Science.gov

Sample records for early phase protective

  1. From protection to entitlement: selecting research subjects for early phase clinical trials involving breakthrough therapies.

    PubMed

    Jecker, Nancy S; Wightman, Aaron G; Rosenberg, Abby R; Diekema, Douglas S

    2017-04-13

    Our goals are to (1) set forth and defend a multiprinciple system for selecting individuals who meet trial eligibility criteria to participate in early phase clinical trials testing chimeric antigen receptor (CAR T-cell) for acute lymphoblastic leukaemia when demand for participation exceeds spaces available in a trial; (2) show the relevance of these selection criteria to other breakthrough experimental therapies; (3) argue that distinct distributive justice criteria apply to breakthrough experimental therapies, standard research and healthcare and (4) argue that as evidence of benefit increases, the emphasis of justice in research shifts from protecting subjects from harm to ensuring fair access to benefits.

  2. 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.

  3. Olaparib protects cardiomyocytes against oxidative stress and improves graft contractility during the early phase after heart transplantation in rats.

    PubMed

    Korkmaz-Icöz, Sevil; Szczesny, Bartosz; Marcatti, Michela; Li, Shiliang; Ruppert, Mihály; Lasitschka, Felix; Loganathan, Sivakkanan; Szabó, Csaba; Szabó, Gábor

    2017-08-14

    Olaparib, rucaparib and niraparib, potent inhibitors of poly(ADP-ribose) polymerase (PARP) are approved as anti-cancer drugs in humans. Considering the previously demonstrated role of PARP in various forms of acute and chronic myocardial injury, we tested the effects of olaparib in in-vitro models of oxidative stress in cardiomyocytes, and in an in vivo model of cardiac transplantation. H9c2-embryonic rat heart-derived myoblasts pretreated with vehicle or olaparib (10μM) were challenged with either hydrogen peroxide (H2 O2 ) or with glucose oxidase (GOx, which generates H2 O2 in the tissue culture medium). Cell viability assays (MTT, lactate dehydrogenase) and Western blotting for PARP and its product, PAR was performed. Heterotopic heart transplantation was performed in Lewis rats; recipients were treated either with vehicle or olaparib (10 mg kg(-1) ). Left ventricular function of transplanted hearts was monitored via a Millar catheter. Multiple gene expression in the graft was measured by qPCR. Olaparib blocked autoPARylation of PARP1 and attenuated the rapid onset of death in H9c2 cells, induced by H2 O2 , but did not affect cell death following chronic, prolonged oxidative stress induced by GOx. In rats, after transplantation, left ventricular systolic and diastolic function were improved by olaparib. In the transplanted hearts, olaparib also reduced gene expression for c-jun, caspase-12, catalase, and NADPH oxidase-2. Olaparib protected cardiomyocytes against oxidative stress and improved graft contractility in a rat model of heart transplantation. These findings raise the possibility of repurposing this clinically approved oncology drug, to be used in heart transplantation. © 2017 The British Pharmacological Society.

  4. Phase protection system for ac power lines

    NASA Technical Reports Server (NTRS)

    Wong, W. J. (Inventor)

    1974-01-01

    The system described provides protection for phase sensitive loads from being or remaining connected to ac power lines whenever a phase reversal occurs. It comprises a solid state phase detection circuit, a dc power relay circuit, an ac-to-dc converter for energizing the relay circuit, and a bistable four terminal transducer coupled between the phase detection circuit and the power relay circuit, for controlling both circuits.

  5. Topological phases protected by point group symmetry

    DOE PAGES

    Song, Hao; Huang, Sheng -Jie; Fu, Liang; ...

    2017-02-21

    We consider symmetry-protected topological (SPT) phases with crystalline point group symmetry, dubbed point group SPT (pgSPT) phases. We show that such phases can be understood in terms of lower-dimensional topological phases with on-site symmetry and that they can be constructed as stacks and arrays of these lower-dimensional states. This provides the basis for a general framework to classify and characterize bosonic and fermionic pgSPT phases, which can be applied for arbitrary crystalline point group symmetry and in arbitrary spatial dimensions. We develop and illustrate this framework by means of a few examples, focusing on three-dimensional states. We classify bosonic pgSPTmore » phases and fermionic topological crystalline superconductors with ZP2 (reflection) symmetry, electronic topological crystalline insulators (TCIs) with U(1)×ZP2 symmetry, and bosonic pgSPT phases with C2v symmetry, which is generated by two perpendicular mirror reflections. We also study surface properties, with a focus on gapped, topologically ordered surface states. For electronic TCIs, we find a Z8 × Z2 classification, where the Z8 corresponds to known states obtained from noninteracting electrons, and the Z2 corresponds to a “strongly correlated” TCI that requires strong interactions in the bulk. Lastly, our approach may also point the way toward a general theory of symmetry-enriched topological phases with crystalline point group symmetry.« less

  6. 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

  7. Feasibility of maternity protection in early pregnancy.

    PubMed

    Von Busch, Tammy A; Frazier, Linda M; Sigler, Samantha J; Molgaard, Craig A

    2002-01-01

    Many countries have maternity protection laws for women who need job modification or medical leave during pregnancy. This approach will prevent birth defects only if maternal job changes can be made before the critical period of organogenesis, which begins at three weeks' gestation. The authors studied the gestational ages at which pregnant women working with chemicals, radiation, and noise presented for occupational safety and health consultations. The work setting promoted early presentation because the consultation was free, convenient, mandatory, and would not result in job loss. Among the 213 pregnant women evaluated between 1996 and 2000, most (89.5%) had their occupational safety evaluations in the first trimester. Although this sounds ideal, the mean gestational age at presentation was 7.5 weeks, and only 3.3% of occupational health evaluations were initiated by three weeks' gestation. Environmental and biological monitoring showed that none of the women was exposed over occupational limits. These data suggest that a workplace free from reproductive hazards needs to be provided before conception.

  8. 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.

  9. Pharmacogenomics in early-phase clinical development

    PubMed Central

    Burt, Tal; Dhillon, Savita

    2015-01-01

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

  10. Ocular Protection from Laser Hazards. Phase 2

    DTIC Science & Technology

    1993-10-31

    failure of the coatings . "ECd CONFIDENTIAL AND PROPRIETARY INFORMATION" 14 E. Absorbing Polycarbonate Ophthalmic Lenses . Glendale Protective ...addressed in another section of this report. CREOL, however, did study the adhesion differences between polycarbonate lenses coated with a protective hard...University of Central Florida Orlando, FL 32826 29 Dielectric Multilayer Laser Protection Coatings on Polycarbonate Lenses Final Report about

  11. Early Work on Defect Driven Phase Transitions

    NASA Astrophysics Data System (ADS)

    Kosterlitz, J. Michael; Thouless, David J.

    2016-12-01

    This article summarizes the early history of the theory of phase transitions driven by topological defects, such as vortices in superfluid helium films or dislocations and disclinations in two-dimensional solids. We start with a review of our two earliest papers, pointing out their errors and omissions as well as their insights. We then describe the work, partly done by Kosterlitz but mostly done by other people, which corrected these oversights, and applied these ideas to experimental systems, and to numerical and experimental simulations.

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

    PubMed

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

    2014-03-26

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

  13. Early-type galaxy core phase densities

    SciTech Connect

    Carlberg, R. G.; Hartwick, F. D. A. E-mail: hartwick@uvic.ca

    2014-07-01

    Early-type galaxies have projected central density brightness profile logarithmic slopes, γ', ranging from about 0 to 1. We show that γ' is strongly correlated, r = 0.83, with the coarse grain phase density of the galaxy core, Q {sub 0} ≡ ρ/σ{sup 3}. The luminosity-γ' correlation is much weaker, r = –0.51. Q {sub 0} also serves to separate the distribution of steep core profiles, γ' > 0.5, from shallow profiles, γ' < 0.3, although there are many galaxies of intermediate slope, at intermediate Q {sub 0}, in a volume-limited sample. The transition phase density separating the two profile types is approximately 0.003 M {sub ☉} pc{sup –3} km{sup –3} s{sup 3}, which is also where the relation between Q {sub 0} and core mass shows a change in slope, the rotation rate of the central part of the galaxy increases, and the ratio of the black hole to core mass increases. These relations are considered relative to the globular cluster inspiral core buildup and binary black hole core scouring mechanisms for core creation and evolution. Mass-enhanced globular cluster inspiral models have quantitative predictions that are supported by data, but no single model yet completely explains the correlations.

  14. Evaluation of Protective Coatings for Aluminum Torpedoes. Phase 2.

    DTIC Science & Technology

    1988-04-01

    48 is primarily made of 6000 and 7000 series aluminum , both of which are lightweight and strong, but have poor -~ resistance to corrosion. On the...D-A195 153 EVALUATION OF PROTECTIVE COATINGS FOR ALUMINUM 1 TORPEDOES PHASE 20U) CONSTRUCTION ENGINEERING RESEARCH LAB (ARMY) CHAMPAIGN IL S R...Engineering Research Laboratory AD-A195 153 Evaluation of Protective Coatings for Aluminum Torpedoes: Phase II by Susan A. Johnston This report

  15. 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.

  16. Gapped symmetric edges of symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Lu, Yuan-Ming; Lee, Dung-Hai

    2014-05-01

    Symmetry-protected topological (SPT) phases are gapped quantum phases which host symmetry-protected gapless edge excitations. On the other hand, the edge states can be gapped by spontaneously breaking symmetry. We show that topological defects on the symmetry-broken edge cannot proliferate due to their fractional statistics. A gapped symmetric boundary, however, can be achieved between an SPT phase and certain fractionalized phases by condensing the bound state of a topological defect and an anyon. We demonstrate this by two examples in two dimensions: an exactly solvable model for the boundary between a topological Ising paramagnet and the double-semion model, and a fermionic example about the quantum spin Hall edge. Such a hybrid structure containing both SPT phase and fractionalized phase generally support ground-state degeneracy on a torus.

  17. Computational Power of Symmetry-Protected Topological Phases

    NASA Astrophysics Data System (ADS)

    Stephen, David T.; Wang, Dong-Sheng; Prakash, Abhishodh; Wei, Tzu-Chieh; Raussendorf, Robert

    2017-07-01

    We consider ground states of quantum spin chains with symmetry-protected topological (SPT) order as resources for measurement-based quantum computation (MBQC). We show that, for a wide range of SPT phases, the computational power of ground states is uniform throughout each phase. This computational power, defined as the Lie group of executable gates in MBQC, is determined by the same algebraic information that labels the SPT phase itself. We prove that these Lie groups always contain a full set of single-qubit gates, thereby affirming the long-standing conjecture that general SPT phases can serve as computationally useful phases of matter.

  18. Selective Prevention Approaches to Build Protective Factors in Early Intervention

    ERIC Educational Resources Information Center

    Shapiro, Cheri J.

    2014-01-01

    Young children with disabilities may be at elevated risk for behavior problems as well as maltreatment. preventive approaches that can be infused into early intervention services are needed to support parents, build competencies among young children, and enhance protective factors that may temper risk. Two interventions--Stepping Stones Triple P,…

  19. Predicting Reading Disability: Early Cognitive Risk and Protective Factors

    ERIC Educational Resources Information Center

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

    2013-01-01

    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…

  20. Predicting Reading Disability: Early Cognitive Risk and Protective Factors

    ERIC Educational Resources Information Center

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

    2013-01-01

    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…

  1. Experiences of establishing an academic early phase clinical trials unit.

    PubMed

    Brown, Sarah R; Sherratt, Debbie; Booth, Gill; Brown, Julia; Collinson, Fiona; Gregory, Walter; Flanagan, Louise

    2017-08-01

    Early phase trials are essential in drug development, determining appropriate dose levels and assessing preliminary activity. These trials are undertaken by industry and academia, with increasing collaborations between the two. There is pressure to perform these trials quickly, safely, and robustly. However, there are inherent differences between developing and managing early phase, compared to late phase, drug trials. This article describes an approach to establishing an academically led early phase trial portfolio, highlighting lessons learned and sharing experiences. In 2009, the University of Leeds Clinical Trials Research Unit became the Clinical Trials Coordinating Office for Myeloma UK's phase I and II trials. We embarked on a transition from working extensively in phase III to early phase trials development and conduct. This involved evaluating and revising our well-established standard operating procedures, visiting other academic early phase units, and developing essential new documentation and processes. A core team of trial and data managers and statisticians was established to facilitate expertise and knowledge retention. A detailed training plan was implemented focussing on essential standard practices for early phase. These included pharmacovigilance, recruitment, trial design and set-up, data and site monitoring, and oversight committees. Training in statistical methods for early phase trials was incorporated. Initial scoping of early phase trial management and conduct was essential in establishing this early phase portfolio. Many of the processes developed were successful. However, regular review and evaluation were implemented to enable changes and ensure efficiencies. It is recommended that others embarking on this venture build on the experiences described in this article.

  2. Floquet topological phases protected by time glide symmetry

    NASA Astrophysics Data System (ADS)

    Morimoto, Takahiro; Po, Hoi Chun; Vishwanath, Ashvin

    2017-05-01

    We study Floquet topological phases in periodically driven systems that are protected by "time glide symmetry", a combination of reflection and half time period translation. Time glide symmetry is an analog of glide symmetry with partial time translation replacing the partial space translation and, hence, is an intrinsically dynamical symmetry which may be engineered in periodically driven systems by exploiting the controllability of driving. We present lattice models of time glide symmetric Floquet topological insulators in two and three dimensions. The topological numbers characterizing those Floquet topological phases are derived from the half-period time-evolution operator along with time glide operator. Moreover, we classify Floquet topological phases protected by time glide symmetry in general dimensions using a Clifford algebra approach. The obtained classification table is similar to that for topological crystalline insulators protected by static reflection symmetry, but shows nontrivial entries in different combination of symmetries, which clarifies that time glide symmetric Floquet topological phases are a distinct set of topological phases from topological crystalline insulators. We also classify Floquet topological phases with "time screw symmetry", defined as a twofold spatial rotation accompanied by half-period time translation.

  3. 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

  4. 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

  5. Interacting fermionic symmetry-protected topological phases in two dimensions

    NASA Astrophysics Data System (ADS)

    Wang, Chenjie; Lin, Chien-Hung; Gu, Zheng-Cheng

    2017-05-01

    We classify and construct models for two-dimensional (2D) interacting fermionic symmetry-protected topological (FSPT) phases with general finite Abelian unitary symmetry Gf. To obtain the classification, we couple the FSPT system to a dynamical discrete gauge field with gauge group Gf and study braiding statistics in the resulting gauge theory. Under reasonable assumptions, the braiding statistics data allows us to infer a potentially complete classification of 2D FSPT phases with Abelian symmetry. The FSPT models that we construct are simple stacks of the following two kinds of existing models: (i) free-fermion models and (ii) models obtained through embedding of bosonic symmetry-protected topological (BSPT) phases. Interestingly, using these two kinds of models, we are able to realize almost all FSPT phases in our classification, except for one class. We argue that this exceptional class of FSPT phases can never be realized through models (i) and (ii), and therefore can be thought of as intrinsically interacting and intrinsically fermionic. The simplest example of this class is associated with Z4f×Z4×Z4 symmetry. In addition, we show that all 2D FSPT phases with a finite Abelian symmetry of the form Z2f×G can be realized through the above models (i), (ii), or a simple stack of them. Finally, we study the stability of BSPT phases when they are embedded into fermionic systems.

  6. 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.

  7. 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.

  8. Symmetry-protected topological phases, generalized Laughlin argument, and orientifolds

    NASA Astrophysics Data System (ADS)

    Hsieh, Chang-Tse; Sule, Olabode Mayodele; Cho, Gil Young; Ryu, Shinsei; Leigh, Robert G.

    2014-10-01

    We generalize Laughlin's flux insertion argument, originally discussed in the context of the quantum Hall effect, to topological phases protected by non-on-site unitary symmetries, in particular by parity symmetry or parity symmetry combined with an on-site unitary symmetry. As a model, we discuss fermionic or bosonic systems in two spatial dimensions with CP symmetry, which are, by the CPT theorem, related to time-reversal symmetric topological insulators (e.g., the quantum spin Hall effect). In particular, we develop the stability/instability (or "gappability"/"ingappablity") criteria for nonchiral conformal field theories with parity symmetry that may emerge as an edge state of a symmetry-protected topological phase. A necessary ingredient, as it turns out, is to consider the edge conformal field theories on unoriented surfaces, such as the Klein bottle, which arises naturally from enforcing parity symmetry by a projection operation.

  9. Protection of Medical Equipment against Electromagnetic Pulse (EMP): phase I

    DTIC Science & Technology

    1986-06-12

    Sphygmomanometer 2.71 14. Angiographic Injection System 2.71 114. Automatic Digital 5lood Cell Counter 2.71 17. Electrolytic Solution Analyzer 2.83 17...TAD PROTECTION OF MEDICAL EQUIPMENT |. AGAINST ELECTROMAGENTIC PULSE (EMP): 0 PHASE I Final Report 12 June 1986 J. Klebers Supported by: U. S. ARMY...identify by block number) FIELD GROUP SUB-GROUjP Electromagentic Pulse, EMP, Medical Equipment, Nuclear 77 7 Hardlening, Stirvivabi IItty, VulnerabilityP

  10. Protection of Lithium (Li) Anodes Using Dual Phase Electrolytes

    SciTech Connect

    Mikhaylik, Yuriy

    2014-09-30

    Sion Power focused on metallic lithium anode protection, employing the Dual-Phase Electrolyte approach. The objective of this project was to develop a unique electrolyte providing two liquid phases having good Li+ conductivity, self-partitioning and immiscibility, serving separately the cathode and anode electrodes. This Dual-Phase Electrolyte was combined with thin film multi-layer, physical barrier membranes developed partially under a separate ARPA-E funded project. All these protective structures were stabilized by externally applied pressure. This strategy was used for Li-S cells. The development directly addressed cell safety, particularly higher thermal stability, while also allowing higher energies and cycle life. Safety tests showed that 100% of cells with Dual-Phase Electrolyte were intact and did not exhibit thermal runaway up to 178 °C and thus met the project objective of increasing the runaway temperature to >165°C. Cells also passed cycling at USABC Dynamic Stress Test conditions developed for Electric Vehicle applications and generated specific energy > 300 Wh/kg.

  11. Chandra Catches Early Phase of Cosmic Assembly

    NASA Astrophysics Data System (ADS)

    2004-08-01

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

  12. 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.

  13. 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.

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

    PubMed Central

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

    2015-01-01

    Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID:26132568

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

    PubMed

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

    2015-06-29

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

  16. Platelet Induction of the Acute Phase Response Is Protective in Murine Experimental Cerebral Malaria

    PubMed Central

    Aggrey, Angela A.; Srivastava, Kalyan; Field, David J.; Morrell, Craig N.

    2013-01-01

    Platelets are most recognized as the cellular mediator of thrombosis, but they are increasingly appreciated for their immunomodulatory roles, including responses to Plasmodium infection. Platelet interactions with endothelial cells and leukocytes contribute significantly to the pathogenesis of experimental cerebral malaria (ECM). Recently it has been suggested that platelets not only have an adverse role in cerebral malaria, but platelets may also be protective in animal models of uncomplicated malaria. We now demonstrate that these diverse and seemingly contradictory roles for platelets extend to cerebral malaria models and are dependent on the timing of platelet activation during infection. Our data shows that platelets are activated very early in ECM and have a central role in initiation of the acute phase response to blood stage infection. Unlike platelet depletion or inhibition post infection, pre-infection platelet depletion or treatment with a platelet inhibitor is not protective. Additionally, we show that platelet driven acute phase responses have a major role in protecting mice from ECM by limiting parasite growth. Our data now suggests that platelets have a complex role in ECM pathogenesis: platelets help limit parasite growth early post infection, but with continued platelet activation as the disease progresses, platelets contribute to ECM associated inflammation. PMID:23536632

  17. Improving early clinical trial phase identification of promising therapeutics.

    PubMed

    Kent, Thomas A; Shah, Shreyansh D; Mandava, Pitchaiah

    2015-07-21

    This review addresses decision-making underlying the frequent failure to confirm early-phase positive trial results and how to prioritize which early agents to transition to late phase. While unexpected toxicity is sometimes responsible for late-phase failures, lack of efficacy is also frequently found. In stroke as in other conditions, early trials often demonstrate imbalances in factors influencing outcome. Other issues complicate early trial analysis, including unequally distributed noise inherent in outcome measures and variations in natural history among studies. We contend that statistical approaches to correct for imbalances and noise, while likely valid for homogeneous conditions, appear unable to accommodate disease complexity and have failed to correctly identify effective agents. While blinding and randomization are important to reduce selection bias, these methods appear insufficient to insure valid conclusions. We found potential sources of analytical errors in nearly 90% of a sample of early stroke trials. To address these issues, we recommend changes in early-phase analysis and reporting: (1) restrict use of statistical correction to studies where the underlying assumptions are validated, (2) select dichotomous over continuous outcomes for small samples, (3) consider pooled samples to model natural history to detect early therapeutic signals and increase the likelihood of replication in larger samples, (4) report subgroup baseline conditions, (5) consider post hoc methods to restrict analysis to subjects with an appropriate match, and (6) increase the strength of effect threshold given these cumulative sources of noise and potential errors. More attention to these issues should lead to better decision-making regarding selection of agents to proceed to pivotal trials.

  18. Early phase Technology Assessment of nanotechnology in oncology.

    PubMed

    Retèl, Valesca P; Hummel, Marjan J M; van Harten, Willem H

    2008-01-01

    To perform early Technology Assessment (TA) of nanotechnology in oncology. The possibilities of nanotechnology for detection (imaging), diagnosis and treatment of cancer are subject of different research programs where major investments are concerned. As a range of bio- nanotechnologies is expected to enter the oncology field it is relevant to consider the various aspects involved in especially early TA. This article provides two cases of early assessment of (predecessors of) nanotechnologies: Microarray Analysis and Photodynamic Therapy implementation, which methodology can be extrapolated to other nanotechnologies in oncology. Constructive Technology Assessment (CTA) is used for the introduction of technologies that are still in a dynamic phase of development or in an early stage of diffusion. The selection of studied aspects in CTA is based on: clinical aspects (safety, efficacy, and effectiveness), economic (cost-effectiveness), patient related (QoL, ethical/juridical and psychosocial), organizational aspects (diffusion and adoption) and scenario drafting. The features of the technology and the phase of implementation are decisive for choices and timing of the specific aspects to be studied. A framework was drafted to decide on the relevant aspects. In the first case, early implementation of Microarray Analysis; clinical effectiveness, logistics, patient centeredness and scenario drafting were given priority. Related to the diffusion-phase of Photodynamic Therapy however other aspects were evaluated, such as early cost-effectiveness analysis for possible reimbursement. Often CTA will result in a mixed method design. Especially scenario drafting is a powerful instrument to predict possible developments that can be anticipated upon in the assessment. CTA is appropriate for the study of early implementation of new technologies in oncology. In early TA small series often necessitate a mix of quantitative and qualitative methods. The features of nanotechnology

  19. Therapeutic misconception in early phase gene transfer trials.

    PubMed

    Henderson, Gail E; Easter, Michele M; Zimmer, Catherine; King, Nancy M P; Davis, Arlene M; Rothschild, Barbra Bluestone; Churchill, Larry R; Wilfond, Benjamin S; Nelson, Daniel K

    2006-01-01

    Many subjects in early phase clinical trials expect to benefit in some way from the research intervention. It is understandable that people hope for improvement in their condition, no matter what the evidence. Yet unreasonable expectation of medical benefit may reflect problems with informed consent: Investigators may not disclose clearly that direct medical benefit from an early phase experimental intervention is unlikely or impossible, or subjects may not appreciate the differences between treatment and research. This paper presents findings from recent interviews with researchers and subjects and analysis of consent forms in early phase gene transfer research, a cutting-edge technology often called 'gene therapy'. We use three variables to construct a composite measure of therapeutic misconception TM, tapping misconceptions about the purposes of early phase research and the potential for direct medical benefit in these trials. Our multivariate model demonstrates the importance of both subject- and study-level factors as predictors of this TM index: education, disease type, and communication by study personnel about the likelihood of benefit. We hope that this work will deepen the discussion of how to define and measure TM, and refine the specification of factors that are related to subjects' TM.

  20. 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.

  1. Early phase of acute pancreatitis: Assessment and management

    PubMed Central

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

    2014-01-01

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

  2. CCL5 participates in early protection against Mycobacterium tuberculosis.

    PubMed

    Vesosky, Bridget; Rottinghaus, Erin K; Stromberg, Paul; Turner, Joanne; Beamer, Gillian

    2010-06-01

    Control of M.tb, the causative agent of TB, requires immune cell recruitment to form lung granulomas. The chemokines and chemokine receptors that promote cell migration for granuloma formation, however, are not defined completely. As immunity to M.tb manifests slowly in the lungs, a better understanding of specific roles for chemokines, in particular those that promote M.tb-protective T(H)1 responses, may identify targets that could accelerate granuloma formation. The chemokine CCL5 has been detected in patients with TB and implicated in control of M.tb infection. To define a role for CCL5 in vivo during M.tb infection, CCL5 KO mice were infected with a low dose of aerosolized M.tb. During early M.tb infection, CCL5 KO mice localized fewer APCs and chemokine receptor-positive T cells to the lungs and had microscopic evidence of altered cell trafficking to M.tb granulomas. Early acquired immunity and granuloma function were transiently impaired when CCL5 was absent, evident by delayed IFN-gamma responses and poor control of M.tb growth. Lung cells from M.tb-infected CCL5 KO mice eventually reached or exceeded the levels of WT mice, likely as a result of partial compensation by the CCL5-related ligand, CCL4, and not because of CCL3. Finally, our results suggest that most T cells use CCR5 but not CCR1 to interact with these ligands. Overall, these results contribute to a model of M.tb granuloma formation dependent on temporal regulation of chemokines rather than on redundant or promiscuous interactions.

  3. 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.

  4. 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

  5. Telomerase protects adult rodent olfactory ensheathing glia from early senescence.

    PubMed

    Llamusí, María-Beatriz; Rubio, Mari-Paz; Ramón-Cueto, Almudena

    2011-05-01

    Adult olfactory bulb ensheathing glia (OB-OEG) promote the repair of acute, subacute, and chronic spinal cord injuries and autologous transplantation is a feasible approach. There are interspecies differences between adult rodent and primate OB-OEG related to their longevity in culture. Whereas primate OB-OEG exhibit a relatively long life span, under the same culture conditions rodent OB-OEG divide just three to four times, are sensitive to oxidative stress and become senescent after the third week in vitro. Telomerase is a "physiological key regulator" of the life span of normal somatic cells and also has extratelomeric functions such as increased resistance to oxidative stress. To elucidate whether telomerase has a role in the senescence of rodent OB-OEG, we have introduced the catalytic subunit of telomerase mTERT into cultures of these cells by retroviral infection. Native and modified adult rat OB-OEG behaved as telomerase-competent cells as they divided while expressing mTERT but entered senescence once the gene switched off. After ectopic expression of mTERT, OB-OEG resumed division at a nonsenescent rate, expressed p75 and other OEG markers, and exhibited the morphology of nonsenescent OB-OEG. The nonsenescent period of mTERT-OEG lasted 9weeks and then ectopic mTERT switched off and cells entered senescence again. Our results suggest a role of telomerase in early senescence of adult rodent OB-OEG cultures and a protection from oxidative damage. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

  6. Solid phase synthesis of partially protected tocinoic acid: optimization with respect to resin and protecting groups.

    PubMed

    Hlavácek, J; Ragnarsson, U

    2001-07-01

    A few solid phase and solution approaches of good repute were applied in parallel with the aim to provide optimized routes to Boc- and Fmoc-tocinoic acid (3a and 3c) and the corresponding Tyr(Bu(t)) derivatives (3b and 3d). Boc-tocinoic acid is known to couple with tripeptide amides to give substituted oxytocin precursors in high yields, requiring only Boc-cleavage to furnish the corresponding hormone analogs with minimal loss of material. For comparison, two protected linear hexapeptides (2a and 2b) were prepared on three polystyrene supports, two with acid-labile handles and one a conventional chloromethylated resin, in yields of 62-82 and 58-76%, respectively. The intermediate 2a could be converted to 3a with physical data in agreement with those earlier reported. Similarly, the intermediate 2b was converted to 3b. The highest yields for both 2a and 2b were obtained with a 2-chlorotrityl chloride resin, which in addition provided advantages with respect to overall speed and convenience. Additional syntheses of 3c and 3d on this and of 3c on SASRIN resin, in conjunction with trityl instead of benzyl for side-chain protection of cysteine, were also elaborated.

  7. Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

    PubMed Central

    Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

    2016-01-01

    Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, p<0.0001), but was not associated with the therapeutic misconception. (Spearman r=−0.075, p=0.329). Dispositional optimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (p<0.0001) were independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

  8. Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia-Reperfusion Injury.

    PubMed

    Danelli, Luca; Madjene, Lydia Celia; Madera-Salcedo, Iris; Gautier, Gregory; Pacreau, Emeline; Ben Mkaddem, Sanae; Charles, Nicolas; Daugas, Eric; Launay, Pierre; Blank, Ulrich

    2017-03-15

    Ischemia-reperfusion injury (IRI) is an important cause of acute kidney injury that can lead to end-stage renal failure. Although the ensuing inflammatory response can restore homeostasis, a consecutive maladaptive repair and persistent inflammation represent important risk factors for postischemic chronic kidney disease development. In this study, we investigated the role of mast cells in both the early and late phases of the inflammatory response in experimental models of acute and chronic renal IRI using our recently developed mouse model that allows conditional ablation of mast cells. Depletion of mast cells prior to IRI resulted in improved renal function due to diminished local inflammatory cytokine/chemokine levels and neutrophil recruitment to the kidneys after the acute injury phase (48 h post-IRI). Furthermore, although not completely protected, mast cell-depleted mice displayed less organ atrophy and fibrosis than did wild-type mice during the chronic phases (2 and 6 wk post-IRI) of disease development. Conversely, mast cell ablation after the acute phase of IRI had no impact on organ atrophy, tubular necrosis, or fibrosis. Thus, our results suggest a deleterious role of mast cells during the acute inflammatory phase of IRI promoting subsequent fibrosis development, but not during the chronic phase of the disease.

  9. Anyon condensation and a generic tensor-network construction for symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Jiang, Shenghan; Ran, Ying

    2017-03-01

    We present systematic constructions of tensor-network wave functions for bosonic symmetry-protected topological (SPT) phases respecting both onsite and spatial symmetries. From the classification point of view, our results show that in spatial dimensions d =1 ,2 ,3 , the cohomological bosonic SPT phases protected by a general symmetry group SG involving onsite and spatial symmetries are classified by the cohomology group Hd +1[SG,U(1 ) ] , in which both the time-reversal symmetry and mirror-reflection symmetries should be treated as antiunitary operations. In addition, for every SPT phase protected by a discrete symmetry group and some SPT phases protected by continuous symmetry groups, generic tensor-network wave functions can be constructed which would be useful for the purpose of variational numerical simulations. As a by-product, our results demonstrate a generic connection between rather conventional symmetry-enriched topological phases and SPT phases via an anyon condensation mechanism.

  10. 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.

  11. 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

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

    2016-07-01

    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. A total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2)) 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 × 10(9)/L), with equivalence confirmed if 90% and 95% confidence intervals (CIs) were within a 1-day margin. 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. 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. The granulocyte colony-stimulating factor pegfilgrastim is widely used

  12. 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

  13. 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…

  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. 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…

  16. 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…

  17. Early Development of a Hazardous Chemical Protective Ensemble.

    DTIC Science & Technology

    1986-10-01

    the outergarment with a full body cooling garment, pump , and field-serviced ice pouch/heat exchanger. Laboratory evaluations included protection factor...non-polar solvents, and is attacked by polar solvents. This .. combinationprovides versatility through a wide range of chemicals. The second garment...of solvent on sample with syringe. 4. Cover solvent drop with cap and weight and allow drop to sit for 5 minutes. 5. Remove cap and blot away excess

  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. Recruitment Early Warning System. Phase II. Volume 1. Research and Development of the Recruitment EWS (Early Warning System).

    DTIC Science & Technology

    1985-09-30

    36? RECRUITMENT EARLY WARNING SYSTEM PHASE 11 VOLUME I / RESEARCH RND EELOPHE..U) ECONMIC RESEARCH LAS INC RSTM YAPGEENSTOM ET AL. 36 SEP 85 OMR-85...Recruitment Early Warning System, Phase II Final Report (unclassified) 12 PERSONAL AUTHOR(S) Goldberg, Lawrencel Greenston, Peter; Hermansen, Sigurd...FIELD [GROUP SUB-GROUP manpower planning, early warning system, I N /A /A forecasting 𔄃 ABSTRACT (Continue on reverse if necesary and identify by block

  20. Early Human Testing Initiative Phase 1 Regenerative Life Support Systems

    NASA Image and Video Library

    1995-08-08

    Early Human Testing (EHT) Initiative Phase 1 Regenerative Life Support Systems Laboratory (RLSSL). Nigel Packham activities in the Variable Pressure Growth Chamber which he lived inside for 15 days. A crowd of well-wishers outside the test chamber, at the console are John Lewis, Ed Mohr and Marybeth Edeen (15577). Packham exiting the chamber (15578-81). Packham is the focus of television cameras and reporters (15582-3). Don Henninger interviewed by reporters (15584). Packham is presented with a jacket after his stay in the chamber (15585). Packham inside the wheat growth chamber checking the condition of the plants (15586-7, 15597). Packham exercising on a recumbant bicycle (15588, 15592). Packham, through the window into the growth chamber, displays a handful of wheat plants to console monitor Dan Barta (15589-90). Group portrait of the team conducting the Early Human Testing Initiative Phase 1 Regenerative Life Support Systems test and include, front row, from left: Jeff Dominick and Don Overton and back row, from left, unidentified member, Marybeth Edeen, Nigel Packham, John Lewis, Ed Mohr, Dan Barta and Tim Monk (15591). Harry Halford prepares to send a package through the airlock to Packham (15593). Packham displays a handful of wheat plants (15594). Packham fixes himself a bowl of cereal (15595) and retrieves a carton of milk from the refrigerator (15596). Packham retrieves a package from the airlock (15598). Packham packs up trash in plastic bag (15599-600) and sends it back through the airlock (15601). Packham gets a cup of water (15602) and heats it in the microwave (15603).

  1. Selection and application of relay protection for six phase demonstration project

    SciTech Connect

    Rebbapragada, R.V.; Panke, H. ); Pierce, H.J. Jr. ); Stewart, J.R.; Oppel, L.J. )

    1992-10-01

    This paper documents investigations of the protection and control requirements needed for the 115kV Goudey-Oakdale line after it is configured to operate as a single circuit six phase line as part of a High Phase Order (HPO) demonstration project. The paper addresses the required modification and/or additions needed for the existing protection and control equipment located at Goudey Station and Oakdale Substation respectively. This paper describes the criteria selected for the protection of the Goudey-Oakdale transmission line including the transformers required for six phase reconfiguration. It reviews the commercially available digital protection systems applicable to the protection of the Goudey-Oakdale line and their limitations. Requirements for protection and control panels, their location for optimal wiring and facilities to perform tests and measurements are also covered.

  2. 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

  3. PLASMA HEATING IN THE VERY EARLY PHASE OF SOLAR FLARES

    SciTech Connect

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

    2009-11-10

    In this Letter, we analyze soft X-ray (SXR) and hard X-ray (HXR) emission of the 2002 September 20 M1.8 GOES class solar flare observed by the RHESSI and GOES satellites. In this flare event, SXR emission precedes the onset of the main bulk HXR emission by approx5 minutes. This suggests that an additional heating mechanism may be at work at the early beginning of the flare. However, RHESSI spectra indicate a presence of the non-thermal electrons also before the impulsive phase. So, we assumed that a dominant energy transport mechanism during the rise phase of solar flares is electron-beam-driven evaporation. We used non-thermal electron beams derived from RHESSI spectra as the heating source in a hydrodynamic model of the analyzed flare. We showed that energy delivered by non-thermal electron beams is sufficient to heat the flare loop to temperatures in which it emits SXR closely following the GOES 1-8 A light curve. We also analyze the number of non-thermal electrons, the low-energy cutoff, electron spectral indices, and the changes of these parameters with time.

  4. Topological crystalline magnets: Symmetry-protected topological phases of fermions

    NASA Astrophysics Data System (ADS)

    Watanabe, Haruki; Fu, Liang

    2017-02-01

    We introduce a novel class of interaction-enabled topological crystalline insulators in two- and three-dimensional electronic systems, which we call "topological crystalline magnet." It is protected by the product of the time-reversal symmetry T and a mirror symmetry or a rotation symmetry R . A topological crystalline magnet exhibits two intriguing features: (i) it cannot be adiabatically connected to any Slater insulator and (ii) the edge state is robust against coupling electrons to the edge. These features are protected by the anomalous symmetry transformation property (RT ) 2=-1 of the edge state. An anisotropic response to the external magnetic field can be an experimental signature.

  5. 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.

  6. 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.

