horizon Oil Spill; Draft Programmatic and Phase III Early Restoration Plan and Draft Early... as a result of the Deepwater Horizon oil spill. The restoration alternatives are comprised of early... the Framework for Early Restoration Addressing Injuries Resulting from the Deepwater Horizon Oil...

  16. A study of cannabinoid-1 receptors during the early phase of excitotoxic damage to rat spinal locomotor networks in vitro.

    PubMed

    Veeraraghavan, Priyadharishini; Dekanic, Ana; Nistri, Andrea

    2016-10-01

    Endocannabinoids acting on cannabinoid-1 receptors (CB1Rs) are proposed to protect brain and spinal neurons from excitotoxic damage. The ability to recover from spinal cord injury (SCI), in which excitotoxicity is a major player, is usually investigated at late times after modulation of CB1Rs whose role in the early phases of SCI remains unclear. Using the rat spinal cord in vitro as a model for studying SCI initial pathophysiology, we investigated if agonists or antagonists of CB1Rs might affect SCI induced by the excitotoxic agent kainate (KA) within 24h from a transient (1h) application of this glutamate agonist. The CB1 agonist anandamide (AEA or pharmacological block of its degradation) did not limit excitotoxic depolarization of spinal networks: cyclic adenosine monophosphate (cAMP) assay demonstrated that CB1Rs remained functional 24h later and similarly expressed among dead or survived cells. Locomotor-like network activity recorded from ventral roots could not recover with such treatments and was associated with persistent depression of synaptic transmission. Motoneurons, that are particularly vulnerable to KA, were not protected by AEA. Application of 2-arachidonoylglycerol also did not attenuate the electrophysiological and histological damage. The intensification of damage by the CB1 antagonist AM251 suggested that endocannabinoids were operative after excitotoxic stimulation, yet insufficient to contrast it efficiently. The present data indicate that the early phases of excitotoxic SCI could not be arrested by pharmacologically exploiting the endocannabinoid system, consistent with the notion that AEA and its derivatives are more useful to treat late SCI phases. PMID:27450568

  17. 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.

  18. Bulk-Boundary Correspondence for Three-Dimensional Symmetry-Protected Topological Phases

    NASA Astrophysics Data System (ADS)

    Wang, Chenjie; Lin, Chien-Hung; Levin, Michael

    2016-04-01

    We derive a bulk-boundary correspondence for three-dimensional (3D) symmetry-protected topological phases with unitary symmetries. The correspondence consists of three equations that relate bulk properties of these phases to properties of their gapped, symmetry-preserving surfaces. Both the bulk and surface data appearing in our correspondence are defined via a procedure in which we gauge the symmetries of the system of interest and then study the braiding statistics of excitations of the resulting gauge theory. The bulk data are defined in terms of the statistics of bulk excitations, while the surface data are defined in terms of the statistics of surface excitations. An appealing property of these data is that it is plausibly complete in the sense that the bulk data uniquely distinguish each 3D symmetry-protected topological phase, while the surface data uniquely distinguish each gapped, symmetric surface. Our correspondence applies to any 3D bosonic symmetry-protected topological phase with finite Abelian unitary symmetry group. It applies to any surface that (1) supports only Abelian anyons and (2) has the property that the anyons are not permuted by the symmetries.

  19. 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.

  20. Cadet Beliefs, Attitudes, and Interactions during the Early Phases of Sex Integration.

    ERIC Educational Resources Information Center

    DeFleur, Lois B.; Gillman, David

    1978-01-01

    In this study, it was found that during the early phases of sex integration into the armed forces there were ambiguous and sex-linked differences, as well as changes in cadet beliefs, attitudes, and interactions. The ensuing integration of women into the squadrons appeared to follow the patterns of other minority integration into the armed forces.…

  1. 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…

  2. 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

    ..., metabolism, and excretion), and pharmacodynamics (i.e., all of the effects of the drug on various physiologic... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase Clinical Studies; Availability AGENCY: Food and Drug Administration,...

  3. 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…

  4. 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...

  5. 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

    ... DEEPWATER HORIZON Oil Spill; Final Phase II Early Restoration Plan and Environmental Review AGENCY: Interior... Addressing Injuries Resulting from the DEEPWATER HORIZON Oil Spill (Framework Agreement), notice is hereby... services injured or lost as a result of the DEEPWATER HORIZON oil spill, which occurred on or about...

  6. 77 FR 23741 - DEEPWATER HORIZON Oil Spill; Final Phase I Early Restoration Plan and Environmental Assessment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-20

    ... Fish and Wildlife Service DEEPWATER HORIZON Oil Spill; Final Phase I Early Restoration Plan and... DEEPWATER HORIZON Oil Spill (Framework Agreement), notice is hereby given that ] the Federal and State... the DEEPWATER HORIZON oil spill, which occurred on or about April 20, 2010, in the Gulf of Mexico....

  7. 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... from the Deepwater Horizon Oil Spill, the Federal and State natural resource trustee agencies (Trustees... resources and services injured or lost as a result of the Deepwater Horizon oil spill, which occurred on...

  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. Early stage domain coarsening of the isotropic-nematic phase transition

    NASA Astrophysics Data System (ADS)

    Bradač, Z.; Kralj, Samo; Žumer, S.

    2011-07-01

    We study numerically the early stage domain coarsening dynamics of the temperature driven isotropic-nematic (I-N) liquid crystal phase transition. System of rod like objects which interact via the modified Lebwohl-Lasher pairwise interaction is considered in 3D. The coarsening dynamics is followed using Brownian molecular dynamics. The box-restricted lattice point fluctuations are allowed in order to get rid of lattice geometry enforced phenomena. We analyze order parameter growth and domain coarsening in the early regime of the I-N phase transition as a function of the quench rate. We show that soon after the transition bimodal distribution of domains appears, where the shorter branch gradually vanishes. The behavior of the system is in accordance with predictions of the Kibble-Zurek mechanism which was originally introduced to model conditions in the early universe.

  10. Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death.

    PubMed

    Zou, X; Gao, J; Zheng, Y; Wang, X; Chen, C; Cao, K; Xu, J; Li, Y; Lu, W; Liu, J; Feng, Z

    2014-01-01

    Zeaxanthin (Zea) is a major carotenoid pigment contained in human retina, and its daily supplementation associated with lower risk of age-related macular degeneration. Despite known property of Zea as an antioxidant, its underlying molecular mechanisms of action remain poorly understood. In this study, we aim to study the regulation mechanism of Zea on phase II detoxification enzymes. In normal human retinal pigment epithelium cells, Zea promoted the nuclear translocation of NF-E2-related factor 2 (Nrf2) and induced mRNA and protein expression of phase II enzymes, the induction was suppressed by specific knockdown of Nrf2. Zea also effectively protected against tert-butyl hydroperoxide-induced mitochondrial dysfunction and apoptosis. Glutathione (GSH) as the most important antioxidant was also induced by Zea through Nrf2 activation in a time- and dose-dependent manner, whereas the protective effects of Zea were decimated by inhibition of GSH synthesis. Finally, Zea activated the PI3K/Akt and MAPK/ERK pathway, whereas only PI3K/Akt activation correlated with phase II enzymes induction and Zea protection. In further in vivo analyses, Zea showed effects of inducing phase II enzymes and increased GSH content, which contributed to the reduced lipid and protein peroxidation in the retina as well as the liver, heart, and serum of the Sprague-Dawley rats. For the first time, Zea is presented as a phase II enzymes inducer instead of being an antioxidant. By activating Nrf2-mediated phase II enzymes, Zea could enhance anti-oxidative capacity and prevent cell death both in vivo and in vitro. PMID:24810054

  11. 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.

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

    PubMed Central

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

    2015-01-01

    [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. PMID:26644690

  13. 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

  14. Early protective effect of mitofusion 2 overexpression in STZ-induced diabetic rat kidney.

    PubMed

    Tang, Wan Xin; Wu, Wei Hua; Zeng, Xiao Xi; Bo, Hong; Huang, Song Min

    2012-04-01

    Diabetic nephropathy (DN) is a serious complication of diabetes with a poorly defined etiology and limited treatment options. Early intervention is key to preventing the progression of DN. Mitofusin 2 (Mfn2) regulates mitochondrial morphology and signaling, and is involved in the pathogenesis of numerous diseases. Furthermore, Mfn2 is also closely associated with the development of diabetes, but its functional roles in the diabetic kidney remain unknown. This study investigated the effect of Mfn2 at an early stage of DN. Mfn2 was overexpressed by adenovirus-mediated gene transfer in streptozotocin-induced diabetic rats. Clinical parameters (proteinuria, albumin/creatinine ratio), pathological changes, ultra-microstructural changes in nephrons, expression of collagen IV and phosph-p38, ROS production, mitochondrial function, and apoptosis were evaluated and compared with diabetic rats expressing control levels of Mfn2. Endogenous Mfn2 expression decreased with time in DN. Compared to the blank transfection control group, overexpression of Mfn2 decreased kidney weight relative to body weight, reduced proteinuria and ACR, and improved pathological changes typical of the diabetic kidney, like enlargement of glomeruli, accumulation of ECM, and thickening of the basement membrane. In addition, Mfn2 overexpression inhibited activation of p38, and the accumulation of ROS; prevented mitochondrial dysfunction; and reduced the synthesis of collagen IV, but did not affect apoptosis of kidney cells. This study demonstrates that Mfn2 overexpression can attenuate pathological changes in the kidneys of diabetic rats. Further studies are needed to clarify the underlying mechanism of this protective function. Mfn2 might be a potential therapeutic target for the treatment of early stage DN. PMID:22095488

  15. 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…

  16. 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

  17. Breast cancer prevention: lessons to be learned from mechanisms of early pregnancy-mediated breast cancer protection.

    PubMed

    Meier-Abt, Fabienne; Bentires-Alj, Mohamed; Rochlitz, Christoph

    2015-03-01

    Pregnancy at early, but not late age, has a strong and life-long protective effect against breast cancer. The expected overall increase in breast cancer incidence demands the development of a pharmaceutical mimicry of early-age pregnancy-mediated protection. Recently, converging results from rodent models and women on molecular and cellular mechanisms underlying the protective effect of early-age pregnancy have opened the door for translational studies on pharmacologic prevention against breast cancer. In particular, alterations in Wnt and TGFβ signaling in mammary stem/progenitor cells reveal new potential targets for preventive interventions, and thus might help to significantly reduce the incidence of breast cancer in the future. PMID:25660950

  18. 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

  19. 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. PMID:23201694

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

    PubMed Central

    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. PMID:18311323

  1. 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. PMID:24491151

  2. 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

  3. Acute care in stroke: the importance of early intervention to achieve better brain protection.

    PubMed

    Díez-Tejedor, E; Fuentes, B

    2004-01-01

    It is known that 'time is brain', and only early therapies in acute stroke have been effective, like thrombolysis within the first 3 h, and useful neuroprotective drugs are searched for that probably would be effective only with their very early administration. General care (respiratory and cardiac care, fluid and metabolic management, especially blood glucose and blood pressure control, early treatment of hyperthermia, and prevention and treatment of neurological and systemic complications) in acute stroke patients is essential and must already start in the prehospital setting and continue at the patient's arrival to hospital in the emergency room and in the stroke unit. A review of published studies analyzing the influence of general care on stroke outcome and the personal experience from observational studies was performed. Glucose levels >8 mmol/l have been found to be predictive of a poor prognosis after correcting for age, stroke severity, and stroke subtype. Although a clinical trial of glucose-insulin-potassium infusions is ongoing, increased plasma glucose levels should be treated. Moreover, insulin therapy in critically ill patients, including stroke patients, is safe and determines lower mortality and complication rates. Both high and low blood pressure levels have been related to a poor prognosis in acute stroke, although the target levels have not been defined yet in clinical trials. The body temperature has been shown to have a negative effect on stroke outcome, and its control and early treatment of hyperthermia are important. Hypoxemia also worsens the stroke prognosis, and oxygen therapy in case of <92% O(2) saturation is recommended. Besides, blood pressure stabilization avoiding falls of the diastolic pressure and the lowering of glycemia and temperature have been related to a better prognosis in stroke units patients, and homeostasis maintenance is associated with a better outcome. General care has become an emergent and first-line brain-protectant

  4. 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.

  5. Early-Phase Clinical Trials In The Community: Results From the National Cancer Institute Community Cancer Centers Program Early-Phase Working Group Baseline Assessment

    PubMed Central

    Zaren, Howard A.; Nair, Suresh; Go, Ronald S.; Enos, Rebecca A.; Lanier, Keith S.; Thompson, Michael A.; Zhao, Jinxiu; Fleming, Deborah L.; Leighton, John C.; Gribbin, Thomas E.; Bryant, Donna M.; Carrigan, Angela; Corpening, Jennifer C.; Csapo, Kimberly A.; Dimond, Eileen P.; Ellison, Christie; Gonzalez, Maria M.; Harr, Jodi L.; Wilkinson, Kathy; Denicoff, Andrea M.

    2013-01-01

    Purpose: The National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) formed an Early-Phase Working Group to facilitate site participation in early-phase (EP) trials. The Working Group conducted a baseline assessment (BA) to describe the sites' EP trial infrastructure and its association with accrual. Methods: EP accrual and infrastructure data for the sites were obtained for July 2010-June 2011 and 2010, respectively. Sites with EP accrual rates at or above the median were considered high-accruing sites. Analyses were performed to identify site characteristics associated with higher accrual onto EP trials. Results: Twenty-seven of the 30 NCCCP sites participated. The median number of EP trials open per site over the course of July 2010-June 2011 was 19. Median EP accrual per site was 14 patients in 1 year. Approximately half of the EP trials were Cooperative Group; most were phase II. Except for having a higher number of EP trials open (P = .04), high-accruing sites (n = 14) did not differ significantly from low-accruing sites (n = 13) in terms of any single site characteristic. High-accruing sites did have shorter institutional review board (IRB) turnaround time by 20 days, and were almost three times as likely to be a lead Community Clinical Oncology Program site (small sample size may have prevented statistical significance). Most sites had at least basic EP trial infrastructure. Conclusion: Community cancer centers are capable of conducting EP trials. Infrastructure and collaborations are critical components of success. This assessment provides useful information for implementing EP trials in the community. PMID:23814525

  6. Effective field theory for one-dimensional valence-bond-solid phases and their symmetry protection

    NASA Astrophysics Data System (ADS)

    Fuji, Yohei

    2016-03-01

    We investigate valence-bond-solid (VBS) phases in one-dimensional spin systems by an effective field theory developed by Schulz [Phys. Rev. B 34, 6372 (1986), 10.1103/PhysRevB.34.6372]. While the distinction among the VBS phases is often understood in terms of different entanglement structures protected by certain symmetries, we adopt a different but more fundamental point of view, that is, different VBS phases are separated by a gap closing under certain symmetries. In this way, the effective field theory reproduces the known three symmetries: time reversal, bond-centered inversion, and dihedral group of π spin rotations. It also predicts that there exists another symmetry: site-centered inversion combined with a spin rotation by π . We demonstrate that the last symmetry gives distinct trivial phases, which cannot be characterized by their entanglement structure, in terms of a simple perturbative analysis in a spin chain. We also discuss several applications of the effective field theory to the phase transitions among VBS phases in microscopic models and an extension of the Lieb-Schultz-Mattis theorem to non-translational-invariant systems.

  7. Comparative Transcriptomics of Sijung and Jumli Marshi Rice during Early Chilling Stress Imply Multiple Protective Mechanisms

    PubMed Central

    Lindlöf, Angelica; Chawade, Aakash; Sikora, Per; Olsson, Olof

    2015-01-01

    Introduction Low temperature is one of the major environmental factors that adversely affect plant growth and yield. Many cereal crops from tropical regions, such as rice, are chilling sensitive and, therefore, are affected already at <10°C. Interestingly, it has been demonstrated that chilling susceptibility varies greatly among rice varieties, which indicates differences in the underlying molecular responses. Understanding these differences is vital for continued development of rational breeding and transgenic strategies for more tolerant varieties. Thus, in this study, we conducted a comparative global gene expression profiling analysis of the chilling tolerant varieties Sijung and Jumli Marshi (spp. Japonica) during early chilling stress (<24 h, 10°C). Methods and Results Global gene expression experiments were conducted with Agilent Rice Gene Expression Microarray 4x44K. The analysed results showed that there was a relatively low (percentage or number) overlap in differentially expressed genes in the two varieties and that substantially more genes were up-regulated in Jumli Marshi than in Sijung but the number of down-regulated genes were higher in Sijung. In broad GO annotation terms, the activated response pathways in Sijung and Jumli Marshi were coherent, as a majority of the genes belonged to the catalytic, transcription regulator or transporter activity categories. However, a more detailed analysis revealed essential differences. For example, in Sijung, activation of calcium and phosphorylation signaling pathways, as well as of lipid transporters and exocytosis-related proteins take place very early in the stress response. Such responses can be coupled to processes aimed at strengthening the cell wall and plasma membrane against disruption. On the contrary, in Jumli Marshi, sugar production, detoxification, ROS scavenging, protection of chloroplast translation, and plausibly the activation of the jasmonic acid pathway were the very first response

  8. Inside information: Financial conflicts of interest for research subjects in early phase clinical trials.

    PubMed

    Helft, Paul R; Ratain, Mark J; Epstein, Richard A; Siegler, Mark

    2004-05-01

    In recent years, several research subjects have told us that they had bought or intended to buy stock in the companies sponsoring the clinical trials in which they were enrolled. This situation has led us to ask what, if any, are physician-investigators' scientific, ethical, and legal responsibilities concerning research subjects who choose to buy stock in the companies sponsoring the clinical trials in which they are participating. Although the scope of this problem is unknown and is likely to be small, this commentary examines the scientific, ethical, and legal concerns raised by such activities on the part of research subjects enrolled in early phase clinical trials. In addition, this commentary also outlines the basis for our opinion that research subjects involved in an early phase clinical trial should avoid the financial conflicts of interest created by trading stock in the company sponsoring the clinical trial. PMID:15126602

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

    PubMed

    Eisen, Rebecca J; Dennis, David T; Gage, Kenneth L

    2015-11-01

    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

  11. 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.

  12. Protective Effect of Surgery Against Early Subtalar Arthrodesis in Displaced Intra-articular Calcaneal Fractures: A Meta-Analysis.

    PubMed

    Liu, Yueju; Li, Zhi; Li, Heng; Zhang, Yingze; Wang, Pengcheng

    2015-11-01

    The aim of this study is to determine whether surgery offers protection against early subtalar arthrodesis in displaced intraarticular calcaneal fractures. Systematic review and meta-analysis: searches of electronic databases 1980 to August 2014, checking of reference lists, hand searching of journals, and contact with experts. Randomized controlled trials (RCTs) in which surgical treatment was compared with nonsurgical treatment of displaced intra-articular calcaneal fractures from 1980 to 2014. The modified Jadad scale was used for trial quality and effective data were pooled for meta-analysis. Study results related to early subtalar arthrodesis were extracted and risk assessment was combined with surgical treatment and nonsurgical treatment. The primary analysis included 4 studies and 966 participants. The estimated overall risk ratio was 4.40 (95% confidence interval 2.67-7.39), indicating the incidence of early subtalar arthrodesis in nonsurgical group is 4.4 times the surgical group. The results showed that surgical treatment was superior to nonsurgical treatment in protection against early subtalar arthrodesis in displaced intra-articular calcaneal fractures (Z = 5.600, P < 0.001).Surgery offers protection against early subtalar arthrodesis in displaced intra-articular calcaneal fractures. PMID:26559281

  13. 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.

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

    PubMed Central

    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. Imaging of early acceleration phase of the 2013-2014 Boso slow slip event

    NASA Astrophysics Data System (ADS)

    Fukuda, J.; Kato, A.; Obara, K.; Miura, S.; Kato, T.

    2014-12-01

    Based on GPS and seismic data, we examine the spatiotemporal evolution of a slow slip event (SSE) and associated seismic activity that occurred off the Boso peninsula, central Japan, from December 2013 to January 2014. We use GPS data from 71 stations of the GEONET and 6 stations operated by Earthquake Research Institute of the University of Tokyo and Tohoku University around the Boso peninsula. We apply a modified version of the Network Inversion Filter to the GPS time series at the 77 stations to estimate the spatiotemporal evolution of daily cumulative slip and slip rate on the subducting Philippine Sea plate. In addition, we create an improved earthquake catalog by applying a matched filter technique to continuous seismograms and examine the spatiotemporal relations between slow slip and seismicity. We find that the SSE started in early December 2013. The spatiotemporal evolution of slow slip and seismicity is divided into two distinct phases, an earlier slow phase from early to 30 December 2013 (Phase I) and a subsequent faster phase from 30 December 2013 to 9 January 2014 (Phase II). During Phase I, slip accelerated slowly up to a maximum rate of 1.6 m/yr with potentially accelerating along-strike propagation at speeds on the order of 1 km/day or less and no accompanying seismicity. On the other hand, during Phase II, slip accelerated rapidly up to a maximum rate of 4.5 m/yr and then rapidly decelerated. The slip front propagated along strike at a constant speed of ~10 km/day. During the Phase II, slow slip was accompanied by seismic swarm activity that was highly correlated in space and time with slip rate, suggesting that the swarm activity was triggered by stress loading due to slow slip. Early slow acceleration of slip has not been identified in the past Boso SSEs in 1996, 2002, 2007, and 2011. It is not clear at this point whether the past Boso SSEs started with slow acceleration similarly to the 2013-2014 SSE. The transition from the slow to the

  16. Classification and description of bosonic symmetry protected topological phases with semiclassical nonlinear sigma models

    NASA Astrophysics Data System (ADS)

    Bi, Zhen; Rasmussen, Alex; Slagle, Kevin; Xu, Cenke

    2015-04-01

    In this paper, we systematically classify and describe bosonic symmetry protected topological (SPT) phases in all physical spatial dimensions using semiclassical nonlinear sigma model (NLSM) field theories. All the SPT phases on a d -dimensional lattice discussed in this paper can be described by the same NLSM, which is an O(d +2 ) NLSM in (d +1 )-dimensional space-time, with a topological Θ term. The field in the NLSM is a semiclassical Landau order parameter with a unit length constraint. The classification of SPT phases discussed in this paper based on their NLSMs is Completely Identical to the more mathematical classification based on group cohomology given in X. Chen, Z.-C. Gu, Z.-X. Liu, and X.-G. Wen, Phys. Rev. B 87, 155114 (2013), 10.1103/PhysRevB.87.155114 and Science 338, 1604 (2012), 10.1126/science.1227224. Besides the classification, the formalism used in this paper also allows us to explicitly discuss the physics at the boundary of the SPT phases, and it reveals the relation between SPT phases with different symmetries. For example, it gives many of these SPT states a natural "decorated defect" construction.

  17. 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

  18. Early Potent Protection against Heterologous SIVsmE660 Challenge Following Live Attenuated SIV Vaccination in Mauritian Cynomolgus Macaques

    PubMed Central

    Berry, Neil; Ham, Claire; Mee, Edward T.; Rose, Nicola J.; Mattiuzzo, Giada; Jenkins, Adrian; Page, Mark; Elsley, William; Robinson, Mark; Smith, Deborah; Ferguson, Deborah; Towers, Greg; Almond, Neil; Stebbings, Richard

    2011-01-01

    Background Live attenuated simian immunodeficiency virus (SIV) vaccines represent the most effective means of vaccinating macaques against pathogenic SIV challenge. However, thus far, protection has been demonstrated to be more effective against homologous than heterologous strains. Immune correlates of vaccine-induced protection have also been difficult to identify, particularly those measurable in the peripheral circulation. Methodology/Principal Findings Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM) against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8. MCM provided a characterised host genetic background with limited Major Histocompatibility Complex (MHC) and TRIM5α allelic diversity. Early protection, observed as soon as 3 weeks post-vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthrough cases where simultaneous identification of vaccine and challenge viruses by virus-specific PCR was indicative of active co-infection. Persistence of the vaccine virus in a range of lymphoid tissues was typified by a consistent level of SIV RNA positive cells in protected vaccinates. However, no association between MHC class I /II haplotype or TRIM5α polymorphism and study outcome was identified. Conclusion/Significance This SIV vaccine study, conducted in MHC-characterised MCM, demonstrated potent protection against the pathogenic, heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level of protection against this viral stock by intravenous challenge has not been hitherto observed. The mechanism(s) of protection by vaccination with live attenuated SIV must account for the heterologous and early protection data described in this study, including those which relate to the innate immune system. PMID:21853072

  19. Early responses of human cancer cells upon photodynamic treatment monitored by laser phase microscopy

    NASA Astrophysics Data System (ADS)

    Roelofs, Theo A.; Graschew, Georgi; Perevedentseva, Elena V.; Rakowsky, Stefan; Dressler, Cathrin; Beuthan, Juergen; Schlag, Peter M.

    2001-04-01

    Photodynamic treatment of cancer cells is known to eventually cause cell death in most cases. The precise pathways and the time course seem to vary among different cell types and modes of photodynamic treatment. In this contribution, the focus was put on the responses of human colon carcinoma cells HCT-116 within the first 15 minutes after laser irradiation in the presence of Photofrin« II (PII). To monitor the cell response in this early time period laser phase microscopic imaging was used, a method sensitive to changes in overall cell shape and intracellular structures, mediated by changes in the local refractive index. Laser irradiation of cells loaded with PII induced a significant reduction of the phase shifts, which probably reflects the induced damage to the different cellular membrane structures. The data suggest that even within the first 30 s after the onset of laser illumination, a significant reduction of the phase shifts can be detected. These results underline that laser phase microscopy is a suitable diagnostic tool for cellular research, also in the early time domain.

  20. 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.

