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Sample records for correcting potential human

  1. Structured methods for identifying and correcting potential human errors in space operations.

    Science.gov (United States)

    Nelson, W R; Haney, L N; Ostrom, L T; Richards, R E

    1998-01-01

    Human performance plays a significant role in the development and operation of any complex system, and human errors are significant contributors to degraded performance, incidents, and accidents for technologies as diverse as medical systems, commercial aircraft, offshore oil platforms, nuclear power plants, and space systems. To date, serious accidents attributed to human error have fortunately been rare in space operations. However, as flight rates go up and the duration of space missions increases, the accident rate could increase unless proactive action is taken to identity and correct potential human errors in space operations. The Idaho National Engineering and Environmental Laboratory (INEEL) has developed and applied structured methods of human error analysis to identify potential human errors, assess their effects on system performance, and develop strategies to prevent the errors or mitigate their consequences. These methods are being applied in NASA-sponsored programs to the domain of commercial aviation, focusing on airplane maintenance and air traffic management. The application of human error analysis to space operations could contribute to minimize the risks associated with human error in the design and operation of future space systems.

  2. Development of correction formula for field potential duration of human induced pluripotent stem cell-derived cardiomyocytes sheets

    Directory of Open Access Journals (Sweden)

    Hiroko Izumi-Nakaseko

    2017-09-01

    Full Text Available Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs have been used in many studies to assess proarrhythmic risks of chemical compounds. In those studies, field potential durations (FPD of hiPSC-CMs have been corrected by clinically used Fridericia's and/or Bazett's formulae, however, the rationale for the use of these formulae has not been well established. In the present study, we developed a correction formula for experiments using hiPSC-CMs. First, we analyzed the effect of beating rate on FPD in the hiPSC-CMs sheets with electrical stimuli and a HCN channel inhibitor zatebradine. Next, we examined the relationship between the electrophysiological properties and the expression levels of ion channel genes in the cell sheets. Zatebradine slowed the beating rate and allowed to analyze FPD changes at various pacing cycle lengths. Rate-dependent change in the repolarization period was smaller in the cell sheets than that reported on the human hearts, which can be partly explained by lower gene expression level of hKCNJ2 and hKCNE1. Thus, non-linear equation for correcting FPD in the cell sheet; FPDc = FPD/RR0.22 with RR given in second was obtained, which may make it feasible to assess net repolarization delay by various chemical compounds with a chronotropic action.

  3. Exemplar-based human action pose correction.

    Science.gov (United States)

    Shen, Wei; Deng, Ke; Bai, Xiang; Leyvand, Tommer; Guo, Baining; Tu, Zhuowen

    2014-07-01

    The launch of Xbox Kinect has built a very successful computer vision product and made a big impact on the gaming industry. This sheds lights onto a wide variety of potential applications related to action recognition. The accurate estimation of human poses from the depth image is universally a critical step. However, existing pose estimation systems exhibit failures when facing severe occlusion. In this paper, we propose an exemplar-based method to learn to correct the initially estimated poses. We learn an inhomogeneous systematic bias by leveraging the exemplar information within a specific human action domain. Furthermore, as an extension, we learn a conditional model by incorporation of pose tags to further increase the accuracy of pose correction. In the experiments, significant improvements on both joint-based skeleton correction and tag prediction are observed over the contemporary approaches, including what is delivered by the current Kinect system. Our experiments for the facial landmark correction also illustrate that our algorithm can improve the accuracy of other detection/estimation systems.

  4. Maintenance of differentiation potential of human bone marrow mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene despite [corrected] extensive proliferation

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Haack-Sørensen, Mandana; Burns, Jorge S

    2005-01-01

    Human bone marrow mesenchymal stem cells (hMSC) represent a population of stem cells that are capable of differentiation into multiple lineages. However, these cells exhibit senescence-associated growth arrest and phenotypic changes during long-term in vitro culture. We have recently demonstrated...

  5. One-loop quantum corrections to cosmological scalar field potentials

    CERN Document Server

    Arbey, A; Arbey, Alexandre; Mahmoudi, Farvah

    2007-01-01

    We study the loop corrections to potentials of complex or coupled real scalar fields used in cosmology to account for dark energy, dark matter or dark fluid. We show that the SUGRA quintessence and dark matter scalar field potentials are stable against the quantum fluctuations, and we propose solutions to the instability of the potentials of coupled quintessence and dark fluid scalar fields. We also find that a coupling to fermions is very restricted, unless this coupling has a structure which already exists in the scalar field potential or which can be compensated by higher order corrections. Finally, we study the influence of the curvature and kinetic term corrections.

  6. Loop corrections to the antibrane potential

    CERN Document Server

    Bena, Iosif; Turton, David

    2016-01-01

    Antibranes provide some of the most generic ways to uplift Anti-de Sitter flux compactifications to de Sitter, and there is a growing body of evidence that antibranes placed in long warped throats such as the Klebanov-Strassler warped deformed conifold solution have a brane-brane-repelling tachyon. This tachyon was first found in the regime of parameters in which the backreaction of the antibranes is large, and its existence was inferred from a highly nontrivial cancellation of certain terms in the inter-brane potential. We use a brane effective action approach, similar to that proposed by Michel, Mintun, Polchinski, Puhm and Saad in arXiv:1412.5702, to analyze antibranes in Klebanov-Strassler when their backreaction is small, and find a regime of parameters where all perturbative contributions to the action can be computed explicitly. We find that the cancellation found at strong coupling is also present in the weak-coupling regime, and we establish its existence to all loops. Our calculation indicates that ...

  7. Loop corrections to the antibrane potential

    Science.gov (United States)

    Bena, Iosif; Blåbäck, Johan; Turton, David

    2016-07-01

    Antibranes provide some of the most generic ways to uplift Anti-de Sitter flux compactifications to de Sitter, and there is a growing body of evidence that antibranes placed in long warped throats such as the Klebanov-Strassler warped deformed conifold solution have a brane-brane-repelling tachyon. This tachyon was first found in the regime of parameters in which the backreaction of the antibranes is large, and its existence was inferred from a highly nontrivial cancellation of certain terms in the inter-brane potential. We use a brane effective action approach, similar to that proposed by Michel, Mintun, Polchinski, Puhm and Saad in [29], to analyze antibranes in Klebanov-Strassler when their backreaction is small, and find a regime of parameters where all perturbative contributions to the action can be computed explicitly. We find that the cancellation found at strong coupling is also present in the weak-coupling regime, and we establish its existence to all loops. Our calculation indicates that the spectrum of the antibrane worldvolume theory is not gapped, and may generically have a tachyon. Hence uplifting mechanisms involving antibranes remain questionable even when backreaction is small.

  8. Assessing atmospheric bias correction for dynamical consistency using potential vorticity

    Science.gov (United States)

    Rocheta, Eytan; Evans, Jason P.; Sharma, Ashish

    2014-12-01

    Correcting biases in atmospheric variables prior to impact studies or dynamical downscaling can lead to new biases as dynamical consistency between the ‘corrected’ fields is not maintained. Use of these bias corrected fields for subsequent impact studies and dynamical downscaling provides input conditions that do not appropriately represent intervariable relationships in atmospheric fields. Here we investigate the consequences of the lack of dynamical consistency in bias correction using a measure of model consistency—the potential vorticity (PV). This paper presents an assessment of the biases present in PV using two alternative correction techniques—an approach where bias correction is performed individually on each atmospheric variable, thereby ignoring the physical relationships that exists between the multiple variables that are corrected, and a second approach where bias correction is performed directly on the PV field, thereby keeping the system dynamically coherent throughout the correction process. In this paper we show that bias correcting variables independently results in increased errors above the tropopause in the mean and standard deviation of the PV field, which are improved when using the alternative proposed. Furthermore, patterns of spatial variability are improved over nearly all vertical levels when applying the alternative approach. Results point to a need for a dynamically consistent atmospheric bias correction technique which results in fields that can be used as dynamically consistent lateral boundaries in follow-up downscaling applications.

  9. Nucleus-nucleus potential with shell-correction contribution

    CERN Document Server

    Denisov, V Yu

    2015-01-01

    The full relaxed-density potential between spherical nuclei is considered as a sum of the macroscopic and shell-correction contributions. The macroscopic part of the potential is related to a nucleus-nucleus potential obtained in the framework of the extended Thomas-Fermi approach with the Skyrme and Coulomb forces and the relaxed-density ansatz for evaluation of proton and neutron densities of interacting nuclei. A simple prescription for the shell-correction part of the total potential is discussed. The parameters of the shell-correction and macroscopic parts of the relaxed-density potential are found by fitting the empirical barrier heights of the 89 nucleus-nucleus systems as well as macroscopic potentials evaluated for 1485 nucleus-nucleus systems at 12 distances around touching points.

  10. GUP parameter from quantum corrections to the Newtonian potential

    CERN Document Server

    Scardigli, Fabio; Vagenas, Elias

    2016-01-01

    We propose a technique to compute the deformation parameter of the generalized uncertainty principle by using the leading quantum corrections to the Newtonian potential. The calculation gives, to first order, an unambiguous numerical result. The physical meaning of this value is discussed, and compared with analogous previous results, as well as with known bounds on the generalized uncertainty principle deformation parameter.

  11. Hadronic correction to Coulomb potential between quarks and diquark structure

    Energy Technology Data Exchange (ETDEWEB)

    Xin-Heng, Guo [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Xue-Qian, Li; Peng-Nian, Shen [Academia Sinica, Beijing, BJ (China). Inst. of High Energy Physics; Chuang, Wang [Nankai Univ., TJ (China). Dept. of Physics

    1997-07-01

    We have studied the hadronic correction from the background pion fields due to the chiral symmetry breaking to the Coulomb potential that governs the short-distance behavior of the interactions between the bound quarks. The background fields are associated with the constituent quark mass. We find a modified form which favors the diquark structure. We also roughly estimate an influence of this correction on the phase shifts in nucleon scattering and find that it may cause an extra middle range attraction between nucleons which is expected. (author) 17 refs., 4 figs.

  12. GUP parameter from quantum corrections to the Newtonian potential

    Directory of Open Access Journals (Sweden)

    Fabio Scardigli

    2017-04-01

    Full Text Available We propose a technique to compute the deformation parameter of the generalized uncertainty principle by using the leading quantum corrections to the Newtonian potential. We just assume General Relativity as theory of Gravitation, and the thermal nature of the GUP corrections to the Hawking spectrum. With these minimal assumptions our calculation gives, to first order, a specific numerical result. The physical meaning of this value is discussed, and compared with the previously obtained bounds on the generalized uncertainty principle deformation parameter.

  13. The Euler characteristic correction to the Kaehler potential - revisited

    CERN Document Server

    Bonetti, Federico

    2016-01-01

    We confirm the leading $\\alpha'^3$ correction to the 4d, $\\mathcal N = 1$ K\\"{a}hler potential of type IIB orientifold compactifications, proportional to the Euler characteristic of the Calabi-Yau threefold (BBHL correction). We present the explicit solution for the $\\alpha'^3$-modified internal background metric in terms of the non-harmonic part of the third Chern form of the leading order Calabi-Yau manifold. The corrected internal manifold is almost Calabi-Yau and admits an $SU(3)$ structure with non-vanishing torsion. We also find that the full ten-dimensional Einstein frame background metric is multiplied by a non-trivial Weyl factor. Performing a Kaluza-Klein reduction on the modified background we derive the $\\alpha'^3$-corrected kinetic terms for the dilaton and the K\\"{a}hler deformations of the internal Calabi-Yau threefold for arbitrary $h^{1,1}$. We analyze these kinetic terms in the 4d, $\\mathcal N = 2$ un-orientifolded theory, confirming the expected correction to the K\\"ahler moduli space prepo...

  14. Human Potential Development.

    Science.gov (United States)

    Tyree, Edna J.

    This paper describes the organization and implementation of 16 seminars on the subject of developing the potentials inherent in the individuals involved. The stated goals of this group project for teacher corps interns are: (1) identify and use personal strengths and potential in many areas; (2) understand achievement patterns and the way in which…

  15. Correction on the Nomenclature of Human Plasmodium.

    Science.gov (United States)

    Sabrosky, C W

    1946-10-25

    In the nomenclatorial and zoological confusion in the names for the human malaria parasites (Sabrosky and Usinger. Science, 1944, 100, 190-192; Beltran. Gaceta Med. Mexico, 1944, 74, 61-74), one further point has been discovered. It has usually been considered that there were only two different proposals involving malariae as a new specific name-Oscillaria malariae Laveran, 1881, and Haemamoeba malariae Feletti and Grassi, 1890. Actually it now appears that there were three!

  16. Task Refinement for Autonomous Robots using Complementary Corrective Human Feedback

    Directory of Open Access Journals (Sweden)

    Cetin Mericli

    2011-06-01

    Full Text Available A robot can perform a given task through a policy that maps its sensed state to appropriate actions. We assume that a hand-coded controller can achieve such a mapping only for the basic cases of the task. Refining the controller becomes harder and gets more tedious and error prone as the complexity of the task increases. In this paper, we present a new learning from demonstration approach to improve the robot's performance through the use of corrective human feedback as a complement to an existing hand-coded algorithm. The human teacher observes the robot as it performs the task using the hand-coded algorithm and takes over the control to correct the behavior when the robot selects a wrong action to be executed. Corrections are captured as new state-action pairs and the default controller output is replaced by the demonstrated corrections during autonomous execution when the current state of the robot is decided to be similar to a previously corrected state in the correction database. The proposed approach is applied to a complex ball dribbling task performed against stationary defender robots in a robot soccer scenario, where physical Aldebaran Nao humanoid robots are used. The results of our experiments show an improvement in the robot's performance when the default hand-coded controller is augmented with corrective human demonstration.

  17. Trypsin potentiates human fibrocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Michael J V White

    Full Text Available Trypsin-containing topical treatments can be used to speed wound healing, although the mechanism of action is unknown. To help form granulation tissue and heal wounds, monocytes leave the circulation, enter the wound tissue, and differentiate into fibroblast-like cells called fibrocytes. We find that 20 to 200 ng/ml trypsin (concentrations similar to those used in wound dressings potentiates the differentiation of human monocytes to fibrocytes in cell culture. Adding trypsin inhibitors increases the amount of trypsin needed to potentiate fibrocyte differentiation, suggesting that the potentiating effect is dependent on trypsin proteolytic activity. Proteases with other site specificities such as pepsin, endoprotease GluC, and chymotrypsin do not potentiate fibrocyte differentiation. This potentiation requires the presence of albumin in the culture medium, and tryptic fragments of human or bovine albumin also potentiate fibrocyte differentiation. These results suggest that topical trypsin speeds wound healing by generating tryptic fragments of albumin, which in turn potentiate fibrocyte differentiation.

  18. Trypsin potentiates human fibrocyte differentiation.

    Science.gov (United States)

    White, Michael J V; Glenn, Melissa; Gomer, Richard H

    2013-01-01

    Trypsin-containing topical treatments can be used to speed wound healing, although the mechanism of action is unknown. To help form granulation tissue and heal wounds, monocytes leave the circulation, enter the wound tissue, and differentiate into fibroblast-like cells called fibrocytes. We find that 20 to 200 ng/ml trypsin (concentrations similar to those used in wound dressings) potentiates the differentiation of human monocytes to fibrocytes in cell culture. Adding trypsin inhibitors increases the amount of trypsin needed to potentiate fibrocyte differentiation, suggesting that the potentiating effect is dependent on trypsin proteolytic activity. Proteases with other site specificities such as pepsin, endoprotease GluC, and chymotrypsin do not potentiate fibrocyte differentiation. This potentiation requires the presence of albumin in the culture medium, and tryptic fragments of human or bovine albumin also potentiate fibrocyte differentiation. These results suggest that topical trypsin speeds wound healing by generating tryptic fragments of albumin, which in turn potentiate fibrocyte differentiation.

  19. Correction

    Directory of Open Access Journals (Sweden)

    2012-01-01

    Full Text Available Regarding Gorelik, G., & Shackelford, T.K. (2011. Human sexual conflict from molecules to culture. Evolutionary Psychology, 9, 564–587: The authors wish to correct an omission in citation to the existing literature. In the final paragraph on p. 570, we neglected to cite Burch and Gallup (2006 [Burch, R. L., & Gallup, G. G., Jr. (2006. The psychobiology of human semen. In S. M. Platek & T. K. Shackelford (Eds., Female infidelity and paternal uncertainty (pp. 141–172. New York: Cambridge University Press.]. Burch and Gallup (2006 reviewed the relevant literature on FSH and LH discussed in this paragraph, and should have been cited accordingly. In addition, Burch and Gallup (2006 should have been cited as the originators of the hypothesis regarding the role of FSH and LH in the semen of rapists. The authors apologize for this oversight.

  20. Correction

    DEFF Research Database (Denmark)

    Pinkevych, Mykola; Cromer, Deborah; Tolstrup, Martin

    2016-01-01

    [This corrects the article DOI: 10.1371/journal.ppat.1005000.][This corrects the article DOI: 10.1371/journal.ppat.1005740.][This corrects the article DOI: 10.1371/journal.ppat.1005679.].......[This corrects the article DOI: 10.1371/journal.ppat.1005000.][This corrects the article DOI: 10.1371/journal.ppat.1005740.][This corrects the article DOI: 10.1371/journal.ppat.1005679.]....

  1. Developing Human Resources through Actualizing Human Potential

    Science.gov (United States)

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  2. Evoked Potentials and Human Intelligence.

    Science.gov (United States)

    Ertl, John P.; Schafer, Edward W. P.

    Evidence of a relationship between the electrical responses of the human brain and psychometric measure of intelligence is presented. These involuntary cortical responses, known as average evoked potentials are considered to be the electrical signs of information processing by the brain. The time delays of these responses from presentation of a…

  3. Human rights and correctional health policy: a view from Europe.

    Science.gov (United States)

    Rogan, Mary

    2017-03-13

    Purpose Correctional healthcare should promote the protection of human rights. The purpose of this paper is to bring a discussion of human rights into debates on how such policy should be best organized. Design/methodology/approach The paper achieves its aim by providing an analysis of European prison law and policy in the area of prison health, through assessing decisions of the European Court of Human Rights, as well as policies created by the European Committee for the Prevention of Torture. Findings The paper describes the position of the European Court of Human Rights on the topics of access to healthcare, ill health and release from prison, mental illness in prison, and the duty to provide rehabilitative programming for those seeking to reduce their level of "risk." It also argues that human rights law can be a source of practical reform, and that legal frameworks have much to offer healthcare leaders seeking to uphold the dignity of those in their care. Originality/value This paper will provide a rare example of the engagement of human rights law with correctional health policy. It provides practical recommendations arising out of an analysis of European human rights law in the area of prisons.

  4. Correcting Acidosis during Hemodialysis: Current Limitations and a Potential Solution.

    Science.gov (United States)

    Tovbin, David; Sherman, Richard A

    2016-01-01

    The deleterious catabolic and pro-inflammatory effects of acidosis in hemodialysis (HD) patients and the importance of its correction for limiting mineral bone disease (MBD) are well known. Although oral base therapy could be a solution for correcting acidosis in HD patients, it increases their already enormous medication load and sodium intake; this approach is not used commonly. Therefore, we need to rely more on correcting acidosis during the HD procedure, which is difficult to achieve, in part, because HD is an intermittent therapy. The currently used fixed dialysate bicarbonate concentrations are associated with pre-HD acidosis and intra-dialytic alkalosis. We suggest that a decreasing dialysate bicarbonate concentration from an initially high concentration be considered as a means of correcting acidosis with limited intra-dialytic alkalosis. Some evidence, as well as theoretical considerations, supports such an approach. © 2015 Wiley Periodicals, Inc.

  5. "Human potential" and progressive pedagogy

    DEFF Research Database (Denmark)

    Øland, Trine

    2012-01-01

    This article examines the cultural constructs of progressive pedagogy in Danish school pedagogy and its emerging focus on the child’s human potential from the 1920s to the 1950s. It draws on Foucault’s notion of ‘dispositifs’ and the ‘elements of history’, encircling a complex transformation...... of continuity and discontinuity of progressive pedagogy. The Danish context is identified as being part of an international and scientific enlightenment movement circulating in, e.g., the New Education Fellowship (NEF). The cultural constructs embedded in progressivism are clarified in the article...

  6. Correcting for purifying selection: an improved human mitochondrial molecular clock.

    Science.gov (United States)

    Soares, Pedro; Ermini, Luca; Thomson, Noel; Mormina, Maru; Rito, Teresa; Röhl, Arne; Salas, Antonio; Oppenheimer, Stephen; Macaulay, Vincent; Richards, Martin B

    2009-06-01

    There is currently no calibration available for the whole human mtDNA genome, incorporating both coding and control regions. Furthermore, as several authors have pointed out recently, linear molecular clocks that incorporate selectable characters are in any case problematic. We here confirm a modest effect of purifying selection on the mtDNA coding region and propose an improved molecular clock for dating human mtDNA, based on a worldwide phylogeny of > 2000 complete mtDNA genomes and calibrating against recent evidence for the divergence time of humans and chimpanzees. We focus on a time-dependent mutation rate based on the entire mtDNA genome and supported by a neutral clock based on synonymous mutations alone. We show that the corrected rate is further corroborated by archaeological dating for the settlement of the Canary Islands and Remote Oceania and also, given certain phylogeographic assumptions, by the timing of the first modern human settlement of Europe and resettlement after the Last Glacial Maximum. The corrected rate yields an age of modern human expansion in the Americas at approximately 15 kya that-unlike the uncorrected clock-matches the archaeological evidence, but continues to indicate an out-of-Africa dispersal at around 55-70 kya, 5-20 ky before any clear archaeological record, suggesting the need for archaeological research efforts focusing on this time window. We also present improved rates for the mtDNA control region, and the first comprehensive estimates of positional mutation rates for human mtDNA, which are essential for defining mutation models in phylogenetic analyses.

  7. Finite-size corrections to the chemical potential

    NARCIS (Netherlands)

    Siepmann, J.I.; McDonald, I.R.; Frenkel, D.

    1992-01-01

    The particle-insertion method of Widom (1963) has been widely used in numerical simulations for the purpose of calculating the excess chemical potential, mu ex. It is known, however, that values of mu ex obtained by Widom's method are strongly dependent on N, the number of particles in the system. T

  8. Analytical Calculation of Radiative Corrections of a THDM Potential

    CERN Document Server

    Díaz, Enrique

    2016-01-01

    We obtain a closed form effective potential at the one-loop level of a Two Higgs Doublet Model. Through the loop expansion we reproduce the expression presented by Weinberg and Coleman, showing explicitly every step involved in the calculation. The formalism is then extended to include interaction terms between two scalar doublets and a final expression of the one-loop level contributions is presented.

  9. Energy eigenvalues of spherical symmetric potentials with relativistic corrections: analytic results

    Energy Technology Data Exchange (ETDEWEB)

    Dineykhan, M; Zhaugasheva, S A [Bogoliubov Laboratory of Theoretical Physics, Joint Institute for Nuclear Research, Dubna (Russian Federation); Toinbaeva, N Sh [al-Farabi Kazak National University, Almaty (Kazakhstan)

    2010-01-14

    Based on the investigation of the asymptotic behaviour of the polarization loop function for charged n scalar particles in an external gauge field, we determine the interaction Hamiltonian including the relativistic corrections. The energy eigenvalues of spherical symmetric potentials for two-particle bound state systems with relativistic corrections are analytically derived. The energy spectra of linear and funnel potentials with orbital and radial excitations are determined. The energy spectrum of a superposition of Coulomb and Yukawa potentials is also determined. Our result shows that the energy spectrum with the relativistic corrections for the linear, harmonic oscillator and funnel potentials is smaller than the upper boundaries for the energy spectrum established in the framework of the spinless Salpeter equation for the orbital and radial excited states. The relativistic corrections to the energy spectrum of a superposition of the attractive Coulomb potential and the Yukawa (exponentially screened Coulomb) potentials are very small.

  10. Correction

    CERN Document Server

    2002-01-01

    Tile Calorimeter modules stored at CERN. The larger modules belong to the Barrel, whereas the smaller ones are for the two Extended Barrels. (The article was about the completion of the 64 modules for one of the latter.) The photo on the first page of the Bulletin n°26/2002, from 24 July 2002, illustrating the article «The ATLAS Tile Calorimeter gets into shape» was published with a wrong caption. We would like to apologise for this mistake and so publish it again with the correct caption.

  11. Evaluation of screening length corrections for interaction potentials in impact-collision ion scattering spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Wataru, E-mail: take@sp.ous.ac.jp

    2013-10-15

    Since in impact-collision ion scattering spectroscopy (ICISS) data analysis the interaction potential represented by the screening length as the screening effect is not satisfactorily established up to the present, we introduce commonly the correction factor in the screening length. Previously, Yamamura, Takeuchi and Kawamura (YTK) have suggested the theory taking the shell effect of electron distributions into account for the correction factor to Firsov screening length in the Moliere potential. The application of YTK theory to the evaluation of screening length corrections for the interaction potentials in ICISS manifested that the screening length corrections calculated by the YTK theory agree almost with those determined by simulations or numerical calculations in ICISS and its variants data analyses, being superior to the evaluation of screening length corrections with the O’Connor and Biersack (OB) formula.

  12. Correction

    CERN Multimedia

    2002-01-01

    The photo on the second page of the Bulletin n°48/2002, from 25 November 2002, illustrating the article «Spanish Visit to CERN» was published with a wrong caption. We would like to apologise for this mistake and so publish it again with the correct caption.   The Spanish delegation, accompanied by Spanish scientists at CERN, also visited the LHC superconducting magnet test hall (photo). From left to right: Felix Rodriguez Mateos of CERN LHC Division, Josep Piqué i Camps, Spanish Minister of Science and Technology, César Dopazo, Director-General of CIEMAT (Spanish Research Centre for Energy, Environment and Technology), Juan Antonio Rubio, ETT Division Leader at CERN, Manuel Aguilar-Benitez, Spanish Delegate to Council, Manuel Delfino, IT Division Leader at CERN, and Gonzalo León, Secretary-General of Scientific Policy to the Minister.

  13. Correction

    Directory of Open Access Journals (Sweden)

    2014-01-01

    Full Text Available Regarding Tagler, M. J., and Jeffers, H. M. (2013. Sex differences in attitudes toward partner infidelity. Evolutionary Psychology, 11, 821–832: The authors wish to correct values in the originally published manuscript. Specifically, incorrect 95% confidence intervals around the Cohen's d values were reported on page 826 of the manuscript where we reported the within-sex simple effects for the significant Participant Sex × Infidelity Type interaction (first paragraph, and for attitudes toward partner infidelity (second paragraph. Corrected values are presented in bold below. The authors would like to thank Dr. Bernard Beins at Ithaca College for bringing these errors to our attention. Men rated sexual infidelity significantly more distressing (M = 4.69, SD = 0.74 than they rated emotional infidelity (M = 4.32, SD = 0.92, F(1, 322 = 23.96, p < .001, d = 0.44, 95% CI [0.23, 0.65], but there was little difference between women's ratings of sexual (M = 4.80, SD = 0.48 and emotional infidelity (M = 4.76, SD = 0.57, F(1, 322 = 0.48, p = .29, d = 0.08, 95% CI [−0.10, 0.26]. As expected, men rated sexual infidelity (M = 1.44, SD = 0.70 more negatively than they rated emotional infidelity (M = 2.66, SD = 1.37, F(1, 322 = 120.00, p < .001, d = 1.12, 95% CI [0.85, 1.39]. Although women also rated sexual infidelity (M = 1.40, SD = 0.62 more negatively than they rated emotional infidelity (M = 2.09, SD = 1.10, this difference was not as large and thus in the evolutionary theory supportive direction, F(1, 322 = 72.03, p < .001, d = 0.77, 95% CI [0.60, 0.94].