  7. 77 FR 58301 - Final Requirements-Race to the Top-Early Learning Challenge; Phase 2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ... Final Requirements--Race to the Top--Early Learning Challenge; Phase 2 AGENCY: Department of Education... requirements for Phase 2 of the Race to the Top--Early Learning Challenge (RTT-ELC) program. In Phase 2, we... funds, those funds that remain unawarded would be used to support grants made under the FY 2012 Race to...

  8. Psychosocial Interventions in Reducing Cannabis Use in Early Phase Psychosis

    PubMed Central

    Aydin, Cristina; Tibbo, Philip G.

    2016-01-01

    Objective: Cannabis use in people with early phase psychosis (EPP) can have a significant impact on long-term outcomes. The purpose of this investigation was to describe current cannabis use treatment practices in English-speaking early intervention services (EISs) in Canada and determine if their services are informed by available evidence. Method: Thirty-five Canadian English-speaking EISs for psychosis were approached to complete a survey through email, facsimile, or online in order to collect information regarding their current cannabis use treatment practices. Results: Data were acquired from 27 of the 35 (78%) programs approached. Only 12% of EISs offered formal services that targeted cannabis use, whereas the majority (63%) of EISs offered informal services for all substance use, not specifically cannabis. In programs with informal services, individual patient psychoeducation (86%) was slightly more common than individual motivational interviewing (MI) (76%) followed by group patient psychoeducation (52%) and information handouts (52%). Thirty-seven percent of EISs offered formal services for substance use, and compared to programs with informal services, more MI, cognitive-behavioural therapy, and family services were offered, with individual treatment modalities more common than groups. No EISs used contingency management, even though it has some preliminary evidence in chronic populations. Evidence-based service implementation barriers included appropriate training and administrative support. Conclusions: While most English-speaking Canadian EIS programs offer individual MI and psychoeducation, which is in line with the available literature, there is room for improvement in cannabis treatment services based on current evidence for both people with EPP and their families. PMID:27254846

  9. Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to recurrent infection.

    PubMed

    Johanns, Tanner M; Law, Calvin Y; Kalekar, Lokeshchandra A; O'Donnell, Hope; Ertelt, James M; Rowe, Jared H; Way, Sing Sing

    2011-04-01

    Typhoid fever is a systemic, persistent infection caused by host-specific strains of Salmonella. Although the use of antibiotics has reduced the complications associated with primary infection, recurrent infection remains an important cause of ongoing human morbidity and mortality. Herein, we investigated the impacts of antibiotic eradication of primary infection on protection against secondary recurrent infection. Using a murine model of persistent Salmonella infection, we demonstrate protection against recurrent infection is sustained despite early eradication of primary infection. In this model, protection is not mediated by CD4(+) or CD8(+) T cells because depletion of these cells either alone or in combination prior to rechallenge does not abrogate protection. Instead, infection followed by antibiotic-mediated clearance primes robust levels of Salmonella-specific antibody that can adoptively transfer protection to naïve mice. Thus, eradication of persistent Salmonella infection primes antibody-mediated protective immunity to recurrent infection.

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

    PubMed

    Flemer, Stevenson

    2011-04-18

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

  11. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  12. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  13. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  14. Symmetry-protected topological phases with uniform computational power in one dimension

    NASA Astrophysics Data System (ADS)

    Raussendorf, Robert; Wang, Dong-Sheng; Prakash, Abhishodh; Wei, Tzu-Chieh; Stephen, David T.

    2017-07-01

    We investigate the usefulness of ground states of quantum spin chains with symmetry-protected topological order (SPTO) for measurement-based quantum computation. We show that, in spatial dimension 1, if an SPTO phase protects the identity gate, then, subject to an additional symmetry condition that is satisfied in all cases so far investigated, it can also be used for quantum computation.

  15. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  16. 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.

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

    PubMed

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

    2012-06-01

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

  18. 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.

  19. 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

    2015-04-03

    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.

  20. 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.

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

    DOE PAGES

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

    2015-11-30

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

  2. 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.

  3. "Good intentions, but inadequate practices"--sun protection in early childhood centres, a qualitative study from New Zealand.

    PubMed

    Duignan, Mary; Signal, Louise; Thomson, George

    2014-02-14

    To examine sun protection policies and practices in New Zealand teacher-led early childhood centres, identifying underlying factors and key steps to support effective sun protection. This qualitative study used a review of sun protection information on the New Zealand Ministry of Education early childhood "ECE Lead" website; 10 key informant interviews; and a review of sun protection policy documents provided by key informants. The data indicated a lack of comprehensive sun protection policies and practices; while sunscreen and hats were focused on, sun protective hats, role-modelling and protective clothing were frequently not emphasised. Key underlying reasons for these failures were: (i) insufficient emphasis on sun protection in government early childhood regulatory and monitoring processes, due to focusing on other priorities, and (ii) centre staff lacking access to sun protection information. Recommendations include: (i) that early childhood regulations specifically include sun protection; and (ii) easy access for staff and parents to appropriate evidenced-based information about sun protection. The implications for other countries are that, despite written sun protection policies, and motivated staff, factors such as insufficient emphasis on sun protection in regulations, and inadequate access to information can undermine the quality of sun protection in early childhood centres.

  4. Relationship between symmetry protected topological phases and boundary conformal field theories via the entanglement spectrum

    NASA Astrophysics Data System (ADS)

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

    2017-07-01

    Quantum phase transitions out of a symmetry-protected topological (SPT) phase in (1  +  1) dimensions into an adjacent, topologically distinct SPT phase protected by the same symmetry or a trivial gapped phase, are typically described by a conformal field theory (CFT). At the same time, the low-lying entanglement spectrum of a gapped phase close to such a quantum critical point is known (Cho et al arXiv:1603.04016), very generally, to be universal and described by (gapless) boundary conformal field theory. Using this connection we show that symmetry properties of the boundary conditions in boundary CFT can be used to characterize the symmetry-protected degeneracies of the entanglement spectrum, a hallmark of non-trivial symmetry-protected topological phases. Specifically, we show that the relevant boundary CFT is the orbifold of the quantum critical point with respect to the symmetry group defining the SPT, and that the boundary states of this orbifold carry a quantum anomaly that determines the topological class of the SPT. We illustrate this connection using various characteristic examples such as the time-reversal breaking ‘Kitaev chain’ superconductor (symmetry class D), the Haldane phase, and the {Z}8 classification of interacting topological superconductors in symmetry class BDI in (1  +  1) dimensions.

  5. 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.

  6. 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

  7. [Capabilities from the very beginning. Analysis of early interventions for child protection within the 13th Children and Youth Report].

    PubMed

    Keupp, H

    2010-10-01

    The 13th Children and Youth Report of the Federal Government was tasked with assessing the achievements attained in health-related prevention and health promotion by the Child and Youth Services and evaluating the goals still to be accomplished. Health-relevant development issues in the first phase of life are attachment and autonomy. The concept of early intervention is defined by the threefold responsibility entrusted to the Child and Youth Services: encouraging opportunities for development, providing assistance where resources are inadequate, and protecting children who are endangered or neglected. The greatest need for support is seen to involve children of impoverished or migrant families. The three specified goals require regional networks, which connect the existing support systems, in addition to the Child and Youth Services including pediatrics and child psychiatry, midwives, and early childhood intervention, to form integrated activity systems. Based on this foundation, the aim is then to strengthen parent competence through measures for family enrichment, to offer support related to the social sphere and family structure (e.g., early excellence programs, multigenerational homes, family centers, or family midwives) and to ensure effective child protective services.

  8. 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 at...

  9. 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 at...

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  11. 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 at...

  12. 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 at...

  13. 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…

  14. Early Retirement Incentives with Upper Age Limits under the Older Workers Benefits Protection Act.

    ERIC Educational Resources Information Center

    Swan, Peter N.

    1992-01-01

    Economic underpinnings of retirement incentives and case law leading to the Older Workers Benefits Protection Act (1986) are reviewed; implications for early retirement incentives for college faculty are considered. It is concluded that congressional intent is not to foreclose such incentives and that the Age Discrimination in Employment Act…

  15. 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…

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

    PubMed

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

    2013-07-01

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

  18. 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.

  19. 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

  20. Classification and surface anomaly of glide symmetry protected topological phases in three dimensions

    NASA Astrophysics Data System (ADS)

    Lu, Fuyan; Shi, Bowen; Lu, Yuan-Ming

    2017-07-01

    We study glide protected topological (GSPT) phases of interacting bosons and fermions in three spatial dimensions with certain on-site symmetries. They are crystalline SPT phases, which are distinguished from a trivial product state only in the presence of non-symmorphic glide symmetry. We classify these GSPT phases with various on-site symmetries such as U(1) and time reversal, and show that they can all be understood by stacking and coupling two-dimensional (2D) short-range-entangled phases in a glide-invariant way. Using such a coupled layer construction we study the anomalous surface topological orders of these GSPT phases, which gap out the 2D surface states without breaking any symmetries. While this framework can be applied to any non-symmorphic SPT phase, we demonstrate it in many examples of GSPT phases including the non-symmorphic topological insulator with ‘hourglass fermion’ surface states.

  1. Reversed-phase high-performance liquid chromatography of protected peptide segments.

    PubMed

    Pedroso, E; Grandas, A; Amor, J C; Giralt, E

    1987-11-13

    There is little evidence that reversed-phase high-performance liquid chromatography can be successfully used in the analysis of protected peptide segments. The use of C18 and CN packings and mobile phases containing water-acetonitrile with or without propionic acid in the separation of complex mixtures of synthetic protected peptides is reported. CN packings show a lower efficiency and exhibit poorer resolution than C18 packings but provide different separations. The addition of propionic acid to the mobile phase increases the retention time of peptides but also provides dramatic and useful changes in selectivity. Retention is not related to the molecular mass of the protected peptides but mainly to their hydrophobicity.

  2. Diagnosing gapless edge theory of symmetry protected topological phases via twist operators

    NASA Astrophysics Data System (ADS)

    Cho, Gil; Ryu, Shinsei

    2014-03-01

    A symmetry protected topological (SPT) phase is a new phase of matter which has been actively studied recently. The bulk of a SPT phase is gapped and disordered, and thus it is featureless and difficult to be distinguished from a trivially disordered phase. Remarkably there are gapless edge modes emerging at the boundary between the vacuum and the SPT phase. The gapless edge state is protected by the symmetries of the SPT phase and is a only measurable signature of the SPT phase, and thus we can learn about the SPT phase by studying only its edge modes. One can write down a conformal field theory describing the edge modes, and we consider twist operators of the theory to diagnose the stability of the conformal field theory against symmetry-respecting perturbations. When acted on a state, a twist operator changes the boundary condition for the quantum fields in the conformal field theories. It manifests in the mode expansion of the fields and changes only the behavior of the ``zero'' mode of the fields. At the edge of the SPT phase, we consider only the twist operators consistent with symmetries. Then we investigate the algebra between the twist operators and their symmetry quantum numbers in various methods to study the stability of the edge theory.

  3. Simple examples of Symmetry-Protected Topological phases and Symmetry-Enriched Topological phases of quantum lines

    NASA Astrophysics Data System (ADS)

    Motrunich, Olexei; Geraedts, Scott

    2015-03-01

    We construct models realizing distinct confining phases of lattice gauge theories envisioned in a formal classification of gapped phases of gauge theories by Kapustin and Thorngreen, arXiv:1309.4721. This generalizes ideas of Symmetry-Protected Topological (SPT) phases in Condensed Matter to systems where fundamental microscopic objects are quantum lines, which is of interest in High Energy Theory. Specifically, in (3+1)D, we consider discrete ZN lattice gauge theory models, with two copies of ZN, and construct N distinct confining phases by engineering condensation of bound states of magnetic fluxes (which are quantum lines in 3d) and ZN electric field lines. In (4+1)D, we consider compact quantum electrodynamics (CQED) models, with two copies of CQED, and engineer condensation of bound states of monopoles (which are quantum lines in 4d) and U(1) electric field lines. When the bound states contain a single monopole, we find SPT-like phases of the lattice gauge theory, while when the bound states contain multiple monopoles, we find analogs of Symmetry-Enriched Topological phases, where in the present case we also have fractionalization of Faraday lines. The distinct character of these topological phases of quantum lines is revealed by unusual physics at a boundary.

  4. Universal measurement-based quantum computation in two-dimensional symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Wei, Tzu-Chieh; Huang, Ching-Yu

    2017-09-01

    Recent progress in the characterization of gapped quantum phases has also triggered the search for a universal resource for quantum computation in symmetric gapped phases. Prior works in one dimension suggest that it is a feature more common than previously thought, in that nontrivial one-dimensional symmetry-protected topological (SPT) phases provide quantum computational power characterized by the algebraic structure defining these phases. Progress in two and higher dimensions so far has been limited to special fixed points. Here we provide two families of two-dimensional Z2 symmetric wave functions such that there exists a finite region of the parameter in the SPT phases that supports universal quantum computation. The quantum computational power appears to lose its universality at the boundary between the SPT and the symmetry-breaking phases.

  5. Monolayer-Protected Gold Nanoparticles as a Stationary Phase for Open Tubular Gas Chromatography

    SciTech Connect

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

    2003-09-01

    The use of a thin film of monolayer protected gold nanoparticles (MPNs) as a stationary phase for gas chromatography (GC) is reported. Dodecanethiol-protected gold nanoparticles were prepared and characterized. Deposition of a MPN film was successfully completed within a 2 m, 530 {micro}m (i.d.) deactivated silica capillary using gravity to force a plug of solution containing the MPN material through the capillary for deposition. The presence of a thin MPN film on the GC capillary inside wall was confirmed with SEM analysis with an average film thickness of 60.7 nm measured. The retention behavior of the dodecanethiol MPN stationary phase was studied using four different classes of compounds (alkanes, alcohols, aromatics and ketones) and their retention orders were compared to a commercially available column (AT-1, 100 nm phase thickness). The separation of an eight-component mixture was performed using both isothermal and temperature programming separation methods with the novel dodecanethiol MPN phase. The isothermal separation was then objectively compared to the commercial AT-1 stationary phase column using the same experimental parameters. The commercial column had an efficiency, N, of 6200 (k{prime} = 0.33) while the dodecanethiol MPN stationary phase had an efficiency, N, of 5700 (k{prime} = 0.21) for the same analyte, octane. The reduced plate height, h, for this same analyte was found to be less than 1 at the optimum linear flow velocity. Based upon the efficiencies and reduced plate height studies as a function of linear flow velocity, we conclude that the MPN stationary phase operated at nearly the optimum possible performance level. The robustness of the MPN phase is also discussed with consistent performance observed over several months. Overall, the use of monolayer protected gold nanoparticles as gas chromatographic stationary phase materials appears promising.

  6. Solid-phase route to Fmoc-protected cationic amino acid building blocks.

    PubMed

    Clausen, Jacob Dahlqvist; Linderoth, Lars; Nielsen, Hanne Mørck; Franzyk, Henrik

    2012-10-01

    Diamino acids are commonly found in bioactive compounds, yet only few are commercially available as building blocks for solid-phase peptide synthesis. In the present work a convenient, inexpensive route to multiple-charged amino acid building blocks with varying degree of hydrophobicity was developed. A versatile solid-phase protocol leading to selectively protected amino alcohol intermediates was followed by oxidation to yield the desired di- or polycationic amino acid building blocks in gram-scale amounts. The synthetic sequence comprises loading of (S)-1-(p-nosyl)aziridine-2-methanol onto a freshly prepared trityl bromide resin, followed by ring opening with an appropriate primary amine, on-resin N(β)-Boc protection of the resulting secondary amine, exchange of the N(α)-protecting group, cleavage from the resin, and finally oxidation in solution to yield the target γ-aza substituted building blocks having an Fmoc/Boc protection scheme. This strategy facilitates incorporation of multiple positive charges into the building blocks provided that the corresponding partially protected di- or polyamines are available. An array of compounds covering a wide variety of γ-aza substituted analogs of simple neutral amino acids as well as analogs displaying high bulkiness or polycationic side chains was prepared. Two building blocks were incorporated into peptide sequences using microwave-assisted solid-phase peptide synthesis confirming their general utility.

  7. Symmetry-protected topological phases of one-dimensional interacting fermions with spin-charge separation

    NASA Astrophysics Data System (ADS)

    Montorsi, Arianna; Dolcini, Fabrizio; Iotti, Rita C.; Rossi, Fausto

    2017-06-01

    The low energy behavior of a huge variety of one-dimensional interacting spinful fermionic systems exhibits spin-charge separation, described in the continuum limit by two sine-Gordon models decoupled in the charge and spin channels. Interaction is known to induce, besides the gapless Luttinger liquid phase, eight possible gapped phases, among which are the Mott, Haldane, charge-/spin-density, and bond-ordered wave insulators, and the Luther Emery liquid. Here we prove that some of these physically distinct phases have nontrivial topological properties, notably the presence of degenerate protected edge modes with fractionalized charge/spin. Moreover, we show that the eight gapped phases are in one-to-one correspondence with the symmetry-protected topological (SPT) phases classified by group cohomology theory in the presence of particle-hole symmetry P. The latter result is also exploited to characterize SPT phases by measurable nonlocal order parameters which follow the system evolution to the quantum phase transition. The implications on the appearance of exotic orders in the class of microscopic Hubbard Hamiltonians, possibly without P symmetry at higher energies, are discussed.

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

    PubMed

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

    2015-01-01

    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). 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. 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. 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.

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

    NASA Astrophysics Data System (ADS)

    Isobe, Hiroki; Fu, Liang

    2015-03-01

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

  10. Early, Partial and Phased Retirement Programs in Public Higher Education: A Report on Institutional Experiences.

    ERIC Educational Resources Information Center

    Chronister, Jay L,; Trainer, Aileen C.

    1985-01-01

    The effectiveness in meeting institutional objectives and the costs of early, partial, and phased retirement plans in operation at 51 public higher education institutions, as reported in a survey, are discussed. (MSE)

  11. Early maternal, genetic and environmental components of antioxidant protection, morphology and immunity of yellow-legged gull (Larus michahellis) chicks.

    PubMed

    Rubolini, D; Romano, M; Bonisoli Alquati, A; Saino, N

    2006-09-01

    Maternal effects mediated by egg quality are important sources of offspring phenotypic variation and can influence the course of evolutionary processes. Mothers allocate to the eggs diverse antioxidants that protect the embryo from oxidative stress. In the yellow-legged gull (Larus michahellis), yolk antioxidant capacity varied markedly among clutches and declined considerably with egg laying date. Analysis of bioptic yolk samples from clutches that were subsequently partially cross-fostered revealed a positive effect of yolk antioxidant capacity on embryonic development and chick growth, but not on immunity and begging behaviour, while controlling for parentage and common environment effects. Chick plasma antioxidant capacity varied according to rearing environment, after statistically partitioning out maternal influences mediated by egg quality. Thus, the results of this study indicate that egg antioxidants are important mediators of maternal effects also in wild bird populations, especially during the critical early post-hatching phase.

  12. Early warning of illegal development for protected areas by integrating cellular automata with neural networks.

    PubMed

    Li, Xia; Lao, Chunhua; Liu, Yilun; Liu, Xiaoping; Chen, Yimin; Li, Shaoying; Ai, Bing; He, Zijian

    2013-11-30

    Ecological security has become a major issue under fast urbanization in China. As the first two cities in this country, Shenzhen and Dongguan issued the ordinance of Eco-designated Line of Control (ELC) to "wire" ecologically important areas for strict protection in 2005 and 2009 respectively. Early warning systems (EWS) are a useful tool for assisting the implementation ELC. In this study, a multi-model approach is proposed for the early warning of illegal development by integrating cellular automata (CA) and artificial neural networks (ANN). The objective is to prevent the ecological risks or catastrophe caused by such development at an early stage. The integrated model is calibrated by using the empirical information from both remote sensing and handheld GPS (global positioning systems). The MAR indicator which is the ratio of missing alarms to all the warnings is proposed for better assessment of the model performance. It is found that the fast urban development has caused significant threats to natural-area protection in the study area. The integration of CA, ANN and GPS provides a powerful tool for describing and predicting illegal development which is in highly non-linear and fragmented forms. The comparison shows that this multi-model approach has much better performances than the single-model approach for the early warning. Compared with the single models of CA and ANN, this integrated multi-model can improve the value of MAR by 65.48% and 5.17% respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  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. Motor memory in childhood: early expression of consolidation phase gains.

    PubMed

    Ashtamker, Lilach; Karni, Avi

    2013-11-01

    Are children faster than adults in consolidating procedural knowledge? In adults, the expression of the full benefits of motor practice requires a few hours of consolidation and sleep. Here we show that, although the processes generating the delayed gains continued beyond the first few hours post-training, children expressed significant gains as early as 1 h post-training, in the awake state. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Recruitment Early Warning System and Accession Contingency Planning Process. Phase II. Part 1.

    DTIC Science & Technology

    1984-11-01

    RD-A154 613 RECRUITMENT EARLY WARNING SYSTEM AND ACCESSION i/7 CONTINGENCY PLANNING PROCE..(U) ECONOMIC RESEARCH LAB INC RESTON YA L GOLDBERG ET AL...11 TITLE (include Security Classification) Recruitment Early Warning System and Accession Contingency Planning Process Phase II, Part 1 Final Report...GROUP Early Warning System, Forecasting, Manpower Planning LV &V WA&Vm 19. ABSTRACT (Continue on reverse if necessary and identify by block ny.1ber

  16. Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage

    PubMed Central

    Gao, Xiangqun; Talalay, Paul

    2004-01-01

    The retinal pigment epithelial cell (RPE cell) layer protects the photoreceptors of the retina against oxidative stress. The decline of this capacity is believed to be a major factor in the impairment of vision in age-related macular degeneration. Exposure of human adult RPE cells to UV light at predominantly 320–400 nm (UVA light) in the presence of all-trans-retinaldehyde results in photooxidative cytotoxicity. Significant protection of RPE cells was obtained by prior treatment with phase 2 gene inducers, such as the isothiocyanate sulforaphane or a bis-2-hydroxybenzylideneacetone Michael reaction acceptor. The degree of protection was correlated with the potencies of these inducers in elevating cytoprotective glutathione levels and activities of NAD(P)H:quinone oxidoreductase. In embryonic fibroblasts derived from mice in which the genes for the transcription factor Nrf2, the repressor Keap1, or both Nrf2 and Keap1 were disrupted, the magnitude of resistance to photooxidative damage paralleled the basal levels of glutathione and NAD(P)H:quinone oxidoreductase in each cell type. Demonstration of protection of RPE cells against photooxidative damage by induction of phase 2 proteins may shed light on the role of oxidative injury in ocular disease. Moreover, the finding that dietary inducers provide indirect antioxidant protection suggests novel strategies for preventing chronic degenerative diseases, such as age-related macular degeneration. PMID:15229324

  17. [Occupational therapy: benefit of early intervention in the manic phase].

    PubMed

    Riou, Gaëlle

    When people experiencing a manic episode arrive in hospital, restrictive measures are often put in place. The priority is to avoid all sources of stimulation, especially anything likely to activate the patient. The prescribing of occupational therapy sessions in a well-defined framework may however be appropriate at an early stage in the care. Aside from its effect on the therapeutic alliance, occupational therapy can help on the cognitive and temporal level, increasing awareness of the condition and engagement in the care. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Early Detection of Amyloid Plaque in Alzheimer’s Disease Via X-ray Phase CT

    DTIC Science & Technology

    2015-06-01

    SUBTITLE 5a. CONTRACT NUMBER W81XWH-12-1-0138 Early Detection of Amyloid Plaque in Alzheimer’s Disease Via X - ray Phase CT 5b. GRANT NUMBER 5c...major tasks of Year 1 and Year 2 are the construction and optimization of a prototype x - ray phase contrast CT system to carry out the tasks specified

  19. 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.

  20. Phase transition effect on efficiency of screen protection against elongated hyper-velocity projectiles

    NASA Astrophysics Data System (ADS)

    Rumiantsev, B. V.; Mikhaylin, A. I.

    2017-06-01

    Parameters of an elongated hyper-velocity projectile formed by a detonation of a cumulative charge are determined. The projectile's mass, impact velocity and energy were determined. Penetration pressures are calculated by the deceleration method. Values obtained are compared with commonly known data on phase states of interacting materials - melting and partial evaporation. An elongated projectile penetration through a screen protection into a target is analyzed. Experimental data obtained reveals high efficiency of a screen protection against an elongated hypervelocity projectile in an area of interacting materials evaporation.

  1. 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.

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Protection of low- and medium-voltage three... Underground Low- and Medium-Voltage Alternating Current Circuits § 75.901 Protection of low- and medium-voltage three-phase circuits used underground. (a) Low- and medium-voltage three-phase alternating-current...

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

    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... Underground Low- and Medium-Voltage Alternating Current Circuits § 75.901 Protection of low- and medium-voltage three-phase circuits used underground. (a) Low- and medium-voltage three-phase...

  4. Designs to balance cost and success rate for an early phase clinical study.

    PubMed

    Foo, Lee Kien; Duffull, Stephen

    2017-01-01

    We present an initial exploration of a fully cost-driven design. A design criterion was proposed that represented the minimum expected cost of an early phase clinical study, where costs include resource use as well as study failure. The design was based on attainment of a target concentration in a cohort of study participants. The model and parameter values arose from a previous population pharmacokinetic analysis of a phase I study. The resulting design naturally balanced the cost and the success rate of an early phase clinical study, without the need to define arbitrary constraints on the design space.

  5. Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krisnan; Vyas, Ruchi J.; Murray, Matthew; Predovic, Marina; Lim, Shiyin; Bryant, Douglas; Yaqian, Duan; Grant, Maria B.; Chalam, K. V.; Parsons-Wingerter, Patricia

    2017-01-01

    compensation of protective RAS during early DR. Migratory dysfunction of CD34+ cells was further associated with DR. Conclusions: As assessed by the fractal dimension in our preliminary study, the space-filling capacity of veins, but not arteries, was greater in early NPDR than in control. Larger patient populations will be examined as we complete our ongoing longitudinal study. Results further suggest the protective RAS axis within diabetic CACs is lost early in DR and is associated with increased vascular remodeling as evidenced by VESGEN analysis.

  6. Soluble complement receptor 1 protects the peripheral nerve from early axon loss after injury.

    PubMed

    Ramaglia, Valeria; Wolterman, Ruud; de Kok, Maryla; Vigar, Miriam Ann; Wagenaar-Bos, Ineke; King, Rosalind Helen Mary; Morgan, Brian Paul; Baas, Frank

    2008-04-01

    Complement activation is a crucial early event in Wallerian degeneration. In this study we show that treatment of rats with soluble complement receptor 1 (sCR1), an inhibitor of all complement pathways, blocked both systemic and local complement activation after crush injury of the sciatic nerve. Deposition of membrane attack complex (MAC) in the nerve was inhibited, the nerve was protected from axonal and myelin breakdown at 3 days after injury, and macrophage infiltration and activation was strongly reduced. We show that both classical and alternative complement pathways are activated after acute nerve trauma. Inhibition of the classical pathway by C1 inhibitor (Cetor) diminished, but did not completely block, MAC deposition in the injured nerve, blocked myelin breakdown, inhibited macrophage infiltration, and prevented macrophage activation at 3 days after injury. However, in contrast to sCR1 treatment, early signs of axonal degradation were visible in the nerve, linking MAC deposition to axonal damage. We conclude that sCR1 protects the nerve from early axon loss after injury and propose complement inhibition as a potential therapy for the treatment of diseases in which axon loss is the main cause of disabilities.

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

    PubMed Central

    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

  8. Early phase clinical trials in pediatric hematology and oncology.

    PubMed

    Corbacioglu, S

    2012-04-01

    Pediatric oncology is an unrivaled success story in the recent history of medicine. This success is mostly based on a persistent refinement of evidence based therapeutic concepts. With that regard physicians and their staff are highly experience in the conduct of prospective evidence based trials and are therefore competent partners for the pharmaceutical industry. In times of personalized medicine the individual target population is diminishing and the borders of indications are not more disease based. A situation that requires new concepts from the industry. Therefore children with cancer could benefit early from the current developments as well as the pharmaceutical industry could benefit from the legislative incentives through highly recruiting and well conducted prospective trials. Pivotal is a functional platform of communication in order to maintain a close dialogue between academia and pharmaceutical companies. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Floquet Symmetry-Protected Topological Phases in Cold-Atom Systems

    NASA Astrophysics Data System (ADS)

    Potirniche, I.-D.; Potter, A. C.; Schleier-Smith, M.; Vishwanath, A.; Yao, N. Y.

    2017-09-01

    We propose and analyze two distinct routes toward realizing interacting symmetry-protected topological (SPT) phases via periodic driving. First, we demonstrate that a driven transverse-field Ising model can be used to engineer complex interactions which enable the emulation of an equilibrium SPT phase. This phase remains stable only within a parametric time scale controlled by the driving frequency, beyond which its topological features break down. To overcome this issue, we consider an alternate route based upon realizing an intrinsically Floquet SPT phase that does not have any equilibrium analog. In both cases, we show that disorder, leading to many-body localization, prevents runaway heating and enables the observation of coherent quantum dynamics at high energy densities. Furthermore, we clarify the distinction between the equilibrium and Floquet SPT phases by identifying a unique micromotion-based entanglement spectrum signature of the latter. Finally, we propose a unifying implementation in a one-dimensional chain of Rydberg-dressed atoms and show that protected edge modes are observable on realistic experimental time scales.

  10. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain

    PubMed Central

    Kawasaki, Yasuhiko; Xu, Zhen-Zhong; Wang, Xiaoying; Park, Jong-Yeon; Zhuang, Zhi-Ye; Tan, Ping-Heng; Gao, Yong-Jing; Roy, Kristine; Corfas, Gabriel; Lo, Eng H.; Ji, Ru-Rong

    2008-01-01

    Treatment of neuropathic pain, triggered by multiple insults to the nervous system, is a clinical challenge because the underlying mechanisms of neuropathic pain development remain poorly understood 1-4. Most treatments do not differentiate between different phases of neuropathic pain pathophysiology and simply focus on blocking neurotransmission, producing transient pain relief. Here, we report that early and late phase neuropathic pain development after nerve injury require different matrix metalloproteinases (MMPs). After spinal nerve ligation, MMP-9 shows a rapid and transient upregulation in injured DRG primary sensory neurons consistent with an early phase of neuropathic pain, whereas MMP-2 shows a delayed response in DRG satellite cells and spinal astrocytes consistent with a late phase of neuropathic pain. Local inhibition of MMP-9 via an intrathecal route inhibits the early phase of neuropathic pain, whereas inhibition of MMP-2 suppresses late phase of neuropathic pain. Further, intrathecal administration of MMP-9 or MMP-2 is sufficient to produce neuropathic pain symptoms. Following nerve injury, MMP-9 induces neuropathic pain through interleukin-1β cleavage and microglia activation at early times, whereas MMP-2 maintains neuropathic pain through interleukin-1β cleavage and astrocyte activation at later times. Inhibition of MMP may provide a novel therapeutic approach for the treatment of neuropathic pain at different phases. PMID:18264108

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

    SciTech Connect

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

    2016-08-25

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

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

    DOE PAGES

    Chen, Cheng-Chien; Muechler, Lukas; Car, Roberto; ...

    2016-08-25

    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 fermionicmore » symmetry-protected topological phase. This state—protected by time-reversal and reflection symmetries—cannot be connected adiabatically to a free-fermion topological phase.« less

  13. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    SciTech Connect

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

    2016-08-25

    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.

  16. 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.

  17. 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.

  18. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Profiling of Burkholderia cepacia Secretome at Mid-Logarithmic and Early-Stationary Phases of Growth

    PubMed Central

    Mariappan, Vanitha; Vellasamy, Kumutha Malar; Hashim, Onn Haji; Vadivelu, Jamuna

    2011-01-01

    Background Burkholderia cepacia is a Gram-negative pathogen that causes serious respiratory infections in immunocompromised patients and individuals with cystic fibrosis. This bacterium is known to release extracellular proteins that may be involved in virulence. Methodology/Principal Findings In the present study, B. cepacia grown to mid-logarithmic and early-stationary phases were investigated on their ability to invade and survive intracellularly in A549 lung epithelial cells in order to discern the fate of these bacteria in the pathogenesis of B. cepacia lung infections in in vitro condition. The early-stationary phase B. cepacia was demonstrated to be more invasive than mid-logarithmic phase. In addition, culture supernatants of B. cepacia obtained from these phases of growth were also demonstrated to cause different cytotoxic potency on the A549 human lung epithelial cells. Profiling of the supernatants using the gel-based proteomics approach identified 43 proteins that were commonly released in both the growth phases and 40 proteins newly-released at the early-stationary phase. The latter proteins may account for the higher cytotoxic activity of the early-stationary culture supernatant compared to that obtained at the mid-logarithmic phase. Among the newly-released proteins in the early-stationary phase supernatant were flagellar hook-associated domain protein (FliD), flagellar hook-associated protein (FlgK), TonB-dependent siderophore (Fiu), Elongation factor G (FusA), phosphoglycerate kinase (Pgk) and sulfatase (AslA) which are known for their virulence. Conclusion/Significance Differences in the ability of B. cepacia to invade and survive intracellularly inside the epithelial cells at different phases of growth may improve our understanding of the varied disease progressions associated with B. cepacia infections. In addition, the identified culture supernatant proteins may be used as targets for the development of new strategies to control B. cepacia

  20. Magnetic fields during the early phase of massive star formation

    NASA Astrophysics Data System (ADS)

    Seifried, Daniel Jürgen

    2013-01-01

    The goal of this work is to improve our current understanding of the formation process of massive stars in the presence of magnetic fields by means of numerical simulations. In particular, I focus on protostellar accretion rates, the evolution and the properties of protostellar discs and their associated outflows, and the interplay of turbulence and magnetic fields and its impact on protostellar disc formation. In a systematic parameter study I show that the accretion rates are remarkably constant over a wide range of initial conditions. Furthermore, I show that in the absence of turbulence for strong initial magnetic fields only sub-Keplerian discs can form which is attributed to the strong magnetic braking effect. This result seems to be in contrast to observational results. The morphology of the outflows, which shows a strong dependence on the initial conditions, can ultimately be linked to the structure of the underlying disc. Well-collimated outflows with high outflows velocities only develop if a Keplerian protostellar disc is present, otherwise slowly expanding, sphere-like outflows develop. Furthermore, I analyse the driving mechanism of outflows with an analytical criterion derived in the course of this work. When including supersonic, turbulent motions in the simulations, Keplerian protostellar discs form in contrast to the non-turbulent simulations. This result is in agreement with observations of early-type protostellar objects.

  1. The relationship between sun protection policy and associated practices in a national sample of early childhood services in Australia.

    PubMed

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

    2011-02-01

    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 self-administered survey about the sun protection policies and practices in their early childhood service (response rate of 59%). Most (95%) had a written sun protection policy. The most common policy inclusions were hat wearing (91%), sunscreen use (87%) and enforcement of policy (97%). Less frequently reported inclusions were protective clothing (69%), information for parents/caregivers (58%) and regular reviews/updates of policies (65%). Basic sun protection practices (e.g. required any type of hat and sunscreen use) were more commonly reported than extensive practices (required protective clothing or regularly applied sunscreen). Higher sun protection policy scores, being a formal childcare service as opposed to a kindergarten/pre-school and having SunSmart status as opposed to not, were associated with higher sun protection practice scores (P < 0.001). Sun protection policies may be improved through encouraging services to have more specific policy inclusions and to model their policies on the SunSmart Early Childhood Program.

  2. Changes in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis.

    PubMed

    Nikolova, Vanya; Papacleovoulou, Georgia; Bellafante, Elena; Borges Manna, Luiza; Jansen, Eugene; Baron, Silvère; Abu-Hayyeh, Shadi; Parker, Malcolm; Williamson, Catherine

    2017-10-01

    Human pregnancy is associated with enhanced de novo lipogenesis in the early stages followed by hyperlipidemia during advanced gestation. Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that stimulate de novo lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues followed by its transport back to the liver for biliary excretion. Although LXR is recognized as a master regulator of triglyceride and cholesterol homeostasis, it is unknown whether it facilitates the gestational adaptations in lipid metabolism. To address this question, biochemical profiling, protein quantification, and gene expression studies were used, and gestational metabolic changes in T0901317-treated wild-type mice and Lxrab(-/-) mutants were investigated. Here, we show that altered LXR signaling contributes to the enhanced lipogenesis in early pregnancy by increasing the expression of hepatic Fas and stearoyl-CoA desaturase 1 (Scd1). Both the pharmacological activation of LXR with T0901317 and the genetic ablation of its two isoforms disrupted the increase in hepatic fatty acid biosynthesis and the development of hypertriglyceridemia during early gestation. We also demonstrate that absence of LXR enhances maternal white adipose tissue lipolysis, causing abnormal accumulation of triglycerides, cholesterol, and free fatty acids in the fetal liver. Together, these data identify LXR as an important factor in early-pregnancy lipogenesis that is also necessary to protect against abnormalities in fetoplacental lipid homeostasis. Copyright © 2017 the American Physiological Society.