  1. 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

  2. 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

  3. Early community contexts, race/ethnicity and young adult CVD risk factors: the protective role of education.

    PubMed

    Wickrama, K A S; O'Neal, Catherine Walker; Lott, Ryan E

    2012-08-01

    Using a sample of 13,500 adolescents (53% female and 47% male) who participated in all four waves of the National Longitudinal Study of Adolescent Health, this study used multilevel regression to examine the influence of early structural community adversity (as measured by rates of community poverty, single-parent headed families, and two indicators of employment) and racial/ethnic status on cardiovascular disease (CVD) risk factors of young adults (systolic blood pressure, diastolic blood pressure, and mean arterial pressure). The moderating role of youth's socioeconomic attainment was also examined. Results indicate that early community adversity and African American racial status place young adults at risk for CVD. Youth's socioeconomic attainment does not erase the persistent influences of early community adversity and African American racial status on CVD risk. However, the level of education attained can protect African American young adults and those experiencing early community adversity from CVD risk factors. PMID:22101680

  4. Protective effects of perfluorooctyl-bromide nanoparticles on early brain injuries following subarachnoid hemorrhage in rats

    PubMed Central

    Zhang, Huan; Xu, Rui; Xie, Fei; Xu, Wei; Zeng, Meng-Fei; Wang, Xin; Zhu, Ji

    2015-01-01

    To investigate the protective effects of perfluorooctyl-bromide (PFOB) nanoparticles on early brain injury (EBI) following subarachnoid hemorrhage (SAH), a total of 120 rats were randomly assigned to the following groups: Sham operation group (n = 40), SAH group (n = 40), and SAH + PFOB group (n = 40). Endovascular perforation was performed to induce subarachnoid hemorrhage. Brain water content was measured 24 h after surgery. Meanwhile, morphological changes in the rat hippocampal CA1 region were examined using light and transmission electron microscopy. The rate of neuronal apoptosis in rat hippocampal CA1 region was determined using TUNEL assay. Protein and mRNA expression levels of Caspase-3, Bax, and Bcl-2 were measured using western blot and RT-PCR assays 12, 24, 48, and 72 h after surgery. Compared to the SAH group, the SAH + PFOB group had significantly lower brain water content (P<0.01), with alleviated morphological abnormalities in HE-stained neurons and significantly decreased neurons with karyopyknosis and hyperchromatism in the hippocampal CA1 region. Electron microscopy revealed reduction of neuronal apoptosis, alleviation of glial cell swelling, and mitigation of perivascular edema in the hippocampal region. Immunohistochemical analysis showed that the expression of apoptosis-related factors Caspase-3 and Bax was significantly reduced, while that of the anti-apoptotic factor Bcl-2 was significantly increased. TUNEL staining showed that neuronal apoptosis was significantly reduced in the hippocampal CA1 region (P<0.01). RT-PCR and Western-blot data indicated that expressions of Caspase-3 and Bax were both significantly reduced, while bcl-2 expression was increased significantly at 12, 24, 48, and 72 h after SAH (P<0.01). Together, our data support that PFOB nanoparticles with high oxygen content could counteract ischemia and hypoxia, block neuronal apoptotic pathways, reduce neuronal apoptosis, and therefore, achieve neuroprotective effects in EBI

  5. Supported liquid membrane-protected molecularly imprinted fibre for solid-phase microextraction of thiabendazole.

    PubMed

    Barahona, Francisco; Turiel, Esther; Martín-Esteban, Antonio

    2011-05-23

    In this work, molecularly imprinted polymer fibres (MIP-fibre) have been prepared and evaluated for solid-phase microextraction (SPME), using thiabendazole (TBZ) as template. Inherent limitations of molecular imprinted polymers, such as target recognition in aqueous media, have been solved with the use of organic supported liquid membrane (SLM) protecting the MI-SPME process. MIP-fibres were located inside a polypropylene hollow capillary and protected by an organic solvent immobilized as a thin SLM in the pores of the capillary wall. The extraction procedure involved two simultaneous processes: liquid phase microextraction using polypropylene hollow fibres (HF-LPME) of the analytes from the sample to an organic acceptor solution through a SLM; and SPME of the analytes from the organic acceptor solution to a MIP-fibre inside the polypropylene capillary. The developed methodology was optimized and applied to the extraction of TBZ form spiked orange juices. Calibration curves showed good linearity in the concentration range under study (0.01-5.00 mg L(-1)) and a regression coefficient better than 0.995 was obtained. The detection limit was 4 μg L(-1), low enough to permit the satisfactory analysis of TBZ in real samples, according to European regulation. Relative standard deviations ranged below 10%, indicating good repeatability. By this manner, the advantages of inherent selectivity of MIP SPME fibres and the enrichment and sample cleanup capability of the HF-LPME have been successfully combined into a single device. PMID:21565306

  6. [Diagnostic importance of pentraxins at the early phase of acute pancreatitis].

    PubMed

    Meryk, Piotr; Dumnicka, Paulina; Kuśnierz-Cabala, Beata; Kuźniewski, Marek; Kapusta, Maria; Gurda-Duda, Anna; Goebels, Marek; Pawlica-Gosiewska, Dorota; Kulig, Jan

    2014-01-01

    Pentraxins are among the main acute phase reactants. There are two types of pentraxins, i.e., long, including pentraxin 3 (PTX3) and short, including C-reactive protein (CRP) and serum amyloid A (SAA). The aim of the study was to assess the increase in serum concentrations of pentraxins (ex- pressed as the multiplicity of the upper reference limits) and their usefulness in prognosing severe course of acute pancreatitis (AP) in the early phase of the disease. Forty patients admitted to Ist Department of Surgery, Jagiel-Ionian University Medical College with the diagnosis of AP were recruited for the study. In the early phase of AP, the concentrations of PTX3 achieved maximum earlier than CRP or SAA, enabling to differentiate between mild and moderate or severe AP in the first day of the disease. Also, during the first 24 hours from beginning of AP, SAA achieved its best prognostic value. Of all pentraxins studied, SAA was characterized by the most significant increase as compared to the upper reference limit. The prognostic utility of CRP increased later, after 48 hours of AP. PMID:25344970

  7. Patellar Subluxation With Early-Phase Synovial Chondromatosis of the Knee.

    PubMed

    Bashaireh, Khaldoon M

    2016-01-01

    Primary synovial chondromatosis is a rare, benign, monoarticular disease process that affects the synovial membrane of the joint, the synovial sheath, or the bursa around the joint. The etiology is unknown, but it has been associated with trauma in some cases. Although it is a benign lesion, if left untreated, it may lead to early secondary osteoarthritis of the joint. The knee joint is affected in 50% to 65% of cases, followed by the elbow and the hip. This article reports a 30-year-old active woman who presented to the author's clinic with a large infrapatellar mass that caused lateral subluxation of the patella, swelling, and episodic pain with crepitations 14 months after direct trauma to the knee. Clinical examination, magnetic resonance imaging, and arthroscopy revealed a large infrapatellar mass causing lateral subluxation of the patella with no loose bodies. Hoffa's disease, para-articular osteochondroma, and early-phase synovial chondromatosis were considered in the differential diagnosis. The histopathologic and clinical features were consistent with early synovial chondromatosis. The patient underwent local excision of the mass through a medial parapatellar arthrotomy. At 5 years of follow-up, she had no recurrence of the lesion or progression of the disease. Early diagnosis of synovial chondromatosis with local excision offers a reliable cure. However, long-term follow-up is advised because of the high recurrence rates as well as the risk of metaplastic transformation. PMID:26726983

  8. Uterine doughnut in early proliferating phase: potential pitfall in gastrointestinal bleeding studies.

    PubMed

    Karacalioglu, Ozgur; Ilgan, Seyfettin; Arslan, Nuri; Ozguven, Mehmet

    2003-12-01

    A 41-year-old woman with rectal bleeding was referred to our department for gastrointestinal (GI) bleeding study. She was in early post-menstrual period and had stable vital signs. A GI bleeding study with Tc-99m SC revealed uterine blush in the pelvis. The shape of activity and quick fading excluded a GI bleeding. To rule out an intermittent bleeding, patient underwent a second bleeding study with Tc-99m RBC. Serial images showed uterine "doughnut" in the pelvis. The activity neither changed in shape nor showed distal movement with time excluding a GI hemorrhage. Uterus in early proliferating phase could be a potential pitfall in GI bleeding studies. PMID:14971611

  9. The Flat Decay Phase in the Early X-Ray Afterglows of Swift GRBs

    SciTech Connect

    Granot, Jonathan; /KIPAC, Menlo Park

    2007-03-27

    Many Swift GRBs show an early phase of shallow decay in their X-ray afterglows, lasting from t {approx} 10{sup 2.5} s to {approx} 10{sup 4} s after the GRB, where the flux decays as {approx} t{sup -0.2} - t{sup -0.8}. This is perhaps the most mysterious of the new features discovered by Swift in the early X-ray afterglow, since it is still not clear what causes it. I discuss different possible explanations for this surprising new discovery, as well as their potential implications for the gamma-ray efficiency, the afterglow kinetic energy, and perhaps even for the physics of collisionless relativistic shocks.

  10. 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

  11. Prevalence and severity of foot pad alterations in German turkey poults during the early rearing phase.

    PubMed

    Bergmann, S; Ziegler, N; Bartels, T; Hübel, J; Schumacher, C; Rauch, E; Brandl, S; Bender, A; Casalicchio, G; Krautwald-Junghanns, M-E; Erhard, M H

    2013-05-01

    In the previously performed field study from 2007 to 2009, it became evident that foot pad alterations were already commonly found in turkeys at the age of 6 wk. At this early age, 45% of the clinically examined birds were diagnosed with epithelial necrosis. Therefore, it became important to specifically analyze the situation during the early rearing phase. The present study reflects the prevalence and severity of foot pad alterations of turkey poults up to the age of 35 d (5 wk), starting as early as the age of 3 d. From 24 turkey farms throughout Germany, in general 5,531 turkeys [3,131 male and 2,400 female] of the British United Turkeys 6 strain from 46 flocks, were examined to that effect. Prevalence and severity increased within the duration of stay in the stable, and the prevalence was higher (P < 0.001) during the second visit between d 22 to 35 (factor: 0.94). Therefore, 27.3% (d 3 to 5; male/female: 39.1/25.0%) and 63.3% (d 22 to 35: 61.3/65.7%) of the examined poults had alterations of the foot pads, such as hyperkeratosis (d 3 to 5: 20.4/14.2%; d 22 to 35: 17.6/17.1%), high-grade hyperkeratosis with adhesive dirt (d 3 to 5: 8.7/10.7%; d 22 to 35: 29.2/39.3%), and epithelial necrosis (d 3 to 5: 0.1/0.1%; d 22 to 35: 14.6/9.3%). Female poults showed a higher risk (P < 0.001) of developing food pad alterations (factor: 0.76) than male poults. Male poults developed a higher percentage of epithelial necrosis than hens shortly before relocation. A higher stocking density during the very early rearing phase (d 3 to 5) led to a worse foot pad health status (P < 0.001). Because even mild alterations in the foot pad condition can be indicators for suboptimal design of the rearing environment and are to be seen as a pre-state for severe cases of foot pad dermatitis, it is important to set the main focus on the early rearing phase. PMID:23571325

  12. Classifying symmetry-protected topological phases through the anomalous action of the symmetry on the edge

    NASA Astrophysics Data System (ADS)

    Else, Dominic V.; Nayak, Chetan

    2014-12-01

    It is well known that (1 +1 )-dimensional [(1 +1 )-D] bosonic symmetry-protected topological (SPT) phases with symmetry group G can be identified by the projective representation of the symmetry at the edge. Here we generalize this result to higher dimensions. We assume that the representation of the symmetry on the spatial edge of a (d +1 )-D SPT is local but not necessarily on site, such that there is an obstruction to its implementation on a region with a boundary. We show that such obstructions are classified by the cohomology group Hd +1(G ,U(1 ) ) , in agreement with the classification of bosonic SPT phases proposed in Chen et al. [Science 338, 1604 (2012), 10.1126/science.1227224]. Our analysis allows for a straightforward calculation of the element of Hd +1(G ,U(1 ) ) corresponding to physically meaningful models such as nonlinear σ models with a θ term in the action. SPT phases outside the classification of Chen et al. are those in which the symmetry cannot be represented locally on the edge. With some modifications, our framework can also be applied to fermionic systems in (2 +1 )-D.

  13. 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.

  14. 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.

  15. 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

    ... clinical trial design, including product characteristics, manufacturing considerations and preclinical... document provides recommendations with respect to these products as to clinical trial design, including... of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Availability AGENCY: Food...

  16. 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.

  17. Feasibility study for early removal of HEU from CPP-651-Phase II

    SciTech Connect

    Smith, C.V.; Henry, R.; Milligan, C.; Harmon, B.; Peterson, J.; Thom, M.A.; Campbell, R.; Hendrix, B.

    1997-09-01

    A two-phase feasibility study was initiated in late 1996 to identify a way to expedite the removal of SNM from the CPP-651 vault. The first phase of this study provided preliminary information that appeared promising, but needed additional detailed planning and evaluate to validate the concepts and conclusions. The focus of Phase 2 was to provide the validation via resource-loaded schedules and more detailed cost estimates. Section 1 describes the purpose and objectives of the Phase 2 tasks and the programmatic drivers that influence related CPP-651 high-enriched uranium (HEU) management issues. Section 2 identifies the evaluation criteria and methodology and the transfer issues and barriers preventing shipment. Section 3 provides site-specific background information for the CPP-651 facility and the Idaho National Engineering and Environmental Laboratory (INEEL) and describes the development of the basic material removal schedule, the proposed base case plan for removal of SNM, and the proposed HEU material management/shipping issues and strategies. Section 4 identifies the proposed options for accelerated removal of SNM and how they were evaluated via detailed scheduling, resource histograms, and cost analysis. Section 5 summarizes principal tasks for implementing this plan and other related HEU CPP-651 management issues that require continued planning efforts to assure successful implementation of this proposed early removal strategy.

  18. A conceptual framework: the early and late phases of skeletal muscle dysfunction in the acute respiratory distress syndrome.

    PubMed

    Files, D Clark; Sanchez, Michael A; Morris, Peter E

    2015-01-01

    Patients with acute respiratory distress syndrome (ARDS) often develop severe diaphragmatic and limb skeletal muscle dysfunction. Impaired muscle function in ARDS is associated with increased mortality, increased duration of mechanical ventilation, and functional disability in survivors. In this review, we propose that muscle dysfunction in ARDS can be categorized into an early and a late phase. These early and late phases are based on the timing in relationship to lung injury and the underlying mechanisms. The early phase occurs temporally with the onset of lung injury, is driven by inflammation and disuse, and is marked predominantly by muscle atrophy from increased protein degradation. The ubiquitin-proteasome, autophagy, and calpain-caspase pathways have all been implicated in early-phase muscle dysfunction. Late-phase muscle weakness persists in many patients despite resolution of lung injury and cessation of ongoing acute inflammation-driven muscle atrophy. The clinical characteristics and mechanisms underlying late-phase muscle dysfunction do not involve the massive protein degradation and atrophy of the early phase and may reflect a failure of the musculoskeletal system to regain homeostatic balance. Owing to these underlying mechanistic differences, therapeutic interventions for treating muscle dysfunction in ARDS may differ during the early and late phases. Here, we review clinical and translational investigations of muscle dysfunction in ARDS, placing them in the conceptual framework of the early and late phases. We hypothesize that this conceptual model will aid in the design of future mechanistic and clinical investigations of the skeletal muscle system in ARDS and other critical illnesses. PMID:26134116

  19. 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)…

  20. Early Cocking Phase Mechanics and Upper Extremity Surgery Risk in Starting Professional Baseball Pitchers

    PubMed Central

    Douoguih, Wiemi A.; Dolce, Donald L.; Lincoln, Andrew E.

    2015-01-01

    Background: Early cocking phase pitching mechanics may affect risk of upper extremity injury requiring surgery in professional baseball players. Purpose: To assess the occurrence of inverted-W arm positioning and early trunk rotation in Major League Baseball (MLB) pitchers and to determine whether this throwing position is associated with upper extremity injury requiring surgery. Study Design: Cross-sectional study; Level of evidence, 3. Methods: For 250 MLB pitchers in the 2010 season, 15 to 20 pitches from the start and end of an outing were reviewed using slow-motion game video for presence of an inverted-W position and early trunk rotation. Previous or current incidence of upper extremity injury requiring surgery for each player was determined using the MLB injury database, minor league injury records, available collegiate data, and publicly available online injury databases. Upper extremity surgery associated with an injury was considered to result from pitching. Results: Consensus between investigators was achieved for 99% of players for inverted-W positioning (248 players) and in 97% of players for early trunk rotation (243 players) for videos reviewed independently. Rate of surgery with and without inverted-W position was 28 of 93 (30%) and 42 of 155 (27%), respectively. Rate of surgery with and without early trunk rotation was 37 of 111 (33%) and 30 of 132 (23%), respectively. Using a Cox proportional hazards model for risk analysis using the measured number of innings pitched at time of surgery as an approximate index of exposure and adjusting for age and fastball speed at time of surgery, early trunk rotation was associated with significantly increased risk of shoulder and/or elbow surgery with hazard ratio estimate of 1.69 (95% CI, 1.02-2.80). Presence of the inverted-W position was not associated with significantly increased risk (hazard ratio, 1.30; 95% CI, 0.79-2.14). Conclusion: The inverted-W throwing position was not associated with significantly

  1. Design of a Protection Thermal Energy Storage Using Phase Change Material Coupled to a Solar Receiver

    NASA Astrophysics Data System (ADS)

    Verdier, D.; Falcoz, Q.; Ferrière, A.

    2014-12-01

    Thermal Energy Storage (TES) is the key for a stable electricity production in future Concentrated Solar Power (CSP) plants. This work presents a study on the thermal protection of the central receiver of CSP plant using a tower which is subject to considerable thermal stresses in case of cloudy events. The very high temperatures, 800 °C at design point, impose the use of special materials which are able to resist at high temperature and high mechanical constraints and high level of concentrated solar flux. In this paper we investigate a TES coupling a metallic matrix drilled with tubes of Phase Change Material (PCM) in order to store a large amount of thermal energy and release it in a short time. A numerical model is developed to optimize the arrangement of tubes into the TES. Then a methodology is given, based from the need in terms of thermal capacity, in order to help the choice of the geometry.

  2. 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

  3. 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. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26526165

  4. 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

  5. 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. PMID:25536843

  6. 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.

  7. 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.

  8. Welcome to the Twilight Zone: a forgotten early phase of human evolutionary studies.

    PubMed

    Delisle, Richard G

    2012-06-01

    The field of paleoanthropology arose out of a strange and unacknowledged early phase of development prior to about the 1930s. It is often assumed that a key pillar of the discipline, the unity of humankind--the notion that humans are clearly separated phylogenetically (genealogically) from other non-human primates--was widely accepted from the inception of paleoanthropology around 1860. However, a final consensus on this fundamental question only appeared later on in the 20th century. This paper will focus on two key areas of disagreement, which reveal the unsettled state of this question during this early period: the question of uncertainty with respect to the number, identity and boundary of primate species (including humans) which prevailed in the 18th, 19th and early 20th centuries; and the matter of uncertainty with respect to the nature of the phylogenetic relationships among the various human populations and the other primate species which prevailed between 1864 and 1931. Consideration of these matters reveals that the modern research structure that paleoanthropologists take for granted today is much more recent than believed. PMID:22305470

  9. 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

  10. 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

  11. Early Exercise Protects against Cerebral Ischemic Injury through Inhibiting Neuron Apoptosis in Cortex in Rats.

    PubMed

    Zhang, Pengyue; Zhang, Yuling; Zhang, Jie; Wu, Yi; Jia, Jie; Wu, Junfa; Hu, Yongshan

    2013-01-01

    Early exercise is an effective strategy for stroke treatment, but the underlying mechanism remains poorly understood. Apoptosis plays a critical role after stroke. However, it is unclear whether early exercise inhibits apoptosis after stroke. The present study investigated the effect of early exercise on apoptosis induced by ischemia. Adult SD rats were subjected to transient focal cerebral ischemia by middle cerebral artery occlusion model (MCAO) and were randomly divided into early exercise group, non-exercise group and sham group. Early exercise group received forced treadmill training initiated at 24 h after operation. Fourteen days later, the cell apoptosis were detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and Fluoro-Jade-B staining (F-J-B). Caspase-3, cleaved caspase-3 and Bcl-2 were determined by western blotting. Cerebral infarct volume and motor function were evaluated by cresyl violet staining and foot fault test respectively. The results showed that early exercise decreased the number of apoptotic cells (118.74 ± 6.15 vs. 169.65 ± 8.47, p < 0.05, n = 5), inhibited the expression of caspase-3 and cleaved caspase-3 (p < 0.05, n = 5), and increased the expression of Bcl-2 (p < 0.05, n = 5). These data were consistent with reduced infarct volume and improved motor function. These results suggested that early exercise could provide neuroprotection through inhibiting neuron apoptosis. PMID:23502470

  12. 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.

  13. Hidden order and flux attachment in symmetry-protected topological phases: A Laughlin-like approach

    NASA Astrophysics Data System (ADS)

    Ringel, Zohar; Simon, Steven H.

    2015-05-01

    Topological phases of matter are distinct from conventional ones by their lack of a local order parameter. Still in the quantum Hall effect, hidden order parameters exist and constitute the basis for the celebrated composite-particle approach. Whether similar hidden orders exist in 2D and 3D symmetry protected topological phases (SPTs) is a largely open question. Here, we introduce a new approach for generating SPT ground states, based on a generalization of the Laughlin wave function. This approach gives a simple and unifying picture of some classes of SPTs in 1D and 2D, and reveals their hidden order and flux attachment structures. For the 1D case, we derive exact relations between the wave functions obtained in this manner and group cohomology wave functions, as well as matrix product state classification. For the 2D Ising SPT, strong analytical and numerical evidence is given to show that the wave function obtained indeed describes the desired SPT. The Ising SPT then appears as a state with quasi-long-range order in composite degrees of freedom consisting of Ising-symmetry charges attached to Ising-symmetry fluxes.

  14. 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

  15. CP7_E2alf oral vaccination confers partial protection against early classical swine fever virus challenge and interferes with pathogeny-related cytokine responses

    PubMed Central

    2013-01-01

    The conventional C-strain vaccine induces early protection against classical swine fever (CSF), but infected animals cannot be distinguished from vaccinated animals. The CP7_E2alf marker vaccine, a pestivirus chimera, could be a suitable substitute for C-strain vaccine to control CSF outbreaks. In this study, single oral applications of CP7_E2alf and C-strain vaccines were compared for their efficacy to induce protection against a CSF virus (CSFV) challenge with the moderately virulent Bas-Rhin isolate, in pigs as early as two days post-immunization. This work emphasizes the powerful potential of CP7_E2alf vaccine administered orally by a rapid onset of partial protection similar to that induced by the C-strain vaccine. Furthermore, our results revealed that both vaccinations attenuated the effects induced by CSFV on production of the pig major acute phase protein (PigMAP), IFN-α, IL-12, IL-10, and TGF-β1 cytokines. By this interference, several cytokines that may play a role in the pathogeny induced by moderately virulent CSFV strains were revealed. New hypotheses concerning the role of each of these cytokines in CSFV pathogeny are discussed. Our results also show that oral vaccination with either vaccine (CP7_E2alf or C-strain) enhanced CSFV–specific IgG2 production, compared to infection alone. Interestingly, despite the similar antibody profiles displayed by both vaccines post-challenge, the production of CSFV-specific IgG1 and neutralizing antibodies without challenge was lower with CP7_E2alf vaccination than with C-strain vaccination, suggesting a slight difference in the balance of adaptive immune responses between these vaccines. PMID:23398967

  16. 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

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

    PubMed

    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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Evaluation of the thermal performance of fire fighter protective clothing with the addition of phase change material

    NASA Astrophysics Data System (ADS)

    McCarthy, Lee K.

    Fire fighters rely on fire fighter protective clothing (FFPC) to provide adequate protection in the various hazardous environments they may encounter during operations. FFPC has seen significant advancement in technology over the past few decades. The addition of phase change material (PCM) to FFPC is a new technology with potential to enhance the thermal protection provided by the FFPC. To explore this technology, data from bench-scale experiments involving FFPC with PCMs are compared with a theoretical finite difference heat transfer model. The results demonstrate an effective method to mathematically model the heat transfer and provide insight into the effectiveness of improving the thermal protection of FFPC. The experiments confirm that the latent heat absorbed during the phase change reduces temperatures that might be experienced at the fire fighter's skin surface, advancing the high temperature performance of FFPC.

  3. 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

  4. 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

  5. [Responsibilities of clinical pharmacology in the early phase of drug development].

    PubMed

    Kuhlmann, J

    2000-05-01

    The path of a new drug from the idea to the product may be divided into 2 phases, namely drug discovery and drug development. Due to the scientific progress new and simple methods could be developed to determine the biological efficacy of a large number of compounds. During the first part of drug development necessary requirements for the first use in man are met by performing preclinical pharmacological, toxicological and pharmacokinetic investigations in the animal and in in-vitro testing. After a first clinical-pharmacological profile of the new substance has been established during phase I on the basis of which a decision for the continuation of the clinical trial is made, the aim of phases II and III is now to answer the important questions of the therapeutic efficacy and tolerability in a large number of patients with the target indication. Due to the continuously increasing time and costs of drug development, drug development should be streamlined combining preclinical and early clinical phases as an exploratory stage and later clinical development as a confirmatory stage. The development and appropriate use of surrogates and models may be helpful to determine drug actions in human and to assist in dose selection as the main requirement for a successful large clinical trial in the confirmatory stage. Identifying the genes responsible for the huge variations in how different patients respond to a drug, in terms of both the product's effectiveness and its side effects, and genotyping patients before including in large clinical trials may prevent selecting the wrong patient population and avoid expensive repetition of these studies. Taking responsibility as the link between research and development gives clinical pharmacology a major opportunity to assume a pivotal role in drug development. To reach this goal, clinical pharmacology must be fully integrated in the whole process of drug development from the candidate selection until the approval. PMID:10851846

  6. [Responsibilities of clinical pharmacology in the early phase of drug development].

    PubMed

    Kuhlmann, J

    1999-05-15

    The path of a new drug from the idea to the product may be divided into 2 phases, namely drug discovery and drug development. Due to the scientific progress new and simple methods could be developed to determine the biological efficacy of a large number of compounds. During the first part of drug development necessary requirements for the first use in man are met by performing preclinical pharmacological, toxicological and pharmacokinetic investigations in the animal and in in-vitro testing. After a first clinical-pharmacological profile of the new substance has been established during phase I on the basis of which a decision for the continuation of the clinical trial is made, the aim of phases II and III is now to answer the important questions of the therapeutic efficacy and tolerability in a large number of patients with the target indication. Due to the continuously increasing time and costs of drug development, drug development should be streamlined combining preclinical and early clinical phases as an exploratory stage and later clinical development as a confirmatory stage. The development and appropriate use of surrogates and models may be helpful to determine drug actions in human and to assist in dose selection as the main requirement for a successful large clinical trial in the confirmatory stage. Identifying the genes responsible for the huge variations in how different patients respond to a drug, in terms of both the product's effectiveness and its side effects, and genotyping patients before including in large clinical trials may prevent selecting the wrong patient population and avoid expensive repetition of these studies. Taking responsibility as the link between research and development gives clinical pharmacology a major opportunity to assume a pivotal role in drug development. To reach this goal, clinical pharmacology must be fully integrated in the whole process of drug development from the candidate selection until the approval. PMID:10408193

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

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

    PubMed

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

    2016-07-01

    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

  13. 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. PMID:27085362

  14. 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

  15. 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.

  16. 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…

  17. Risk and Protective Factors Associated with Disordered Eating during Early Adolescence.

    ERIC Educational Resources Information Center

    McVey, Gail L.; Pepler, Debra; Davis, Ron; Flett, Gordon L.; Abdolell, Mohamed

    2002-01-01

    Risk and protective factors associated with disordered eating were examined in girls in middle-level school. Analysis showed that low competence in physical appearance, high importance of social acceptance, high self-oriented perfectionism, and low parental support were correlated significantly with reports of high levels of disordered eating.…

  18. 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.…

  19. 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...

  20. 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…

  1. The chemical evolution in the early phases of massive star formation

    NASA Astrophysics Data System (ADS)

    Gerner, Thomas; Beuther, Henrik; Semenov, Dmitry; Linz, Hendrik; Vasyunina, Tatiana; Dullemond, Cornelis; Bihr, Simon; Henning, Thomas

    2013-07-01

    Understanding the chemical evolution of young (high-mass) star-forming regions is a central topic in star formation research. The chemistry is employed as a unique tool: 1) to investigate the underlying physical processes and 2) to characterize the evolution of the chemical composition. With these aims in mind, we observed a sample of 59 high-mass star-forming regions at different evolutionary stages varying from the early starless phase of Infrared Dark Clouds (IRDC) to High Mass Protostellar Objects (HMPO) to Hot Molecular Cores (HMC) and, finally, Ultra Compact HII regions (UCHII) at 1mm and 3mm with the IRAM 30m telescope. We determined their large-scale chemical abundances and column densities and found that the chemical composition evolves along with the evolutionary stages. We modeled the chemical evolution in these environments, using a 1D physical model where density and temperature vary from stage to stage coupled with an advanced gas-grain chemical model. By varying the temperature and density structure the best-fit chi-square values of all the relevant parameters were derived. A satisfying overall agreement between observed and modeled column densities for most of the molecules in all evolutionary stages was obtained. In addition the best-fit model provided chemical ages for each phase.