  14. Correction.

    Science.gov (United States)

    2015-10-01

    In the article by Quintavalle et al (Quintavalle C, Anselmi CV, De Micco F, Roscigno G, Visconti G, Golia B, Focaccio A, Ricciardelli B, Perna E, Papa L, Donnarumma E, Condorelli G, Briguori C. Neutrophil gelatinase–associated lipocalin and contrast-induced acute kidney injury. Circ Cardiovasc Interv. 2015;8:e002673. DOI: 10.1161/CIRCINTERVENTIONS.115.002673.), which published online September 2, 2015, and appears in the September 2015 issue of the journal, a correction was needed. On page 1, the institutional affiliation for Elvira Donnarumma, PhD, “SDN Foundation,” has been changed to read, “IRCCS SDN, Naples, Italy.” The institutional affiliation for Laura Papa, PhD, “Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy,” has been changed to read, “Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy” and “Humanitas Research Hospital, Rozzano, Italy.” The authors regret this error.

  15. Relativistic corrections to the central force problem in a generalized potential approach

    CERN Document Server

    Singh, Ashmeet

    2014-01-01

    We present a novel technique to obtain the relativistic corrections to the central force problem in the Lagrangian formulation, using a generalized potential energy. Throughout the paper, we focus on the attractive inverse square law central force. The generalised potential can be made a part of the regular classical lagrangian which can reproduce the relativistic force equation upto second order in $|\\vec{v}|/c$. We then go on to derive the relativistically corrected Hamiltonian from the Lagrangian and estimate the corrections to the total energy of the system. We employ our methodology to calculate the relativistic correction to the circular orbit in attractive gravitational force. We also estimate to the first order energy correction in the ground state of the hydrogen atom in the semi-classical approach. Our predictions in both problems give the reasonable agreement with the known results. Thus we feel that this work has pedagogical value and can be used by undergraduate students to better understand the ...

  16. Correction

    CERN Multimedia

    2007-01-01

    From left to right: Luis, Carmen, Mario, Christian and José listening to speeches by theorists Alvaro De Rújula and Luis Alvarez-Gaumé (right) at their farewell gathering on 15 May.We unfortunately cut out a part of the "Word of thanks" from the team retiring from Restaurant No. 1. The complete message is published below: Dear friends, You are the true "nucleus" of CERN. Every member of this extraordinary human mosaic will always remain in our affections and in our thoughts. We have all been very touched by your spontaneous generosity. Arrivederci, Mario Au revoir,Christian Hasta Siempre Carmen, José and Luis PS: Lots of love to the theory team and to the hidden organisers. So long!

  17. An explicit expression for finite-size corrections to the chemical potential

    NARCIS (Netherlands)

    Smit, B.; Frenkel, D.

    1989-01-01

    In this article an expression is derived for the finite-size corrections to the excess chemical potential in an N-particle system with periodic boundary conditions. The leading N-dependence of the chemical potential is predicted to be proportional to 1/N. The authors derive a simple expression relat

  18. Electroweak Corrections for the Study of the Higgs Potential at the LC

    CERN Document Server

    Boudjema, F; Ishikawa, T; Kaneko, T; Kato, K; Kurihara, Y; Shimizu, Y; Yasui, Y

    2005-01-01

    The full electroweak radiative correction is calculated for the process ee--> nunubarHH which is a window for the study of the Higgs potential at the future linear collider. The calculation is done by using GRACE, the automated system for the calculation of Feynman diagrams. The magnitude of the weak correction in the G-mu scheme is small in the high energy region where this process dominates over the ZHH production.

  19. The Euler characteristic correction to the Kähler potential — revisited

    Science.gov (United States)

    Bonetti, Federico; Weissenbacher, Matthias

    2017-01-01

    We confirm the leading α '3 correction to the 4d, N=1 Kähler potential of type IIB orientifold compactifications, proportional to the Euler characteristic of the Calabi-Yau threefold (BBHL correction). We present the explicit solution for the α '3-modified internal background metric in terms of the non-harmonic part of the third Chern form of the leading order Calabi-Yau manifold. The corrected internal manifold is almost Calabi-Yau and admits an SU(3) structure with non-vanishing torsion. We also find that the full ten-dimensional Einstein frame background metric is multiplied by a non-trivial Weyl factor. Performing a Kaluza-Klein reduction on the modified background we derive the α '3-corrected kinetic terms for the dilaton and the Kähler deformations of the internal Calabi-Yau threefold for arbitrary h 1,1. We analyze these kinetic terms in the 4d, N=2 un-orientifolded theory, confirming the expected correction to the Kähler moduli space pre-potential, as well as in the 4d, N=1 orientifolded theory, thus determining the corrections to the Kähler potential and Kähler coordinates.

  20. Chromatic aberration correction of the human eye for retinal imaging in the near infrared.

    Science.gov (United States)

    Fernández, Enrique J; Unterhuber, Angelika; Povazay, Boris; Hermann, Boris; Artal, Pablo; Drexler, Woflgang

    2006-06-26

    An achromatizing lens has been designed for the human eye in the near infrared range, from 700 to 900 nm, for retinal imaging purposes. Analysis of the performance of the lens, including tolerance to misalignments, has been mathematically accomplished by using an existing eye model. The calculations have shown a virtually perfect correction of the ocular longitudinal chromatic aberration, while still keeping a high optical quality. Ocular aberrations in five subjects have been measured with and without the achromatizing lens by using a Hartmann-Shack wavefront sensor and a broad bandwidth femtosecond Ti:sapphire laser in the spectral range of interest with a set of interference filters, studying the benefits and limits in the use of the achromatizing lens. Ocular longitudinal chromatic aberration has been experimentally demonstrated to be fully corrected by the proposed lens, with no induction of any other parasitic aberration. The practical implementation of the achromatizing lens for Ophthalmoscopy, specifically for optical coherence tomography where the use of polychromatic light sources in the near infrared portion of the spectrum is mandatory, has been considered. The potential benefits of using this lens in combination with adaptive optics to achieve a full aberration correction of the human eye for retinal imaging have also been discussed.

  1. Corrected Newtonian potentials in the two-body problem with applications

    Science.gov (United States)

    Anisiu, M.-C.; Szücs-Csillik, I.

    2016-12-01

    The paper deals with an analytical study of various corrected Newtonian potentials. We offer a complete description of the corrected potentials, for the entire range of the parameters involved. These parameters can be fixed for different models in order to obtain a good concordance with known data. Some of the potentials are generated by continued fractions, and another one is derived from the Newtonian potential by adding a logarithmic correction. The zonal potential, which models the motion of a satellite moving in the equatorial plane of the Earth, is also considered. The range of the parameters for which the potentials behave or not similarly to the Newtonian one is pointed out. The shape of the potentials is displayed for all the significant cases, as well as the orbit of Raduga-1M 2 satellite in the field generated by the continued fractional potential U3, and then by the zonal one. For the continued fractional potential U2 we study the basic problem of the existence and linear stability of circular orbits. We prove that such orbits exist and are linearly stable. This qualitative study offers the possibility to choose the adequate potential, either for modeling the motion of planets or satellites, or to explain some phenomena at galactic scale.

  2. Generalized gradient approximation exchange energy functional with correct asymptotic behavior of the corresponding potential

    Energy Technology Data Exchange (ETDEWEB)

    Carmona-Espíndola, Javier, E-mail: jcarmona-26@yahoo.com.mx [Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, México D. F. 09340, México (Mexico); Gázquez, José L., E-mail: jlgm@xanum.uam.mx [Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, México D. F. 09340, México (Mexico); Departamento de Química, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional 2508, México D. F. 07360, México (Mexico); Vela, Alberto [Departamento de Química, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional 2508, México D. F. 07360, México (Mexico); Trickey, S. B. [Quantum Theory Project, Department of Physics and Department of Chemistry, University of Florida, P.O. Box 118435, Gainesville, Florida 32611-8435 (United States)

    2015-02-07

    A new non-empirical exchange energy functional of the generalized gradient approximation (GGA) type, which gives an exchange potential with the correct asymptotic behavior, is developed and explored. In combination with the Perdew-Burke-Ernzerhof (PBE) correlation energy functional, the new CAP-PBE (CAP stands for correct asymptotic potential) exchange-correlation functional gives heats of formation, ionization potentials, electron affinities, proton affinities, binding energies of weakly interacting systems, barrier heights for hydrogen and non-hydrogen transfer reactions, bond distances, and harmonic frequencies on standard test sets that are fully competitive with those obtained from other GGA-type functionals that do not have the correct asymptotic exchange potential behavior. Distinct from them, the new functional provides important improvements in quantities dependent upon response functions, e.g., static and dynamic polarizabilities and hyperpolarizabilities. CAP combined with the Lee-Yang-Parr correlation functional gives roughly equivalent results. Consideration of the computed dynamical polarizabilities in the context of the broad spectrum of other properties considered tips the balance to the non-empirical CAP-PBE combination. Intriguingly, these improvements arise primarily from improvements in the highest occupied and lowest unoccupied molecular orbitals, and not from shifts in the associated eigenvalues. Those eigenvalues do not change dramatically with respect to eigenvalues from other GGA-type functionals that do not provide the correct asymptotic behavior of the potential. Unexpected behavior of the potential at intermediate distances from the nucleus explains this unexpected result and indicates a clear route for improvement.

  3. Corrected Newtonian potentials in the two-body problem with applications

    CERN Document Server

    Anisiu, M -C

    2016-01-01

    The paper deals with an analytical study of various corrected Newtonian potentials. We offer a complete description of the corrected potentials, for the entire range of the parameters involved. These parameters can be fixed for different models in order to obtain a good concordance with known data. Some of the potentials are generated by continued fractions, and another one is derived from the Newtonian potential by adding a logarithmic correction. The zonal potential, which models the motion of a satellite moving in the equatorial plane of the Earth, is also considered. The range of the parameters for which the potentials behave or not similarly to the Newtonian one is pointed out. The shape of the potentials is displayed for all the significant cases, as well as the orbit of Raduga-1M 2 satellite in the field generated by the continued fractional potential U3, and then by the zonal one. For the continued fractional potential U2 we study the basic problem of the existence and linear stability of circular orb...

  4. Noncommutative correction to the Cornell potential in heavy-quarkonium atoms

    Science.gov (United States)

    Mirjalili, A.; Taki, M.

    2016-02-01

    We investigate the effect of space-time noncommutativity on the Cornell potential in heavy-quarkonium systems. It is known that the space-time noncommutativity can create bound states, and we therefore consider the noncommutative geometry of the space-time as a correction in quarkonium models. Furthermore, we take the experimental hyperfine measurements of the bottomium ground state as an upper limit on the noncommutative energy correction and derive the maximum possible value of the noncommutative parameter θ, obtaining θ ≤ 37.94 · 10-34 m2. Finally, we use our model to calculate the maximum value of the noncommutative energy correction for energy levels of charmonium and bottomium in 1S and 2S levels. The energy correction as a binding effect in quarkonium system is smaller for charmonium than for bottomium, as expected.

  5. 75 FR 21508 - Health and Human Services Acquisition Regulation; Corrections

    Science.gov (United States)

    2010-04-26

    ... maintenance, and other activities involving live vertebrate animals conducted under contract (see Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy), Rev. 1986, Repr. 1996... Compliance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals,...

  6. Cosmological dynamics of scalar fields with kinetic corrections: Beyond the exponential potential

    CERN Document Server

    Dutta, Jibitesh; Tamanini, Nicola

    2016-01-01

    We expand the dynamical systems investigation of cosmological scalar fields characterised by kinetic corrections presented in [N. Tamanini, Phys. Rev. D 89 (2014) 083521]. In particular we do not restrict the analysis to exponential potentials only, but we consider arbitrary scalar field potentials and derive general results regarding the corresponding cosmological dynamics. Two specific potentials are then used as examples to show how these models can be employed not only to describe dark energy, but also to achieve dynamical crossing of the phantom barrier at late times. Stability and viability issues at the classical level are also discussed.

  7. Potential Prognostic Markers for Human Prostate Cancer

    Science.gov (United States)

    2001-03-01

    Prostate 35: 185-192, 1998 osteoblasts on prostate carcinoma proliferation and chemo- 32. Trikha M, Cai Y, Grignon D, Honn KV: Identification taxis ...Markers for Human Prostate Cancer PRINCIPAL INVESTIGATOR: Bruce R. Zetter, Ph.D. CONTRACTING ORGANIZATION: Children’s Hospital Boston, Massachusetts...March 2001 Final (1 Sep 98 - 28 Feb 01) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Potential Prognostic Markers for Human Prostate Cancer DAMD17-98-1

  8. 75 FR 5536 - Pipeline Safety: Control Room Management/Human Factors, Correction

    Science.gov (United States)

    2010-02-03

    ... Safety: Control Room Management/Human Factors, Correction AGENCY: Pipeline and Hazardous Materials Safety... Regulations to address human factors and other aspects of control room management for pipelines where... 63310) entitled ``Pipeline Safety: Control Room Management/Human Factors.'' This final rule...

  9. Spatio-temporal separation of roll and pitch balance-correcting commands in humans.

    NARCIS (Netherlands)

    Gruneberg, C.; Duysens, J.E.J.; Honegger, F.; Allum, J.H.J.

    2005-01-01

    This study was designed to provide evidence for the hypothesis that human balance corrections in response to pitch perturbations are controlled by muscle action mainly about the ankle and knee joints, whereas balance corrections for roll perturbations are controlled predominantly by motion about the

  10. Heteroparental blastocyst production from microsurgically corrected tripronucleated human embryos.

    Science.gov (United States)

    Escribá, María-José; Martín, Julio; Rubio, Carmen; Valbuena, Diana; Remohí, José; Pellicer, Antonio; Simón, Carlos

    2006-12-01

    To prove the efficiency of identification and removal of one of the surplus paternal pronuclei in dispermic IVF zygotes to obtain heteroparental blastocysts. Experimental. One hundred fourteen tripronucleated (3PN) embryos from conventional IVF. After informed and signed consent, the patients from Instituto Valenciano Infertilidad (IVI), Valencia, donated their abnormally fertilized embryos. Seventy-two embryos were diploidized by microsurgical removal of the pronucleus located at the farthest position to the second polar body. Forty-two 3PN embryos served as controls. Survival and correction rate; in vitro development up to the blastocyst stage; X, Y, and 18 chromosome determination by triple fluorescent in situ hybridization and, inheritance analysis for 10 polymorphic repeat regions using polymerase chain reaction (PCR) amplification and sequencing. Seventy-eight percent of 3PN zygotes (56/72) survived manipulation and eventually 51 zygotes had two pronuclei (71%). Forty-one percent of manipulated embryos progressed in vitro to the blastocyst stage (21/51). Fluorescent in situ hybridization analysis performed on eight manipulated embryos confirmed their diploid state; all four controls were triploid. Heteroparental inheritances were also confirmed in four of six manipulated embryos. Heteroparental blastocysts can be derived from corrected dispermic zygotes.

  11. Quantum Scalar Corrections to the Gravitational Potentials on de Sitter Background

    CERN Document Server

    Park, Sohyun; Woodard, R P

    2015-01-01

    We employ the graviton self-energy induced by a massless, minimally coupled (MMC) scalar on de Sitter background to compute the quantum corrections to the gravitational potentials of a static point particle with a mass $M$. The Schwinger-Keldysh formalism is used to derive real and causal effective field equations. When evaluated at the one-loop order, the gravitational potentials exhibit a secular decrease in the observed gravitational coupling $G$. This can also be interpreted as a (time dependent) anti-screening of the mass $M$.

  12. Quantum scalar corrections to the gravitational potentials on de Sitter background

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sohyun [Korea Astronomy and Space Science Institute,Daejeon, 305-348 (Korea, Republic of); Prokopec, Tomislav [Institute of Theoretical Physics, Spinoza Instituteand the Center for Extreme Matter and Emergent Phenomena (EMME),Utrecht University, Leuvenlaan 4, 3584 CE Utrecht (Netherlands); Woodard, R.P. [Department of Physics, University of Florida,Gainesville, FL 32611 (United States)

    2016-01-13

    We employ the graviton self-energy induced by a massless, minimally coupled (MMC) scalar on de Sitter background to compute the quantum corrections to the gravitational potentials of a static point particle with a mass M. The Schwinger-Keldysh formalism is used to derive real and causal effective field equations. When evaluated at the one-loop order, the gravitational potentials exhibit a secular decrease in the observed gravitational coupling G. This can also be interpreted as a (time dependent) anti-screening of the mass M.

  13. Scalar-QED {Dirac_h}-corrections to the Coulomb potential

    Energy Technology Data Exchange (ETDEWEB)

    Helayel-Neto, J.A. [Centro Brasileiro de Pesquisas Fisica (CBPF), Rio de Janeiro, RJ (Brazil). E-mail: helayel@cbpf.br; Penna-Firme, A.B. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Educacao. E-mail: andrepf@cbpf.br; Shapiro, I.L. [Juiz de Fora Univ., MG (Brazil). Dept. de Fisica. E-mail: shapiro@fisica.ufjf.br

    2000-05-01

    The leading long-distance 1-loop quantum corrections to the Coulomb potential are derived for scalar QED and their gauge-independence is explicitly checked. The potential is obtained from the direct calculation of the 2-particle scattering amplitude, taking into account all relevant 1-loop diagrams. Our investigation should be regarded as first step towards the same programme for effective Quantum Gravity. In particular, with our calculation in the framework of scalar QED, we are able to demonstrate the incompleteness of some previous studies concerning the quantum Gravity counterpart. (author)

  14. Influence of Misalignment on High-Order Aberration Correction for Normal Human Eyes

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hao-Xin; XU Bing; XUE Li-Xia; DAI Yun; LIU Qian; RAO Xue-Jun

    2008-01-01

    @@ Although a compensation device can correct aberrations of human eyes, the effect will be degraded by its misalignment, especially for high-order aberration correction. We caJculate the positioning tolerance of correction device for high-order aberrations, and within what degree the correcting effect is better than low-order aberration (defocus and astigmatism) correction. With fixed certain misalignment within the positioning tolerance, we calculate the residual wavefront rms aberration of the first-6 to first-35 terms along with the 3rd-5th terms of aberrations corrected, and the combined first-13 terms of aberrations are also studied under the same quantity of misalignment. However, the correction effect of high-order aberrations does not meliorate along with the increase of the high-order terms under some misalignment, moreover, some simple combined terms correction can achieve similar result as complex combinations. These results suggest that it is unnecessary to correct too much the terms of high-order aberrations which are diffcult to accomplish in practice, and gives confdence to correct high-order aberrations out of the laboratory.

  15. Stimulation artifact correction method for estimation of early cortico-cortical evoked potentials.

    Science.gov (United States)

    Trebaul, Lena; Rudrauf, David; Job, Anne-Sophie; Mălîia, Mihai Dragos; Popa, Irina; Barborica, Andrei; Minotti, Lorella; Mîndruţă, Ioana; Kahane, Philippe; David, Olivier

    2016-05-01

    Effective connectivity can be explored using direct electrical stimulations in patients suffering from drug-resistant focal epilepsies and investigated with intracranial electrodes. Responses to brief electrical pulses mimic the physiological propagation of signals and manifest as cortico-cortical evoked potentials (CCEP). The first CCEP component is believed to reflect direct connectivity with the stimulated region but the stimulation artifact, a sharp deflection occurring during a few milliseconds, frequently contaminates it. In order to recover the characteristics of early CCEP responses, we developed an artifact correction method based on electrical modeling of the electrode-tissue interface. The biophysically motivated artifact templates are then regressed out of the recorded data as in any classical template-matching removal artifact methods. Our approach is able to make the distinction between the physiological responses time-locked to the stimulation pulses and the non-physiological component. We tested the correction on simulated CCEP data in order to quantify its efficiency for different stimulation and recording parameters. We demonstrated the efficiency of the new correction method on simulations of single trial recordings for early responses contaminated with the stimulation artifact. The results highlight the importance of sampling frequency for an accurate analysis of CCEP. We then applied the approach to experimental data. The model-based template removal was compared to a correction based on the subtraction of the averaged artifact. This new correction method of stimulation artifact will enable investigators to better analyze early CCEP components and infer direct effective connectivity in future CCEP studies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Excitation Potentials and Shell Corrections for the Elements Z2=20 to Z2=30

    DEFF Research Database (Denmark)

    Andersen, H.H.; Sørensen, H.; Vadja, P.

    1969-01-01

    Excitation potentials and shell corrections for the elements Z 2=20 to Z2=30 are evaluated from experimental stopping-power data for 5-12-MeV protons and deuterons. Use is made of Walske's K- and L-shell corrections and shell corrections calculated by Bonderup (1967) on the basis of the Thomas-Fe...... are found by means of Bonderup's shell corrections. Within the Z2 interval treated here, it is found that I/Z2 increases with increasing Z2, contrary to the general trend through the periodic system of elements......Excitation potentials and shell corrections for the elements Z 2=20 to Z2=30 are evaluated from experimental stopping-power data for 5-12-MeV protons and deuterons. Use is made of Walske's K- and L-shell corrections and shell corrections calculated by Bonderup (1967) on the basis of the Thomas...

  17. Human Defensins: Potential Tools for Clinical Applications

    Directory of Open Access Journals (Sweden)

    Matthias Wenghoefer

    2012-02-01

    Full Text Available As components of the innate immune system, antimicrobial peptides in the form of human defensins play an important role in host defense by serving as the epithelial layer’s biochemical barrier against local infections. Recent studies have shown these molecules to have far more additional cellular functions besides their antimicrobial activity. Defensins play a role in cell division, attraction and maturation of immune cells, differentiation and reorganization of epithelial tissues, wound healing and tumor suppression. This multitude of function makes human defensins appear to be excellent tools for therapeutic approaches. These antimicrobial peptides may be used directly as a remedy against bacterial and viral infections. Furthermore, the application of human defensins can be used to promote wound healing and epithelial reorganization. In particular, human β-defensins have a strong impact on osteoblast proliferation and differentiation. Human β-defensins have already been applied as a vaccination against HIV-1. Another potentially useful characteristic of defensins is their suitability as diagnostic markers in cancer therapy. In particular, α-defensins have already been used for this purpose. Human α-defensin-3, for example, has been described as a tumor marker for lymphocytes. High gene expression levels of α-defensin-3 and -4 have been detected in benign oral neoplasia, α-defensin-6 is considered to be a tumor marker for colon cancer.

  18. Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs.

    Science.gov (United States)

    Sun, Ning; Zhao, Huimin

    2014-05-01

    Sickle cell disease (SCD) is the most common human genetic disease which is caused by a single mutation of human β-globin (HBB) gene. The lack of long-term treatment makes the development of reliable cell and gene therapies highly desirable. Disease-specific patient-derived human induced pluripotent stem cells (hiPSCs) have great potential for developing novel cell and gene therapies. With the disease-causing mutations corrected in situ, patient-derived hiPSCs can restore normal cell functions and serve as a renewable autologous cell source for the treatment of genetic disorders. Here we successfully utilized transcription activator-like effector nucleases (TALENs), a recently emerged novel genome editing tool, to correct the SCD mutation in patient-derived hiPSCs. The TALENs we have engineered are highly specific and generate minimal off-target effects. In combination with piggyBac transposon, TALEN-mediated gene targeting leaves no residual ectopic sequences at the site of correction and the corrected hiPSCs retain full pluripotency and a normal karyotype. Our study demonstrates an important first step of using TALENs for the treatment of genetic diseases such as SCD, which represents a significant advance toward hiPSC-based cell and gene therapies.

  19. [Music-Acoustic Signals Controlled by Subject's Brain Potentials in the Correction of Unfavorable Functional States].

    Science.gov (United States)

    Fedotchev, A I; Bondar, A T; Bakhchina, A V; Parin, S B; Polevaya, S A; Radchenko, G S

    2016-01-01

    Literature review and the results of own studies on the development and experimental testing of musical EEG neurofeedback technology are presented. The technology is based on exposure of subjects to music or music-like signals that are organized in strict accordance with the current values of brain potentials of the patient. The main attention is paid to the analysis of the effectiveness of several versions of the technology, using specific and meaningful for the individual narrow-frequency EEG oscillators during the correction of unfavorable changes of the functional state.

  20. Long Range Corrections for Inhomogeneous Simulations of Mie n-m Potential.

    Science.gov (United States)

    Janeček, Jiří; Said-Aizpuru, Olivier; Paricaud, Patrice

    2017-09-12

    The long-range correction scheme for dispersion interactions in inhomogeneous simulations is generalized to Mie n-m potential. The influence of the cutoff distance and lateral dimensions of the simulation box are studied for 8-6, 12-6, and 20-6 Mie fluids at two different temperatures (close and far from the critical point). For sufficiently large systems (2400 particles, Rc = 3.5σ) equilibrium properties are simulated over the whole vapor-liquid coexistence using the inhomogeneous Monte Carlo simulations, and the results are compared with the Gibbs Ensemble technique and with the square gradient theory combined with the SAFT Mie equation of state.

  1. Transcranial motor evoked potential waveform changes in corrective fusion for adolescent idiopathic scoliosis.

    Science.gov (United States)

    Kobayashi, Kazuyoshi; Imagama, Shiro; Ito, Zenya; Ando, Kei; Hida, Tetsuro; Ito, Kenyu; Tsushima, Mikito; Ishikawa, Yoshimoto; Matsumoto, Akiyuki; Nishida, Yoshihiro; Ishiguro, Naoki

    2017-01-01

    OBJECTIVE Corrective surgery for spinal deformities can lead to neurological complications. Several reports have described spinal cord monitoring in surgery for spinal deformity, but only a few have included patients younger than 20 years with adolescent idiopathic scoliosis (AIS). The goal of this study was to evaluate the characteristics of cases with intraoperative transcranial motor evoked potential (Tc-MEP) waveform deterioration during posterior corrective fusion for AIS. METHODS A prospective database was reviewed, comprising 68 patients with AIS who were treated with posterior corrective fusion in a prospective database. A total of 864 muscles in the lower extremities were chosen for monitoring, and acceptable baseline responses were obtained from 819 muscles (95%). Intraoperative Tc-MEP waveform deterioration was defined as a decrease in intraoperative amplitude of ≥ 70% of the control waveform. Age, Cobb angle, flexibility, operative time, estimated blood loss (EBL), intraoperative body temperature, blood pressure, number of levels fused, and correction rate were examined in patients with and without waveform deterioration. RESULTS The patients (3 males and 65 females) had an average age of 14.4 years (range 11-19 years). The mean Cobb angles before and after surgery were 52.9° and 11.9°, respectively, giving a correction rate of 77.4%. Fourteen patients (20%) exhibited an intraoperative waveform change, and these occurred during incision (14%), after screw fixation (7%), during the rotation maneuver (64%), during placement of the second rod after the rotation maneuver (7%), and after intervertebral compression (7%). Most waveform changes recovered after decreased correction or rest. No patient had a motor deficit postoperatively. In multivariate analysis, EBL (OR 1.001, p = 0.085) and number of levels fused (OR 1.535, p = 0.045) were associated with waveform deterioration. CONCLUSIONS Waveform deterioration commonly occurred during rotation maneuvers

  2. Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting.

    Science.gov (United States)

    Chang, Chia-Wei; Lai, Yi-Shin; Westin, Erik; Khodadadi-Jamayran, Alireza; Pawlik, Kevin M; Lamb, Lawrence S; Goldman, Frederick D; Townes, Tim M

    2015-09-08

    Mutations of the Janus family kinase JAK3 gene cause severe combined immunodeficiency (SCID). JAK3 deficiency in humans is characterized by the absence of circulating T cells and natural killer (NK) cells with normal numbers of poorly functioning B cells (T(-)B(+)NK(-)). Using SCID patient-specific induced pluripotent stem cells (iPSCs) and a T cell in vitro differentiation system, we demonstrate a complete block in early T cell development of JAK3-deficient cells. Correction of the JAK3 mutation by CRISPR/Cas9-enhanced gene targeting restores normal T cell development, including the production of mature T cell populations with a broad T cell receptor (TCR) repertoire. Whole-genome sequencing of corrected cells demonstrates no CRISPR/Cas9 off-target modifications. These studies describe an approach for the study of human lymphopoiesis and provide a foundation for gene correction therapy in humans with immunodeficiencies.