  3. The early phase of vascularization in intraocular telencephalic transplants.

    PubMed

    Tuba, A; Kálmán, M

    1997-01-01

    The present study focused on the early events of vascularization of intraocular cerebral transplants. Telencephalic pieces of rat embryos (E15) were transplanted into the anterior eye chamber of adult rats in deep ketamine-xylazine narcosis. At 3-, 4-, 5-, 6-, or 7-day postoperative survival periods, the rats were perfused and the transplants, with their iridic beds, were processed into serial, semi-thin sections. In 3- and 4-day transplants, neither dilated (perfused) nor collapsed blood vessels were found, but tissue defects, without proper wall and filled by non-nucleated (mature, host) erythrocytes, were seen. On post-operative day 5, large sinusoids were seen lines by endothelium and free of blood cells (as a consequence of perfusion). On days 6 and 7, the usual, although large, blood vessels were found. Our results suggest that the critical period of transplant vascularization is between postoperative days 4 and 5, and that the original vessels of donor tissue degenerate and disappear during the first postoperative days and thus, do not participate directly in transplant vascularization. Our hypothesis is that vascular invasion begins with the opening of host blood vessels into clefts formed by degeneration of graft tissue. For a period, a hemostasis occurs in these blood-filled lacunae, and then endothelium invasion from host vessels forms the proper wall. The transplant vasculature develops from these large sinusoids. The results challenge the role of the pre-existing donor vessels in transplant vascularization. A possible explanation of such paradoxical results is that the donor tissue must reach a stage of maturation to receive the ingrowing vessels, either host vessels, and the presence of vessels in the donor brain is the sign of this stage of maturation but has no direct role in transplant vascularization.

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

    PubMed

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

    2010-10-01

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

  5. 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.

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  7. 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…

  8. 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…

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

    PubMed

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

    2009-01-01

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

  10. ``Gauging'' Non-on-site Symmetries and Symmetry Protected Topological Phases

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    We gauge non-on-site symmetries, such as parity symmetries, for a general (1+1)D conformal field theory (CFT) which is the boundary of (2+1)D symmetry protected topological (SPT) phases. This provides an efficient method to diagnose stability of SPT phases with the discrete non-on-site symmetries. To gauge the non-on- site symmetries, we are naturally led to consider field theories defined on a non-orientied manifold, such as Klein bottle. The partner states of the ``vortices'' (or twist operators) of the gauged non-on-site symmetries, the so-called crosscap states, provide information about the classification of the corresponding SPT phases. Our method also provide a way to gauging time-reversal symmetry, which is ``topologically'' related to parity symmetry by CPT theorem. NSF Grants DMR-1064319.

  11. The phase transitions between Zn × Zn bosonic topological phases in 1 + 1D, and a constraint on the central charge for the critical points between bosonic symmetry protected topological phases

    NASA Astrophysics Data System (ADS)

    Tsui, Lokman; Huang, Yen-Ta; Jiang, Hong-Chen; Lee, Dung-Hai

    2017-06-01

    The study of continuous phase transitions triggered by spontaneous symmetry breaking has brought revolutionary ideas to physics. Recently, through the discovery of symmetry protected topological phases, it is realized that continuous quantum phase transition can also occur between states with the same symmetry but different topology. Here we study a specific class of such phase transitions in 1 + 1 dimensions - the phase transition between bosonic topological phases protected by Zn ×Zn. We find in all cases the critical point possesses two gap opening relevant operators: one leads to a Landau-forbidden symmetry breaking phase transition and the other to the topological phase transition. We also obtained a constraint on the central charge for general phase transitions between symmetry protected bosonic topological phases in 1 + 1D.

  12. The phase transitions between Zn × Zn bosonic topological phases in 1 + 1D, and a constraint on the central charge for the critical points between bosonic symmetry protected topological phases

    DOE PAGES

    Tsui, Lokman; Huang, Yen-Ta; Jiang, Hong-Chen; ...

    2017-03-27

    The study of continuous phase transitions triggered by spontaneous symmetry breaking has brought revolutionary ideas to physics. Recently, through the discovery of symmetry protected topological phases, it is realized that continuous quantum phase transition can also occur between states with the same symmetry but different topology. Here in this paper we study a specific class of such phase transitions in 1+1 dimensions – the phase transition between bosonic topological phases protected by Zn × Zn. We find in all cases the critical point possesses two gap opening relevant operators: one leads to a Landau-forbidden symmetry breaking phase transition and themore » other to the topological phase transition. We also obtained a constraint on the central charge for general phase transitions between symmetry protected bosonic topological phases in 1+1D.« less

  13. Quantum phase transitions between a class of symmetry protected topological states

    SciTech Connect

    Tsui, Lokman; Jiang, Hong-Chen; Lu, Yuan-Ming; Lee, Dung-Hai

    2015-07-01

    The subject of this paper is the phase transition between symmetry protected topological states (SPTs). We consider spatial dimension d and symmetry group G so that the cohomology group, Hd+1(G,U(1)), contains at least one Z2n or Z factor. We show that the phase transition between the trivial SPT and the root states that generate the Z2n or Z groups can be induced on the boundary of a (d+1)-dimensional View the MathML source-symmetric SPT by a View the MathML source symmetry breaking field. Moreover we show these boundary phase transitions can be “transplanted” to d dimensions and realized in lattice models as a function of a tuning parameter. The price one pays is for the critical value of the tuning parameter there is an extra non-local (duality-like) symmetry. In the case where the phase transition is continuous, our theory predicts the presence of unusual (sometimes fractionalized) excitations corresponding to delocalized boundary excitations of the non-trivial SPT on one side of the transition. This theory also predicts other phase transition scenarios including first order transition and transition via an intermediate symmetry breaking phase.

  14. Quantum phase transitions between a class of symmetry protected topological states

    DOE PAGES

    Tsui, Lokman; Jiang, Hong -Chen; Lu, Yuan -Ming; ...

    2015-04-30

    The subject of this paper is the phase transition between symmetry protected topological states (SPTs). We consider spatial dimension d and symmetry group G so that the cohomology group, Hd+1(G,U(1)), contains at least one Z2n or Z factor. We show that the phase transition between the trivial SPT and the root states that generate the Z2n or Z groups can be induced on the boundary of a (d+1)-dimensional G x ZT2-symmetric SPT by a ZT2 symmetry breaking field. Moreover we show these boundary phase transitions can be “transplanted” to d dimensions and realized in lattice models as a function ofmore » a tuning parameter. The price one pays is for the critical value of the tuning parameter there is an extra non-local (duality-like) symmetry. In the case where the phase transition is continuous, our theory predicts the presence of unusual (sometimes fractionalized) excitations corresponding to delocalized boundary excitations of the non-trivial SPT on one side of the transition. This theory also predicts other phase transition scenarios including first order transition and transition via an intermediate symmetry breaking phase.« less

  15. [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.

  16. 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).…

  17. Using a Strengths Approach to Early Childhood Teacher Preparation in Child Protection Using Work-Integrated Education

    ERIC Educational Resources Information Center

    Fenton, Angela

    2013-01-01

    This paper explores a collaborative strengths-based approach to investing in pre-service early childhood teacher education in the area of child protection. The doctoral research of the author, which evaluated a Strengths Approach as a cross-sector tool for implementing change in early-childhood education and in doing so researched a potential…

  18. 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).…

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

    PubMed

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

    2000-11-01

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

  20. 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

  1. 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.

  2. Critical-entanglement spectrum of one-dimensional symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Rao, Wen-Jia; Wan, Xin; Zhang, Guang-Ming

    2014-08-01

    Under an appropriate symmetric extensive bipartition in a one-dimensional symmetry-protected topological (SPT) phase, a bulk critical-entanglement spectrum can be obtained, resembling the excitation spectrum of the critical point separating the SPT phase from the trivial (vacuum) state. Such a critical point is beyond the standard Landau-Ginzburg-Wilson paradigm for symmetry-breaking phase transitions. For the S =1 SPT (Haldane) phase with the Affleck-Kennedy-Lieb-Tasaki exact wave function, the resulting critical-entanglement spectrum has a residual entropy per lattice site sr=0.67602, showing a delocalized version of the edge excitations in the SPT phase. From the wave function corresponding to the lowest entanglement energy level, the central charge of the critical point can be extracted c ≈1.01±0.01. The critical theory can be identified as the same effective field theory as the spin-1/2 antiferromagnetic Heisenberg chain or the spin-1/2 Haldane-Shastry model with inverse-square long-range interaction.

  3. 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.

  4. 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.

  5. Protective effect of resveratrol in endotoxemia-induced acute phase response in rats.

    PubMed

    Sebai, Hichem; Ben-Attia, Mossadok; Sani, Mamane; Aouani, Ezzedine; Ghanem-Boughanmi, Néziha

    2009-04-01

    Lipopolysaccharide (LPS), a glycolipid component of the cell wall of gram-negative bacteria can elicit a systemic inflammatory process leading to septic shock and death. Acute phase response is characterized by fever, leucocytosis, thrombocytopenia, altered metabolic responses and redox balance by inducing excessive reactive oxygen species (ROS) generation. Resveratrol (trans-3,5,4' trihydroxystilbene) is a natural polyphenol exhibiting antioxidant and anti-inflammatory properties. We investigated the protective effect of resveratrol on endotoxemia-induced acute phase response in rats. When acutely administered by i.p. route, resveratrol (40 mg/kg b.w.) counteracted the effect of a single injection of LPS (4 mg/kg b.w.) which induced fever, a decrease in white blood cells (WBC) and platelets (PLT) counts. When i.p. administered during 7 days at 20 mg/kg per day (subacute treatment), resveratrol abrogated LPS-induced erythrocytes lipoperoxidation and catalase (CAT) activity depression to control levels. In the plasma compartment, LPS increased malondialdehyde (MDA) via nitric monoxide (NO) elevation and decreased iron level. All these deleterious LPS effects were reversed by a subacute resveratrol pre-treatment via a NO independent way. Resveratrol exhibited potent protective effect on LPS-induced acute phase response in rats.

  6. Vincristine pharmacokinetics pathway and neurotoxicity during early phases of treatment in pediatric acute lymphoblastic leukemia.

    PubMed

    Lopez-Lopez, Elixabet; Gutierrez-Camino, Angela; Astigarraga, Itziar; Navajas, Aurora; Echebarria-Barona, Aizpea; Garcia-Miguel, Purificacion; Garcia de Andoin, Nagore; Lobo, Carmen; Guerra-Merino, Isabel; Martin-Guerrero, Idoia; Garcia-Orad, Africa

    2016-05-01

    Vincristine is an important component of acute lymphoblastic leukemia (ALL) treatment protocols that can cause neurotoxicity. Patients treated with LAL/SHOP protocols often suffer from vincristine-related neurotoxicity in early phases of treatment. Recently, a genome-wide association study connected a SNP in CEP72, involved in vincristine pharmacodynamics, with neurotoxicity during later phases of therapy, which was not replicated during induction phase. These results, together with previous studies indicating that polymorphisms in pharmacokinetic genes are associated with drug toxicity, suggest that changes in the activity or levels of vincristine transporters or metabolizers could work as predictors of vincristine-related neurotoxicity in early phases of treatment in pediatric ALL. We analyzed 150 SNPs in eight key genes involved in vincristine pharmacokinetics and in 13 miRNAs that regulate them. We studied their correlation with neurotoxicity during induction phase in 152 ALL patients treated with LAL/SHOP protocols. The strongest associations with neurotoxicity were observed for two SNPs in ABCC2. The genotypes rs3740066 GG and rs12826 GG were associated with increased neurotoxicity. Polymorphisms in ABCC2 could be novel markers for vincristine-related neurotoxicity in pediatric ALL in early phases.

  7. 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.

  8. Microwave-assisted cleavage of Alloc and Allyl Ester protecting groups in solid phase peptide synthesis.

    PubMed

    Wilson, Krista R; Sedberry, Seth; Pescatore, Robyn; Vinton, Daniel; Love, Brian; Ballard, Sarah; Wham, Bradley C; Hutchison, Stacy K; Williamson, Eric J

    2016-10-01

    Orthogonal protection of amino acid side chains in solid phase peptide synthesis allows for selective deprotection of side chains and the formation of cyclic peptides on resin. Cyclizations are useful as they may improve the activity of the peptide or improve the metabolic stability of peptides in vivo. One cyclization method often used is the formation of a lactam bridge between an amine and a carboxylic acid. It is desirable to perform the cyclization on resin as opposed to in solution to avoid unwanted side reactions; therefore, a common strategy is to use -Alloc and -OAllyl protecting groups as they are compatible with Fmoc solid phase peptide synthesis conditions. Alloc and -OAllyl may be removed using Pd(PPh3 )4 and phenylsilane in DMF. This method can be problematic as the reaction is most often performed at room temperature under argon gas. It is not usually done at higher temperatures because of the fear of poisoning the palladium catalyst. As a result, the reaction is long and reagent-intensive. Herein, we report the development of a method in which the -Alloc/-OAllyl groups are removed using a microwave synthesizer under atmospheric conditions. The reaction is much faster, allowing for the removal of the protecting groups before the catalyst is oxidized, as well as being less reagent-intensive. This method of deprotection was tested using a variety of amino acid sequences and side chain protecting groups, and it was found that after two 5-min deprotections at 38°C, all -Alloc and -OAllyl groups were removed with >98% purity. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  9. Protecting two-qubit quantum states by π-phase pulses

    NASA Astrophysics Data System (ADS)

    Hu, Jia-Zhong; Wang, Xiang-Bin; Kwek, Leong Chuan

    2010-12-01

    We study the state decay of two qubits interacting with a common harmonic oscillator reservoir. We find both a decoherence error and the error caused by the amplitude change of the superradiant state. We show that frequent π-phase pulses can eliminate both types of errors and therefore protect a two-qubit odd-parity state more effectively than the frequent measurement method. This shows that the methods using dynamical decoupling and the quantum Zeno effects actually can give rather different results when the operation frequency is finite.

  10. Transcriptome analyses of early cucumber fruit growth identifies distinct gene modules associated with phases of development.

    PubMed

    Ando, Kaori; Carr, Kevin M; Grumet, Rebecca

    2012-10-02

    ABBACKGROUND: Early stages of fruit development from initial set through exponential growth are critical determinants of size and yield, however, there has been little detailed analysis of this phase of development. In this study we combined morphological analysis with 454 pyrosequencing to study transcript level changes occurring in young cucumber fruit at five ages from anthesis through the end of exponential growth. The fruit samples produced 1.13 million ESTs which were assembled into 27,859 contigs with a mean length of 834 base pairs and a mean of 67 reads per contig. All contigs were mapped to the cucumber genome. Principal component analysis separated the fruit ages into three groups corresponding with cell division/pre-exponential growth (0 and 4 days post pollination (dpp)), peak exponential expansion (8dpp), and late/post-exponential expansion stages of growth (12 and 16 dpp). Transcripts predominantly expressed at 0 and 4 dpp included homologs of histones, cyclins, and plastid and photosynthesis related genes. The group of genes with peak transcript levels at 8dpp included cytoskeleton, cell wall, lipid metabolism and phloem related proteins. This group was also dominated by genes with unknown function or without known homologs outside of cucurbits. A second shift in transcript profile was observed at 12-16dpp, which was characterized by abiotic and biotic stress related genes and significant enrichment for transcription factor gene homologs, including many associated with stress response and development. The transcriptome data coupled with morphological analyses provide an informative picture of early fruit development. Progressive waves of transcript abundance were associated with cell division, development of photosynthetic capacity, cell expansion and fruit growth, phloem activity, protection of the fruit surface, and finally transition away from fruit growth toward a stage of enhanced stress responses. These results suggest that the interval

  11. 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.

  12. Orthogonally Protected Furanoid Sugar Diamino Acids for Solid-Phase Synthesis of Oligosaccharide Mimetics.

    PubMed

    John, Franklin; Wittmann, Valentin

    2015-08-07

    Sugar diamino acids (SDAs), which differ from the widely used sugar amino acids in the presence of a second amino group connected to the carbohydrate core, share structural features of both amino acids and carbohydrates. They can be used for the preparation of linear and branched amide-linked oligosaccharide mimetics. Such oligomers carry free amino groups, which are positively charged at neutral pH, in a spatially defined way and, thus, represent a potential class of aminoglycoside mimetics. We report here the first examples of orthogonally protected furanoid SDAs and their use in solid-phase synthesis. Starting from d-glucose, we developed a divergent synthetic route to three derivatives of 3,5-diamino-3,5-dideoxy-d-ribofuranose. These building blocks are compatible with solid-phase peptide synthesis following the 9-fluorenylmethoxycarbonyl (Fmoc) strategy, which we demonstrate by the synthesis of an SDA tetramer.

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

    PubMed

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

    2015-12-31

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

  14. 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.

  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…

  16. 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…

  17. 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…

  18. Statistical controversies in clinical research: early-phase adaptive design for combination immunotherapies.

    PubMed

    Wages, N A; Slingluff, C L; Petroni, G R

    2017-04-01

    In recent years, investigators have asserted that the 3 + 3 design lacks flexibility, making its use in modern early-phase trial settings, such as combinations and/or biological agents, inefficient. More innovative approaches are required to address contemporary research questions, such as those posed in trials involving immunotherapies. We describe the implementation of an adaptive design for identifying an optimal treatment regimen, defined by low toxicity and high immune response, in an early-phase trial of a melanoma helper peptide vaccine plus novel adjuvant combinations. Operating characteristics demonstrate the ability of the method to effectively recommend optimal regimens in a high percentage of trials with reasonable sample sizes. The proposed design is a practical, early-phase, adaptive method for use with combined immunotherapy regimens. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of two small molecule inhibitors in relapsed/refractory mantle cell lymphoma.

  19. Men Managing, Not Teaching Foundation Phase: Teachers, Masculinity and the Early Years of Primary Schooling

    ERIC Educational Resources Information Center

    Moosa, Shaaista; Bhana, Deevia

    2017-01-01

    In this article we argue that eliminating the divisions of labour between men and women could work towards counteracting gender inequality within professions. Globally women are over-represented in the teaching of young children in the early years of primary school, or Foundation Phase (FP), as it is known in South Africa. We are concerned to go…

  20. 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…

  1. Adaptive Clinical Trials: Overview of Early-Phase Designs and Challenges

    PubMed Central

    Marchenko, Olga; Fedorov, Valerii; Lee, J. Jack; Nolan, Christy; Pinheiro, José

    2016-01-01

    In this paper, we describe developments in adaptive design methodology and discuss implementation strategies and operational challenges in early phase adaptive clinical trials. The BATTLE trial – the first completed, biomarker-based, Bayesian adaptive randomized study in lung cancer – is presented as a case study to illustrate main ideas and share learnings. PMID:28670507

  2. 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 or...

  3. 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

    ... HORIZON oil spill. The Framework Agreement provides a mechanism through which the Trustees and BP can work... 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...

  4. 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 April...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  6. Teacher Identity in the Early Career Phase: Trajectories that Explain and Influence Development

    ERIC Educational Resources Information Center

    Morrison, Chad M.

    2013-01-01

    Early career teaching is a difficult phase to navigate with many newly qualified teachers choosing to leave the profession within the first few years. The professional identities of these and other teachers are shaped by challenging and unanticipated experiences. The schools where this teaching takes place also have profound influence on these…

  7. 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…

  8. 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.…

  9. 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.…

  10. 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.

  11. Grandmother Involvement as a Protective Factor for Early Childhood Social Adjustment

    PubMed Central

    Barnett, Melissa A.; Scaramella, Laura V.; Neppl, Tricia K.; Ontai, Lenna L.; Conger, Rand D.

    2010-01-01

    Despite high rates of grandmother involvement with young grandchildren, very little research has examined the associations between non-residential grandmother involvement and grandchild social adjustment. The present study draws 127 families enrolled in the Family Transitions Project to consider the degree to which mother-reported maternal grandmother involvement buffers 3- and 4-year old grandchildren from economic, parenting, and child temperamental risks for reduced social competence and elevated externalizing behaviors. Findings indicate that higher levels of mother-reported grandmother involvement reduced the negative association between observed grandchild negative emotional reactivity and social competence. Further, high levels of mother-reported grandmother involvement protected grandchildren from the positive association between observed harsh mother parenting and grandchild externalizing behaviors. These findings underscore the relevance of moving beyond the nuclear family to understand factors linked to social adjustment during early childhood. PMID:20954774

  12. Auditory-driven phase reset in visual cortex: Human electrocorticography reveals mechanisms of early multisensory integration

    PubMed Central

    Mercier, Manuel R.; Foxe, John J.; Fiebelkorn, Ian C.; Butler, John S.; Schwartz, Theodore H.; Molholm, Sophie

    2013-01-01

    Findings in animal models demonstrate that activity within hierarchically early sensory cortical regions can be modulated by cross-sensory inputs through resetting of the phase of ongoing intrinsic neural oscillations. Here, subdural recordings evaluated whether phase resetting by auditory inputs would impact multisensory integration processes in human visual cortex. Results clearly showed auditory-driven phase reset in visual cortices and, in some cases, frank auditory event-related potentials (ERP) were also observed over these regions. Further, when audiovisual bisensory stimuli were presented, this led to robust multisensory integration effects which were observed in both the ERP and in measures of phase concentration. These results extend findings from animal models to human visual cortices, and highlight the impact of cross-sensory phase resetting by a non-primary stimulus on multisensory integration in ostensibly unisensory cortices. PMID:23624493

  13. Matrix product operators for symmetry-protected topological phases: Gauging and edge theories

    NASA Astrophysics Data System (ADS)

    Williamson, Dominic J.; Bultinck, Nick; Mariën, Michael; Şahinoǧlu, Mehmet B.; Haegeman, Jutho; Verstraete, Frank

    2016-11-01

    Projected entangled pair states (PEPS) provide a natural ansatz for the ground states of gapped, local Hamiltonians in which global characteristics of a quantum state are encoded in properties of local tensors. We develop a framework to describe onsite symmetries, as occurring in systems exhibiting symmetry-protected topological (SPT) quantum order, in terms of virtual symmetries of the local tensors expressed as a set of matrix product operators (MPOs) labeled by distinct group elements. These MPOs describe the possibly anomalous symmetry of the edge theory, whose local degrees of freedom are concretely identified in a PEPS. A classification of SPT phases is obtained by studying the obstructions to continuously deforming one set of MPOs into another, recovering the results derived for fixed-point models [Chen et al., Phys. Rev. B 87, 155114 (2013), 10.1103/PhysRevB.87.155114]. Our formalism accommodates perturbations away from fixed-point models, opening the possibility of studying phase transitions between different SPT phases. We also demonstrate that applying the recently developed quantum state gauging procedure to a SPT PEPS yields a PEPS with topological order determined by the initial symmetry MPOs. The MPO framework thus unifies the different approaches to classifying SPT phases, via fixed-point models, boundary anomalies, or gauging the symmetry, into the single problem of classifying inequivalent sets of matrix product operator symmetries that are defined purely in terms of a PEPS.

  14. Swatch Test Results of Phase 2 Commercial Chemical Protective Gloves to Challenge by Chemical Warfare Agents: Summary Report

    DTIC Science & Technology

    2001-01-01

    TEST RESULTS OF PHASE 2 COMMERCIAL CHEMICAL PROTECTIVE GLOVES TO CHALLENGE BY CHEMICAL WARFARE AGENTS : SUMMARY REPORT Robert S...Swatch testing Permeation testing GB Chemical protective gloves 15. NUMBER OF PAGES 53 16. PRICE CODE 17... warfare (CW) agent environment. Swatches of material from each glove design were tested for resistance to

  15. Improved oxygen uptake efficiency slope in acute myocardial infarction patients after early phase I cardiac rehabilitation.

    PubMed

    Tsai, Yun-Jeng; Li, Min-Hui; Chen, Chia-Hsin; Tuan, Sheng-Hui; Chen, Yi-Jen; Lin, Ko-Long

    2017-09-01

    A predischarge submaximal exercise test is often recommended after acute myocardial infarction (AMI) as part of phase I cardiac rehabilitation. In this study, a submaximal exercise parameter, oxygen uptake efficiency slope (OUES), was used to monitor the benefit of early mobilization within 48 h after AMI. An early mobilization protocol within 48 h after AMI has been initiated since 1 September 2012 in our center. Patients with onset time of AMI within 1 year before and 1 year after initiation of the early mobilization protocol were recruited for comparisons. Sixty patients were analyzed on the basis of this criterion, and were subjected to predischarge submaximal exercise tests. The OUES calculated with 100% exercise duration (OUES100) and calculated with the first 50% of exercise duration (OUES50) were obtained and analyzed. Both OUES100 and OUES50 of the AMI patients with early mobilization were significantly higher than those without early mobilization (P=0.025 and 0.007, respectively). The OUES100 and OUES50 were also highly correlated (r=0.891, P<0.001). The subgroup analysis using patients within 3 months before and 3 months after initiation of the protocol also showed a significant difference. OUES could be used to measure the exercise capacity and monitor the effect of phase I cardiac rehabilitation in patients soon after AMI. Early mobilization within 48 h following AMI significantly enhanced the patient's exercise capacity.

  16. 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.

  17. Inflammasome-Independent NLRP3 Restriction of a Protective Early Neutrophil Response to Pulmonary Tularemia

    PubMed Central

    Periasamy, Sivakumar; Duffy, Ellen B.

    2016-01-01

    Francisella tularensis (Ft) causes a frequently fatal, acute necrotic pneumonia in humans and animals. Following lethal Ft infection in mice, infiltration of the lungs by predominantly immature myeloid cells and subsequent myeloid cell death drive pathogenesis and host mortality. However, following sub-lethal Ft challenge, more mature myeloid cells are elicited and are protective. In addition, inflammasome-dependent IL-1β and IL-18 are important for protection. As Nlrp3 appears dispensable for resistance to infection with Francisella novicida, we considered its role during infection with the virulent Type A strain SchuS4 and the attenuated Type B live vaccine strain LVS. Here we show that both in vitro macrophage and in vivo IL-1β and IL-18 responses to Ft LVS and SchuS4 involve both the Aim2 and Nlrp3 inflammasomes. However, following lethal infection with Francisella, IL-1r-, Caspase-1/11-, Asc- and Aim2-deficient mice exhibited increased susceptibility as expected, while Nlrp3-deficient mice were more resistant. Despite reduced levels of IL-1β and IL-18, in the absence of Nlrp3, Ft infected mice have dramatically reduced lung pathology, diminished recruitment and death of immature myeloid cells, and reduced bacterial burden in comparison to wildtype and inflammasome-deficient mice. Further, increased numbers of mature neutrophil appear in the lung early during lethal Ft infection in Nlrp3-deficient mice. Finally, Ft infection induces myeloid and lung stromal cell death that in part requires Nlrp3, is necrotic/necroptotic in nature, and drives host mortality. Thus, Nlrp3 mediates an inflammasome-independent process that restricts the appearance of protective mature neutrophils and promotes lethal necrotic lung pathology. PMID:27926940

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

    PubMed

    O'Connor, Cliodhna; Joffe, Helene

    2013-11-01

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

  19. Symmetry protected topological phases in two dimensions: Generalized Laughlin's argument and quantum pumps

    NASA Astrophysics Data System (ADS)

    Hsieh, Chang-Tse; Sule, Olabode Mayodele; Ryu, Shinsei; Leigh, Rob

    2014-03-01

    We generalize Laughlin's flux insertion argument in a way that it is applicable to interacting topological phases protected by unitary symmetries - either on-site or non-on-site - in two spatial dimensions. Large gauge invariance of the symmetry projected partition function of the one-dimensional edge theory can be used to argue the (non)conservation of the quantum number (corresponding to the projected unitary symmetry) under the large gauge transformation. If the edge does not conserve such quantum number, there is a flux-driven ``quantum pump'' between edges of the two dimensional system, which can be diagnosed as the nontrivial symmetry protected topological phase. This also gives the criteria of stability/gappability of the edge states that respect the symmetry. For non-on-site symmetry such as parity symmetry, the one dimensional edge theory is considered as the conformal field theory on an unoriented surface, such as Klein bottle, which arise naturally from a parity symmetry projection operation.

  20. 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. ©2015 American Association for Cancer Research.

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

    PubMed

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

    2015-12-01

    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. 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. 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). 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.

  2. 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

  3. Alcohol Use Among Hispanic Early Adolescents in the United States: An Examination of Behavioral Risk and Protective Profiles

    PubMed Central

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

    2014-01-01

    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

  4. 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

  5. Thermal buffering performance of composite phase change materials applied in low-temperature protective garments

    NASA Astrophysics Data System (ADS)

    Yang, Kai; Jiao, Mingli; Yu, Yuanyuan; Zhu, Xueying; Liu, Rangtong; Cao, Jian

    2017-07-01

    Phase change material (PCM) is increasingly being applied in the manufacturing of functional thermo-regulated textiles and garments. This paper investigated the thermal buffering performance of different composite PCMs which are suitable for the application in functional low-temperature protective garments. First, according to the criteria selecting PCM for functional textiles/garments, three kinds of pure PCM were selected as samples, which were n-hexadecane, n-octadecane and n-eicosane. To get the adjustable phase change temperature range and higher phase change enthalpy, three kinds of composite PCM were prepared using the above pure PCM. To evaluate the thermal buffering performance of different composite PCM samples, the simulated low-temperature experiments were performed in the climate chamber, and the skin temperature variation curves in three different low temperature conditions were obtained. Finally composite PCM samples’ thermal buffering time, thermal buffering capacity and thermal buffering efficiency were calculated. Results show that the comprehensive thermal buffering performance of n-octadecane and n-eicosane composite PCM is the best.

  6. 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.

  7. 78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Availability AGENCY: Food and... Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products'' dated July 2013. The draft... (CT) and gene therapy (GT) products (referred to collectively as CGT products) with recommendations to...

  8. Accuracy of early-phase versus dual-phase single-photon emission computed tomography/computed tomography in the localization of parathyroid disease.

    PubMed

    Mandal, Rajarsi; Muthukrishnan, Ashok; Ferris, Robert L; de Almeida, John R; Duvvuri, Umamaheswar

    2015-06-01

    Preoperative localization for parathyroid disease has improved in recent years with the advent of dual-phase (99m) Tc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. However, dual-phase imaging is associated with increased cost, time, and radiation dose. The aim of this study was to investigate the need for late-phase imaging when using SPECT/CT for the preoperative localization of parathyroid disease. Retrospective chart analysis. A retrospective review of 75 patients who underwent preoperative imaging localization and subsequent surgical resection for parathyroid disease at a tertiary referral center was performed. Of these, 50 patients met study criteria including preoperative SPECT/CT imaging and specific reporting of early- and late-phase focal radiotracer uptake. Localization accuracy was verified with definitive surgical findings confirmed by histological analysis and evidence of biochemical cure. Accurate localization of adenoma(s) was seen in 78.0% of patients using dual-phase SPECT/CT. Early-phase imaging alone localized 76.0%, whereas late-phase imaging alone localized 74.0%. Sensitivity and specificity for dual-phase imaging was 84.8% and 89.6%, respectively. In comparison, early-phase localization alone was found to have a sensitivity/specificity of 84.4%/89.4%; sensitivity/specificity of late-phase scanning alone was found to be 80.4%/89.1%. Dual-phase SPECT/CT scanning did not provide a statistically significant improvement in adenoma localization when compared to early-phase scanning alone. Although further investigation is needed, the results of this study suggest that early-phase SPECT/CT scanning alone may obviate the need for dual-phase SPECT/CT scanning in the initial preoperative localization workup of parathyroid disease. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Self-injury among early adolescents: identifying segments protected and at risk.

    PubMed

    Alfonso, Moya L; Kaur, Ravneet

    2012-11-01

    Self-injury has been described as a "silent school crisis," reflecting insufficient knowledge, confusion, lack of effective interventions, and the tendency for adults and youth to shy away from dealing directly with the issue. This purpose of this study was to identify distinct subgroups of youth who may be at increased risk of or reduced risk of nonsuicidal self-injury (NSSI). The middle-school Youth Risk Behavior Survey was administered in 8 district public middle schools in a large, southeastern county in Florida. A final sample size of 1748, representing approximately 92% of participants who self-reported attendance at 1 of the 8 middle schools (N = 1907) and 74% of the 2350 surveys originally distributed, was used in this study. Chi-squared automatic interaction detection (CHAID) was used to identify distinct segments at risk for or protected from NSSI. CHAID analyses suggested large groups of youth at risk for (and not at risk) having ever tried self-injury including suicidal tendencies, substance use, low belief in life possibilities, and exposure to peer self-injury. Protective factors identified included having low to zero levels of suicidal tendencies, high belief in life possibilities, lack of substance use, and not being a victim of bullying. Engaging adolescents in prevention programs at early stage can reduce the chances of suicidal behavior as well as physical injury. Schools should take the lead in advocating for the development of evidence-based interventions that are capable of addressing factors that contribute to self-injury at multiple levels of youth's environments. © 2012, American School Health Association.

  10. 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

  11. Controlled oxygen reperfusion protects the lung against early ischemia-reperfusion injury in cardiopulmonary bypasses by downregulating high mobility group box 1.

    PubMed

    Rong, Jian; Ye, Sheng; Wu, Zhong-Kai; Chen, Guang-Xian; Liang, Meng-Ya; Liu, Hai; Zhang, Jin-Xin; Huang, Wei-Ming

    2012-05-01

    Restricting oxygen delivery during the reperfusion phase of cardiopulmonary bypass (CPB) protects the heart, but effects on lung ischemia reperfusion (IR) in CPB are unknown. We examined whether extracellular high mobility group box 1 (HMGB1) mediated inflammation during early lung IR injury in CPB. Fourteen healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Following surgery, the animals were randomized into control (n = 7) or test (n = 7) groups. Control animals received a constant level of 80% FiO(2) during the entire procedure, and the test group received a gradual increase in FiO(2) during the first 25 minutes of reperfusion. In the test group, the FiO(2) was initiated at 40% and increased by 10% every 5 minutes, to 80%. Histology, lung injury variables, HMGB1 expression, and inflammatory responses were assessed at baseline (T1) and at 25 minutes (T2) and 90 minutes (T3) after starting reperfusion. Treatment with controlled oxygen significantly suppressed lung pathologies, lung injury variables, and inflammatory responses (all P < .001). After lung IR injury, HMGB1 mRNA and protein expressions were significantly decreased in the controlled oxygen group (all P < .001). Controlled oxygen reperfusion is protective in the early stages of lung IR injury in a canine CPB model, and this protection is linked to HMGB1 downregulation.

  12. Interaction of incidental microbleeds and prior use of antithrombotics with early hemorrhagic transformation: Causative or protective?

    PubMed

    Malhotra, Konark; Khunger, Monica; Ouyang, Bichun; Liebeskind, David S; Mohammad, Yousef M

    2016-01-01

    Gradient echo (GRE) sequence of magnetic resonance imaging (MRI) is a sensitive tool to detect hemorrhagic transformation (HT) and old cerebral microbleeds (CMBs). Presence of CMBs and prior use of antithrombotics pose a risk of HT in ischemic stroke. We evaluated the association of CMBs and antithrombotic use with resultant HT in acute ischemic stroke (AIS). This retrospective study included AIS patients admitted to our center between January 2009 and August 2010 who underwent GRE-weighted MRI within 48 h of admission. Demographic and clinical data including diabetes mellitus, hypertension, hyperlipidemia, prior intake of antiplatelets/anticoagulants/statins, and presence of CMBs at admission were collected and compared between patients who developed HT and those who did not. We did a multivariate analysis using logistic regression to assess the effect of CMBs and prior use of antithrombotic agents on the risk of development for early HT in ischemic stroke. Of 529 AIS patients, 81 (15%) were found to have HT during the initial hospital course. CMBs were found in only 9 of 81 patients (11%) with HT and in 40 out of remaining 448 patients (9%) who did not develop HT. The presence of CMBs was not associated with increased risk of HT (P = 0.53). However, prior use of antiplatelets (33% vs. 47% in the patients without HT, P = 0.02) was associated with decreased risk of HT in ischemic stroke. Presence of incidental CMBs was not associated with increased risk for early HT of an ischemic stroke. Interestingly, the prior intake of antiplatelets was found to be protective against HT of ischemic stroke.

  13. Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats

    PubMed Central

    Zhang, Xiang-Sheng; Wu, Qi; Wu, Ling-Yun; Ye, Zhen-Nan; Jiang, Tian-Wei; Li, Wei; Zhuang, Zong; Zhou, Meng-Liang; Zhang, Xin; Hang, Chun-Hua

    2016-01-01

    Increasing evidence indicates that sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions, such as oxidative stress, inflammation and apoptosis. The aim of this study was to investigate the change of SIRT1 in the brain after subarachnoid hemorrhage (SAH) and its role on SAH-induced early brain injury (EBI). In the first set of experiments, rats were randomly divided into sham group and SAH groups at 2, 6, 12, 24, 48 and 72 h. The expression of SIRT1 was evaluated by western blot analysis, immunohistochemistry and immunofluorescence. In another set of experiments, SIRT1-specific inhibitor (sirtinol) and activator (activator 3) were exploited to study the role of SIRT1 in SAH-induced EBI. It showed that the protein level of SIRT1 was markedly elevated at the early stage of SAH and peaked at 24 h after SAH. The expression of SIRT1 could be observed in neurons and microglia, and the enhanced SIRT1 was mainly located in neurons after SAH. Administration of sirtinol inhibited the expression and activation of SIRT1 pathways after SAH, while activator 3 enhanced the expression and activation of SIRT1 pathways after SAH. In addition, inhibition of SIRT1 could exacerbate forkhead transcription factors of the O class-, nuclear factor-kappa B- and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis, leading to aggravated brain injury after SAH. In contrast, activator 3 treatment could reduce forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis to protect against EBI. These results suggest that SIRT1 plays an important role in neuroprotection against EBI after SAH by deacetylation and subsequent inhibition of forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative, inflammatory and apoptotic pathways. SIRT1 might be a new promising molecular target for SAH. PMID:27735947

  14. Interaction of incidental microbleeds and prior use of antithrombotics with early hemorrhagic transformation: Causative or protective?