  2. 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

  3. 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

  4. 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…

  5. 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…

  6. Externalizing and Internalizing Problems in Low-Income Latino Early Adolescents: Risk, Resource, and Protective Factors

    ERIC Educational Resources Information Center

    Loukas, Alexandra; Prelow, Hazel M.

    2004-01-01

    The current investigation examined the role of cumulative risk, family routines, maternal monitoring, mother-child relationship quality, and youth socioemotional competence in adjustment outcomes of 521 10- to 14-year-old low-income Latino early adolescents. Results showed that, as the number of risk factors increased, levels of externalizing and…

  7. ["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. PMID:26875309

  8. The influence of phase changes on debris-cloud interactions with protected structures

    SciTech Connect

    Lawrence, R.J.; Kmetyk, L.N.; Chhabildas, L.C.

    1994-05-16

    The physical state of the debris cloud generated by the interaction of a projectile with a thin target depends on the energy balance associated with above the sound speeds of the impact event. At impact velocities well materials involved, the cloud is expected to be primarily molten, but with some vapor present. A series of numerical calculations using the multi-dimensional finite-difference hydrocode CTH has been used to evaluate the effect of phase changes (i.e., different vapor fractions) on these clouds, and their subsequent interaction with backwall structures. In the calculations, higher concentrations of vapor are achieved by increasing the initial temperature of both the projectile and the thin shield while keeping the impact velocity constant, and by actually increasing the impact velocity. The nature of the debris cloud and its subsequent loading on the protected structure depend on both its thermal and physical state. This interaction can cause rupture, spallation or simply bulging of the backwall. These computational results are discussed and compared with new experimental observations obtained at an impact velocity of {approximately}10 km/s. In the experiment, the debris cloud was generated by the impact of a plate-shaped titanium projectile with a thin titanium shield.

  9. Multi-phased screen for the evaluation of topical skin protectants against various chemicals

    SciTech Connect

    Snider, T.H.; Hobson, D.W.

    1993-05-13

    A multi-phased screen involving both in vivo and in vitro tests was used to evaluate the efficacy of 108 topical skin protectants (TSPs) against dermal exposure to sulfur mustard (HD), pinacolyl methylphosphonofluoridate (soman or GD), thickened soman (TGD), and 0-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX). Assessment of TSPs in vivo involved the application of chemical agents onto a 0.1 mm thickness of TSP spread on the dorsa of rabbits. For the nerve agents GD, TGD, and VX, acetylcholinesterase (AChE) inhibition in lysed red blood cells sampled periodically to 24 hr after dose application was used as an end point. Efficacy against the vesicating agent HD was assessed using the areas of dermal lesions from 1 microns L dosed at multiple sites on rabbits. The in vitro model involved delivery of 8 microns L HD or nerve agent on candidate TSPs applied at 0.015 mL/sq cm on U.S. Army M-8 chemical agent detection paper. The in vitro end point for TSP efficacy evaluation was the time to M-8 paper color change, indicating time to agent penetration. In vitro/in vivo correlations indicated good agreement for HD, GD, and TGD challenges, but not for VX.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. MER Surface Phase; Blurring the Line Between Fault Protection and What is Supposed to Happen

    NASA Technical Reports Server (NTRS)

    Reeves, Glenn E.

    2008-01-01

    An assessment on the limitations of communication with MER rovers and how such constraints drove the system design, flight software and fault protection architecture, blurring the line between traditional fault protection and expected nominal behavior, and requiring the most novel autonomous and semi-autonomous elements of the vehicle software including communication, surface mobility, attitude knowledge acquisition, fault protection, and the activity arbitration service.

  16. 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

  17. 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

  18. Nitric Oxide Chemical Donor Affects the Early Phases of In Vitro Wound Healing Process.

    PubMed

    La Torre, Cristina; Cinque, Benedetta; Lombardi, Francesca; Miconi, Gianfranca; Palumbo, Paola; Evtoski, Zoran; Placidi, Giuseppe; Fanini, Donatella; Cimini, Anna Maria; Benedetti, Elisabetta; Giuliani, Maurizio; Cifone, Maria Grazia

    2016-10-01

    An artificial wound in a confluent monolayer of human keratinocyte HaCaT cells or mouse embryo fibroblast Swiss NIH 3T3 cells was used to analyze the effects of the nitric oxide (NO) chemical donor, S-nitroso-N-acetylpenicillamine (SNAP). SNAP exposure promoted an enhanced rate of wound closure and accelerated motility of both keratinocytes and fibroblasts compared to control cells. The wounded monolayer cultures of HaCaT and NIH 3T3 cells, treated with or without SNAP, were monitored under a phase contrast microscope. Structural and ultrastructural modifications were analyzed by scanning electron microscopy (SEM). The images were captured by a digital camera at different time points (0-28 h) and the wound area was analyzed through software included in Matlab®. As early as 15 min, SNAP induced significant cytoskeletal remodeling, as shown by immunostaining (phalloidin-labelling), which in turn was associated with increased filopodium number and length rise. NO donor treatment also induced overexpression of Ki-67 protein, a typical marker of cell proliferation, as shown by immunostaining. Both SNAP-induced migration and proliferation were antagonized by the NO-sensitive GC inhibitor 1H-[1,2,4]oxadiazolo[-4,3-a]quinoxalin-1-one (ODQ), which suggests activation of the NO/cGMP signalling cascade in the observed SNAP-induced effects in the early stages of the healing process. Moreover, we provide evidence that PPAR-β antagonist (GSK0660) may interfere with NO-mediated wound healing process. J. Cell. Physiol. 231: 2185-2195, 2016. © 2016 Wiley Periodicals, Inc. PMID:26841260

  19. 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.

  20. 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.

  1. 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

  2. Blocking HMGB1 signal pathway protects early radiation-induced lung injury

    PubMed Central

    Wang, Liping; Zhang, Jing; Wang, Baozhong; Wang, Guifu; Xu, Junlong

    2015-01-01

    It has been reported that HMGB1 participated in various types of lung injury. In this study, we explored whether blocking HMGB1 has a preventive effect on the early radiation-induced lung injury and investigate the mechanism. Mice model of radiation-induced lung injury were accomplished by a single dose irradiation (15 Gy) to the whole thorax. Irradiated mice were treated with HMGB1-neutralizing antibody intraperitoneally dosed 10 μg, 50 μg, 100 μg/mouse respectively and were sacrificed after one week post-irradiation. Lung tissue slices were stained by H&E, and alveolitis was quantified by Szapiel scoring system. The level of cytokines TNF-γ in bronchoalveolar lavage fluid was detected by ELISA method. And p65NF-κB, p50NF-κB protein expression in mice lung tissues was detected by Western blot analysis. The results showed that blocking HMGB1 inhibited the inflammatory response, and thereby decreased the degree of alveolitis of irradiated lung tissue. In addition, HMGB1 antagonist can restrain the expression of type Th2 or Th17 derived inflammatory cytokines TNF-α, IL-6 and IL-17A, promote the expression of Th1 type cytokines INF-γ, and inhibit p65 NF-κB but promote p50 NF-κB activation, which promoted the resolution of the radiation-induced inflammatory response. In conclusion, blocking HMGB1 can reduce the degree of early radiation-induced lung injury, and its mechanism may be related to the promotion of p50NF-κB activation and its downstream molecules expression. Inhibiting HMGB1 may be a new target to deal with early radiation-induced lung injury. PMID:26191172

  3. Blocking HMGB1 signal pathway protects early radiation-induced lung injury.

    PubMed

    Wang, Liping; Zhang, Jing; Wang, Baozhong; Wang, Guifu; Xu, Junlong

    2015-01-01

    It has been reported that HMGB1 participated in various types of lung injury. In this study, we explored whether blocking HMGB1 has a preventive effect on the early radiation-induced lung injury and investigate the mechanism. Mice model of radiation-induced lung injury were accomplished by a single dose irradiation (15 Gy) to the whole thorax. Irradiated mice were treated with HMGB1-neutralizing antibody intraperitoneally dosed 10 μg, 50 μg, 100 μg/mouse respectively and were sacrificed after one week post-irradiation. Lung tissue slices were stained by H&E, and alveolitis was quantified by Szapiel scoring system. The level of cytokines TNF-γ in bronchoalveolar lavage fluid was detected by ELISA method. And p65NF-κB, p50NF-κB protein expression in mice lung tissues was detected by Western blot analysis. The results showed that blocking HMGB1 inhibited the inflammatory response, and thereby decreased the degree of alveolitis of irradiated lung tissue. In addition, HMGB1 antagonist can restrain the expression of type Th2 or Th17 derived inflammatory cytokines TNF-α, IL-6 and IL-17A, promote the expression of Th1 type cytokines INF-γ, and inhibit p65 NF-κB but promote p50 NF-κB activation, which promoted the resolution of the radiation-induced inflammatory response. In conclusion, blocking HMGB1 can reduce the degree of early radiation-induced lung injury, and its mechanism may be related to the promotion of p50NF-κB activation and its downstream molecules expression. Inhibiting HMGB1 may be a new target to deal with early radiation-induced lung injury. PMID:26191172

  4. Molecular assembly of lethal factor enzyme and pre-pore heptameric protective antigen in early stage of translocation.

    PubMed

    Alisaraie, Laleh; Rouiller, Isabelle

    2016-01-01

    During intoxication, the anthrax toxin lethal (LF) and edema (EF) factors initially assemble with the protective antigen (PA) on the plasma membrane of cells expressing the membrane-bound surface-exposed anthrax toxin receptor (ATR). This takes place at the physiological pH prior to entering the acidic environment of the endosome. We elucidated the molecular dynamics (MD) behaviors of the three-dimensional structure of the (PA63)7LF3 complex in various conformations and analyzed the dynamical properties of the fully loaded pre-pore complex on the plasma membrane at the physiological pH. The analysis points to the interaction networks of amino acids conserved between PA63 octamer and heptamer, which are not affected during the initial stage of the LFs binding. The simulations show an asymmetrical movement of the complex domains that directly affect LFs conformations. The conformational and structural alterations of the 2β2-2β3 loops of PA subunits are associated with pore formation. The early conformational changes of the loops appear as they peel off from the domain 2 toward domain 4 of each PA subunit. The LFs unfold in 1α1 segments of their N-terminal initiating the early stage of the pre-pore formation. The results indicate instable regions within the complex and provide important clues concerning the detail of fluctuating residues of the LF-PA interface regions at the early steps of toxins translocation. PMID:26659402

  5. AN EFFICIENT EARLY PHASE 2 PROCEDURE TO SCREEN MEDICATIONS FOR EFFICACY IN SMOKING CESSATION

    PubMed Central

    Perkins, Kenneth A.; Lerman, Caryn

    2014-01-01

    Rationale Initial screening of new medications for potential efficacy (i.e. FDA early Phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing. Objectives This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested, as model drugs, in 3 separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil. Results This crossover procedure showed sensitivity (increased days of abstinence) during week-long “practice” quit attempts with each of the active cessation medications (positive controls) vs. placebo, but not with modafinil (negative control) vs. placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e. already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation). Conclusions A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent Phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction. PMID:24297304

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

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

    PubMed

    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

  12. 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

  13. 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.

  14. 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.

  15. Identification of the microRNA transcriptome during the early phases of mammalian fracture repair.

    PubMed

    Hadjiargyrou, Michael; Zhi, Jizu; Komatsu, David E

    2016-06-01

    Fracture repair is a complex process that involves multiple biological processes requiring spatiotemporal expression of thousands of genes. The molecular regulation of this process is not completely understood. MicroRNAs (miRNAs) regulate gene expression by promoting mRNA degradation or blocking translation. To identify miRNAs expressed during fracture repair, we generated murine bone fractures and isolated miRNA-enriched RNA from intact and post-fracture day (PFD) 1, 3, 5, 7, 11, and 14 femurs. RNA samples were individually hybridized to mouse miRNA microarrays. Results indicated that 959 (51%) miRNAs were absent while 922 (49%) displayed expression in at least one sample. Of the 922 miRNAs, 306 (33.2%) and 374 (40.6%) were up- and down-regulated, respectively, in the calluses in comparison to intact bone. Additionally, 20 (2.2%) miRNAs displayed combined up- and down-regulated expression within the time course and the remaining 222 (24%) miRNAs did not exhibit any changes between calluses and intact bone. Quantitative-PCR validated the expression of several miRNAs. Further, we identified 2048 and 4782 target genes that were unique to the up- and down-regulated miRNAs, respectively. Gene ontology and pathway enrichment analyses indicated relevant biological processes. These data provide the first complete analysis of the miRNA transcriptome during the early phases of fracture repair. PMID:27058875

  16. EXPERIMENTAL INFECTION WITH Toxocara cati IN PIGS: MIGRATORY PATTERN AND PATHOLOGICAL RESPONSE IN EARLY PHASE

    PubMed Central

    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. PMID:25076437

  17. Increased ER–mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress

    PubMed Central

    Bravo, Roberto; Vicencio, Jose Miguel; Parra, Valentina; Troncoso, Rodrigo; Munoz, Juan Pablo; Bui, Michael; Quiroga, Clara; Rodriguez, Andrea E.; Verdejo, Hugo E.; Ferreira, Jorge; Iglewski, Myriam; Chiong, Mario; Simmen, Thomas; Zorzano, Antonio; Hill, Joseph A.; Rothermel, Beverly A.; Szabadkai, Gyorgy; Lavandero, Sergio

    2011-01-01

    Increasing evidence indicates that endoplasmic reticulum (ER) stress activates the adaptive unfolded protein response (UPR), but that beyond a certain degree of ER damage, this response triggers apoptotic pathways. The general mechanisms of the UPR and its apoptotic pathways are well characterized. However, the metabolic events that occur during the adaptive phase of ER stress, before the cell death response, remain unknown. Here, we show that, during the onset of ER stress, the reticular and mitochondrial networks are redistributed towards the perinuclear area and their points of connection are increased in a microtubule-dependent fashion. A localized increase in mitochondrial transmembrane potential is observed only in redistributed mitochondria, whereas mitochondria that remain in other subcellular zones display no significant changes. Spatial re-organization of these organelles correlates with an increase in ATP levels, oxygen consumption, reductive power and increased mitochondrial Ca2+ uptake. Accordingly, uncoupling of the organelles or blocking Ca2+ transfer impaired the metabolic response, rendering cells more vulnerable to ER stress. Overall, these data indicate that ER stress induces an early increase in mitochondrial metabolism that depends crucially upon organelle coupling and Ca2+ transfer, which, by enhancing cellular bioenergetics, establishes the metabolic basis for the adaptation to this response. PMID:21628424

  18. Inhibitory function of NKT cells during early induction phase of nickel allergy.

    PubMed

    Okuno, Hironori; Satoh, Masashi; Takeuchi, Emiko; Eshima, Koji; Terashima, Masazumi; Komotori, Jun; Habu, Sonoko; Tamauchi, Hidekazu; Iwabuchi, Kazuya

    2016-07-01

    Until now, metal allergies have been regarded as a Th1-type immune response. However, because the contribution of a Th2-type immune response has been suggested by clinical findings, we previously examined the Th2-type immune response during the development of metal allergies using a GATA-3 transgenic (GATA-3 Tg) mouse model. As a result, a Th2-type immunization reaction was suggested to be involved in the early phase of metal allergies. Recently, the involvement of NKT cells in metal allergies has been suggested. We examined this possibility using the activation of NKT cells and an NKT cell-deficient mouse model to determine the contribution of NKT cells to nickel allergy in the present study. In NKT cell-deficient mice, ear swelling was remarkably increased, compared with that in control mice. Also, in mice that had been treated with α-galactosylceramide (α-GalCer) to activate NKT cells, the ear swelling response was remarkably inhibited, compared with that in untreated mice. These facts show that NKT cells are involved in the inhibition of nickel allergy-induced ear swelling responses. PMID:26868431

  19. 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

    ... Fish and Wildlife Service Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early... Addressing Injuries Resulting from the Deepwater Horizon Oil Spill, the Federal and State natural resource... natural resources and services injured or lost as a result ] of the Deepwater Horizon oil spill,...

  20. 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

    ... and Gene Therapy Products'' that appeared in the Federal Register of July 2, 2013 (78 FR 39736). The... 2, 2013 (78 FR 39736), FDA published a notice announcing the availability of a draft guidance... of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Extension of Comment...

  1. Hazardous waste management program: phase I interim authorization for Nebraska--Environmental Protection Agency, region VII. Phase I interim authorization.

    PubMed

    1982-05-14

    The State of Nebraska has applied for interim authorization of its hazardous waste program under Subtitle C of the Resource Conservation and Recovery Act and EPA guidelines for the approval of State hazardous waste programs [40 CFR Part 123]. EPA has determined that the State's program meets all applicable statutory and regulatory requirements and is granting Phase I interim authorization to Nebraska to operate in its jurisdiction a hazardous waste program in lieu of Phase I of the Federal hazardous waste program. PMID:10255462

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

    SciTech Connect

    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% or more (95% 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. Early-phase circulating miRNAs predict tumor recurrence and survival of hepatocellular carcinoma patients after liver transplantation

    PubMed Central

    NG, Kevin Tak-Pan; Lo, Chung Mau; Wong, Nathalie; Li, Chang Xian; Qi, Xiang; Liu, Xiao Bing; Geng, Wei; Yeung, Oscar Wai-Ho; Ma, Yuen Yuen; Chan, See Ching; Man, Kwan

    2016-01-01

    Post-liver transplantation tumor recurrence is a major challenge for hepatocellular carcinoma (HCC) recipients. We aimed to identify early-phase circulating microRNAs after liver transplantation for predicting tumor recurrence and survival of HCC recipients. Circulating microRNA profiles at early-phase (2-hour after portal vein reperfusion) after liver transplantation were compared between HCC recipients with (n=4) and without tumor recurrence (n=8) by microarray analyses. Candidate microRNAs were validated in 62 HCC recipients by quantitative RT-PCR. The prognostic values of microRNAs for tumor recurrence and survival were examined. Simulated in vitro ischemia-reperfusion injury models were employed to characterize the possible mechanism of up-regulation of circulating microRNAs. Our results showed that up-regulation of circulating miR-148a, miR-1246 or miR-1290 at early-phase was significantly associated with HCC recurrence after liver transplantation. Among them, miR-148a (p=0.030) and miR-1246 (p=0.009) were significant predictors of HCC recurrence. MiR-1246 was an independent predictor of overall (p=0.023) and disease-free survival (p=0.020) of HCC recipients. The level of early-phase circulating miR-1246 was positively correlated with serum AST and ALT levels in HCC recipients after liver transplantation. The expression of hepatic miR-1246 was positively correlated with TNFα mRNA. In vitro experiments indicated that injury-induced activation and differentiation of macrophages significantly elevated the expression and secretion of miR-1246. In conclusion, early-phase circulating miR-1246 is an indicator of hepatic injury and a novel prognostic biomarker for tumor recurrence and survival of HCC recipients after liver transplantation. PMID:26918346

  4. 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

  5. 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

  6. Berberine Prevents Intestinal Mucosal Barrier Damage During Early Phase of Sepsis in Rat through the Toll-Like Receptors Signaling Pathway

    PubMed Central

    Li, Guo-xun; Wang, Xi-mo; Jiang, Tao; Gong, Jian-feng; Niu, Ling-ying

    2015-01-01

    Our previous study has shown berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway. In this study, we explored the regulatory effects of berberine on Toll-like receptors during the intestinal mucosal damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with berberine for 5 d before undergoing cecal ligation and puncture (CLP) to induce polymicrobial sepsis. The expression of Toll-like receptor 2 (TLR 2), TLR 4, TLR 9, the activity of nuclear factor-kappa B (NF-κB), the levels of selected cytokines and chemokines, percentage of cell death in intestinal epithelial cells, and mucosal permeability were investigated at 0, 2, 6, 12 and 24 h after CLP. Results showed that the tumor necrosis factor-α (TNF-α ) and interleukin-6 (IL-6) level were significantly lower in berberine-treated rats compared to the control animals. Conversely, the expression level of tight junction proteins, percentage of cell death in intestinal epithelial cells and the mucosal permeability were significantly higher in berberine-treated rats. The mRNA expression of TLR 2, TLR 4, and TLR 9 were significantly affected by berberine treatment. Our results indicate that pretreatment with berberine attenuates tissue injury and protects the intestinal mucosal barrier in early phase of sepsis and this may possibly have been mediated through the TLRs pathway. PMID:25605990

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Alterations of voltage-dependent K(+) channels in the mesenteric artery during the early and chronic phases of diabetes.

    PubMed

    Hong, Da Hye; Li, Hongliang; Kim, Hye Won; Kim, Han Sol; Son, Youn Kyoung; Yang, Se-Ran; Park, Jeong-Ran; Ha, Kwon-Soo; Han, Eun-Taek; Hong, Seok-Ho; Firth, Amy L; Na, Sung Hun; Park, Won Sun

    2016-09-01

    This study investigated the alteration of voltage-dependent K(+) (Kv) channels in mesenteric arterial smooth muscle cells from control (Long-Evans Tokushima Otsuka [LETO]) and diabetic (Otsuka Long-Evans Tokushima Fatty [OLETF]) rats during the early and chronic phases of diabetes. We demonstrated alterations in the mesenteric Kv channels during the early and chronic phase of diabetes using the patch-clamp technique, the arterial tone measurement system, and RT-PCR in Long-Evans Tokushima (LETO; for control) and Otsuka Long-Evans Tokushima Fatty (OLETF; for diabetes) type 2 diabetic model rats. In the early phase of diabetes, the amplitude of mesenteric Kv currents induced by depolarizing pulses was greater in OLETF rats than in LETO rats. The contractile response of the mesenteric artery induced by the Kv inhibitor, 4-aminopyridine (4-AP), was also greater in OLETF rats. The expression of most Kv subtypes- including Kv1.1, Kv1.2, Kv1.4, Kv1.5, Kv1.6, Kv2.1, Kv3.2, Kv4.1, Kv4.3, Kv5.1, Kv6.2, Kv8.1, Kv9.3, and Kv10.1-were increased in mesenteric arterial smooth muscle from OLETF rats compared with LETO rats. However, in the chronic phase of diabetes, the Kv current amplitude did not differ between LETO and OLETF rats. In addition, the 4-AP-induced contractile response of the mesenteric artery and the expression of Kv subtypes did not differ between the two groups. The increased Kv current amplitude and Kv channel-related contractile response were attributable to the increase in Kv channel expression during the early phase of diabetes. The increased Kv current amplitude and Kv channel-related contractile response were reversed during the chronic phase of diabetes. PMID:27218229

  13. 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

  14. 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

  15. 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

  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. Very early-initiated physical rehabilitation protects against ischemic brain injury.

    PubMed

    Zhang, Pengyue; Zhang, Qi; Pu, Hongjian; Wu, Yi; Bai, Yulong; Vosler, Peter S; Chen, Jun; Shi, Hong; Gao, Yanqin; Hu, Yongshan

    2012-01-01

    Recent clinical data suggest that very early initiated physical rehabilitation (VEIPR) within 24 hours after stroke may reduce morbidity. However, there is limited evidence to support the beneficial effects of VEIPR and the underlying mechanisms are yet unknown. The present study investigated the effect of VEIPR on brain damage, inflammation, and neurobehavioral outcomes following cerebral ischemia. Rats that underwent transient focal cerebral ischemia (tFCI) were randomly assigned to VEIPR or non-exercise (NE) groups. VEIPR was induced 24 hours after the insult by initiating treadmill training for a maximum of 14 days while the NE group remained sedentary in their cages during this period. The results indicated that VEIPR significantly improved recovery of functional behavior as measured by neurological score, foot fault test, and Morris water maze performance. We also demonstrated that VEIPR significantly reduced infarct volume, brain water content, BBB damage, and acute inflammatory response. In summary, our results provide novel evidence that VEIPR confers marked neuroprotection against experimental stroke by attenuating pro-inflammatory reactions, brain edema, BBB damage, and cognitive and behavioral deficits. PMID:22652654

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

    PubMed

    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. Akt Specific Activator SC79 Protects against Early Brain Injury following Subarachnoid Hemorrhage.

    PubMed

    Zhang, Dingding; Zhang, Huasheng; Hao, Shuangying; Yan, Huiying; Zhang, Zihuan; Hu, Yangchun; Zhuang, Zong; Li, Wei; Zhou, Mengliang; Li, Kuanyu; Hang, Chunhua

    2016-06-15

    A growing body of evidence demonstrates that Akt may serve as a therapeutic target for treatment of early brain injury following subarachnoid hemorrhage (SAH). The purpose of the current study was to evaluate the neuroprotective effect of Akt specific activator SC79 in an experimental rat model of SAH. SAH was induced by injecting 300 μL of blood into the prechiasmatic cistern. Intracerebroventricular (ICV) injection of SC79 (30 min post-SAH) induced the p-Akt (Ser473) expression in a dose-dependent manner. A single ICV dose treatment of SC79 (100 μg/rat) significantly increased the expression of Bcl-2 and p-GSK-3β (Ser9), decreased the protein levels of Bax, cytoplasm cytochrome c, and cleaved caspase-3, indicating the antiapoptotic effect of SC79. As a result, the number of apoptotic cells was reduced 24 h post SAH. Moreover, SC79 treatment alleviated SAH-induced oxidative stress, restored mitochondrial morphology, and improved neurological deficits. Strikingly, treatment of SC79 provided a beneficial outcome against neurologic deficit with a therapeutic window of at least 4 h post SAH by ICV injection and 30 min post SAH by intraperitoneal injection. Collectively, SC79 exerts its neuroprotective effect likely through the dual activities of antioxidation and antiapoptosis. These data provide a basic platform to consider SC79 as a novel therapeutic agent for treatment of SAH. PMID:26983552

  20. Elevated transcription of the p53 gene in early S-phase leads to a rapid DNA-damage response during S-phase of the cell cycle.