  3. NaCl potentiates human fibrocyte differentiation.

    Science.gov (United States)

    Cox, Nehemiah; Pilling, Darrell; Gomer, Richard H

    2012-01-01

    Excessive NaCl intake is associated with a variety of fibrosing diseases such as renal and cardiac fibrosis. This association has been attributed to increased blood pressure as the result of high NaCl intake. However, studies in patients with high NaCl intake and fibrosis reveal a connection between NaCl intake and fibrosis that is independent of blood pressure. We find that increasing the extracellular concentration of NaCl to levels that may occur in human blood after high-salt intake can potentiate, in serum-free culture conditions, the differentiation of freshly-isolated human monocytes into fibroblast-like cells called fibrocytes. NaCl affects the monocytes directly during their adhesion. Potassium chloride and sodium nitrate also potentiate fibrocyte differentiation. The plasma protein Serum Amyloid P (SAP) inhibits fibrocyte differentiation. High levels of extracellular NaCl change the SAP Hill coefficient from 1.7 to 0.8, and cause a four-fold increase in the concentration of SAP needed to inhibit fibrocyte differentiation by 95%. Together, our data suggest that NaCl potentiates fibrocyte differentiation. NaCl-increased fibrocyte differentiation may thus contribute to NaCl-increased renal and cardiac fibrosis.

  4. NaCl potentiates human fibrocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Nehemiah Cox

    Full Text Available Excessive NaCl intake is associated with a variety of fibrosing diseases such as renal and cardiac fibrosis. This association has been attributed to increased blood pressure as the result of high NaCl intake. However, studies in patients with high NaCl intake and fibrosis reveal a connection between NaCl intake and fibrosis that is independent of blood pressure. We find that increasing the extracellular concentration of NaCl to levels that may occur in human blood after high-salt intake can potentiate, in serum-free culture conditions, the differentiation of freshly-isolated human monocytes into fibroblast-like cells called fibrocytes. NaCl affects the monocytes directly during their adhesion. Potassium chloride and sodium nitrate also potentiate fibrocyte differentiation. The plasma protein Serum Amyloid P (SAP inhibits fibrocyte differentiation. High levels of extracellular NaCl change the SAP Hill coefficient from 1.7 to 0.8, and cause a four-fold increase in the concentration of SAP needed to inhibit fibrocyte differentiation by 95%. Together, our data suggest that NaCl potentiates fibrocyte differentiation. NaCl-increased fibrocyte differentiation may thus contribute to NaCl-increased renal and cardiac fibrosis.

  5. HIV Tat Domain Improves Cross-correction of Human Galactocerebrosidase in a Gene- and Flanking Sequence-dependent Manner

    Directory of Open Access Journals (Sweden)

    Xing-Li Meng

    2013-01-01

    Full Text Available Krabbe disease is a devastating neurodegenerative lysosomal storage disorder caused by a deficiency of β-galactocerebrosidase (GALC. Gene therapy is a promising therapeutic approach for Krabbe disease. As the human brain is large and it is difficult to achieve global gene transduction, the efficacy of cross-correction is a critical determinant of the outcome of gene therapy for this disease. We investigated whether HIV Tat protein transduction domain (PTD can improve the cross-correction of GALC. Tat-PTD significantly increased (~6-fold cross-correction of GALC through enhanced secretion and uptake in a cell-culture model system. The effects of Tat-PTD were gene and flanking amino acids dependent. Tat-fusion increased the secretion of α-galactosidase A (α-gal A, but this did not improve its cross-correction. Tat-fusion did not change either secretion or uptake of β-glucocerebrosidase (GC. Tat-PTD increased GALC protein synthesis, abolished reactivity of GC to the 8E4 antibody, and likely reduced mannose phosphorylation in all these lysosomal enzymes. This study demonstrated that Tat-PTD can be useful for increasing cross-correction efficiency of lysosomal enzymes. However, Tat-PTD is not a mere adhesive motif but possesses a variety of biological functions. Therefore, the potential beneficial effect of Tat-PTD should be assessed individually on each lysosomal enzyme.

  6. Postural adjustments for online corrections of arm movements in standing humans.

    Science.gov (United States)

    Leonard, Julia A; Gritsenko, Valeriya; Ouckama, Ryan; Stapley, Paul J

    2011-05-01

    The aim of this study was to investigate how humans correct ongoing arm movements while standing. Specifically, we sought to understand whether the postural adjustments in the legs required for online corrections of arm movements are predictive or rely on feedback from the moving limb. To answer this question we measured online corrections in arm and leg muscles during pointing movements while standing. Nine healthy right-handed subjects reached with their dominant arm to a visual target in front of them and aligned with their midline. In some trials, the position of the target would switch from the central target to one of the other targets located 15°, 30°, or 45° to the right of the central (midline) target. For each target correction, we measured the time at which arm kinematics, ground reaction forces, and arm and leg muscle electromyogram significantly changed in response to the target displacement. Results show that postural adjustments in the left leg preceded kinematic corrections in the limb. The corrective postural muscle activity in the left leg consistently preceded the corrective reaching muscle activity in the right arm. Our results demonstrate that corrections of arm movements in response to target displacement during stance are preceded by postural adjustments in the leg contralateral to the direction of target shift. Furthermore, postural adjustments preceded both the hand trajectory correction and the arm-muscle activity responsible for it, which suggests that the central nervous system does not depend on feedback from the moving arm to modify body posture during voluntary movement. Instead, postural adjustments lead the online correction in the arm the same way they lead the initiation of voluntary arm movements. This suggests that forward models for voluntary movements executed during stance incorporate commands for posture that are produced on the basis of the required task demands.

  7. Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

    Directory of Open Access Journals (Sweden)

    Maria Lorella Giannì

    2016-10-01

    Full Text Available (1 Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2 Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3 Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = −47.9, 95% confidence interval (CI = −95.7; −0.18; p = 0.049; β = −89.6, 95% CI = −131.5; −47.7; p < 0.0001; β = −104.1, 95% CI = −151.4; −56.7, p < 0.0001; (4 Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants.

  8. Correction: Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

    Science.gov (United States)

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

    2016-02-01

    Correction for `Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents' by Roxanne Hachani et al., Nanoscale, 2015, DOI: 10.1039/c5nr03867g.

  9. Toward Best Practices For Assessing Near Surface Sensor Fouling: Potential Correction Approaches Using Underway Ferry Measurements

    Science.gov (United States)

    Sastri, A. R.; Dewey, R. K.; Pawlowicz, R.; Krogh, J.

    2016-02-01

    Data from long term deployments of sensors on autonomous, mobile and cabled observation platforms suffer potential quality issues associated with bio-fouling. This issue is of particular concern for optical sensors, such as fluorescence and/or absorbance-based instruments for which light emitting/receiving surfaces are prone to fouling due constant contact with the marine environment. Here we examine signal quality for backscatter, chlorophyll and CDOM fluorescence from a single triplet instrument installed in a ferry box system (nominal depth of 3m) operated by Ocean Networks Canada. The time series consists of 22 months of 8-10 daily transits across the productive waters of the Strait of Georgia, British Columbia, Canada (Nanaimo on Vancouver Island and Vancouver on mainland BC). Instruments were cleaned every 2 weeks since all three instruments experienced significant signal attenuation during that period throughout the year. We experimented with a variety of pre- and post-cleaning measurements in an effort to develop `correction factors' with which to account for the effects of fouling. We found that CDOM fluorescence was especially sensitive to fouling and that correction factors derived from measurements of the fluorescence of standardized solutions successfully accounted for fouling. Similar results were found for chlorophyll fluorescence. Here we present results from our measurements and assess the efficacy of each of these approaches using comparisons against additional instruments less prone to signal attenuation over short periods.

  10. Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

    Science.gov (United States)

    Giannì, Maria Lorella; Consonni, Dario; Liotto, Nadia; Roggero, Paola; Morlacchi, Laura; Piemontese, Pasqua; Menis, Camilla; Mosca, Fabio

    2016-10-23

    (1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = -47.9, 95% confidence interval (CI) = -95.7; -0.18; p = 0.049; β = -89.6, 95% CI = -131.5; -47.7; p milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants.

  11. The correction of the distortion of human face based on three-dimensional modeling methods

    Science.gov (United States)

    Ye, Qingmin; Chen, Kuo; Feng, Huajun; Xu, Zhihai; Li, Qi

    2015-08-01

    When the human face is on the edge of field of the camera which has a large view, serious deformation will be captured. To correct the distortion of the human face, we present an approach based on setting up a 3D model. Firstly, we construct 3D target face modeling by using the data and depth information of the standard human face, which is set up by the three-dimensional model with three-dimensional Gaussian function with sectional type. According to the size of the face in the image and the parameters of the camera, we can obtain the information of relative position and depth of the human face. Then by translating the virtual camera axis to the center of the face, we can achieve the goal to correct the distortion of the face based on the theory of three-dimensional imaging. Finally, we have made a lot of experiments, and we study the influence of parameters of the 3D model of human face. The result indicates that the method presented by this paper can play an effective role in correcting the distortion of the face in the edge of the view, and we can get better results if the model appreciates the real human face.

  12. Quarkonium spectroscopy in a potential model with vacuum-polarization corrections

    Energy Technology Data Exchange (ETDEWEB)

    Barik, N.; Jena, S.N.

    1980-05-01

    We consider a potential model taking long-distance vacuum-polarization corrections as suggested by Poggio and Schnitzer, which enables one to interpolate between cc-bar, bb-bar, and tt-bar systems. Taking special care for the accuracy of the numerical integration near the origin, we have developed a numerical method to obtain the heavy-quark--antiquark bound states along with their leptonic widths. We obtain the above flavor-independent potential giving good agreement with the so-called experimental mass splitting of the 1S-2S states of the psi and UPSILON family with reasonable values of the quark-gluon coupling constant ..cap alpha../sub s/, which do not deviate very much from the quantum-chromodynamics value. We obtain some of the bound states of the hypothetical tt-bar family and observe that the effect of screening of the potential due to the vacuum-polarization cloud decreases with increase of the mass of the heavy quark forming the quarkonium.

  13. Latency correction of event-related potentials between different experimental protocols

    Science.gov (United States)

    Iturrate, I.; Chavarriaga, R.; Montesano, L.; Minguez, J.; Millán, JdR

    2014-06-01

    Objective. A fundamental issue in EEG event-related potentials (ERPs) studies is the amount of data required to have an accurate ERP model. This also impacts the time required to train a classifier for a brain-computer interface (BCI). This issue is mainly due to the poor signal-to-noise ratio and the large fluctuations of the EEG caused by several sources of variability. One of these sources is directly related to the experimental protocol or application designed, and may affect the amplitude or latency of ERPs. This usually prevents BCI classifiers from generalizing among different experimental protocols. In this paper, we analyze the effect of the amplitude and the latency variations among different experimental protocols based on the same type of ERP. Approach. We present a method to analyze and compensate for the latency variations in BCI applications. The algorithm has been tested on two widely used ERPs (P300 and observation error potentials), in three experimental protocols in each case. We report the ERP analysis and single-trial classification. Main results. The results obtained show that the designed experimental protocols significantly affect the latency of the recorded potentials but not the amplitudes. Significance. These results show how the use of latency-corrected data can be used to generalize the BCIs, reducing the calibration time when facing a new experimental protocol.

  14. Field of view extension and truncation correction for MR-based human attenuation correction in simultaneous MR/PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Blumhagen, Jan O., E-mail: janole.blumhagen@siemens.com; Ladebeck, Ralf; Fenchel, Matthias [Magnetic Resonance, Siemens AG Healthcare Sector, Erlangen 91052 (Germany); Braun, Harald; Quick, Harald H. [Institute of Medical Physics, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen 91052 (Germany); Faul, David [Siemens Medical Solutions, New York, New York 10015 (United States); Scheffler, Klaus [MRC Department, Max Planck Institute for Biological Cybernetics, Tübingen 72076, Germany and Department of Biomedical Magnetic Resonance, University Hospital Tübingen, Tübingen 72076 (Germany)

    2014-02-15

    Purpose: In quantitative PET imaging, it is critical to accurately measure and compensate for the attenuation of the photons absorbed in the tissue. While in PET/CT the linear attenuation coefficients can be easily determined from a low-dose CT-based transmission scan, in whole-body MR/PET the computation of the linear attenuation coefficients is based on the MR data. However, a constraint of the MR-based attenuation correction (AC) is the MR-inherent field-of-view (FoV) limitation due to static magnetic field (B{sub 0}) inhomogeneities and gradient nonlinearities. Therefore, the MR-based human AC map may be truncated or geometrically distorted toward the edges of the FoV and, consequently, the PET reconstruction with MR-based AC may be biased. This is especially of impact laterally where the patient arms rest beside the body and are not fully considered. Methods: A method is proposed to extend the MR FoV by determining an optimal readout gradient field which locally compensates B{sub 0} inhomogeneities and gradient nonlinearities. This technique was used to reduce truncation in AC maps of 12 patients, and the impact on the PET quantification was analyzed and compared to truncated data without applying the FoV extension and additionally to an established approach of PET-based FoV extension. Results: The truncation artifacts in the MR-based AC maps were successfully reduced in all patients, and the mean body volume was thereby increased by 5.4%. In some cases large patient-dependent changes in SUV of up to 30% were observed in individual lesions when compared to the standard truncated attenuation map. Conclusions: The proposed technique successfully extends the MR FoV in MR-based attenuation correction and shows an improvement of PET quantification in whole-body MR/PET hybrid imaging. In comparison to the PET-based completion of the truncated body contour, the proposed method is also applicable to specialized PET tracers with little uptake in the arms and might

  15. Non-self-conjugate mesons in a potential model with vacuum-polarization corrections

    Energy Technology Data Exchange (ETDEWEB)

    Barik, N.; Jena, S.N.

    1980-10-01

    We present a unified approach to the study of non-self-conjugate mesons including both light and heavy mesons in the framework of the vacuum-polarization-corrected flavor-independent potential. We have found that the quark-confining potential in the form of an almost equal admixture of vector and scalar parts successfully explains the S-wave hyperfine levels of the observed light and heavy mesons. Finally we calculate the electromagnetic mass differences of the heavy-quark mesons and obtain (K-bar*/sup 0/-K*/sup -/)=3.79 MeV, (K-bar/sup 0/-K/sup -/)=6 MeV, (D*/sup +//sub c/-D*/sup 0//sub c/)=2.4 MeV, (D/sup +//sub c/-D/sup 0//sub c/)=5.8 MeV, (D*/sup 0//sub b/-D*/sup -//sub b/)=3.547 MeV, and (D/sup 0//sub b/-D/sup -//sub b/)=3.558 MeV.

  16. Human potential development as a prerequisite of public policy efficiency

    Directory of Open Access Journals (Sweden)

    Polishchuk Iryna Viktorivna

    2014-12-01

    Full Text Available The article analyses the role of the public officers’ human potential for the efficiency of making public policy. It introduces features and criteria of human potential in the context of its development of civil service. The article designates some key directions for the development of human potential of public officers.

  17. Adaptive correction of human-eye aberrations in a subjective feedback loop.

    Science.gov (United States)

    Vdovin, G; Loktev, M; Simonov, A; Kijko, V; Volkov, S

    2005-04-01

    An adaptive optical system with a subjective feedback loop is used to improve the visual acuity and to determine the aberrations of the human eye. Corrections of as many as 12 low-order aberration modes were made, based on the perceived sharpness of the test object observed through the adaptive optical system. The acuity of vision was improved by adjustment of the weights of the orthogonal modes produced by a deformable mirror. Objective measurements of the correcting aspherical figures, obtained in independent subjective correction cycles for one person, demonstrated good repeatability. Participants in the study with strong ocular aberrations reported moderate to significant improvement of their visual acuity, estimated with the U.S. Air Force 1951 acuity chart.

  18. Self-correction in human embryos%胚胎自我修复

    Institute of Scientific and Technical Information of China (English)

    徐艳文

    2013-01-01

    Reanalysis of aneuploid embryos diagnosed by preimplantation genetic screening (PGS) using fluorescence in situ hybridization(FISH) showed that part or all cells in some human cleavage-stage embryos may undergo self-correction during preimplantation development. Putative embryo self-correction mechanisms include embryonic mosaicism, preferential segregation of chromosomal abnormalities to the trophectoderm and extrusion or duplication of aneuploid chromosomes resulting in uniparental disomy. However, embryo self-correction has not been proved in the study using a single nucleotide polymorphism (SNP)microarray-based 24 chromosome aneuploidy screening technology. Neither preferential segregation of aneuploidy to trophectoderm nor uniparental disomy was found. Further study to improve the accuracy of karyotyping on cleavage-stage embryos is definitely needed.

  19. Three-dimensional ray tracing for refractive correction of human eye ametropies

    Science.gov (United States)

    Jimenez-Hernandez, J. A.; Diaz-Gonzalez, G.; Trujillo-Romero, F.; Iturbe-Castillo, M. D.; Juarez-Salazar, R.; Santiago-Alvarado, A.

    2016-09-01

    Ametropies of the human eye, are refractive defects hampering the correct imaging on the retina. The most common ways to correct them is by means of spectacles, contact lenses, and modern methods as laser surgery. However, in any case it is very important to identify the ametropia grade for designing the optimum correction action. In the case of laser surgery, it is necessary to define a new shape of the cornea in order to obtain the wanted refractive correction. Therefore, a computational tool to calculate the focal length of the optical system of the eye versus variations on its geometrical parameters is required. Additionally, a clear and understandable visualization of the evaluation process is desirable. In this work, a model of the human eye based on geometrical optics principles is presented. Simulations of light rays coming from a punctual source at six meter from the cornea are shown. We perform a ray-tracing in three dimensions in order to visualize the focusing regions and estimate the power of the optical system. The common parameters of ametropies can be easily modified and analyzed in the simulation by an intuitive graphic user interface.

  20. Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting

    Directory of Open Access Journals (Sweden)

    Chia-Wei Chang

    2015-09-01

    Full Text Available Mutations of the Janus family kinase JAK3 gene cause severe combined immunodeficiency (SCID. JAK3 deficiency in humans is characterized by the absence of circulating T cells and natural killer (NK cells with normal numbers of poorly functioning B cells (T–B+NK–. Using SCID patient-specific induced pluripotent stem cells (iPSCs and a T cell in vitro differentiation system, we demonstrate a complete block in early T cell development of JAK3-deficient cells. Correction of the JAK3 mutation by CRISPR/Cas9-enhanced gene targeting restores normal T cell development, including the production of mature T cell populations with a broad T cell receptor (TCR repertoire. Whole-genome sequencing of corrected cells demonstrates no CRISPR/Cas9 off-target modifications. These studies describe an approach for the study of human lymphopoiesis and provide a foundation for gene correction therapy in humans with immunodeficiencies.

  1. Shape corrections to exchange-correlation potentials by gradient-regulated seamless connection of model potentials for inner and outer region

    Science.gov (United States)

    Grüning, M.; Gritsenko, O. V.; van Gisbergen, S. J. A.; Baerends, E. J.

    2001-01-01

    Shape corrections to the standard approximate Kohn-Sham exchange-correlation (xc) potentials are considered with the aim to improve the excitation energies (especially for higher excitations) calculated with time-dependent density functional perturbation theory. A scheme of gradient-regulated connection (GRAC) of inner to outer parts of a model potential is developed. Asymptotic corrections based either on the potential of Fermi and Amaldi or van Leeuwen and Baerends (LB) are seamlessly connected to the (shifted) xc potential of Becke and Perdew (BP) with the GRAC procedure, and are employed to calculate the vertical excitation energies of the prototype molecules N2, CO, CH2O, C2H4, C5NH5, C6H6, Li2, Na2, K2. The results are compared with those of the alternative interpolation scheme of Tozer and Handy as well as with the results of the potential obtained with the statistical averaging of (model) orbital potentials. Various asymptotically corrected potentials produce high quality excitation energies, which in quite a few cases approach the benchmark accuracy of 0.1 eV for the electronic spectra. Based on these results, the potential BP-GRAC-LB is proposed for molecular response calculations, which is a smooth potential and a genuine "local" density functional with an analytical representation.

  2. Rovibrational spectra of ammonia. I. Unprecedented accuracy of a potential energy surface used with nonadiabatic corrections

    Science.gov (United States)

    Huang, Xinchuan; Schwenke, David W.; Lee, Timothy J.

    2011-01-01

    In this work, we build upon our previous work on the theoretical spectroscopy of ammonia, NH3. Compared to our 2008 study, we include more physics in our rovibrational calculations and more experimental data in the refinement procedure, and these enable us to produce a potential energy surface (PES) of unprecedented accuracy. We call this the HSL-2 PES. The additional physics we include is a second-order correction for the breakdown of the Born-Oppenheimer approximation, and we find it to be critical for improved results. By including experimental data for higher rotational levels in the refinement procedure, we were able to greatly reduce our systematic errors for the rotational dependence of our predictions. These additions together lead to a significantly improved total angular momentum (J) dependence in our computed rovibrational energies. The root-mean-square error between our predictions using the HSL-2 PES and the reliable energy levels from the HITRAN database for J = 0-6 and J = 7/8 for 14NH3 is only 0.015 cm-1 and 0.020/0.023 cm-1, respectively. The root-mean-square errors for the characteristic inversion splittings are approximately 1/3 smaller than those for energy levels. The root-mean-square error for the 6002 J = 0-8 transition energies is 0.020 cm-1. Overall, for J = 0-8, the spectroscopic data computed with HSL-2 is roughly an order of magnitude more accurate relative to our previous best ammonia PES (denoted HSL-1). These impressive numbers are eclipsed only by the root-mean-square error between our predictions for purely rotational transition energies of 15NH3 and the highly accurate Cologne database (CDMS): 0.00034 cm-1 (10 MHz), in other words, 2 orders of magnitude smaller. In addition, we identify a deficiency in the 15NH3 energy levels determined from a model of the experimental data .

  3. The impact of highly correlated potential energy surfaces on the anharmonically corrected IR spectrum of acetonitrile

    Science.gov (United States)

    Lutz, Oliver M. D.; Rode, Bernd M.; Bonn, Günther K.; Huck, Christian W.

    2014-10-01

    This paper discusses the quality and feasibility of highly correlated ab initio techniques in a vibrational self-consistent field (VSCF) approach using acetonitrile as a model system. The topical renormalized coupled-cluster technique exploiting the similarity-transformed Hamiltonian's left eigenstates (i.e. CR-CC(2,3)) is investigated alongside the well-known Hartree-Fock (HF), Møller-Plesset second-order perturbation theory (MP2) and coupled cluster (CCSD(T)) methods. The inclusion of mode triple interactions is discussed and it is found that the use of an effective core potential (ECP) serves as a viable compromise during the highly demanding task of computing such contributions, thus enabling a grid-based evaluation of three mode interaction terms with coupled cluster techniques also for larger molecules. In this context, a previously proposed reduced coupling scheme [1] is investigated, confirming the applicability of this technique to a system exhibiting a rather complex electronic structure. A combination of Ahlrichs' triple-ζ valence polarized (TZVP) basis set with Dunning's set of core-valence correlation functions is found to deliver results in good agreement with experiment while being computationally very feasible. Since CH3CN exhibits four degenerate vibrational degrees of freedom, it serves as an ideal model system for critically assessing the qualities of the degenerate second-order perturbation theory corrected (DPT2) VSCF technique. Besides fundamental vibrations, a thorough investigation of overtone transitions and combination bands is conducted by means of comparing the results to both available and newly recorded experimental data.

  4. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    Energy Technology Data Exchange (ETDEWEB)

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

  5. Adaptive Optics Analysis of Visual Benefit with Higher-order Aberrations Correction of Human Eye - Poster Paper

    Science.gov (United States)

    Xue, Lixia; Dai, Yun; Rao, Xuejun; Wang, Cheng; Hu, Yiyun; Liu, Qian; Jiang, Wenhan

    2008-01-01

    Higher-order aberrations correction can improve visual performance of human eye to some extent. To evaluate how much visual benefit can be obtained with higher-order aberrations correction we developed an adaptive optics vision simulator (AOVS). Dynamic real time optimized modal compensation was used to implement various customized higher-order ocular aberrations correction strategies. The experimental results indicate that higher-order aberrations correction can improve visual performance of human eye comparing with only lower-order aberration correction but the improvement degree and higher-order aberration correction strategy are different from each individual. Some subjects can acquire great visual benefit when higher-order aberrations were corrected but some subjects acquire little visual benefit even though all higher-order aberrations were corrected. Therefore, relative to general lower-order aberrations correction strategy, customized higher-order aberrations correction strategy is needed to obtain optimal visual improvement for each individual. AOVS provides an effective tool for higher-order ocular aberrations optometry for customized ocular aberrations correction.

  6. Measurement of human potential in organizations

    Directory of Open Access Journals (Sweden)

    Rosa María Fuchs Ángeles

    2015-09-01

    Full Text Available Companies around the world are concerned about talent management in their organizations. The concern is to retain talented employees and this may not be possible if they are not properly identified. Performance and potential evaluations become then important. Performance evaluations qualify the historical record of the employee, so their measurement is provided. However, measuring the potential performance assesses potential future charges, therefore it is not a simple task. In this paper, characteristics evaluated in potential employees and tools that are commonly used are presented. Also, the case of four companies operating in Peru is shown.

  7. In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases.

    Science.gov (United States)

    Sebastiano, Vittorio; Maeder, Morgan L; Angstman, James F; Haddad, Bahareh; Khayter, Cyd; Yeo, Dana T; Goodwin, Mathew J; Hawkins, John S; Ramirez, Cherie L; Batista, Luis F Z; Artandi, Steven E; Wernig, Marius; Joung, J Keith

    2011-11-01

    The combination of induced pluripotent stem cell (iPSC) technology and targeted gene modification by homologous recombination (HR) represents a promising new approach to generate genetically corrected, patient-derived cells that could be used for autologous transplantation therapies. This strategy has several potential advantages over conventional gene therapy including eliminating the need for immunosuppression, avoiding the risk of insertional mutagenesis by therapeutic vectors, and maintaining expression of the corrected gene by endogenous control elements rather than a constitutive promoter. However, gene targeting in human pluripotent cells has remained challenging and inefficient. Recently, engineered zinc finger nucleases (ZFNs) have been shown to substantially increase HR frequencies in human iPSCs, raising the prospect of using this technology to correct disease causing mutations. Here, we describe the generation of iPSC lines from sickle cell anemia patients and in situ correction of the disease causing mutation using three ZFN pairs made by the publicly available oligomerized pool engineering method (OPEN). Gene-corrected cells retained full pluripotency and a normal karyotype following removal of reprogramming factor and drug-resistance genes. By testing various conditions, we also demonstrated that HR events in human iPSCs can occur as far as 82 bps from a ZFN-induced break. Our approach delineates a roadmap for using ZFNs made by an open-source method to achieve efficient, transgene-free correction of monogenic disease mutations in patient-derived iPSCs. Our results provide an important proof of principle that ZFNs can be used to produce gene-corrected human iPSCs that could be used for therapeutic applications.

  8. Consolidated Quarterly Report: Number of potential release sites subject to corrective action

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John R.; Cochran, John R.

    2017-04-01

    This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit and the Compliance Order on Consent. The 12 sites in the corrective action process are listed in Table I-1.

  9. Time transients in the quantum corrected Newtonian potential induced by a massless nonminimally coupled scalar field

    NARCIS (Netherlands)

    Marunovic, A.; Prokopec, T.

    2011-01-01

    We calculate the one-loop graviton vacuum polarization induced by a massless, nonminimally coupled scalar field on Minkowski background. We make use of the Schwinger-Keldysh formalism, which allows us to study time dependent phenomena. As an application we compute the leading quantum correction to

  10. NaCl Potentiates Human Fibrocyte Differentiation

    OpenAIRE

    Nehemiah Cox; Darrell Pilling; Gomer, Richard H.