    PubMed Central

    Malhotra, Konark; Khunger, Monica; Ouyang, Bichun; Liebeskind, David S.; Mohammad, Yousef M.

    2016-01-01

    Background: Gradient echo (GRE) sequence of magnetic resonance imaging (MRI) is a sensitive tool to detect hemorrhagic transformation (HT) and old cerebral microbleeds (CMBs). Presence of CMBs and prior use of antithrombotics pose a risk of HT in ischemic stroke. We evaluated the association of CMBs and antithrombotic use with resultant HT in acute ischemic stroke (AIS). Methods: This retrospective study included AIS patients admitted to our center between January 2009 and August 2010 who underwent GRE-weighted MRI within 48 h of admission. Demographic and clinical data including diabetes mellitus, hypertension, hyperlipidemia, prior intake of antiplatelets/anticoagulants/statins, and presence of CMBs at admission were collected and compared between patients who developed HT and those who did not. We did a multivariate analysis using logistic regression to assess the effect of CMBs and prior use of antithrombotic agents on the risk of development for early HT in ischemic stroke. Results: Of 529 AIS patients, 81 (15%) were found to have HT during the initial hospital course. CMBs were found in only 9 of 81 patients (11%) with HT and in 40 out of remaining 448 patients (9%) who did not develop HT. The presence of CMBs was not associated with increased risk of HT (P = 0.53). However, prior use of antiplatelets (33% vs. 47% in the patients without HT, P = 0.02) was associated with decreased risk of HT in ischemic stroke. Conclusion: Presence of incidental CMBs was not associated with increased risk for early HT of an ischemic stroke. Interestingly, the prior intake of antiplatelets was found to be protective against HT of ischemic stroke. PMID:27994355

  15. C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure.

    PubMed

    Krijnen, Paul A J; Kupreishvili, Koba; de Vries, Margreet R; Schepers, Abbey; Stooker, Wim; Vonk, Alexander B A; Eijsman, Leon; Van Hinsbergh, Victor W M; Zeerleder, Sacha; Wouters, Diana; van Ham, Marieke; Quax, Paul H A; Niessen, Hans W M

    2012-01-01

    Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations

    PubMed Central

    Nandal, Savita; Burt, Tal

    2017-01-01

    Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development. PMID:28218733

  17. 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

    2004-05-05

    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.

  18. Ultra-Early Phase pathologies of Alzheimer's disease and other neurodegenerative diseases.

    PubMed

    Okazawa, Hitoshi

    2017-01-01

    The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-Aβ antibodies against Alzheimer's disease. In this review article, I summarize the critical issues that should be successfully and consistently answered by a new concept of neurodegeneration. For reevaluating old concepts and reconstructing a new concept of neurodegeneration that will replace the old ones, non-biased comprehensive approaches including proteome combined with systems biology analyses will be a powerful tool. I introduce our recent efforts in this orientation that have reached to the stage of non-clinical proof of concept applicable to clinical trials.

  19. Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations.

    PubMed

    Nandal, Savita; Burt, Tal

    2017-02-19

    Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development.

  20. The New Phases due to Symmetry Protected Piecewise Berry Phases; Enhanced Pumping and Non-reciprocity in Trimer Lattices.

    PubMed

    Liu, Xuele; Agarwal, G S

    2017-03-24

    Finding new phase of matter is a fundamental task in physics. Generally, various phases or states of matter (for instance solid/liquid/gas phases) have different symmetries, the phase transitions among them can be explained by Landau's symmetry breaking theory. The topological phases discovered in recent years show that different phases may have the same symmetry. The different topological phases are characterized by different integer values of the Berry phases. By studying one dimensional (1D) trimer lattices we report new phases beyond topological phases. The new phases that we find are characterized by piecewise continuous Berry phases with the discontinuity occurring at the transition point. With time-dependent changes in trimer lattices, we can generate two dimensional (2D) phases, which are characterized by the Berry phase of half period. This half-period Berry phase changes smoothly within one state of the system while changes discontinuously at the transition point. We further demonstrate the existence of adiabatic pumping for each phase and gain assisted enhanced pumping. The non reciprocity of the pumping process makes the system a good optical diode.

  1. The New Phases due to Symmetry Protected Piecewise Berry Phases; Enhanced Pumping and Non-reciprocity in Trimer Lattices

    PubMed Central

    Liu, Xuele; Agarwal, G. S.

    2017-01-01

    Finding new phase of matter is a fundamental task in physics. Generally, various phases or states of matter (for instance solid/liquid/gas phases) have different symmetries, the phase transitions among them can be explained by Landau’s symmetry breaking theory. The topological phases discovered in recent years show that different phases may have the same symmetry. The different topological phases are characterized by different integer values of the Berry phases. By studying one dimensional (1D) trimer lattices we report new phases beyond topological phases. The new phases that we find are characterized by piecewise continuous Berry phases with the discontinuity occurring at the transition point. With time-dependent changes in trimer lattices, we can generate two dimensional (2D) phases, which are characterized by the Berry phase of half period. This half-period Berry phase changes smoothly within one state of the system while changes discontinuously at the transition point. We further demonstrate the existence of adiabatic pumping for each phase and gain assisted enhanced pumping. The non reciprocity of the pumping process makes the system a good optical diode. PMID:28337994

  2. The New Phases due to Symmetry Protected Piecewise Berry Phases; Enhanced Pumping and Non-reciprocity in Trimer Lattices

    NASA Astrophysics Data System (ADS)

    Liu, Xuele; Agarwal, G. S.

    2017-03-01

    Finding new phase of matter is a fundamental task in physics. Generally, various phases or states of matter (for instance solid/liquid/gas phases) have different symmetries, the phase transitions among them can be explained by Landau’s symmetry breaking theory. The topological phases discovered in recent years show that different phases may have the same symmetry. The different topological phases are characterized by different integer values of the Berry phases. By studying one dimensional (1D) trimer lattices we report new phases beyond topological phases. The new phases that we find are characterized by piecewise continuous Berry phases with the discontinuity occurring at the transition point. With time-dependent changes in trimer lattices, we can generate two dimensional (2D) phases, which are characterized by the Berry phase of half period. This half-period Berry phase changes smoothly within one state of the system while changes discontinuously at the transition point. We further demonstrate the existence of adiabatic pumping for each phase and gain assisted enhanced pumping. The non reciprocity of the pumping process makes the system a good optical diode.

  3. 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

    ... the Deepwater Horizon Oil Spill (Framework Agreement), the Trustees have previously selected, and BP... 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...

  4. 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

  5. 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

  6. Effects of temperature on early-phase transmission of Yersina pestis by the flea, Xenopsylla cheopis.

    PubMed

    Schotthoefer, Anna M; Bearden, Scott W; Vetter, Sara M; Holmes, Jennifer; Montenieri, John A; Graham, Christine B; Woods, Michael E; Eisen, Rebecca J; Gage, Kenneth L

    2011-03-01

    Sharp declines in human and animal cases of plague, caused by the bacterium Yersinia pestis (Yersin), have been observed when outbreaks coincide with hot weather. Failure of biofilm production, or blockage, to occur in the flea, as temperatures reach 30 degrees C has been suggested as an explanation for these declines. Recent work demonstrating efficient flea transmission during the first few days after fleas have taken an infectious blood meal, in the absence of blockage (e.g., early-phase transmission), however, has called this hypothesis into question. To explore the potential effects of temperature on early-phase transmission, we infected colony-reared Xenopsylla cheopis (Rothchild) fleas with a wild-type strain of plague bacteria using an artificial feeding system, and held groups of fleas at 10, 23, 27, and 30 degrees C. Naive Swiss Webster mice were exposed to fleas from each of these temperatures on days 1-4 postinfection, and monitored for signs of infection for 21 d. Temperature did not significantly influence the rates of transmission observed for fleas held at 23, 27, and 30 degrees C. Estimated per flea transmission efficiencies for these higher temperatures ranged from 2.32 to 4.96% (95% confidence interval [CI]: 0.96-8.74). In contrast, no transmission was observed in mice challenged by fleas held at 10 degrees C (per flea transmission efficiency estimates, 0-1.68%). These results suggest that declines in human and animal cases during hot weather are not related to changes in the abilities of X. cheopis fleas to transmit Y. pestis infections during the early-phase period. By contrast, transmission may be delayed or inhibited at low temperatures, indicating that epizootic spread of Y. pestis by X. cheopis via early-phase transmission is unlikely during colder periods of the year.

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

    PubMed

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

    2015-01-01

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

  8. Publication and reporting conduct for pharmacodynamic analyses of tumor tissue in early-phase oncology trials.

    PubMed

    Freeman, Georgina A; Kimmelman, Jonathan

    2012-12-01

    In principle, nondiagnostic biopsies for pharmacodynamic (PD) studies are carried out to inform decision-making in drug development. Because such procedures have no therapeutic value, their ethical justification requires that results be published. We aimed to assess the frequency of nonpublication of PD data in early phase cancer trials and to identify factors that prevent full publication of data. We identified a sample of early-phase cancer trials containing invasive nondiagnostic tissue procurement for PD analysis from American Society of Clinical Oncology and American Association for Cancer Research meeting abstracts published between 1995 and 2005. These trials were followed to publication to determine frequency of nonpublication of PD data. Corresponding authors on early-phase cancer trials using invasive nondiagnostic research procedures were also surveyed to identify factors preventing full publication of PD data. In a sample of 90 trials, 22.2% (20 trials) resulted in no trial publication. Of published trials expected to contain PD reports, 16 (17.8%) did not include any PD data, and 21 (23.3%) reported incomplete PD data. We surveyed 92 authors; nonpublication was regarded as a frequent occurrence, and the most commonly cited barrier to full publication of PD data was strategic considerations in publication (58.8% of responding authors). Our results suggest ways that investigators, study planners, and reviewers can improve the burden/knowledge value balance in PD studies. ©2012 AACR.

  9. 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

  10. Association of medial prefrontal resting state functional connectivity and metacognitive capacity in early phase psychosis.

    PubMed

    Francis, Michael M; Hummer, Tom A; Leonhardt, Bethany L; Vohs, Jenifer L; Yung, Matt G; Mehdiyoun, Nicole F; Lysaker, Paul H; Breier, Alan

    2017-04-30

    Metacognition refers to a range of cognitive processes that allow one to form complex ideas of self and others and to use this information to navigate psychosocial challenges. Several studies in both early-phase and prolonged schizophrenia have demonstrated not only that significant deficits in metacognitive ability are present, but importantly that they are associated with significant functional impairment and decreased quality of life. In spite of the importance of metacognitive impairment in schizophrenia, relatively little is known about the biological substrates that may contribute to this dysfunction. In this study, we examined the relationship between resting state functional connectivity of the medial prefrontal cortex (mPFC), a structure shown in prior voxel-based morphometry studies to be associated with metacognition, with metacognitive function in an early-phase psychosis cohort (n=18). Analyses revealed a positive association of resting state functional connectivity between the mPFC and precuneus and posterior cingulate structures and metacognitive ability. These results provide evidence of disrupted resting state connectivity in structures relevant to metacognitive dysfunction in early-phase psychosis, which may have implications for pathophysiological models of complex cognitive deficits in this illness. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  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. The subthalamic nucleus modulates the early phase of probabilistic classification learning.

    PubMed

    Weiss, Daniel; Lam, Judith M; Breit, Sorin; Gharabaghi, Alireza; Krüger, Rejko; Luft, Andreas R; Wächter, Tobias

    2014-07-01

    Previous models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. Thirteen idiopathic Parkinson's disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, and medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high-probability patterns, and more differentiated strategy analyses were used. The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials '41-60' that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high-probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention toward unacquainted content. The STN might play a role in balancing the short-term success against strategy optimization for improved long-term outcome.

  13. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis.

    PubMed

    Lin, Yan-Ren; Li, Chao-Jui; Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Wu, Han-Ping; Hsu Chen, Cheng; Lu, Huai-En; Chen, Wen-Liang

    2016-01-01

    Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.

  15. The protective effect of parental expectations against early adolescent smoking initiation.

    PubMed

    Simons-Morton, Bruce G

    2004-10-01

    Substantial research and theory suggests that smoking initiation is socially mediated, with both peers and parents playing important roles. To learn more about how parenting behaviors influence smoking initiation, students (n=1002) from four middle schools were surveyed at the beginning of the sixth grade (T1), and the end of the sixth (T2) and seventh (T3) grades. T1 and T2-T1 predictors were regressed on smoking initiation at the end of seventh grade. In bivariate logistic regression analyses, association with friends who smoke, attitudes toward deviance, outcome expectations for smoking, perceived school climate, parental expectations, parental involvement at T1 and increases in these variables (T2-T1) were associated with smoking initiation at T3, but only the T1 measures of social competence, academic engagement, school adjustment, perceived prevalence, parental monitoring and parental involvement were associated with smoking initiation at T3. In multivariate logistic regression analyses, parental expectations were negatively associated, and increases in attitudes accepting of deviance and affiliation with friends who smoke were positively associated with smoking initiation. Analysis of interactions indicated that parental expectations and monitoring did not mediate the effect on smoking initiation of attitudes toward deviance or the number of friends who smoke. These findings provide evidence that parental expectations may protect early adolescents against smoking even in the context of increases in favorable attitudes and friends who smoking.

  16. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis

    PubMed Central

    Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Hsu Chen, Cheng

    2016-01-01

    Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level. PMID:28058255

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

    PubMed Central

    Watanabe, Hama; Shitara, Yoshihiko; Aoki, Yoshinori; Inoue, Takanobu; Tsuchida, Shinya; Takahashi, Naoto; Taga, Gentaro

    2017-01-01

    A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants. PMID:28196885

  2. Elevated soft tissue activity in early but not delayed phase of bone scan in Klippel-Trenaunay syndrome.

    PubMed

    Liu, Bin; Servaes, Sabah; Zhuang, Hongming

    2013-03-01

    Triple-phase bone scan is commonly used in the diagnosis of osteomyelitis. Elevated bone tracer activity in early but not delayed phase of the study favors cellulitis over osteomyelitis. We reported that Klippel-Trenaunay syndrome, a congenital disorder characterized by malformations of the capillary, venous, and lymphatic systems, can have images similar to cellulitis on triple-phase bone scan.

  3. Recruitment Early Warning System. Phase II. Volume 2. System Documentation and Users’ Manual for the Automated EWS (Early Warning System).

    DTIC Science & Technology

    1985-09-30

    GOUPmanpower planning, early warning system, N/A N /Aforecasting 19 ABSTRACT (Continue on reverse if necessary and identify by block number) * The...purpose of the Recruitment Early Warning System Project is to provide (SD1. and the Services with a source of timely, reliable information on the near-term...status of the recruitic. market. Phase I of the study determined the feasibility of developing and imtplemeniting an early warning system for

  4. Domestic Preparedness: Phase 2 Sarin Vapor Challenge and Corn Oil Protection Factor (PF) Testing of Commercial Powered Air Purifying Respirator (PAPR) Systems and Cartridges

    DTIC Science & Technology

    2002-10-01

    ECBC-TR Domestic Preparedness: Phase 2 Sarin Vapor Challenge and Corn Oil Protection Factor (PF) Testing of Commercial...Phase 2 Sarin Vapor Challenge and Corn Oil Protection Factor (PF) Testing of Commercial Powered Air Purifying Respirator (PAPR) Systems and Cartridges...PAPR systems using manikin headform and simulated breathing, and (3) corn - oil protection factor determinations of PAPR systems using human subjects

  5. cAMP initiates early phase neuron-like morphology changes and late phase neural differentiation in mesenchymal stem cells

    PubMed Central

    Zhang, Linxia; Seitz, Linsey C.; Abramczyk, Amy M.; Liu, Li

    2010-01-01

    The intracellular second messenger cAMP is frequently used in induction media to induce mesenchymal stem cells (MSCs) into neural lineage cells. To date, an understanding of the role cAMP exerts on MSCs and whether cAMP can induce MSCs into functional neurons is still lacking. We found cAMP initiated neuron-like morphology changes early and neural differentiation much later. The early phase changes in morphology were due to cell shrinkage, which subsequently rendered some cells apoptotic. While the morphology changes occurred prior to the expression of neural markers, it is not required for neural marker expression and the two processes are differentially regulated downstream of cAMP-activated protein kinase A. cAMP enabled MSCs to gain neural marker expressions with neuronal function, such as, calcium rise in response to neuronal activators, dopamine, glutamate, and potassium chloride. However, only some of the cells induced by cAMP responded to the three neuronal activators and further lack the neuronal morphology, suggesting that although cAMP is able to direct MSCs towards neural differentiation, they do not achieve terminal differentiation. PMID:20725762

  6. Protections for Workers Who Must Enter Pesticide-Treated Areas Early

    EPA Pesticide Factsheets

    The Worker Protection Standard allows entry into a pesticide-treated area that remains under a restricted-entry interval only in a few narrow work situations. Learn about special protections that must be provided for workers in these situations.

  7. 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.

  8. Protein export marks the early phase of gametocytogenesis of the human malaria parasite Plasmodium falciparum.

    PubMed

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

    2010-07-01

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

  9. Variations in Unrealistic Optimism Between Acceptors and Decliners of Early Phase Cancer Trials.

    PubMed

    Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Degnin, Catherine; Sulmasy, Daniel P

    2017-10-01

    Research has found that patient-subjects in early phase cancer trials exhibit unrealistic optimism regarding the risks and possible benefits of trial participation. Unrealistic optimism is associated with therapeutic misconception and failures to appreciate research-related information. This is the first study to assess whether those who decline to participate in these trials also exhibit unrealistic optimism. It is also the first study to assess whether there are significant differences in appreciation of research-related risks/benefits and therapeutic misconception between these two groups. We approached 261 patients at two academic medical centers who were offered enrollment in a Phase I, II, or I/II cancer trial (between 2012 and 2016). Two hundred thirty-three patients agreed to enroll in an early phase cancer trial, 171 of whom agreed to be interviewed for the study. Twenty-eight patients declined the offer to enroll, 15 of whom agreed to be interviewed for the study. Subjects participated in a structured face-to-face interview with a research associate trained to administer the study questionnaires. Acceptors demonstrated a significantly higher level of unrealistic optimism than decliners ( p < .05). Decliners had significantly less therapeutic misconception than acceptors (3.37 [ SD = 0.85] vs. 3.79 [ SD = 0.77], p = .042). There was a significant difference on one of the appreciation questions between acceptors and decliners ( p = .009). Comparative assessment of acceptors and decliners to early phase cancer trials casts light on whether unrealistic optimism is consequential for the decision to participate in these trials. The different levels of unrealistic optimism exhibited by these groups suggest that it may be a factor that affects the decision to participate.

  10. 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

  11. Breast Milk Protects Against Gastrointestinal Symptoms in Infants at High Risk for Autism During Early Development

    PubMed Central

    Penn, Alexander H.; Carver, Leslie J.; Herbert, Carrie A.; Lai, Tiffany S.; McIntire, Melissa J.; Howard, Jeffrey T.; Taylor, Sharon F.; Schmid-Schönbein, Geert W.; Dobkins, Karen R.

    2015-01-01

    Objectives Parents of children with Autism spectrum disorders (ASD) often report gastrointestinal dysfunction in their children. The objectives of the current study were to: 1) determine if infants at high risk for developing ASD (i.e. siblings of children diagnosed with ASD) show greater prevalence of gastrointestinal problems, and 2) whether this prevalence is associated with diet and age at weaning from breast milk. Methods Using questionnaires, diet history and gastrointestinal problems were tracked prospectively and retrospectively in 57 High-risk infants, and for comparison, in 114 Low-risk infants (infants from families without ASD history). Results In Low-risk infants, prevalence of GI symptoms, in aggregate, did not vary with diet or age of weaning. By contrast, High-risk infants with GI symptoms were weaned earlier than those without symptoms (p<0.04), and High-risk infants showed greater prevalence of GI symptoms, in aggregate, on a no breast milk (NBM) diet than on an exclusive breast milk (EBM) diet (p<0.017). Constipation, in particular, was more prevalent in High-risk infants compared to Low-risk infants (p=0.01), especially on a NBM diet (p=0.002). High-risk infants who completed weaning earlier than 6 months showed greater prevalence of constipation (p=0.001) and abdominal distress (p=0.004) than those fully weaned after 6 months. Conclusions 1) The greater prevalence of GI symptoms in High-risk infants suggests that GI dysfunction during early infant development may be a part of the ASD endophenotype. 2) Late weaning and EBM were associated with protection against GI symptoms in High-risk infants. PMID:26230900

  12. Breast Milk Protects Against Gastrointestinal Symptoms in Infants at High Risk for Autism During Early Development.

    PubMed

    Penn, Alexander H; Carver, Leslie J; Herbert, Carrie A; Lai, Tiffany S; McIntire, Melissa J; Howard, Jeffrey T; Taylor, Sharon F; Schmid-Schönbein, Geert W; Dobkins, Karen R

    2016-02-01

    Parents of children with autism spectrum disorders (ASDs) often report gastrointestinal (GI) dysfunction in their children. The objectives of the present study were to determine whether infants at high risk for developing ASD (ie, siblings of children diagnosed as having ASD) show greater prevalence of GI problems and whether this prevalence is associated with diet and age at weaning from breast milk. Using questionnaires, diet history and GI problems were tracked prospectively and retrospectively in 57 high-risk infants and for comparison in 114 low-risk infants (infants from families without ASD history). In low-risk infants, prevalence of GI symptoms, in aggregate, did not vary with diet or age of weaning. By contrast, high-risk infants with GI symptoms were weaned earlier than those without symptoms (P < 0.04), and high-risk infants showed greater prevalence of GI symptoms, in aggregate, on a no breast milk diet than on an exclusive breast milk diet (P < 0.017). Constipation, in particular, was more prevalent in high-risk infants compared with low-risk infants (P = 0.01), especially on a no breast milk diet (P = 0.002). High-risk infants who completed weaning earlier than 6 months showed greater prevalence of constipation (P = 0.001) and abdominal distress (P = 0.004) than those fully weaned after 6 months. The greater prevalence of GI symptoms in high-risk infants suggests that GI dysfunction during early infant development may be a part of the ASD endophenotype. Late weaning and exclusive breast milk were associated with protection against GI symptoms in high-risk infants.

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

    PubMed

    Kawakami, Kohsaku

    2009-09-01

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

  14. Human Exposure to Early Morning Anopheles funestus Biting Behavior and Personal Protection Provided by Long-Lasting Insecticidal Nets

    PubMed Central

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

    2014-01-01

    A shift towards early morning biting behavior of the major malaria vector Anopheles funestus have been observed in two villages in south Benin following distribution of long-lasting insecticidal nets (LLINs), but the impact of these changes on the personal protection efficacy of LLINs was not evaluated. Data from human and An. funestus behavioral surveys were used to measure the human exposure to An. funestus bites through previously described mathematical models. We estimated the personal protection efficacy provided by LLINs and the proportions of exposure to bite occurring indoors and/or in the early morning. Average personal protection provided by using of LLIN was high (≥80% of the total exposure to bite), but for LLIN users, a large part of remaining exposure occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoué) and/or in the early morning (38.5% in Tokoli-V and 69.4% in Lokohoué). This study highlights the crucial role of LLIN use and the possible need to develop new vector control strategies targeting malaria vectors with outdoor and early morning biting behavior. This multidisciplinary approach that supplements entomology with social science and mathematical modeling illustrates just how important it is to assess where and when humans are actually exposed to malaria vectors before vector control program managers, policy-makers and funders conclude what entomological observations imply. PMID:25115830

  15. High-frequency rTMS on leg motor area in the early phase of stroke.

    PubMed

    Sasaki, Nobuyuki; Abo, Masahiro; Hara, Takatoshi; Yamada, Naoki; Niimi, Masachika; Kakuda, Wataru

    2017-03-01

    Although repetitive transcranial magnetic stimulation (rTMS) for upper limb motor area in stroke patients is beneficial, it has been poorly investigated in rTMS for leg motor area. Furthermore, no study has examined the usefulness of rTMS for leg motor area in patients in the early phase of stroke. Twenty-one patients with a hemispheric stroke lesion in the early phase were randomly assigned into two groups: the high-frequency (HF)-rTMS group [N = 11] and the sham stimulation group [N = 10]. Patients received rTMS for 5 consecutive days, beginning 10.9 ± 6.6 days on average after the onset. Brunnstrom Recovery Stages (BRS) for the lower limbs and the Ability for Basic Movement Scale Revised (ABMS II) were assessed before and after the intervention. The improvement in BRS for the lower limbs was significant after the intervention in the HF-rTMS group. Although both the HF-rTMS and sham stimulation groups had significant improvements in ABMS II scores, the extent of improvement in the AMBS II was significantly greater in the HF-rTMS group than in the sham stimulation group. Application of HF-rTMS over the bilateral leg motor areas has potential to be a new rehabilitation therapy for patients in the acute phase of stroke.

  16. 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.

  17. Keeping Our Children Safe: Protective Behaviour Programs in Early Childhood Settings. Australian Early Childhood Resource Booklets No. 2.

    ERIC Educational Resources Information Center

    Clare, Coleen; Roe, Diana

    This booklet discusses the problem of child abuse in Australia, profiles four child abuse prevention programs, and provides practical suggestions for early childhood educators to help prevent child abuse. The profiled sexual abuse prevention and awareness programs include: (1) CARE Kit, which includes workshops for community agencies, parents, and…

  18. Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans.

    PubMed Central

    Philipp, M T; Aydintug, M K; Bohm, R P; Cogswell, F B; Dennis, V A; Lanners, H N; Lowrie, R C; Roberts, E D; Conway, M D; Karaçorlu, M

    1993-01-01

    We demonstrate that Borrelia burgdorferi infection in the rhesus monkey mimics the early and early disseminated phases of human Lyme disease. Clinical, bacteriological, immunological, and pathological signs of infection were investigated during 13 weeks after inoculation of the spirochete. Three animals were given B. burgdorferi (strain JD1) by needle inoculations, six animals were exposed to the bite of B. burgdorferi-infected Ixodes dammini ticks, and three animals were uninfected controls. B. burgdorferi could be recovered from all animals that were given the spirochete. Bacteria were detectable until week 6 postinoculation (p.i.) in blood, until week 8 p.i. in skin biopsies, and at 10 weeks p.i. in the conjunctiva of one of two animals which developed conjunctivitis. Erythema migrans (EM) appeared in one of the three animals infected by needle inoculation and in five of the six animals infected by ticks. Deep dermal perivascular lymphocytic infiltrations (characteristic of human EM) were observed in all animals showing EM clinically. Both EM and conjunctivitis were documented concomitantly with the presence of the spirochete. Lethargy, splenomegaly, and cerebrospinal fluid pleocytosis were also noted in some animals, but the direct connection of these signs with the infection was not shown. The appearance rate of immunoglobulin M and immunoglobulin G antibodies to B. burgdorferi, as well as the antigen spectra recognized, were remarkably similar to those seen in humans. Serum antibodies from infected animals were able to kill B. burgdorferi in vitro in the presence of rhesus complement. The rhesus monkey model appears to be useful for the investigation of the immunology and pathogenesis of Lyme disease and for the development of immunoprophylactic, diagnostic, and chemotherapeutic protocols. Images PMID:8514412

  19. Restoration of energy level in the early phase of acute pediatric pancreatitis.

    PubMed

    Mosztbacher, Dóra; Farkas, Nelli; Solymár, Margit; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Rumbus, Zoltán; Varjú, Péter; Hegyi, Péter; Párniczky, Andrea

    2017-02-14

    Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better

  20. Restoration of energy level in the early phase of acute pediatric pancreatitis

    PubMed Central

    Mosztbacher, Dóra; Farkas, Nelli; Solymár, Margit; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Rumbus, Zoltán; Varjú, Péter; Hegyi, Péter; Párniczky, Andrea

    2017-01-01

    Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better

  1. 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.

  2. Early origins of child obesity: bridging disciplines and phases of development -- September 30--October 1, 2010.

    PubMed

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

    2012-04-16

    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.

  3. Ultrastructural Complexity of Nuclear Components During Early Apoptotic Phases in Breast Cancer Cells

    PubMed Central

    Castelli, Christian; Losa, Gabriele A.

    2001-01-01

    Fractal morphometry was used to investigate the ultrastructural features of the plasma membrane, perinuclear membrane and nuclear chromatin in SK‐BR‐3 human breast cancer cells undergoing apoptosis. Cells were incubated with 1 μM calcimycin (A23187) for 24 h. Cells in the early stage of apoptosis had fractal dimension (FD) values indicating that their plasma membranes were less rough (lower FD) than those of control cells, while their perinuclear membranes were unaffected. Changes of the chromatin texture within the entire nucleus and in selected nuclear domains were more pronounced in treated cells. This confirms that the morphological reorganization imputable to a loss of structural complexity (reduced FD) occurs in the early stage of apoptosis, is accompanied by the inhibition of distinct enzymatic events and precedes the onset of conventional cellular markers, which can only be detected during the active phases of the apoptotic process. PMID:11790854

  4. Numerical investigation of the early flight phase in ski-jumping.

    PubMed

    Gardan, N; Schneider, A; Polidori, G; Trenchard, H; Seigneur, J M; Beaumont, F; Fourchet, F; Taiar, R

    2017-07-05

    The purpose of this study is to develop a numerical methodology based on real data from wind tunnel experiments to investigate the effect of the ski jumper's posture and speed on aerodynamic forces in a wide range of angles of attack. To improve our knowledge of the aerodynamic behavior of the ski jumper and his equipment during the early flight phase of the ski jump, we applied CFD methodology to evaluate the influence of angle of attack (α=14°, 21.5°, 29°, 36.5° and 44°) and speed (u=23, 26 and 29m/s) on aerodynamic forces in the situation of stable attitude of the ski jumper's body and skis. The standard k-ω turbulence model was used to investigate both the influence of the ski jumper's posture and speed on aerodynamic performance during the early flight phase. Numerical results show that the ski jumper's speed has very little impact on the lift and drag coefficients. Conversely, the lift and drag forces acting on the ski jumper's body during the early flight phase of the jump are strongly influenced by the variations of the angle of attack. The present results suggest that the greater the ski jumper's angle of inclination, with respect to the relative flow, the greater the pressure difference between the lower and upper parts of the skier. Further studies will focus on the dependency of the parameters with both the angle of attack α and the body-ski angle β as control variables. It will be possible to test and optimize different ski jumping styles in different ski jumping hills and investigate different environmental conditions such as temperature, altitude or crosswinds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Specific prebiotic oligosaccharides modulate the early phase of a murine vaccination response.

    PubMed

    Vos, Arjan P; Knol, Jan; Stahl, Bernd; M'rabet, Laura; Garssen, Johan

    2010-05-01

    The immune-modulatory effect of specific prebiotic oligosaccharides was shown in previous preclinical and clinical studies. To enhance the understanding of this effect, kinetic aspects of immune modulation and the correlation between microbiological and immunological parameters were investigated in a murine vaccination model. C57BL/6 mice were supplemented with short-chain galactooligosaccharides and long-chain fructooligosaccharides (ratio 9:1; Immunofortis()) in combination with pectin-derived acidic oligosaccharides. The timing of supplementation was varied around the primary (day 0) and secondary (day 21) vaccinations. Supplementation before the primary vaccination was necessary to increase delayed-type hypersensitivity responses (DTH) significantly at day 30. Supplementation after day 8 did not affect the DTH response at day 30, indicating that immune modulation occurred during the early phase. Therefore, correlation analysis of microbiological and immunological parameters was performed in a shortened experiment to focus on the early phase. At day 9 post-priming, the percentages of cecal lactobacilli were correlated to the DTH responses (p=0.01). Furthermore, the results suggested that yet unidentified factors may play a role. Additional analysis of intestinal Peyer's patch major lymphocyte populations did not show effects of supplementation. In conclusion, a specific oligosaccharide mixture was shown to exert its immune-modulatory effect during the early phase of a murine immune response. The results are consistent with a role of the microbiota and possibly other factors in oligosaccharide-induced immune modulation. Furthermore, the results demonstrate that it is critical to consider kinetic aspects of immune-modulatory and prebiotic effects in order to study their interaction in a meaningful way. Copyright 2010 Elsevier B.V. All rights reserved.

  6. 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

  7. Dispositional optimism and therapeutic expectations in early-phase oncology trials.

    PubMed

    Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

    2016-04-15

    Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have

  8. Perceptions of control and unrealistic optimism in early-phase cancer trials.

    PubMed

    Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Degnin, Catherine; Sulmasy, Daniel P

    2017-08-03

    Recent research has found unrealistic optimism (UO) among patient-subjects in early-phase oncology trials. Our aim was to investigate the cognitive and motivational factors that evoke this bias in this context. We expected perceptions of control to be a strong correlate of unrealistic optimism. A study of patient-subjects enrolled in early-phase oncology trials was conducted at two sites in the USA. Respondents completed questionnaires designed to assess unrealistic optimism and several risk attribute variables that have been found to evoke the bias in other contexts. One hundred and seventy-one patient-subjects agreed to be interviewed for our study. Significant levels of perceived controllability were found with respect to all nine research-related questions. Perceptions of control were found to predict unrealistic optimism. Two other risk attribute variables, awareness of indicators (p=0.024) and mental image (p=0.022), were correlated with unrealistic optimism. However, in multivariate regression analysis, awareness and mental image dropped out of the model and perceived controllability was the only factor independently associated with unrealistic optimism (p<0.0001). Patient-subjects reported that they can, at least partially, control the benefits they receive from participating in an early-phase oncology trial. This sense of control may underlie unrealistic optimism about benefiting personally from trial participation. Effective interventions to counteract unrealistic optimism may need to address the psychological factors that give rise to distorted risk/benefit processing. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. 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.

  10. 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.

  11. Across an early Holocene humid phase in western Sahara:Pollen and isotope stratigraphy

    NASA Astrophysics Data System (ADS)

    Lézine, Anne-Marie; Casanova, Joël; Hillaire-Marcel, Claude

    1990-03-01

    Paleohydrology and paleoecology of the region around the Chemchane sabkha (Mauritania) are reconstructed from the comparative analyses of mineralogy, stable isotope ratios of bulk carbonates, and palynology from sediment cores. The age of the section is from ca. 13.5 ka to the middle Holocene. Maximum lake expansion between about 8.3 and 6.5 ka is recorded in a girdle of stromatolite carbonates. These document a lower-salinity lake concomitant with a general establishment of Sahel-Sudan vegetation. The Chemchane area is the northernmost (lat 21°N) occurrence of humid- phase elements that are related to maximum intensity of monsoon activity during the early Holocene.

  12. The convergence of cancer prevention and therapy in early-phase clinical drug development.

    PubMed

    Abbruzzese, James L; Lippman, Scott M

    2004-10-01

    After decades of separate but not equal drug development, prevention and therapy are beginning to converge at the level of early-phase clinical testing. This highly beneficial convergence is due to spectacular molecular advances in our understanding of neoplasia (both cancer and precancer), cancer risk and prognosis, and the mechanisms by which novel drugs with less toxicity and more cytostatic activity profiles target specific molecular events to suppress malignant and premalignant cells. The future full convergence of prevention-therapy drug development (aided by technological advances, such as in molecular imaging) promises to hasten the progress of oncology in reducing the public health impact of the major cancers.

  13. Neil3 induced neurogenesis protects against prion disease during the clinical phase

    PubMed Central

    Jalland, Clara M. O.; Scheffler, Katja; Benestad, Sylvie L.; Moldal, Torfinn; Ersdal, Cecilie; Gunnes, Gjermund; Suganthan, Rajikala; Bjørås, Magnar; Tranulis, Michael A.

    2016-01-01

    Base excision repair (BER) is the major pathway for repair of oxidative DNA damage. Mice with genetic knockout of the BER enzyme Neil3 display compromised neurogenesis in the sub-ventricular zone of the lateral ventricle and sub-granular layer of the dentate gyrus of the hippocampus. To elucidate the impact of oxidative DNA damage-induced neurogenesis on prion disease we applied the experimental prion disease model on Neil3-deficient mice. The incubation period for the disease was similar in both wild type and Neil3−/− mice and the overall neuropathology appeared unaffected by Neil3 function. However, disease in the Neil3−/− mice was of shorter clinical duration. We observed a mildly reduced astrogliosis in the hippocampus and striatum in the Neil3-deficient mice. Brain expression levels of neuronal progenitor markers, nestin (Nestin), sex determining region Box 2 (Sox2), Class III beta-tubulin (Tuj1) decreased towards end-stage prion disease whereas doublecortin (Dcx) levels were less affected. Neuronal nuclei (NeuN), a marker for mature neurons declined during prion disease and more pronounced in the Neil3−/− group. Microglial activation was prominent and appeared unaffected by loss of Neil3. Our data suggest that neurogenesis induced by Neil3 repair of oxidative DNA damage protects against prion disease during the clinical phase. PMID:27886261

  14. 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.