    PubMed

    Takahashi, Paula; Polson, Amanda; Reisman, David

    2011-09-01

    p53 induces the transcription of genes that negatively regulate progression of the cell cycle in response to DNA damage or other cellular stressors, and thus participates in maintaining genome stability. Under stress conditions, p53 must be activated to prohibit the replication of cells containing damaged DNA. However, in normal, non-stressed cells, p53 activity must be inhibited. Previous studies have demonstrated that p53 transcription is activated before or during early S-phase in cells progressing from G(0)/G(1) into S-phase. Since this is not what would be predicted from a gene involved in growth arrest and apoptosis, in this study, we provide evidence that this induction occurs to provide sufficient p53 mRNA to ensure a rapid response to DNA damage before exiting S-phase. When comparing exponentially growing Swiss3T3 cells to those synchronized to enter S-phase simultaneously and treated with the DNA damaging agent camptothecin, we found that with cells in S-phase, p53 protein levels increased earlier, Bax and p21 transcription was activated earlier and to a greater extent and apoptosis occurred earlier and to a greater extent. These findings are consistent with p53 transcription being induced in S-phase to provide for a rapid DNA-damage response during S-phase of the cell cycle. PMID:21710255

  1. The application of the AMB protective group in the solid-phase synthesis of methylphosphonate DNA analogues.

    PubMed Central

    Kuijpers, W H; Kuyl-Yeheskiely, E; van Boom, J H; van Boeckel, C A

    1993-01-01

    Partially methylphosphonate-modified oligodeoxynucleotides were synthesized on solid-phase by employing the easily removable 2-(acetoxymethyl)benzoyl (AMB) group as base-protecting group. Although a rapid AMB deprotection can be accomplished in methanolic potassium carbonate, the lability of the methylphosphonate linkage towards potassium carbonate/methanol excludes the use of this deprotection reagent. Thus, saturated ammonia solution in methanol was investigated as an alternative reagent for AMB removal. It is demonstrated that the combination of the AMB protective group and ammonia/methanol as deprotection reagent significantly improves the synthesis of methylphosphonate-modified DNA fragments. A mild overnight treatment at room temperature is sufficient for complete removal of the AMB group, whereas deprotection of conventionally protected oligonucleotides requires much longer exposure to basic conditions at elevated temperatures. PMID:8346028

  2. 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

  3. Protective effects of recombinant osteopontin on early brain injury after subarachnoid hemorrhage in rats

    PubMed Central

    Suzuki, Hidenori; Ayer, Robert; Sugawara, Takashi; Chen, Wanqiu; Sozen, Takumi; Hasegawa, Yu; Kanamaru, Kenji; Zhang, John H.

    2009-01-01

    Objective Accumulated evidence suggests that the primary cause of poor outcome after subarachnoid hemorrhage (SAH) is not only cerebral arterial narrowing, but also early brain injury (EBI). Our objective was to determine the effect of recombinant osteopontin (r-OPN), a pleiotropic extracellular matrix glycoprotein, on post-SAH EBI in rats. Design Controlled in vivo laboratory study. Setting Animal research laboratory. Subjects One hundred seventy-seven male adult Sprague-Dawley rats, 300–370g. Interventions The endovascular perforation model of SAH was produced. SAH or sham-operated rats were treated with an equal volume (1μL) of pre-SAH intracerebroventricular administration of two dosages (0.02 and 0.1μg) of r-OPN, albumin or vehicle. Body weight, neurological scores, brain edema and blood-brain barrier (BBB) disruption were evaluated, and Western blot analyses were performed to determine the effect of r-OPN on matrix metalloproteinase (MMP)-9, substrates of MMP-9 (zona occludens [ZO]-1, laminin), tissue inhibitor of MMP (TIMP)-1, inflammation (interleukin-1β), and nuclear factor (NF)-κ B signaling pathways. Measurements and Main Results Treatment with r-OPN prevented a significant loss in body weight, neurological impairment, brain edema, and BBB disruption after SAH. These effects were associated with the deactivation of NF-κB activity, inhibition of MMP-9 induction, the maintenance of TIMP-1, and the consequent preservation of the cerebral microvessel basal lamina protein laminin, and the tight junction protein ZO-1. Conclusions These results demonstrate that r-OPN treatment is effective for post-SAH EBI. PMID:19851092

  4. 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.

  5. Musculoskeletal Symptoms in Nurses in the Early Implementation Phase of California's Safe Patient Handling Legislation.

    PubMed

    Lee, Soo-Jeong; Lee, Joung Hee; Gershon, Robyn R M

    2015-06-01

    Musculoskeletal injuries and symptoms are prevalent in nurses and are largely associated with strenuous patient handling. In 2011, California enacted legislation that required acute-care hospitals to implement safe patient handling (SPH) policies and programs. To assess the early phase of this legislation, we conducted an epidemiological assessment of organizational SPH practices, musculoskeletal symptoms, and perceptions in a random sample of 396 registered nurses. Among those who worked in hospitals and had patient handling duties (n = 220), the 12 month prevalence of work-related musculoskeletal symptoms was 69% (lower back 54%, neck 41%, shoulders 34%, and hands/wrists 26%). Twenty-two percent of the nurses reported that their hospitals had a "no-lift" policy, 37% reported that their hospitals had lift teams, and 61% reported the availability of mechanical lift equipment such as floor or ceiling lifts. Nurses whose facilities employed lift teams were significantly less likely to report low back pain (OR = 0.54, 95% CI [0.30-0.97]). Nurses whose units had ceiling lifts were significantly less likely to report shoulder pain than nurses with no access to lifts (OR = 0.32, 95% CI [0.10-0.98]). Roughly 60% of respondents were aware of the SPH law, and 33% reported changes in their hospital's patient handling policies or programs since the law went into effect. Hospital SPH practices reported by the nurses in our sample were generally sub-optimal, but our findings suggest positive effects of elements required by SPH legislation. These data will serve as the baseline for future evaluation of the impact of this law in California. PMID:25914203

  6. Posturo-kinetic organisation during the early phase of voluntary upper limb movement. 1. Normal subjects.

    PubMed Central

    Zattara, M; Bouisset, S

    1988-01-01

    The nature and organisation of anticipatory postural adjustments (APA) associated with the early phase of a voluntary upper limb movement were studied. Upper limb elevations, performed at maximal velocity, were studied according to three conditions: bilateral flexions (BF) and unilateral flexions without and with an additional inertia (respectively OUF and IUF). Activities of the anterior part of the deltoid (DA) and of main muscles of the lower limbs, pelvis, trunk and scapular girdle were recorded by surface electromyography. Miniature-accelerometers enabled the recording of the tangential acceleration of the arm at wrist level (Aw) and the antero-posterior accelerations of various body links. Systematic investigations allow a precise description of the segmental phenomena which precede the onset of the voluntary movement. Before the activation of the anterior deltoid, a sequence of EMG modifications occurred in muscles of lower limbs, pelvis and trunk. The onset of Aw was preceded by anticipatory local accelerations of all the body links. Anticipatory EMG activities and local accelerations were organised according to patterns which were specific to the forthcoming voluntary movement. By comparing anticipatory EMG activities with anticipatory local accelerations, the nature of anticipatory postural movements can be determined. They appear to counteract the disturbing effects of the forthcoming voluntary movement. Because of their reproducibility and specificity, the anticipatory postural movements can be considered as preprogrammed. Postural adjustments and voluntary movement appear to be parts of the same motor program. Anticipatory postural movements should result from muscular functional synergies selected from a pre-evaluation of the perturbative aspects of the forthcoming movement. PMID:3204405

  7. High-content analysis of sequential events during the early phase of influenza A virus infection.

    PubMed

    Banerjee, Indranil; Yamauchi, Yohei; Helenius, Ari; Horvath, Peter

    2013-01-01

    Influenza A virus (IAV) represents a worldwide threat to public health by causing severe morbidity and mortality every year. Due to high mutation rate, new strains of IAV emerge frequently. These IAVs are often drug-resistant and require vaccine reformulation. A promising approach to circumvent this problem is to target host cell determinants crucial for IAV infection, but dispensable for the cell. Several RNAi-based screens have identified about one thousand cellular factors that promote IAV infection. However, systematic analyses to determine their specific functions are lacking. To address this issue, we developed quantitative, imaging-based assays to dissect seven consecutive steps in the early phases of IAV infection in tissue culture cells. The entry steps for which we developed the assays were: virus binding to the cell membrane, endocytosis, exposure to low pH in endocytic vacuoles, acid-activated fusion of viral envelope with the vacuolar membrane, nucleocapsid uncoating in the cytosol, nuclear import of viral ribonucleoproteins, and expression of the viral nucleoprotein. We adapted the assays to automated microscopy and optimized them for high-content screening. To quantify the image data, we performed both single and multi-parametric analyses, in combination with machine learning. By time-course experiments, we determined the optimal time points for each assay. Our quality control experiments showed that the assays were sufficiently robust for high-content analysis. The methods we describe in this study provide a powerful high-throughput platform to understand the host cell processes, which can eventually lead to the discovery of novel anti-pathogen strategies. PMID:23874633

  8. Cognitive Enhancement Therapy Protects Against Gray Matter Loss in Early Schizophrenia: Results From a Two-Year Randomized Controlled Trial

    PubMed Central

    Eack, Shaun M.; Hogarty, Gerard E.; Cho, Raymond Y.; Prasad, Konasale M. R.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

    2013-01-01

    improved cognition and mediated the beneficial cognitive effects of cognitive enhancement therapy. Conclusion Cognitive enhancement therapy may offer neurobiologic protective and enhancing effects in early schizophrenia that are associated with improved long-term cognitive outcomes. Trial Registration clinicaltrials.gov Identifier: NCT00167362 PMID:20439824

  9. 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

  10. 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

  11. 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.

  12. Live birth following early follicular phase oocyte collection and vitrified-warmed embryo transfer 8 days later.

    PubMed

    Hatırnaz, Safak; Hatırnaz, Ebru; Ata, Baris

    2015-12-01

    A 30-year-old woman with premature ovarian insufficiency had two follicles measuring 17 mm and 14 mm on day 3 of her menstrual cycle. Serum oestradiol concentration was 210 pg/ml. Recombinant human chorionic gonadotrophin was given and 5 mg/day letrozole started orally. One metaphase II oocyte was collected 36 h later. A 4-cell embryo was vitrified on the second day after fertilization. Letrozole was stopped on cycle day 8 due to absence of any other visible antral follicles. Oestradiol valerate 6 mg/day was started and the endometrium was 9.2 mm on cycle day 11. The embryo was warmed and transferred on cycle day 13, the 8th day after oocyte retrieval. Luteal phase support with progesterone, oestradiol and low molecular weight heparin was started on the day of transfer and continued until the 10th gestational week. A healthy girl weighing 3200 g was born at term. Early follicular phase oocyte collection did not result in early opening of the implantation window. Apparently secretory transformation was not started until luteal phase support, enabling a cleavage stage embryo transferred 8 days later to implant. Either corpus luteum formation could be disrupted or the endometrium could remain unresponsive to progesterone during the early follicular phase. PMID:26507278

  13. 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

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

    PubMed Central

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

    1998-01-01

    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. Images Figure 3 Figure 5 Figure 6 Figure 7 PMID:9626051

  15. 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.

  16. Traumatic axonal injury: Relationships between lesions in the early phase and diffusion tensor imaging parameters in the chronic phase of traumatic brain injury.

    PubMed

    Moen, Kent Gøran; Vik, Anne; Olsen, Alexander; Skandsen, Toril; Håberg, Asta Kristine; Evensen, Kari Anne I; Eikenes, Live

    2016-07-01

    This prospective study of traumatic brain injury (TBI) patients investigates fractional anisotropy (FA) from chronic diffusion tensor imaging (DTI) in areas corresponding to persistent and transient traumatic axonal injury (TAI) lesions detected in clinical MRI from the early phase. Thirty-eight patients (mean 24.7 [range 13-63] years of age) with moderate-to-severe TBI and 42 age- and sex-matched healthy controls were included. Patients underwent 1.5-T clinical MRI in the early phase (median 7 days), including fluid-attenuated inversion recovery (FLAIR) and T2* gradient echo (T2*GRE) sequences. TAI lesions from the early phase were characterized as nonhemorrhagic or microhemorrhagic. In the chronic phase (median 3 years), patients and controls were imaged at 3 T with FLAIR, T2*GRE, T1, and DTI sequences. TAI lesions were classified as transient or persistent. The FLAIR/T2*GRE images from the early phase were linearly registered to the FA images from the chronic phase and lesions manually segmented on the FA-registered FLAIR/T2*GRE images. For regions of interest (ROIs) from both nonhemorrhagic and microhemorrhagic lesion, we found a significant linear trend of lower mean FA from ROIs in healthy controls to ROIs in patients without either nonhemorrhagic or microhemorrhagic lesions and further to transient and finally persistent lesion ROIs (P < 0.001). Histogram analyses showed lower FA in persistent compared with transient nonhemorrhagic lesion ROIs (P < 0.001), but this was not found in microhemorrhagic lesion ROIs (P = 0.08-0.55). The demonstrated linear trend of lower FA values from healthy controls to persistent lesion ROIs was found in both nonhemorrhagic and microhemorrhagic lesions and indicates a gradual increasing disruption of the microstructure. Lower FA values in persistent compared with transient lesions were found only in nonhemorrhagic lesions. Thus, clinical MRI techniques are able to depict important aspects of white matter pathology across the

  17. A new low-cost, fully fault-protected PWM-VSI inverter with true phase-current information

    SciTech Connect

    Blaabjerg, F.; Pedersen, J.K.

    1997-01-01

    This paper proposes a new topology for a low-cost three-phase pulse width modulation (PWM) VSI inverter where a true phase current information exists with the use of only one current sensor in the dc link. The topology also has the benefits of full protection of the inverter such as short circuits in the dc link, output phase faults, and output earth faults. Previously suggested methods have problems at low speed in detecting the phase current, but by the use of space vector modulation in a double-sided implementation, the PWM-pulses are adjusted so true information about the phase current exists even at very low speed. The dc link current is sampled twice during one switching period, and it is proposed to sample in the center of the PWM-pulses to obtain a real average phase current. The effects of blanking-time and overmodulation are also discussed. The strategy is implemented in a 16-b microcontroller, and the test results show the technique is useful in the whole speed range. It is concluded by the use of the proposed topology that only one current sensor will be necessary in the future for PWM-VSI inverters.

  18. 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.

  19. Strategies for Early Non-response to Antipsychotic Drugs in the Treatment of Acute-phase Schizophrenia

    PubMed Central

    Ito, Hiroto

    2014-01-01

    As a strategy for antipsychotic treatment of schizophrenia, monotherapy is clearly optimal when both effective and tolerated. When a patient fails to respond to an adequate dose of an antipsychotic, alternatives include switching, administering a higher dose (above the licensed dose), polypharmacy or clozapine. Clozapine is the only option with established efficacy, but is less manageable than other antipsychotics. We therefore reviewed other options, focusing on the treatment of acute-phase schizophrenia. According to recent evidence, an antipsychotic may be viewed as ineffective within 1-4 weeks in acute-phase practice, although some differences may exist among antipsychotics. Whether a switching strategy is effective might depend on the initial antipsychotic and which antipsychotic is switched to. As weak evidence points toward augmentation being superior to continuation of the initial antipsychotic, inclusion of augmentation arms in larger studies comparing strategies for early non-responders in the acute-phase is justified. With respect to high-doses, little evidence is available regarding acute-phase treatment, and the issue remains controversial. Although evidence for antipsychotic switching, augmentation, and high-doses has gradually been accumulating, more studies performed in real clinical practice with minimal bias are required to establish strategies for early non-response to an antipsychotic drug in the treatment of acute-phase schizophrenia. PMID:24851115

  20. Early Childhood Technology Integrated Instructional System (EC-TIIS): Phase 3. Final Report

    ERIC Educational Resources Information Center

    Robinson, Linda; Schneider, Carol; Daytner, Gary; Johanson, Joyce; Hutinger, Patricia

    2009-01-01

    The Early Childhood Technology Integrated Instructional System 3 (EC-TIIS 3), housed in the Center for Best Practices in Early Childhood (the Center) within the College of Education and Human Services at Western Illinois University (WIU), was funded in 2004 by the U.S. Department of Education's Office of Special Education Programs (OSEP) as a…

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Early Phases of Jupiter's Formation from an Evolving Disk of Solids

    NASA Astrophysics Data System (ADS)

    D'Angelo, G.; Weidenschilling, S. J.; Lissauer, J. J.; Bodenheimer, P.

    2014-12-01

    We are performing calculations of the formation of Jupiter via core nucleated accretion and gas capture. The calculations model the growth of a solid core from an evolving disk of planetesimals and the growth of a contracting gaseous envelope. We present results of the early phases of formation. The evolution of the solids accounts for growth and fragmentation, viscous and gravitational stirring, and for drag-assisted migration and velocity damping operated by the disk's gas. The envelope structure accounts for mass and energy deposition due to the ablation of planetesimals that move through the envelope. The envelope's opacity takes into account coagulation and sedimentation of dust particles released by ablating planetesimals. The core starts as a seed body of 350 km in radius, orbiting at 5.2 AU in a disk of planetesimals whose initial radii range from 15 m to 50 km. The initial surface density of the solids is 10 g/cm^2 at the seed's location. During the evolution of the solids, most of the mass resides in bodies of several tens of km in radius. These are also the planetesimals that provide most of the solids accretion to the planet. By comparing results with a calculation that does not account for the envelope bound to the core, we find that the size-dependent cross-section of the planet for the accretion of planetesimals is substantially enhanced by a low-mass, but voluminous envelope. The calculation without the envelope produces a core of 4.4 Earth masses (Mearth) after about 1 Myr, and an extrapolated mass of about 5 Mearth after 6 Myr. The full calculation with envelope yields a core of 7.3 Mearth and an envelope of 0.15 Mearth after about 0.4 Myr. At this point of the planet's evolution, the envelope accretion rate exceeds that of the core. Over the following 1 Myr, the core mass reaches about 8 Mearth and the envelope mass grows to about 4 Mearth. Support from NASA Outer Planets Research Program is gratefully acknowledged.

  6. Chemical evolution in the early phases of massive star formation. I

    NASA Astrophysics Data System (ADS)

    Gerner, T.; Beuther, H.; Semenov, D.; Linz, H.; Vasyunina, T.; Bihr, S.; Shirley, Y. L.; Henning, Th.

    2014-03-01

    Understanding the chemical evolution of young (high-mass) star-forming regions is a central topic in star formation research. Chemistry is employed as a unique tool 1) to investigate the underlying physical processes and 2) to characterize the evolution of the chemical composition. With these aims in mind, we observed a sample of 59 high-mass star-forming regions at different evolutionary stages varying from the early starless phase of infrared dark clouds to high-mass protostellar objects to hot molecular cores and, finally, ultra-compact Hii regions at 1 mm and 3 mm with the IRAM 30 m telescope. We determined their large-scale chemical abundances and found that the chemical composition evolves along with the evolutionary stages. On average, the molecular abundances increase with time. We modeled the chemical evolution, using a 1D physical model where density and temperature vary from stage to stage coupled with an advanced gas-grain chemical model and derived the best-fit χ2 values of all relevant parameters. A satisfying overall agreement between observed and modeled column densities for most of the molecules was obtained. With the best-fit model we also derived a chemical age for each stage, which gives the timescales for the transformation between two consecutive stages. The best-fit chemical ages are ~10 000 years for the IRDC stage, ~60 000 years for the HMPO stage, ~40 000 years for the HMC stage, and ~10 000 years for the UCHii stage. Thus, the total chemical timescale for the entire evolutionary sequence of the high-mass star formation process is on the order of 105 years, which is consistent with theoretical estimates. Furthermore, based on the approach of a multiple-line survey of unresolved data, we were able to constrain an intuitive and reasonable physical and chemical model. The results of this study can be used as chemical templates for the different evolutionary stages in high-mass star formation. Based on observations carried out with the IRAM

  7. 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

  8. 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

  9. 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

  10. Divided attention can enhance early-phase memory encoding: the attentional boost effect and study trial duration.

    PubMed

    Mulligan, Neil W; Spataro, Pietro

    2015-07-01

    Divided attention during encoding typically produces marked reductions in later memory. The attentional boost effect (ABE) is a surprising variation on this phenomenon. In this paradigm, each study stimulus (e.g., a word) is presented along with a target or a distractor (e.g., different colored circles) in a detection task. Later memory is better for stimuli co-occurring with targets. The present experiments indicate that the ABE arises during an early phase of memory encoding that involves initial stimulus perception and comprehension rather than at a later phase entailing controlled, elaborative rehearsal. Experiment 1 demonstrated that the ABE was robust at a short study duration (700 ms) and did not increase with increasing study trial durations (1,500 ms and 4,000 ms). Furthermore, the target condition is boosted to the level of memory performance in a full-attention condition for the short duration but not the long duration. Both results followed from the early-phase account. This account also predicts that for very short study times (limiting the influence of late-phase controlled encoding and thus minimizing the usual negative effect of divided attention), the target condition will produce better memory than will the full-attention condition. Experiment 2 used a study time of 400 ms and found that words presented with targets lead to greater recognition accuracy than do either words presented with distractors or words in the full-attention condition. Consistent with the early-phase account, a divided attention condition actually produced superior memory than did the full-attention condition, a very unusual but theoretically predicted result. PMID:25181494

  11. Kondo spin liquid in the Kondo necklace model: Classical disordered phase versus symmetry-protected topological state

    NASA Astrophysics Data System (ADS)

    Zhong, Yin; Wang, Yu-Feng; Lu, Han-Tao; Luo, Hong-Gang

    2014-08-01

    We have studied Kondo spin liquid phase of Kondo necklace models from the perspective of quantum O(N) non-linear sigma model (NLSM) field theory, particularly we focus on its possible topologically nontrivial phases. In the one-dimensional case, the Kondo spin liquid phase is a usual quantum disordered phase in contrast to the well-known topologically nontrivial Haldane phase due to destructive interference effect of topological θ term. In the two-dimensional case, the system can be mapped onto an O(4)-like NLSM with some O(3) anisotropy. Interestingly, if hedgehog-like point defects are included together with the restoration of the full O(4) symmetry, our model is identical to a kind of SU(2) symmetry-protected topological (SPT) state, which highlights a possible link between the extended Kondo necklace models and the desirable SPT states. Additionally, if the system has the expanded O(5) symmetry instead, the effective NLSM with the Wess-Zumino-Witten term is just a description of the surface modes of a three-dimensional SPT state. The deviations from fully symmetrical cases are discussed. We expect that the results might provide useful threads to identify certain microscopic bilayer antiferromagnet models (and related materials), which can support the SPT states.

  12. A REVIEW OF THE EARLY DEVELOPMENT OF THE THERMODYNAMICS OF THE COMPLEX COACERVATION PHASE SEPARATION

    PubMed Central

    Veis, Arthur

    2011-01-01

    Coacervation was defined as the phenomenon in which a colloidal dispersion separated into colloid-rich (the coacervate), and colloid-poor phases, both with the same solvent. Complex coacervation covered the situation in which a mixture of two polymeric polyions with opposite charge separated into liquid dilute and concentrated phases, in the same solvent, with both phases, at equilibrium, containing both polyions. Voorn and Overbeek provided the first theoretical analysis of complex coacervation by applying Flory-Huggins polymer statistics to model the random mixing of the polyions and their counter ions in solution, assuming completely random mixing of the polyions in each phase, with the electrostatic free energy, ΔGelect, providing the driving force. However, experimentally complete randomness does not apply: polyion size, heterogeneity, chain stiffness and charge density (σ) all affect the equilibrium phase separation and phase concentrations. Moreover, in pauci-disperse systems multiple phases are often observed. As an alternative, Veis and Aranyi proposed the formation of charge paired Symmetrical Aggregates (SA) as an initial step, followed by phase separation driven by the interaction parameter, χ23, combining both entropy and enthalpy factors other than the ΔGelect electrostatic term. This two stage path to equilibrium phase separation allows for understanding and quantifying and modeling the diverse aggregates produced by interactions between polyampholyte molecules of different charge density, σ, and intrinsic polyion structure. PMID:21377640

  13. 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. PMID:24960609

  14. Ground-State Phase Diagram of the Bond-Alternating S = 2 Quantum Spin Chain with the XXZ and On-Site Anisotropies - Symmetry Protected Topological Phase versus Trivial Phase

    NASA Astrophysics Data System (ADS)

    Okamoto, Kiyomi; Tonegawa, Takashi; Sakai, Tôru

    2016-06-01

    We investigate the ground-state phase diagram of the bond-alternating S = 2 quantum spin chain with the XXZ and on-site anisotropies. For the on-site anisotropies, in addition to the popular D2sumnolimitsj (Sjz)2 term, we consider the D4sumnolimitsj (Sjz)4 term. Mainly we use the exact diagonalization and the level spectroscopy analysis. We show that the Haldane state, large-D state and the Dimer2 state belong to the same trivial phase, by finding the existence of adiabatic paths directly connecting these states without the quantum phase transition. Similarly, we show that the intermediate-D state and the Dimer1 state belong to the same symmetry protected topological phase.

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

    PubMed Central

    Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

    2016-01-01

    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

  16. 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

  17. A new Bayesian Inference-based Phase Associator for Earthquake Early Warning

    NASA Astrophysics Data System (ADS)

    Meier, Men-Andrin; Heaton, Thomas; Clinton, John; Wiemer, Stefan

    2013-04-01

    State of the art network-based Earthquake Early Warning (EEW) systems can provide warnings for large magnitude 7+ earthquakes. Although regions in the direct vicinity of the epicenter will not receive warnings prior to damaging shaking, real-time event characterization is available before the destructive S-wave arrival across much of the strongly affected region. In contrast, in the case of the more frequent medium size events, such as the devastating 1994 Mw6.7 Northridge, California, earthquake, providing timely warning to the smaller damage zone is more difficult. For such events the "blind zone" of current systems (e.g. the CISN ShakeAlert system in California) is similar in size to the area over which severe damage occurs. We propose a faster and more robust Bayesian inference-based event associator, that in contrast to the current standard associators (e.g. Earthworm Binder), is tailored to EEW and exploits information other than only phase arrival times. In particular, the associator potentially allows for reliable automated event association with as little as two observations, which, compared to the ShakeAlert system, would speed up the real-time characterizations by about ten seconds and thus reduce the blind zone area by up to 80%. We compile an extensive data set of regional and teleseismic earthquake and noise waveforms spanning a wide range of earthquake magnitudes and tectonic regimes. We pass these waveforms through a causal real-time filterbank with passband filters between 0.1 and 50Hz, and, updating every second from the event detection, extract the maximum amplitudes in each frequency band. Using this dataset, we define distributions of amplitude maxima in each passband as a function of epicentral distance and magnitude. For the real-time data, we pass incoming broadband and strong motion waveforms through the same filterbank and extract an evolving set of maximum amplitudes in each passband. We use the maximum amplitude distributions to check

  18. 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+.

  19. 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.

  20. 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

  1. A Lithium Amide Protected Against Protonation in the Gas Phase: Unexpected Effect of LiCl.

    PubMed

    Lesage, Denis; Barozzino-Consiglio, Gabriella; Duwald, Romain; Fressigné, Catherine; Harrison-Marchand, Anne; Faull, Kym F; Maddaluno, Jacques; Gimbert, Yves

    2015-06-19

    In cold THF and in the presence of LiCl, a lithium pyrrolidinylamide forms a 1:1 mixed aggregate, which is observed directly by ESI-MS. Gas-phase protonation of this species leads to selective transfer of H(+) to the chlorine, suggesting that LiCl shields the amide nitrogen and prevents its direct protonation. PMID:25997158

  2. No Evidence for Activated Autophagy in Left Ventricular Myocardium at Early Reperfusion with Protection by Remote Ischemic Preconditioning in Patients Undergoing Coronary Artery Bypass Grafting

    PubMed Central

    Gedik, Nilgün; Thielmann, Matthias; Kottenberg, Eva; Peters, Jürgen; Jakob, Heinz; Heusch, Gerd; Kleinbongard, Petra

    2014-01-01

    Objective Remote ischemic preconditioning (RIPC) by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG). Activation of signal transducer and activator of transcription 5 (STAT5) in left ventricular (LV) myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy. Methods CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation) or placebo (cuff deflated) before skin incision (n = 10/10). Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline) and at early (5–10 min) reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002). Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5–12 (ATG5-12) complex, light chain 3 (LC3), parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2)-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion. Results Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02). STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05). Conclusion Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion. PMID:24797938

  3. 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.