    2012-01-01

    Excessive NaCl intake is associated with a variety of fibrosing diseases such as renal and cardiac fibrosis. This association has been attributed to increased blood pressure as the result of high NaCl intake. However, studies in patients with high NaCl intake and fibrosis reveal a connection between NaCl intake and fibrosis that is independent of blood pressure. We find that increasing the extracellular concentration of NaCl to levels that may occur in human blood after high-salt intake can p...

  11. Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures.

    Science.gov (United States)

    Amano, Tomokazu; Jeffries, Emiko; Amano, Misa; Ko, Akihiro C; Yu, Hong; Ko, Minoru S H

    2015-10-01

    Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndrome—the most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar results were obtained for cells with the trisomy 18 of Edwards syndrome. Thus a direct, efficient correction of aneuploidy in human fibroblast cells seems possible in vitro using human ZSCAN4.

  12. Static properties of the nucleon octet in a relativistic potential model with center-of-mass correction

    Energy Technology Data Exchange (ETDEWEB)

    Barik, N.; Dash, B.K.; Das, M.

    1985-04-01

    The static properties, such as magnetic moment, charge radius, and axial-vector coupling constants, of the quark core of baryons in the nucleon octet have been studied in an independent-quark model based on the Dirac equation with equally mixed scalar-vector potential in harmonic form in the current quark mass limit. The results obtained with the corrections due to center-of-mass motion are in reasonable agreement with experimental values.

  13. Towards next-to-leading order corrections to the heavy quark potential in the effective string theory

    Science.gov (United States)

    Hwang, Sungmin

    2017-03-01

    We present our calculation of the non-relativistic corrections to the heavy quark-antiquark potential up to leading and next-to-leading order (NLO) via the effective string theory (EST). Full systematics of effective field theory (EFT) are discussed in order for including the NLO contribution that arises in the EST. We also show how the number of dimensionful parameters arising from the EST are reduced by the constraints between the Wilson coeffcients from non-relativistic EFTs for QCD.

  14. Quark number density and susceptibility calculation under one-loop correction in the mean-field potential

    Indian Academy of Sciences (India)

    S SOMORENDRO SINGH; G SAXENA

    2017-06-01

    We calculate quark number density and susceptibility under one-loop correction in the mean-field potential. The calculation shows continuous increase in the number density and susceptibility up to the temperature $T = 0.4 \\rm{GeV}$. Then the values of number density and susceptibility approach the very weakly result with higher values of temperature. The result indicates that the calculated values fit well with increase in temperature to match the lattice QCD simulations of the same quantities.

  15. Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

    Science.gov (United States)

    Bershteyn, Marina; Hayashi, Yohei; Desachy, Guillaume; Hsiao, Edward C.; Sami, Salma; Tsang, Kathryn M.; Weiss, Lauren A.; Kriegstein, Arnold R.; Yamanaka, Shinya; Wynshaw-Boris, Anthony

    2014-03-01

    Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of `chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.

  16. Efficient genomic correction methods in human iPS cells using CRISPR-Cas9 system.

    Science.gov (United States)

    Li, Hongmei Lisa; Gee, Peter; Ishida, Kentaro; Hotta, Akitsu

    2016-05-15

    Precise gene correction using the CRISPR-Cas9 system in human iPS cells holds great promise for various applications, such as the study of gene functions, disease modeling, and gene therapy. In this review article, we summarize methods for effective editing of genomic sequences of iPS cells based on our experiences correcting dystrophin gene mutations with the CRISPR-Cas9 system. Designing specific sgRNAs as well as having efficient transfection methods and proper detection assays to assess genomic cleavage activities are critical for successful genome editing in iPS cells. In addition, because iPS cells are fragile by nature when dissociated into single cells, a step-by-step confirmation during the cell recovery process is recommended to obtain an adequate number of genome-edited iPS cell clones. We hope that the techniques described here will be useful for researchers from diverse backgrounds who would like to perform genome editing in iPS cells.

  17. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH

    Science.gov (United States)

    Gordon Research Conference: Mammalian Gametogenesis and Embryogenesis New London, CT, July 1-6, 2000Molecular Analysis of Human Spermatozoa: Potential for Infertility ResearchDavid Miller 1, David Dix2, Robert Reid 3, Stephen A Krawetz 3 1Reproductive ...

  18. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH

    Science.gov (United States)

    Gordon Research Conference: Mammalian Gametogenesis and Embryogenesis New London, CT, July 1-6, 2000Molecular Analysis of Human Spermatozoa: Potential for Infertility ResearchDavid Miller 1, David Dix2, Robert Reid 3, Stephen A Krawetz 3 1Reproductive ...

  19. Structure-based sampling and self-correcting machine learning for accurate calculations of potential energy surfaces and vibrational levels

    Science.gov (United States)

    Dral, Pavlo O.; Owens, Alec; Yurchenko, Sergei N.; Thiel, Walter

    2017-06-01

    We present an efficient approach for generating highly accurate molecular potential energy surfaces (PESs) using self-correcting, kernel ridge regression (KRR) based machine learning (ML). We introduce structure-based sampling to automatically assign nuclear configurations from a pre-defined grid to the training and prediction sets, respectively. Accurate high-level ab initio energies are required only for the points in the training set, while the energies for the remaining points are provided by the ML model with negligible computational cost. The proposed sampling procedure is shown to be superior to random sampling and also eliminates the need for training several ML models. Self-correcting machine learning has been implemented such that each additional layer corrects errors from the previous layer. The performance of our approach is demonstrated in a case study on a published high-level ab initio PES of methyl chloride with 44 819 points. The ML model is trained on sets of different sizes and then used to predict the energies for tens of thousands of nuclear configurations within seconds. The resulting datasets are utilized in variational calculations of the vibrational energy levels of CH3Cl. By using both structure-based sampling and self-correction, the size of the training set can be kept small (e.g., 10% of the points) without any significant loss of accuracy. In ab initio rovibrational spectroscopy, it is thus possible to reduce the number of computationally costly electronic structure calculations through structure-based sampling and self-correcting KRR-based machine learning by up to 90%.

  20. Promoting safety improvements via potential human error audits

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, G.C. (International Mining Consultants (United Kingdom). Ergonomics and Safety Management)

    1994-08-01

    It has become increasingly recognised that human error plays a major role in mining accident causation. Moreover, it also recognised that this aspect of accident causation has had relatively little systematic attention in the past. Recent studies within British Coal have succeeded in developing a Potential Human Error Audit as a means of targeting accident prevention initiatives. 7 refs., 2 tabs.

  1. Coding potential of the products of alternative splicing in human.

    KAUST Repository

    Leoni, Guido

    2011-01-20

    BACKGROUND: Analysis of the human genome has revealed that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized genes. A number of these transcripts are alternatively spliced forms of known protein coding genes; however, it is becoming clear that many of them do not necessarily correspond to a functional protein. RESULTS: In this study we analyze alternative splicing isoforms of human gene products that are unambiguously identified by mass spectrometry and compare their properties with those of isoforms of the same genes for which no peptide was found in publicly available mass spectrometry datasets. We analyze them in detail for the presence of uninterrupted functional domains, active sites as well as the plausibility of their predicted structure. We report how well each of these strategies and their combination can correctly identify translated isoforms and derive a lower limit for their specificity, that is, their ability to correctly identify non-translated products. CONCLUSIONS: The most effective strategy for correctly identifying translated products relies on the conservation of active sites, but it can only be applied to a small fraction of isoforms, while a reasonably high coverage, sensitivity and specificity can be achieved by analyzing the presence of non-truncated functional domains. Combining the latter with an assessment of the plausibility of the modeled structure of the isoform increases both coverage and specificity with a moderate cost in terms of sensitivity.

  2. Attitudes of young adults to prenatal screening and genetic correction for human attributes and psychiatric conditions.

    Science.gov (United States)

    Milner, K K; Collins, E E; Connors, G R; Petty, E M

    1998-03-05

    With recent advances in DNA technology, questions have arisen as to how this technology should be appropriately used. In this article, results obtained from a survey designed to elicit attitudes of college students to prenatal testing and gene therapy for human attributes and psychiatric conditions are reported. The eleven hypothetical disease phenotypes included schizophrenia, alcoholism, tendency toward violent behavior, attention deficit/hyperactivity disorder, depression requiring medical treatment, obesity, involvement in "dangerous" sports activities, homosexuality, borderline normal IQ (80-100), proportional short stature, and inability to detect perfect pitch. Most students supported prenatal genetic testing for psychiatric disorders and behavior that might result in harm to others (i.e., tendency towards violent behavior) and found prenatal genetic testing for human attributes less desirable. However, the lack of unilateral agreement or disagreement toward any one condition or attribute suggests the potential difficulties ahead in the quest for guidelines for the application of new technologies available to manipulate the human genome.

  3. Quarkonium fine-hyperfine splittings and the Lorentz structure of the confining potential with vacuum-polarization corrections

    Energy Technology Data Exchange (ETDEWEB)

    Barik, N.; Jena, S.N.

    1980-06-01

    Within the framework of the Poggio-Schnitzer flavor-independent static-potential model with long-distance vacuum-polarization correction, we analyze the Lorentz-Dirac structure of the confinement potential with reference to the charmonium hyperfine splittings. In view of the questionable existence and/or doubtful identity of the X(2830) and chi(3455) states, we give preference to the Lorentz-Dirac character of the confinement potential in the form of an approximately equal admixture of scalar and vector components with no anomalous moment. This in turn predicts the /sup 1/S/sub 0/ partners of psi and psi' to be near the 3.0- and 3.6-GeV mass regions, respectively. This also suggests the /sup 1/P/sub 1/ state of charmonium is to be found above the /sup 3/P/sub 0/ state near the mass region of 3.48 GeV.

  4. Unified approach to the study of light and heavy mesons in the frameworkof the vacuum-polarization-corrected potential model

    Energy Technology Data Exchange (ETDEWEB)

    Barik, N.; Jena, S.N.

    1981-08-01

    Phenomenological evidence from meson spectroscopy is presented to support the view that a unified description of bound light- and heavy-quark systems is possible within the scope of a nonrelativistic-potential-model approach. The vacuum-polarization-corrected potential with its confinement part in the form of an approximately equal admixture of vector and scalar components is found to be a suitable one for the purpose. The overall systematics of the predictions based on this potential model for the meson masses, fine-hyperfine splittings, leptonic decay widths, and the Regge slopes are observed to be consistent with the premise that the forces between quarks and antiquarks are independent of the quark flavors.

  5. Quantum corrections to the gravitational potentials of a point source due to conformal fields in de Sitter

    CERN Document Server

    Fröb, Markus B

    2016-01-01

    We derive the leading quantum corrections to the gravitational potentials in a de Sitter background, due to the vacuum polarization from loops of conformal fields. Our results are valid for arbitrary conformal theories, even strongly interacting ones, and are expressed using the coefficients $b$ and $b'$ appearing in the trace anomaly. Apart from the de Sitter generalization of the known flat-space results, we find two additional contributions: one which depends on the finite coefficients of terms quadratic in the curvature appearing in the renormalized effective action, and one which grows logarithmically with physical distance. While the first contribution corresponds to a rescaling of the effective mass, the second contribution leads to a faster fall-off of the Newton potential at large distances, and is potentially measurable.

  6. One-loop Quantum Electrodynamic Correction to the Gravitational Potentials on de Sitter

    CERN Document Server

    Wang, C L

    2015-01-01

    We compute the one loop photon contribution to the graviton self-energy on de Sitter background and use it to solve the linearized Einstein equation for a point mass. Our results show that a co-moving observer sees a logarithmic spatial running Newton's constant. Equivalently a static observer reports a secular suppression of the Newtonian potential.

  7. Phospholipids in Human Milk and Infant Formulas: Benefits and Needs for Correct Infant Nutrition.

    Science.gov (United States)

    Cilla, Antonio; Diego Quintaes, Késia; Barberá, Reyes; Alegría, Amparo

    2016-08-17

    The composition of human milk has served as a basis for the development of infant formulas, which are used when breastfeeding is not possible. Among the human milk nutrients, 50% of the total energetic value corresponds to fat, with a high level of fatty acids and 0.2-2.0% present in the form of phospholipids (PLs). The PL contents and fatty acid distribution in PL species have been investigated as bioactive elements for the production of infant formulas, since they offer potential benefits for the optimum growth and health of the newborn infant. The differences in the amount of PLs and in fatty acid distribution in PL species between human milk and infant formulas can imply biologically significant differences for newborn infants fed with infant formulas versus human milk-mainly due to the greater proportion of sphingomyelin with respect to phosphatidylcholine in infant formulas. The limited information referred to the characterization of fatty acid distribution in PL species in infant formulas or in ingredients used to enrich them merits further research in order to obtain products with benefits similar to those of human milk in terms of infant growth, visual acuity, and neurological development. The present review establishes the scientific basis for helping to adjust formulations to the requirements of infant nutrition.

  8. "Replicable effects of primes on human behavior": Correction to Payne et al. (2016).

    Science.gov (United States)

    2016-12-01

    Reports an error in "Replicable effects of primes on human behavior" by B. Keith Payne, Jazmin L. Brown-Iannuzzi and Chris Loersch (Journal of Experimental Psychology: General, 2016[Oct], Vol 145[10], 1269-1279). In the article, the graph in Figure 5 did not contain the asterisk mentioned in the figure caption, which was intended to indicate a statistically significant difference between bet and pass prime. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2016-46925-002.) The effect of primes (i.e., incidental cues) on human behavior has become controversial. Early studies reported counterintuitive findings, suggesting that primes can shape a wide range of human behaviors. Recently, several studies failed to replicate some earlier priming results, raising doubts about the reliability of those effects. We present a within-subjects procedure for priming behavior, in which participants decide whether to bet or pass on each trial of a gambling game. We report 6 replications (N = 988) showing that primes consistently affected gambling decisions when the decision was uncertain. Decisions were influenced by primes presented visibly, with a warning to ignore the primes (Experiments 1 through 3) and with subliminally presented masked primes (Experiment 4). Using a process dissociation procedure, we found evidence that primes influenced responses through both automatic and controlled processes (Experiments 5 and 6). Results provide evidence that primes can reliably affect behavior, under at least some conditions, without intention. The findings suggest that the psychological question of whether behavior priming effects are real should be separated from methodological issues affecting how easily particular experimental designs will replicate. (PsycINFO Database Record

  9. Human Auditory Processing: Insights from Cortical Event-related Potentials

    Directory of Open Access Journals (Sweden)

    Alexandra P. Key

    2016-04-01

    Full Text Available Human communication and language skills rely heavily on the ability to detect and process auditory inputs. This paper reviews possible applications of the event-related potential (ERP technique to the study of cortical mechanisms supporting human auditory processing, including speech stimuli. Following a brief introduction to the ERP methodology, the remaining sections focus on demonstrating how ERPs can be used in humans to address research questions related to cortical organization, maturation and plasticity, as well as the effects of sensory deprivation, and multisensory interactions. The review is intended to serve as a primer for researchers interested in using ERPs for the study of the human auditory system.

  10. Towards next-to-leading order corrections to the heavy quark potential in the effective string theory

    Directory of Open Access Journals (Sweden)

    Hwang Sungmin

    2017-01-01

    Full Text Available We present our calculation of the non-relativistic corrections to the heavy quark-antiquark potential up to leading and next-to-leading order (NLO via the effective string theory (EST. Full systematics of effective field theory (EFT are discussed in order for including the NLO contribution that arises in the EST. We also show how the number of dimensionful parameters arising from the EST are reduced by the constraints between the Wilson coeffcients from non-relativistic EFTs for QCD.

  11. Slug signaling is up-regulated by CCL21/CCR7 [corrected] to induce EMT in human chondrosarcoma.

    Science.gov (United States)

    Li, Guosong; Yang, Yanjun; Xu, Siliang; Ma, Lifeng; He, Mingtang; Zhang, Ziqing

    2015-02-01

    In recent decades, the CXC chemokine receptor 7 (CCR7) [corrected] and its ligand CCL21 have been extensively reported to be associated with tumorigenesis. Meanwhile, Slug signaling induces the epithelial-mesenchymal transition (EMT) process in chondrosarcoma development. In the present study, we explored the functions of CCL21/CCR7 [corrected] in Slug-mediated EMT in the chondrosarcoma. We analyzed protein expression of CCR7 [corrected] and Slug in human chondrosarcoma samples. Effects of CCR7 [corrected] on chondrosarcoma cells were assessed by in vitro assays. Additionally, CCR7 [corrected] pathways were further investigated by pharmacological and genetic approaches. We found that the altered CCR7 [corrected] (81.7 %) and Slug (85.0 %) expression in human chondrosarcoma tissues were significantly associated with grade, recurrence, and 5-year overall survival. According to in vitro assays, CCL21 stimulation induced the expression of phosph-ERK, phosph-AKT, Slug and N-cadherin in SW1353 cells, while the expression of E-cadherin was down-regulated. Furthermore, Slug signaling modulated E- to N-cadherin switch, which was influenced by the kinase inhibitor PD98059 and LY294002. In addition, the genetic silencing of Slug inhibited the capacity of migration and invasion of SW1353 cells. In conclusion, CCL21/CCR7 [corrected] pathway activates ERK and PI3K/AKT signallings to up-regulate Slug pathway, leading to the occurrence of EMT process in human chondrosarcoma. This study lays a new foundation for molecule-targeted therapy of human chondrosarcoma.

  12. Surface-wave potential for triggering tectonic (nonvolcanic) tremor-corrected

    Science.gov (United States)

    Hill, David P.

    2012-01-01

    Source processes commonly posed to explain instances of remote dynamic triggering of tectonic (nonvolcanic) tremor by surface waves include frictional failure and various modes of fluid activation. The relative potential for Love- and Rayleigh-wave dynamic stresses to trigger tectonic tremor through failure on critically stressed thrust and vertical strike-slip faults under the Coulomb-Griffith failure criteria as a function of incidence angle are anticorrelated over the 15- to 30-km-depth range that hosts tectonic tremor. Love-wave potential is high for strike-parallel incidence on low-angle reverse faults and null for strike-normal incidence; the opposite holds for Rayleigh waves. Love-wave potential is high for both strike-parallel and strike-normal incidence on vertical, strike-slip faults and minimal for ~45° incidence angles. The opposite holds for Rayleigh waves. This pattern is consistent with documented instances of tremor triggered by Love waves incident on the Cascadia megathrust and the San Andreas fault (SAF) in central California resulting from shear failure on weak faults (apparent friction is μ* ≤ 0:2). Documented instances of tremor triggered by surface waves with strike-parallel incidence along the Nankai megathrust beneath Shikoku, Japan, however, are associated primarily with Rayleigh waves. This is consistent with the tremor bursts resulting from mixed-mode failure (crack opening and shear failure) facilitated by near-lithostatic ambient pore pressure, low differential stress, with a moderate friction coefficient (μ ~ 0:6) on the Nankai subduction interface. Rayleigh-wave dilatational stress is relatively weak at tectonic tremor source depths and seems unlikely to contribute significantly to the triggering process, except perhaps for an indirect role on the SAF in sustaining tremor into the Rayleigh-wave coda that was initially triggered by Love waves.

  13. Corrected Analytical Solution of the Generalized Woods-Saxon Potential for Arbitrary $\\ell$ States

    CERN Document Server

    Bayrak, O

    2015-01-01

    The bound state solution of the radial Schr\\"{o}dinger equation with the generalized Woods-Saxon potential is carefully examined by using the Pekeris approximation for arbitrary $\\ell$ states. The energy eigenvalues and the corresponding eigenfunctions are analytically obtained for different $n$ and $\\ell$ quantum numbers. The obtained closed forms are applied to calculate the single particle energy levels of neutron orbiting around $^{56}$Fe nucleus in order to check consistency between the analytical and Gamow code results. The analytical results are in good agreement with the results obtained by Gamow code for $\\ell=0$.

  14. Increased glycation of hemoglobin in chronic renal failure: [corrected] potential role of oxidative stress.

    Science.gov (United States)

    Selvaraj, Nambiar; Bobby, Zachariah; Sridhar, Magadi Gopalakrishna

    2008-04-01

    Among the various mechanisms proposed, the process of non-enzymatic glycation of proteins is believed to play an important role in the pathogenesis of chronic complications associated with renal failure. The two traditional factors found to modulate the early glycation of proteins are the prevailing concentration of glucose and half life of the protein. Among the various proteins that are known to undergo nonenzymatic glycation in vivo, hemoglobin has been the most thoroughly investigated. Determination of glycated hemoglobin in diabetic patients is currently acknowledged as the most reliable indicator for assessment of retrospective glycemic control and the planning of clinical management. The clinical utility of glycated hemoglobin measurements, however, in renal failure is controversial, given the numerous earlier studies showing no correlation between glycated hemoglobin and other indicators of blood glucose control in uremic subjects. With few exceptions, previous studies have suggested that the concentration of glycated hemoglobin was increased in uremic patients. There is documented evidence that increased glycated hemoglobin levels are found in certain non-diabetic states. So it stands to reason that hyperglycemia, although clearly being the culprit in diabetes, does not provide the complete answer to the etiology of increased early glycated products in non-diabetic conditions including chronic renal failure. This article reviews available evidence supporting increased glycation of hemoglobin in patients with chronic renal failure. Potential mechanisms for this increase are examined with special emphasis on the potential role of oxidative stress.

  15. QED radiative corrections and many-body effects in atoms: the Uehling potential and shifts in alkali metals

    CERN Document Server

    Ginges, J S M

    2015-01-01

    We consider the largest (Uehling) contribution to the one-loop vacuum polarization correction to the binding energies in neutral alkali atoms, from Na through to the superheavy element E119. We use the relativistic Hartree-Fock method to demonstrate the importance of core relaxation effects. These effects are sizeable everywhere, though particularly important for orbitals with angular momentum quantum number l > 0. For d waves, the Uehling shift is enhanced by many orders of magnitude: for Cs the enhancement is more than four orders of magnitude and for the lighter alkali atoms it is even larger. We also study the effects of second- and higher-order many-body perturbation theory on the valence level shifts through inclusion of the correlation potential. The many-body enhancement mechanisms that operate in the case of the Uehling potential apply also to the case of the larger QED self-energy radiative corrections. The huge enhancement for d level shifts makes high-precision studies of transition frequencies in...

  16. Error-Correcting Output Codes in Classification of Human Induced Pluripotent Stem Cell Colony Images

    Directory of Open Access Journals (Sweden)

    Henry Joutsijoki

    2016-01-01

    Full Text Available The purpose of this paper is to examine how well the human induced pluripotent stem cell (hiPSC colony images can be classified using error-correcting output codes (ECOC. Our image dataset includes hiPSC colony images from three classes (bad, semigood, and good which makes our classification task a multiclass problem. ECOC is a general framework to model multiclass classification problems. We focus on four different coding designs of ECOC and apply to each one of them k-Nearest Neighbor (k-NN searching, naïve Bayes, classification tree, and discriminant analysis variants classifiers. We use Scaled Invariant Feature Transformation (SIFT based features in classification. The best accuracy (62.4% is obtained with ternary complete ECOC coding design and k-NN classifier (standardized Euclidean distance measure and inverse weighting. The best result is comparable with our earlier research. The quality identification of hiPSC colony images is an essential problem to be solved before hiPSCs can be used in practice in large-scale. ECOC methods examined are promising techniques for solving this challenging problem.

  17. Error-Correcting Output Codes in Classification of Human Induced Pluripotent Stem Cell Colony Images.

    Science.gov (United States)

    Joutsijoki, Henry; Haponen, Markus; Rasku, Jyrki; Aalto-Setälä, Katriina; Juhola, Martti

    2016-01-01

    The purpose of this paper is to examine how well the human induced pluripotent stem cell (hiPSC) colony images can be classified using error-correcting output codes (ECOC). Our image dataset includes hiPSC colony images from three classes (bad, semigood, and good) which makes our classification task a multiclass problem. ECOC is a general framework to model multiclass classification problems. We focus on four different coding designs of ECOC and apply to each one of them k-Nearest Neighbor (k-NN) searching, naïve Bayes, classification tree, and discriminant analysis variants classifiers. We use Scaled Invariant Feature Transformation (SIFT) based features in classification. The best accuracy (62.4%) is obtained with ternary complete ECOC coding design and k-NN classifier (standardized Euclidean distance measure and inverse weighting). The best result is comparable with our earlier research. The quality identification of hiPSC colony images is an essential problem to be solved before hiPSCs can be used in practice in large-scale. ECOC methods examined are promising techniques for solving this challenging problem.

  18. Potential applications and human biosafety of nanomaterials used in nanomedicine.

    Science.gov (United States)

    Su, Hong; Wang, Yafei; Gu, Yuanliang; Bowman, Linda; Zhao, Jinshun; Ding, Min

    2017-06-06

    With the rapid development of nanotechnology, potential applications of nanomaterials in medicine have been widely researched in recent years. Nanomaterials themselves can be used as image agents or therapeutic drugs, and for drug and gene delivery, biological devices, nanoelectronic biosensors or molecular nanotechnology. As the composition, morphology, chemical properties, implant sites as well as potential applications become more and more complex, human biosafety of nanomaterials for clinical use has become a major concern. If nanoparticles accumulate in the human body or interact with the body molecules or chemical components, health risks may also occur. Accordingly, the unique chemical and physical properties, potential applications in medical fields, as well as human biosafety in clinical trials are reviewed in this study. Finally, this article tries to give some suggestions for future work in nanomedicine research. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Influence and Correction from the Human Body on the Measurement of a Power-Frequency Electric Field Sensor.

    Science.gov (United States)

    Xiao, Dongping; Liu, Huaitong; Zhou, Qiang; Xie, Yutong; Ma, Qichao

    2016-06-10

    According to the operating specifications of existing electric field measuring instruments, measuring technicians must be located far from the instruments to eliminate the influence of the human body occupancy on a spatial electric field. Nevertheless, in order to develop a portable safety protection instrument with an effective electric field warning function for working staff in a high-voltage environment, it is necessary to study the influence of an approaching human body on the measurement of an electric field and to correct the measurement results. A single-shaft electric field measuring instrument called the Type LP-2000, which was developed by our research team, is used as the research object in this study. First, we explain the principle of electric field measurement and describe the capacitance effect produced by the human body. Through a theoretical analysis, we show that the measured electric field value decreases as a human body approaches. Their relationship is linearly proportional. Then, the ratio is identified as a correction coefficient to correct for the influence of human body proximity. The conclusion drawn from the theoretical analysis is proved via simulation. The correction coefficient kb = 1.8010 is obtained on the basis of the linear fitting of simulated data. Finally, a physical experiment is performed. When no human is present, we compare the results from the Type LP-2000 measured with Narda EFA-300 and the simulated value to verify the accuracy of the Type LP-2000. For the case of an approaching human body, the correction coefficient kb* = 1.9094 is obtained by comparing the data measured with the Type LP-2000 to the simulated value. The correction coefficient obtained from the experiment (i.e., kb*) is highly consistent with that obtained from the simulation (i.e., kb). Two experimental programs are set; under these programs, the excitation voltages and distance measuring points are regulated to produce different electric field

  20. Influence and Correction from the Human Body on the Measurement of a Power-Frequency Electric Field Sensor

    Science.gov (United States)

    Xiao, Dongping; Liu, Huaitong; Zhou, Qiang; Xie, Yutong; Ma, Qichao

    2016-01-01

    According to the operating specifications of existing electric field measuring instruments, measuring technicians must be located far from the instruments to eliminate the influence of the human body occupancy on a spatial electric field. Nevertheless, in order to develop a portable safety protection instrument with an effective electric field warning function for working staff in a high-voltage environment, it is necessary to study the influence of an approaching human body on the measurement of an electric field and to correct the measurement results. A single-shaft electric field measuring instrument called the Type LP-2000, which was developed by our research team, is used as the research object in this study. First, we explain the principle of electric field measurement and describe the capacitance effect produced by the human body. Through a theoretical analysis, we show that the measured electric field value decreases as a human body approaches. Their relationship is linearly proportional. Then, the ratio is identified as a correction coefficient to correct for the influence of human body proximity. The conclusion drawn from the theoretical analysis is proved via simulation. The correction coefficient kb = 1.8010 is obtained on the basis of the linear fitting of simulated data. Finally, a physical experiment is performed. When no human is present, we compare the results from the Type LP-2000 measured with Narda EFA-300 and the simulated value to verify the accuracy of the Type LP-2000. For the case of an approaching human body, the correction coefficient kb* = 1.9094 is obtained by comparing the data measured with the Type LP-2000 to the simulated value. The correction coefficient obtained from the experiment (i.e., kb*) is highly consistent with that obtained from the simulation (i.e., kb). Two experimental programs are set; under these programs, the excitation voltages and distance measuring points are regulated to produce different electric field

  1. Neuroanatomic localization of priming effects for famous faces with latency-corrected event-related potentials.

    Science.gov (United States)

    Kashyap, Rajan; Ouyang, Guang; Sommer, Werner; Zhou, Changsong

    2016-02-01

    The late components of event-related brain potentials (ERPs) pose a difficult problem in source localization. One of the reasons is the smearing of these components in conventional averaging because of trial-to-trial latency-variability. The smearing problem may be addressed by reconstructing the ERPs after latency synchronization with the Residue Iteration Decomposition (RIDE) method. Here we assessed whether the benefits of RIDE at the surface level also improve source localization of RIDE-reconstructed ERPs (RERPs) measured in a face priming paradigm. Separate source models for conventionally averaged ERPs and RERPs were derived and sources were localized for both early and late components. Jackknife averaging on the data was used to reduce the residual variance during source localization compared to conventional source model fitting on individual subject data. Distances between corresponding sources of both ERP and RERP models were measured to check consistency in both source models. Sources for activity around P100, N170, early repetition effect (ERE/N250r) and late repetition effect (LRE/N400) were reported and priming effects in these sources were evaluated for six time windows. Significant improvement in priming effect of the late sources was found from the RERP source model, especially in the Medio-Temporal Lobe, Prefrontal Cortex, and Anterior Temporal Lobe. Consistent with previous studies, we found early priming effects in the right hemisphere and late priming effects in the left hemisphere. Also, the priming effects in right hemisphere outnumbered the left hemisphere, signifying dominance of right hemisphere in face recognition. In conclusion, RIDE reconstructed ERPs promise a comprehensive understanding of the time-resolved dynamics the late sources play during face recognition. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Stephanie C Stotz

    Full Text Available Transient receptor potential (TRP ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1, and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate, consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

  3. Clinical evaluation of the computed tomography attenuation correction map for myocardial perfusion imaging: the potential for incidental pathology detection.