  15. 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.

  16. 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. 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.

  18. 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.

  19. CpG Type A Induction of an Early Protective Environment in Experimental Multiple Sclerosis

    PubMed Central

    Crooks, James; Gargaro, Marco; Vacca, Carmine; Pirro, Matteo; Scalisi, Giulia; Turco, Antonella; Romani, Rita; Matino, Davide; Rostami, Abdolmohamad; Gran, Bruno

    2017-01-01

    Experimental autoimmune encephalomyelitis (EAE) is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS), and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4+ T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs), typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs). In this study, we compared the effects of two types of CpG, namely, type A and type B, on EAE. We found that treatment with CpG type A ODN (CpG-A), known to induce high amounts of IFN-α in pDCs, significantly reduced disease severity in EAE, relative to controls (12.63 ± 1.86 versus 23.49 ± 1.46, resp.; p = 0.001). Treatment also delayed onset of neurological deficits and reduced spinal cord demyelination, while increasing the percentage of splenic regulatory (Foxp3+ CD4+) T cells. CpG-A likewise reduced the levels of IL-17 and IFN-γ in the CNS. Mechanistic insight into those events showed that CpG-A promoted a regulatory phenotype in pDCs. Moreover, adoptive transfer of pDCs isolated from CpG-A-treated mice inhibited CNS inflammation and induced disease remission in acute-phase EAE. Our data thus identify a link between TLR9 activation by specific ligands and the induction of tolerance via innate immunity mechanisms. PMID:28356656

  20. Many-body topological invariants in fermionic symmetry-protected topological phases: Cases of point group symmetries

    NASA Astrophysics Data System (ADS)

    Shiozaki, Ken; Shapourian, Hassan; Ryu, Shinsei

    2017-05-01

    We propose the definitions of many-body topological invariants to detect symmetry-protected topological phases protected by point group symmetry, using partial point group transformations on a given short-range entangled quantum ground state. Here, partial point group transformations gD are defined by point group transformations restricted to a spatial subregion D , which is closed under the point group transformations and sufficiently larger than the bulk correlation length ξ . By analytical and numerical calculations, we find that the ground state (GS) expectation value of the partial point group transformations behaves generically as ˜exp [i θ +γ -α Area/(∂ D ) ξd -1] . Here, Area (∂ D ) is the area of the boundary of the subregion D , and α is a dimensionless constant. The complex phase of the expectation value θ is quantized and serves as the topological invariant, and γ is a scale-independent topological contribution to the amplitude. The examples we consider include the Z8 and Z16 invariants of topological superconductors protected by inversion symmetry in (1 +1 ) and (3 +1 ) dimensions, respectively, and the lens space topological invariants in (2 +1 ) -dimensional fermionic topological phases. Connections to topological quantum field theories and cobordism classification of symmetry-protected topological phases are discussed.

  1. 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.

  2. Optical Embedded Dust Sensor for Engine Protection and Early Warning on M1 Abrams/Ground Combat Vehicles

    DTIC Science & Technology

    2012-04-11

    Optical embedded dust sensor for engine protection and early warning on M1 Abrams/ground combat vehicles Hai Lina, Gregor A. Waldherrb, Timothy...Burch*a aIntelligent Optical Systems, 73 N. Vinedo Ave., Pasadena, CA, USA 91107-3759 bHal Technology, LLC, 7970 Cherry Avenue, Suite 303, Fontana, CA...the DoA, and shall not be used for advertising or product endorsement purposes. ABSTRACT The Dual Optical Embedded Dust Sensor (DOEDS) is designed

  3. 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.

  4. 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.

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

    PubMed

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

    2004-12-03

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

  6. 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)…

  7. Child Developmental Impact of Pittsburgh's Early Childhood Initiative (ECI) in High-Risk Communities: First-Phase Authentic Evaluation Research.

    ERIC Educational Resources Information Center

    Bagnato, Stephen J.; Suen, Hoi K.; Brickley, Dale; Smith-Jones, Janell; Dettore, Ernie

    2002-01-01

    This study used an "enhanced constructed comparison group" statistical model to conduct longitudinal research on the child developmental impact of Pittsburgh's early childhood initiative (ECI), a partnership to provide high-quality early care and education for children in high-risk neighborhoods. First-phase findings indicate that…

  8. Risk and protective factors in early child development: Results from the All Our Babies (AOB) pregnancy cohort.

    PubMed

    McDonald, Sheila; Kehler, Heather; Bayrampour, Hamideh; Fraser-Lee, Nonie; Tough, Suzanne

    2016-11-01

    Understanding factors that protect against early developmental delay among children who are experiencing adversity can inform prevention and early intervention strategies. To identify risk factors for development delay at one year and protective factors for developmental delay in 'at risk' environments (poor maternal mental health and socio-demographic risk). Data was analyzed from 3360 mother-child dyads who participated in the All Our Babies (AOB) pregnancy cohort. Participants completed four questionnaires spanning pregnancy to one year postpartum and provided access to medical records. Risk factors for developmental delay at age one were identified using bivariate methods and multivariable modeling. Protective factors for child development in 'at risk' family environments were identified using bivariate analyses. At one year, 17% of children were developmentally delayed, defined as scoring in the monitoring zone on at least 2 of the 5 developmental domains of the Ages and Stages Questionnaire. Prenatal depression, preterm birth, low community engagement, and non-daily parent-child interaction increased the risk of delay. Protective factors for children in 'at risk' environments included relationship happiness, parenting self-efficacy, community engagement, higher social support, and daily parent-child interaction. The study results suggest that maternal and infant outcomes would be improved, even for vulnerable women, through identification and intervention to address poor mental health and through normalizing engagement with low cost, accessible community resources that can also support parent-child interaction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. 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.

  10. A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

    PubMed

    Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

    2011-10-01

    In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

  11. 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

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

    PubMed

    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 (F ST < 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.

  13. 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.

  14. Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections

    PubMed Central

    Yu, Yanbao; Kwon, Keehwan; Tsitrin, Tamara; Sikorski, Patricia; Nelson, Karen E.; Pieper, Rembert

    2017-01-01

    Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs. The effector proteins were further enriched in DNA-protein complexes isolated in native PAGE gels. Immunofluorescence microscopy revealed a flattened morphology of neutrophils associated with decondensed chromatin, remnants of granules in the cell periphery, and myeloperoxidase co-localized with extracellular DNA, features consistent with early-phase NETs. Nuclear staining revealed that a considerable fraction of bacterial cells in these structures were dead. The proteomes of two pathogens, Staphylococcus aureus and Escherichia coli, were indicative of adaptive responses to early-phase NETs, specifically the release of virulence factors and arrest of ribosomal protein synthesis. Finally, we discovered patterns of proteolysis consistent with widespread cleavage of proteins by neutrophil elastase, proteinase 3 and cathepsin G and evidence of citrullination in many nuclear proteins. PMID:28129394

  15. Internal Dose from Food and Drink Ingestion in the Early Phase after the Accident

    NASA Astrophysics Data System (ADS)

    Kawai, Masaki; Yoshizawa, Nobuaki; Hirakawa, Sachiko; Murakami, Kana; Takizawa, Mari; Sato, Osamu; Takagi, Shunji; Miyatake, Hirokazu; Takahashi, Tomoyuki; Suzuki, Gen

    2017-09-01

    Activity concentrations in food and drink, represented by water and vegetables, have been monitored continuously since the Fukushima Daiichi Nuclear Power Plant accident, with a focus on radioactive cesium. On the other hand, iodine-131 was not measured systematically in the early phase after the accident. The activity concentrations of iodine-131 in food and drink are important to estimate internal exposure due to ingestion pathway. When the internal dose from ingestion in the evacuation areas is estimated, water is considered as the main ingestion pathway. In this study, we estimated the values of activity concentrations in water in the early phase after the accident, using a compartment model as an estimation method. The model uses measurement values of activity concentration and deposition rate of iodine-131 onto the ground, which is calculated from an atmospheric dispersion simulation. The model considers how drinking water would be affected by radionuclides deposited into water. We estimated the activity concentrations of water on Kawamata town and Minamisouma city during March of 2011 and the committed effective doses were 0.08 mSv and 0.06 mSv. We calculated the transfer parameters in the model for estimating the activity concentrations in the areas with a small amount of measurement data. In addition, we estimated the committed effective doses from vegetables using atmospheric dispersion simulation and FARMLAND model in case of eating certain vegetables as option information.

  16. Worldwide isotope ratios of the Fukushima release and early-phase external dose reconstruction

    PubMed Central

    Chaisan, Kittisak; Smith, Jim T.; Bossew, Peter; Kirchner, Gerald; Laptev, Gennady V.

    2013-01-01

    Measurements of radionuclides (RNs) in air made worldwide following the Fukushima accident are quantitatively compared with air and soil measurements made in Japan. Isotopic ratios RN:137Cs of 131I, 132Te, 134,136Cs, are correlated with distance from release. It is shown, for the first time, that both within Japan and globally, ratios RN:137Cs in air were relatively constant for primarily particle associated radionuclides (134,136Cs; 132Te) but that 131I shows much lower local (<80 km) isotope ratios in soils relative to 137Cs. Derived isotope ratios are used to reconstruct external dose rate during the early phase post-accident. Model “blind” tests show more than 95% of predictions within a factor of two of measurements from 15 sites to the north, northwest and west of the power station. It is demonstrated that generic isotope ratios provide a sound basis for reconstruction of early-phase external dose rates in these most contaminated areas. PMID:24018776

  17. Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections.

    PubMed

    Yu, Yanbao; Kwon, Keehwan; Tsitrin, Tamara; Bekele, Shiferaw; Sikorski, Patricia; Nelson, Karen E; Pieper, Rembert

    2017-01-01

    Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs. The effector proteins were further enriched in DNA-protein complexes isolated in native PAGE gels. Immunofluorescence microscopy revealed a flattened morphology of neutrophils associated with decondensed chromatin, remnants of granules in the cell periphery, and myeloperoxidase co-localized with extracellular DNA, features consistent with early-phase NETs. Nuclear staining revealed that a considerable fraction of bacterial cells in these structures were dead. The proteomes of two pathogens, Staphylococcus aureus and Escherichia coli, were indicative of adaptive responses to early-phase NETs, specifically the release of virulence factors and arrest of ribosomal protein synthesis. Finally, we discovered patterns of proteolysis consistent with widespread cleavage of proteins by neutrophil elastase, proteinase 3 and cathepsin G and evidence of citrullination in many nuclear proteins.

  18. AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3beta.

    PubMed

    Fumoto, K; Lee, P-C; Saya, H; Kikuchi, A

    2008-07-24

    Glycogen synthase kinase-3 (GSK-3beta) regulates microtubule dynamics and cellular polarity through phosphorylating various microtubule associating proteins and plus-end tracking proteins. Although it was also reported that GSK-3beta is inactivated by protein kinase B at the spindle poles, functions and targets of GSK-3beta in the mitotic phase are unknown. Here, we identified Aurora-A-interacting protein (AIP), a negative regulator of Aurora-A, as a binding partner of GSK-3beta. AIP was colocalized with Aurora-A and GSK-3beta to the spindle poles in metaphase, and its depletion in cells stabilized and activated Aurora-A in early mitotic phase and caused mitotic cell arrest. Treatment of the cells with a GSK-3beta inhibitor reduced the protein level of Aurora-A and this reduction was suppressed by AIP knockdown. AIP was phosphorylated by GSK-3beta, and an AIP mutant in which the GSK-3beta phosphorylation site was mutated could bind and downregulate Aurora-A more efficiently. These results suggest that GSK-3beta modulates the early mitotic Aurora-A level through binding and phosphorylating AIP.

  19. Unknown loads affect force production capacity in early phases of bench press throws.

    PubMed

    Hernández Davó, J L; Sabido Solana, R; Sarabia Marínm, J M; Sánchez Martos, Á; Moya Ramón, M

    2015-10-01

    Explosive strength training aims to improve force generation in early phases of movement due to its importance in sport performance. The present study examined the influence of lack of knowledge about the load lifted in explosive parameters during bench press throws. Thirteen healthy young men (22.8±2.0 years) participated in the study. Participants performed bench press throws with three different loads (30, 50 and 70% of 1 repetition maximum) in two different conditions (known and unknown loads). In unknown condition, loads were changed within sets in each repetition and participants did not know the load, whereas in known condition the load did not change within sets and participants had knowledge about the load lifted. Results of repeated-measures ANOVA revealed that unknown conditions involves higher power in the first 30, 50, 100 and 150 ms with the three loads, higher values of ratio of force development in those first instants, and differences in time to reach maximal rate of force development with 50 and 70% of 1 repetition maximum. This study showed that unknown conditions elicit higher values of explosive parameters in early phases of bench press throws, thereby this kind of methodology could be considered in explosive strength training.

  20. Maintaining Traditions: A Qualitative Study of Early Childhood Caries Risk and Protective Factors in an Indigenous Community.

    PubMed

    Levin, Ana; Sokal-Gutierrez, Karen; Hargrave, Anita; Funsch, Elizabeth; Hoeft, Kristin S

    2017-08-11

    In lower middle-income economies (LMIE), the nutrition transition from traditional diets to sugary foods and beverages has contributed to widespread early childhood dental caries. This qualitative study explores perceived risk and protective factors, and overall experiences of early childhood nutrition and oral health in indigenous Ecuadorian families participating in a community-based oral health and nutrition intervention. Dental exams of 698 children age 6 months through 6 years determined each child's caries burden. A convenience sample of 18 "outlier" families was identified: low-caries children with ≤2 carious teeth vs. high-caries children with ≥10 carious teeth. Semi-structured in-depth interviews with parents/caregivers explored the child's diet, dental habits, and family factors related to nutrition and oral health. Interviews were transcribed and thematically analyzed using grounded theory. In the high-caries families, proximity to highway and stores, consumption of processed-food, and low parental monitoring of child behavior were identified as risk factors for ECC (early childhood caries). In the low-caries families, protective factors included harvesting and consuming food from the family farm, remote geography, and greater parental monitoring of child behavior. The study results suggest that maintaining traditional family farms and authoritative parenting to avoid processed foods/drinks and ensure tooth brushing could improve early childhood nutrition and oral health.

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

    PubMed

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

    2015-04-01

    Early cocking phase pitching mechanics may affect risk of upper extremity injury requiring surgery in professional baseball players. 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. Cross-sectional study; Level of evidence, 3. 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. 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). The inverted-W throwing position was not associated with significantly greater risk of upper extremity injury requiring surgery in MLB

  2. 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

  3. IFN-gamma treatment at early stages of influenza virus infection protects mice from death in a NK cell-dependent manner.

    PubMed

    Weiss, Ido D; Wald, Ori; Wald, Hanna; Beider, Katia; Abraham, Michal; Galun, Eithan; Nagler, Arnon; Peled, Amnon

    2010-06-01

    Influenza pandemics are imminent and represent a major world health concern. Since vaccinations are expected to be less efficient in the coming years due to newly emerging influenza virus strains, novel antiviral therapies are urgently needed. Here, we show that influenza-infected mice, capable of clearing the virus in the early stages of infection, failed to control inflammation and death. Sequential administration of Interferon-gamma (IFN-gamma) at early stage of the infection protected infected mice from death in a NK cell-dependent manner. IFN-gamma treatment stimulated NK cell proliferation and function and increased their number in the bone marrow, blood, spleen, and infected lungs, keeping viral clearance intact. In parallel, IFN-gamma treatment significantly reduced the number of T cells and NKT cells in the lungs at the inflammatory phase following infection. Thus, rapidly clearing the virus and reducing inflammation by shaping the cellular and cytokine profiles in the early stages of infection may favorably change the fate of influenza pathogenesis.

  4. Phase Contrast MRI is an Early Marker of Micrometastatic Breast Cancer Development in the Rat Brain

    PubMed Central

    Budde, Matthew D; Gold, Eric; Jordan, E. Kay; Smith-Brown, Melissa; Frank, Joseph A

    2011-01-01

    The early growth of micrometastatic breast cancer in the brain often occurs through vessel co-option and is independent of angiogenesis. Remodeling of the existing vasculature is an important step in the evolution of co-opting micrometastases into angiogenesis-dependent solid tumor masses. The purpose of this study was to determine if phase contrast MRI, an intrinsic source of contrast exquisitely sensitive to the magnetic susceptibility properties of deoxygenated hemoglobin, could detect vascular changes occurring independent of angiogenesis in a rat model of breast cancer metastases to the brain. Twelve nude rats were administered with 106 MDA-MB-231BRL “brain seeking” breast cancer cells through intracardiac injection. Serial, multiparametric MRI of the brain was performed weekly until metastatic disease was detected. The results demonstrate that images of the signal phase were more sensitive to metastatic brain lesions (area under receiver operating characteristic curve, AUC = 0.97) compared to T2* gradient echo magnitude images, (AUC = 0.73). The difference between the two techniques was likely the result of the confounding effects of edema on the magnitude signal. A region of interest analysis revealed that vascular abnormalities detected with phase contrast MRI preceded tumor permeability as measured with contrast-enhanced MRI by 1 to 2 weeks. Tumor size was correlated with permeability (R2 = 0.23, p < 0.01), but phase contrast was independent of tumor size (R2 = 0.03). Histopathological analysis demonstrated that capillary endothelial cells coopted by tumor cells were significantly enlarged, but less dense, compared to the normal brain vasculature. Whereas co-opted vessels were VEGF-negative, vessels within larger tumor masses were VEGF-positive. In conclusion, phase contrast MRI is believed to be sensitive to vascular remodeling in co-opting brain tumor metastases independent of sprouting angiogenesis and may therefore aid in pre-clinical studies of

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

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

  6. Metabolic reprogramming identifies the most aggressive lesions at early phases of hepatic carcinogenesis

    PubMed Central

    Perra, Andrea; Menegon, Silvia; Masgras, Ionica; Trevisan, Elena; Angioni, Maria Maddalena; Fornari, Francesca; Quagliata, Luca; Ledda-Columbano, Giovanna Maria; Gramantieri, Laura; Terracciano, Luigi; Giordano, Silvia; Chiarugi, Paola; Rasola, Andrea; Columbano, Amedeo

    2016-01-01

    Metabolic changes are associated with cancer, but whether they are just bystander effects of deregulated oncogenic signaling pathways or characterize early phases of tumorigenesis remains unclear. Here we show in a rat model of hepatocarcinogenesis that early preneoplastic foci and nodules that progress towards hepatocellular carcinoma (HCC) are characterized both by inhibition of oxidative phosphorylation (OXPHOS) and by enhanced glucose utilization to fuel the pentose phosphate pathway (PPP). These changes respectively require increased expression of the mitochondrial chaperone TRAP1 and of the transcription factor NRF2 that induces the expression of the rate-limiting PPP enzyme glucose-6-phosphate dehydrogenase (G6PD), following miR-1 inhibition. Such metabolic rewiring exclusively identifies a subset of aggressive cytokeratin-19 positive preneoplastic hepatocytes and not slowly growing lesions. No such metabolic changes were observed during non-neoplastic liver regeneration occurring after two/third partial hepatectomy. TRAP1 silencing inhibited the colony forming ability of HCC cells while NRF2 silencing decreased G6PD expression and concomitantly increased miR-1; conversely, transfection with miR-1 mimic abolished G6PD expression. Finally, in human HCC patients increased G6PD expression levels correlates with grading, metastasis and poor prognosis. Our results demonstrate that the metabolic deregulation orchestrated by TRAP1 and NRF2 is an early event restricted to the more aggressive preneoplastic lesions. PMID:27070090

  7. Multiphoton microscopic imaging of esophagus during the early phase of tumor progression.

    PubMed

    Xu, Jian; Kang, Deyong; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Chen, Jianxin

    2013-01-01

    Esophageal cancer is one of the most common cancer and leading cause of cancer death worldwide. Multiphoton microscopy (MPM) has become a novel optical tool of choice for imaging tissue architecture and cellular morphology based on two-photon excited fluorescence and second harmonic generation. In this study, we used MPM to image microstructure of human normal esophagus, carcinoma in situ, and early invasive carcinoma in order to investigate the morphological change of tissue structure during the early phase of tumor progression. The diagnostic features such as the appearance of cancerous cells, the absence of the basement membrane were extracted to distinguish between normal and cancerous esophagus tissue. The infiltration depth during tumor progression was determined by the appearance of cancerous cells. The significant change of layer structure between cancerous tissue and normal esophagus was described. We also quantitatively described the differences of morphology between normal and cancerous cells. These results correlated well with the corresponding 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. © Wiley Periodicals, Inc.

  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.

  9. Discriminating among stellar population synthesis models of the TP-AGB phase in early quiescent galaxies

    NASA Astrophysics Data System (ADS)

    MacDougall, Mason; Newman, Andrew; Belli, Sirio; Ellis, Richard S.

    2017-01-01

    Galactic evolution at high redshifts is largely understood through stellar population synthesis (SPS) modeling of spectra and photometry integrated over all starlight of a galaxy. However, complex and poorly understood stellar phases like the unstable thermally-pulsating asymptotic giant branch (TP-AGB) phase make SPS modeling a difficult task. Recent models fail to agree on the TP-AGB contribution to the infrared luminosity, leading to significant discrepancy among the properties derived from modern SPS models when applied to early galaxies. Here we provide a thorough assessment of each of the most widely used SPS models by comparing their results and assessing their accuracy in modeling our unique dataset. We combine high-resolution spectroscopic observations from Keck/MOSFIRE with photometric data for 21 early quiescent galaxies with redshifts of z ~ 2. These galaxies are around the age of peak TP-AGB activity, between ~0.3 and 2 Gyr, and therefore provide an ideal test of the models. We find that models with a “light” TP-AGB contribution provide much better descriptions of our galaxies at ages of ~1 Gyr or less. This is true at high statistical significance and holds for models with or without dust reddening. However, contrary to previous studies, the model-dependent photometrically estimated ages are similar among the models, but they show only moderate agreement with the more model-independent spectroscopic ages derived from stellar absorption lines. The largest discrepancies are found for the Charlot & Bruzual (2007) models which show an artificial clustering of ages around 1 Gyr. The TP-AGB “light” models require more reddening, which can be independently tested by examining dust emission in the mid-infrared. The modeled fluxes are also mostly consistent with mid-infrared observations, with the exception of one model. Resolving these differences among the models will substantially strengthen our estimates of the properties of early quiescent

  10. Transference patterns and working alliance during the early phase of psychodynamic psychotherapy.

    PubMed

    Samardzić, Ljiljana; Nikolić, Gordana

    2014-02-01

    Working alliance, as a collaborative part of the therapeutic relationship has been proven to be one of the most powerful therapeutic factors in psychotherapy in general, regardless many technical differences between numerous psychotherapeutic modalities. On the other hand, transference is the basic concept of psychodynamic psychotherapy, and, according to the psychoanalytic theory and practice, it forms a major part of the therapeutic relationship. The aim of our paper was to determine the differences between the groups of patients with low, middle, and high working alliance scores and the dropout group in transference patterns, sociodemographic and clinical parameters, during the early phase of psychodynamic psychotherapy. Our sample consisted of 61 non-psychotic patients, randomly selected by the method of consecutive admissions and treated with psychoanalytic psychotherapy in the outpatient clinical setting. The patients were prospectively followed during 5 initial sessions of the therapeutic process. The working alliance inventory and Core conflictual relationship theme method were used for the estimation of working alliance and transference patterns, respectively. According to the Working Alliance Inventory scores, four groups of patients were formed and than compared. Our results show a significant difference between the groups of patients with low, middle, and high working alliance inventory scores and the dropout group on the variable--transference patterns in the therapeutic relationship. Disharmonious transference patterns are more frequent in patients who form poor quality working alliance in the early phase of psychotherapy, or early dropout psychotherapy. It is of great importance to recognize transference patterns of a patient at the beginning of the psychotherapeutic process, because of their potentially harmful influence on the quality of working alliance.

  11. Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

    PubMed

    Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

    2008-01-01

    The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.

  12. Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

    PubMed

    Farid, Karim; Hong, Young T; Aigbirhio, Franklin I; Fryer, Tim D; Menon, David K; Warburton, Elizabeth A; Baron, Jean-Claude

    2015-01-01

    Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1-6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD.

  13. Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

    PubMed Central

    Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

    2015-01-01

    Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

  14. Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.

    PubMed

    Massett, Holly A; Mishkin, Grace; Rubinstein, Larry; Ivy, S Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A; Abrams, Jeffrey S

    2016-11-15

    Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397.

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

    PubMed

    Cao, Zhuoxiao; Li, Yunbo

    2004-04-05

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

  16. 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

  17. 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

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

    SciTech Connect

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

    2013-09-20

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

  19. 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

    2016-02-19

    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 structure 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.

  20. 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

  1. Phase-field simulations of nuclei and early stage solidification microstructures

    NASA Astrophysics Data System (ADS)

    Nestler, B.; Selzer, M.; Danilov, D.

    2009-11-01

    To investigate the local properties of heterogeneous nuclei on substrates, a phase-field model is extended to incorporate volume constraints and a third order line tension in the gradient free energy density formulation. The new model is applied to sessile drop simulations of Cu nuclei on Ni substrates to precisely analyse 3D equilibrium shapes and diffusion processes across the phase boundaries. In particular, the formalism with higher order potentials is used to investigate the length-scale dependent effect of the line tension on Young's force balance at triple lines in 3D. The employment of parallel and adaptive simulation techniques is essential for three-dimensional numerical computations. Early stage solidification microstructures of cubic Ni crystals are simulated by scale-bridging molecular dynamics (MD) and phase-field (PF) simulations. The domain of the PF computations is initialized by transferring MD data of the atomic positions and of the shape of the nuclei. The combined approach can be used to study the responses of microstructures upon nucleation.

  2. 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.

  3. The accelerating effect of chitosan-silica hybrid dressing materials on the early phase of wound healing.

    PubMed

    Park, Ji-Ung; Jung, Hyun-Do; Song, Eun-Ho; Choi, Tae-Hyun; Kim, Hyoun-Ee; Song, Juha; Kim, Sukwha

    2017-10-01

    Commercialized dressing materials with or without silver have played a passive role in early-phase wound healing, protecting the skin defects from infections, absorbing exudate, and preventing dehydration. Chitosan (CTS)-based sponges have been developed in pure or hybrid forms for accelerating wound healing, but their wound-healing capabilities have not been extensively compared with widely used commercial dressing materials, providing limited information in a practical aspect. In this study, we have developed CTS-silica (CTS-Si) hybrid sponges with water absorption, flexibility, and mechanical behavior similar to those of CTS sponges. In vitro and in vivo tests were performed to compare the CTS-Si sponges with three commercial dressing materials [gauze, polyurethane (PU), and silver-containing hydrofiber (HF-Ag)] in addition to CTS sponges. Both in vitro and in vivo tests showed that CTS-Si sponges promoted fibroblast proliferation, leading to accelerated collagen synthesis, whereas the CTS sponges did not exhibit significant differences in fibroblast proliferation and collagen synthesis from gauze, PU, and HF-Ag sponges. In case of CTS-Si, the inflammatory cells were actively recruited to the wound by the influence of the released silicon ions from CTS-Si sponges, which, in return, led to an enhanced secretion of growth factors, particularly TGF-β during the early stage. The higher level of TGF-β likely improved the proliferation of fibroblasts, and as a result, collagen synthesis by fibroblasts became remarkably productive, thereby increasing collagen density at the wound site. Therefore, the CTS-Si hybrid sponges have considerable potential as a wound-dressing material for accelerating wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1828-1839, 2017. © 2016 Wiley Periodicals, Inc.

  4. Early risk and protective factors for problem gambling: A systematic review and meta-analysis of longitudinal studies.

    PubMed

    Dowling, N A; Merkouris, S S; Greenwood, C J; Oldenhof, E; Toumbourou, J W; Youssef, G J

    2017-02-01

    This systematic review aimed to identify early risk and protective factors (in childhood, adolescence or young adulthood) longitudinally associated with the subsequent development of gambling problems. A systematic search of peer-reviewed and grey literature from 1990 to 2015 identified 15 studies published in 23 articles. Meta-analyses quantified the effect size of 13 individual risk factors (alcohol use frequency, antisocial behaviours, depression, male gender, cannabis use, illicit drug use, impulsivity, number of gambling activities, problem gambling severity, sensation seeking, tobacco use, violence, undercontrolled temperament), one relationship risk factor (peer antisocial behaviours), one community risk factor (poor academic performance), one individual protective factor (socio-economic status) and two relationship protective factors (parent supervision, social problems). Effect sizes were on average small to medium and sensitivity analyses revealed that the results were generally robust to the quality of methodological approaches of the included articles. These findings highlight the need for global prevention efforts that reduce risk factors and screen young people with high-risk profiles. There is insufficient investigation of protective factors to adequately guide prevention initiatives. Future longitudinal research is required to identify additional risk and protective factors associated with problem gambling, particularly within the relationship, community, and societal levels of the socio-ecological model. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. SunSmart: evaluation of a pilot school-based sun protection intervention in Hispanic early adolescents

    PubMed Central

    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 neighborhoods in Los Angeles. The analytic sample was restricted to students identifying as Hispanic or Latino (n = 777). A mixed effects linear model was used to test mean changes from pre- to posttest on students’ sun protection knowledge, attitudes and behaviors. Significant improvements were observed across several cognitive outcomes related to sun protection, including knowledge of and attitudes toward sun protection and self-efficacy to wear sunscreen. However, changes in sun protective behaviors were not achieved. Although some improvements were observed, future studies should identify the factors that motivate sun protection in this population and develop tailored prevention strategies, as improving the sun safe behaviors of Hispanic youths may aid in reducing the risk of melanoma in adulthood in this population. PMID:25801103

  6. SunSmart: evaluation of a pilot school-based sun protection intervention in Hispanic early adolescents.

    PubMed

    Miller, K A; Langholz, B M; Ly, T; Harris, S C; Richardson, J L; Peng, D H; Cockburn, M G

    2015-06-01

    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 neighborhoods in Los Angeles. The analytic sample was restricted to students identifying as Hispanic or Latino (n = 777). A mixed effects linear model was used to test mean changes from pre- to posttest on students' sun protection knowledge, attitudes and behaviors. Significant improvements were observed across several cognitive outcomes related to sun protection, including knowledge of and attitudes toward sun protection and self-efficacy to wear sunscreen. However, changes in sun protective behaviors were not achieved. Although some improvements were observed, future studies should identify the factors that motivate sun protection in this population and develop tailored prevention strategies, as improving the sun safe behaviors of Hispanic youths may aid in reducing the risk of melanoma in adulthood in this population. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. 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

  8. The Rate of Conversion from Immune-tolerant Phase to Early Immune-clearance Phase in Children with Chronic Hepatitis B Virus Infection.

    PubMed

    Hong, Suk Jin; Park, Hyo Jung; Chu, Mi Ae; Choi, Bong Seok; Choe, Byung-Ho

    2014-03-01

    The spontaneous seroconversion rate of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) virus infection in children is lower than that in adults. However, few studies have investigated the rate of transition from the immune-tolerant to the early immune-clearance phase in children. From February 2000 to August 2011, we enrolled 133 children aged <18 years who had visited the Department of Pediatrics, Kyungpook National University Hospital. All subjects were in the immune-tolerant phase of HBeAg-positive CHB virus infection. The estimated transition rate into the early immune-clearance phase was calculated using the Kaplan-Meier method. Among the 133 enrolled pediatric CHB virus infection patients in the HBeAg-positive immune-tolerant phase, only 21 children (15.8%) had converted to the early immune-clearance phase. The average age at entry into active hepatitis was 10.6±4.8 years. The incidence of transition from the immune-tolerant to the early immune-clearance phase in these children was 1.7 episodes/100 patient-years. When analyzed by age, the estimated transition rate was 4.6%, 7.1%, and 28.0% for patients aged <6, 6-12, >12 years, respectively. In children with CHB virus infection, the estimated rate of entry into the early immune-clearance phase was 28.0% for patients aged 12-18 years, which was significantly higher than that observed for children aged <12 years (11.7%; p=0.001).

  9. 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

  10. 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

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

    PubMed

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

    2010-02-01

    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. 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. 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. 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 lineages of angiosperms.

  12. 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.

  13. Role of Occult and Post-acute Phase Replication in Protective Immunity Induced with a Novel Live Attenuated SIV Vaccine

    PubMed Central

    Ham, Claire; Ferguson, Deborah; Tudor, Hannah; Mattiuzzo, Giada; Klaver, Bep; Page, Mark; Stebbings, Richard; Das, Atze T.; Berkhout, Ben; Almond, Neil; Cranage, Martin P.

    2016-01-01

    In order to evaluate the role of persisting virus replication during occult phase immunisation in the live attenuated SIV vaccine model, a novel SIVmac239Δnef variant (SIVrtTA) genetically engineered to replicate in the presence of doxycycline was evaluated for its ability to protect against wild-type SIVmac239. Indian rhesus macaques were vaccinated either with SIVrtTA or with SIVmac239Δnef. Doxycycline was withdrawn from 4 of 8 SIVrtTA vaccinates before challenge with wild-type virus. Unvaccinated challenge controls exhibited ~107 peak plasma viral RNA copies/ml persisting beyond the acute phase. Six vaccinates, four SIVmac239Δnef and two SIVrtTA vaccinates exhibited complete protection, defined by lack of wild-type viraemia post-challenge and virus-specific PCR analysis of tissues recovered post-mortem, whereas six SIVrtTA vaccinates were protected from high levels of viraemia. Critically, the complete protection in two SIVrtTA vaccinates was associated with enhanced SIVrtTA replication in the immediate post-acute vaccination period but was independent of doxycycline status at the time of challenge. Mutations were identified in the LTR promoter region and rtTA gene that do not affect doxycycline-control but were associated with enhanced post-acute phase replication in protected vaccinates. High frequencies of total circulating CD8+T effector memory cells and a higher total frequency of SIV-specific CD8+ mono and polyfunctional T cells on the day of wild-type challenge were associated with complete protection but these parameters were not predictive of outcome when assessed 130 days after challenge. Moreover, challenge virus-specific Nef CD8+ polyfunctional T cell responses and antigen were detected in tissues post mortem in completely-protected macaques indicating post-challenge control of infection. Within the parameters of the study design, on-going occult-phase replication may not be absolutely required for protective immunity. PMID:28002473

  14. Aural exostoses (surfer's ear) provide vital fossil evidence of an aquatic phase in Man's early evolution.

    PubMed

    Rhys Evans, P H; Cameron, M

    2017-09-15

    For over a century, otolaryngologists have recognised the condition of aural exostoses, but their significance and aetiology remains obscure, although they tend to be associated with frequent swimming and cold water immersion of the auditory canal. The fact that this condition is usually bilateral is predictable since both ears are immersed in water. However, why do exostoses only grow in swimmers and why do they grow in the deep bony meatus at two or three constant sites? Furthermore, from an evolutionary point of view, what is or was the purpose and function of these rather incongruous protrusions? In recent decades, paleoanthropological evidence has challenged ideas about early hominid evolution. In 1992 the senior author suggested that aural exostoses were evolved in early hominid Man for protection of the delicate tympanic membrane during swimming and diving by narrowing the ear canal in a similar fashion to other semiaquatic species. We now provide evidence for this theory and propose an aetiological explanation for the formation of exostoses.

  15. Changes in nucleosome repeat lengths precede replication in the early replicating metallothionein II gene region of cells synchronized in early S phase

    SciTech Connect

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

    1989-04-04

    Previous investigations showed that inhibition of DNA synthesis by hydroxyurea, aphidicolin, or 5-fluorodeoxyuridine produced large changes in the composition and nucleosome repeat lengths of bulk chromatin. There the authors report results of investigations to determine whether the changes in nucleosome repeat lengths might be localized in the initiated replicons, as postulated. In most experiments, Chinese hamster (line CHO) cells were synchronized in G1, or they were synchronized in early S phase by allowing G1 cells to enter S phase in medium containing 1 mM hydroxyurea or 5 {mu}g mL{sup {minus}1} aphidicolin, a procedure believed to produce an accumulation of initiated replicons that arise from normally early replicating DNA. Measurements of nucleosome repeat lengths of bulk chromatin, the early replicating unexpressed metallothionein II (MTII) gene region, and a later replicating repeated sequence indicate that the changes in repeat lengths occur preferentially in the early replicating MTII gene region as G1 cells enter and become synchronized in early S phase. During that time, the MTII gene region is not replicated nor is there any evidence for induction of MTII messenger RNA. Thus, the results are consistent with the hypothesis that changes in chromatin structure occur preferentially in the early replicating (presumably initiated) replicons at initiation or that changes in chromatin structure can precede replication during inhibition of DNA synthesis. The shortened repeat lengths that precede MTII replication are, potentially, reversible, because they become elongated when the synchronized early S-phase cells are released to resume cell cycle progression.