  4. 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

  5. A statistical index for early diagnosis of ventricular arrhythmia from the trend analysis of ECG phase-portraits.

    PubMed

    Cappiello, Grazia; Das, Saptarshi; Mazomenos, Evangelos B; Maharatna, Koushik; Koulaouzidis, George; Morgan, John; Puddu, Paolo Emilio

    2015-01-01

    In this paper, we propose a novel statistical index for the early diagnosis of ventricular arrhythmia (VA) using the time delay phase-space reconstruction (PSR) technique, from the electrocardiogram (ECG) signal. Patients with two classes of fatal VA-with preceding ventricular premature beats (VPBs) and with no VPBs-have been analysed using extensive simulations. Three subclasses of VA with VPBs viz. ventricular tachycardia (VT), ventricular fibrillation (VF) and VT followed by VF are analyzed using the proposed technique. Measures of descriptive statistics like mean (µ), standard deviation (σ), coefficient of variation (CV = σ/µ), skewness (γ) and kurtosis (β) in phase-space diagrams are studied for a sliding window of 10 beats of the ECG signal using the box-counting technique. Subsequently, a hybrid prediction index which is composed of a weighted sum of CV and kurtosis has been proposed for predicting the impending arrhythmia before its actual occurrence. The early diagnosis involves crossing the upper bound of a hybrid index which is capable of predicting an impending arrhythmia 356 ECG beats, on average (with 192 beats standard deviation) before its onset when tested with 32 VA patients (both with and without VPBs). The early diagnosis result is also verified using a leave one out cross-validation (LOOCV) scheme with 96.88% sensitivity, 100% specificity and 98.44% accuracy. PMID:25500749

  6. Marek's disease virus influences the core gut microbiome of the chicken during the early and late phases of viral replication.

    PubMed

    Perumbakkam, Sudeep; Hunt, Henry D; Cheng, Hans H

    2014-10-01

    Marek's disease (MD) is an important neoplastic disease of chickens caused by the Marek's disease virus (MDV), an oncogenic alphaherpesvirus. In this study, dysbiosis induced by MDV on the core gut flora of chicken was assessed using next generation sequence (NGS) analysis. Total fecal and cecum-derived samples from individual birds were used to estimate the influence of MDV infection on the gut microbiome of chicken. Our analysis shows that MDV infection alters the core gut flora in the total fecal samples relatively early after infection (2-7 days) and in the late phase of viral infection (28-35 days) in cecal samples, corresponding well with the life cycle of MDV. Principle component analyses of total fecal and cecal samples showed clustering at the early and late time points, respectively. The genus Lactobacillus was exclusively present in the infected samples in both total fecal and cecal bird samples. The community colonization of core gut flora was altered by viral infection, which manifested in the enrichment of several genera during the early and late phases of MDV replication. The results suggest a relationship between viral infection and microbial composition of the intestinal tract that may influence inflammation and immunosuppression of T and B cells in the host. PMID:25065611

  7. 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.

  8. 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. PMID:23234854

  9. 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.

  10. 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.

  11. 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

    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. PMID:26984188

  12. Fractalkine Receptor Deficiency Is Associated with Early Protection but Late Worsening of Outcome following Brain Trauma in Mice.

    PubMed

    Zanier, Elisa R; Marchesi, Federica; Ortolano, Fabrizio; Perego, Carlo; Arabian, Maedeh; Zoerle, Tommaso; Sammali, Eliana; Pischiutta, Francesca; De Simoni, Maria-Grazia

    2016-06-01

    An impaired ability to regulate microglia activation by fractalkine (CX3CL1) leads to microglia chronic sub-activation. How this condition affects outcome after acute brain injury is still debated, with studies showing contrasting results depending on the timing and the brain pathology. Here, we investigated the early and delayed consequences of fractalkine receptor (CX3CR1) deletion on neurological outcome and on the phenotypical features of the myeloid cells present in the lesions of mice with traumatic brain injury (TBI). Wild type (WT) and CX3CR1(-/-) C57Bl/6 mice were subjected to sham or controlled cortical impact brain injury. Outcome was assessed at 4 days and 5 weeks after TBI by neuroscore, neuronal count, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Compared with WT mice, CX3CR1(-/-) TBI mice showed a significant reduction of sensorimotor deficits and lower cellular damage in the injured cortex 4 days post-TBI. Conversely, at 5 weeks, they showed a worsening of sensorimotor deficits and pericontusional cell death. Microglia (M) and macrophage (μ) activation and polarization were assessed by quantitative immunohistochemistry for CD11b, CD68, Ym1, and inducible nitric oxide synthase (iNOS)-markers of M/μ activation, phagocytosis, M2, and M1 phenotypes, respectively. Morphological analysis revealed a decreased area and perimeter of CD11b(+) cells in CX3CR1(-/-) mice at 4 days post-TBI, whereas, at 5 weeks, both parameters were significantly higher, compared with WT mice. At 4 days, CX3CR1(-/-) mice showed significantly decreased CD68 and iNOS immunoreactivity, while at 5 weeks post-injury, they showed a selective increase of iNOS. Gene expression on CD11b(+) sorted cells revealed an increase of interleukin 10 and insulin-like growth factor 1 (IGF1) at 1 day and a decrease of IGF1 4 days and 5 weeks post-TBI in CX3CR1(-/-), compared with WT mice. These data show an early protection followed by a chronic exacerbation of

  13. Hydroxytyrosol induces phase II detoxifying enzyme expression and effectively protects dopaminergic cells against dopamine- and 6-hydroxydopamine induced cytotoxicity.

    PubMed

    Yu, Guohua; Deng, Ajun; Tang, Wanbin; Ma, Junzhi; Yuan, Chonggang; Ma, Jiyan

    2016-06-01

    Parkinson's disease (PD) is the second most common late-age onset neurodegenerative disease. Except for the symptomatic alleviating treatment, no disease modifying therapy is currently available. In this study, we investigated the potential neuroprotective role of hydroxytyrosol (HT), a major phenolic compound present in olive oil, against dopaminergic cell death. We found that HT effectively protected dopaminergic SH-SY5Y cells against dopamine (DA) and 6-hydroxydopamine (6-OHDA) induced cell death, but had no apparent effect on 1-methyl-4-phenylpyridinium (MPP(+))-induced cytotoxicity. Furthermore, we have shown that HT efficiently induced the expression of phase II detoxifying enzymes, including NAD(P)H quinone oxidoreductase 1 (NQO1). Using an NQO1 inhibitor, we revealed that increased NQO1 expression contributed to the protective effect of HT against dopaminergic cell death. Together, our findings suggest that HT has a protective effect against DA- and 6-OHDA-induced dopaminergic cell death, supporting the beneficial effect of olive oil in preventing DA-metabolism related dopaminergic neuron dysfunction. PMID:26970393

  14. 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.

  15. 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…

  16. On the role of carbonic anhydrase in the early phase of fish otolith mineralization

    NASA Astrophysics Data System (ADS)

    Beier, M.; Anken, R.

    2006-01-01

    The first step in the formation of fish otoliths, calcified structures which are responsible for the internalization of gravitational information, is based on the action of so-called Tether- (T-) cells. These T-cells appear during the very early development of the inner ear and persist only a few hours. They are characterized by a kinocilium, which is in contrast to the kinocilium of the later developing sensory hair cells not mechanosensory, but binds seeding particles containing glycogen, thereby localizing otolith formation (otolith seeding). Beating cilia distributed throughout the ear agitate seeding particles, thereby inhibiting premature agglutination. In the later development, a protein matrix is formed and mineralization/crystallization takes place. Since the enzyme carbonic anhydrase (CAH) plays a prominent role in otolith mineralization (it provides carbonate for CaCO3 precipitation), we were prompted to investigate histochemically using larval cichlid fish (Oreochromis mossambicus), whether CAH might be present as early as T-cells. Indeed, CAH was present in T-cells with prominent amounts of reaction product being located along the kinocilia and around the seeding particles. These results strongly indicate that kinocilia of T-cells act as structural guides for CAH/bicarbonate transportation towards the early otoliths’ calcification sites. Besides its role in calcification, CAH in the very early stage of otolith seeding may moreover aid in the accretion process of the precursor particles.

  17. Ultra-Fast Flash Observatory: Fast Response Space Missions for Early Time Phase of Gamma Ray Bursts

    NASA Astrophysics Data System (ADS)

    Park, I. H.; Ahmad, S.; Barrillon, P.; Brandt, S.; Budtz-Jørgensen, C.; Castro-Tirado, A. J.; Chen, P.; Choi, J. N.; Choi, Y. J.; Connell, P.; Dagoret-Campagne, S.; Eyles, C.; Grossan, B.; Huang, M.-H. A. Huang; Jung, A.; Jeong, S.; Kim, J. E.; Kim, M. B.; Kim, S.-W.; Kim, Y. W.; Krasnov, A. S.; Lee, J.; Lim, H.; Linder, E. V.; Liu, T.-C.; Min, K. W.; Na, G. W.; Nam, J. W.; Panasyuk, M. I.; Park, H. W.; Ripa, J.; Reglero, V.; Rodrigo, J. M.; Smoot, G. F.; Svertilov, S.; Vedenkin, N.; Wang, M.-Z.; Yashin, I.

    2013-07-01

    One of the unexplored domains in the study of gamma-ray bursts (GRBs) is the early time phase of the optical light curve. We have proposed Ultra-Fast Flash Observatory (UFFO) to address this question through extraordinary opportunities presented by a series of small space missions. The UFFO is equipped with a fast-response Slewing Mirror Telescope that uses a rapidly moving mirror or mirror array to redirect the optical beam rather than slewing the entire spacecraft or telescope to aim the optical instrument at the GRB position. The UFFO will probe the early optical rise of GRBs with sub-second response, for the first time, opening a completely new frontier in GRB and transient studies. Its fast response measurements of the optical emission of dozens of GRB each year will provide unique probes of the burst mechanism and test the prospect of GRB as a new standard candle, potentially opening up the z > 10 universe. We describe the current limit in early photon measurements, the aspects of early photon physics, our soon-to-be-launched UFFO-pathfinder mission, and our next planned mission, the UFFO-100.

  18. 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

  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. PMID:26086367

  20. Murine cytomegalovirus perturbs endosomal trafficking of major histocompatibility complex class I molecules in the early phase of infection.

    PubMed

    Tomas, Maja Ilić; Kucić, Natalia; Mahmutefendić, Hana; Blagojević, Gordana; Lucin, Pero

    2010-11-01

    Murine cytomegalovirus (MCMV) functions interfere with protein trafficking in the secretory pathway. In this report we used Δm138-MCMV, a recombinant virus with a deleted viral Fc receptor, to demonstrate that MCMV also perturbs endosomal trafficking in the early phase of infection. This perturbation had a striking impact on cell surface-resident major histocompatibility complex class I (MHC-I) molecules due to the complementary effect of MCMV immunoevasins, which block their egress from the secretory pathway. In infected cells, constitutively endocytosed cell surface-resident MHC-I molecules were arrested and retained in early endosomal antigen 1 (EEA1)-positive and lysobisphosphatidic acid (LBPA)-negative perinuclear endosomes together with clathrin-dependent cargo (transferrin receptor, Lamp1, and epidermal growth factor receptor). Their progression from these endosomes into recycling and degradative routes was inhibited. This arrest was associated with a reduction of the intracellular content of Rab7 and Rab11, small GTPases that are essential for the maturation of recycling and endolysosomal domains of early endosomes. The reduced recycling of MHC-I in Δm138-MCMV-infected cells was accompanied by their accelerated loss from the cell surface. The MCMV function that affects cell surface-resident MHC-I was activated in later stages of the early phase of viral replication, after the expression of known immunoevasins. MCMV without the three immunoevasins (the m04, m06, and m152 proteins) encoded a function that affects endosomal trafficking. This function, however, was not sufficient to reduce the cell surface expression of MHC-I in the absence of the transport block in the secretory pathway. PMID:20719942

  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. 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.

  3. 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.

  4. 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

  5. On the Role of Carbonic Anhydrase in the early Phase of Fish Otolith Mineralization

    NASA Astrophysics Data System (ADS)

    Beier, M.; Anken, R.

    The first step in the formation of fish otoliths, calcified structures which are responsible for the internalization of gravitational information, is based on the action of so-called Tether- (T-) cells. These T-cells appear during the very early development of the inner ear and persist only a few hours. They are characterized by a kinocilium, which is - in contrast to the kinocilium of the later developing sensory hair cells - not mechanosensory, but binds seeding particles containing glycogen, thereby localizing otolith formation. Beating cilia distributed throughout the ear agitate seeding particles, thereby inhibiting premature agglutination. In the later development, a protein matrix is formed and mineralization/crystallization takes place. Since the enzyme carbonic anhydrase (CA) plays a prominent role in otolith mineralization (it provides carbonate for CaCO_3 precipitation), we were prompted to investigate histochemically using larval cichlid fish (Oreochromis mossambicus), whether CA might be present as early as T-cells. Indeed, CA was present in T-cells with prominent amounts of reaction product being located along the kinocilium and around the seeding particles. These results strongly indicate that kinocilia of T-cells may act as structural guides for bicarbonate transportation towards the early otoliths' calcification sites. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

  6. Evidence that an early pregnancy causes a persistent decrease in the number of functional mammary epithelial stem cells—implications for pregnancy-induced protection against breast cancer

    PubMed Central

    Siwko, Stefan K.; Dong, Jie; Lewis, Michael T.; Liu, Hao; Hilsenbeck, Susan G.; Li, Yi

    2009-01-01

    A completed pregnancy at a young age reduces a woman’s lifetime risk of breast cancer by up to 50%. A similar protective effect of an early pregnancy has been observed in rodent models using chemical carcinogens. However, the mechanisms responsible for this protective effect remain unclear. Stem cells have been proposed to be the cells of origin for breast cancer. We hypothesized that an early pregnancy reduces adult levels of either mammary stem cells or mammary multipotent progenitor cells. Unsorted mammary cells from adult mice that had undergone an early parity had the same mammosphere formation efficiency as cells from age-matched virgin mice. However, when we transplanted adult mammary cells in limiting dilutions into cleared fat pads of syngeneic mice, we found a significant reduction in the outgrowth potential of the cells from early parous mice as compared with age-matched virgin mice. The extent of fat pad filling in successful outgrowths did not change, suggesting that while mammary stem cells in parous mice retained their functional competence, the number of mammary stem cells was reduced. Our results provide the first direct evidence that an early pregnancy has an effect on mammary stem cells. PMID:18787212

  7. 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

  8. 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...

  9. 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.

  10. 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

  11. Identification of ABCC8 as a contributory gene to impaired early-phase insulin secretion in NZO mice.

    PubMed

    Andrikopoulos, Sofianos; Fam, Barbara C; Holdsworth, Anita; Visinoni, Sherley; Ruan, Zheng; Stathopoulos, Maria; Thorburn, Anne W; Joannides, Christos N; Cancilla, Michael; Balmer, Lois; Proietto, Joseph; Morahan, Grant

    2016-01-01

    Type 2 diabetes (T2D) is associated with defective insulin secretion, which in turn contributes to worsening glycaemic control and disease progression. The genetic cause(s) associated with impaired insulin secretion in T2D are not well elucidated. Here we used the polygenic New Zealand Obese (NZO) mouse model, which displays all the cardinal features of T2D including hyperglycaemia to identify genes associated with β-cell dysfunction. A genome-wide scan identified a major quantitative trait locus (QTL) on chromosome 7 associated with defective glucose-mediated insulin secretion. Using congenic strains, the locus was narrowed to two candidate genes encoding the components of the KATP channel: Abcc8 (SUR1) and Kcnj11 (Kir6.2). The NZO Abcc8 allele was associated with a ∼211 bp deletion in its transcript and reduced expression of SUR1. Transgenic NZO mice were generated that expressed the WT Abcc8/Kcnj11 genes and displayed significant improvements in early-phase glucose-mediated insulin secretion and glucose tolerance, confirming Abcc8 as a causative gene. Importantly, we showed that despite improving β-cell function in the NZO transgenic mice, there was no enhancement of insulin sensitivity or body weight. This study provides evidence for a role of Abcc8 in early-phase glucose-mediated insulin secretion and validates this gene as a contributor to β-cell dysfunction in T2D. PMID:26493453

  12. Early Investigational Therapeutics for Gastrointestinal Motility Disorders: From Animal Studies to Phase II Trials

    PubMed Central

    Valentin, Nelson; Acosta, Andres; Camilleri, Michael

    2015-01-01

    Introduction The most common gastrointestinal disorders which include evidence of dysmotility include: gastroparesis, the lower functional gastrointestinal disorders associated with altered bowel function [such as chronic (functional) diarrhea, chronic idiopathic constipation (CIC)], and opioid induced constipation (OIC). These conditions, which are grouped as gastrointestinal motility and functional disorders, are characterized by abnormal motor, sensory, or secretory functions that alter bowel function and result in a significant disease burden, since currently available treatments do not completely alleviate symptoms. New drugs are being developed for these disorders, targeting mechanisms involved in the pathophysiology of these diseases, specifically, motor function, intestinal secretion and bile acid modulation. Areas Covered The article provides a brief overview of motility disorders and the drugs approved and currently available for these indications. It also provides an evaluation of the efficacy, safety and possible mechanisms of the drugs currently under investigation for the treatment of gastroparesis, chronic diarrhea, CIC and OIC, based on animal to phase II studies. Medications with complete phase III trials are excluded from this discussion. Expert opinion Treatment of gastrointestinal motility disorders requires the understanding of the pathophysiological mechanisms, biomarkers to identify subgroups of these disorders, and robust pharmacological studies from animal to phase II studies. These are prerequisites for the development of efficacious medications and individualizing therapy in order to enhance the treatment of these patients. PMID:25971881

  13. Serum levels of acute phase proteins: SAA, Hp and progesterone (P4) in mares with early embryonic death.

    PubMed

    Krakowski, L; Krawczyk, C H; Kostro, K; Stefaniak, T; Novotny, F; Obara, J

    2011-08-01

    The study involved 46 healthy purebred Arabian mares exhibiting regular oestrous cycles that underwent artificial insemination (AI). Pregnancy was detected ultrasonographically (US) in 40 mares. In 15 mares in foal, early embryonic death (EED) was observed during the pregnancy days 14-21. Blood for determinations of serum acute phase proteins (SAA and Hp) and progesterone (P4) was sampled 12-24 h before ovulation and the first insemination, at 12, 24, 72, 96 h and on day 7, 10, 14, 21, 35 and 55 after ovulation. The results revealed that in 25 mares without EED, the serum levels of P4, SAA and Hp were within physiological limits; in 15 mares with EED, the levels of SAA and Hp were significantly increased. In seven mares with EED, high levels of SAA and Hp were already found before ovulation and at 12, 24, 72, 96 h as well as on day 7 and 10 post-ovulation, whereas the level of P4 was normal for early pregnancy. In the remaining eight mares with EED, increased levels of SAA and Hp were found at 72 h after ovulation and maintained until day 55. In this group, the level of P4 decreased since 96 h after ovulation. Determinations of SAA, Hp and P4 in mares in early pregnancy (EP) are useful for monitoring normal development of pregnancy and for diagnosis of subclinical genital inflammations, which may lead to EED. PMID:21241377

  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. 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

  16. 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

  17. 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. PMID:10361282

  18. The hyperbaric oxygen preconditioning-induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia

    PubMed Central

    Ostrowski, Robert P.; Graupner, Gerhart; Titova, Elena; Zhang, Jennifer; Chiu, Jeffrey; Dach, Neal; Corleone, Dalia; Tang, Jiping; Zhang, John H.

    2008-01-01

    We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis. One hundred ten male Sprague Dawley (SD) rats (300–350 g body weight) were allocated to the sham group and three other groups with 10 minutes of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments. We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation. PMID:17822911

  19. 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

  20. Cognitive Interventions Targeting Brain Plasticity in the Prodromal and Early Phases of Schizophrenia

    PubMed Central

    Fisher, Melissa; Loewy, Rachel; Hardy, Kate; Schlosser, Danielle; Vinogradov, Sophia

    2016-01-01

    Several important paradigm shifts have occurred in the field of schizophrenia treatment, including an increased focus on early detection, the development of preemptive interventions, and the view of schizophrenia as a neurodevelopmental disease characterized by decreased efficiency and abnormal connectivity in cortical and subcortical neural networks. In this review article, we will briefly describe some of the neural impairments that contribute to the development of schizophrenia, with an emphasis on the impact of stress and trauma on cognitively vulnerable neural systems. We will then present current data on two behavioral interventions that target these critical risk factors and that aim to preempt the onset of schizophrenia in vulnerable individuals or improve the clinical course in recent onset schizophrenia: cognitive therapy and computerized cognitive training. PMID:23297786

  1. 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

  2. [Persistence of negative symptoms in the early phase of schizophrenic psychosis].

    PubMed

    Anczewska, M

    1996-01-01

    103 patients were for the first time admitted to the psychiatric hospital (Institute of Psychiatry and Neurology in Warsaw) between 1976-1983 and received a research diagnosis of schizophrenia (in accordance with the ICD-9 criteria). The course and clinical pattern of the illness were analyzed at a follow-up in 65 patients--re-hospitalized in the 5th year from their first admission. As regards the clinical pattern analysis, it was focused mostly on negative symptoms occurrence, as assessed using the Andreasen Scales (SANS). The data obtained from the case reports were statistically tested and the results were presented in the tables according to the research questions. The stability of the negative symptoms in the early stage of the schizophrenia psychosis was examined. The author confirms that presence of negative symptoms (alogia, apathy and anhedonia) at first hospitalization has been associated with the symptoms recurrence during rehospitalization at the five-year follow-up. PMID:8848505

  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. 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.

  5. 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

  6. Early vulnerability in the development of the sense of maleness: Castration depression in the phallic-narcissistic phase.

    PubMed

    Bell, Silvia M

    2004-01-01

    This paper considers Brenner's (1975, 1979, 1982) modification of Freud's theory that anxiety is the only signal affect. Brenner introduced the notion that castration depressive affect also can trigger psychic conflict, defense, and symptom formation. Clinical material from the first year of treatment of a three-year-old boy who suffered a regression in daytime bladder control is presented. The focus is threefold: First, to show that the often cited but poorly studied symptom of regression in bladder control may be an indicator of the child 's struggle with the three calamities of childhood (object loss, loss of love, and castration); second, to present data that support the importance in early symptom formation of both anxiety and depressive affect tied to the ideation of castration as well as of object loss; third, to suggest that vulnerability to castration depression is a concept more pertinent to the stage presently labeled the phallic-narcissistic phase, rather than to the oedipal phase of development. The discussion addresses the importance of castration depressive affect as a concept in guiding therapeutic intervention. Vulnerability to castration depressive affect is postulated to be more prominent in the phallic-narcissistic phase because phallic self representation is not yet consolidated. PMID:16240608

  7. Metabolic and structural changes during early maturation of Inga vera seeds are consistent with the lack of a desiccation phase.

    PubMed

    Caccere, Rodrigo; Teixeira, Simone P; Centeno, Danilo C; Figueiredo-Ribeiro, Rita de Cássia L; Braga, Márcia R

    2013-06-15

    Inga vera, native to South America, is an important leguminous species used for ecological restoration of riparian forests and its seeds are among the most recalcitrant ones described up to date. In this work, we analysed the metabolic profile, cell ultrastructure as well as cell wall polysaccharides of I. vera seeds in order to better understand its maturation, which allows embryo germination without a quiescent phase. Increased amounts of citric, glutamic, pyroglutamic, and aspartic acids from stages I to II (120 and 129 days after flowering (DAF)) corroborate the hypothesis of high metabolism, shifting from fermentative to aerobic respiration at seed maturity. This phase was characterized by an extensive vacuolization of embryonic cells, which also indicate high metabolic activity. The proportion of arabinose in the cell walls of embryonic axis (approx. 20%) was lower than those found in some orthodox seeds (nearly 40%), suggesting that arabinose-containing polysaccharides, which are thought to provide more flexibility to the cell wall during natural drying, are less abundant in I. vera seeds. Taken together, our results provide evidence that the major changes occurred during early stages of seed maturation of I. vera, indicating that the rapid temporary metabolic shift observed between stages I and II may be related to the lack of desiccation phase, moving directly to germination. PMID:23384756

  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. 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

  11. Replication stress in early S phase generates apparent micronuclei and chromosome rearrangement in fission yeast

    PubMed Central

    Sabatinos, Sarah A.; Ranatunga, Nimna S.; Yuan, Ji-Ping; Green, Marc D.; Forsburg, Susan L.

    2015-01-01

    DNA replication stress causes genome mutations, rearrangements, and chromosome missegregation, which are implicated in cancer. We analyze a fission yeast mutant that is unable to complete S phase due to a defective subunit of the MCM helicase. Despite underreplicated and damaged DNA, these cells evade the G2 damage checkpoint to form ultrafine bridges, fragmented centromeres, and uneven chromosome segregations that resembles micronuclei. These micronuclei retain DNA damage markers and frequently rejoin with the parent nucleus. Surviving cells show an increased rate of mutation and chromosome rearrangement. This first report of micronucleus-like segregation in a yeast replication mutant establishes underreplication as an important factor contributing to checkpoint escape, abnormal chromosome segregation, and chromosome instability. PMID:26246602

  12. [A case of severe systemic juvenile idiopathic arthritis introduced tocilizumab in early phase of the disease].