    Science.gov (United States)

    Tootell, Andrew; Vinjamuri, Sobhan; Elias, Mark; Hogg, Peter

    2012-11-01

    The benefits of hybrid imaging in nuclear medicine have been proven to increase the diagnostic accuracy and sensitivity of many procedures by localizing or characterizing lesions or by correcting emission data to more accurately represent radiopharmaceutical distribution. Single-photon emission computed tomography/computed tomography (SPECT/CT) has a significant role in the diagnosis and follow-up of ischaemic heart disease with attenuation correction data being obtained on an integrated CT scanner. Initially, the CT component of hybrid SPECT/CT systems was what could be described as low specification utilizing fixed output parameters. As technology has progressed, the CT component of newer systems has specifications that are identical to that of stand-alone diagnostic systems. Irrespective of the type of scanner used, the computed tomography attenuation correction (CTAC) for myocardial perfusion imaging produces low-quality, limited-range CT images of the chest that include the mediastinum, lung fields and surrounding soft tissues. The diagnostic potential of this data set is unclear; yet, examples exist whereby significant pathology can be identified and investigated further. Despite guidance from a number of professional bodies suggesting that evaluation of the resulting images for every medical exposure be carried out, there is no indication as to whether this should include the evaluation of CTAC images. This review aims to initiate discussion by examining the ethical, legal, financial and practical issues (e.g. CT specification and image quality) surrounding the clinical evaluation of the CTAC for myocardial perfusion imaging images. Reference to discussions that have taken place, and continue to take place, in other modalities, current European and UK legislations, and guidelines and research in the field will be made.

  4. De-racialising intelligence, human potentiality and consciousness: A ...

    African Journals Online (AJOL)

    Sophia: An African Journal of Philosophy ... And the most fundamental biological differencing mechanism links to a purported racial ... a causal relationship between race and human potentiality, by which a black man can neither be as ... capacities inherent in the productions of Africans and people of generally black origin.

  5. Does recombinant human erythropoietin accelerate correction of post-ulcer-bleeding anaemia? A pilot study

    Institute of Scientific and Technical Information of China (English)

    Spiros D. Ladas; Dimitrios Polymeros; Thomas Pagonis; Konstantinos Triantafyllou; Gregorios Paspatis; Maria Hatziargiriou; Sotirios A.Raptis

    2004-01-01

    AIM: Anaemia caused by acute upper gastrointestinal bleeding is treated with blood transfusion or iron, but patients usually face a two-month recovery period from posthaemorrhage anaemia. This prospective, randomised, open,pilot study was designed to investigate whether recombinant human erythropoietin (Epoetin) therapy accelerate haematocrit increase in the post-bleeding recovery period.METHODS: We studied hospitalised patients admitted because of acute ulcer bleeding or haemorrhagic gastritis,who had a haematocrit of 27-33% and did not receive blood transfusions. One day after the endoscopic confirmation of cessation of bleeding, they were randomised either to erythropoietin (20 000 IU Epoetin alfa subcutaneously, on days 0, 4 and 6) plus iron (100 mg im, on days 1- 6, (G1) or iron only (G2). Haematocrit was measured on days 0, 6, 14,30, 45, and 60, respectively.RESULTS: One patient from G1 and two from G2 were lost to follow-up. Therefore, 14 and 13 patients from G1 and G2respectively were analysed. Demographic characteristics, serum iron, ferritin, total iron binding capacity, reticulocytes, and haematocrit were not significantly different at entry to the study.Median reticulocyte counts were significantly different between groups on day six (G1: 4.0, 3.0-6.4 vsG2: 3.5, 2.1-4.4%,P=0.03) and median haematocrit on day fourteen [G1: 35.9,30.7-41.0 vsG2: 32.5, 29.5-37.0% (median, range), P=0.04].CONCLUSION: Erythropoietin administration significantly accelerates correction of anemia after acute ulcer bleeding.The haematocrit gain is equivalent to one unit of transfused blood two weeks after the bleeding episode.

  6. Individual differences in the learning potential of human beings

    Science.gov (United States)

    Stern, Elsbeth

    2017-01-01

    To the best of our knowledge, the genetic foundations that guide human brain development have not changed fundamentally during the past 50,000 years. However, because of their cognitive potential, humans have changed the world tremendously in the past centuries. They have invented technical devices, institutions that regulate cooperation and competition, and symbol systems, such as script and mathematics, that serve as reasoning tools. The exceptional learning ability of humans allows newborns to adapt to the world they are born into; however, there are tremendous individual differences in learning ability among humans that become obvious in school at the latest. Cognitive psychology has developed models of memory and information processing that attempt to explain how humans learn (general perspective), while the variation among individuals (differential perspective) has been the focus of psychometric intelligence research. Although both lines of research have been proceeding independently, they increasingly converge, as both investigate the concepts of working memory and knowledge construction. This review begins with presenting state-of-the-art research on human information processing and its potential in academic learning. Then, a brief overview of the history of psychometric intelligence research is combined with presenting recent work on the role of intelligence in modern societies and on the nature-nurture debate. Finally, promising approaches to integrating the general and differential perspective will be discussed in the conclusion of this review.

  7. Density functional study of photoabsorption in metallic clusters using an exchange-correlation potential with correct long-range behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Torres, M.B. [Dpto. de Matematicas y Computacion, Universidad de Burgos, Burgos (Spain); Balbas, L.C. [Dpto. de Fisica Teorica, Universidad de Valladolid, Valladolid (Spain)

    2002-06-17

    The atomic exchange-correlation (xc) potential with the correct -1/r asymptotic behaviour constructed by Parr and Ghosh (Parr R G and Ghosh S K 1995 Phys. Rev. A 51 3564) is adapted here to study, within time density functional theory, the linear response to external fields of (i) neutral and charged sodium clusters, and (ii) doped clusters of the type Na{sub n}Pb (n=4, 6, 16). The resulting photoabsorption cross sections are compared to experimental results, when available, and to results from previous calculations using local and non-local xc functionals. The calculated static polarizabilities and plasmon frequencies are closer to the experimental values than previous results. (author)

  8. Understanding Complex Spectral Signatures of Embedded Excess Protons in Molecular Scaffolds with Third Order Corrections to the Harmonic Potential Surface

    Science.gov (United States)

    Deblase, Andrew F.; Johnson, Mark A.; Lectka, Thomas; Wang, Xun; Jordan, Kenneth D.; McCoy, Anne B.

    2013-06-01

    Overtones and combination bands observed in vibrational predissociation spectra of cold ions can often be anticipated by expanding the potential energy surface to third order. This is achieved by relating the third derivatives to the matrix elements that couple the allowed and forbidden states in the harmonic basis. Such a strategy has been successful in predicting Fermi resonances in formic acid clusters and some charged H-bonded complexes. Furthermore, third order couplings have been used to develop a vibrational adiabatic model in which excitation of a bright state is distributed over a Franck-Condon envelop of a lower energy mode, such as a water rocking against triatomic domains of molecular anions. Previous applications include the analysis of long vibrational progressions of soft modes in the OH stretching region of the actetate-water binary complex. Here we explore to extent to which this order of correction captures the irregular patterns associated with intramolecular proton bonds.

  9. Synthetic Biology and Human Health: Potential Applications for Spaceflight

    Science.gov (United States)

    Karouia, Fathi; Carr, Christopher; Cai, Yizhi; Chen, Y.; Grenon, Marlene; Larios-Sanz, Maia; Jones, Jeffrey A.; Santos, Orlando

    2011-01-01

    Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. Spaceflight-related changes have been reported in the musculo-skeletal, cardiovascular, neurovestibular, endocrine, and immune systems. The spacecraft environment further subjects the traveler to noise and gravitational forces, as well as airborne chemical, microbiological contaminants, and radiation exposure. As humans prepare for longer duration missions effective countermeasures must be developed, verified, and implemented to ensure mission success. Over the past ten years, synthetic biology has opened new avenues for research and development in areas such as biological control, biomaterials, sustainable energy production, bioremediation, and biomedical therapies. The latter in particular is of great interest to the implementation of long-duration human spaceflight capabilities. This article discusses the effects of spaceflight on humans, and reviews current capabilities and potential needs associated with the health of the astronauts where synthetic biology could play an important role in the pursuit of space exploration.

  10. Potentiators exert distinct effects on human, murine, and Xenopus CFTR.

    Science.gov (United States)

    Cui, Guiying; Khazanov, Netaly; Stauffer, Brandon B; Infield, Daniel T; Imhoff, Barry R; Senderowitz, Hanoch; McCarty, Nael A

    2016-08-01

    VX-770 (Ivacaftor) has been approved for clinical usage in cystic fibrosis patients with several CFTR mutations. Yet the binding site(s) on CFTR for this compound and other small molecule potentiators are unknown. We hypothesize that insight into this question could be gained by comparing the effect of potentiators on CFTR channels from different origins, e.g., human, mouse, and Xenopus (frog). In the present study, we combined this comparative molecular pharmacology approach with that of computer-aided drug discovery to identify and characterize new potentiators of CFTR and to explore possible mechanism of action. Our results demonstrate that 1) VX-770, NPPB, GlyH-101, P1, P2, and P3 all exhibited ortholog-specific behavior in that they potentiated hCFTR, mCFTR, and xCFTR with different efficacies; 2) P1, P2, and P3 potentiated hCFTR in excised macropatches in a manner dependent on the degree of PKA-mediated stimulation; 3) P1 and P2 did not have additive effects, suggesting that these compounds might share binding sites. Also 4) using a pharmacophore modeling approach, we identified three new potentiators (IOWH-032, OSSK-2, and OSSK-3) that have structures similar to GlyH-101 and that also exhibit ortholog-specific potentiation of CFTR. These could potentially serve as lead compounds for development of new drugs for the treatment of cystic fibrosis. The ortholog-specific behavior of these compounds suggest that a comparative pharmacology approach, using cross-ortholog chimeras, may be useful for identification of binding sites on human CFTR.

  11. Diagnostic accuracy of motor evoked potentials to detect neurological deficit during idiopathic scoliosis correction: a systematic review.

    Science.gov (United States)

    Thirumala, Parthasarathy D; Crammond, Donald J; Loke, Yoon K; Cheng, Hannah L; Huang, Jessie; Balzer, Jeffrey R

    2017-03-01

    OBJECTIVE The goal of this study was to evaluate the efficacy of intraoperative transcranial motor evoked potential (TcMEP) monitoring in predicting an impending neurological deficit during corrective spinal surgery for patients with idiopathic scoliosis (IS). METHODS The authors searched the PubMed and Web of Science database for relevant lists of retrieved reports and/or experiments published from January 1950 through October 2014 for studies on TcMEP monitoring use during IS surgery. The primary analysis of this review fit the operating characteristic into a hierarchical summary receiver operating characteristic curve model to determine the efficacy of intraoperative TcMEP-predicted change. RESULTS Twelve studies, with a total of 2102 patients with IS were included. Analysis found an observed incidence of neurological deficits of 1.38% (29/2102) in the sample population. Of the patients who sustained a neurological deficit, 82.8% (24/29) also had irreversible TcMEP change, whereas 17.2% (5/29) did not. The pooled analysis using the bivariate model showed TcMEP change with sensitivity (mean 91% [95% CI 34%-100%]) and specificity (mean 96% [95% CI 92-98%]). The diagnostic odds ratio indicated that it is 250 times more likely to observe significant TcMEP changes in patients who experience a new-onset motor deficit immediately after IS correction surgery (95% CI 11-5767). TcMEP monitoring showed high discriminant ability with an area under the curve of 0.98. CONCLUSIONS A patient with a new neurological deficit resulting from IS surgery was 250 times more likely to have changes in TcMEPs than a patient without new deficit. The authors' findings from 2102 operations in patients with IS show that TcMEP monitoring is a highly sensitive and specific test for detecting new spinal cord injuries in patients undergoing corrective spinal surgery for IS. They could not assess the value of TcMEP monitoring as a therapeutic adjunct owing to the limited data available and their

  12. "It's doom alone that counts": can international human rights law be an effective source of rights in correctional conditions litigation?

    Science.gov (United States)

    Perlin, Michael L; Dlugacz, Henry A

    2009-01-01

    Over the past three decades, the U.S. judiciary has grown increasingly less receptive to claims by convicted felons as to the conditions of their confinement while in prison. Although courts have not articulated a return to the "hands off" policy of the 1950s, it is clear that it has become significantly more difficult for prisoners to prevail in constitutional correctional litigation. The passage and aggressive implementation of the Prison Litigation Reform Act has been a powerful disincentive to such litigation in many areas of prisoners' rights law. From the perspective of the prisoner, the legal landscape is more hopeful in matters that relate to mental health care and treatment. Here, in spite of a general trend toward more stringent applications of standards of proof and a reluctance to order sweeping, intrusive remedies, some courts have aggressively protected prisoners' rights to be free from "deliberate indifference" to serious medical needs, and to be free from excessive force on the part of prison officials. A mostly hidden undercurrent in some prisoners' rights litigation has been the effort on the part of some plaintiffs' lawyers to look to international human rights doctrines as a potential source of rights, an effort that has met with some modest success. It receives support by the inclination of other courts to turn to international human rights conventions-even in nations where such conventions have not been ratified-as a kind of "best practice" in the area. The recent publication and subsequent ratification (though not, as of yet, by the United States) of the UN Convention on the Rights of Persons with Disabilities (CRPD) may add new support to those using international human rights documents as a basis for litigating prisoners' rights claims. To the best of our knowledge, there has, as of yet, been no scholarly literature on the question of the implications of the CRPD on the state of prisoners' rights law in a U.S. domestic context. In this

  13. Brown adipose tissue in humans: therapeutic potential to combat obesity.

    Science.gov (United States)

    Carey, Andrew L; Kingwell, Bronwyn A

    2013-10-01

    Harnessing the considerable capacity of brown adipose tissue (BAT) to consume energy was first proposed as a potential target to control obesity nearly 40years ago. The plausibility of this approach was, however, questioned due to the prevailing view that BAT was either not present or not functional in adult humans. Recent definitive identification of functional BAT in adult humans as well as a number of important advances in the understanding of BAT biology has reignited interest in BAT as an anti-obesity target. Proof-of-concept evidence demonstrating drug-induced BAT activation provides an important foundation for development of targeted pharmacological approaches with clinical application. This review considers evidence from both human and relevant animal studies to determine whether harnessing BAT for the treatment of obesity via pharmacological intervention is a realistic goal. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. CRISPR/Cas9-Mediated Correction of the Sickle Mutation in Human CD34+ cells.

    Science.gov (United States)

    Hoban, Megan D; Lumaquin, Dianne; Kuo, Caroline Y; Romero, Zulema; Long, Joseph; Ho, Michelle; Young, Courtney S; Mojadidi, Michelle; Fitz-Gibbon, Sorel; Cooper, Aaron R; Lill, Georgia R; Urbinati, Fabrizia; Campo-Fernandez, Beatriz; Bjurstrom, Carmen F; Pellegrini, Matteo; Hollis, Roger P; Kohn, Donald B

    2016-09-01

    Targeted genome editing technology can correct the sickle cell disease mutation of the β-globin gene in hematopoietic stem cells. This correction supports production of red blood cells that synthesize normal hemoglobin proteins. Here, we demonstrate that Transcription Activator-Like Effector Nucleases (TALENs) and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system can target DNA sequences around the sickle-cell mutation in the β-globin gene for site-specific cleavage and facilitate precise correction when a homologous donor template is codelivered. Several pairs of TALENs and multiple CRISPR guide RNAs were evaluated for both on-target and off-target cleavage rates. Delivery of the CRISPR/Cas9 components to CD34+ cells led to over 18% gene modification in vitro. Additionally, we demonstrate the correction of the sickle cell disease mutation in bone marrow derived CD34+ hematopoietic stem and progenitor cells from sickle cell disease patients, leading to the production of wild-type hemoglobin. These results demonstrate correction of the sickle mutation in patient-derived CD34+ cells using CRISPR/Cas9 technology.

  15. Human Resource – Potential Factor of Organiztional Crisis

    Directory of Open Access Journals (Sweden)

    Mihail Cristian Negrulescu

    2008-10-01

    Full Text Available At the level of any economic system, the change brings about the modification of the internal operating method of the relations between the actors and of the work habits. In other words, the substance (main, important modifications can be shaped on each of the organizational dominant of the system at a structural, functional or cultural level, in which the main actor, the human resource, intends to be part of this equation of changes. In this context, significant is the role played by the main organization actors, a role which can be materialized either as a factor of innovation, prevention and even progress, or as a conflict promoting factor, which, in time, generates a state of abnormality, of crisis. That is why major importance must be allotted to the human resources at the level of each organisation, considering the progress focused on knowledge, experience, experiments, attitude, behaviour and competences, these implying factors of correction and efficient reaction for the administration of the organizational crises.

  16. Development of the human potential in Russian and foreign countries

    Directory of Open Access Journals (Sweden)

    Mikhail Ivanovich Maslennikov

    2013-09-01

    Full Text Available In the article, theoretical and methodical approaches to human development in Russia and foreign countries are analyzed. The contribution of the various countries to its formation and development is revealed. The indicators showing a level of development of human potential and components forming it in the creation of gross domestic product are analyzed. The alternative options of development of education, health care and science, expenses and benefit from their commercialization are revealed. The role of the state, federal regions and local authorities in management and development of health care, education, science during periods of crises, depressions and increases of economic activity is investigated. The interrelation of levels of development of the economy and human potential, with the levels and the population living conditions are revealed. The reasons of close attention of the governments of the developed countries to human development, and also the measures undertaken on minimization of interregional disproportions in its development become clear. Mechanisms and tools of development of health care, education, science in various regions of the world, a way of use of transfers, subsidies and grants on their development are investigated

  17. ADVANCED DEVELOPMENT MODEL OF TERRITORIAL HUMAN RESOURCES POTENTIAL

    Directory of Open Access Journals (Sweden)

    Alexander G. Моkronosov

    2015-03-01

    Full Text Available The aim of the study is to substantiate the need for eliminating the excessive spatial polarization of territorial socio-economic development as a necessary condition for advanced development of human resources potential. The authors explore the basic problems and contradictions of modern regional and local labor markets in Russia. Based on generalization and systematization of foreign and domestic research outcomes, the paper reveals the main condition for eliminating the territorial polarization threats, which implies formation of a new institutional environment in order to provide co-operation of participants in the territorial interest zone in personnel training and new jobs creating.The research findings demonstrate the increased disproportions between the workforce and labor markets of municipal formations in Sverdlovsk region, and emphasize the need for territorial industrial educational clusters maximizing the network co-operation of the involved parties.The scientific novelty combines adaptation of theoretical concepts of the “new economic geography” applied to reorganization processes in the Russian economy; and elaboration of the cluster model of advanced development of territorial human resources potential by means of territorial centers coordinating the interests of administration, business society, and households.Practical significance of the research results is related to facilitating the administrative efficiency of regional and municipal formations, employers, territorial employment centers, and thereby the advanced development of human resources potential.

  18. ADVANCED DEVELOPMENT MODEL OF TERRITORIAL HUMAN RESOURCES POTENTIAL

    Directory of Open Access Journals (Sweden)

    Alexander G. Моkronosov

    2014-01-01

    Full Text Available The aim of the study is to substantiate the need for eliminating the excessive spatial polarization of territorial socio-economic development as a necessary condition for advanced development of human resources potential. The authors explore the basic problems and contradictions of modern regional and local labor markets in Russia. Based on generalization and systematization of foreign and domestic research outcomes, the paper reveals the main condition for eliminating the territorial polarization threats, which implies formation of a new institutional environment in order to provide co-operation of participants in the territorial interest zone in personnel training and new jobs creating.The research findings demonstrate the increased disproportions between the workforce and labor markets of municipal formations in Sverdlovsk region, and emphasize the need for territorial industrial educational clusters maximizing the network co-operation of the involved parties.The scientific novelty combines adaptation of theoretical concepts of the “new economic geography” applied to reorganization processes in the Russian economy; and elaboration of the cluster model of advanced development of territorial human resources potential by means of territorial centers coordinating the interests of administration, business society, and households.Practical significance of the research results is related to facilitating the administrative efficiency of regional and municipal formations, employers, territorial employment centers, and thereby the advanced development of human resources potential.

  19. Potential misinterpretation of the nutritional value of dietary fiber: correcting fiber digestibility values for nondietary gut-interfering material.

    Science.gov (United States)

    Montoya, Carlos A; Henare, Sharon J; Rutherfurd, Shane M; Moughan, Paul J

    2016-08-01

    The aim of this review is to identify the origin and implications of a nondietary material present in digesta and feces that interferes with the determination of dietary fiber in gastrointestinal contents. Negative values for ileal and fecal digestibility of dietary fiber are commonly reported in the literature for monogastric animal species, including humans. As negative values are not possible physiologically, this suggests the existence of a nondietary material in the gastrointestinal contents and feces that interferes with the accurate determination of dietary fiber digestibility when conventional methods of fiber determination are applied. To date, little attention has been given to this nondietary interfering material, which appears to be influenced by the type and concentration of fiber in the diet. Interestingly, estimates of dietary fiber digestibility increase substantially when corrected for the nondietary interfering material, which suggests that currently reported values underestimate the digestibility of dietary fiber and may misrepresent where, in the digestive tract, fermentation of fiber occurs. A new perspective of dietary fiber digestion in the gastrointestinal tract is developing, leading to a better understanding of the contribution of dietary fiber to health.

  20. Murine and human CFTR exhibit different sensitivities to CFTR potentiators.

    Science.gov (United States)

    Cui, Guiying; McCarty, Nael A

    2015-10-01

    Development of therapeutic molecules with clinical efficacy as modulators of defective CFTR includes efforts to identify potentiators that can overcome or repair the gating defect in mutant CFTR channels. This has taken a great leap forward with the identification of the potentiator VX-770, now available to patients as "Kalydeco." Other small molecules with different chemical structure also are capable of potentiating the activity of either wild-type or mutant CFTR, suggesting that there are features of the protein that may be targeted to achieve stimulation of channel activity by structurally diverse compounds. However, neither the mechanisms by which these compounds potentiate mutant CFTR nor the site(s) where these compounds bind have been identified. This knowledge gap partly reflects the lack of appropriate experimental models to provide clues toward the identification of binding sites. Here, we have compared the channel behavior and response to novel and known potentiators of human CFTR (hCFTR) and murine (mCFTR) expressed in Xenopus oocytes. Both hCFTR and mCFTR were blocked by GlyH-101 from the extracellular side, but mCFTR activity was increased with GlyH-101 applied directly to the cytoplasmic side. Similarly, glibenclamide only exhibited a blocking effect on hCFTR but both blocked and potentiated mCFTR in excised membrane patches and in intact oocytes. The clinically used CFTR potentiator VX-770 transiently increased hCFTR by ∼13% but potentiated mCFTR significantly more strongly. Our results suggest that mCFTR pharmacological sensitivities differ from hCFTR, which will provide a useful tool for identifying the binding sites and mechanism for these potentiators.

  1. Adenoviral-mediated correction of methylmalonyl-CoA mutase deficiency in murine fibroblasts and human hepatocytes

    Directory of Open Access Journals (Sweden)

    Korson Mark

    2007-04-01

    Full Text Available Abstract Background Methylmalonic acidemia (MMA, a common organic aciduria, is caused by deficiency of the mitochondrial localized, 5'deoxyadenosylcobalamin dependent enzyme, methylmalonyl-CoA mutase (MUT. Liver transplantation in the absence of gross hepatic dysfunction provides supportive therapy and metabolic stability in severely affected patients, which invites the concept of using cell and gene delivery as future treatments for this condition. Methods To assess the effectiveness of gene delivery to restore the defective metabolism in this disorder, adenoviral correction experiments were performed using murine Mut embryonic fibroblasts and primary human methylmalonyl-CoA mutase deficient hepatocytes derived from a patient who harbored two early truncating mutations, E224X and R228X, in the MUT gene. Enzymatic and expression studies were used to assess the extent of functional correction. Results Primary hepatocytes, isolated from the native liver after removal subsequent to a combined liver-kidney transplantation procedure, or Mut murine fibroblasts were infected with a second generation recombinant adenoviral vector that expressed the murine methylmalonyl-CoA mutase as well as eGFP from distinct promoters. After transduction, [1-14C] propionate macromolecular incorporation studies and Western analysis demonstrated complete correction of the enzymatic defect in both cell types. Viral reconstitution of enzymatic expression in the human methylmalonyl-CoA mutase deficient hepatocytes exceeded that seen in fibroblasts or control hepatocytes. Conclusion These experiments provide proof of principle for viral correction in methylmalonic acidemia and suggest that hepatocyte-directed gene delivery will be an effective therapeutic treatment strategy in both murine models and in human patients. Primary hepatocytes from a liver that was unsuitable for transplantation provided an important resource for these studies.

  2. Exploring the existence and potential underpinnings of dog-human and horse-human attachment bonds.

    Science.gov (United States)

    Payne, Elyssa; DeAraugo, Jodi; Bennett, Pauleen; McGreevy, Paul

    2016-04-01

    This article reviews evidence for the existence of attachment bonds directed toward humans in dog-human and horse-human dyads. It explores each species' alignment with the four features of a typical attachment bond: separation-related distress, safe haven, secure base and proximity seeking. While dog-human dyads show evidence of each of these, there is limited alignment for horse-human dyads. These differences are discussed in the light of the different selection paths of domestic dogs and horses as well as the different contexts in which the two species interact with humans. The role of emotional intelligence in humans as a potential mediator for human-animal relationships, attachment or otherwise, is also examined. Finally, future studies, which may clarify the interplay between attachment, human-animal relationships and emotional intelligence, are proposed. Such avenues of research may help us explore the concepts of trust and bonding that are often said to occur at the dog-human and horse-human interface.