  16. The effect of defective early phase insulin secretion on postload glucose intolerance in impaired fasting glucose.

    PubMed

    Sargin, Mehmet; Ikiişik, Murat; Sargin, Haluk; Orçun, Asuman; Kaya, Müjgan; Gözü, Hülya; Dabak, Reşat; Bayramiçli, Oya Uygur; Yayla, Ali

    2005-10-01

    Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk groups for type 2 diabetes. Type 2 diabetes is characterized by both impaired insulin secretion and insulin resistance but their relative contribution to the development of hyperglycemia may differ due to heterogeneity of the disease. Combined glucose intolerance (CGI), on the other hand, seems to represent a more advanced stage of prediabetes that bears a distinctly higher risk of progression to diabetes and its comorbidities. This study has the aim to compare isolated IFG and CGI categories with respect to the degree of early phase insulin secretion abnormalities and insulin resistance. Subjects who had IFG (fasting glucose: 110-126 mg/dl) were included in the study. A 75-g oral glucose tolerance test (OGTT) with insulin response was done and subjects were classified according to the WHO criteria. Six subjects were excluded because they had diabetic glucose tolerance. A total of 66 patients (53.4 +/- 11.1 years, female/male: 48/18) were divided into two groups according to their glucose tolerance in OGGT (Group 1: isolated IFG and group 2: CGI). Early phase insulin secretion was measured by intravenous glucose tolerance test (IVGTT) and OGTT. Insulin resistance was assessed by the R value of the homeostasis model assessment (HOMA). We did not find any statistically significant difference between groups according to age, gender, body mass index (BMI), fasting glucose, fasting insulin, insulin-AUC (0-180 min) and HOMA-R values. In OGGT there was no statistically significant difference between 0', 30', 60' and 90' insulin levels of the groups; only 120' and 180' insulin levels were higher in CGI than in IFG group (p<0.05). In IVGTT, there was no statistically significant difference between glucose levels of the groups. Furthermore, insulin response to intravenous glucose was higher in IFG than in CGI (p<0.05). Our data demonstrate that isolated IFG and CGI are similar with respect to

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

    PubMed

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

    2014-01-01

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

  18. 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

  19. 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.

  20. 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.

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

    SciTech Connect

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

    1988-06-01

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

  2. Kinetic study of model reactions in the gas phase at the early stage of coke formation

    SciTech Connect

    Nohara, D.; Sakai, T. )

    1992-01-01

    This paper reports that the most probable gas-phase reactions at the early stage of coke formation were elucidated by kinetic study on the model reactions adopted for formation of cyclic compounds and growth of ring. It was revealed that the formation and growth of ring proceeded mainly through cycloaddition of butadiene or allyl radicals to unsaturated hydrocarbons at relatively low temperatures ({approximately}600{degrees}C), i.e., through a Diels-Alder type reaction. On the other hand, such growth of ring as formation of biphenyl accompanying dehydrogenation from benzene can proceed only at the higher temperatures. It was also revealed that in the growth of the ring, cycloaddition of butadiene favors a cyclic olefin molecule that possesses a nonconjugated double bond and a nearly planar structure.

  3. 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.

  4. 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

  5. Ethical Challenges in Early-Phase Pediatric Research for Life-Limiting Illness.

    PubMed

    Unguru, Yoram

    2015-09-01

    Research with children is necessary to assure more effective treatments and potential cures of childhood illnesses. Ethical conduct of research requires minimizing the inherent risks of research, especially when it involves vulnerable populations such as children. Duchenne muscular dystrophy (DMD) is a progressive and fatal disease with no Food and Drug Administration-approved treatment. Clinical trials investigating so-called gene therapies are viewed by many in the DMD community with great promise. The goal of research is to secure generalizable knowledge and not directly benefit patients, yet many parents of boys with DMD hope, and even expect, that their sons will derive medical benefit by participating in early-phase "gene therapy" trials, raising concern for the therapeutic misconception. Physician-investigators must assist patient-subjects to distinguish realistic from unrealistic hope while maintaining reasonable expectations. In this article, I examine the therapeutic misconception and related concepts as framed within the context of "gene therapy" for DMD.

  6. Topical tacrolimus and cyclosporin A differentially inhibit early and late effector phases of cutaneous delayed-type and immunoglobulin E hypersensitivity

    PubMed Central

    Geba, Gregory P; Ptak, Wlodzimierz; Askenase, Philip W

    2001-01-01

    Systemic and topical administration routes of tacrolimus and cyclosporin A (CsA) were compared in effects on early and late phases of elicited T-cell-mediated contact sensitivity (CS), and effects on early and late phases of cutaneous immunoglobulin E (IgE) antibody-mediated hypersensitivity responses in mice. Thus, both CS and IgE responses in the skin have an early mast-cell-dependent phase, and also a late inflammatory phase. We measured the effects of both immunosuppressants on both phases of the respective T cell versus IgE responses. Systemic administration of both agents completely suppressed CS and IgE late-phase responses, but failed to affect either early phase. In contrast, when topical CsA was used, low doses abolished the early phase of IgE responses, but even high doses did not inhibit the early phase of CS. Conversely, topical tacrolimus inhibited the early phase of CS more potently than the early phase of cutaneous IgE hypersensitivity responses. Thus, topical treatment was needed to inhibit the early phases and the two agents acted differentially, suggesting differing susceptibility of the early phases, that are probably due to different signalling mechanisms. These studies underscore the potential value of topical administration of these powerful immunosuppressive agents in the treatment of allergic diseases that exhibit features of early-phase mast-cell-dependent inflammation, and late inflammation due to mast cells or to T cells, such as atopic dermatitis or asthma, since the early phase is predominantly susceptible to topical application, while the last phase of both IgE and T-cell inflammation responds to systemic treatment with both agents. PMID:11683964

  7. Prolonged Administration of Twice-Daily Bolus Intravenous Tacrolimus in the Early Phase After Lung Transplantation.

    PubMed

    Hirano, Yutaka; Sugimoto, Seiichiro; Mano, Toshifumi; Kurosaki, Takeshi; Miyoshi, Kentaroh; Otani, Shinji; Yamane, Masaomi; Kobayashi, Motomu; Miyoshi, Shinichiro; Oto, Takahiro

    2017-08-11

    BACKGROUND Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation. MATERIAL AND METHODS We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015. RESULTS The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the follow-up period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively. CONCLUSIONS These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

  8. 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.

  9. Differences in carotid artery atherosclerosis between men and women in the early phase after ischemic event.

    PubMed

    Skowronska, Marta; Piorkowska, Anna; Czlonkowska, Anna

    2017-09-20

    There is little data about sex differences in carotid atherosclerosis in the early phase after an ischemic event. The aim of this study was to examine the carotid artery atherosclerosis differences between men and women in early phase after TIA or stroke. Consecutive patients with recent ischemic event, admitted during the first week after symptom onset were examined with ultrasound. Sex differences in degree of stenosis, number of plaques and plaque morphology were compared. Plaque morphology was assessed by gray-scale median (GSM), according to which lower values were associated with hemorrhagic/necrotic core indicating plaque instability. Of the 316 patients with ischemic events, 196 (50.5% male) entered the study. Men had more often moderate as well as severe ipsilateral carotid stenosis (12.1% vs 7.2% for moderate and 12.1% vs 2.1% for severe; p=0.024). Men had more often the largest plaque hypoechogenic contralateral (62.6% vs 37.1%, p=0.0008), but not ipsilateral. Men had 3 or more hypoechogenic plaques (24.2% vs 4.1%, p=0.0001; 17.2% vs 4.1%, p<0.0001) both ipsi and contralateral respectively. Male sex was a risk factor for having 3 or more ipsilateral hypoechogenic plaques (p=0.002, OR=20 CI 95% [5.5-75]. Men had more often carotid stenosis and higher number of hypoechogenic plaques. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. A randomised controlled trial of nurse-managed trial conclusion following early phase cancer trial participation.

    PubMed

    Cox, K; Wilson, E; Arthur, A; Elkan, R; Armstrong, S

    2005-07-11

    The effect of a nurse-managed intervention, for early phase cancer trial participants at trial conclusion, on psychosocial outcomes was evaluated at two cancer centres in the Midlands, England using a randomised controlled trial. It involved 117 patients who were participating in an early phase cancer clinical trial. It was a nurse-managed trial exit, which included a trial exit interview, trial feedback information leaflet and telephone follow-up compared with standard care at trial conclusion. Psychological distress at 1 week and 4-6 weeks post-trial conclusion, patient's knowledge and understanding and patient's satisfaction were assessed. The results showed there was no significant difference between the two groups regarding scores for anxiety and depression at time one and time two. There is some suggestion that the intervention reduced anxiety from trial conclusion to follow-up (P=0.27). Patients in both groups felt they had contributed to cancer research through trial participation. However, intervention patients were more likely to feel that they knew how the trial was going (P<0.001), knew how other people in the trial were doing (P=0.001), had all the feedback they needed about the trial they took part in (P<0.01) and knew how they would be followed up (P=0.02). Patient satisfaction with the intervention was high (median score=4.5 where 5 is greatest satisfaction). In conclusion, nurse-managed trial conclusion led to positive outcomes for patients who had recently completed a clinical trial.

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

    PubMed Central

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

    2014-01-01

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

  12. Alteration in endometrial proteins during early- and mid-secretory phases of the cycle in women with unexplained infertility.

    PubMed

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

    2014-01-01

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

  13. 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.

  14. 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

  15. 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

  16. Tubular cell apoptosis and proliferation in the early phase of renal damage in uninephrectomized SHR.

    PubMed

    Rodríguez-López, Ana M; Flores, Olga; Arévalo, Miguel A; López-Novoa, José M

    2002-01-01

    In the present study, we measured tubular cell apoptosis and proliferation and Bcl-2 expression during the early phase (3 months) of the process of renal fibrosis in the experimental model of uninephrectomized spontaneously hypertensive rats (SHR). Tubulointerstitial fibrosis was evaluated by automated quantitative morphometry using selective staining of the extracellular matrix with sirius red. Apoptosis was quantified by both in situ dUTP biotin nick end-labeling method (TUNEL) and by propidium iodide staining. Proliferation rate was measured by counting cells expressing the proliferating cell nuclear antigen. Bcl-2 expression was assessed by immunohistochemistry. Tubulointerstitial fibrosis increased progressively during the 3 months of follow-up. Proliferation and apoptosis rates in tubular cells increased from the first to the second month after UNX. In the third month after UNX, the proliferating tubular cell number continued to increase, whereas the apoptotic cell number was maintained, coinciding with an increase in the expression of Bcl-2. Our observations demonstrate a different profile of tubular cell proliferation and apoptosis during the genesis of early tubulointerstitial damage in UNX-SHR. Copyright 2002 S. Karger AG, Basel

  17. Serum Uromodulin Levels in Prediction of Acute Kidney Injury in the Early Phase of Acute Pancreatitis.

    PubMed

    Kuśnierz-Cabala, Beata; Gala-Błądzińska, Agnieszka; Mazur-Laskowska, Małgorzata; Dumnicka, Paulina; Sporek, Mateusz; Matuszyk, Aleksandra; Gil, Krzysztof; Ceranowicz, Piotr; Walocha, Jerzy; Kucharz, Jakub; Pędziwiatr, Michał; Bartuś, Krzysztof; Trąbka, Rafał; Kuźniewski, Marek

    2017-06-14

    In health, uromodulin is the main protein of urine. Serum uromodulin concentrations (sUMOD) have been shown to correlate with kidney function. Acute kidney injury (AKI) is among the main complications of severe acute pancreatitis (AP). No reports exist on sUMOD in patients with AP, including the diagnostic usefulness for early prediction of AP severity. We measured sUMOD during first 72 h of AP. Sixty-six adult patients with AP were recruited at the surgical ward of the District Hospital in Sucha Beskidzka, Poland. AP was diagnosed according to the Revised Atlanta Classification. Blood samples were collected at 24, 48 and 72 h of AP, and sUMOD concentrations were measured with enzyme-linked immunosorbent test. sUMOD decreased non-significantly during the study. Patients with severe AP had non-significantly lower sUMOD concentrations than those with mild disease. Significant positive correlation was observed between sUMOD and estimated glomerular filtration rate on each day of the study and negative correlations were shown between sUMOD and age, serum creatinine, cystatin C and urea. Patients with AKI tended to have lower sUMOD. Although sUMOD correlated significantly with kidney function in the early phase of AP, measuring sUMOD did not allow to reliably predict AP severity or development of AKI.

  18. The new pre-preclinical paradigm: compound optimization in early and late phase drug discovery.

    PubMed

    Caldwell, G W; Ritchie, D M; Masucci, J A; Hageman, W; Yan, Z

    2001-11-01

    The attrition rates of new chemical entities (NCEs) in preclinical and clinical development are staggeringly high. NCEs are abandoned due to insufficient efficacy, safety issues, and economic reasons. Uncovering drug defects that produce these failures as early as possible in drug discovery would be highly effective in lowing the cost and time of developing therapeutically useful drugs. Unfortunately, there is no single factor that can account for these NCE failures in preclinical and clinical development since factors, such as solubility, pKa, absorption, metabolism, formulation, pharmacokinetics, toxicity and efficacy, to name a few, are all interrelated. In addition, there are many problems in scaling-up drug candidates from the laboratory bench scale to the pilot plant scale. To address the problem of attrition rates of NCEs in preclinical and clinical development and drug scale-up issues, pharmaceutical companies need to reorganize their preclinical departments from a traditional linear approach to a parallel approach. In this review, a strategy is put forth to integrate certain aspects of drug metabolism/pharmacokinetics, toxicology functions and process chemistry into drug discovery. Compound optimization in early and late phase drug discovery occurs by relating factors such as physicochemical properties, in vitro absorption, in vitro metabolism, in vivo pharmacokinetics and drug scale-up issues to efficacy optimization. This pre-preclinical paradigm will improve the success rate of drug candidates entering development.

  19. Traumatic Brain Injury Pathophysiology and Treatments: Early, Intermediate, and Late Phases Post-Injury

    PubMed Central

    Algattas, Hanna; Huang, Jason H.

    2014-01-01

    Traumatic Brain Injury (TBI) affects a large proportion and extensive array of individuals in the population. While precise pathological mechanisms are lacking, the growing base of knowledge concerning TBI has put increased emphasis on its understanding and treatment. Most treatments of TBI are aimed at ameliorating secondary insults arising from the injury; these insults can be characterized with respect to time post-injury, including early, intermediate, and late pathological changes. Early pathological responses are due to energy depletion and cell death secondary to excitotoxicity, the intermediate phase is characterized by neuroinflammation and the late stage by increased susceptibility to seizures and epilepsy. Current treatments of TBI have been tailored to these distinct pathological stages with some overlap. Many prophylactic, pharmacologic, and surgical treatments are used post-TBI to halt the progression of these pathologic reactions. In the present review, we discuss the mechanisms of the pathological hallmarks of TBI and both current and novel treatments which target the respective pathways. PMID:24381049

  20. Genome-Wide Transcription Profiling of the Early Phase of Biofilm Formation by Candida albicans†

    PubMed Central

    Murillo, Luis A.; Newport, George; Lan, Chung-Yu; Habelitz, Stefan; Dungan, Jan; Agabian, Nina M.

    2005-01-01

    The ability to adhere to surfaces and develop as a multicellular community is an adaptation used by most microorganisms to survive in changing environments. Biofilm formation proceeds through distinct developmental phases and impacts not only medicine but also industry and evolution. In organisms such as the opportunistic pathogen Candida albicans, the ability to grow as biofilms is also an important mechanism for persistence, facilitating its growth on different tissues and a broad range of abiotic surfaces used in medical devices. The early stage of C. albicans biofilm is characterized by the adhesion of single cells to the substratum, followed by the formation of an intricate network of hyphae and the beginning of a dense structure. Changes in the transcriptome begin within 30 min of contact with the substrate and include expression of genes related to sulfur metabolism, in particular MET3, and the equivalent gene homologues of the Ribi regulon in Saccharomyces cerevisiae. Some of these changes are initiated early and maintained throughout the process; others are restricted to the earliest stages of biofilm formation. We identify here a potential alternative pathway for cysteine metabolism and the biofilm-associated expression of genes involved in glutathione production in C. albicans. PMID:16151249

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

    SciTech Connect

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

    2011-03-18

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

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

    PubMed

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

    2012-09-01

    Parabens are widely used as anti-microbial agents in the cosmetic and pharmaceutical industries. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In the present study, 55 female pups were given daily subcutaneous injections of methyl-, propyl-, and butyl-paraben or 17beta-estradiol (E2) during neonatal Day 1-7. The ovaries were excised on postnatal Day 8, then fixed and stained with hematoxylin and eosin for histological analysis. The follicles were counted and classified as being in the primordial, early primary, or primary stages. The number of primordial follicles increased while early primary follicles decreased at the high doses of propyl- and butyl-paraben. The levels of anti-Mullerian hormone (AMH) and Foxl2 mRNA increased by propyl- and butyl-parabens whereas kit ligand/stem cell factor (KITL) expression was up regulated only by butyl-paraben. The mRNA levels of StAR and Cyp11a1 were significantly decreased after treatment with methyl-, propyl-, and butyl-parabens. Consistent with its use as a positive control, E2 regulated the expression of KITL, StAR, and Cyp11a1 genes, but surprisingly did not affect AMH and Foxl2 levels. Thus, E2 and parabens had different effects on the regulation of folliculogenic and steroidogenic genes, demonstrating the estrogenic and nonestrogenic properties of parabens in the ovary. Taken together, our data show that parabens stimulated AMH mRNA expression and consequently inhibited the early phase of folliculogenesis in the ovaries of neonatal female rat. The levels of steroidogenic enzymes, indicators of follicle differentiation, appeared to be regulated by parabens through inhibition of their transcriptional repressor, Foxl2. Copyright © 2012 Wiley Periodicals, Inc.

  3. Mucosal immunization of sheep with a Maedi-Visna virus (MVV) env DNA vaccine protects against early MVV productive infection.

    PubMed

    González, Belén; Reina, Ramsés; García, Iker; Andrés, Sara; Glaria, Idoia; Alzueta, María; Mora, María Isabel; Jugo, Begoña M; Arrieta-Aguirre, Inés; de la Lastra, José M Pérez; Rodríguez, Dolores; Rodríguez, Juan Ramón; Esteban, Mariano; Grilló, María Jesús; Blacklaws, Barbara A; Harkiss, Gordon D; Chebloune, Yahia; Luján, Lluís; de Andrés, Damián; Amorena, Beatriz

    2005-07-29

    Gene gun mucosal DNA immunization of sheep with a plasmid expressing the env gene of Maedi-Visna virus (MVV) was used to examine the protection against MVV infection in sheep from a naturally infected flock. For immunization, sheep were primed with a pcDNA plasmid (pcDNA-env) encoding the Env glycoproteins of MVV and boosted with combined pcDNA-env and pCR3.1-IFN-gamma plasmid inoculations. The pcDNA plasmid used in the control group contained the lacZ coding sequences instead of the env gene. Within a month post-challenge, the viral load in the vaccinated group was lower (p < or = 0.05) and virus was only detected transiently compared with the control group. Furthermore, 2 months later, neutralizing antibodies (NtAb) were detected in all the control animals and none of the vaccinated animals (p < or = 0.01). These results demonstrated a significant early protective effect of this immunization strategy against MVV infection that restricts the virus replication following challenge in the absence of NtAb production. This vaccine protective effect against MVV infection disappeared after two years post-challenge, when active replication of MVV challenge strain was observed. Protection conferred by the vaccine could not be explained by OLA DRB1 allele or genotype differences. Most of the individuals were DRB1 heterozygous and none was totally resistant to infection.

  4. Early life DNA vaccination with the H gene of Canine distemper virus induces robust protection against distemper.

    PubMed

    Jensen, Trine Hammer; Nielsen, Line; Aasted, Bent; Blixenkrone-Møller, Merete

    2009-08-20

    Young mink kits (n=8) were vaccinated with DNA plasmids encoding the viral haemagglutinin protein (H) of a vaccine strain of Canine distemper virus (CDV). Virus neutralising (VN) antibodies were induced after 2 immunisations and after the third immunisation all kits had high VN antibody titres. The VN antibody titres remained high for more than 4 months and the mink were protected against viraemia, lymphopenia, clinical disease and changes in the percentage of IFN-gamma producing peripheral blood leucocytes after challenge inoculation with a recent wild type strain of CDV. Essentially, these results demonstrate that early life DNA vaccination with the H gene of a CDV vaccine strain induced robust protective immunity against a recent wild type CDV.

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

    PubMed Central

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

    2014-01-01

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

  6. Flare Ribbons In The Early Phase Of An SDO Flare: Emission Measure And Energetics

    NASA Astrophysics Data System (ADS)

    Fletcher, Lyndsay; Hannah, I. G.; Hudson, H. S.; Innes, D. E.

    2012-05-01

    We report on the M1.0 flare of 7th August 2010, which displayed extended early phase chromospheric ribbons, well observed by SDO/AIA and RHESSI. Most large flares saturate rapidly in the high-temperature AIA channels, however this event could be followed in unsaturated AIA images for ten minutes in the build-up to and first few minutes of the impulsive phase. Analysis of GOES, RHESSI and SDO/AIA demonstrates the presence of high temperature ( 10MK), compact plasma volumes in the chromospheric flare ribbons, with a column emission measure of on average 3-7 x 1028 cm-5. We construct a time-resolved energy budget for the ribbon plasma, including also SDO/EVE data, and discuss the implications of the observed ribbon properties for flare energisation. This work was supported by the UK’s Science and Technology Facilities Council (ST/1001801), and by the European Commission through the FP7 HESPE project (FP7-2010-SPACE-263086).

  7. Association between GSTP1 CpG methylation and the early phase of lead exposure.

    PubMed

    Li, Chunping; Yang, Xiaolin; Xu, Ming; Zhang, Jinlong; Sun, Na

    2014-02-01

    GSTP1 is induced by lead, and thus serves as a biomarker of lead exposure. Lead exposure changes DNA methylation status. We attempted to prove that the methylation of the GSTP1 promoter plays an important role in lead toxicity. We conducted a case-control study of 53 workers from a battery plant and 53 age and sex matched healthy volunteers to determine whether the methylation level of the GSTP1 promoter is associated with the risk of lead poisoning. We employed methylation-specific PCR (MSP) in cell models to determine the relationship between the GSTP1 methylation level and lead exposure. We found no association between GSTP1 methylation and lead exposure. The difference in methylation frequencies between the exposure group and the controls was not statistically significant (p = 0.401), and individuals with the methylated GSTP1 gene was not associated with the risk of lead poisoning (adjusted OR = 1.36, 95% CI, 0.22-8.24). This study suggests that GSTP1 methylation is not involved in the early phase of lead toxicity. Further studies should be performed to detect the association between GSTP1 methylation and the risk of lead poisoning in later phases.

  8. 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.

  9. 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

    2016-07-02

    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.

  10. Physio-biochemical and proteome analysis of chickpea in early phases of cold stress.

    PubMed

    Heidarvand, Leila; Maali-Amiri, Reza

    2013-03-15

    Intensive and short-term strategies can aid in more rapid screening with informative and reliable results for long-term investigations under cold stress (CS). The integration of cellular analysis of chickpea during 0, 2, 4, 8, and 12h CS supplied us with novel possible responsive components and the possible interactions embedded inside, still remaining a Maze. Seedlings showed a biphasic pattern of responses over time. The transitory phase happened after 8h, when cells are presumably experiencing a new stage of responses and setting the stage for long-term adjustments. Physio-biochemical analysis confirmed the direct effect of fatty acids composition, lipoxygenase activity and antioxidant systems in cell responses under CS. Also, proteome results using MALDI-TOF-TOF and/or LC-MS/MS were able to differentiate changes in early phases of CS. Two-dimensional gel analysis results showed the possible targets of CS as mitochondria, chloroplast, organelle-nucleus communications, storage resources, stress and defense, protein degradation and signal transduction that confirmed the cell intended to re-establish a new homeostasis, in energy and primary metabolites to adapt to long-term CS. Here we propose a time course dynamic assessing multi-dimensional approaches for CS studies as one of the first studies in short-term treatment to progressively fill in the gaps between physio-biochemical and molecular events and touch the cell architecture for a better comprehension of the nature of plant stress response.

  11. Induction of cystic oviducts and protection against early challenge with infectious bronchitis virus serotype D388 (genotype QX) by maternally derived antibodies and by early vaccination.

    PubMed

    de Wit, J J; Nieuwenhuisen-van Wilgen, J; Hoogkamer, A; van de Sande, H; Zuidam, G J; Fabri, T H F

    2011-10-01

    Since the end of 2003, strains of the D388 serotype (QX genotype) of infectious bronchitis virus (IBV) have caused considerable damage to the Dutch poultry industry. In order to better understand the pathogenesis of infection caused by this infectious bronchitis variant and to be able to support the poultry industry with substantiated advice to prevent or decrease the damage caused by the D388 strain, several vaccination and challenge experiments were performed in young specific pathogen free layers, young layers with maternally derived antibodies against the D388 strain and young commercial broiler breeders. The experiments confirmed the field observations that the D388 strain of the QX genotype is a very pathogenic strain that is able to cause cystic oviducts in a high percentage of birds, mortality due to nephritis and respiratory distress with complete tracheal ciliostasis and airsacculitis. Vaccination programmes using different combinations of heterologous live vaccines at day 0 or at days 0 and 14 induced a reasonable to high level of protection in the trachea, kidney, oviduct and air sacs against challenge with the D388 strain at 28 days of age. However, for very early protection, maternally-derived D388-neutralizing antibodies were shown to be very important. Titres of 9 to 10 log(2) maternally-derived D388 virus-neutralizing antibodies, which provided partial protection against tracheal damage and a high protection against replication of D388 in the kidney after challenge at 6 or 10 days of age, could be achieved using a broad heterologous live priming and subsequent boosting using inactivated IBV vaccines containing two or three heterologous IBV antigens.

  12. 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…

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  14. 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…

  15. 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…

  16. 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…

  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. 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.…

  1. 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...

  2. Protection of temperature sensitive biomedical products using molecular alloys as phase change material.

    PubMed

    Mondieig, Denise; Rajabalee, Fazil; Laprie, Alain; Oonk, Harry A J; Calvet, Thereza; Cuevas-Diarte, Miguel Angel

    2003-04-01

    In this paper we present an example of the application of molecular alloys for thermal protection of biomedical products during transport or storage. Particularly, thermal protection of blood elements have been considered at different temperatures. All steps from basic research to marketing have been addressed. The high latent heat of fusion of the components allows us to propose molecular alloys as materials for thermal energy storage and also for thermal protection over a large range of temperatures, which can be used in many industrial sectors.

  3. Phase contrast MRI is an early marker of micrometastatic breast cancer development in the rat brain.

    PubMed

    Budde, Matthew D; Gold, Eric; Jordan, E Kay; Smith-Brown, Melissa; Frank, Joseph A

    2012-05-01

    The early growth of micrometastatic breast cancer in the brain often occurs through vessel co-option and is independent of angiogenesis. Remodeling of the existing vasculature is an important step in the evolution of co-opting micrometastases into angiogenesis-dependent solid tumor masses. The purpose of this study was to determine whether phase contrast MRI, an intrinsic source of contrast exquisitely sensitive to the magnetic susceptibility properties of deoxygenated hemoglobin, could detect vascular changes occurring independent of angiogenesis in a rat model of breast cancer metastases to the brain. Twelve nude rats were administered 10(6) MDA-MB-231BRL 'brain-seeking' breast cancer cells through intracardiac injection. Serial, multiparametric MRI of the brain was performed weekly until metastatic disease was detected. The results demonstrated that images of the signal phase (area under the receiver operating characteristic curve, 0.97) were more sensitive than T(2)* gradient echo magnitude images (area under the receiver operating characteristic curve, 0.73) to metastatic brain lesions. The difference between the two techniques was probably the result of the confounding effects of edema on the magnitude of the signal. A region of interest analysis revealed that vascular abnormalities detected with phase contrast MRI preceded tumor permeability measured with contrast-enhanced MRI by 1-2  weeks. Tumor size was correlated with permeability (R(2)= 0.23, p < 0.01), but phase contrast was independent of tumor size (R(2)= 0.03). Histopathologic analysis demonstrated that capillary endothelial cells co-opted by tumor cells were significantly enlarged, but less dense, relative to the normal brain vasculature. Although co-opted vessels were vascular endothelial growth factor-negative, vessels within larger tumor masses were vascular endothelial growth factor-positive. In conclusion, phase contrast MRI is believed to be sensitive to vascular remodeling in co

  4. Ring current activity during the early Bz<0 phase of the January 1997 magnetic cloud

    NASA Astrophysics Data System (ADS)

    Jordanova, V. K.; Torbert, R. B.; Thorne, R. M.; Collin, H. L.; Roeder, J. L.; Foster, J. C.

    1999-11-01

    The passage at Earth of the January 10-11, 1997, magnetic cloud induced a storm of moderate geomagnetic activity with Dst index reaching minimum values of about -83 nT. We study ring current formation during the early Bz negative phase of this magnetic cloud, using energetic particle data from three instruments on the Polar spacecraft and geosynchronous plasma data from the LANL spacecraft. We use our kinetic drift-loss model to simulate the evolution of ring current H+, He+, and O+ ion distributions and associated aeronomical effects during this period. The results from two Volland-Stern type magnetospheric electric field model formulations are compared: (1) Kp-dependent and (2) interplanetary magnetic field (IMF) dependent. We demonstrate that while both electric field models reproduce well the main trends of ring current formation and decay during the storm, the IMF-dependent model reproduces the rapidity of the main storm growth phase and its strength better. Comparing model results during the main phase of the storm with HYDRA, TIMAS, and CAMMICE data we find that the model reproduces very well the ring current distributions near dawn. The formation of the nose event, i.e., the rise of the 10-30 keV energy particles near dusk due to abruptly increased convection is, however, overestimated by the model. We compute plasmaspheric heating through Coulomb collisions as the storm evolves and find that maximum heating occurs initially on the nightside near L~3.5 and subsequently moves earthward to L~2.75, in agreement with Millstone Hill radar observations of midlatitude electron temperature enhancement on January 10. However, the magnitude of the energy transferred to plasmaspheric electrons through Coulomb collisions appears to be not sufficient to yield the observed elevated electron temperature at ~0830 UT, suggesting that additional energy sources should be considered during this event.

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

    PubMed

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

    2014-08-07

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

  6. Replication of alpha and beta globin DNA sequences occurs during early S phase in murine erythroleukemia cells.

    PubMed Central

    Epner, E; Rifkind, R A; Marks, P A

    1981-01-01

    Murine erythroleukemia cells (MELC) can be induced to express the characteristics of erythroid differentiation by a variety of agents. Previous studies indicate that an action of inducer, occurring during early S phase, may be critical to the expression of differentiated characteristics such as initiation of accumulation of newly synthesized alpha and beta globin mRNAs. In this investigation, the time of replication of globin genes in MELC was studied. DNA was isolated from synchronous populations of cells obtained by centrifugal elutriation. Newly replicated DNA sequences were prepared from synchronized cells cultured for 1 1/2 hr with 5-bromodeoxyuridine; bromodeoxyuridine-containing DNA was isolated by CsCl gradient centrifugation. By employing cloned probes for hybridization to newly synthesized DNA, it was found that alpha and beta globin gene sequences are replicated early in S phase, while ribosomal RNA gene sequences are replicated to about the same extent in early, middle, and late S phases. PMID:6942415

  7. Early and Moderate Sensory Stimulation Exerts a Protective Effect on Perilesion Representations of Somatosensory Cortex after Focal Ischemic Damage

    PubMed Central

    Xerri, Christian; Zennou-Azogui, Yoh'i

    2014-01-01

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

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

    PubMed

    Xerri, Christian; Zennou-Azogui, Yoh'i

    2014-01-01

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

  9. 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.

  10. 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.

  11. Association Between Increased Vascular Density and Loss of Protective RAS in Early-stage NPDR

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krishnan; Raghunandan, Sneha; Vyas, Ruchi J.; Vu, Amanda C.; Bryant, Douglas; Yaqian, Duan; Knecht, Brenda E.; Grant, Maria B.; Chalam, K. V.; Parsons-Wingerter, Patricia

    2016-01-01

    Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The renin-angiotensin system (RAS) is implicated in the pathogenesis of DR and in the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population that is instrumental in vascular repair.

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  13. 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…

  14. Protecting the Health and Finances of the Elderly With Early Cognitive Impairment.

    PubMed

    Edersheim, Judith; Murray, Evan D; Padmanabhan, Jaya L; Price, Bruce H

    2017-03-01

    The projected expansion of the nation's elderly population necessitates the revision of health care and policy strategies for safeguarding the health and assets of this community. The elderly are at greatly increased risk for developing mild cognitive impairment and Alzheimer's disease. These conditions are associated with diminished complex decision-making abilities that adversely affect patients, their families, and society, even during early stages of Alzheimer's disease. We present three composite patient histories that demonstrate problems routinely encountered by families, health care providers, and legal professionals during the course of early AD and MCI. We review the prevalence of cognitive and behavioral symptoms associated with MCI and early AD. Obstacles to early detection of cognitive decline, limitations of current testing modalities and benefits of earlier detection are discussed. Central themes common to medical and judicial approaches toward capacity assessment are discussed. We argue that an emphasis on earlier detection will result in benefits for patient health and result in financial savings to patients and the country as a whole. Finally, we recommend national guidelines for the evaluation of task-specific decision-making capacities to reduce the variability of outcome and improve quality of evaluations found among medical professionals, forensic evaluators, and legal actors. © 2017 American Academy of Psychiatry and the Law.

  15. 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…

  16. Free Trehalose Accumulation in Dormant Mycobacterium smegmatis Cells and Its Breakdown in Early Resuscitation Phase

    PubMed Central

    Shleeva, Margarita O.; Trutneva, Kseniya A.; Demina, Galina R.; Zinin, Alexander I.; Sorokoumova, Galina M.; Laptinskaya, Polina K.; Shumkova, Ekaterina S.; Kaprelyants, Arseny S.

    2017-01-01

    Under gradual acidification of growth medium resulting in the formation of dormant Mycobacterium smegmatis, a significant accumulation of free trehalose in dormant cells was observed. According to 1H- and 13C-NMR spectroscopy up to 64% of total organic substances in the dormant cell extract was represented by trehalose whilst the trehalose content in an extract of active cells taken from early stationary phase was not more than 15%. Trehalose biosynthesis during transition to the dormant state is provided by activation of genes involved in the OtsA-OtsB and TreY-TreZ pathways (according to RT-PCR). Varying the concentration of free trehalose in dormant cells by expression of MSMEG_4535 coding for trehalase we found that cell viability depends on trehalose level: cells with a high amount of trehalose survive much better than cells with a low amount. Upon resuscitation of dormant M. smegmatis, a decrease of free trehalose and an increase in glucose concentration occurred in the early period of resuscitation (after 2 h). Evidently, breakdown of trehalose by trehalase takes place at this time as a transient increase in trehalase activity was observed between 1 and 3 h of resuscitation. Activation of trehalase was not due to de novo biosynthesis but because of self-activation of the enzyme from the inactive state in dormant cells. Because, even a low concentration of ATP (2 mM) prevents self-activation of trehalase in vitro and after activation the enzyme is still sensitive to ATP we suggest that the transient character of trehalase activation in cells is due to variation in intracellular ATP concentration found in the early resuscitation period. The negative influence of the trehalase inhibitor validamycin A on the resuscitation of dormant cells proves the importance of trehalase for resuscitation. These experiments demonstrate the significance of free trehalose accumulation for the maintenance of dormant mycobacterial viability and the involvement of trehalose

  17. Heavy episodic drinking in early adolescence: gender-specific risk and protective factors.

    PubMed

    Danielsson, Anna-Karin; Romelsjö, Anders; Tengström, Anders

    2011-01-01

    This longitudinal study examined possible gender differences regarding risk and protective factors for heavy episodic drinking among 1,222 seventh-grade students (aged 13) in the City of Stockholm, Sweden, with follow-up 2 years later. Logistic regression analyses showed that several factors predicted heavy episodic drinking. The strongest predictors for boys' heavy episodic drinking in the ninth grade were heavy episodic drinking (odds ratio [OR] = 5.30) and smoking in the seventh grade (OR = 5.80). Drinking peers (OR = 2.47) and smoking (OR = 2.44) in the seventh grade showed the strongest association for girls. Furthermore, high parental monitoring and having a secure attachment to parents may have a protective effect when risk factors are present. Our results lend support to prevention initiatives to strengthen the parent-child relation and focus on adolescents' ability to resist peer pressure and of limiting parental provision of alcohol. The study's limitations are noted.

  18. Protective and Promotive Effects of Latino Early Adolescents' Cultural Assets Against Multiple Types of Discrimination.