    PubMed

    Ikegawa, Takeshi; Yamazaki, Kazuko; Nishimura, Kenichi; Kanetaka, Taichi; Kikuchi, Masako; Nozawa, Tomo; Hara, Ryouki; Sato, Tomomi; Sakurai, Nodoka; Yokota, Shumpei

    2014-01-01

    A 14-year-old boy was admitted in the former hospital with remittent fever, erythematous rash, joint pain, and muscle pain. Antibiotics were ineffectively administered and then, methylprednisolone (mPSL) pulse therapy with methotrexate was introduced under the diagnosis of suspected systemic juvenile idiopathic arthritis (JIA). However, he still had clinical symptoms and signs, and was transferred to our hospital. Re-examination revealed no malignancies including acute leukemia by bone marrow aspiration, no infectious agents by septic work, and no significant increases of antibodies against several viruses including CMV, EBV, HSV, Parvovirus B19, adenovirus, and so forth. FDG-PET demonstrated the accumulation of (18)F-FDG in bone marrows suggesting systemic JIA. Laboratory findings were leukocytosis and granulocytosis, elevated levels of C-reactive protein, D-dimer, ferritin, and interleukin-6. He was finally diagnosed as having severe systemic JIA. Thus, soon after the additional mPSL pulse therapy, tocilizumab (TCZ) was successfully introduced. In conclusion, for systemic JIA patients with severe systemic inflammation, it will be reasonable to introduce tocilizumab earlier than the guideline suggested to reduce side effects of long-term and large amounts of steroids and to protect the transition to macrophage activation syndrome. Further studies will be needed to recommend appropriate timing of tocilizumab introduction. PMID:24974931

  13. Stress protein expression in early phase spinal cord ischemia/reperfusion injury.

    PubMed

    Zhang, Shanyong; Wu, Dankai; Wang, Jincheng; Wang, Yongming; Wang, Guoxiang; Yang, Maoguang; Yang, Xiaoyu

    2013-08-25

    Spinal cord ischemia/reperfusion injury is a stress injury to the spinal cord. Our previous studies using differential proteomics identified 21 differentially expressed proteins (n > 2) in rabbits with spinal cord ischemia/reperfusion injury. Of these proteins, stress-related proteins included protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70. In this study, we established New Zealand rabbit models of spinal cord ischemia/reperfusion injury by abdominal aorta occlusion. Results demonstrated that hind limb function initially improved after spinal cord ischemia/reperfusion injury, but then deteriorated. The pathological morphology of the spinal cord became aggravated, but lessened 24 hours after reperfusion. However, the numbers of motor neurons and interneurons in the spinal cord gradually decreased. The expression of protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70 was induced by ischemia/reperfusion injury. The expression of these proteins increased within 12 hours after reperfusion, and then decreased, reached a minimum at 24 hours, but subsequently increased again to similar levels seen at 6-12 hours, showing a characterization of induction-inhibition-induction. These three proteins were expressed only in cytoplasm but not in the nuclei. Moreover, the expression was higher in interneurons than in motor neurons, and the survival rate of interneurons was greater than that of motor neurons. It is assumed that the expression of stress-related proteins exhibited a protective effect on neurons. PMID:25206532

  14. 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

  15. Practical Guidance for Implementing Predictive Biomarkers into Early Phase Clinical Studies

    PubMed Central

    Marton, Matthew J.; Weiner, Russell

    2013-01-01

    The recent U.S. Food and Drug Administration (FDA) coapprovals of several therapeutic compounds and their companion diagnostic devices (FDA News Release, 2011, 2013) to identify patients who would benefit from treatment have led to considerable interest in incorporating predictive biomarkers in clinical studies. Yet, the translation of predictive biomarkers poses unique technical, logistic, and regulatory challenges that need to be addressed by a multidisciplinary team including discovery scientists, clinicians, biomarker experts, regulatory personnel, and assay developers. These issues can be placed into four broad categories: sample collection, assay validation, sample analysis, and regulatory requirements. In this paper, we provide a primer for drug development teams who are eager to implement a predictive patient segmentation marker into an early clinical trial in a way that facilitates subsequent development of a companion diagnostic. Using examples of nucleic acid-based assays, we briefly review common issues encountered when translating a biomarker to the clinic but focus primarily on key practical issues that should be considered by clinical teams when planning to use a biomarker to balance arms of a study or to determine eligibility for a clinical study. PMID:24236296

  16. 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

  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. PMID:18413605

  18. An initial phase of JNK activation inhibits cell death early in the endoplasmic reticulum stress response.

    PubMed

    Brown, Max; Strudwick, Natalie; Suwara, Monika; Sutcliffe, Louise K; Mihai, Adina D; Ali, Ahmed A; Watson, Jamie N; Schröder, Martin

    2016-06-15

    Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR). In mammalian cells, UPR signals generated by several ER-membrane-resident proteins, including the bifunctional protein kinase endoribonuclease IRE1α, control cell survival and the decision to execute apoptosis. Processing of XBP1 mRNA by the RNase domain of IRE1α promotes survival of ER stress, whereas activation of the mitogen-activated protein kinase JNK family by IRE1α late in the ER stress response promotes apoptosis. Here, we show that activation of JNK in the ER stress response precedes activation of XBP1. This activation of JNK is dependent on IRE1α and TRAF2 and coincides with JNK-dependent induction of expression of several antiapoptotic genes, including cIap1 (also known as Birc2), cIap2 (also known as Birc3), Xiap and Birc6 ER-stressed Jnk1(-/-) Jnk2(-/-) (Mapk8(-/-) Mapk9(-/-)) mouse embryonic fibroblasts (MEFs) display more pronounced mitochondrial permeability transition and increased caspase 3/7 activity compared to wild-type MEFs. Caspase 3/7 activity is also elevated in ER-stressed cIap1(-/-) cIap2(-/-) and Xiap(-/-) MEFs. These observations suggest that JNK-dependent transcriptional induction of several inhibitors of apoptosis contributes to inhibiting apoptosis early in the ER stress response. PMID:27122189

  19. 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

  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. Electronic Monitoring of Medication Adherence in Early Maintenance Phase Treatment for Pediatric Leukemia and Lymphoma: Identifying Patterns of Nonadherence

    PubMed Central

    Drotar, Dennis; Alderfer, Melissa; Donewar, Crista Wetherington; Ewing, Linda; Katz, Ernest R.; Muriel, Anna

    2015-01-01

    Objective To describe patterns of treatment adherence to early maintenance phase therapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). Methods Using an objective observational method (electronic monitoring), adherence was examined for 139 patients aged 7–19 years diagnosed with ALL or LBL across 6 centers. Results The mean adherence percentage was 86.2%. Adherence rates declined over the 1-month of follow-up to 83%. 3 linear trajectories of 6-mercaptopurine adherence were identified: (1) exemplary adherence (n = 99): Averaging nearly 100%; (2) deteriorating (n = 23): Adherence decreased from 100 to 60%; and (3) chronically poor adherence (n = 9): Averaging 40%. Conclusions Adherence promotion interventions might be tailored to subgroups of patients who demonstrated problematic patterns of treatment adherence that could place them at risk for relapse. This research demonstrates the importance of using objective real-time measures of medication adherence for measuring and documenting adherence patterns. PMID:24365698

  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. 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

  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. 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

  6. 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.

  7. 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

  8. Prostaglandin F(2alpha) suppresses early phase of adipogenesis, but is not associated with osteoblastogenesis in mouse mesenchymal stem cells.

    PubMed

    Fujimori, Ko; Ueno, Toshiyuki; Amano, Fumio

    2010-09-01

    In this study, we investigated the roles of prostaglandin (PG) F(2alpha) in the differentiation of mouse ST2 mesenchymal stem cells (MSC) into adipocytes and osteoblasts. PGF(2alpha) was not produced in the undifferentiated ST2 MSC, but its highest level of production was detected at 3h after the initiation of adipogenesis and then quickly decreased. On the contrary, apparent PGF(2alpha) production was not detected during the osteoblastogenesis of ST2 MSC. The PGF(2alpha) production pattern during adipogenesis well resembled the expression profiles of aldo-keto reductase (AKR) 1B3, which acted as the PGF(2alpha) synthase, and cyclooxygenase-2 genes; but the pattern showed a slight delay compared with these profiles. The siRNA for AKR1B3, but not that for AKR1B8 or 1B10, decreased PGF(2alpha) production and enhanced the expression of adipogenic genes, but did not affect the mRNA levels of osteoblastogenic genes, during the adipogenesis of ST2 MSC. The FP receptor was expressed during adipogenesis of ST2 MSC, and its agonist or antagonist suppressed or enhanced, respectively, the lipid accumulation and the adipogenic gene expression; but this receptor was not associated with the osteoblastogenesis. These results indicate that AKR1B3-mediated PGF(2alpha) suppressed the early phase of adipogenesis through FP receptors, but did not affect osteoblastogenesis in ST2 MSC. Therefore, PGF(2alpha) suppressed the progression of early phase adipogenesis after determination of the cell fate that causes MSC to differentiate into adipocytes. PMID:20601070

  9. 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

  10. Effects of Type I Collagen Degradation on the Durability of Three Adhesive Systems in the Early Phase of Dentin Bonding

    PubMed Central

    Hu, Lin; Xiao, Yu-hong; Fang, Ming; Gao, Yu; Huang, Li; Jia, An-qi; Chen, Ji-hua

    2015-01-01

    Objective This study was designed to evaluate the effects of type I collagen degradation on the durability of three adhesive systems in the early phase of dentin bonding. Methods Bonded dentin specimens were prepared using three different types of adhesive systems. Micro-tensile bond strength and degradation of collagen were tested before, and after 1 month or 4 months of aging in artificial saliva. The relationship between micro-tensile bond strength and collagen degradation was analyzed by calculating their Pearson’s correlation coefficient. Results Aging induced time-dependent reduction in micro-tensile bond strengths for all the tested adhesive systems, although such reduction for the single-step self-etching adhesive G-Bond (GB) was not statistically significant. The bond strength of the two-step self-etching primer adhesive system Clearfil SE Bond (SEB) was similar to that of the two-step etch-and-rinse self-priming adhesive system Single Bond 2 (SB), and they were both significantly reduced after one or four months of aging. A negative correlation was found between the degree of collagen degradation and magnitude of micro-tensile bond strength (r = - 0.65, p = 0.003). The Pearson’s correlation coefficient was 0.426, indicating that 42.6% of the aging-induced reduction in bond strength can be explained by the degradation of collagen. Conclusions In the early phase of dentin bonding, there was a negative correlation between the degree of collagen degradation and the magnitude of micro-tensile bond strength. The reduction of bond strength was accompanied by the degradation of collagen. These results provide evidence for the causative relationship between the degradation of collagen and the deterioration of dentin-adhesive interface. PMID:25689141

  11. Sexual polymorphisms of vomeronasal 1 receptor family gene expression in bulls, steers, and estrous and early luteal-phase heifers

    PubMed Central

    KUBO, Haruna; OTSUKA, Midori; KADOKAWA, Hiroya

    2015-01-01

    Vomeronasal 1 receptors (V1R) are a family of receptors for intraspecies chemosignals, including pheromones, and are expressed in the olfactory epithelium (OE) and vomeronasal organ (VO). Even in the well-studied rodents, it is unclear which members of the V1R family cause sexual polymorphisms, as there are numerous genes and it is difficult to quantify their expressions individually. Bovine species carry only 34 V1R homologs, and the OE and VOs are large enough to sample. Here, V1R expression was quantified in the OE and VOs of individual bovines. Based on the 34 gene sequences, we obtained a molecular dendrogram consisting of four clusters and six independent branches. Semi-quantitative RT-PCR was used to obtain gene expression profiles in the VOs and OE of 5 Japanese Black bulls, 5 steers, 7 estrous heifers and 6 early luteal-phase heifers. Ten genes showed significant between-group differences, and 22 showed high expression in VOs than in OE. The bulls showed higher expression of one gene more in OE and another in VOs (both P<0.05) than did steers; both genes belonged to the first cluster. No genes were expressed more abundantly in steers than in bulls. The estrous heifers showed higher expression of a gene of the second cluster in OE, and a gene of the third cluster in VOs (both P<0.05) than did early luteal-phase heifers. These results suggest V1R expression exhibits sexual polymorphisms in cattle. PMID:26477467

  12. Sexual polymorphisms of vomeronasal 1 receptor family gene expression in bulls, steers, and estrous and early luteal-phase heifers.

    PubMed

    Kubo, Haruna; Otsuka, Midori; Kadokawa, Hiroya

    2016-02-01

    Vomeronasal 1 receptors (V1R) are a family of receptors for intraspecies chemosignals, including pheromones, and are expressed in the olfactory epithelium (OE) and vomeronasal organ (VO). Even in the well-studied rodents, it is unclear which members of the V1R family cause sexual polymorphisms, as there are numerous genes and it is difficult to quantify their expressions individually. Bovine species carry only 34 V1R homologs, and the OE and VOs are large enough to sample. Here, V1R expression was quantified in the OE and VOs of individual bovines. Based on the 34 gene sequences, we obtained a molecular dendrogram consisting of four clusters and six independent branches. Semi-quantitative RT-PCR was used to obtain gene expression profiles in the VOs and OE of 5 Japanese Black bulls, 5 steers, 7 estrous heifers and 6 early luteal-phase heifers. Ten genes showed significant between-group differences, and 22 showed high expression in VOs than in OE. The bulls showed higher expression of one gene more in OE and another in VOs (both P<0.05) than did steers; both genes belonged to the first cluster. No genes were expressed more abundantly in steers than in bulls. The estrous heifers showed higher expression of a gene of the second cluster in OE, and a gene of the third cluster in VOs (both P<0.05) than did early luteal-phase heifers. These results suggest V1R expression exhibits sexual polymorphisms in cattle. PMID:26477467

  13. 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

  14. 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.

  15. 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

  16. Expansion and activation kinetics of immune cells during early phase of GVHD in mouse model based on chemotherapy conditioning.

    PubMed

    Sadeghi, Behnam; Al-Hashmi, Suleiman; Hassan, Zuzana; Rozell, Bjorn; Concha, Hernan; Lundmark, Carin; Grönvik, Kjell-Olov; Abedi-Valugerdi, Manuchehr; Hassan, Moustapha

    2010-01-01

    In the present paper, we have investigated early pathophysiological events in graft-versus-host disease (GVHD), a major complication to hematopoietic stem cell transplantation (HSCT). BLLB/c female mice conditioned with busulfan/cyclophosphamide (Bu-Cy) were transplanted with allogeneic male C57BL/6. Control group consisted of syngeneic transplanted Balb/c mice. In allogeneic settings, significant expansion and maturation of donor dendritic cells (DCs) were observed at day +3, while donor T-cells CD8+ were increased at day +5 (230%) compared to syngeneic HSCT. Highest levels of inflammatory cytokines IL-2, IFN-gamma, and TNF-alfa at day +5 matched T-cell activation. Concomitantly naïve T-cells gain effecr-memory phenotype and migrated from spleen to peripheral lymphoid organs. Thus, in the very early phase of GHVD following Bu-Cy conditioning donor, DCs play an important role in the activation of donor T cells. Subsequently, donor naïve T-cells gain effector-memory phenotype and initiate GVHD. PMID:21197273

  17. Human cytomegalovirus mediates cell cycle progression through G(1) into early S phase in terminally differentiated cells.

    PubMed

    Sinclair, J; Baillie, J; Bryant, L; Caswell, R

    2000-06-01

    Terminal differentiation of embryonal carcinoma cells and monocytes has been shown to be important for their permissiveness for human cytomegalovirus (HCMV) infection, even though such terminally differentiated cells have withdrawn from the cell cycle and are, essentially, in G(0) arrest. Recently, data from a number of laboratories have shown that productive infection with HCMV of quiescent fibroblasts held reversibly in G(0) of the cell cycle can result in cell cycle progression, which results eventually in cycle arrest. In contrast to quiescent fibroblasts, the effect of HCMV on cells that have withdrawn irreversibly from the cell cycle due to terminal differentiation has not, so far, been addressed. Here, it is shown that, in cells that have arrested in G(0) as a result of terminal differentiation, HCMV is able to induce cell functions associated with progression of the cell cycle through G(1) into early S phase. This progression is correlated with a direct physical and functional interaction between the HCMV 86 kDa major immediate-early protein (IE86) and the cyclin-dependent kinase inhibitor p21(Cip1). PMID:10811939

  18. Expansion and Activation Kinetics of Immune Cells during Early Phase of GVHD in Mouse Model Based on Chemotherapy Conditioning

    PubMed Central

    Sadeghi, Behnam; Al-Hashmi, Suleiman; Hassan, Zuzana; Rozell, Bjorn; Concha, Hernan; Lundmark, Carin; Grönvik, Kjell-Olov; Abedi-Valugerdi, Manuchehr; Hassan, Moustapha

    2010-01-01

    In the present paper, we have investigated early pathophysiological events in graft-versus-host disease (GVHD), a major complication to hematopoietic stem cell transplantation (HSCT). BLLB/c female mice conditioned with busulfan/cyclophosphamide (Bu-Cy) were transplanted with allogeneic male C57BL/6. Control group consisted of syngeneic transplanted Balb/c mice. In allogeneic settings, significant expansion and maturation of donor dendritic cells (DCs) were observed at day +3, while donor T-cells CD8+ were increased at day +5 (230%) compared to syngeneic HSCT. Highest levels of inflammatory cytokines IL-2, IFN-gamma, and TNF-alfa at day +5 matched T-cell activation. Concomitantly naïve T-cells gain effecr-memory phenotype and migrated from spleen to peripheral lymphoid organs. Thus, in the very early phase of GHVD following Bu-Cy conditioning donor, DCs play an important role in the activation of donor T cells. Subsequently, donor naïve T-cells gain effector-memory phenotype and initiate GVHD. PMID:21197273

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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...

  7. 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…

  8. Early consumption of blueberry diet protects against sex steroid deficiency-induced bone loss in adult female rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We studied the effects of blueberry consumption in early development on bone loss in ovariectomized (OVX) female rats later in life. Weanling female rats were fed AIN-93G semi-purified diets supplemented with 10% whole blueberry powder from PND 21 to PND34 (short-term group), or PND21 to PND81 (chro...

  9. Children with adrenergic manifestations of envenomation after Tityus serrulatus scorpion sting are protected from early anaphylactic antivenom reactions.

    PubMed

    Amaral, C F; Dias, M B; Campolina, D; Proietti, F A; de Rezende, N A

    1994-02-01

    The incidence of early anaphylactic reactions to scorpion antivenom given i.v. after Tityus serrulatus scorpion sting was evaluated in 103 children aged up to 15 years in Belo Horizonte, Brazil. Patients without adrenergic manifestations (Group 1, n = 28) were compared with those who presented systemic involvement that included adrenergic manifestations (Group 2, n = 75). Data were recorded on a proforma and the presence or absence of early anaphylactic reaction was cross-tabulated according to clinical features, sex, age and volume of antivenom used in the treatment. Unpaired Student's t-test was used to calculate significance of differences in age and volume of antivenom used. Multivariate logistic regression was used to determine the effects of clinical features and volume of antivenom as predictors of early anaphylactic reaction to antivenom treatment. Twelve (42.9%) of 28 children included in Group 1 presented early anaphylactic reactions compared with 6 (8%) of 75 children of Group 2 (OR = 8.63; 95% CI: 2.88, 25.7). The reactions were more severe in Group 1. There were no significant differences with respect to age and sex. After adjusting for clinical form, volume of antivenom was not significantly associated with presence of reactions (OR = 1.11; 95% CI: 0.70, 2.80 for each 5.0 ml of antivenom administered). The results show that children with adrenergic manifestations after T. serrulatus scorpion sting had significantly lower anaphylactic reactions to antivenom than those without these manifestations. PMID:8153960

  10. 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…

  11. 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…

  12. Early Effects of Blueberry and Concord Grape Intake on Rat Mammary Gland Development Suggest Potential Protective Mechanisms for Mammary Tumorigenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blueberries (BB) and Concord grapes (CG) are rich in anthocyanins and other polyphenols, which may be linked to reduced incidence of chemically induced mammary carcinogenesis in animal models. We evaluated the early effects of dietary exposure to BB and CG on mammary glands of female rat offspring. ...

  13. 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.

  14. Expression of mitogen-activated protein kinase phosphatase-1 in the early phases of human epithelial carcinogenesis.

    PubMed Central

    Loda, M.; Capodieci, P.; Mishra, R.; Yao, H.; Corless, C.; Grigioni, W.; Wang, Y.; Magi-Galluzzi, C.; Stork, P. J.

    1996-01-01

    Many mitogens and human oncogenes activate extracellular regulated kinases (ERKs), which in turn convey proliferation signals. ERKs or mitogen-activated protein (MAP) kinases are inactivated in vitro by MAP kinase phosphatases (MKPs). The gene encoding one of these MKPs, MKP-1, is a serum-inducible gene and is transcriptionally activated by mitogenic signals in cultured cells. As MKP-1 has been shown to block DNA synthesis by inhibiting ERKs when expressed at elevated levels in cultured cells, it has been suggested that it may act as a tumor suppressor. MKP-1 mRNA and MAP kinase (ERK-1 and -2) protein expression was assessed in 164 human epithelial tumors of diverse tissue origin by in situ hybridization and immunohistochemistry. MKP-1 was overexpressed in the early phases of prostate, colon, and bladder carcinogenesis, with progressive loss of expression with higher histological grade and in metastases. In contrast, breast carcinomas showed significant MKP-1 expression even when poorly differentiated or in late stages of the disease. MKP-1, ERK-1, and ERK-2 were co-expressed in most tumors examined. In a subset of 15 tumors, ERK-1 enzymatic activity as well as structural alterations that might be responsible for loss of function of MKP-1 during tumor progression, were examined. ERK-1 enzymatic activity was found to be elevated despite MKP-1 overexpression. No loss of 5q35-ter (containing the MKP-1 locus) was detected by polymerase chain reaction in metastases compared with primary tumors. Finally, no mutations were found in the catalytic domain of MKP-1. These data indicate that MKP-1 is an early marker for a wide range of human epithelial tumors and suggest that MKP-1 does not behave as a tumor suppressor in epithelial tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8909245

  15. Effect of Metals in Biomimetic Dimetal Complexes on Affinity and Gas-Phase Protection of Phosphate Esters.

    PubMed

    Svane, Simon; Jørgensen, Thomas J D; McKenzie, Christine J; Kjeldsen, Frank

    2015-07-21

    Although the biomimetic dimetal complex [LGa2(OH)2(H2O)2](3+) [L = 2,6-bis((N,N'-bis(2-picolyl)amino)methyl)-4-tertbutylphenolate] provides efficient protection against phosphate loss in phosphopeptides upon collision-induced dissociation tandem mass spectrometry (CID MS/MS), the underlying mechanism remains unknown. Here, we explored the mechanism in detail and investigated the selective binding to phosphate groups in solution. Dimetal complexes containing combinations of Ga(3+), In(3+), Fe(3+), Co(3+), Zn(2+), Cu(2+), and V(2+) were reacted with HPO4(2-), phosphoserine, and a phosphopeptide (FQpSEEQQQTEDELQDK, abbreviated "βcas") and studied with isothermal titration calorimetry (ITC), CID MS/MS, and density functional theory (DFT). Ka for HPO4(2-) binding scaled with the metal charge and was 35-fold larger for [LGa2(OH)2(H2O)2](3+) (3.08 ± 0.31 × 10(6) M(-1)) than for [LZn2(HCOO)2](+). CID MS/MS of [LGa2(βcas)](n+) revealed protection against phosphate detachment (<3% of the total ion intensity). Phosphate detachment from βcas was 22-40% and increased to 42-71% when bound to dimetal complexes of lower charge than {LGa2}(5+). CID data suggests that facile metal-phosphate dissociation is associated with proton transfer from the intermediate oxazoline ring formed in the phosphopeptide to the metal-phosphate complex. The observed phosphate stabilization was attributed to a significant reduction in the gas-phase basicity (GB) of the phosphate group when bound to {LGa2}(5+)/{LIn2}(5+) complex cores. Absence of proton transfer results in formation of an ion-zwitterion intermediate with a greater dissociation threshold. This hypothesis is supported by DFT calculations for [LGa2(PO4)](2+), [LGaZn(PO4)](+), [LZn2(PO4)], and 2,4-dimethyl-3-oxazoline showing that [LGa2(PO4)](2+) is the only compound with a substantial lower GB (321 kJ/mol less) than 2,4-dimethyl-3-oxazoline. PMID:26068532

  16. 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

  17. Caspr3-Deficient Mice Exhibit Low Motor Learning during the Early Phase of the Accelerated Rotarod Task.

    PubMed

    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

  18. Fine scale structures of pulsating auroras in the early recovery phase of substorm using ground-based EMCCD camera

    NASA Astrophysics Data System (ADS)

    Nishiyama, Takanori; Sakanoi, Takeshi; Miyoshi, Yoshizumi; Kataoka, Ryuho; Hampton, Donald; Katoh, Yuto; Asamura, Kazushi; Okano, Shoichi

    2012-10-01

    We have carried out ground-based observations, optimized to temporal and spatial characteristics of pulsating auroras (PAs) in the micro/meso scale, using an electron multiplying charge coupled device (EMCCD) camera with a wide field of view corresponding to 100 × 100 km at an altitude of 110 km and a high sampling rate up to 100 frames per second. We focus on transient PAs propagating southward around 1100 UT, in the early recovery phase of the substorm, on 4th March 2011. Three independent patches (PA1-3) each with different periods between 4 and 7 s were observed, which means that the periodicity was not explained by the electron bounce motion and strongly depended on local plasma conditions in the magnetosphere or in the ionosphere. One more insight is that only PA1 had also a sharp peak of modulations around 1.5 Hz, with a narrow frequency width of 0.30 Hz, and the strong modulations existed as a small spot in the center of PA1. We have also conducted cross spectrum analysis and have obtained coherence and phase distributions for auroral variations between 0.1 and 3.0 Hz. The results indicated that low frequency variations from 0.2 to 0.5 Hz inside PA1-3 propagated as a collective motion in well-defined directions. The estimated horizontal propagation velocities ranged from 50 to 120 km/s at the auroral altitude. The velocities are almost consistent with the Alfven speed at the magnetic equator, which suggests that compressional waves have an effect on PA via modulations of the ambient plasma environment.

  19. 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

  20. 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

    2014-01-01

    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

  1. Early-phase strength gains during traditional resistance training compared with an upper-body air-resistance training device.

    PubMed

    McGinley, Cian; Jensen, Randall L; Byrne, Ciarán A; Shafat, Amir

    2007-05-01

    The purpose of this study was to examine the early-phase adaptations of traditional dynamic constant external resistance (DCER) training vs. a portable upper-body training device (Fortex). The Fortex is a concentric training device based on air resistance. Contractions using this device are slow (1.5-3 s) and have a limited range of motion. The exercises potentially allow maximal muscle action during each contraction. Healthy, sedentary men (n = 30) were assigned to begin either 8 weeks of weight training (W, n = 12) or 8 weeks of Fortex training (F, n = 9), and were compared with a control group (C, n = 9). Exercises were chosen for the W group that would train similar muscle groups and contain a similar volume of repetitions as the F group. However, movement patterns and force curves were not identical. Increases in the upper-arm cross-sectional area were not detected in any of the groups. Both training groups showed strength gains in the various strength tests that were distinct from each other. Our results indicate that both Fortex and DCER training proved effective in eliciting strength gains in sedentary men over an 8-week training period. There are, however, limitations with the Fortex in terms of progression needs and training asymmetry that indicate it should be used as a complement to other training. PMID:17530937

  2. 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

  3. Effects of prior treatment with simvastatin on skeletal muscle structure and mitochondrial enzyme activities during early phases of sepsis

    PubMed Central

    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. PMID:25674200

  4. 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.

  5. Considering baseline factors and early response rates to optimize therapy for chronic myeloid leukemia in chronic phase.

    PubMed

    Akard, Luke P; Bixby, Dale

    2016-05-01

    Multiple BCR-ABL tyrosine kinase inhibitors (TKIs) are available for the treatment of chronic myeloid leukemia in chronic phase (CML-CP), and several baseline and on-treatment predictive factors have been identified that can be used to help guide TKI selection for individual patients. In particular, early molecular response (EMR; BCR-ABL ≤10% on the International Scale at 3 months) has become an accepted benchmark for evaluating whether patients with CML-CP are responding optimally to frontline TKI therapy. Failure to achieve EMR is considered an inadequate initial response according to the National Comprehensive Cancer Network guidelines and a warning response according to the European LeukemiaNet recommendations. Here we review data supporting the importance of achieving EMR for improving patients' long-term outcomes and discuss key considerations for selecting a frontline TKI in light of these data. Because a higher proportion of patients achieve EMR with second-generation TKIs such as nilotinib and dasatinib than with imatinib, these TKIs may be preferable for many patients, particularly those with known negative prognostic factors at baseline. We also discuss other considerations for frontline TKI choice, including toxicities, cost-effectiveness, and the emerging goals of deep molecular response and treatment-free remission. PMID:26726949

  6. 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.