  3. Metallothioneins in human tumors and potential roles in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

    2003-12-10

    Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

  4. Validation of Correction Algorithms for Near-IR Analysis of Human Milk in an Independent Sample Set-Effect of Pasteurization.

    Science.gov (United States)

    Kotrri, Gynter; Fusch, Gerhard; Kwan, Celia; Choi, Dasol; Choi, Arum; Al Kafi, Nisreen; Rochow, Niels; Fusch, Christoph

    2016-02-26

    Commercial infrared (IR) milk analyzers are being increasingly used in research settings for the macronutrient measurement of breast milk (BM) prior to its target fortification. These devices, however, may not provide reliable measurement if not properly calibrated. In the current study, we tested a correction algorithm for a Near-IR milk analyzer (Unity SpectraStar, Brookfield, CT, USA) for fat and protein measurements, and examined the effect of pasteurization on the IR matrix and the stability of fat, protein, and lactose. Measurement values generated through Near-IR analysis were compared against those obtained through chemical reference methods to test the correction algorithm for the Near-IR milk analyzer. Macronutrient levels were compared between unpasteurized and pasteurized milk samples to determine the effect of pasteurization on macronutrient stability. The correction algorithm generated for our device was found to be valid for unpasteurized and pasteurized BM. Pasteurization had no effect on the macronutrient levels and the IR matrix of BM. These results show that fat and protein content can be accurately measured and monitored for unpasteurized and pasteurized BM. Of additional importance is the implication that donated human milk, generally low in protein content, has the potential to be target fortified.

  5. Myeloid dendritic cells are potential players in human neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Paola eBossù

    2015-12-01

    Full Text Available Alzheimer’s (AD and Parkinson’s (PD diseases are devastating neurodegenerative disturbances wherein neuroinflammation is a chronic pathogenic process with high therapeutic potential. Major mediators of AD/PD neuroimmune processes are resident immune cells, but immune cells derived from periphery may also participate and to some extent modify neuroinflammation. Specifically, blood borne myeloid cells emerge as crucial components of AD/PD progression and susceptibility. Among these, dendritic cells (DCs are key immune orchestrators and players of brain immune surveillance: we candidate them as potential mediators of both AD and PD and as relevant cell model for unraveling myeloid cell role in neurodegeneration. Hence, we recapitulate and discuss emerging data suggesting that blood-derived DCs play a role in experimental and human neurodegenerative diseases. In humans, in particular, DCs are modified by in vitro culture with neurodegeneration-associated pathogenic factors and dysregulated in AD patients, while the levels of DC precursors are decreased in AD and PD patients’ blood, possibly as an index of their recruitment to the brain. Overall, we emphasize the need to explore the impact of DCs on neurodegeneration to uncover peripheral immune mechanisms of pathogenic importance, recognize potential biomarkers and improve therapeutic approaches for neurodegenerative diseases.

  6. Decade of the Brain 1990--2000: Maximizing human potential

    Energy Technology Data Exchange (ETDEWEB)

    1991-04-01

    The US Decade of the Brain offers scientists throughout the Federal Government a unique opportunity to advance and apply scientific knowledge about the brain and nervous system. During the next 10 years, scientists hope to maximize human potential through studies of human behavior, senses and communication, learning and memory, genetic/chemical alterations, and environmental interactions. Progress in these areas should lead to reductions in mortality from brain and nervous system disorders and to improvements in the quality of life. This report identifies nine research areas that could form the basis of an integrated program in the brain and behavioral sciences. A chart summarizing the Federal activities in these nine areas may be found at the back of the report. In addition, three areas that span the nine research areas -- basic research, technology and international activities -- are considered.

  7. Beyond abortion: the potential reach of a human life amendment.

    Science.gov (United States)

    Westfall, D

    1982-01-01

    In Roe v. Wade, the Supreme Court held that the constitutionally protected right to privacy includes a woman's right to terminate pregnancy. Following the decision, anti-abortion groups turned to Congress to limit or negate that right. As a result of their efforts, several "human life" statutes and constitutional amendments have been proposed. This Article focuses on the implications of proposed amendments that seek to ban or limit the availability of abortions indirectly by broadening the definition of "person" to include unborn individuals. The Article discusses the potentially serious effects such an amendment would have in areas unrelated to abortion. It finds that the resulting chaos and uncertainty would have great social costs, and concludes that if abortions are to be banned or restricted, a human life amendment that directly deals with abortion is preferable to one that defines "person" to include the unborn.

  8. Nutritional Evaluation of Australian Microalgae as Potential Human Health Supplements

    Science.gov (United States)

    Kent, Megan; Welladsen, Heather M.; Mangott, Arnold; Li, Yan

    2015-01-01

    This study investigated the biochemical suitability of Australian native microalgal species Scenedesmus sp., Nannochloropsis sp., Dunaliella sp., and a chlorophytic polyculture as nutritional supplements for human health. The four microalgal cultures were harvested during exponential growth, lyophilized, and analysed for proximate composition (moisture, ash, lipid, carbohydrates, and protein), pigments, and amino acid and fatty acid profiles. The resulting nutritional value, based on biochemical composition, was compared to commercial Spirulina and Chlorella products. The Australian native microalgae exhibited similar, and in several cases superior, organic nutritional properties relative to the assessed commercial products, with biochemical profiles rich in high-quality protein, nutritious polyunsaturated fats (such as α-linolenic acid, arachidonic acid, and eicosapentaenoic acid), and antioxidant pigments. These findings indicate that the microalgae assessed have great potential as multi-nutrient human health supplements. PMID:25723496

  9. Scatter correction for large non-human primate brain imaging using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo-Variawa, S; Lehnert, W; Banati, R B; Meikle, S R, E-mail: snai3212@uni.sydney.edu.au [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia)

    2011-04-07

    The baboon is well suited to pre-clinical evaluation of novel radioligands for positron emission tomography (PET). We have previously demonstrated the feasibility of using a high resolution animal PET scanner for this application in the baboon brain. However, the non-homogenous distribution of tissue density within the head may give rise to photon scattering effects that reduce contrast and compromise quantitative accuracy. In this study, we investigated the magnitude and distribution of scatter contributing to the final reconstructed image and its variability throughout the baboon brain using phantoms and Monte Carlo simulated data. The scatter fraction is measured up to 36% at the centre of the brain for a wide energy window (350-650 keV) and 19% for a narrow (450-650 keV) window. We observed less than 3% variation in the scatter fraction throughout the brain and found that scattered events arising from radioactivity outside the field of view contribute less than 1% of measured coincidences. In a contrast phantom, scatter and attenuation correction improved contrast recovery compared with attenuation correction on its own and reduced bias to less than 10% at the expense of the reduced signal-to-noise ratio. We conclude that scatter correction is a necessary step for ensuring high quality measurements of the radiotracer distribution in the baboon brain with a microPET scanner, while it is not necessary to model out of field of view scatter or a spatially variant scatter function.

  10. Climate Change in the US: Potential Consequences for Human Health

    Science.gov (United States)

    Maynard, Nancy G.

    2001-01-01

    The U.S. National Assessment identified five major areas of consequences of climate change in the United States: temperature-related illnesses and deaths, health effects related to extreme weather events, air pollution-related health effects, water- and food-borne diseases, and insect-, tick-, and rodent-borne diseases. The U.S. National Assessment final conclusions about these potential health effects will be described. In addition, a summary of some of the new tools for studying human health aspects of climate change as well as environment-health linkages through remotely sensed data and observations will be provided.

  11. Under-correction of human myopia--is it myopigenic?: a retrospective analysis of clinical refraction data.

    Science.gov (United States)

    Vasudevan, Balamurali; Esposito, Christina; Peterson, Cody; Coronado, Cory; Ciuffreda, Kenneth J

    2014-01-01

    To investigate retrospectively, based on routine clinical records in an optometric office, the effect of refractive under-correction of the myopic spectacle prescription on myopic progression in children and young adults. Patient records of children and young-adult myopes in a private optometric practice in Glendale, Arizona, USA, were initially reviewed to identify those that met the criteria. Information collected from the patient records included: age, gender, the dates and number of their visits (more than one visit was required for use of the data), final prescription, and non-cycloplegic subjective refraction. For each patient visit, the difference in spherical equivalent (SE) between the subjective refraction for maximum visual acuity and the final prescription was calculated for both the left and right eyes. Myopia progression was defined as the difference in SE between the final subjective refraction of the previous visit and that of the subsequent visit. Based on the study criteria, a total of 275 patient visits were obtained from the data collected in 76 patients. A significant positive correlation was found between the magnitude of under-correction of the refractive error and myopic progression (r=0.301, prefraction (r=0.166, p=0.006); that is, the greater the degree of myopia, the greater the effect of under-correction. However, there was no significant correlation between myopia progression and either age (r=-0.11, p=0.86) or gender (r=-0.82, p=0.17). Under-correction of myopia produced a small but progressively greater degree of myopic progression than did full correction. The present finding is consistent with earlier clinical trials and modeling of human myopia. Copyright © 2013 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

  12. 基于人差错纠正能力的人因可靠性模型研究%Human Reliability Method Analysis Based on Human Error Correcting Ability

    Institute of Scientific and Technical Information of China (English)

    陈炉云; 张裕芳

    2011-01-01

    Based on the theory of time sequence and error correcting ability character of the human operator behaviors in man-machine system, combining the key performance shaping factor analysis, the human reliability analysis of the vessel chamber is investigated. By the time sequence parameter and error correcting parameter in the human errors analysis, the operator behaviors shaping model of man-machine system and human errors event tree are proposed. By the error correcting ability analysis, the quantitative model and allowance theory in human reliability analysis are discussed. In the end, with the monitoring task of the operation desk in the vessel chamber as an example, a human reliability analysis was conducted to quantitatively assess the mission reliability of the operator.%根据人-机系统中人的操作行为具有时序性和差错可纠正性的特点,结合船舶舱室行为形成主因子,开展船舶舱室人因可靠性研究.以人因失误的时序性和差错纠正参数为基础,建立人-机系统中操作者行为模式和人因失误事件树模型.通过对人的差错纠正能力的分析,开展人因可靠性量化模型纠正理论研究.最后,以船舶舱室操作台的监控任务人因可靠性为例进行量化计算,定量评估操作人员执行任务的可靠度.

  13. [Impact of the method choice and the extent of correction on the development of visual evoked potentials in children and adolescents with refractive anomalies].

    Science.gov (United States)

    Lobanova, I V; Leshchenko, I A; Markova, E Iu; Khatsenko, I E

    2013-01-01

    The article discusses a possible impact of different refraction correction methods, providing full or partial correction, on visual acuity and the development of visual evoked potentials in children and adolescents with myopia and myopic astigmatism. The accuracy of identification of visual evoked potentials depends, as shown in the article, on the extent of the correction chosen and the method used. In childhood the visual system is very susceptible to visual afferent deficit. The permanent deficit of visual information impedes further maturation of the visual analyzer, i.e. the development of central vision, binocular vision, and stereopsis. In high myopia it is important to decide not only on the extent of the correction but also on the method to use. In patients wearing soft contact lenses the visual evoked potentials have more regular shape, amplitude, and latency. The introduction of silicone hydrogel and daily disposal contact lenses, spherical and toric (for astigmatism correction), provided an opportunity to solve hygienic problems associated with contact lens use in children and adolescents and to decrease the risk of hypoxia complications.

  14. 'Cebiche'--a potential source of human anisakiasis in Mexico?

    Science.gov (United States)

    Laffon-Leal, S M; Vidal-Martínez, V M; Arjona-Torres, G

    2000-06-01

    Five fish species used for preparation of a popular dish (cebiche) made with raw fish flesh in Mexico were obtained from five localities of the coast of Yucatan. Lutjanus synagris, Gerres cinereus, Sphyraena barracuda, Epinephelus morio and Haemulon plumieriwere examined for the presence of larvae of anisakid nematodes, causative agents of human anisakiasis. The nematode Pseudoterranova sp. was found in E. morio and S. barracuda with a total prevalence of 83% and 6.5 +/- 6.2 worms per fish for E. morio, and a prevalence of 33% and 10.2 +/- 30.0 worms per fish for S. barracuda. Contracaecumsp. was found to infect G. cinereus with a prevalence of 57% and 7.6 +/- 11.4 worms per fish. The relatively high prevalence of Pseudoterranova sp. indicates that this parasite is a potential causal agent of anisakiasis on the coast of Yucatan. Although all larvae were found only in the mesentery of the fish host, their importance as a potential source of human infection cannot be excluded as larval migration to the muscles in dead fish is possible.

  15. Potential drug development candidates for human soil-transmitted helminthiases.

    Directory of Open Access Journals (Sweden)

    Piero Olliaro

    2011-06-01

    Full Text Available Few drugs are available for soil-transmitted helminthiasis (STH; the benzimidazoles albendazole and mebendazole are the only drugs being used for preventive chemotherapy as they can be given in one single dose with no weight adjustment. While generally safe and effective in reducing intensity of infection, they are contra-indicated in first-trimester pregnancy and have suboptimal efficacy against Trichuris trichiura. In addition, drug resistance is a threat. It is therefore important to find alternatives.We searched the literature and the animal health marketed products and pipeline for potential drug development candidates. Recently registered veterinary products offer advantages in that they have undergone extensive and rigorous animal testing, thus reducing the risk, cost and time to approval for human trials. For selected compounds, we retrieved and summarised publicly available information (through US Freedom of Information (FoI statements, European Public Assessment Reports (EPAR and published literature. Concomitantly, we developed a target product profile (TPP against which the products were compared.The paper summarizes the general findings including various classes of compounds, and more specific information on two veterinary anthelmintics (monepantel, emodepside and nitazoxanide, an antiprotozoal drug, compiled from the EMA EPAR and FDA registration files.Few of the compounds already approved for use in human or animal medicine qualify for development track decision. Fast-tracking to approval for human studies may be possible for veterinary compounds like emodepside and monepantel, but additional information remains to be acquired before an informed decision can be made.

  16. MicroRNAs: potential regulators involved in human anencephaly.

    Science.gov (United States)

    Zhang, Zhiping; Chang, Huibo; Li, Yuanyuan; Zhang, Ting; Zou, Jizhen; Zheng, Xiaoying; Wu, Jianxin

    2010-02-01

    MicroRNAs (miRNAs) are posttranscriptional regulators of messenger RNA activity. Neural tube defects (NTDs) are severe congenital anomalies that substantially impact an infant's morbidity and mortality. The miRNAs are known to be dynamically regulated during neurodevelopment; their role in human NTDs, however, is still unknown. In this study, we show the presence of a specific miRNA expression profile from tissues of fetuses with anencephaly, one of the most severe forms of NTDs. Furthermore, we map the target genes of these miRNAs in the human genome. In comparison to healthy human fetal brain tissues, tissues from fetuses with anencephaly exhibited 97 down-regulated and 116 up-regulated miRNAs. The microarray findings were extended using real-time qRT-PCR for nine miRNAs. Specifically, of these validated miRNAs, miR-126, miR-198, and miR-451 were up-regulated, while miR-9, miR-212, miR-124, miR-138, and miR-103/107 were down-regulated in the tissues of fetuses with anencephaly. A bioinformatic analysis showed 881 potential target genes that are regulated by the validated miRNAs. Seventy-nine of these potential genes are involved in a protein interaction network. There were 6 co-occurrence annotations within the GOSlim process and 7 co-occurrence annotations within the GOSlim function found by GeneCodis 2.0. Our results suggest that miRNA dysregulation is possibly involved in the pathogenesis of anencephaly.

  17. Bacteriophage and their potential roles in the human oral cavity

    Directory of Open Access Journals (Sweden)

    Anna Edlund

    2015-04-01

    Full Text Available The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts.

  18. MR-based PET motion correction procedure for simultaneous MR-PET neuroimaging of human brain.

    Directory of Open Access Journals (Sweden)

    Marcus Görge Ullisch

    Full Text Available Positron Emission Tomography (PET images are prone to motion artefacts due to the long acquisition time of PET measurements. Recently, simultaneous magnetic resonance imaging (MRI and PET have become available in the first generation of Hybrid MR-PET scanners. In this work, the elimination of artefacts due to head motion in PET neuroimages is achieved by a new approach utilising MR-based motion tracking in combination with PET list mode data motion correction for simultaneous MR-PET acquisitions. The method comprises accurate MR-based motion measurements, an intra-frame motion minimising and reconstruction time reducing temporal framing algorithm, and a list mode based PET reconstruction which utilises the Ordinary Poisson Algorithm and avoids axial and transaxial compression. Compared to images uncorrected for motion, an increased image quality is shown in phantom as well as in vivo images. In vivo motion corrected images show an evident increase of contrast at the basal ganglia and a good visibility of uptake in tiny structures such as superior colliculi.

  19. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells

    Science.gov (United States)

    Hoban, Megan D.; Cost, Gregory J.; Mendel, Matthew C.; Romero, Zulema; Kaufman, Michael L.; Joglekar, Alok V.; Ho, Michelle; Lumaquin, Dianne; Gray, David; Lill, Georgia R.; Cooper, Aaron R.; Urbinati, Fabrizia; Senadheera, Shantha; Zhu, Allen; Liu, Pei-Qi; Paschon, David E.; Zhang, Lei; Rebar, Edward J.; Wilber, Andrew; Wang, Xiaoyan; Gregory, Philip D.; Holmes, Michael C.; Reik, Andreas; Hollis, Roger P.

    2015-01-01

    Sickle cell disease (SCD) is characterized by a single point mutation in the seventh codon of the β-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrate efficient targeted cleavage at the β-globin locus with minimal off-target modification. By codelivering a homologous donor template (either an integrase-defective lentiviral vector or a DNA oligonucleotide), high levels of gene modification were achieved in CD34+ hematopoietic stem and progenitor cells. Modified cells maintained their ability to engraft NOD/SCID/IL2rγnull mice and to produce cells from multiple lineages, although with a reduction in the modification levels relative to the in vitro samples. Importantly, ZFN-driven gene correction in CD34+ cells from the bone marrow of patients with SCD resulted in the production of wild-type hemoglobin tetramers. PMID:25733580

  20. Asymptotic correction approach to improving approximate exchange-correlation potentials: Time-dependent density-functional theory calculations of molecular excitation spectra

    Science.gov (United States)

    Casida, Mark E.; Salahub, Dennis R.

    2000-11-01

    The time-dependent density functional theory (TD-DFT) calculation of excitation spectra places certain demands on the DFT exchange-correlation potential, vxc, that are not met by the functionals normally used in molecular calculations. In particular, for high-lying excitations, it is crucial that the asymptotic behavior of vxc be correct. In a previous paper, we introduced a novel asymptotic-correction approach which we used with the local density approximation (LDA) to yield an asymptotically corrected LDA (AC-LDA) potential [Casida, Casida, and Salahub, Int. J. Quantum Chem. 70, 933 (1998)]. The present paper details the theory underlying this asymptotic correction approach, which involves a constant shift to incorporate the effect of the derivative discontinuity (DD) in the bulk region of finite systems, and a spliced asymptotic correction in the large r region. This is done without introducing any adjustable parameters. We emphasize that correcting the asymptotic behavior of vxc is not by itself sufficient to improve the overall form of the potential unless the effect of the derivative discontinuity is taken into account. The approach could be used to correct vxc from any of the commonly used gradient-corrected functionals. It is here applied to the LDA, using the asymptotically correct potential of van Leeuwen and Baerends (LB94) in the large r region. The performance of our AC-LDA vxc is assessed for the calculation of TD-DFT excitation energies for a large number of excitations, including both valence and Rydberg states, for each of four small molecules: N2, CO, CH2O, and C2H4. The results show a significant improvement over those from either the LB94 or the LDA functionals. This confirms that the DD is indeed an important element in the design of functionals. The quality of TDLDA/LB94 and TDLDA/AC-LDA oscillator strengths were also assessed in what we believe to be the first rigorous assessment of TD-DFT molecular oscillator strengths in comparison with

  1. The Transmembrane Electrical Potential in Rhodopseudomonas sphaeroides Determined from the Distribution of Tetraphenylphosphonium after Correction for Its Binding to Cell Components

    NARCIS (Netherlands)

    Lolkema, Juke S.; Abbing, Arend; Hellingwerf, K; Konings, Wilhelmus

    1983-01-01

    The membrane potential was determined in intact cells of Rhodopseudomonas sphaeroides from the distribution of the lipophilic cation tetraphenylphosphonium (Ph4P+) after correction for probe binding to cell components. The concentration of Ph4P+ in the external medium of the cells was recorded with

  2. Gait curves for human recognition, backpack detection, and silhouette correction in a nighttime environment

    Science.gov (United States)

    DeCann, Brian; Ross, Arun

    2010-04-01

    The need for an automated surveillance system is pronounced at night when the capability of the human eye to detect anomalies is reduced. While there have been significant efforts in the classification of individuals using human metrology and gait, the majority of research assumes a day-time environment. The aim of this study is to move beyond traditional image acquisition modalities and explore the issues of object detection and human identification at night. To address these issues, a spatiotemporal gait curve that captures the shape dynamics of a moving human silhouette is employed. Initially proposed by Wang et al., this representation of the gait is expanded to incorporate modules for individual classification, backpack detection, and silhouette restoration. Evaluation of these algorithms is conducted on the CASIA Night Gait Database, which includes 10 video sequences for each of 153 unique subjects. The video sequences were captured using a low resolution thermal camera. Matching performance of the proposed algorithms is evaluated using a nearest neighbor classifier. The outcome of this work is an efficient algorithm for backpack detection and human identification, and a basis for further study in silhouette enhancement.

  3. Analysis of measured data of human body based on error correcting frequency

    Science.gov (United States)

    Jin, Aiyan; Peipei, Gao; Shang, Xiaomei

    2014-04-01

    Anthropometry is to measure all parts of human body surface, and the measured data is the basis of analysis and study of the human body, establishment and modification of garment size and formulation and implementation of online clothing store. In this paper, several groups of the measured data are gained, and analysis of data error is gotten by analyzing the error frequency and using analysis of variance method in mathematical statistics method. Determination of the measured data accuracy and the difficulty of measured parts of human body, further studies of the causes of data errors, and summarization of the key points to minimize errors possibly are also mentioned in the paper. This paper analyses the measured data based on error frequency, and in a way , it provides certain reference elements to promote the garment industry development.

  4. Optical study on the vision correction and supernormal vision based on the wave-front aberrations of human eye

    Institute of Scientific and Technical Information of China (English)

    MU GuoGuang; WANG ZhaoQi; LIU YongJi; QUAN Wei; WANG Yang; WANG Wei

    2007-01-01

    In this paper we present the recent research results in the field of vision correction and supernormal vision according to the actual measurements of the wave-front aberrations and the corneal surface topography, the clinical detection of the visual function and the laser corneal refractive surgery, and the optimization of the optical system. These include the features of the aberrations of human eye with different pupil sizes, different fields of view and temporal accommodation, the influence of the polychromatic illumination of the visible wavelength on the supernormal vision,and the effect of the existing laser corneal refractive surgery on the wave-front aberrations of the eye. It is shown that the wave-front aberration of human eye is of temporal variation and of synthesis with multi impact factors. To achieve supernormal vision, an optimum engineering data for the customized laser corneal surgery should be firstly acquired, which may involve the dynamic free-form optical surface. Although the myopia can be corrected by the laser in situ keratomileusis (LASlK) in a certain degree, it brings about negative effects under scotopic conditions.

  5. Optical study on the vision correction and supernormal vision based on the wave-front aberrations of human eye

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this paper we present the recent research results in the field of vision correction and supernormal vision according to the actual measurements of the wave-front aberrations and the corneal surface topography,the clinical detection of the visual function and the laser corneal refractive surgery,and the optimization of the optical system. These include the features of the aberrations of human eye with different pupil sizes,different fields of view and temporal accommodation,the influence of the polychromatic illumination of the visible wavelength on the supernormal vision,and the effect of the existing laser corneal refractive surgery on the wave-front ab-errations of the eye. It is shown that the wave-front aberration of human eye is of temporal variation and of synthesis with multi impact factors. To achieve super-normal vision,an optimum engineering data for the customized laser corneal sur-gery should be firstly acquired,which may involve the dynamic free-form optical surface. Although the myopia can be corrected by the laser in situ keratomileusis(LASIK) in a certain degree,it brings about negative effects under scotopic condi-tions.

  6. Free Radical Oxidation Induced by Iron Metabolism Disorder in Femoral and Pelvic Fractures and Potential for Its Correction

    Directory of Open Access Journals (Sweden)

    Y. P. Orlov

    2016-01-01

    development of traumatic disease and demon strate the potential of Desferal to correct the traumainduced alterations of oxidantantioxidant system in patients with femoral and pelvic fractions.

  7. The therapeutic potential of human olfactory-derived stem cells.

    Science.gov (United States)

    Marshall, C T; Lu, C; Winstead, W; Zhang, X; Xiao, M; Harding, G; Klueber, K M; Roisen, F J

    2006-06-01

    Stem cells from fetal and adult central nervous system have been isolated and characterized, providing populations for potential replacement therapy for traumatic injury repair and neurodegenerative diseases. The regenerative capacity of the olfactory system has attracted scientific interest. Studies focusing on animal and human olfactory bulb ensheathing cells (OECs) have heightened the expectations that OECs can enhance axonal regeneration and repair demyelinating diseases. Harvest of OECs from the olfactory bulb requires highly invasive surgery, which is a major obstacle. In contrast, olfactory epithelium (OE) has a unique regenerative capacity and is readily accessible from its location in the nasal cavity, allowing for harvest without lasting damage to the donor. Adult OE contains progenitors responsible for the normal life-long continuous replacement of neurons and supporting cells. Culture techniques have been established for human OE that generate populations of mitotically active neural progenitors that form neurospheres (Roisen et al., 2001; Winstead et al., 2005). The potential application of this technology includes autologous transplantation where minimal donor material can be isolated, expanded ex vivo, and lineage restricted to a desired phenotype prior to/or after re-implantation. Furthermore, these strategies circumvent the ethical issues that arise with embryonic or fetal tissues. The long term goal is to develop procedures through which a victim of a spinal cord injury or neurodegenerative condition would serve as a source of progenitors for his/her own regenerative grafts, avoiding the need for immunosuppression and ethical controversy. In addition, these cells can provide populations for pharmacological and/or diagnostic evaluation.

  8. Closantel; a veterinary drug with potential severe morbidity in humans.

    Science.gov (United States)

    Tabatabaei, Seyed Ali; Soleimani, Mohammad; Mansouri, Mohammad Reza; Mirshahi, Ahmad; Inanlou, Bahman; Abrishami, Mojtaba; Pakrah, Ahmad Reza; Masarat, Hamideh

    2016-11-29

    Closantel is a halogenated salicylanilide with a potent anti parasitic activity. It is widely used in management of parasitic infestation in animals, but is contraindicated in humans. A 34-year-old man with depression was referred to our center with progressive loss of vision in both eyes 10 days after unintentional ingestion of three 500 mg tablets of Closantel. On fundus examination, left optic disc margin was blurred. His bilateral visual acuity was no light perception (NLP) despite prescribed IV erythropoietin injections 20,000 units daily for 3 days and 1gr intravenous methylprednisolone acetate for 3 days followed by 1 mg/kg oral prednisolone. On macular optical coherence tomography (OCT), a disruption in outer retina was observed. Electroretinogram and visual evoked potential tests showed visual pathway involvement. Destruction of neurosensory retina and visual pathways after accidental Closantel use is related to severe visual loss. This case alerts us about the destructive effect of this drug on humans even in low dosage which necessitates preventive efforts to reduce the chance of this morbid side effect.