    PubMed

    Cavanaugh, Alyson M; Stein, Gabriela L; Supple, Andrew J; Gonzalez, Laura M; Kiang, Lisa

    2017-08-21

    Given adversity associated with discrimination, it is important to identify culturally relevant factors that may protect against its harmful effects. Using latent variable interactions, this study examined the moderating effects of cultural assets on the association between multiple types of discrimination and adolescents' adjustment. Participants included 174 seventh- and eighth-grade Latino adolescents (51% girls); majority were of Mexican origin. Peer discrimination was associated with higher internalizing symptoms, whereas cultural assets predicted higher academic motivation above and beyond racial-ethnic discrimination, demonstrating a promotive effect. Adolescents' Latino cultural assets also protected against higher levels of externalizing symptoms in the context of high peer discrimination and foreigner objectification. The discussion focuses on the conceptual and applied implications of these findings. © 2017 The Authors. Journal of Research on Adolescence © 2017 Society for Research on Adolescence.

  19. Protecting Small Communities Through Domestic Policing: Adopting an Early Warning System to Recognize Potential Terrorist Activity

    DTIC Science & Technology

    2009-09-01

    communities . Due to the evolving nature of terrorism, public safety organizations must modify the way they respond to crime and acts of terrorism. This...develop new capabilities to protect their communities . Due to the evolving nature of terrorism, public safety organizations must modify the way they...Hills Village, Centennial, and unincorporated Arapahoe County. Originally, a small rural community , Greenwood Village has grown significantly. Today

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

    PubMed

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

    2016-02-01

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

  1. 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

  2. Proteomic analysis of egg white proteins during the early phase of embryonic development.

    PubMed

    Qiu, Ning; Ma, Meihu; Cai, Zhaoxia; Jin, Yongguo; Huang, Xi; Huang, Qun; Sun, Shuguo

    2012-03-16

    Avian egg albumen participates in embryonic development by providing essential nutrients as well as antimicrobial protection. Although various biological functions of egg white proteins were suggested during embryogenesis, global changes of these proteins under incubation conditions remained uninvestigated. This study presents a proteomic analysis on the change of egg white proteins during the first week of embryonic development. By using 2-DE, together with MALDI-TOF MS/MS, thirty protein spots representing eight proteins were identified showing significant changes in abundance during incubation. An accelerating degradation of ovalbumin was observed in a wide range of molecular weight. In addition, four protein complexes were predicted according to the detected molecular weight increase. Among these speculated protein complexes, an ovalbumin spot coupled with RNA-binding protein was detected. The absence of these protein complexes before incubation, followed by the constant increase in abundance during incubation indicates conceivable pivotal roles in embryonic development. To better understand the function of the proteins identified in this study, discrepancies of egg white protein changes between fertilized and unfertilized chicken eggs were additionally demonstrated. These findings will provide insight into the embryogenesis process to improve our knowledge of egg white proteins in regulating and supporting early embryonic development. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Acceptable results of early closure of loop ileostomy to protect low rectal anastomosis.

    PubMed

    Perdawid, Sharafaden Karim; Andersen, Ole Bjørn

    2011-06-01

    This was a pilot project performed prior to full implementation of early loop ileostomy closure (within two weeks) following low anterior resection of the rectum in a group of patients selected according to previously recommended criteria for safe, early ileostomy closure. Retrospective review of medical records. Patients undergoing loop ileostomy closure between December 2009 and October 2010 were analyzed. Data were collected on demographics, tumour characteristics, information about the perioperative period, operative details, postoperative complications, closure operation, the postoperative closure period and follow-up. Eleven patients were included (men, n = 4) with a median age of 58 years (range 47-79 years). Ileostomy closure was performed at a median of ten days (range 8-13 days) following rectum resection. The median hospital stay was 16 days (range 14-24 days). No re-laparotomies were performed. One patient developed a pelvic pus collection ten days post closure and was treated conservatively. One patient died 32 days after closure for reasons not related to surgery. The results of this small retrospective study show morbidity rates associated with early loop ileostomy closure that are probably acceptable. Safety, feasibility, timing and selection criteria should be clarified in large randomized studies. not relevant. not relevant.

  4. Protective effects of salidroside on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

    PubMed

    Zhang, Hua; Shen, Wei-sheng; Gao, Chun-heng; Deng, Li-chun; Shen, Dong

    2012-06-01

    Salidroside [2-(4-hydroxyphenyl)ethyl-β-D-glucopyranoside], one of the most potent ingredients extracted from the plant Rhodiola rosea L., has been shown to have a cardiovascular protective effect as an antioxidant, and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer. However, the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity, especially early left ventricular regional systolic dysfunction, have to date been sparsely investigated. The aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin. Sixty patients with histologically confirmed breast cancer were enrolled. Eligible patients were randomized to receive salidroside (600 mg/day; n = 30) or placebo (n = 30) starting 1 week before chemotherapy. Patients were investigated by means of echocardiography and strain rate (SR) imaging. We also measured plasma concentrations of reactive oxygen species (ROS). All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2. A decline of the SR peak was observed at an epirubicin dose of 200 mg/m2, with no significant differences between salidroside and placebo (1.35 ± 0.36 vs 1.42 ± 0.49/second). At growing cumulative doses of epirubicin, the SR normalized only with salidroside, showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m2 (1.67 ± 0.43 vs 1.32 ± 0.53/second, p < 0.05) and 400 mg/m2 (1.68 ± 0.29 vs 1.40 ± 0.23/second, p < 0.05). Moreover, a significant increase in plasma concentrations of ROS was found with placebo, but they remained unchanged with salidroside. Salidroside can provide a protective effect on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

  5. 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.

  6. Systematic analysis of early phase clinical studies for patients with breast cancer: Inclusion of patients with brain metastasis.

    PubMed

    Costa, R; Gill, N; Rademaker, A W; Carneiro, B A; Chae, Y K; Kumthekar, P; Gradishar, W J; Kurzrock, R; Giles, F J

    2017-04-01

    This systematic review aims to better define the limitations and patterns with which patients with MBC and CNS metastasis are enrolled into early phase developmental therapeutics trials. In June 2016, PubMed search was conducted using the following keywords: "Breast cancer". Drug-development phase 1, phase 2 or phase 1/2 trials for patients with MBC were included. Multiple-histology trials and trials without an efficacy endpoint were excluded. In total, 1474 studies were included; Inclusion criteria for 423 (29%) allowed for CNS metastasis, 770 (52%) either excluded or did not document eligibility of patients with CNS disease. Trials accruing patients with HER2-positive MBC and including targeted therapies had higher odds of allowing for patients with CNS disease (adjusted OR 1.56, 95% CI 1.08-2.2.6; p=0.019 and 1.49, 95% 1.08-2.06; p=0.014, respectively). There were also higher odds of accrual of patients with CNS involvement into clinical trials over time (odds ratio=1.10, 95% CI 1.07-1.12; p<0.0001). Most published early phase clinical trials either did not clearly document or did not allow for accrual of patients with CNS disease. Early phase trials with targeted agents or enrolling HER2+ MBC had higher odds of permitting CNS metastases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Phase III randomized trial of toremifene versus tamoxifen for Japanese postmenopausal patients with early breast cancer.

    PubMed

    Kimura, Morihiko; Tominaga, Takeshi; Kimijima, Izo; Takatsuka, Yuichi; Takashima, Shigemitsu; Nomura, Yasuo; Kasumi, Fujio; Yamaguchi, Akihiro; Masuda, Norikazu; Noguchi, Shinzaburo; Eshima, Nobuoki

    2014-05-01

    Toremifene, a selective estrogen receptor modulator, is used as adjuvant therapy for postmenopausal patients with breast cancer in Japan. For Japanese patients, however, only limited data are available on the efficacy and safety profile of toremifene. To establish the long term efficacy and safety of toremifene for Japanese patients, we conducted a prospective, multicenter, randomized phase III trial comparing toremifene and tamoxifen. The subjects were postmenopausal Japanese patients who had undergone surgery for node-negative breast cancer. Toremifene or tamoxifen was administered for 2 years. The primary endpoint was demonstration of the non-inferiority of toremifene compared with tamoxifen in respect of 5-year survival. Secondary endpoints were cumulative overall survival, cumulative disease-free survival, effects on lipid profiles, and adverse events. A total of 253 patients were enrolled. The baseline characteristics of the two treatment groups were well-balanced. Median follow-up was 66.5 months. Five-year survival was similar for toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1), indicating that toremifene is not inferior to tamoxifen for postmenopausal Japanese patients with early breast cancer. Cumulative overall survival and cumulative disease-free survival were also very similar for toremifene and tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank test P = 0.3359, respectively). Adverse events in both groups were similar and mostly mild or moderate. Thus, both are equally effective and well tolerated. Our results suggest that the efficacy and safety of toremifene and tamoxifen are equivalent for postmenopausal Japanese patients with early breast cancer.

  8. 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.

  9. 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. © 2016 Wiley Periodicals, Inc.

  10. Early Aqueous Suppressant Therapy on Hypertensive Phase Following Glaucoma Drainage Device Procedure: A Randomized Prospective Trial.

    PubMed

    Law, Simon K; Kornmann, Helen L; Giaconi, JoAnn A; Kwong, Allen; Tran, Eric; Caprioli, Joseph

    2016-03-01

    To prospectively evaluate the effect of early aqueous suppression (therapy) on hypertensive phase (HP) and intraocular pressure (IOP) control after implantation of silicone Ahmed glaucoma valve (AGV). Patients who underwent AGV implantation were randomized to initiate therapy (including β-blockers, α-agonists, or carbonic anhydrase inhibitors) when postoperative IOP>10 mm Hg (low-IOP initiation group) or >17 mm Hg (moderate-IOP initiation group). HP was defined as an IOP>21 mm Hg during the first 6 postoperative months, after an initial IOP reduction to <22 mm Hg in the first postoperative week. Primary outcome measures included the occurrence of HP and IOP control. Fifty-two eyes (50 patients) underwent AGV implantation. Average follow-up was 21.9±10.7 months. HP was observed in 21 eyes (40.4%) with average peak IOP of 30±8 mm Hg, onset at 32±30 days, and duration of 15±32 days. One year postoperatively, those eyes with HP had higher IOP than eyes that did not develop HP (15.1±5.2, 11.4±4.3, respectively; P=0.021) and required more additional glaucoma surgeries (28.6%, 3.2%, respectively; P=0.013). The peak IOP at week 3 postoperatively in the low-IOP initiation group (26 eyes) was significantly lower than in the moderate-IOP initiation group (26 eyes; 15.7±3.6, 20.6±8.9, respectively; P=0.012). Eyes with therapy started after HP onset had significantly higher postoperative IOP from 2 to 4 months. Therapy initiated before the development of HP was not associated with a higher complication rate. Aqueous suppression initiated in the early postoperative period while IOPs were still in the low-teens and was able to reduce the incidence of IOP spike associated with the HP without an increased complication rate.

  11. Evaluation of measles-rubella vaccination for mothers in early puerperal phase.

    PubMed

    Hisano, Michi; Kato, Tatsuo; Inoue, Eisuke; Sago, Haruhiko; Yamaguchi, Koushi

    2016-02-24

    The postpartum period is an ideal opportunity to vaccinate mothers with inadequate immunity to vaccine-preventable diseases including measles and rubella. A prospective study of measles-rubella (MR) vaccination in the early puerperal phase was conducted in 171 mothers, who had insufficient antibody titers when screened for immunity to measles (≤ 1:4 on the neutralization test [NT]) or rubella (≤ 1:16 on the hemagglutination inhibition [HI] test) during pregnancy. To evaluate the efficacy of MR vaccination in the postpartum period, we determined their post-vaccination antibody titers and immune responses to vaccination, and investigated the association between these and their prolactin (PRL) levels and Th1/Th2 ratios at the time of vaccination. We also examined the passage of viral RNA and antigen into breast milk. Of the 169 participants who completed the study schedule, 117 and 101 had low antibody titers against measles and rubella, respectively. In the measles-seronegative group, the antibody-positive rate was 87% on the NT assay, and the NT geometric mean antibody titer was 11.4 (95% confidence interval [CI], 10.0-13.0). In the rubella-seronegative group, the antibody-positive rate was 88% on the HI test assay, and the HI geometric mean antibody titer was 64.0 (95% CI, 53.9-76.0). There was no association between the post-vaccination antibody titers and the PRL levels or Th1/Th2 ratios at the time of vaccination. In the rubella-seronegative group, subjects with higher Th1/Th2 ratios showed higher rates of responsiveness than those with lower ratios (P=0.045). Although measles virus RNA was isolated from the breast milk of two vaccinated mothers, breastfeeding was not associated with clinical disease in any infants. MR vaccination in the early puerperal phase is considered an effective way to prevent the diseases, regardless of the mother's immunological status and hormonal milieu. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Enhanced release of IgE-dependent early phase mediators from nasal polyp tissue

    PubMed Central

    Patou, Joke; Holtappels, Gabriele; Affleck, Karen; Gevaert, Philippe; Perez-Novo, Claudina; Van Cauwenberge, Paul; Bachert, Claus

    2009-01-01

    Background The mast cell is a crucial effector cell in allergic rhinitis and other inflammatory diseases. During the acute allergic reaction preformed mediators such as histamine, but also de novo produced mediators such as leukotrienes (LTC4/D4/E4) and prostaglandins (PGD2) are released. Mast cells represent targets for therapeutic intervention, and thus a human ex-vivo model to stimulate mast cells taken from mucosal sites would be instrumental for drug intervention studies. We have aimed to activate mast cells within ex-vivo human nasal tissue by IgE/anti-IgE specific (ε chain specific) stimulations and in this respect to test the usability of nasal polyps versus inferior turbinates Methods Biopsy samples were collected from patients with nasal polyps and inferior turbinates from patients who underwent sinus or septal surgery. Tissue fragments were primed with IgE 1 μg/ml for 60 minutes and then stimulated for 30 minutes with tissue culture medium (negative control), anti-IgE 10 μg/ml, anti-IgE 30 μg/ml and ionomycin 10 μM (positive control). Histamine, leukotrienes and PGD2 were measured in supernatants. To help provide an understanding of the extent of the response, the number of tryptase and FcεRIα positive cells was evaluated by means of immunohistochemistry and the FcεRIα-chain was measured by means of quantitative PCR in the nasal polyp and inferior turbinate tissues. Finally, the correlation between IgE concentrations in the nasal tissue and the release of mediators was analysed. Results Stimulations with anti-IgE on IgE-primed nasal tissue fragments lead to a concentration-dependent release of histamine, leukotrienes and PGD2. The release of these early phase mediators was significantly higher in nasal polyps compared to inferior turbinates, although tryptase, FcεRIα positive cells and FcεRIα-chain transcripts were equally present in both groups. No correlation was found between baseline concentrations of IgE, and the release of histamine

  13. FLARE RIBBON ENERGETICS IN THE EARLY PHASE OF AN SDO FLARE

    SciTech Connect

    Fletcher, L.; Hannah, I. G.; Hudson, H. S.; Innes, D. E.

    2013-07-10

    The sites of chromospheric excitation during solar flares are marked by extended extreme ultraviolet ribbons and hard X-ray (HXR) footpoints. The standard interpretation is that these are the result of heating and bremsstrahlung emission from non-thermal electrons precipitating from the corona. We examine this picture using multi-wavelength observations of the early phase of an M-class flare SOL2010-08-07T18:24. We aim to determine the properties of the heated plasma in the flare ribbons, and to understand the partition of the power input into radiative and conductive losses. Using GOES, SDO/EVE, SDO/AIA, and RHESSI, we measure the temperature, emission measure (EM), and differential emission measure of the flare ribbons, and deduce approximate density values. The non-thermal EM, and the collisional thick target energy input to the ribbons are obtained from RHESSI using standard methods. We deduce the existence of a substantial amount of plasma at 10 MK in the flare ribbons, during the pre-impulsive and early-impulsive phase of the flare. The average column EM of this hot component is a few times 10{sup 28} cm{sup -5}, and we can calculate that its predicted conductive losses dominate its measured radiative losses. If the power input to the hot ribbon plasma is due to collisional energy deposition by an electron beam from the corona then a low-energy cutoff of {approx}5 keV is necessary to balance the conductive losses, implying a very large electron energy content. Independent of the standard collisional thick-target electron beam interpretation, the observed non-thermal X-rays can be provided if one electron in 10{sup 3}-10{sup 4} in the 10 MK (1 keV) ribbon plasma has an energy above 10 keV. We speculate that this could arise if a non-thermal tail is generated in the ribbon plasma which is being heated by other means, for example, by waves or turbulence.

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

    PubMed Central

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

    1996-01-01

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

  15. 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

  16. Early-phase adaptations to intrahospital training in strength and functional mobility of children with leukemia.

    PubMed

    San Juan, Alejandro F; Fleck, Steven J; Chamorro-Viña, Carolina; Maté-Muñoz, José L; Moral, Susana; García-Castro, Javier; Ramírez, Manuel; Madero, Luis; Lucia, Alejandro

    2007-02-01

    Improvements in chemotherapy and radiotherapy have contributed to the high survival rate (approximately 70%) of childhood acute lymphoblastic leukemia (ALL). However, during treatment, lack of physical activity and treatment cause various short- to long-term side effects, such as muscle atrophy and physical deconditioning. The purpose of this study was to determine the effects of an intrahospital, short-duration (8 weeks) exercise training program on muscle strength and endurance and functional mobility of children with ALL. Seven children (4 boys and 3 girls; 4-7 years of age) who were in the maintenance phase of treatment for ALL were selected as subjects. Three training sessions of 90- to 120-minute duration were performed each week. Each session included 11 different strength exercises engaging the major muscle groups and aerobic training. Gains in strength and endurance were assessed with a 6 repetition maximum test for upper (seated bench press and seated lateral row) and lower extremities (leg press). Gains in functional mobility were assessed with the time up and go test (TUG) and the timed up and down stairs test (TUDS). Performance was significantly improved after the training program in all strength tests (p < 0.01 for seated bench press and p < 0.05 for both seated lateral row and seated leg press) and in the TUG test (p < 0.05). In summary, a period of time as short as 8 weeks is enough to produce clinically relevant early-phase adaptations in children receiving treatment against ALL (i.e., improved functional mobility and muscle strength). Although more research is needed in the area of exercise training and pediatric cancer, exercise sciences can play a beneficial role in assisting both oncologists in treating cancer and improving children's quality of life during and after treatment.

  17. Non-Ischemic Cerebral Energy Dysfunction at the Early Brain Injury Phase following Aneurysmal Subarachnoid Hemorrhage.

    PubMed

    Carteron, Laurent; Patet, Camille; Solari, Daria; Messerer, Mahmoud; Daniel, Roy T; Eckert, Philippe; Meuli, Reto; Oddo, Mauro

    2017-01-01

    The pathophysiology of early brain injury following aneurysmal subarachnoid hemorrhage (SAH) is still not completely understood. Using brain perfusion CT (PCT) and cerebral microdialysis (CMD), we examined whether non-ischemic cerebral energy dysfunction may be a pathogenic determinant of EBI. A total of 21 PCTs were performed (a median of 41 h from ictus onset) among a cohort of 18 comatose mechanically ventilated SAH patients (mean age 58 years, median admission WFNS score 4) who underwent CMD and brain tissue PO2 (PbtO2) monitoring. Cerebral energy dysfunction was defined as CMD episodes with lactate/pyruvate ratio (LPR) >40 and/or lactate >4 mmol/L. PCT-derived global CBF was categorized as oligemic (CBF < 28 mL/100 g/min), normal (CBF 28-65 mL/100 g/min), or hyperemic (CBF 69-85 mL/100 g/min), and was matched to CMD/PbtO2 data. Global CBF (57 ± 14 mL/100 g/min) and PbtO2 (25 ± 9 mm Hg) were within normal ranges. Episodes with cerebral energy dysfunction (n = 103 h of CMD samples, average duration 7.4 h) were frequent (66% of CMD samples) and were associated with normal or hyperemic CBF. CMD abnormalities were more pronounced in conditions of hyperemic vs. normal CBF (LPR 54 ± 12 vs. 42 ± 7, glycerol 157 ± 76 vs. 95 ± 41 µmol/L; both p < 0.01). Elevated brain LPR correlated with higher CBF (r = 0.47, p < 0.0001). Cerebral energy dysfunction is frequent at the early phase following poor-grade SAH and is associated with normal or hyperemic brain perfusion. Our data support the notion that mechanisms alternative to ischemia/hypoxia are implicated in the pathogenesis of early brain injury after SAH.

  18. [Risk epidemiology and child protection statistics in early childhood – a pilot study in southern Germany].

    PubMed

    Thurn, Leonore; Besier, Tanja; Ziegenhain, Ute; Jud, Andreas; Kindler, Heinz; Fischer, Dieter; Fegert, Jörg M; Künster, Anne Katrin

    2017-07-01

    In contrast to many other countries in Europe, Germany lacks sufficient empirical data on the incidence/prevalence of child maltreatment and its risk factors. This pilot study generated systematic data on the prevalence of child abuse and neglect and its risk factors in Germany. Using a newly developed questionnaire (ESM1 and ESM2) on child abuse and neglect as well as indicators for risk factors, we conducted a survey on 35 child daycare centers in a county in southern Germany, the goal being to generate reliable data. The questionnaire and the Strength and Difficulties Questionnaire (SDQ) was completed by daycare professionals for every child between 4 and under 7 years who was attending the participating daycare center (1,122 children). Child maltreatment was reported in 13.2 % of the cases, and risk factors for future child maltreatment were detected in 38.4 % cases. This study demonstrates that systematic data collection concerning child protection is feasible in child daycare centers. In the future, we recommend that local child protection networks be modified on the basis of reliable empirical data.

  19. 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.

  20. Gradual Solar Coronal Dimming and Evolution of Coronal Mass Ejection in the Early Phase

    NASA Astrophysics Data System (ADS)

    Qiu, Jiong; Cheng, Jianxia

    2017-03-01

    We report observations of a two-stage coronal dimming in an eruptive event of a two-ribbon flare and a fast coronal mass ejection (CME). Weak gradual dimming persists for more than half an hour before the onset of the two-ribbon flare and the fast rise of the CME. It is followed by abrupt rapid dimming. The two-stage dimming occurs in a pair of conjugate dimming regions adjacent to the two flare ribbons, and the flare onset marks the transition between the two stages of dimming. At the onset of the two-ribbon flare, transient brightenings are also observed inside the dimming regions, before rapid dimming occurs at the same places. These observations suggest that the CME structure, most probably anchored at the twin dimming regions, undergoes a slow rise before the flare onset, and its kinematic evolution has significantly changed at the onset of flare reconnection. We explore diagnostics of the CME evolution in the early phase with analysis of the gradual dimming signatures prior to the CME eruption.

  1. Detection of Cystic Fibrosis Transmembrane Conductance Regulator Activity in Early-Phase Clinical Trials

    PubMed Central

    Rowe, Steven M.; Accurso, Frank; Clancy, John P.

    2007-01-01

    Advances in our understanding of cystic fibrosis pathogenesis have led to strategies directed toward treatment of underlying causes of the disease rather than treatments of disease-related symptoms. To expedite evaluation of these emerging therapies, early-phase clinical trials require extension of in vivo cystic fibrosis transmembrane conductance regulator (CFTR)–detecting assays to multicenter trial formats, including nasal potential difference and sweat chloride measurements. Both of these techniques can be used to fulfill diagnostic criteria for the disease, and can discriminate various levels of CFTR function. Full realization of these assays in multicenter clinical trials requires identification of sources of nonbiological intra- and intersite variability, and careful attention to study design and statistical analysis of study-generated data. In this review, we discuss several issues important to the performance of these assays, including efforts to identify and address aspects that can contribute to inconsistent and/or potentially erroneous results. Adjunctive means of detecting CFTR including mRNA expression, immunocytochemical localization, and other methods are also discussed. Recommendations are presented to advance our understanding of these biomarkers and to improve their capacity to predict cystic fibrosis outcomes. PMID:17652506

  2. 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

  3. The early phase of the SMBH-galaxy coevolution in low-z "young" galaxies

    NASA Astrophysics Data System (ADS)

    Nagao, Tohru

    2014-01-01

    It is now widely recognized that most galaxies have a supermassive black hole (SMBH) in their nucleus, and the evolution of SMBHs is closely related with that of their host galaxies (the SMBH-galaxy coevolution). This is suggested by the correlation in the mass of SMBHs and their host galaxies, that has been observed in low redshifts. However, the physics of the coevolution is totally unclear, that prevents us from complete understandings of the galaxy evolution. One possible strategy to tackle this issue is measuring the mass ratio between SMBHs and their host galaxies (M_BH/M_host) at high redshifs, since different scenarios predict different evolution of the ratio ofMBH/Mhost. However it is extremely challenging to measure the mass of the host of high-z quasars, given the faint surface brightness of the host at close to the glaring quasar nucleus. Here we propose a brand-new approach to assess the early phase of the SMBH-galaxy coevolution, by focusing on low-z AGN-hosting "young" galaxies. Specifically, we focus on some very metal-poor galaxies with broadline Balmer lines at z ~ 0.1 - 0.3. By examining the SMBH scaling relations in some low-z metal-poor AGNs through high-resolution IRCS imaging observations, we will discriminate various scenarios for the SMBH-galaxy coevolution.

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

    PubMed

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

    2014-01-01

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

  5. The Role of Galaxy Mergers and Molecular Gas in the Early Phase of Galaxy Cluster Assembly

    NASA Astrophysics Data System (ADS)

    Hung, Chao-Ling

    2017-08-01

    High-redshift protoclusters are ideal places to study the formation of the largest structures in the Universe and the early environmental influences on galaxy evolution. Recent discoveries of z>2 protoclusters with extremely rich populations of dusty star-forming galaxies (DSFGs; SFR>100 Msun/yr) represent the most active assembly phases of massive galaxy clusters. Understanding the triggering mechanisms of these unusual concentrations of extreme star-forming galaxies can provide critical insights into the formation of most massive galaxies in these clusters and the assembly of massive clusters themselves. For example, an increased probability of galaxy interactions and/or enhanced gas supply may trigger an excess of DSFGs. Using the extensive ancillary data in the COSMOS field, we study the role of galaxy mergers through measuring the frequency of galaxy pairs in two such DSFG-rich protoclusters at z=2.10 and 2.47, respectively. We also investigate the mean molecular gas content of protocluster galaxies by stacking SCUBA-2 850 micron images. These independent investigations provide complementary views into the physical nature of these DSFG-rich protoclusters.

  6. Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children.

    PubMed

    The, Hao Chung; Florez de Sessions, Paola; Jie, Song; Pham Thanh, Duy; Thompson, Corinne N; Nguyen Ngoc Minh, Chau; Chu, Collins Wenhan; Tran, Tuan-Anh; Thomson, Nicholas R; Thwaites, Guy E; Rabaa, Maia A; Hibberd, Martin; Baker, Stephen

    2017-08-02

    Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiological agents. Here, by profiling an extended region of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of gut microbiome perturbations during the early phase of infectious diarrhea caused by various etiological agents in Vietnamese children. Fecal samples from 145 diarrheal cases with a confirmed infectious etiology before antimicrobial therapy and 54 control subjects were analyzed. We found that the diarrheal fecal microbiota could be robustly categorized into 4 microbial configurations that either generally resembled or were highly divergent from a healthy state. Factors such as age, nutritional status, breastfeeding, and the etiology of the infection were significantly associated with these microbial community structures. We observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and oral microorganisms in all diarrheal fecal microbiome configurations, proposing similar mechanistic interactions, even in the absence of global dysbiosis. We additionally found that Bifidobacterium pseudocatenulatum was significantly depleted during dysenteric diarrhea regardless of the etiological agent, suggesting that further investigations into the use of this species as a dysentery-orientated probiotic therapy are warranted. Our findings contribute to the understanding of the complex influence of infectious diarrhea on gut microbiome and identify new opportunities for therapeutic interventions.

  7. Radiocaesium partitioning in Japanese cedar forests following the "early" phase of Fukushima fallout redistribution.

    PubMed

    Coppin, Frederic; Hurtevent, Pierre; Loffredo, Nicolas; Simonucci, Caroline; Julien, Anthony; Gonze, Marc-Andre; Nanba, Kenji; Onda, Yuichi; Thiry, Yves

    2016-11-23

    Our study focused on radiocaesium ((137)Cs) partitioning in forests, three vegetation periods after the Fukushima Daiichi nuclear power plant accident. (137)Cs distribution in forest components (organic and mineral soil layers as well as tree compartments: stem, bark, needles, branches and roots) was measured for two Japanese cedar stand ages (17 and 33 years old). The results showed that around 85% of the initial deposit was found in the forest floor and topsoil. For the youngest stand almost 70% of the deposit is present in the forest floor, whereas for the oldest stand 50% is present in the 0-3 cm mineral soil layer. For trees, old and perennial organs (including dead and living needles and branches, litter fall and outer bark) directly exposed to the fallout remained the most contaminated. The crown concentrated 61-69% of the total tree contamination. Surprisingly the dead organs concentrated 25 ± 9% (young cedars) to 36 ± 20% (mature cedar) of the trees' residual activity, highlighting the importance of that specific compartment in the early post-accident phase for Japanese cedar forests. Although the stem (including bark) represents the highest biomass pool, it only concentrates 3.3% and 4.6% of the initial (137)Cs deposit for mature and young cedars, respectively.

  8. 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.

  9. 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

  10. Media Messages and Perceptions of the Affordable Care Act during the Early Phase of Implementation.

    PubMed

    Fowler, Erika Franklin; Baum, Laura M; Barry, Colleen L; Niederdeppe, Jeff; Gollust, Sarah E

    2017-02-01

    Public opinion about the Affordable Care Act (ACA) has been polarized since the law's passage. Past research suggests these conditions would make any media influence on the public limited at best. However, during the early phase of implementation, locally broadcast ACA-related media messages-in the form of paid health insurance and political advertisements and news media stories-abounded as advocates, insurance marketers, and politicians sought to shape the public's perceptions of the law. To what extent did message exposure affect ACA perceptions during the first open enrollment period? We merge data on volumes of messaging at the media market level with nationally representative survey data to examine the relationship between estimated exposure to media messaging and the public's perceptions of how informed they were about and favorable toward the ACA in October 2013. We find that higher volumes of insurance advertising and local news coverage are associated with participants' perceptions of being informed about the law. Volumes of insurance advertising and of local news coverage are also associated with participants' favorability toward the law, but the relationship varies with partisanship, supporting the growing body of research describing partisan perceptual bias.

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

    PubMed

    Boeckel, Tillmann; Schaffner-Bielich, Jürgen

    2010-07-23

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

  12. 2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

    PubMed

    2015-12-01

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

  13. Pokemon proto-oncogene in oral cancer: potential role in the early phase of tumorigenesis.

    PubMed

    Sartini, D; Lo Muzio, L; Morganti, S; Pozzi, V; Di Ruscio, G; Rocchetti, R; Rubini, C; Santarelli, A; Emanuelli, M

    2015-05-01

    Oral squamous cell carcinoma (OSCC) represents about 90% of all oral neoplasms with a poor clinical prognosis. To improve survival of OSCC patients, it is fundamental to understand the basic molecular mechanisms characterizing oral carcinogenesis. Dysregulation of oncogenes and tumor suppressor genes seems to play a central role in tumorigenesis, including malignant transformation of the oral cavity. We analyzed the expression levels of the pro-oncogenic transcription factor Pokemon through real-time PCR, Western blot and immunohistochemistry in tumor, and normal oral tissue samples obtained from 22 patients with OSCC. The relationship between tumor characteristics and the level of Pokemon intratumor expression was also analyzed. Pokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor vs normal tissue) inversely correlated with histological grading, suggesting its potential role as a prognostic factor for OSCC. Moreover, a significant inverse correlation was found between Pokemon protein expression levels (OSCC vs normal oral mucosa) and tumor size, supporting the hypothesis that Pokemon could play an important role in the early phase of tumor expansion. This work shows that reduced expression of Pokemon is a peculiar feature of OSCC. Additional studies may establish the effective role of Pokemon in oral tumorigenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. The life-saving effect of hyperbaric oxygenation during early-phase severe blunt chest injuries.

    PubMed

    Rogatsky, G G; Mayevsky, A

    2007-01-01

    The effect of hyperbaric oxygenation (HBO2) on survival during the early phase of severe blunt chest injury (BChI) has not been elucidated. Our aim was to investigate this effect on human victims of BChI. We monitored cardiac index (CI), stroke volume index (SVI), PaO2 and PaO2/FiO2 in 18 victims treated conventionally, and 8 victims treated under combined conventional and HBO2 treatment. Out of the 18 victims, 4 survived (Group A) and 14 died (Group B). Another 8 victims, in Group C, received HBO, and all survived. Human victims showed marked reductions in all cardiorespiratory values during the first 24 h. Group B persistently tended towards a decrease in SVI, PaO2/FiO2 and PaO2, eventually reaching fatal levels. The survivors developed a cardiorespiratory function characterized by a tendency towards recovery of all monitored parameters, more notable in Group C, which showed an earlier and more significant normalization vs. Group A (P<0.01). Our clinical data suggest that the earliest possible HBO2 treatment after severe blunt trauma can significantly enhance victims' survival.

  15. Increased ER-mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress.

    PubMed

    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

    2011-07-01

    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.

  16. Early stage reversed crystal growth of zeolite A and its phase transformation to sodalite.

    PubMed

    Greer, Heather; Wheatley, Paul S; Ashbrook, Sharon E; Morris, Russell E; Zhou, Wuzong

    2009-12-16

    Microstructural analysis of the early stage crystal growth of zeolite A in hydrothermal synthetic conditions revealed a revised crystal growth route from surface to core in the presence of the biopolymer chitosan. The mechanism of this extraordinary crystal growth route is discussed. In the first stage, the precursor and biopolymer aggregated into amorphous spherical particles. Crystallization occurred on the surface of these spheres, forming the typical cubic morphology associated with zeolite A with a very thin crystalline cubic shell and an amorphous core. With a surface-to-core extension of crystallization, sodalite nanoplates were crystallized within the amorphous cores of these zeolite A cubes, most likely due to an increase of pressure. These sodalite nanoplates increased in size, breaking the cubic shells of zeolite A in the process, leading to the phase transformation from zeolite A to sodalite via an Ostwald ripening process. Characterization of specimens was performed using scanning electron microscopy and transmission electron microscopy, supported by other techniques including X-ray diffraction, solid-state NMR, and N(2) adsorption/desorption.

  17. Patients' experiences with symptoms and needs in the early rehabilitation phase after coronary artery bypass grafting.

    PubMed

    Lie, Irene; Bunch, Eli H; Smeby, Nina Aarhus; Arnesen, Harald; Hamilton, Glenys

    2012-03-01

    The first month after discharge for Coronary artery bypass graft (CABG) is particularly challenging for the patients. A larger interview study is warranted to elicit CABG patients' detailed experiences, and give direction for future clinical practice. To explore the CABG patients' symptoms and needs in the early rehabilitation phase. A qualitative, mixed method design integrating qualitative and quantitative approaches was used. Ninety-three CABG patients aged 39-77, participated in interviews at home after 2 and 4 weeks. The semi-structured interview guide covered: experiences of relief of angina pectoris after surgery, experiences with prescribed discharge medications, psychological experiences: anxiety, depression, sexuality, health professional contact persons, and patient defined experiences. Two weeks after CABG the patients symptoms and needs were characterised by a substantial amount of uncertainty and worries related to what to expect and what was normal for postoperative pain, assessment and sensation of surgical site, different experiences with physical activity/exercise, uncertainty about medications, difficulties with sleep pattern, irritability, postoperative complications,uncertainty about return to work, and insufficient information at discharge. Four weeks after surgery the patients' symptom level was decreased, and they experienced life beginning to return back to normal. Patency with grafts after CABG, decision to drive a car, impotence (erectile dysfunction), and a missing link to the hospital remained challenges. CABG patients' experiences indicate a need to extend the hospital's discharge care to the first month after surgery for specific themes to promote rehabilitation outcomes.

  18. [Classification of dengue hemorrhagic fever using decision trees in the early phase of the disease].

    PubMed

    Vega Riverón, Beatriz; Sánchez Valdés, C Lizet; Cortiñas Abrahantes, C José; Castro Peraza, Osvaldo; González Rubio, C Daniel; Castro Peraza, Marta

    2012-01-01

    dengue is a viral disease with endemic behavior. At the beginning of the illness it is not possible to know which patients will have an unfavorable evolution and develop a severe form of dengue. However, some warning symptoms and signs may be present. to apply decision tree techniques to the exploration of signs of severity in the early phase of the illness. the study sample was made up of 230 patients admitted with dengue to "Pedro Kouri" Institute of Tropical Medicine in 2001. The variables considered for the classification were the signs, symptoms and laboratory exams on the third day of evolution of the illness. The algorithm of classification and regression trees using the Gini's index was applied. Different loss matrices to improve the sensitivity were considered. the algorithm CART, corresponding to the best loss, had a sensitivity of 98,68% and global error of 0,36. Without considering loss, it obtained its sensitivity reached 74% with an error of 0,25. In both cases, the most important variables were platelets and hemoglobin. the study submitted rules of decision with high sensitivity and negative predictive value of utility in the clinical practice. The laboratory variables resulted more important from the informational viewpoint than the clinical ones to discriminate clinical forms of dengue.