  7. The early phases of bone healing can be differentiated in a rat osteotomy model by focused transverse-transmission ultrasound.

    PubMed

    Rohrbach, Daniel; Preininger, Bernd; Hesse, Bernhard; Gerigk, Hinnerk; Perka, Carsten; Raum, Kay

    2013-09-01

    Here we describe the use of a 5-MHz focused transmission system to image the bone repair region and to distinguish the early healing phases in a rat osteotomy (OT) model. Twelve-month-old female rats underwent a 2-mm OT. After 6 wk of consolidation, 2-D projection images of time-of-flight, speed of sound, and ultrasound attenuation were measured in vitro. The tissue types in the OT gap region were assessed by site-matched histology sections and micro-computed tomography (μCT). In the cases investigated, OT gap regions containing fibrous tissue (group A) were found to have similar properties compared with adjacent muscle tissue, whereas regions filled with cartilage and mineralized callus tissues (group B) differed significantly. Analysis of variance revealed that the healing group had a stronger effect on acoustic parameters (F < 35) than on μCT-based parameters (F < 22). This pilot study reports the feasibility of transverse transmission quantitative ultrasound in assessment of the onset of cartilage formation during callus formation. PMID:23830097

  8. Leaders’ and followers’ individual experiences during the early phase of simulation-based team training: an exploratory study

    PubMed Central

    Meurling, Lisbet; Hedman, Leif; Felländer-Tsai, Li; Wallin, Carl-Johan

    2013-01-01

    Background A growing body of evidence shows that team training can develop essential team skills and contribute to better patient outcomes. Current simulation-based team training (SBTT) programmes most often include targets and feedback focused on the whole team and/or leader, ignoring the follower as a unique entity. By considering followers’ individual experiences, and tailoring behavioural targets for training and feedback, SBTT could be improved. Our aim was to explore the individual experiences and behaviours of leaders and followers during the early phase of SBTT, and we hypothesised that leaders and followers would show different responses. Methods Medical students (n=54) participated in half-day SBTT including three video-recorded scenarios. Self-efficacy was assessed pretraining and post-training. For each scenario (n=36), the individual teamwork behaviours, concentration, mental strain and the team's clinical performance were recorded. Data were analysed using a mixed model allowing for participants to be their own control in their roles as leader or follower. Results Self-efficacy improved. In the role of leader, participants communicated to a greater extent and experienced higher mental strain and concentration than they did in the role of follower. Discussion The increased self-efficacy enables a positive learning outcome after only three scenarios. Individual experiences and behaviours differed between the role of leader and that of follower. By shedding further light on leaders’ and followers’ individual experiences and behaviours, targets for training and feedback could be specified in order to improve SBTT. PMID:23293119

  9. Reduction of Tubular Flow Rate as a Mechanism of Oliguria in the Early Phase of Endotoxemia Revealed by Intravital Imaging.

    PubMed

    Nakano, Daisuke; Doi, Kent; Kitamura, Hiroaki; Kuwabara, Takashige; Mori, Kiyoshi; Mukoyama, Masashi; Nishiyama, Akira

    2015-12-01

    Urine output is widely used as a criterion for the diagnosis of AKI. Although several potential mechanisms of septic AKI have been identified, regulation of urine flow after glomerular filtration has not been evaluated. This study evaluated changes in urine flow in mice with septic AKI. The intratubular urine flow rate was monitored in real time by intravital imaging using two-photon laser microscopy. The tubular flow rate, as measured by freely filtered dye (FITC-inulin or Lucifer yellow), time-dependently declined after LPS injection. At 2 hours, the tubular flow rate was slower in mice injected with LPS than in mice injected with saline, whereas BP and GFR were similar in the two groups. Importantly, fluorophore-conjugated LPS selectively accumulated in the proximal tubules that showed reduced tubular flow at 2 hours and luminal obstruction with cell swelling at 24 hours. Delipidation of LPS or deletion of Toll-like receptor 4 in mice abolished these effects, whereas neutralization of TNF-α had little effect on LPS-induced tubular flow retention. Rapid intravenous fluid resuscitation within 6 hours improved the tubular flow rate only when accompanied by the dilation of obstructed proximal tubules with accumulated LPS. These findings suggest that LPS reduces the intratubular urine flow rate during early phases of endotoxemia through a Toll-like receptor 4-dependent mechanism, and that the efficacy of fluid resuscitation may depend on the response of tubules with LPS accumulation. PMID:25855781

  10. 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

  11. 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.

  12. 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. PMID:23112094

  13. The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells

    PubMed Central

    Hemmingsen, Mette; Vedel, Søren; Skafte-Pedersen, Peder; Sabourin, David; Collas, Philippe; Bruus, Henrik; Dufva, Martin

    2013-01-01

    Introduction High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. Methods and results Adipogenic differentiation of human adipose-derived stem cells (ASCs) cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium). Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin). The positive effects of conditioned medium were observed early in the differentiation process. Conclusions Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment phase of the differentiation process. PMID:23723991

  14. Antibodies against Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion during early phase of acute otitis media.

    PubMed

    Karjalainen, H; Koskela, M; Luotonen, J; Herva, E; Sipilä, P

    1990-01-01

    Serum type (IgG, IgM and IgA-class) and secretory type antibodies specific to Streptococcus pneumoniae (Pn), Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) were measured by enzyme-linked immunosorbent assay (ELISA) in 46 serum and 114 middle ear effusion (MEE) samples from 85 children with acute otitis media (AOM). The samples were obtained within 12 h from the onset of the ear symptoms. Serum (but not secretory) type antibodies to the infecting Pn serotype were found in 24% of the MEE samples of the patients with Pn AOM and, correspondingly, serum and/or secretory type antibodies to Hi and Br were seen in 54% and 63% of the MEE samples of the patients with Hi or Br AOM, respectively. Moreover, antibodies against bacteria other than the causative one could also be found in the MEE. The occurrence of the serum type antibodies against these bacteria in the MEE was closely correlated with their serum levels. The findings of this study indicate that during the very early phase of AOM, the MEE contains both serum type antibodies originating from the serum, and secretory antibodies of middle ear origin. Among them there are antibodies specific to the three most common bacteria causing AOM (Pn, Hi, and Br) regardless of the bacterial etiology of the AOM attack in question. PMID:2106760

  15. 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. PMID:24735209

  16. Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage.

    PubMed

    Li, Jianru; Chen, Jingsen; Mo, Hangbo; Chen, Jingyin; Qian, Cong; Yan, Feng; Gu, Chi; Hu, Qiang; Wang, Lin; Chen, Gao

    2016-05-01

    Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague-Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline's anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH. PMID:26143258

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Grape seed proanthocyanidin extract protects the retina against early diabetic injury by activating the Nrf2 pathway

    PubMed Central

    SUN, YAN; XIU, CAIMEI; LIU, WEI; TAO, YUAN; WANG, JIANRONG; QU, YI

    2016-01-01

    The present study aimed to investigate whether grape seed proanthocyanidin extract (GSPE) has a protective effect on diabetic retinal function. A total of 30 Wistar rats were randomly divided into three equal groups, including the control, diabetic and GSPE-treated diabetic groups. Retinal tissue was harvested and subsequently stained with hematoxylin and eosin. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and methane dicarboxylic aldehyde (MDA) levels were evaluated using respective assay kits; whereas nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression levels were assessed by immunohistochemical and western blot analysis. Cell apoptosis in the retina was determined using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method. The results showed that the structure of the retina was damaged in diabetic rats, as compared with the control rats. Notably, the structure of the retina improved in the GSPE-treated diabetic group, as compared with the diabetic group. SOD and GSH-Px activities were significantly increased in the retina of rats in the GSPE-treated diabetic group, as compared with the diabetic group (P=0.011 and P=0.001, respectively). Furthermore, a significant reduction in MDA was detected (P=0.013) and the expression levels of Nrf2 and HO-1 in the bladders of rats in the GSPE-treated diabetic group were significantly increased, as compared with the diabetic group (P=0.038 and P=0.043, respectively). Apoptosis of retinal cells was significantly increased in the diabetic group, as compared with the control group (P<0.001); a significant reduction was also detected in the GSPE-treated diabetic group, as compared with the diabetic group (P=0.014). These results demonstrate that GSPE administration may protect the retina against hyperglycemic damage, possibly by ameliorating oxidative stress-mediated injury via the activation of the Nrf2 pathway. PMID:27073432

  2. 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

  3. 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. PMID:21491803

  4. 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

  5. Indiana application for interim authorization, phase I, hazardous waste management program--Environmental Protection Agency. Notice of public hearing and public comment period.

    PubMed

    1982-04-12

    EPA regulations to protect human health and the environment from the improper management of hazardous waste were published in the Federal Register on May 19, 1980 (45 FR 33063). These regulations include provisions for authorization of State programs to operate in lieu of the Federal program. Today EPA is announcing the availability for public review of the Indiana application for Phase I Interim Authorization, inviting public comment, and giving notice of a public hearing to be held on the application. PMID:10278124

  6. 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.

  7. 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

  8. 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

  9. 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. PMID:26474039

  10. Neutrophils have a protective role during early stages of Leishmania amazonensis infection in BALB/c mice.

    PubMed

    Sousa, L M A; Carneiro, M B H; Resende, M E; Martins, L S; Dos Santos, L M; Vaz, L G; Mello, P S; Mosser, D M; Oliveira, M A P; Vieira, L Q

    2014-01-01

    Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post-infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6-8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti-L. amazonensis IgG and increased production of IL-10 and IL-17. Because IL-10 is a mediator of susceptibility to Leishmania infection, we blocked IL-10 signalling in neutrophil-depleted mice using anti-IL-10R. Interestingly, inhibition of IL-10 signalling abrogated the increase in parasite loads observed in neutrophil-depleted mice, suggesting that parasite proliferation is at least partially mediated by IL-10. Additionally, we tested the effect of IL-17 in inflammatory macrophages and observed that IL-17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice. PMID:24102495

  11. 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.

  12. 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.

  13. Essential Engagement of Toll-Like Receptor 2 in Initiation of Early Protective Th1 Response against Rough Variants of Mycobacterium abscessus

    PubMed Central

    Kim, Jong-Seok; Kang, Min-Jung; Kim, Woo Sik; Han, Seung Jung; Kim, Hong Min; Kim, Ho Won; Kwon, Kee Woong; Kim, So Jeong; Cha, Seung Bin; Eum, Seok-Yong; Koh, Won-Jung; Cho, Sang-Nae

    2015-01-01

    Although Mycobacterium abscessus (M. abscessus) is becoming more prevalent in patients without overt immunodeficiency, little is known about the factors that contribute to disease susceptibility. This study was undertaken to investigate how Toll-like receptor 2 (TLR2) functionally contributes to the generation of protective immunity against M. abscessus in a morphotype-specific manner. We found that Tlr2−/− mice were extremely susceptible to an intravenous (i.v.) model of infection by M. abscessus rough variants, displaying uncontrolled infection in the lungs and a significantly lower survival rate than with wild-type (WT) mice. This uncontrolled infection resulted from failures in the following processes: (i) production of the crucial cytokines gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70); (ii) early infiltration of neutrophils, monocytes, and dendritic cells (DCs) in the lungs of Tlr2−/− mice; (iii) rapid influx of CD4+ and CD8+ T cells; and (iv) the expansion of memory/effector T cells. Notably, systemic administration of M. abscessus culture filtrate-treated syngeneic DCs from WT mice greatly strengthened immune priming in vivo, resulting in a dramatic reduction in bacterial growth and improved long-term survival in Tlr2−/− mice, with a recovery of protective immunity. Our findings demonstrate that TLR2 is an essential contributor to instructive and effector immunity during M. abscessus infection in a morphotype-specific manner. PMID:25644006

  14. 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

  15. 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

  16. Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes.

    PubMed

    Asensio-López, Mari C; Soler, Fernando; Sánchez-Más, Jesús; Pascual-Figal, Domingo; Fernández-Belda, Francisco; Lax, Antonio

    2016-03-15

    In atrial-derived HL-1 cells, ryanodine receptor and Na(+)/Ca(2+)-exchanger were altered early by 5 μM doxorubicin. The observed effects were an increase of cytosolic Ca(2+) at rest, ensuing ryanodine receptor phosphorylation, and the slowing of Ca(2+) transient decay after caffeine addition. Doxorubicin triggered a linear rise of reactive oxygen species (ROS) with no early effect on mitochondrial inner membrane potential. Doxorubicin and ROS were both detected in mitochondria by colocalization with fluorescence probes and doxorubicin-induced ROS was totally blocked by mitoTEMPO. The NADPH oxidase activity in the mitochondrial fraction was sensitive to inhibition by GKT137831, and doxorubicin-induced ROS decreased gradually as the GKT137831 concentration added in preincubation was increased. When doxorubicin-induced ROS was prevented by GKT137831, the kinetic response revealed a permanent degree of protection that was consistent with mitochondrial NADPH oxidase inhibition. In contrast, the ROS induction by doxorubicin after melatonin preincubation was totally eliminated at first but the effect was completely reversed with time. Limiting the source of ROS production is a better alternative for dealing with oxidative damage than using ROS scavengers. The short-term effect of doxorubicin on Ca(2+) transporters involved in myocardiac contractility was dependent on oxidative damage, and so the impairment was subsequent to ROS production. PMID:26906075

  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. 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

  19. Topologically protected Dirac plasmons and their evolution across the quantum phase transition in a (Bi(1-x)In(x))2Se3 topological insulator.

    PubMed

    Autore, Marta; Giorgianni, Flavio; D' Apuzzo, Fausto; Di Gaspare, Alessandra; Lo Vecchio, Irene; Brahlek, Matthew; Koirala, Nikesh; Oh, Seongshik; Schade, Urlich; Ortolani, Michele; Lupi, Stefano

    2016-02-28

    A 3D Topological Insulator (TI) is an intrinsically stratified electronic material characterized by an insulating bulk and Dirac free electrons at the interface with vacuum or another dielectric. In this paper, we investigate, through terahertz (THz) spectroscopy, the plasmon excitation of Dirac electrons on thin films of (Bi1-xInx)2Se3 TI patterned in the form of a micro-ribbon array, across a Quantum Phase Transition (QPT) from the topological to a trivial insulating phase. The latter is achieved by In doping onto the Bi-site and is characterized by massive electrons at the surface. While the plasmon frequency is nearly independent of In content, the plasmon width undergoes a sudden broadening across the QPT, perfectly mirroring the single particle (free electron) behavior as measured on the same films. This strongly suggests that the topological protection from backscattering characterizing Dirac electrons in the topological phase extends also to their plasmon excitations. PMID:26852877

  20. 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... of each transformer to trip and shut down the diesel engine when a phase-to-frame fault of not more... interrupting device(s) to trip and cause shutdown of the diesel engine when a phase-to-frame fault occurs....

  1. 30 CFR 75.901 - Protection of low- and medium-voltage three-phase circuits used underground.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... diesel engine powering the electrical generator must be approved under 30 CFR part 7, subpart E. (2) A... of each transformer to trip and shut down the diesel engine when a phase-to-frame fault of not more... interrupting device(s) to trip and cause shutdown of the diesel engine when a phase-to-frame fault occurs....

  2. 30 CFR 75.901 - Protection of low- and medium-voltage three-phase circuits used underground.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... diesel engine powering the electrical generator must be approved under 30 CFR part 7, subpart E. (2) A... of each transformer to trip and shut down the diesel engine when a phase-to-frame fault of not more... interrupting device(s) to trip and cause shutdown of the diesel engine when a phase-to-frame fault occurs....

  3. 30 CFR 75.901 - Protection of low- and medium-voltage three-phase circuits used underground.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... diesel engine powering the electrical generator must be approved under 30 CFR part 7, subpart E. (2) A... of each transformer to trip and shut down the diesel engine when a phase-to-frame fault of not more... interrupting device(s) to trip and cause shutdown of the diesel engine when a phase-to-frame fault occurs....

  4. 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.

  5. The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase II gene expression

    PubMed Central

    Johnson, Jennifer; Maher, Pamela

    2009-01-01

    Purpose Eriodictyol, a flavonoid found in citrus fruits, is among the most potent compounds reported to protect human RPE cells from oxidative stress-induced cell death. In the present study, we determined whether eriodictyol-induced phase II protein expression further enhances the resistance of human ARPE-19 cells to oxidative stress. Methods We analyzed the ability of eriodictyol to activate Nrf2 and induce the phase II proteins, heme-oxygenase (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO-1), and the cellular antioxidant glutathione, (GSH). We performed cytoprotection assays in ARPE-19 cells that were overexpressing HO-1 or NQO-1. We compared cell survival after short-term and long-term eriodictyol treatment and tested the mechanism of protection using a dominant negative Nrf2 and an shRNA specific for HO-1. Results We demonstrate that eriodictyol induces the nuclear translocation of Nrf2, enhances the expression of HO-1 and NQO-1, and increases the levels of intracellular glutathione. We show that ARPE-19 cells that overexpress HO-1 or NQO-1 are more resistant to oxidative stress-induced cell death than control cells. We demonstrate that eriodictyol induces long-term protection that is significantly greater than its short-term protection, and this effect is correlated temporally with both the activation of Nrf2 and the induction of phase II enzymes. We demonstrate that this effect can be blocked with the use of a dominant negative to Nrf2 and an shRNA specific to HO-1. Conclusions These findings indicate the greatest benefit from eriodictyol may be its ability to regulate gene expression and enhance multiple cellular defenses to oxidative injury. PMID:19117929

  6. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures.

    PubMed Central

    Van Lenten, B J; Hama, S Y; de Beer, F C; Stafforini, D M; McIntyre, T M; Prescott, S M; La Du, B N; Fogelman, A M; Navab, M

    1995-01-01

    We previously reported that high density lipoprotein (HDL) protects against the oxidative modification of low density lipoprotein (LDL) induced by artery wall cells causing these cells to produce pro-inflammatory molecules. We also reported that enzyme systems associated with HDL were responsible for this anti-inflammatory property of HDL. We now report studies comparing HDL before and during an acute phase response (APR) in both humans and a croton oil rabbit model. In rabbits, from the onset of APR the protective effect of HDL progressively decreased and was completely lost by day three. As serum amyloid A (SAA) levels in acute phase HDL (AP-HDL) increased, apo A-I levels decreased 73%. Concomitantly, paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH) levels in HDL declined 71 and 90%, respectively, from days one to three. After day three, there was some recovery of the protective effect of HDL. AP-HDL from human patients and rabbits but not normal or control HDL (C-HDL) exhibited increases in ceruloplasmin (CP). This increase in CP was not seen in acute phase VLDL or LDL. C-HDL incubated with purified CP and re-isolated (CP-HDL), lost its ability to inhibit LDL oxidation. Northern blot analyses demonstrated enhanced expression of MCP-1 in coculture cells treated with AP-HDL and CP-HDL compared to C-HDL. Enrichment of human AP-HDL with purified PON or PAF-AH rendered AP-HDL protective against LDL modification. We conclude that under basal conditions HDL serves an anti-inflammatory role but during APR displacement and/or exchange of proteins associated with HDL results in a pro-inflammatory molecule. Images PMID:8675645

  7. Topologically protected Dirac plasmons and their evolution across the quantum phase transition in a (Bi1-xInx)2Se3 topological insulator

    NASA Astrophysics Data System (ADS)

    Autore, Marta; Giorgianni, Flavio; D'Apuzzo, Fausto; di Gaspare, Alessandra; Lo Vecchio, Irene; Brahlek, Matthew; Koirala, Nikesh; Oh, Seongshik; Schade, Urlich; Ortolani, Michele; Lupi, Stefano

    2016-02-01

    A 3D Topological Insulator (TI) is an intrinsically stratified electronic material characterized by an insulating bulk and Dirac free electrons at the interface with vacuum or another dielectric. In this paper, we investigate, through terahertz (THz) spectroscopy, the plasmon excitation of Dirac electrons on thin films of (Bi1-xInx)2Se3 TI patterned in the form of a micro-ribbon array, across a Quantum Phase Transition (QPT) from the topological to a trivial insulating phase. The latter is achieved by In doping onto the Bi-site and is characterized by massive electrons at the surface. While the plasmon frequency is nearly independent of In content, the plasmon width undergoes a sudden broadening across the QPT, perfectly mirroring the single particle (free electron) behavior as measured on the same films. This strongly suggests that the topological protection from backscattering characterizing Dirac electrons in the topological phase extends also to their plasmon excitations.A 3D Topological Insulator (TI) is an intrinsically stratified electronic material characterized by an insulating bulk and Dirac free electrons at the interface with vacuum or another dielectric. In this paper, we investigate, through terahertz (THz) spectroscopy, the plasmon excitation of Dirac electrons on thin films of (Bi1-xInx)2Se3 TI patterned in the form of a micro-ribbon array, across a Quantum Phase Transition (QPT) from the topological to a trivial insulating phase. The latter is achieved by In doping onto the Bi-site and is characterized by massive electrons at the surface. While the plasmon frequency is nearly independent of In content, the plasmon width undergoes a sudden broadening across the QPT, perfectly mirroring the single particle (free electron) behavior as measured on the same films. This strongly suggests that the topological protection from backscattering characterizing Dirac electrons in the topological phase extends also to their plasmon excitations. Electronic

  8. Illinois, phase I interim authorization of state hazardous waste management program--Environmental Protection Agency, Region V. Granting of phase I interim authorization to state hazardous waste program.

    PubMed

    1982-05-17

    The State of Illinois has applied for Interim Authorization of its hazardous waste program under Subtitle C of the Resource Conservation and Recovery Act of 1976, as amended (RCRA) and EPA guidelines for the approval of State hazardous waste programs (40 CFR Part 123, Subpart F). USEPA has reviewed the Illinois hazardous waste program and has determined that the Illinois hazardous waste program is substantially equivalent to the Federal program. USEPA is hereby granting Phase I Interim Authorization to Illinois to operate a hazardous waste program in lieu of Phase I of the Federal hazardous waste program in its jurisdiction. PMID:10278121

  9. Mechanism of heat stress-induced cellular senescence elucidates the exclusive vulnerability of early S-phase cells to mild genotoxic stress

    PubMed Central

    Velichko, Artem K.; Petrova, Nadezhda V.; Razin, Sergey V.; Kantidze, Omar L.

    2015-01-01

    Heat stress is one of the best-studied cellular stress factors; however, little is known about its delayed effects. Here, we demonstrate that heat stress induces p21-dependent cellular senescence-like cell cycle arrest. Notably, only early S-phase cells undergo such an arrest in response to heat stress. The encounter of DNA replication forks with topoisomerase I-generated single-stranded DNA breaks resulted in the generation of persistent double-stranded DNA breaks was found to be a primary cause of heat stress-induced cellular senescence in these cells. This investigation of heat stress-induced cellular senescence elucidates the mechanisms underlying the exclusive sensitivity of early S-phase cells to ultra-low doses of agents that induce single-stranded DNA breaks. PMID:26032771

  10. 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

  11. Profiles of mRNA expression for genes involved in implantation, early and middle phases of secretion stage in human endometrium.

    PubMed

    Maslova, M A; Smol'nikova, V Yu; Savilova, A M; Burmenskaya, O V; Bystritskii, A A; Tabolova, V K; Korneeva, I E; Demura, T A; Donnikov, A E

    2015-04-01

    The expression of mRNA of 36 genes involved in implantation was studied by reverse transcription and real-time PCR. Significant differences in mRNA expression during the early and middle stages of the secretion phase were detected for genes mmp7, vegf, il2m, il1β, il8, il18, tnfα, il10, tgfβ, igfbp2, etc. PMID:25894777

  12. 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

  13. 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. PMID:27388912

  14. Staphylococcus Coagulase-Positive Skin Inflammation Associated with Epidermal Growth Factor Receptor-Targeted Therapy: An Early and a Late Phase of Papulopustular Eruptions

    PubMed Central

    David, Michael; Stemmer, Salomon M.

    2010-01-01

    Objective. Cutaneous eruptions, mainly papulopustular, are the most common associated side effects of epidermal growth factor receptor inhibitors (EGFRIs). This study investigated the possible role of bacterial infection in EGFRI-induced eruptions and its relation to clinical morphology. Patients and Methods. The study group consisted of all 29 patients referred for dermatologic evaluation of side effects of cetuximab or erlotinib from March 2008 to November 2009. Specimens were taken for bacterial culture from pustules in patients with grade >1 papulopustular rash and from periungual secretions in patients with paronychia. Results. Twenty-four of 29 patients had a papulopustular reaction; five of 29 had paronychia/xerosis. Of the papulopustular eruption patients, time to rash appearance yielded two distinct groups: early-phase, median 8 days after drug initiation, located mainly on the face (n = 17) and late-phase, median ∼200 days after drug initiation, located mainly on the trunk (n = 7). Bacterial culture grew Staphylococcus aureus (SA) in seven of 13 early-phase patients tested and in all late-phase patients. Treatment consisted of topical steroids with or without topical/systemic antibiotics. All patients had a clear improvement in their cutaneous symptoms within a few days. Dose reduction or temporary discontinuation of the EGFRI was necessary in only four of 29 patients. Conclusions. As described in the literature, EGFRI-induced papulopustular eruption may appear early and probably is an inflammatory process with or without SA secondary infection. The papulopustular eruption may also appear as a late phase, described here for the first time, which is an infectious process with all patients being SA+. The >50% overall incidence of SA infection in our study highlights the need for routine bacterial cultures from EGFRI-induced eruption. PMID:20709888

  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. Interactions of amino acids with oxidized guanine in the gas phase associated with the protection of damaged DNA.

    PubMed

    Zhao, Jing; Yang, Hongfang; Zhang, Meng; Bu, Yuxiang

    2013-04-01

    Density functional theory calculations were employed to study the stabilization process of the guanine radical cation through amino acid interactions as well as to understand the protection mechanisms. On the basis of our calculations, several protection mechanisms are proposed in this work subject to the type of the amino acid. Our results indicate that a series of three-electron bonds can be formed between the amino acids and the guanine radical cation which may serve as relay stations supporting hole transport. In the three-electron-bonded, π-π-stacked, and H-bonded modes, amino acids can protect guanine from oxidation or radiation damage by sharing the hole, while amino acids with reducing properties can repair the guanine radical cation through proton-coupled electron transfer or electron transfer. Another important finding is that positively charged amino acids (ArgH(+), LysH(+), and HisH(+)) can inhibit ionization of guanine through raising its ionization potential. In this situation, a negative dissociation energy for hydrogen bonds in the hole-trapped and positively charged amino acid-Guanine dimer is observed, which explains the low hole-trapping efficiency. We hope that this work provides valuable information on how to protect DNA from oxidation- or radiation-induced damages in biological systems. PMID:23427004

  17. Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes protective T helper 17 cell responses in a toll-like receptor-2-dependent manner.