  9. Spontaneous Food Fermentations and Potential Risks for Human Health

    Directory of Open Access Journals (Sweden)

    Vittorio Capozzi

    2017-09-01

    Full Text Available Fermented foods and beverages are a heterogeneous class of products with a relevant worldwide significance for human economy, nutrition and health for millennia. A huge diversity of microorganisms is associated with the enormous variety in terms of raw materials, fermentative behavior and obtained products. In this wide microbiodiversity it is possible that the presence of microbial pathogens and toxic by-products of microbial origin, including mycotoxins, ethyl carbamate and biogenic amines, are aspects liable to reduce the safety of the consumed product. Together with other approaches (e.g., use of preservatives, respect of specific physico-chemical parameters, starter cultures technology has been conceived to successfully dominate indigenous microflora and to drive fermentation to foresee the desired attributes of the matrix, assuring quality and safety. Recent trends indicate a general return to spontaneous food fermentation. In this review, we point out the potential risks for human health associated with uncontrolled (uninoculated food fermentation and we discuss biotechnological approaches susceptible to conciliate fermented food safety, with instances of an enhanced contribution of microbes associated to spontaneous fermentation.

  10. Labour Market Intermediaries: A Corrective to the Human Capital Paradigm (Mis)matching Skills and Jobs?

    Science.gov (United States)

    Dobbins, Tony; Plows, Alexandra

    2017-01-01

    The orthodox supply-side human capital theory (HCT) paradigm is inadequate for understanding and adjusting to labour market volatility in UK regional economies like Wales. This article explores the role of regional labour market intermediaries (LMIs) in matching supply (skills) and demand (job opportunities) in regional labour markets. Some LMIs…

  11. Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles.

    Science.gov (United States)

    Yu, Kyung-Rok; Natanson, Hannah; Dunbar, Cynthia E

    2016-08-02

    Hematopoietic stem and progenitor cells (HSPCs) have great therapeutic potential because of their ability to both self-renew and differentiate. It has been proposed that, given their unique properties, a small number of genetically modified HSPCs could accomplish lifelong, corrective reconstitution of the entire hematopoietic system in patients with various hematologic disorders. Scientists have demonstrated that gene addition therapies-targeted to HSPCs and using integrating retroviral vectors-possess clear clinical benefits in multiple diseases, among them immunodeficiencies, storage disorders, and hemoglobinopathies. Scientists attempting to develop clinically relevant gene therapy protocols have, however, encountered a number of unexpected hurdles because of their incomplete knowledge of target cells, genomic control, and gene transfer technologies. Targeted gene-editing technologies using engineered nucleases such as ZFN, TALEN, and/or CRISPR/Cas9 RGEN show great clinical promise, allowing for the site-specific correction of disease-causing mutations-a process with important applications in autosomal dominant or dominant-negative genetic disorders. The relative simplicity of the CRISPR/Cas9 system, in particular, has sparked an exponential increase in the scientific community's interest in and use of these gene-editing technologies. In this minireview, we discuss the specific applications of gene-editing technologies in human HSPCs, as informed by prior experience with gene addition strategies. HSPCs are desirable but challenging targets; the specific mechanisms these cells evolved to protect themselves from DNA damage render them potentially more susceptible to oncogenesis, especially given their ability to self-renew and their long-term proliferative potential. We further review scientists' experience with gene-editing technologies to date, focusing on strategies to move these techniques toward implementation in safe and effective clinical trials.

  12. Pharmacological Correction of the Human Functional State in High Altitude Conditions

    Science.gov (United States)

    2001-06-01

    Kinetics in Rat. J. Farmacologia i toxicologia (J. Pharmacology and Toxicology), Vol. 50, No.5, pp.5 4 -5 6 (in Russian). 5. Boiko, S.S., Bobkov, U.G... Farmacologia i toxicologia (J. Pharmacology and Toxicology), Vol. 50, No.3, pp. 7 9 -8 1 (in Russian). 6. Bratlid, D., 1972, Bilirubin Binding of Human...Antihypoxic Compounds on Animals with Different Level o Resistance to Oxygen Deficiency. In: Farmacologia and nauchno-tehnicheskii progress (Pharmacology

  13. Crystal structure of human CRMP-4: correction of intensities for lattice-translocation disorder

    Energy Technology Data Exchange (ETDEWEB)

    Ponnusamy, Rajesh [Universidade Nova de Lisboa, Avenida da República, EAN, 2781-901 Oeiras (Portugal); Lebedev, Andrey A. [Research Complex at Harwell, STFC Rutherford Appleton Laboratory, Didcot OX11 0FA (United Kingdom); Pahlow, Steffen [University of Hamburg, Ohnhorststrasse 18, 22609 Hamburg (Germany); Lohkamp, Bernhard, E-mail: bernhard.lohkamp@ki.se [Karolinska Institutet, Tomtebodavägen 6, 4tr, 17177 Stockholm (Sweden); Universidade Nova de Lisboa, Avenida da República, EAN, 2781-901 Oeiras (Portugal)

    2014-06-01

    Crystals of human CRMP-4 showed severe lattice-translocation disorder. Intensities were demodulated using the so-called lattice-alignment method and a new more general method with simplified parameterization, and the structure is presented. Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins that are mainly involved in neuronal cell development. In humans, the CRMP family comprises five members. Here, crystal structures of human CRMP-4 in a truncated and a full-length version are presented. The latter was determined from two types of crystals, which were either twinned or partially disordered. The crystal disorder was coupled with translational NCS in ordered domains and manifested itself with a rather sophisticated modulation of intensities. The data were demodulated using either the two-lattice treatment of lattice-translocation effects or a novel method in which demodulation was achieved by independent scaling of several groups of intensities. This iterative protocol does not rely on any particular parameterization of the modulation coefficients, but uses the current refined structure as a reference. The best results in terms of R factors and map correlation coefficients were obtained using this new method. The determined structures of CRMP-4 are similar to those of other CRMPs. Structural comparison allowed the confirmation of known residues, as well as the identification of new residues, that are important for the homo- and hetero-oligomerization of these proteins, which are critical to nerve-cell development. The structures provide further insight into the effects of medically relevant mutations of the DPYSL-3 gene encoding CRMP-4 and the putative enzymatic activities of CRMPs.

  14. Potential applications of gut microbiota to control human physiology.

    Science.gov (United States)

    Umu, Ozgün Candan Onarman; Oostindjer, Marije; Pope, Phillip B; Svihus, Birger; Egelandsdal, Bjørg; Nes, Ingolf F; Diep, Dzung B

    2013-11-01

    The microorganisms living in our gut have been a black box to us for a long time. However, with the recent advances in high throughput DNA sequencing technologies, it is now possible to assess virtually all microorganisms in our gut including non-culturable ones. With the use of powerful bioinformatics tools to deal with multivariate analyses of huge amounts of data from metagenomics, metatranscriptomics, metabolomics, we now start to gain some important insights into these tiny gut inhabitants. Our knowledge is increasing about who they are, to some extent, what they do and how they affect our health. Gut microbiota have a broad spectrum of possible effects on health, from preventing serious diseases, improving immune system and gut health to stimulating the brain centers responsible for appetite and food intake control. Further, we may be on the verge of being capable of manipulating the gut microbiota by diet control to possibly improve our health. Diets consisting of different components that are fermentable by microbiota are substrates for different kinds of microbes in the gut. Thus, diet control can be used to favor the growth of some selected gut inhabitants. Nowadays, the gut microbiota is taken into account as a separate organ in human body and their activities and metabolites in gut have many physiological and neurological effects. In this mini-review, we discuss the diversity of gut microbiota, the technologies used to assess them, factors that affect microbial composition and metabolites that affect human physiology, and their potential applications in satiety control via the gut-brain axis.

  15. Calculation of radar signal delays in the vicinity of the Sun due to the contribution of a Yukawa correction term in the gravitational potential

    Science.gov (United States)

    Haranas, Ioannis; Ragos, Omiros

    2011-07-01

    There has been a renewed interest in the recent years in the possibility of deviations from the predictions of Newton's "inverse-square law" of universal gravitation. One of the reasons for renewing this interest lies in various theoretical attempts to construct a unified elementary particle theory, in which there is a natural prediction of new forces over macroscopic distances. Therefore the existence of such a force would only coexist with gravity, and in principle could only be detected as a deviation from the inverse square law, or in the "universality of free fall" experiments. New experimental techniques such that of Sagnac interferometry can help explore the range of the Yukawa correction λ≥1014 m where such forces might be present. It may be, that future space missions might be operating in this range which has been unexplored for very long time. To study the effect of the Yukawa correction to the gravitational potential and its corresponding signal delay in the vicinity of the Sun, we use a spherically symmetric modified space time metric where the Yukawa correction its added to the gravitational potential. Next, the Yukawa correction contribution to the signal delay is evaluated. In the case where the distance of closest approach is much less than the range λ, it results to a signal time delay that satisfies the relation t( b< λ)≅37.7 t( b= λ).

  16. Efficient cDNA cloning by direct phenotypic correction of a mutant human cell line (HPRT-) using an Epstein-Barr virus derived cDNA expression vector.

    NARCIS (Netherlands)

    P.B.G.M. Belt; W. Jongmans; J. de Wit (Jan); J.H.J. Hoeijmakers (Jan); C.M.P. Backendorf (Claude); P. van de Putte (Pieter)

    1991-01-01

    textabstractHuman cells are, in general, poor recipients of foreign DNA, which has severely hampered the cloning of genes by direct phenotypic correction of deficient human cell lines after DNA mediated gene transfer. In this communication a methodology is presented which largely circumvents this pr

  17. mTORC1 Inhibition Corrects Neurodevelopmental and Synaptic Alterations in a Human Stem Cell Model of Tuberous Sclerosis.

    Science.gov (United States)

    Costa, Veronica; Aigner, Stefan; Vukcevic, Mirko; Sauter, Evelyn; Behr, Katharina; Ebeling, Martin; Dunkley, Tom; Friedlein, Arno; Zoffmann, Sannah; Meyer, Claas A; Knoflach, Frédéric; Lugert, Sebastian; Patsch, Christoph; Fjeldskaar, Fatiha; Chicha-Gaudimier, Laurie; Kiialainen, Anna; Piraino, Paolo; Bedoucha, Marc; Graf, Martin; Jessberger, Sebastian; Ghosh, Anirvan; Bischofberger, Josef; Jagasia, Ravi

    2016-04-05

    Hyperfunction of the mTORC1 pathway has been associated with idiopathic and syndromic forms of autism spectrum disorder (ASD), including tuberous sclerosis, caused by loss of either TSC1 or TSC2. It remains largely unknown how developmental processes and biochemical signaling affected by mTORC1 dysregulation contribute to human neuronal dysfunction. Here, we have characterized multiple stages of neurogenesis and synapse formation in human neurons derived from TSC2-deleted pluripotent stem cells. Homozygous TSC2 deletion causes severe developmental abnormalities that recapitulate pathological hallmarks of cortical malformations in patients. Both TSC2(+/-) and TSC2(-/-) neurons display altered synaptic transmission paralleled by molecular changes in pathways associated with autism, suggesting the convergence of pathological mechanisms in ASD. Pharmacological inhibition of mTORC1 corrects developmental abnormalities and synaptic dysfunction during independent developmental stages. Our results uncouple stage-specific roles of mTORC1 in human neuronal development and contribute to a better understanding of the onset of neuronal pathophysiology in tuberous sclerosis.

  18. Potentials of speech disorders correction in 4-6 yrs children by means of ergo and art therapy

    Directory of Open Access Journals (Sweden)

    Petrenko N. B.

    2017-04-01

    Full Text Available Purpose: to work out methodic of speech disorders correction in 4-6 yrs children by ergo and art therapy means. Material: during academic year three groups of children (n=97 were being observed: two groups - with speech disorders (control and main and one group of healthy children. Psycho-motor and cognitive functions were assessed with the help of tests for motor coordination (speed of their fulfillment, verbal thinking. Results: it was found that characteristic feature of such children is critical estimation of own speech insufficiency and conscious avoiding oral answers. By cluster analysis results increase of homogeneity in psycho-physical condition’s positive changes, cognitive functions and dance abilities resulted from dance-correction training program were shown. Conclusions: the worked out dance-correction choreographic trainings helps in the following: developing rhythm sense; strengthening of skeleton and muscles; memory, attention, thinking and imagination simulation. Acquiring of such experience will help a child to further successfully train different art-creative and sports kinds of activities; to master choreography and gymnastic as well as different musical instruments.

  19. Oncogenic potential diverge among human papillomavirus type 16 natural variants

    Energy Technology Data Exchange (ETDEWEB)

    Sichero, Laura, E-mail: lsichero@gmail.com [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Simao Sobrinho, Joao [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Lina Villa, Luisa [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Department of Radiology, School of Medicine, University of Sao Paulo (Brazil)

    2012-10-10

    We compared E6/E7 protein properties of three different HPV-16 variants: AA, E-P and E-350G. Primary human foreskin keratinocytes (PHFK) were transduced with HPV-16 E6 and E7 and evaluated for proliferation and ability to grow in soft agar. E-P infected keratinocytes presented the lowest efficiency in colony formation. AA and E-350G keratinocytes attained higher capacity for in vitro transformation. We observed similar degradation of TP53 among HPV-16 variants. Furthermore, we accessed the expression profile in early (p5) and late passage (p30) transduced cells of 84 genes commonly involved in carcinogenesis. Most differences could be attributed to HPV-16 E6/E7 expression. In particular, we detected different expression of ITGA2 and CHEK2 in keratinocytes infected with AA and AA/E-350G late passage cells, respectively, and higher expression of MAP2K1 in E-350G transduced keratinocytes. Our results indicate differences among HPV-16 variants that could explain, at least in part, differences in oncogenic potential attributed to these variants.

  20. Myogenic potential of human alveolar mucosa derived cells.

    Science.gov (United States)

    Zorin, Vadim L; Pulin, Andrey A; Eremin, Ilya I; Korsakov, Ivan N; Zorina, Alla I; Khromova, Natalia V; Sokova, Olga I; Kotenko, Konstantin V; Kopnin, Pavel B

    2017-03-19

    Difficulties related to the obtainment of stem/progenitor cells from skeletal muscle tissue make the search for new sources of myogenic cells highly relevant. Alveolar mucosa might be considered as a perspective candidate due to availability and high proliferative capacity of its cells. Human alveolar mucosa cells (AMC) were obtained from gingival biopsy samples collected from 10 healthy donors and cultured up to 10 passages. AMC matched the generally accepted multipotent mesenchymal stromal cells criteria and possess population doubling time, caryotype and immunophenotype stability during long-term cultivation. The single myogenic induction of primary cell cultures resulted in differentiation of AMC into multinucleated myotubes. The myogenic differentiation was associated with expression of skeletal muscle markers: skeletal myosin, skeletal actin, myogenin and MyoD1. Efficiency of myogenic differentiation in AMC cultures was similar to that in skeletal muscle cells. Furthermore, some of differentiated myotubes exhibited contractions in vitro. Our data confirms the sufficiently high myogenic potential and proliferative capacity of AMC and their ability to maintain in vitro proliferation-competent myogenic precursor cells regardless of the passage number.

  1. The oncogenic potential of human cytomegalovirus and breast cancer.

    Directory of Open Access Journals (Sweden)

    Georges eHerbein

    2014-08-01

    Full Text Available Breast cancer is among the leading causes of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Numerous articles indicate that breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses and therapeutic possibilities. The human cytomegalovirus (HCMV is a multifaceted highly host specific betaherpesvirus that is regarded as asymptomatic or mildly pathogenic virus in immunocompetent host. HCMV may cause serious in utero infections as well as acute and chronic complications in immunocompromised individual. The involvement of HCMV in late inflammatory complications underscores its possible role in inflammatory diseases and cancer. HCMV targets a variety of cell types in vivo, including macrophages, epithelial cells, endothelial cells, fibroblasts, stromal cells, neuronal cells, smooth muscle cells, and hepatocytes. HCMV can be detected in the milk after delivery and thereby HCMV could spread to adjacent mammary epithelial cells. HCMV also infects macrophages and induces an atypical M1/M2 phenotype, close to the tumor associated macrophage phenotype, which is associated with the release of cytokines involved in cancer initiation or promotion and breast cancer of poor prognosis. HCMV antigens and DNA have been detected in tissue biopsies of breast cancers and elevation in serum HCMV IgG antibody levels has been reported to precede the development of breast cancer in some women. In this review, we will discuss the potential role of HCMV in the initiation and progression of breast cancer.

  2. Better band gaps for wide-gap semiconductors from a locally corrected exchange-correlation potential that nearly eliminates self-interaction errors

    Science.gov (United States)

    Singh, Prashant; Harbola, Manoj K.; Johnson, Duane D.

    2017-10-01

    This work constitutes a comprehensive and improved account of electronic-structure and mechanical properties of silicon-nitride (Si3 N4 ) polymorphs via van Leeuwen and Baerends (LB) exchange-corrected local density approximation (LDA) that enforces the exact exchange potential asymptotic behavior. The calculated lattice constant, bulk modulus, and electronic band structure of Si3 N4 polymorphs are in good agreement with experimental results. We also show that, for a single electron in a hydrogen atom, spherical well, or harmonic oscillator, the LB-corrected LDA reduces the (self-interaction) error to exact total energy to  ∼10%, a factor of three to four lower than standard LDA, due to a dramatically improved representation of the exchange-potential.

  3. Stewardship and Accountability: Valued Elements in Maximising Human Potential.

    Science.gov (United States)

    Todd, Sally M.

    1998-01-01

    Explains the application of five principles of stewardship to the education of gifted children: (1) teachers/parents teach correct principles; (2) students set their own goals in harmony with these principles; (3) teachers serve students as a source of help; (4) students ask for and receive help when needed; and (5) students give an accounting of…

  4. Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators.

    Science.gov (United States)

    Loo, T W; Clarke, D M

    1997-01-10

    There is growing evidence that abnormal protein folding or trafficking (protein kinesis) leads to diseases. We have used P-glycoprotein as a model protein to develop strategies to overcome defects in protein kinesis. Misprocessed mutants of the human P-glycoprotein are retained in the endoplasmic reticulum as core-glycosylated biosynthetic intermediates and rapidly degraded. Synthesis of the mutant proteins in the presence of drug substrates or modulators such as capsaicin, cyclosporin, vinblastine, or verapamil, however, resulted in the appearance of a fully glycosylated and functional protein at the cell surface. These effects were dose-dependent and occurred within a few hours after the addition of substrate. The ability to facilitate processing of the misfolded mutants appeared to be independent of the cell lines used and location of the mutation. P-glycoproteins with mutations in transmembrane segments, extracellular or cytoplasmic loops, the nucleotide-binding domains, or the linker region were processed to the fully mature form in the presence of these substrates. These drug substrates or modulators acted as specific chemical chaperones for P-glycoprotein because they were ineffective on the deltaF508 mutant of cystic fibrosis transmembrane conductance regulator. Therefore, one possible strategy to prevent protein misfolding is to carry out synthesis in the presence of specific substrates or modulators of the protein.

  5. Is there a relationship between dietary MSG and [corrected] obesity in animals or humans?

    Science.gov (United States)

    Brosnan, John T; Drewnowski, Adam; Friedman, Mark I

    2014-09-01

    The sodium salt of glutamate (monosodium glutamate; MSG) imparts a savory/meaty taste to foods, and has been used as a flavoring agent for millennia. Past research on MSG/glutamate has evaluated its physiologic, metabolic and behavioral actions, and its safety. Ingested MSG has been found to be safe, and to produce no remarkable effects, except on taste. However, some recent epidemiologic and animal studies have associated MSG use with obesity and aberrations in fat metabolism. Reported effects are usually attributed to direct actions of ingested MSG in brain. As these observations conflict with past MSG research findings, a symposium was convened at the 13th International Congress on Amino Acids, Peptides and Proteins to discuss them. The principal conclusions were: (1) the proposed link between MSG intake and weight gain is likely explained by co-varying environmental factors (e.g., diet, physical activity) linked to the "nutrition transition" in developing Asian countries. (2) Controlled intervention studies adding MSG to the diet of animals and humans show no effect on body weight. (3) Hypotheses positing dietary MSG effects on body weight involve results from rodent MSG injection studies that link MSG to actions in brain not applicable to MSG ingestion studies. The fundamental reason is that glutamate is metabolically compartmentalized in the body, and generally does not passively cross biologic membranes. Hence, almost no ingested glutamate/MSG passes from gut into blood, and essentially none transits placenta from maternal to fetal circulation, or crosses the blood-brain barrier. Dietary MSG, therefore, does not gain access to brain. Overall, it appears that normal dietary MSG use is unlikely to influence energy intake, body weight or fat metabolism.

  6. Reversible femtosecond laser-assisted myopia correction: a non-human primate study of lenticule re-implantation after refractive lenticule extraction.

    Directory of Open Access Journals (Sweden)

    Andri K Riau

    Full Text Available LASIK (laser-assisted in situ keratomileusis is a common laser refractive procedure for myopia and astigmatism, involving permanent removal of anterior corneal stromal tissue by excimer ablation beneath a hinged flap. Correction of refractive error is achieved by the resulting change in the curvature of the cornea and is limited by central corneal thickness, as a thin residual stromal bed may result in biomechanical instability of the cornea. A recently developed alternative to LASIK called Refractive Lenticule Extraction (ReLEx utilizes solely a femtosecond laser (FSL to incise an intrastromal refractive lenticule (RL, which results in reshaping the corneal curvature and correcting the myopia and/or astigmatism. As the RL is extracted intact in the ReLEx, we hypothesized that it could be cryopreserved and re-implanted at a later date to restore corneal stromal volume, in the event of keratectasia, making ReLEx a potentially reversible procedure, unlike LASIK. In this study, we re-implanted cryopreserved RLs in a non-human primate model of ReLEx. Mild intrastromal haze, noted during the first 2 weeks after re-implantation, subsided after 8 weeks. Refractive parameters including corneal thickness, anterior curvature and refractive error indices were restored to near pre-operative values after the re-implantation. Immunohistochemistry revealed no myofibroblast formation or abnormal collagen type I expression after 8 weeks, and a significant attenuation of fibronectin and tenascin expression from week 8 to 16 after re-implantation. In addition, keratocyte re-population could be found along the implanted RL interfaces. Our findings suggest that RL cryopreservation and re-implantation after ReLEx appears feasible, suggesting the possibility of potential reversibility of the procedure, and possible future uses of RLs in treating other corneal disorders and refractive errors.

  7. [Analysis, identification and correction of some errors of model refseqs appeared in NCBI Human Gene Database by in silico cloning and experimental verification of novel human genes].

    Science.gov (United States)

    Zhang, De-Li; Ji, Liang; Li, Yan-Da

    2004-05-01

    We found that human genome coding regions annotated by computers have different kinds of many errors in public domain through homologous BLAST of our cloned genes in non-redundant (nr) database, including insertions, deletions or mutations of one base pair or a segment in sequences at the cDNA level, or different permutation and combination of these errors. Basically, we use the three means for validating and identifying some errors of the model genes appeared in NCBI GENOME ANNOTATION PROJECT REFSEQS: (I) Evaluating the support degree of human EST clustering and draft human genome BLAST. (2) Preparation of chromosomal mapping of our verified genes and analysis of genomic organization of the genes. All of the exon/intron boundaries should be consistent with the GT/AG rule, and consensuses surrounding the splice boundaries should be found as well. (3) Experimental verification by RT-PCR of the in silico cloning genes and further by cDNA sequencing. And then we use the three means as reference: (1) Web searching or in silico cloning of the genes of different species, especially mouse and rat homologous genes, and thus judging the gene existence by ontology. (2) By using the released genes in public domain as standard, which should be highly homologous to our verified genes, especially the released human genes appeared in NCBI GENOME ANNOTATION PROJECT REFSEQS, we try to clone each a highly homologous complete gene similar to the released genes in public domain according to the strategy we developed in this paper. If we can not get it, our verified gene may be correct and the released gene in public domain may be wrong. (3) To find more evidence, we verified our cloned genes by RT-PCR or hybrid technique. Here we list some errors we found from NCBI GENOME ANNOTATION PROJECT REFSEQs: (1) Insert a base in the ORF by mistake which causes the frame shift of the coding amino acid. In detail, abase in the ORF of a gene is a redundant insertion, which causes a reading frame

  8. Potential benefits of second-generation human papillomavirus vaccines.

    Directory of Open Access Journals (Sweden)

    Sorapop Kiatpongsan

    Full Text Available BACKGROUND: Current prophylactic vaccines against human papillomavirus (HPV target two oncogenic types (16 and 18 that contribute to 70% of cervical cancer cases worldwide. Our objective was to quantify the range of additional benefits conferred by second-generation HPV prophylactic vaccines that are expected to expand protection to five additional oncogenic types (31, 33, 45, 52 and 58. METHODS: A microsimulation model of HPV and cervical cancer calibrated to epidemiological data from two countries (Kenya and Uganda was used to estimate reductions in lifetime risk of cervical cancer from the second-generation HPV vaccines. We explored the independent and joint impact of uncertain factors (i.e., distribution of HPV types, co-infection with multiple HPV types, and unidentifiable HPV types in cancer and vaccine properties (i.e., cross-protection against non-targeted HPV types, compared against currently-available vaccines. RESULTS: Assuming complete uptake of the second-generation vaccine, reductions in lifetime cancer risk were 86.3% in Kenya and 91.8% in Uganda, representing an absolute increase in cervical cancer reduction of 26.1% in Kenya and 17.9% in Uganda, compared with complete uptake of current vaccines. The range of added benefits was 19.6% to 29.1% in Kenya and 14.0% to 19.5% in Uganda, depending on assumptions of cancers attributable to multiple HPV infections and unidentifiable HPV types. These effects were blunted in both countries when assuming vaccine cross-protection with both the current and second-generation vaccines. CONCLUSION: Second-generation HPV vaccines that protect against additional oncogenic HPV types have the potential to improve cervical cancer prevention. Co-infection with multiple HPV infections and unidentifiable HPV types can influence vaccine effectiveness, but the magnitude of effect may be moderated by vaccine cross-protective effects. These benefits must be weighed against the cost of the vaccines in future

  9. The potential of using meteorological data to correct for water surface roughness impacts on soil moisture retrieval in the Arctic

    Science.gov (United States)

    Högström, Elin; Bartsch, Annett

    2017-04-01

    Permafrost temperatures have risen significantly over the past two to three decades, and the Arctic, which to a large extent is underlain by permafrost, is expected to warm rapidly compared to the global mean temperature until the end of the 21st century. In remote areas that are difficult to access for ground measurements, such as the Arctic, satellite-derived data are essential. For permafrost studies in particular, satellite derived soil moisture data is one important parameter which is needed for modelling purposes. To assess the applicability of such data at high latitudes has been given little attention but recent studies have pointed out that seasonal land cover variations and the presence of small water bodies. The presence of small water bodies is characteristic for the Arctic and we expect it to cause complications for soil moisture retrieval from satellite data in these regions. In the present study, we hypothesize that a bias related to water fraction is caused by variations in the water surface roughness (wind, precipitation). The impact is quantified for the active microwave remote sensing instrument Metop Advanced Scatterometer (ASCAT) by investigating the higher spatial resolution synthetic aperture radar (SAR) data acquired by ENVISAT Advanced SAR. The bias is calculated as an average over time for 11 sites across the Siberian Arctic. It is concluded that a water fraction higher than 20% causes a bias of more than 10% relative surface soil moisture. Comparisons with in situ collected meteorological data showed that the bias to a great extent could be attributed to the wind and therefore a bias correction was developed based on this. The wind correction was applied and evaluated with in-situ soil moisture data, which were available from one of the sites: the Lena Delta. The results from the correction were weak, which is likely explained by the fact that the water surfaces at this specific site mainly correspond to rivers: variations in discharge

  10. The mesenchymal stem cells derived from transgenic mice carrying human coagulation factor VIII can correct phenotype in hemophilia A mice.