  19. The Early Phases of Genetic Code Origin: Conjectures on the Evolution of Coded Catalysis

    NASA Astrophysics Data System (ADS)

    Di Giulio, Massimo

    2003-10-01

    A review of the most significant contributions on the early phases of genetic code origin is presented. After stressing the importance of the key intermediary role played in protein synthesis, by peptidyl-tRNA, which is attributed with a primary function in ancestral catalysis, the general lines leading to the codification of the first amino acids in the genetic code are discussed. This is achieved by means of a model of protoribosome evolution which sees protoribosome as the central organiser of ancestral biosynthesis and the mediator of the encounter between compounds (metabolite-pre-tRNAs) and catalysts (peptidyl-pre-tRNAs). The encounter between peptidyl-pre-tRNA catalysts in protoribosome is favoured by metabolic pre-mRNAs and later resulted (given the high temperature at which this evolution is supposed to have taken place) in the evolution of mRNAs with codons of the type GNS. These mRNAs codified only for those amino acids that the coevolution theory of genetic code origin sees as the precursors of all other amino acids. Some aspects of the model here discussed might be rendered real by the transfer-messenger RNA molecule (tmRNA) which is here considered a molecular fossil of ancestral protein synthesis.

  20. An Unconventional Acid-Labile Nucleobase Protection Concept for Guanosine Phosphoramidites in RNA Solid-Phase Synthesis

    PubMed Central

    Jud, Lukas; Micura, Ronald

    2017-01-01

    We present an innovative O6-tert-butyl/N2-tert-butyloxycarbonyl protection concept for guanosine (G) phosphoramidites. This concept is advantageous for 2′-modified G building blocks because of very efficient synthetic access when compared with existing routes that usually employ O6-(4-nitrophenyl)ethyl/N2-acyl protection or that start from 2-aminoadenosine involving enzymatic transformation into guanosine later on in the synthetic path. The new phosphoramidites are fully compatible with 2′-O-tBDMS or TOM phosphoramidites in standard RNA solid-phase synthesis and deprotection, and provide excellent quality of tailored RNAs for the growing range of applications in RNA biophysics, biochemistry, and biology. PMID:27943429

  1. An Unconventional Acid-Labile Nucleobase Protection Concept for Guanosine Phosphoramidites in RNA Solid-Phase Synthesis.

    PubMed

    Jud, Lukas; Micura, Ronald

    2017-03-08

    We present an innovative O(6) -tert-butyl/N(2) -tert-butyloxycarbonyl protection concept for guanosine (G) phosphoramidites. This concept is advantageous for 2'-modified G building blocks because of very efficient synthetic access when compared with existing routes that usually employ O(6) -(4-nitrophenyl)ethyl/N(2) -acyl protection or that start from 2-aminoadenosine involving enzymatic transformation into guanosine later on in the synthetic path. The new phosphoramidites are fully compatible with 2'-O-tBDMS or TOM phosphoramidites in standard RNA solid-phase synthesis and deprotection, and provide excellent quality of tailored RNAs for the growing range of applications in RNA biophysics, biochemistry, and biology.

  2. Immunogenicity of a protective whole cell mycobacterial vaccine in HIV-infected adults: a phase III study in Tanzania.

    PubMed

    Lahey, Timothy; Arbeit, Robert D; Bakari, Muhammad; Horsburgh, C Robert; Matee, Mecky; Waddell, Richard; Mtei, Lillian; Vuola, Jenni M; Pallangyo, Kisali; von Reyn, C Fordham

    2010-11-10

    Preventive immunization with whole inactivated Mycobacterium vaccae (MV) confers protection against HIV-associated tuberculosis (TB) in BCG-immunized adults with CD4 counts ≥200 cells/μl. We evaluated the immunogenicity of MV in the 2013 subjects of the phase III DarDarTrial using an interferon gamma (IFN-γ) enzyme linked immunosorbent assay (ELISA), tritiated thymidine lymphocyte proliferation assay (LPA) and an ELISA for antibodies to the TB glycolipid lipoarabinomannan (LAM). MV immunization boosts IFN-γ and LPA responses to MV sonicate, and antibody responses to LAM. Post-immunization immune responses to MV correlated with baseline clinical factors, but the responses did not predict protection from HIV-associated TB.

  3. 78 FR 69690 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Extension of Comment Period... and Gene Therapy Products'' that appeared in the Federal Register of July 2, 2013 (78 FR 39736). The... (CT) and gene therapy (GT) products (referred to collectively as CGT products) with recommendations to...

  4. 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,...

  5. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia.

    PubMed

    Green, Margaret L; Leisenring, Wendy M; Xie, Hu; Walter, Roland B; Mielcarek, Marco; Sandmaier, Brenda M; Riddell, Stanley R; Boeckh, Michael

    2013-08-15

    The association between cytomegalovirus (CMV) reactivation and relapse was evaluated in a large cohort of patients with acute myeloid leukemia (AML) (n = 761), acute lymphoblastic leukemia (ALL) (n = 322), chronic myeloid leukemia (CML) (n = 646), lymphoma (n = 254), and myelodysplastic syndrome (MDS) (n = 371) who underwent allogeneic hematopoietic cell transplantation (HCT) between 1995 and 2005. In multivariable models, CMV pp65 antigenemia was associated with a decreased risk of relapse by day 100 among patients with AML (hazard ratio [HR] = 0.56; 95% confidence interval [CI], 0.3-0.9) but not in patients with ALL, lymphoma, CML, or MDS. The effect appeared to be independent of CMV viral load, acute graft-versus-host disease, or ganciclovir-associated neutropenia. At 1 year after HCT, early CMV reactivation was associated with reduced risk of relapse in all patients, but this did not reach significance for any disease subgroup. Furthermore, CMV reactivation was associated with increased nonrelapse mortality (HR = 1.31; 95% CI, 1.1-1.6) and no difference in overall mortality (HR = 1.05; 95% CI, 0.9-1.3). This report demonstrates a modest reduction in early relapse risk after HCT associated with CMV reactivation in a large cohort of patients without a benefit in overall survival.

  6. Early treatment with xenon protects against the cold ischemia associated with chronic allograft nephropathy in rats.

    PubMed

    Zhao, Hailin; Luo, Xianghong; Zhou, Zhaowei; Liu, Juying; Tralau-Stewart, Catherine; George, Andrew J T; Ma, Daqing

    2014-01-01

    Chronic allograft nephropathy (CAN) is a common finding in kidney grafts with functional impairment. Prolonged hypothermic storage-induced ischemia-reperfusion injury is associated with the early onset of CAN. As the noble gas xenon is clinically used as an anesthetic and has renoprotective properties in a rodent model of ischemia-reperfusion injury, we studied whether early treatment with xenon could attenuate CAN associated with prolonged hypothermic storage. Exposure to xenon enhanced the expression of insulin growth factor-1 (IGF-1) and its receptor in human proximal tubular (HK-2) cells, which, in turn, increased cell proliferation. Xenon treatment before or after hypothermia-hypoxia decreased cell apoptosis and cell inflammation after reoxygenation. The xenon-induced HK-2 cell proliferation was abolished by blocking the IGF-1 receptor, mTOR, and HIF-1α individually. In the Fischer-to-Lewis rat allogeneic renal transplantation model, xenon exposure of donors before graft retrieval or recipients after engraftment enhanced tubular cell proliferation and decreased tubular cell death and cell inflammation associated with ischemia-reperfusion injury. Compared with control allografts, xenon treatment significantly suppressed T-cell infiltration and fibrosis, prevented the development of CAN, and improved renal function. Thus, xenon treatment promoted recovery from ischemia-reperfusion injury and reduced susceptibility to the subsequent development of CAN in allografts.

  7. MLN4924 protects against bleomycin-induced pulmonary fibrosis by inhibiting the early inflammatory process

    PubMed Central

    Deng, Qi; Zhang, Jiaojiao; Gao, Yaqun; She, Xiaofei; Wang, Yunchao; Wang, Yilin; Ge, Xin

    2017-01-01

    Pulmonary fibrosis is a complex pathological process characterized by massive destruction of the structure of lung tissues and aggravated pulmonary function impairment. The underlying mechanisms of pulmonary fibrosis are incompletely understood and therefore limited treatment options are available currently. Here, we report that MLN4924, an NEDD8 activation enzyme (NAE) activity-inhibiting molecule, blocks the maintenance and progression of established pulmonary fibrosis. We found that MLN4924 acts against bleomycin-induced pulmonary fibrosis mainly at the early inflammatory stage. Pharmacologically targeting the neddylation of Cullin-Ring E3 ligase (CRL) by MLN4924, significantly abrogated NF-κB responses, suppressed MAPK activity, and reduced secretion of TNF-α-elicited pro-inflammatory cytokines and MCP1-induced chemokines. MLN4924 inhibited pro-inflammatory responses while maintaining or increasing the production of the anti-inflammatory mediators such as anti-inflammatory interleukins (ILs) following bleomycin administration, which is closely correlated to its blocking NF-κB-mediated signaling. Consistently, our studies identified MLN4924 as a promising therapeutic drug for pulmonary fibrosis and suggested a potential role of MLN4924 that fine tunes the MAPK signaling pathway controlling the inflammatory reactions at the early stages of pulmonary fibrosis. In addition, our findings may broaden the potential practical application of MLN4924 as an effective therapeutic strategy against other inflammation-associated diseases. PMID:28469786

  8. Aquaporin-4 gene silencing protects injured neurons after early cerebral infarction

    PubMed Central

    He, Zhan-ping; Lu, Hong

    2015-01-01

    Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffusion-weighted imaging (DWI). We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and siRNA-aquaporin-4 was immediately injected via the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefficient value on T2-weighted imaging (T2WI) and DWI gradually increased within 0.5–6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2WI and DWI reduced, relative apparent diffusion coefficient value was increased, and cellular edema was obviously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefficient value was similar between treatment and model groups, but angioedema was still obvious in the treatment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefficient value and the area of high signal intensity on T2WI and DWI can reflect therapeutic effects of aquaporin-4 gene silencing on cellular edema. PMID:26330830

  9. Silyl protection in the solid-phase synthesis of N-linked glycopeptides. Preparation of glycosylated fluorogenic substrates for subtilisins.

    PubMed

    Christiansen-Brams, I; Jansson, A M; Meldal, M; Breddam, K; Bock, K

    1994-11-01

    The trimethylsilyl (TMS) group was used for protection of the hydroxy groups of three disaccharide 1-amino-alditols and of the glycosylamines of glucose, maltotriose and maltoheptose. The per-O-trimethylsilylated derivatives were coupled with N alpha-Fmoc-Asp(Cl)-OPfp 7 to give six glycosylated building blocks for the solid-phase synthesis of N-linked glycopeptides. Building block 8 was used in the synthesis of five internally quenched fluorescent substrates which were studied by enzymatic hydrolysis with savinase, a subtilisin-type enzyme.

  10. Short-circuit protection of intercomponent cables on 3 phase, alternating current, permissible mining equipment

    SciTech Connect

    Carey, W.L.

    1995-05-01

    Magnetic and thermal magnetic circuit breakers are used to provide short-circuit protection for intercomponent cables on permissible mining equipment. Limits are needed for the circuit breaker settings which will adequately protect intercomponent cables under a short-circuit fault condition. Calculations reveal that the maximum allowable settings for large ampacity power cables are limited by the minimum available short-circuit currents while the maximum settings for small control cables are limited by the amount of current the cable can withstand. When the available short-circuit current is greater than the current the cable can withstand, no circuit breaker setting is practical. The use of some small control cables with large trailing cables will be eliminated from future approvals due to large available short-circuit currents. Present approvals would not be affected. A computer program is available from the Approval and Certification Center to calculate circuit breaker settings.

  11. White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

    PubMed

    Cookey, Jacob; Bernier, Denise; Tibbo, Philip G

    2014-07-01

    The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. 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.

  13. Polyfibroblast Phase 4: A Self-Healing and Galvanic Protection Additive

    DTIC Science & Technology

    2014-11-26

    crack. No catalysts or curing agents are needed since the polymerization is driven by ambient humidity. 15. SUBJECT TERMS corrosion protection, self...describe the fundamental mechanisms that underpin the corrosion resistance of the self-healing paint. The manuscript shows that the synergistic effects...healing paint technology, as well as future self-healing paint designs. 3 Key Accomplishments 3.1 Self-Heailng Mechanisms Paper Corrosion costs

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

    PubMed Central

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

    2009-01-01

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

  15. Triamcinolone acetonide protects the rat retina from STZ-induced acute inflammation and early vascular leakage.

    PubMed

    Kim, Y H; Choi, M Y; Kim, Y S; Park, C H; Lee, J H; Chung, I Y; Yoo, J M; Choi, W S; Cho, G J; Kang, S S

    2007-09-15

    Streptozotocin (STZ) has been commonly used to induce in vivo and in vitro hyperglycemic diabetes and its toxicity leads to inflammation and vascular injury. Triamcinolone acetonide (TA), as an anti-angiogenic/anti-inflammatory drug, is clinically used to improve the visual acuity in neovascular and edematous ocular diseases. The aim of this study was to investigate the effect of TA on early inflammation and vascular leakage in the retina of STZ-induced hyperglycemic rats. Hyperglycemia was induced in 8-week-old male Sprague-Dawley (SD) rats by a single intraperitoneal injection of STZ (65 mg/kg); only rats with blood glucose levels >13.9 mmol/l 1 day after STZ injection were included in STZ-hyperglycemic group. Sex- and age-matched SD rats injected with buffer were used as the control group. One day before STZ and buffer injection, 2 microl TA (4 mg/ml in saline) and 2 microl saline were intravitreal-injected into the right and the left eyes of rats, respectively. Retinal vascular leakage was measured using the Evans-blue method. Changes in pro-inflammatory target genes, such as tumor necrotic factor (TNF)-alpha, intracellular adhesion molecule (ICAM)-1, and vascular endothelial growth factor (VEGF) were assessed by immunoblottings, immunostaining, and ELISA analyses. Vascular hyperleakage and up-regulation of most pro-inflammatory genes peaked within a few days after STZ injection and had recovered. However, these changes were blocked by TA pretreatment. Our data suggest that TA controls STZ-induced early vascular leakage and temporary pro-inflammatory signals in the rat retina.

  16. 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.

  17. [Rapid diagnostics of early phosphorus deficiency in mini-cucumber plants under protected cultivation by near infrared spectroscopy].

    PubMed

    Shi, Ji-yong; Zou, Xiao-bo; Zhao, Jie-wen; Mao, Han-ping; Wang, Kai-liang; Chen, Zheng-wei; Huang, Xiao-wei

    2011-12-01

    The morphological symptom of phosphorus deficiency at early stage is similar to the appearance of leaf aging process in preliminary phase, so that visual diagnostics of phosphorus deficiency in mini-cucumber plants at early stage is practically impossible. Near infrared reflectance spectra contain information about differences in compositions of leaf tissues between phosphorus-deficient plants and healthy plants. In the present paper, near infrared reflectance spectroscopy was used to provide diagnostic information on phosphorus deficiency of mini-cucumber plants grown under non-soil conditions. Near infrared spectra was collected from 90 leaves of mini-cucumber plants. Raw cucumber spectra was preprocessed by SNV and divided into 27 intervals. The top 10 principal components (PCs) were extracted as the input of BP-ANN classifiers by principal component analysis (PCA) while the values of nutrient deficient were used as the output variables of BP-ANN and three layers BP-ANN discrimination model was built. The best experiment results were based on the top 3 principal components of No. 7 interval when the spectra was divided into 27 intervals and identification rates of the ANN model are 100% in both training set and the prediction set. The overall results show that NIR spectroscopy combined with BP-ANN can be efficiently utilized for rapid and early diagnostics of phosphorus deficiency in mini-cucumber plants.

  18. Evaluation of models to induce low progesterone during the early luteal phase in cattle.

    PubMed

    Beltman, M E; Roche, J F; Lonergan, P; Forde, N; Crowe, M A

    2009-10-15

    Two experiments were designed to evaluate models for generation of low circulating progesterone concentrations during early pregnancy in cattle. In Experiment 1, 17 crossbred heifers (Bos taurus) were assigned to either prostaglandin F(2alpha) (PGF(2alpha)) administration on Days 3, 3.5, and 4 (PG3; n=9) or to control (n=8). Blood samples were collected from heifers from Days 1 to 9 for progesterone assay. Progesterone concentrations were decreased (P<0.03) between 18 and 48h after first PGF(2alpha) treatment in heifers assigned to PG3 compared with that of controls. In Experiment 2, 39 crossbred heifers detected in estrus were inseminated (Day 0) and assigned to either (1) PGF(2alpha) administration on Days 3, 3.5, and 4 (PG3; n=10), (2) PGF(2alpha) administration on Days 3, 3.5, 4, and 4.5 (PG4; n=10), (3) Progesterone Releasing Intravaginal Device (PRID) insertion on Day 4.5 with PGF(2alpha) administration on Days 5 and 6 (PRID+PGF(2alpha); n=10), or (4) control (n=9). Blood samples were collected daily until Day 15, and conceptus survival rate was determined at slaughter on Day 16. Progesterone concentrations during the sampling period in the PG3 and PG4 groups did not differ but were less than that of controls (P<0.01). After an initial peak, progesterone concentrations in the PRID+PGF(2alpha) group were similar to that of controls. More heifers in the PG4 group (6 of 10) had complete luteal regression than did those in the PG3 group (3 of 10). Conceptus survival rate on Day 16 did not differ between groups. There was a significant correlation between progesterone concentration on Days 5 and 6 and conceptus size on Day 16. In summary, treatment with PGF(2alpha) on Days 3, 3.5, and 4 postestrus appeared to provide the best model to induce reduced circulating progesterone concentrations during the early luteal phase in cattle.

  19. Early stage attenuation of phase amplitude coupling in the hippocampus and medial prefrontal cortex in a transgenic rat model of AD.

    PubMed

    Bazzigaluppi, Paolo; Beckett, Tina L; Koletar, Margaret M; Lai, Aaron Y; Joo, Illsung L; Brown, Mary E; Carlen, Peter L; McLaurin, JoAnne; Stefanovic, Bojana

    2017-08-04

    Alzheimer's disease (AD) is pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration. Preclinical studies on neuronal impairments associated with progressive amyloidosis have demonstrated some Aβ-dependent neuronal dysfunction including modulation of GABAergic signalling. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broad repertoire of AD-like pathologies to investigate the neuronal network functioning using simultaneous intracranial recordings from the hippocampus (HPC) and the medial prefrontal cortex (mPFC), followed by pathological analyses of gamma-aminobutyric acid (GABAA ) receptors subunits α1, α5 and δ, and glutamic acid decarboxylases (GAD65 and GAD67). Concomitant to amyloid deposition and tau hyperphosphorylation, low-gamma band power was strongly attenuated in the HPC and mPFC of TgF344-AD rats in comparison to those in non-transgenic littermates. In addition, the phase-amplitude coupling of the neuronal networks in both areas was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude in TgF344-AD animals. Finally, the gamma coherence between HPC and mPFC was attenuated as well. These results demonstrate significant neuronal network dysfunction at an early stage of AD-like pathology. This network dysfunction precedes the onset of cognitive deficits and is likely driven by Aβ and tau pathologies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. 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.

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

    PubMed

    Dietert, Rodney R

    2014-08-01

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

  2. The Protective Role of Parental Media Monitoring Style from Early to Late Adolescence.

    PubMed

    Padilla-Walker, Laura M; Coyne, Sarah M; Kroff, Savannah L; Memmott-Elison, Madison K

    2017-08-08

    The goal of the current study was to examine the protective role that maternal media monitoring might have for adolescents. This was done by considering whether styles of media monitoring either directly reduced media use, or whether they buffered the associations between aggressive media use and adolescents' prosocial behavior, aggression, and delinquency. Participants were 681 adolescents from two cities in the United States (51% female; 73% white), and their mothers, who provided data at two different time points, 2 years apart (when adolescents were roughly ages 13 and 15). Mixture modeling results revealed that mothers used four different styles of media monitoring made up of combinations of active and restrictive monitoring as well as forms of co-use. Styles that included active monitoring and connective co-use (i.e., engaging in media with the intent to connect with children) were directly associated with less media use, and moderated links between adolescents' media use and behavioral outcomes concurrently but not longitudinally. The discussion was focused on the strength of considering multiple strategies of media monitoring together, and how this approach can inform future research in the area of parental media monitoring.

  3. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Early Results from the Advanced Radiation Protection Thick GCR Shielding Project

    NASA Technical Reports Server (NTRS)

    Norman, Ryan B.; Clowdsley, Martha; Slaba, Tony; Heilbronn, Lawrence; Zeitlin, Cary; Kenny, Sean; Crespo, Luis; Giesy, Daniel; Warner, James; McGirl, Natalie; hide

    2017-01-01

    The Advanced Radiation Protection Thick Galactic Cosmic Ray (GCR) Shielding Project leverages experimental and modeling approaches to validate a predicted minimum in the radiation exposure versus shielding depth curve. Preliminary results of space radiation models indicate that a minimum in the dose equivalent versus aluminum shielding thickness may exist in the 20-30 g/cm2 region. For greater shield thickness, dose equivalent increases due to secondary neutron and light particle production. This result goes against the long held belief in the space radiation shielding community that increasing shielding thickness will decrease risk to crew health. A comprehensive modeling effort was undertaken to verify the preliminary modeling results using multiple Monte Carlo and deterministic space radiation transport codes. These results verified the preliminary findings of a minimum and helped drive the design of the experimental component of the project. In first-of-their-kind experiments performed at the NASA Space Radiation Laboratory, neutrons and light ions were measured between large thicknesses of aluminum shielding. Both an upstream and a downstream shield were incorporated into the experiment to represent the radiation environment inside a spacecraft. These measurements are used to validate the Monte Carlo codes and derive uncertainty distributions for exposure estimates behind thick shielding similar to that provided by spacecraft on a Mars mission. Preliminary results for all aspects of the project will be presented.

  6. Hippocampal Injury Induced Cognitive and Mood Dysfunction, Altered Neurogenesis and Epilepsy: Can Early Neural Stem Cell Grafting Intervention Provide Protection?

    PubMed Central

    Shetty, Ashok K.

    2014-01-01

    Damage to hippocampus can occur through many causes including head trauma, ischemia, stroke, status epilepticus and Alzheimer’s disease. Certain changes such as increased levels of neurogenesis and elevated concentrations of multiple neurotrophic factors that ensue in the acute phase after injury seem beneficial for restraining hippocampal dysfunction. However, many alterations that arise in the intermediate to chronic phase after injury such as abnormal migration of newly born neurons, aberrant synaptic reorganization, progressive loss of inhibitory gamma-amino butyric acid positive interneurons including those expressing reelin, greatly declined neurogenesis and sustained inflammation are detrimental. Consequently, the net effect of post-injury plasticity in the hippocampus remains inadequate for promoting significant functional recovery. Hence, ideal therapeutic interventions ought to be efficient for restraining these detrimental changes in order to block the propensity of most hippocampal injuries to evolve into learning deficits, memory dysfunction, depression, and temporal lobe epilepsy. Neural stem cell (NSC) grafting into the hippocampus early after injury appears alluring from this perspective because several recent studies have demonstrated therapeutic value of this intervention, especially for preventing/easing memory dysfunction, depresion and temporal lobe epilepsy development in the chronic phase after injury. These beneficial effects of NSC grafting appeared to be mediated through considerable modulation of aberrant hippocampal post-injury plasticity with additions of new inhibitory gamma-amino butyric acid positive interneurons, and astrocytes secreting a variety of neurotrophic factors and anticonvulsant proteins. This review confers advancements made in NSC grafting therapy for treating hippocampal injury in animal models of excitotoxic injury, traumatic brain injury, Alzheimer’s disease and status epilepticus, potential mechanisms of

  7. Asthma in US Mexican-Origin Children in Early Childhood: Differences in Risk and Protective Factors by Parental Nativity.

    PubMed

    Hillemeier, Marianne M; Landale, Nancy S; Oropesa, R S

    2015-01-01

    Over 900,000 Mexican-origin children in the United States have asthma, but little is known about the extent to which development of this condition reflects early childhood exposure to social and environmental risks. The objectives of this research are to demonstrate the roles of risk and protective factors in the prevalence and severity of asthma in this population and provide comparisons with other racial/ethnic groups. Nationally representative data from the Early Childhood Longitudinal Study, Birth Cohort (n = 6900), with county-level ozone data appended to this file were analyzed using descriptive and multivariate regression methods. The odds of asthma diagnosis by 60 months are approximately 50% higher among Mexican-origin children than for non-Hispanic whites (P < .05) in multivariate analyses. Compared to those with foreign-born parents, Mexican-origin children with native-born parents have a lower likelihood of being breast-fed and greater chances of having risks including a family history of asthma, having respiratory illnesses and allergies, living with a smoker, and attending center-based child care. Mexican-origin children live in counties with over 3 times more elevated ozone days annually than non-Hispanic whites. Mexican-origin children experience a constellation of risk and protective factors, but those with US-born parents have elevated asthma risks compared to those with foreign-born parents. Asthma incidence and severity will likely increase as this population becomes increasingly integrated into US society. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  8. Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years

    PubMed Central

    Rosenberger, Albert; Illig, Thomas; Korb, Katrin; Klopp, Norman; Zietemann, Vera; Wölke, Gabi; Meese, Eckart; Sybrecht, Gerhard; Kronenberg, Florian; Cebulla, Matthias; Degen, Maria; Drings, Peter; Gröschel, Andreas; Konietzko, Nikolaus; Kreymborg, Karsten grosse; Häußinger, Karl; Höffken, Gerd; Jilge, Bettina; Ko, You-Dschun; Morr, Harald; Schmidt, Christine; Schmidt, E-Wilhelm; Täuscher, Dagmar; Bickeböller, Heike; Wichmann, H-Erich

    2008-01-01

    Background Early onset lung cancer shows some familial aggregation, pointing to a genetic predisposition. This study was set up to investigate the role of candidate genes in the susceptibility to lung cancer patients younger than 51 years at diagnosis. Methods 246 patients with a primary, histologically or cytologically confirmed neoplasm, recruited from 2000 to 2003 in major lung clinics across Germany, were matched to 223 unrelated healthy controls. 11 single nucleotide polymorphisms of genes with reported associations to lung cancer have been genotyped. Results Genetic associations or gene-smoking interactions was found for GPX1(Pro200Leu) and EPHX1(His113Tyr). Carriers of the Leu-allele of GPX1(Pro200Leu) showed a significant risk reduction of OR = 0.6 (95% CI: 0.4–0.8, p = 0.002) in general and of OR = 0.3 (95% CI:0.1–0.8, p = 0.012) within heavy smokers. We could also find a risk decreasing genetic effect for His-carriers of EPHX1(His113Tyr) for moderate smokers (OR = 0.2, 95% CI:0.1–0.7, p = 0.012). Considered both variants together, a monotone decrease of the OR was found for smokers (OR of 0.20; 95% CI: 0.07–0.60) for each protective allele. Conclusion Smoking is the most important risk factor for young lung cancer patients. However, this study provides some support for the T-Allel of GPX1(Pro200Leu) and the C-Allele of EPHX1(His113Tyr) to play a protective role in early onset lung cancer susceptibility. PMID:18298806

  9. 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.

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

    PubMed

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

    2014-01-01

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

  11. 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

  12. Symmetry Protection of Critical Phases and a Global Anomaly in 1 +1 Dimensions

    NASA Astrophysics Data System (ADS)

    Furuya, Shunsuke C.; Oshikawa, Masaki

    2017-01-01

    We derive a selection rule among the (1 +1 )-dimensional SU(2) Wess-Zumino-Witten theories, based on the global anomaly of the discrete Z2 symmetry found by Gepner and Witten. In the presence of both the SU(2) and Z2 symmetries, a renormalization-group flow is possible between level-k and level-k' Wess-Zumino-Witten theories only if k ≡k' mod 2 . This classifies the Lorentz-invariant, SU(2)-symmetric critical behavior into two "symmetry-protected" categories corresponding to even and odd levels, restricting possible gapless critical behavior of translation-invariant quantum spin chains.

  13. 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.

  14. 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.

  15. 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.

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

    PubMed

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

    2008-05-01

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

  17. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

    PubMed

    Mithal, Leena B; Palac, Hannah L; Yogev, Ram; Ernst, Linda M; Mestan, Karen K

    2017-01-01

    Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

  18. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants

    PubMed Central

    Palac, Hannah L.; Yogev, Ram; Ernst, Linda M.; Mestan, Karen K.

    2017-01-01

    Background Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. Methods In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. Results cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. Conclusion This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and

  19. 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.

  20. High-Content Analysis of Sequential Events during the Early Phase of Influenza A Virus Infection

    PubMed Central

    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

  1. NOD2 dependent neutrophil recruitment is required for early protective immune responses against infectious Litomosoides sigmodontis L3 larvae

    PubMed Central

    Ajendra, Jesuthas; Specht, Sabine; Ziewer, Sebastian; Schiefer, Andrea; Pfarr, Kenneth; Parčina, Marijo; Kufer, Thomas A.; Hoerauf, Achim; Hübner, Marc P.

    2016-01-01

    Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) recognizes muramyl dipeptide (MDP) of bacterial cell walls, triggering NFκB-induced pro-inflammation. As most human pathogenic filariae contain Wolbachia endobacteria that synthesize the MDP-containing cell wall precursor lipid II, NOD2’s role during infection with the rodent filaria Litomosoides sigmodontis was investigated. In NFκB reporter-cells, worm-extract containing Wolbachia induced NOD2 and NOD1. NOD2-deficient mice infected with L. sigmodontis had significantly more worms than wildtype controls early in infection. Increased worm burden was not observed after subcutaneous infection, suggesting that protective NOD2-dependent immune responses occur within the skin. Flow cytometry demonstrated that neutrophil recruitment to the skin was impaired in NOD2−/− mice after intradermal injection of third stage larvae (L3), and blood neutrophil numbers were reduced after L. sigmodontis infection. PCR array supported the requirement of NOD2 for recruitment of neutrophils to the skin, as genes associated with neutrophil recruitment and activation were downregulated in NOD2−/− mice after intradermal L3 injection. Neutrophil depletion before L. sigmodontis infection increased worm recovery in wildtype mice, confirming that neutrophils are essential against invading L3 larvae. This study indicates that NOD-like receptors are implemented in first-line protective immune responses against filarial nematodes. PMID:28004792

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

    PubMed

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

    2014-08-29

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

  3. Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity.

    PubMed

    Chen, Zheng; Odstrcil, Elizabeth A; Tu, Benjamin P; McKnight, Steven L

    2007-06-29

    When prototrophic yeast cells are cultured under nutrient-limited conditions that mimic growth in the wild, rather than in the high-glucose solutions used in most laboratory studies, they exhibit a robustly periodic metabolic cycle. Over a cycle of 4 to 5 hours, yeast cells rhythmically alternate between glycolysis and respiration. The cell division cycle is tightly constrained to the reductive phase of this yeast metabolic cycle, with DNA replication taking place only during the glycolytic phase. We show that cell cycle mutants impeded in metabolic cycle-directed restriction of cell division exhibit substantial increases in spontaneous mutation rate. In addition, disruption of the gene encoding a DNA checkpoint kinase that couples the cell division cycle to the circadian cycle abolishes synchrony of the metabolic and cell cycles. Thus, circadian, metabolic, and cell division cycles may be coordinated similarly as an evolutionarily conserved means of preserving genome integrity.

  4. 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.

  5. 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.

  6. 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

  7. Tetramethylpyrazine Protects against Early Brain Injury after Experimental Subarachnoid Hemorrhage by Affecting Mitochondrial-Dependent Caspase-3 Apoptotic Pathway

    PubMed Central

    Xiao, Xiaolan

    2017-01-01

    This study was to test the hypothesis that tetramethylpyrazine (TMP) protected against early brain injury after subarachnoid hemorrhage (SAH) by affecting the mitochondrial-dependent caspase-3 apoptotic pathway. TMP was administrated after the rats' prechiasmatic SAH mode. Animal neurobehavioral functions were assessed and the mitochondrial morphology, mitochondrial and cytoplasmic calcium, and mitochondrial membrane potential changes (Δψm) of the brain tissues were measured. The expressions of cytoplasmic cytochrome c (cyt c), second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3 B-cell lymphoma 2 (bcl-2) in cells were determined and cellular apoptosis was detected. The treatment of TMP resulted in less apoptotic cells and milder mitochondrial injury and potentially performed better in the neurobehavioral outcome compared to those with saline. Also, TMP ameliorated calcium overload in mitochondria and cytoplasm and alleviated the decrease of Δψm. In addition, TMP inhibited the expression of cytoplasmic cyt c, Smac, and cleaved caspase-3, yet it upregulated the expression of bcl-2. These findings suggest that TMP exerts an antiapoptosis property in the SAH rat model and this is probably mediated by the caspase-3 apoptotic pathway triggered by mitochondrial calcium overload. The finding offers a new therapeutic candidate for early brain injury after SAH. PMID:28337226

  8. Gender differences exist in neuromuscular control patterns during the pre-contact and early stance phase of an unanticipated side-cut and cross-cut maneuver in 15-18 years old adolescent soccer players.

    PubMed

    Landry, Scott C; McKean, Kelly A; Hubley-Kozey, Cheryl L; Stanish, William D; Deluzio, Kevin J

    2009-10-01

    Non-contact ACL injuries generally occur as the foot contacts the ground during cutting or landing maneuvers and the non-contact ACL injury rate is 2-8 times greater in females compared to males. To provide insight into the gender bias of this injury, this study set out to identify gender differences in the neuromuscular response of the quadriceps, hamstrings and gastrocnemii muscles in elite adolescent soccer players during the pre-contact and early stance phases of an unanticipated side-cut and cross-cut. For the early stance phase of the two maneuvers, females demonstrated greater rectus femoris activity compared to males. Throughout the pre-contact phase of the maneuvers, a rectus femoris activation difference was identified with females having an earlier and more rapid rise in muscle activity as initial ground contact approached. Females demonstrated greater lateral and medial gastrocnemii activity for the pre-contact and early stance phases of the side-cut and greater lateral gastrocnemii activity during early stance of the cross-cut. Timing of hamstring activity also differed between genders prior to foot contact. The differences suggest that the activation patterns observed in females might not be providing adequate joint protection and stability, thereby possibly having a contributing role towards increased non-contact ACL injuries in females.

  9. Early-time solution of the horizontal unconfined aquifer in the build-up phase

    NASA Astrophysics Data System (ADS)

    Gravanis, Elias; Akylas, Evangelos

    2017-04-01

    goes away. Nonetheless, no analogue of the kinematic wave or the Boussinesq separable solution exists in this case. The late time state of the build-up phase under constant recharge rate is very simply the steady state solution. Our aim is to construct the early time asymptotic solution of this problem. The solution is expressed as a power series of a suitable similarity variable, which is constructed so that to satisfy the boundary conditions at both ends of the aquifer, that is, it is a polynomial approximation of the exact solution. The series turn out to be asymptotic and it is regularized by re-summation techniques which are used to define divergent series. The outflow rate in this regime is linear in time, and the (dimensionless) coefficient is calculated to eight significant figures. The local error of the series is quantified by its deviation from satisfying the self-similar Boussinesq equation at every point. The local error turns out to be everywhere positive, hence, so is the integrated error, which in turn quantifies the degree of convergence of the series to the exact solution.

  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. Canonical quantization of nonlinear sigma models with a theta term and applications to symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Lapa, Matthew F.; Hughes, Taylor L.

    2017-08-01

    We canonically quantize O (D +2 ) nonlinear sigma models (NLSMs) with a theta term on arbitrary smooth, closed, connected, oriented D -dimensional spatial manifolds M , with the goal of proving the suitability of these models for describing symmetry-protected topological (SPT) phases of bosons in D spatial dimensions. We show that in the disordered phase of the NLSM, and when the coefficient θ of the theta term is an integer multiple of 2 π , the theory on M has a unique ground state and a finite energy gap to all excitations. We also construct the ground state wave functional of the NLSM in this parameter regime, and we show that it is independent of the metric on M and given by the exponential of a Wess-Zumino term for the NLSM field, in agreement with previous results on flat space. Our results show that the NLSM in the disordered phase and at θ =2 π k , k ∈Z , has a symmetry-preserving ground state but no topological order (i.e., no topology-dependent ground state degeneracy), making it an ideal model for describing SPT phases of bosons. Thus, our work places previous results on SPT phases derived using NLSMs on solid theoretical ground. To canonically quantize the NLSM on M , we use Dirac's method for the quantization of systems with second class constraints, suitably modified to account for the curvature of space. In a series of four Appendixes, we provide the technical background needed to follow the discussion in the main sections of the paper.

  12. 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.

  13. Current, luminosity, and X-ray emission in the early phase of dielectric surface flashover in vacuum

    SciTech Connect

    Hegeler, F.; Masten, G.; Krompholz, H.; Hatfield, L.L. )

    1993-04-01

    With high-speed electrical and optical diagnostics, an attempt is made to elucidate the physical mechanisms leading to surface flashover. The experimental device uses a cable discharge to study self-breakdown along the surface of an insulator in vacuum. Preflashover current, breakdown voltage, luminosity, and soft X-ray emission are measured in temporal correlation with a resolution of one nanosecond. The results show a linearly increasing current in the sub-ampere range, and a corresponding linearly increasing luminosity, before an exponential increase of both signals takes over. The