    PubMed

    Chatterjee, Samit; Dwivedi, Ved Prakash; Singh, Yogesh; Siddiqui, Imran; Sharma, Pawan; Van Kaer, Luc; Chattopadhyay, Debprasad; Das, Gobardhan

    2011-11-01

    Despite its relatively poor efficacy, Bacillus Calmette-Guérin (BCG) has been used as a tuberculosis (TB) vaccine since its development in 1921. BCG induces robust T helper 1 (Th1) immune responses but, for many individuals, this is not sufficient for host resistance against Mycobacterium tuberculosis (M. tb) infection. Here we provide evidence that early secreted antigenic target protein 6 (ESAT-6), expressed by the virulent M. tb strain H37Rv but not by BCG, promotes vaccine-enhancing Th17 cell responses. These activities of ESAT-6 were dependent on TLR-2/MyD88 signalling and involved IL-6 and TGF-β production by dendritic cells. Thus, animals that were previously infected with H37Rv or recombinant BCG containing the RD1 region (BCG::RD1) exhibited improved protection upon re-challenge with virulent H37Rv compared with mice previously infected with BCG or RD1-deficient H37Rv (H37RvΔRD1). However, TLR-2 knockout (TLR-2⁻/⁻) animals neither showed Th17 responses nor exhibited improved protection in response to immunization with H37Rv. Furthermore, H37Rv and BCG::RD1 infection had little effect on the expression of the anti-inflammatory microRNA-146a (miR146a) in dendritic cells (DCs), whereas BCG and H37RvΔRD1 profoundly induced its expression in DCs. Consistent with these findings, ESAT-6 had no effect on miR146a expression in uninfected DCs, but dramatically inhibited its upregulation in BCG-infected or LPS-treated DCs. Collectively, our findings indicate that, in addition to Th1 immunity induced by BCG, RD1/ESAT-6-induced Th17 immune responses are essential for optimal vaccine efficacy. PMID:22102818

  18. Synthesis of all nineteen appropriately protected chiral alpha-hydroxy acid equivalents of the alpha-amino acids for Boc solid-phase depsi-peptide synthesis.

    PubMed

    Deechongkit, Songpon; You, Shu-Li; Kelly, Jeffery W

    2004-02-19

    [reaction: see text] The preparation of depsi-peptides, amide-to-ester-substituted peptides used to probe the role of hydrogen bonding in protein folding energetics, is accomplished by replacing specific l-alpha-amino acid residues by their alpha-hydroxy acid counterparts in a solid-phase synthesis employing a t-Boc strategy. Herein we describe the efficient stereoselective synthesis of all 19 appropriately protected alpha-hydroxy acid equivalents of the l-alpha-amino acids, employing commercially available materials, expanding the number of available alpha-hydroxy acids from 9 to 19. PMID:14961607

  19. Outlook on the phase equilibria of the innovative system of "protected glycerol": 1,4-dioxaspiro[4.5]decane-2-methanol and alternative solvents.

    PubMed

    Melo, Catarina I; Rodrigues, Ana I; Bogel-Łukasik, Rafał; Bogel-Łukasik, Ewa

    2012-02-23

    Fundamental data on 1,4-dioxaspiro[4.5]decane-2-methanol are scarce. This work presents the foremost systematic data on the solubility of 1,4-dioxaspiro[4.5]decane-2-methanol in sustainable solvents such as water and ionic liquids accompanied by the interpretation of interactions occurring in such binary systems. 1,4-Dioxaspiro[4.5]decane-2-methanol, here called protected glycerol, has been synthesized in order to protect the two hydroxyl groups of glycerol, thus avoiding the formation of side products in a specific process. A series of imidazolium salts accompanied by pyridinium, phosphonium, and ammonium ones with various types of counterions were used in this study. The liquid-liquid and solid-liquid equilibrium measurements in binary systems were carried out by using a dynamic method at atmospheric pressure over the temperature range from 273.00 to 378.30 K or below the boiling point of the solvent. Among all tested sustainable solvents, protected glycerol exhibited limited solubility, with only a few of them in the temperature range studied. The majority of the examined ionic liquids, either hydrophilic or hydrophobic, showed complete miscibility with this monohydroxyol. The Fourier-transform infrared (FTIR) spectroscopy studies of solute and solvents showing a miscibility gap and of their mixtures were performed to obtain insight into major inter- and intramolecular interactions in the investigated systems. Furthermore, the differential scanning calorimetry was used for the first time to determine the melting point, the enthalpy of melting, and the temperature and enthalpy of the solid-solid phase transition of 1-allyl-3-methylimidazolium chloride [Amim][Cl]. The results for the solubility of protected glycerol in sustainable solvents can be used to design future alternative reactions, such as telomerization with protected glycerol in ionic liquids for more specific building blocks and extraction/or separation that involves these mixtures. PMID:22236350

  20. Near-infrared studies of nova V5584 Sgr in the pre-maximum and early decline phase

    NASA Astrophysics Data System (ADS)

    Raj, Ashish; Banerjee, D. P. K.; Ashok, N. M.; Kim, Sang Chul

    2015-07-01

    We present near-infrared spectroscopic and photometric observations of nova V5584 Sgr taken during the first 12 d following its discovery on Oct. 26.439 UT 2009. The evolution of the spectra is shown from the initial P Cygni phase to an emission line phase. The prominent carbon lines seen in the JHK spectra closely match those observed in an Fe II class nova outburst. The spectra show first-overtone CO bands in emission between 2.29-2.40 μm. By examining WISE and other publicly available data, we show that the nova underwent a pronounced dust formation phase between February - April 2010.

  1. 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.

  2. 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

  3. 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

  4. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION).

    PubMed

    Jabbour, Elias; Kantarjian, Hagop M; Saglio, Giuseppe; Steegmann, Juan Luis; Shah, Neil P; Boqué, Concepción; Chuah, Charles; Pavlovsky, Carolina; Mayer, Jirí; Cortes, Jorge; Baccarani, Michele; Kim, Dong-Wook; Bradley-Garelik, M Brigid; Mohamed, Hesham; Wildgust, Mark; Hochhaus, Andreas

    2014-01-23

    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

  5. 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

  6. KAP-1 Promotes Resection of Broken DNA Ends Not Protected by γ-H2AX and 53BP1 in G1-Phase Lymphocytes

    PubMed Central

    Tubbs, Anthony T.; Dorsett, Yair; Chan, Elizabeth; Helmink, Beth; Lee, Baeck-Seung; Hung, Putzer; George, Rosmy; Bredemeyer, Andrea L.; Mittal, Anuradha; Pappu, Rohit V.; Chowdhury, Dipanjan; Mosammaparast, Nima; Krangel, Michael S.

    2014-01-01

    The resection of broken DNA ends is required for DNA double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal repair by nonhomologous end joining (NHEJ), the main DSB repair pathway in G1-phase cells. Antigen receptor gene assembly proceeds through DNA DSB intermediates generated in G1-phase lymphocytes by the RAG endonuclease. These DSBs activate ATM, which phosphorylates H2AX, forming γ-H2AX in flanking chromatin. γ-H2AX prevents CtIP from initiating resection of RAG DSBs. Whether there are additional proteins required to promote resection of these DNA ends is not known. KRAB-associated protein 1 (KAP-1) (TRIM28) is a transcriptional repressor that modulates chromatin structure and has been implicated in the repair of DNA DSBs in heterochromatin. Here, we show that in murine G1-phase lymphocytes, KAP-1 promotes resection of DSBs that are not protected by H2AX and its downstream effector 53BP1. In these murine cells, KAP-1 activity in DNA end resection is attenuated by a single-amino-acid change that reflects a KAP-1 polymorphism between primates and other mammalian species. These findings establish KAP-1 as a component of the machinery that can resect DNA ends in G1-phase cells and suggest that there may be species-specific features to this activity. PMID:24842905

  7. 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

  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. 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.

  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. 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.

  12. Changes in histone H1 content and chromatin structure of cells blocked in early S phase by 5-fluorodeoxyuridine and aphidicolin

    SciTech Connect

    D'Anna, J.A.; Tobey, R.A.

    1984-01-01

    The authors have measured changes in histone H1 content and changes in chromatin structure of Chinese hamster (line CHO) cells blocked in early S phase by sequential use of isoleucine deprivation and blockade with 5-fluorodeoxyuridine or aphidicolin. Both the H1:core histone ratio in isolated nuclei and the H1 content of the cell are reduced 20-60%, depending on the duration of the block. The new deoxyribonucleic acid synthesized during S-phase block has a shorter nucleosome repeat length than that of bulk chromatin, but it is nearly equally resistant as bulk DNA to attack by micrococcal nuclease. During the time that H1 content is decreasing, bulk chromatin also undergoes structural changes so that its nucleosome cores appear to be more closely packed along the DNA chain. The losses in H1 content and changes in chromatin structure are similar to those reported for cells blocked in early S phase by hydroxyurea. The results suggest that losses of H1 and changes in chromatin structure are general events which occur when the elongation of initiated replicons or the joining of intermediate-sized DNA fragments is retarded during replication. They are consistent with the notions that (1) H1 is lost from initiated replicons and/or (2) the loss of H1 is part of an alarm response in the cell which might facilitate events leading to gene amplification. 39 references, 5 figures, 3 tables.

  13. Discriminating Characteristics of Families Watching Sesame Street. Early Developmental Adversity Program: Phase III, EDAP Technical Note 15.1.

    ERIC Educational Resources Information Center

    Jordan, Thomas E.

    "Sesame Street" is a television program aimed at stimulating young viewers. This study, a part of the Early Developmental Adversity Program, attempts to discover what demographic characteristics are associated with children who view or do not view "Sesame Street." The subjects of the study were 69 3-year-old children. Black and white, as well as…

  14. Early Identification of Delinquency Prone Youth. The Eau Claire County Youth Study, Phase IV, 1969-1972.

    ERIC Educational Resources Information Center

    Feldhusen, John F.; And Others

    Procedures for early identification of delinquency-prone youth in Eau Claire County, Wisconsin, are described in this report of a 1961-1972 study designed to delineate the problems of aggressive and disruptive classroom behavior as related to delinquency. Data collection began in 1961, when each 3rd-, 6th-, and 9th-grade teacher in Eau Claire…

  15. 4-Hydroxy-2-nonenal upregulates endogenous antioxidants and phase 2 enzymes in rat H9c2 myocardiac cells: protection against overt oxidative and electrophilic injury.

    PubMed

    Zhu, Hong; Zhang, Li; Xi, Xiaoqing; Zweier, Jay L; Li, Yunbo

    2006-08-01

    This study was undertaken to determine if 4-hydroxy-2-nonenal (HNE) could upregulate antioxidants and phase 2 enzymes in rat H9c2 myocardiac cells, and if the upregulated defenses led to cytoprotection against oxidative and electrophilic injury. Incubation of H9c2 cells with HNE at noncytotoxic concentrations resulted in significant induction of cellular catalase, glutathione (GSH), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1), as determined by enzyme activity and/or protein expression. HNE treatment caused increased mRNA expression of catalase, gamma-glutamylcysteine ligase, GST-A1, and NQO1. Pretreatment of H9c2 cells with HNE led to significant protection against cytotoxicity induced by reactive oxygen and nitrogen species. HNE-pretreated cells also exhibited increased resistance to injury elicited by subsequent cytotoxic concentrations of HNE. Taken together, this study demonstrates that several antioxidants and phase 2 enzymes in H9c2 cells are upregulated by HNE and that the increased defenses afford protection against overt oxidative and electrophilic cardiac cell injury. PMID:17015266

  16. 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

  17. Extracting flow parameters of H 1743-322 during early phase of its 2010 outburst using two component advective flow model

    NASA Astrophysics Data System (ADS)

    Debnath, Dipak; Chakrabarti, Sandip K.; Mondal, Santanu

    We study the spectral properties of Galactic transient black hole candidate H~1743-322 during its early phase of 2010 outburst with Two Component Advective Flow (TCAF) model, after its inclusion in spectral analysis software package XSPEC as a local model. For the analysis, spectral data from RXTE/PCA instrument in 2.5-25 keV energy band are used. From the spectral fit, accretion flow parameters such as Keplerian (disk) rate, sub-Keplerian (halo) rate, location of the shock and strength of the shock are directly extracted. QPO frequencies are predicted from the TCAF model spectral fitted shock parameters, `closely' matches with the observed frequencies.

  18. Paclitaxel and carboplatin in early phase studies: Roswell Park Cancer Institute experience in the subset of patients with lung cancer.

    PubMed

    Creaven, P J; Raghavan, D; Pendyala, L; Loewen, G; Kindler, H L; Berghorn, E J

    1997-08-01

    The combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 3-hour infusion followed by carboplatin infused over 30 minutes has been evaluated in a series of phase I studies and is currently being explored in a phase II study in patients with limited- and extensive-stage small cell lung cancer. Pharmacokinetic measurements were performed at all dose levels in the phase I studies, in which the use of granulocyte colony-stimulating factor in previously treated patients enabled more than twice the dose of paclitaxel to be given with low to moderate doses of carboplatin (dosed to a target area under the concentration-time curve of 4.0 mg x min x mL[-1]). Treatment-naive patients tolerated high paclitaxel doses (270 mg/m2) with carboplatin (dosed to a target area under the curve of 4.5 mg x min x mL[-1]) without granulocyte colony-stimulating factor support. Twenty-three patients (including previously treated and untreated) with non-small cell lung cancer were entered at a variety of paclitaxel doses in the phase I studies. At 100 to 205 mg/m2 paclitaxel, none of nine treated patients responded; at 230 to 290 mg/m2, four (29%) of 14 responded. In the phase II study of paclitaxel 250 mg/m2 in previously untreated patients with small cell lung cancer, two of five evaluable patients with extensive-stage disease have shown a partial response. In a preliminary analysis of the pharmacodynamics of paclitaxel in relation to neurotoxicity (dose limiting in two of three phase I studies), neurotoxicity correlated with the total dose of paclitaxel, the area under the curve, and the peak paclitaxel concentration, but not with the length of time plasma paclitaxel levels remained above 0.05 micromol/L. These correlations were not strong, however, and analysis of these data is ongoing. PMID:9331139

  19. 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

  20. [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

  1. Interleukin-1β and Interleukin-6 in Arthritis Animal Models: Roles in the Early Phase of Transition from Acute to Chronic Inflammation and Relevance for Human Rheumatoid Arthritis

    PubMed Central

    Ferraccioli, Gianfranco; Bracci-Laudiero, Luisa; Alivernini, Stefano; Gremese, Elisa; Tolusso, Barbara; De Benedetti, Fabrizio

    2010-01-01

    Tumor necrosis factor-α (TNF-α) is the major target of the therapeutic approach in rheumatoid arthritis. A key issue in the approach to chronic arthritis is the understanding of the crucial molecules driving the transition from the acute phase to the chronic irreversible phase of the disease. In this review we analyzed five experimental arthritis animal models (antigen-induced arthritis, adjuvant-induced arthritis, streptococcal cell wall arthritis, collagen-induced arthritis and SKG) considered as possible scenarios to facilitate interpretation of the biology of human rheumatoid arthritis. The SKG model is strictly dependent on interleukin (IL)-6. In the other models, IL-1β and IL-6, more than TNF-α, appear to be relevant in driving the transition, which suggests that these should be the targets of an early intervention to stop the course toward the chronic form of the disease. PMID:20683549

  2. 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.

  3. 77 FR 58359 - Applications for New Awards; Race to the Top-Early Learning Challenge; Phase 2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ... FR 49654). Conversely, the Department of Education may use any unused FY 2012 funds from the Race to... Federal Register on August 26, 2011 (76 FR 53564), apply to the RTT-ELC Phase 2 application process. The... in the Federal Register on August 26, 2011 (76 FR 53564).) (f) The State will comply with...

  4. Synthesis of protected enantiopure (R) and (S)-α-trifluoromethylalanine containing dipeptide building blocks ready to use for solid phase peptide synthesis.

    PubMed

    Devillers, Emmanuelle; Pytkowicz, Julien; Chelain, Evelyne; Brigaud, Thierry

    2016-06-01

    Considering the increasing importance of fluorinated peptides, the development of efficient and reliable synthetic methods for the incorporation of unnatural fluorinated amino acids into peptides is a current matter of interest. In this study, we report the convenient Boc/benzyl and Cbz/tert-butyl protection of both enantiomers of the quaternarized amino acid α-trifluoromethylalanine [(R)- and (S)-α-Tfm-Ala]. Because of the deactivation of the nitrogen atom of this synthetic amino acid by the strong electron withdrawing trifluoromethyl group, the peptide coupling on this position is a challenge. In order to provide a robust synthetic methodology for the incorporation of enantiopure (R)- and (S)-α-trifluoromethylalanines into peptides, we report herein the preparation of dipeptides ready to use for solid phase peptide synthesis. The difficult peptide coupling on the nitrogen atom of the α-trifluoromethylalanines was performed in solution phase by means of highly electrophilic amino acid chlorides or mixed anhydrides. The synthetic effectiveness of this fluorinated dipeptide building block strategy is illustrated by the solid phase peptide synthesis (SPPS) of the Ac-Ala-Phe-(R)-α-Tfm-Ala-Ala-NH2 tetrapeptide. PMID:26920748

  5. Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early-stage breast cancer

    PubMed Central

    Ng, Terence; Teo, Shu Mei; Yeo, Hui Ling; Shwe, Maung; Gan, Yan Xiang; Cheung, Yin Ting; Foo, Koon Mian; Cham, Mooi Tai; Lee, Jung Ah; Tan, Yee Pin; Fan, Gilbert; Yong, Wei Sean; Preetha, Madhukumar; Loh, Wei-Jen Kiley; Koo, Si-Lin; Jain, Amit; Lee, Guek Eng; Wong, Mabel; Dent, Rebecca; Yap, Yoon Sim; Ng, Raymond; Khor, Chiea Chuen; Ho, Han Kiat; Chan, Alexandre

    2016-01-01

    Background Brain-derived neurotrophic factor (BDNF), a neurotrophin that regulates neuronal function and development, is implicated in several neurodegenerative conditions. Preliminary data suggest that a reduction of BDNF concentrations may lead to postchemotherapy cognitive impairment. We hypothesized that a single nucleotide polymorphism (rs6265) of the BDNF gene may predispose patients to cognitive impairment. This study aimed to evaluate the effect of BDNF gene polymorphism on chemotherapy-associated cognitive impairment. Methods Overall, 145 patients receiving chemotherapy for early-stage breast cancer (mean age: 50.8 ± 8.8 y; 82.1% Chinese) were recruited. Patients' cognitive functions were assessed longitudinally using the validated Functional Assessment of Cancer Therapy–Cognitive Function (v.3) and an objective computerized tool, Headminder. Genotyping was performed using Sanger sequencing. Logistic regression was used to evaluate the association between BDNF Val66Met polymorphism and cognition after adjusting for ethnicity and clinically important covariates. Results Of the 145 patients, 54 (37%) reported cognitive impairment postchemotherapy. The Met/Met genotype was associated with statistically significant lower odds of developing cognitive impairment (odds ratio [OR] = 0.26; 95% CI: 0.08–0.92; P = .036). The Met carriers were less likely to experience impairment in the domains of verbal fluency (OR = 0.34; 95% CI: 0.12–0.90; P = .031) and multitasking ability (OR = 0.37; 95% CI: 0.15–0.91; P = .030) compared with the Val/Val homozygote. No associations were observed between Headminder and the BDNF Val66Met polymorphism. Conclusions This is the first study to provide evidence that carriers of the BDNF Met allele are protected against chemotherapy-associated cognitive impairment. Further studies are required to validate the findings. PMID:26289590

  6. α-Synuclein Protects Against Manganese Neurotoxic Insult During the Early Stages of Exposure in a Dopaminergic Cell Model of Parkinson’s Disease

    PubMed Central

    Harischandra, Dilshan S.; Jin, Huajun; Anantharam, Vellareddy; Kanthasamy, Arthi; Kanthasamy, Anumantha G.

    2015-01-01

    The pathological role of α-synuclein (α-Syn) aggregation in neurodegeneration is well recognized, but the physiological function of normal α-Syn remains unknown. As α-Syn protein contains multiple divalent metal binding sites, herein we conducted a comprehensive characterization of the role of α-Syn in manganese-induced dopaminergic neurotoxicity. We established transgenic N27 dopaminergic neuronal cells by stably expressing human wild-type α-Syn at normal physiological levels. α-Syn-expressing dopaminergic cells significantly attenuated Mn-induced neurotoxicity for 24-h exposures relative to vector control cells. To further explore cellular mechanisms, we studied the mitochondria-dependent apoptotic pathway. Analysis of a key mitochondrial apoptotic initiator, cytochrome c, revealed that α-Syn significantly reduces the Mn-induced cytochrome c release into cytosol. The downstream caspase cascade, involving caspase-9 and caspase-3 activation, during Mn exposure was also largely attenuated in Mn-treated α-Syn cells in a time-dependent manner. α-Syn cells also showed a dramatic reduction in the Mn-induced proteolytic activation of the pro-apoptotic kinase PKCδ. The generation of Mn-induced reactive oxygen species (ROS) did not differ between α-Syn and vector control cells, indicating that α-Syn exerts its protective effect independent of altering ROS generation. Inductively coupled plasma-mass spectrometry (ICP-MS) revealed no significant differences in intracellular Mn levels between treated vector and α-Syn cells. Notably, the expression of wild-type α-Syn in primary mesencephalic cells also rescued cells from Mn-induced neurotoxicity. However, prolonged exposure to Mn promoted protein aggregation in α-Syn-expressing cells. Collectively, these results demonstrate that wild-type α-Syn exhibits neuroprotective effects against Mn-induced neurotoxicity during the early stages of exposure in a dopaminergic neuronal model of PD. PMID:25416158

  7. 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

  8. 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.

  9. Effect of Non-local Thermodynamic Equilibrium Model Atmospheres on Photometric Amplitudes and Phases of Early B-type Pulsating Stars

    NASA Astrophysics Data System (ADS)

    Daszyńska-Daszkiewicz, J.; Szewczuk, W.

    2011-02-01

    Amplitudes and phases of the light variation of a pulsating star in various photometric passbands contain information about the geometry of observed modes. Because oscillation spectra of early B-type main-sequence stars do not exhibit regular patterns, these observables are very often the only ones from which mode identification can be derived. Moreover, these data can yield valuable constraints on mean stellar parameters, subphotospheric convection, microphysics, and atmospheres. We study all possible sources of inaccuracy in theoretical values of the photometric observables, i.e., amplitude ratios and phase differences, of early B-type main-sequence pulsators. Here, we discuss the effects of parameters coming from both model atmospheres and linear nonadiabatic theory of stellar pulsation. In particular, we evaluate for the first time the effect of the departure from the local thermodynamic equilibrium (LTE) approximation. To this end, for non-LTE model atmospheres, we compute tables with the passband fluxes, flux derivatives over effective temperature and gravity, as well as the nonlinear limb-darkening coefficients in 12 passbands most often used. We make these tables publicly available at the Wrocław HELAS Web site.

  10. 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

  11. Increased serum levels of interleukin-6 and von Willenbrand Factor in early phase of acute coronary syndrome in a young and multiethnic Malaysian population

    PubMed Central

    Tiong, Wen Ni; Fong, Alan Yean Yip; Sim, Edmund Ui Hang; Chan, Hiang Chuan; Ong, Tiong Kiam; Chang, Boon Cheng; Sim, Kui Hian

    2012-01-01

    Objective Interleukin-6 (IL6; proinflammatory marker), von Willebrand Factor (vWF; endothelial dysfunction marker) and P-selectin (platelet activation marker), may play important roles in defining the pathogenesis of vulnerable plaques in acute coronary syndrome (ACS). This study aims to investigate the expression and relationship of these markers in early phases of ACS in a young and multiethnic Malaysian population. Design Peripheral whole blood mRNA, and serum levels of IL6, vWF and P-selectin were measured in 22 patients with ACS, and in 28 controls with angiographically significant coronary artery disease without previous ACS events. Venous blood from ACS patients was obtained within 1 h of hospital admission. Results No significant differences of IL6, vWF and P-selectin mRNA levels between ACS and controls were seen. ACS patients had significantly higher serum levels of IL6 and vWF (p<0.001), compared with controls. P-selectin correlated with IL6 (r=0.697, p=0.003) and vWF (r=0.497, p=0.05) at mRNA levels, indicating a possible association between these three indices of ACS pathogenesis. Conclusions Increased serum levels of IL6 and vWF suggest that inflammation and endothelial dysfunction may play a prominent role in the pathogenesis of the disease during the early phase of ACS.

  12. In Vivo Tracking of Human Hematopoiesis Reveals Patterns of Clonal Dynamics during Early and Steady-State Reconstitution Phases.

    PubMed

    Biasco, Luca; Pellin, Danilo; Scala, Serena; Dionisio, Francesca; Basso-Ricci, Luca; Leonardelli, Lorena; Scaramuzza, Samantha; Baricordi, Cristina; Ferrua, Francesca; Cicalese, Maria Pia; Giannelli, Stefania; Neduva, Victor; Dow, David J; Schmidt, Manfred; Von Kalle, Christof; Roncarolo, Maria Grazia; Ciceri, Fabio; Vicard, Paola; Wit, Ernst; Di Serio, Clelia; Naldini, Luigi; Aiuti, Alessandro

    2016-07-01

    Hematopoietic stem/progenitor cells (HSPCs) are capable of supporting the lifelong production of blood cells exerting a wide spectrum of functions. Lentiviral vector HSPC gene therapy generates a human hematopoietic system stably marked at the clonal level by vector integration sites (ISs). Using IS analysis, we longitudinally tracked >89,000 clones from 15 distinct bone marrow and peripheral blood lineages purified up to 4 years after transplant in four Wiskott-Aldrich syndrome patients treated with HSPC gene therapy. We measured at the clonal level repopulating waves, populations' sizes and dynamics, activity of distinct HSPC subtypes, contribution of various progenitor classes during the early and late post-transplant phases, and hierarchical relationships among lineages. We discovered that in-vitro-manipulated HSPCs retain the ability to return to latency after transplant and can be physiologically reactivated, sustaining a stable hematopoietic output. This study constitutes in vivo comprehensive tracking in humans of hematopoietic clonal dynamics during the early and late post-transplant phases. PMID:27237736

  13. A phase I/II trial of stereotactic body radiation therapy (SBRT) for lung metastases: Initial report of dose escalation and early toxicity

    SciTech Connect

    Schefter, Tracey E. . E-mail: Tracey.Schefter@uchsc.edu; Kavanagh, Brian D.; Raben, David; Kane, Madeleine; Chen Changhu; Stuhr, Kelly; Kelly, Karen; Mitchell, John D.; Bunn, Paul A.; Gaspar, Laurie E.

    2006-11-15

    Purpose: To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) for lung metastases. Methods and Materials: A Phase I clinical trial was conducted. Eligible patients had one to three pulmonary metastases from a solid tumor, cumulative tumor diameter <7 cm, and adequate pulmonary function (forced expiratory volume in 1 s {>=}1.0 L). The planning target volume (PTV) was typically constructed from the gross tumor volume (GTV) by adding a 5-mm radial and 10-mm craniocaudal margin. The first cohort received 48 Gy to the PTV in three fractions (F). SBRT dose was escalated in subsequent cohorts up to a preselected maximum of 60 Gy/3 F. The percent of normal lung receiving more than 15 Gy (V{sub 15}) was restricted to less than 35%. Respiratory control and a dynamic conformal arc SBRT technique were used. Dose-limiting toxicity (DLT) included acute Grade 3 lung or esophageal toxicity or any acute Grade 4 toxicity within 3 months. After the Phase I dose escalation, the trial continued as a Phase II study, and patients in this cohort are included to increase the number of patients evaluable for early toxicity assessment. Results: Twenty-five eligible patients have been enrolled to date. In the Phase I component of the trial, there were 12 patients (7 male, 5 female):