    Science.gov (United States)

    Wang, Qing; Gong, Xiuli; Gong, Zhijuan; Ren, Xiaoyie; Ren, Zhaorui; Huang, Shuzhen; Zeng, Yitao

    2013-12-20

    Hemophilia A (HA) is an inherited X-linked recessive bleeding disorder caused by coagulant factor VIII (FVIII) deficiency. Previous studies showed that introduction of mesenchymal stem cells (MSCs) modified by FVIII-expressing retrovirus may result in phenotypic correction of HA animals. This study aimed at the investigation of an alternative gene therapy strategy that may lead to sustained FVIII transgene expression in HA mice. B-domain-deleted human FVIII (hFVIIIBD) vector was microinjected into single-cell embryos of wild-type mice to generate a transgenic mouse line, from which hFVIIIBD-MSCs were isolated, followed by transplantation into HA mice. RT-PCR and real-time PCR analysis demonstrated the expression of hFVIIIBD in multi-organs of recipient HA mice. Immunohistochemistry showed the presence of hFVIIIBD positive staining in multi-organs of recipient HA mice. ELISA indicated that plasma hFVIIIBD level in recipient mice reached its peak (77 ng/mL) at the 3rd week after implantation, and achieved sustained expression during the 5-week observation period. Plasma FVIII activities of recipient HA mice increased from 0% to 32% after hFVIIIBD-MSCs transplantation. APTT (activated partial thromboplastin time) value decreased in hFVIIIBD-MSCs transplanted HA mice compared with untreated HA mice (45.5 s vs. 91.3 s). Our study demonstrated an effective phenotypic correction in HA mice using genetically modified MSCs from hFVIIIBD transgenic mice. Copyright © 2013. Published by Elsevier Ltd.

  11. POTENTIAL FOR GULLS TO TRANSPORT BACTERIA FROM HUMAN WASTE SITES

    Science.gov (United States)

    This study was designed as a first step in assessing whether gulls visiting human waste sites can acquire human microorganisms and distribute them across the coastal landscape. Beaches, landfills, and a lagoon of treated wastewater located in a coastal Lake Michigan county were t...

  12. Efficient replication of the novel human betacoronavirus EMC on primary human epithelium highlights its zoonotic potential.

    Science.gov (United States)

    Kindler, Eveline; Jónsdóttir, Hulda R; Muth, Doreen; Hamming, Ole J; Hartmann, Rune; Rodriguez, Regulo; Geffers, Robert; Fouchier, Ron A M; Drosten, Christian; Müller, Marcel A; Dijkman, Ronald; Thiel, Volker

    2013-02-19

    The recent emergence of a novel human coronavirus (HCoV-EMC) in the Middle East raised considerable concerns, as it is associated with severe acute pneumonia, renal failure, and fatal outcome and thus resembles the clinical presentation of severe acute respiratory syndrome (SARS) observed in 2002 and 2003. Like SARS-CoV, HCoV-EMC is of zoonotic origin and closely related to bat coronaviruses. The human airway epithelium (HAE) represents the entry point and primary target tissue for respiratory viruses and is highly relevant for assessing the zoonotic potential of emerging respiratory viruses, such as HCoV-EMC. Here, we show that pseudostratified HAE cultures derived from different donors are highly permissive to HCoV-EMC infection, and by using reverse transcription (RT)-PCR and RNAseq data, we experimentally determined the identity of seven HCoV-EMC subgenomic mRNAs. Although the HAE cells were readily responsive to type I and type III interferon (IFN), we observed neither a pronounced inflammatory cytokine nor any detectable IFN responses following HCoV-EMC, SARS-CoV, or HCoV-229E infection, suggesting that innate immune evasion mechanisms and putative IFN antagonists of HCoV-EMC are operational in the new host. Importantly, however, we demonstrate that both type I and type III IFN can efficiently reduce HCoV-EMC replication in HAE cultures, providing a possible treatment option in cases of suspected HCoV-EMC infection. IMPORTANCE A novel human coronavirus, HCoV-EMC, has recently been described to be associated with severe respiratory tract infection and fatalities, similar to severe acute respiratory syndrome (SARS) observed during the 2002-2003 epidemic. Closely related coronaviruses replicate in bats, suggesting that, like SARS-CoV, HCoV-EMC is of zoonotic origin. Since the animal reservoir and circumstances of zoonotic transmission are yet elusive, it is critically important to assess potential species barriers of HCoV-EMC infection. An important first

  13. Murine and human CFTR exhibit different sensitivities to CFTR potentiators

    OpenAIRE

    Cui, Guiying; McCarty, Nael A.

    2015-01-01

    Development of therapeutic molecules with clinical efficacy as modulators of defective CFTR includes efforts to identify potentiators that can overcome or repair the gating defect in mutant CFTR channels. This has taken a great leap forward with the identification of the potentiator VX-770, now available to patients as “Kalydeco.” Other small molecules with different chemical structure also are capable of potentiating the activity of either wild-type or mutant CFTR, suggesting that there are ...

  14. Therapeutic potentials of human embryonic stem cells in Parkinson's disease

    National Research Council Canada - National Science Library

    Newman, Mary B; Bakay, Roy A E

    2008-01-01

    .... The isolation, differentiation, and long-term cultivation of human embryonic stem cells and the therapeutic research discovery made in relation to the beneficial properties of neurotrophic and neural...

  15. Potential Therapy for Neisseria Gonorrhoeae Infections With Human Chorionic Gonadotropin.

    Science.gov (United States)

    Rao, C V

    2015-12-01

    The scientific evidence suggests that Neisseria gonorrhoeae (NG) infects human fallopian tubes by molecular mimicry in which pathogens act like a ligand to bind to epithelial cell surface human chorionic gonadotrophin (hCG)/luteinizing hormone (LH) receptors. The hCG-like molecule has been identified as ribosomal protein L12 in NG coat surface. Human fallopian tube epithelial cells have been shown to contain functional hCG/LH receptors. As previously shown in human fallopian tube organ and cell culture studies, cellular invasion and infection can be prevented by exposing the cells to excess hCG, which would outnumber and outcompete NG for receptor binding. Based on these data, we suggest testing hCG in clinical trials on infected women.

  16. CD56 marks human dendritic cell subsets with cytotoxic potential

    NARCIS (Netherlands)

    Roothans, D.; Smits, E.; Lion, E.; Tel, J.; Anguille, S.

    2013-01-01

    Human plasmacytoid and myeloid dendritic cells (DCs), when appropriately stimulated, can express the archetypal natural killer (NK)-cell surface marker CD56. In addition to classical DC functions, CD56+ DCs are endowed with an unconventional cytotoxic capacity.

  17. Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A.

    Science.gov (United States)

    Zanolini, Diego; Merlin, Simone; Feola, Maria; Ranaldo, Gabriella; Amoruso, Angela; Gaidano, Gianluca; Zaffaroni, Mauro; Ferrero, Alessandro; Brunelleschi, Sandra; Valente, Guido; Gupta, Sanjeev; Prat, Maria; Follenzi, Antonia

    2015-07-01

    A large fraction of factor VIII in blood originates from liver sinusoidal endothelial cells although extrahepatic sources also contribute to plasma factor VIII levels. Identification of cell-types other than endothelial cells with the capacity to synthesize and release factor VIII will be helpful for therapeutic approaches in hemophilia A. Recent cell therapy and bone marrow transplantation studies indicated that Küpffer cells, monocytes and mesenchymal stromal cells could synthesize factor VIII in sufficient amount to ameliorate the bleeding phenotype in hemophilic mice. To further establish the role of blood cells in expressing factor VIII, we studied various types of mouse and human hematopoietic cells. We identified factor VIII in cells isolated from peripheral and cord blood, as well as bone marrow. Co-staining for cell type-specific markers verified that factor VIII was expressed in monocytes, macrophages and megakaryocytes. We additionally verified that factor VIII was expressed in liver sinusoidal endothelial cells and endothelial cells elsewhere, e.g., in the spleen, lungs and kidneys. Factor VIII was well expressed in sinusoidal endothelial cells and Küpffer cells isolated from human liver, whereas by comparison isolated human hepatocytes expressed factor VIII at very low levels. After transplantation of CD34(+) human cord blood cells into NOD/SCIDγNull-hemophilia A mice, fluorescence activated cell sorting of peripheral blood showed >40% donor cells engrafted in the majority of mice. In these animals, plasma factor VIII activity 12 weeks after cell transplantation was up to 5% and nine of 12 mice survived after a tail clip-assay. In conclusion, hematopoietic cells, in addition to endothelial cells, express and secrete factor VIII: this information should offer further opportunities for understanding mechanisms of factor VIII synthesis and replenishment.

  18. Water graphene contact surface investigated by pairwise potentials from force-matching PAW-PBE with dispersion correction

    Science.gov (United States)

    Li, Jicun; Wang, Feng

    2017-02-01

    A pairwise additive atomistic potential was developed for modeling liquid water on graphene. The graphene-water interaction terms were fit to map the PAW-PBE-D3 potential energy surface using the adaptive force matching method. Through condensed phase force matching, the potential developed implicitly considers the many-body effects of water. With this potential, the graphene-water contact angle was determined to be 86° in good agreement with a recent experimental measurement of 85° ± 5° on fully suspended graphene. Furthermore, the PAW-PBE-D3 based model was used to study contact line hysteresis. It was found that the advancing and receding contact angles of water do agree on pristine graphene, however a long simulation time was required to reach the equilibrium contact angle. For water on suspended graphene, sharp peaks in the water density profile disappear when the flexibility of graphene was explicitly considered. The water droplet induces graphene to wrap around it leading to a slightly concave contact interface.

  19. Accuracy of geometries : influence of basis set, exchange-correlation potential, inclusion of core electrons, and relativistic corrections

    NARCIS (Netherlands)

    Swart, M; Snijders, JG

    The geometries of a set of small molecules were optimized using eight different exchange-correlation (xc) potentials in a few different basis sets of Slater-type orbitals, ranging from a minimal basis (I) to a triple-zeta valence basis plus double polarization functions (VII). This enables a

  20. Lentivirus-mediated gene transfer of uroporphyrinogen III synthase fully corrects the porphyric phenotype in human cells.

    Science.gov (United States)

    Géronimi, F; Richard, E; Lamrissi-Garcia, I; Lalanne, M; Ged, C; Redonnet-Vernhet, I; Moreau-Gaudry, F; de Verneuil, H

    2003-05-01

    Congenital erythropoietic porphyria (CEP) is an inherited disease due to a deficiency in the uroporphyrinogen III synthase, the fourth enzyme of the heme biosynthesis pathway. It is characterized by accumulation of uroporphyrin I in the bone marrow, peripheral blood and other organs. The prognosis of CEP is poor, with death often occurring early in adult life. For severe transfusion-dependent cases, when allogeneic cell transplantation cannot be performed, the autografting of genetically modified primitive/stem cells may be the only alternative. In vitro gene transfer experiments have documented the feasibility of gene therapy via hematopoietic cells to treat this disease. In the present study lentiviral transduction of porphyric cell lines and primary CD34(+) cells with the therapeutic human uroporphyrinogen III synthase (UROS) cDNA resulted in both enzymatic and metabolic correction, as demonstrated by the increase in UROS activity and the suppression of porphyrin accumulation in transduced cells. Very high gene transfer efficiency (up to 90%) was achieved in both cell lines and CD34(+) cells without any selection. Expression of the transgene remained stable over long-term liquid culture. Furthermore, gene expression was maintained during in vitro erythroid differentiation of CD34(+) cells. Therefore the use of lentiviral vectors is promising for the future treatment of CEP patients by gene therapy.

  1. Nephroprotective Potential of Human Albumin Infusion: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Christian J. Wiedermann

    2015-01-01

    Full Text Available Albumin infusion improves renal function in cirrhosis; however, mechanisms are incompletely understood. In clinical practice, human albumin is used in various intensive care unit indications to deal with a wide range of problems, from volume replacement in hypovolemic shock, or sepsis, to treatment of ascites in patients with liver cirrhosis. Against the background of the results of recent studies on the use of human albumin in septic patients, the importance of the natural colloid in these critically ill patients is being redefined. In addition to the hemodynamic effects of administration of human albumin impacting on sympathetic tone, attention is being paid to other effects in which its pharmacodynamics is associated with the physiological importance of endogenous albumin. The morbidity and mortality data discussed in this paper support the importance of both the hemodynamic and the pharmacological effects of the administration of human albumin in various indications. The contribution that human albumin could make towards the maintenance of renal function in the course and treatment of severe sepsis and cirrhosis of the liver is the subject of this narrative review.

  2. Correction: Van Beek, J. et al. Stem Water Potential Monitoring in Pear Orchards through WorldView-2 Multispectral Imagery. Remote Sens. 2013, 5, 6647–6666

    Directory of Open Access Journals (Sweden)

    Jonathan Van Beek

    2014-02-01

    Full Text Available The suitability of high resolution satellite imagery to provide the water status in orchard crops, i.e. stem water potential (Ψstem was evaluated in [1]. However, the contribution of a number of collaborators was not properly acknowledged. Pieter Janssens, Wendy Odeurs, Hilde Vandendriessche and Tom Deckers all provided a substantial contribution to the conception and the design of the work. They furthermore had a leading role in the acquisition, processing, analysis, and interpretation of the reference evapotranspiration (ETo and Ψstem data. The article [1] would not have been possible without their valuable input, and the authors would like to correct the authors list as follows.

  3. Methanol clusters (CH3OH)n: putative global minimum-energy structures from model potentials and dispersion-corrected density functional theory.

    Science.gov (United States)

    Kazachenko, Sergey; Bulusu, Satya; Thakkar, Ajit J

    2013-06-14

    Putative global minima are reported for methanol clusters (CH3OH)n with n ≤ 15. The predictions are based on global optimization of three intermolecular potential energy models followed by local optimization and single-point energy calculations using two variants of dispersion-corrected density functional theory. Recurring structural motifs include folded and/or twisted rings, folded rings with a short branch, and stacked rings. Many of the larger structures are stabilized by weak C-H···O bonds.

  4. The Potential of the Human Connectome as a Biomarker of Brain Disease

    Directory of Open Access Journals (Sweden)

    Marcus eKaiser

    2013-08-01

    Full Text Available The human connectome at the level of fiber tracts between brain regions has been shown to differ in patients with brain disorders compared to healthy control groups. Nonetheless, there is a potentially large number of different network organizations for individual patients that could lead to cognitive deficits prohibiting correct diagnosis. Therefore changes that can distinguish groups might not be sufficient to diagnose the disease that an individual patient suffers from and to indicate the best treatment option for that patient. We describe the challenges introduced by the large variability of connectomes within healthy subjects and patients and outline three common strategies to use connectomes as biomarkers of brain diseases. Finally, we propose a fourth option in using models of simulated brain activity (the dynamic connectome based on structural connectivity rather than the structure (connectome itself as a biomarker of disease. Dynamic connectomes, in addition to currently used structural, functional, or effective connectivity, could be an important future biomarker for clinical applications.

  5. Human reporter genes: potential use in clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Serganova, Inna [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Ponomarev, Vladimir [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Blasberg, Ronald [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States)], E-mail: blasberg@neuro1.mskcc.org

    2007-10-15

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  6. CORRECTION OF POTENTIALLY MODIFIED RISK FACTORS IN THE HEMODIALYSIS : STANDARDS OF TREATMENT AND INDIVIDUALISED PROGRAMS OF DIALYSIS

    Directory of Open Access Journals (Sweden)

    I. L. Kuchma

    2015-05-01

    Full Text Available In the effect prognosis of dialysis a possible adjustment of the modified potential death risk factors of patients who are on renal replacement therapy by hemodialysis techniques are discussed. The conclusions about the possibility of modern dialysis techniques to effectively influence on arterial hypertension of patients with chronic kidney disease stage 5 - D and the need for further study in order to develop treatment standards using mathematical models for individualised dialysis programs.

  7. Transfection of the cloned human excision repair gene ERCC-1 to UV-sensitive CHO mutants only corrects the repair defect in complementation group 2 mutants.

    NARCIS (Netherlands)

    M. van Duin (Mark); J.H. Janssen; J. de Wit (Jan); J.H.J. Hoeijmakers (Jan); L.H. Thompson; D. Bootsma (Dirk); A. Westerveld (Andries)

    1988-01-01

    textabstractThe human DNA-excision repair gene ERCC-1 is cloned by its ability to correct the excision-repair defect of the ultraviolet light- and mitomycin-C-sensitive CHO mutant cell line 43-3B. This mutant is assigned to complementation group 2 of the excision-repair-deficient CHO mutants. In ord

  8. Mapping of potential neurogenic niche in the human temporal lobe

    Directory of Open Access Journals (Sweden)

    Adriano Barreto Nogueira

    2014-10-01

    Full Text Available The subgranular zone (SGZ of the dentate gyrus and the subventricular zone (SVZ are known neurogenic niches in adult mammals. Nonetheless, the existence of neurogenic niches in adult humans is controversial. We hypothesized that mapping neurogenic niches in the human temporal lobe could clarify this issue. Neurogenic niches and neurogenesis were investigated in 28 temporal lobes via immunostaining for nestin and doublecortin (DCX, respectively. Nestin was observed in a continuous layer formed by the SVZ, the subpial zone of the medial temporal lobe and the SGZ, terminating in the subiculum. In the subiculum, remarkable DCX expression was observed through the principal efferent pathway of the hippocampus to the fimbria. A possible explanation for the results is that the SVZ, the subpial zone of the medial temporal lobe and the SGZ form a unit containing neural stem cells that differentiate into neurons in the subiculum. Curiously, the area previously identified as the human rostral migratory stream may in truth be the fornix, which contains axons that originate in the subiculum. This study suggests that neurogenesis may occur in an orchestrated manner in a broad area of the human temporal lobe.

  9. Heavy metals in vegetables and potential risk for human health

    Directory of Open Access Journals (Sweden)

    Fernando Guerra

    2012-02-01

    Full Text Available Ingestion of vegetables containing heavy metals is one of the main ways in which these elements enter the human body. Once entered, heavy metals are deposited in bone and fat tissues, overlapping noble minerals. Slowly released into the body, heavy metals can cause an array of diseases. This study aimed to investigate the concentrations of cadmium, nickel, lead, cobalt and chromium in the most frequently consumed foodstuff in the São Paulo State, Brazil and to compare the heavy metal contents with the permissible limits established by the Brazilian legislation. A value of intake of heavy metals in human diets was also calculated to estimate the risk to human health. Vegetable samples were collected at the São Paulo General Warehousing and Centers Company, and the heavy metal content was determined by atomic absorption spectrophotometry. All sampled vegetables presented average concentrations of Cd and Ni lower than the permissible limits established by the Brazilian legislation. Pb and Cr exceeded the limits in 44 % of the analyzed samples. The Brazilian legislation does not establish a permissible limit for Co contents. Regarding the consumption habit of the population in the São Paulo State, the daily ingestion of heavy metals was below the oral dose of reference, therefore, consumption of these vegetables can be considered safe and without risk to human health.

  10. [Human babesiosis - a rare but potentially dangerous zoonosis].

    Science.gov (United States)

    Hildebrandt, A; Hunfeld, K-P

    2014-05-01

    Human babesiosis is caused by the intraerythrocytic parasite of the genus Babesia (phylum Apicomplexa). Humans are commonly infected by the bite of Ixodid ticks. Rarely, transmission does occur perinatal or via contaminated blood transfusion. There is only insufficient data available on the clinical relevance in Europe, whereas there are known endemic states in the United States with an increasing importance of the disease in transfusion medicine. The following article gives an overview of the situation in Germany. Human babesiosis is a zoonotic disease with a worldwide increasing importance according to the increasing number of immunocompromised patients. Clinical symptoms have a wide range from asymptomatic to severe and letal cases. So far, the detection of the parasites in ticks and seroepidemiological data in Europe identified 3 humanpathogenic species: B. microti, B. divergens und B. venatorum (EU1-3). The relative small number of approximately 50 documented human cases is probably due to the lack of knowledge of the disease and the availability of diagnostic tools. Comprehensive systematic investigations of the prevalence in ticks, seroepidemiological data and improved diagnostic tests are urgently needed to evaluate the importance of the parasite.

  11. Untapped Potential of Disordered Proteins in Current Druggable Human Proteome.

    Science.gov (United States)

    Hu, Gang; Wu, Zhonghua; Wang, Kui; Uversky, Vladimir N; Kurgan, Lukasz

    2016-01-01

    Current efforts in design and characterization of drugs often rely on the structure of their protein targets. However, a large fraction of proteins lack unique 3-D structures and exist as highly dynamic structural ensembles. These intrinsically disordered proteins are involved in pathogenesis of various human diseases and are highly abundant in eukaryotes. Based on a comprehensive analysis of the current druggable human proteome covering 12 drug classes and 18 major classes of drug targets we show a significant bias toward high structural coverage and low abundance of intrinsic disorder. We review reasons for this bias including widespread use of the structural information in various stages of drug development and characterization process and difficulty with attaining structures for the intrinsically disordered proteins. We also discuss future of intrinsically disordered proteins as drug targets. Given the overall high disorder content of the human proteome and current bias of the druggable human proteome toward structural proteins, it is inevitable that disordered proteins will have to raise up on the list of prospective drug targets. The protein disorder-assisted drug design can draw from current rational drug design techniques and would also need novel approaches that no longer rely on a unique protein structure.

  12. Potential immunomodulatory effects of latent toxoplasmosis in humans

    Directory of Open Access Journals (Sweden)

    Stříž Ilja

    2011-10-01

    Full Text Available Abstract Background About 30% of the population worldwide are infected with the protozoan parasite Toxoplasma gondii. Latent toxoplasmosis has many specific behavioral and physiological effects on the human organism. Modified reactivity of the immune system has been suggested to play a key role in many of these effects. For example, the immunosuppression hypothesis explains the higher probability of the birth of male offspring observed in Toxoplasma-positive humans and mice by the protection of the (more immunogenic male embryos against abortion. Methods Here we searched for indices of immunosuppression in Toxoplasma-positive subjects by comparing clinical records of immunology outpatients. Results Our cohort study showed that the male patients with latent toxoplasmosis had decreased and the Toxoplasma-positive women had increased leukocyte, NK-cell and monocyte counts in comparison with controls. The B-cell counts were reduced in both Toxoplasma-positive men and women. The difference between Toxoplasma-positive and Toxoplasma-negative subjects diminished with the decline of the specific Toxoplasma antibody titre (a proxy for the length of infection, which is consistent with the observed decreasing strength of the effect of latent toxoplasmosis on human reproduction. The prevalence of toxoplasmosis in 128 male patients was unusually low (10.9% which contrasted with normal prevalence in 312 female patients (23.7% and in general population Prague (20-30%. Conclusions Latent toxoplasmosis has immunomodulatory effects in human and probably protects men against some classes of immunopathological diseases. The main limitation of the present study was the absence of the data on the immunoreactivity of immune cells subpopulations. Therefore further studies are needed to search for indices of immunosuppression in human using more specific markers.

  13. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    , with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers......The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities...... at different conduction distances are determined by summation of SFAPs of varying fiber diameters, and differ in this respect, also, from the compound muscle action potential (CMAP) for which conduction velocities are determined by the very fastest fibers in the nerve. The effect and extent of temporal...

  14. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities...... at different conduction distances are determined by summation of SFAPs of varying fiber diameters, and differ in this respect, also, from the compound muscle action potential (CMAP) for which conduction velocities are determined by the very fastest fibers in the nerve. The effect and extent of temporal......, with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers...

  15. Human Amnion Membrane: Potential Applications in Oral and Periodontal Field.

    Science.gov (United States)

    Mohan, Ranjana; Bajaj, Aashima; Gundappa, Mohan

    2017-01-01

    Human amniotic membrane (HAM) is derived from the fetal membranes which consist of the inner amniotic membrane made of single layer of amnion cells fixed to collagen-rich mesenchyme attached to chorion. HAM has low immunogenicity, anti-inflammatory properties and their cells can be isolated without the sacrifice of human embryos. Amniotic membrane has biological properties which are important for the experimental and clinical applications in managing patients of various medical specialties. Abundant, natural and wonderful biomembrane not only protects the foetus but also has various clinical applications in the field of dermatology, ophthalmology, ENT surgery, orthopedics and dental surgery. As it is discarded post-partum it may be useful for regenerative medicine and cell therapy to treat damaged or diseased tissues.

  16. Human Amnion Membrane: Potential Applications in Oral and Periodontal Field

    Science.gov (United States)

    Mohan, Ranjana; Bajaj, Aashima; Gundappa, Mohan

    2017-01-01

    Human amniotic membrane (HAM) is derived from the fetal membranes which consist of the inner amniotic membrane made of single layer of amnion cells fixed to collagen-rich mesenchyme attached to chorion. HAM has low immunogenicity, anti-inflammatory properties and their cells can be isolated without the sacrifice of human embryos. Amniotic membrane has biological properties which are important for the experimental and clinical applications in managing patients of various medical specialties. Abundant, natural and wonderful biomembrane not only protects the foetus but also has various clinical applications in the field of dermatology, ophthalmology, ENT surgery, orthopedics and dental surgery. As it is discarded post-partum it may be useful for regenerative medicine and cell therapy to treat damaged or diseased tissues. PMID:28316944

  17. Potential applications of human saliva as diagnostic fluid.

    Science.gov (United States)

    Castagnola, M; Picciotti, P M; Messana, I; Fanali, C; Fiorita, A; Cabras, T; Calò, L; Pisano, E; Passali, G C; Iavarone, F; Paludetti, G; Scarano, E

    2011-12-01

    The use of human saliva as a diagnostic and prognostic fluid has until recently been somewhat disregarded. Although sample collection is non-invasive, physiological and genetic variations were largely responsible for its infrequent application in the past. Recently, several proteomic studies contributed to partial elucidation of the salivary proteome (more than 2400 protein components have been characterized), both in terms of composition, contributions to whole saliva and genetic/physiological variability. On this basis, is not too optimistic to believe that in the near future human saliva could become a relevant diagnostic fluid. In this review, the characterization by proteomic approaches of new salivary markers in oncology, head and neck carcinoma (oral cavity, oropharynx, larynx, and salivary glands), breast and gastric cancers, salivary gland function and disease, Sjögren syndrome, systemic sclerosis, dental and gingival pathology, systemic, psychiatric and neurological diseases, is described.

  18. Cocoa Polyphenols and Their Potential Benefits for Human Health

    OpenAIRE

    Andújar, I.; Recio, M C; R. M. Giner; Ríos, J. L.

    2012-01-01

    This paper compiles the beneficial effects of cocoa polyphenols on human health, especially with regard to cardiovascular and inflammatory diseases, metabolic disorders, and cancer prevention. Their antioxidant properties may be responsible for many of their pharmacological effects, including the inhibition of lipid peroxidation and the protection of LDL-cholesterol against oxidation, and increase resistance to oxidative stress. The phenolics from cocoa also modify the glycemic response and t...

  19. Introductory Electrochemistry for Kids - Food for Thought, and Human Potential

    Science.gov (United States)

    Stroebel, Gary G.; Myers, Stephanie A.

    1998-02-01

    A simple, inexpensive experiment using fruit, a voltmeter, and wires made of various metals allows children to discover many electrochemical principles including: circuits, series connections, the chemical nature of batteries, electrodes, and potential/voltage. Because the experiment uses familiar, portable, and safe materials, it can be conducted in nearly any location and everyone involved can participate.

  20. F-wave of single firing motor units: correct or misleading criterion of motoneuron excitability in humans?

    Science.gov (United States)

    Kudina, Lydia P; Andreeva, Regina E

    2017-03-01

    Motoneuron excitability is a critical property for information processing during motor control. F-wave (a motoneuronal recurrent discharge evoked by a motor antidromic volley) is often used as a criterion of motoneuron pool excitability in normal and neuromuscular diseases. However, such using of F-wave calls in question. The present study was designed to explore excitability of single low-threshold motoneurons during their natural firing in healthy humans and to ascertain whether F-wave is a correct measure of motoneuronal excitability. Single motor units (MUs) were activated by gentle voluntary muscle contractions. MU peri-stimulus time histograms and motoneuron excitability changes within a target interspike interval were analysed during testing by motor antidromic and Ia-afferent volleys. It was found that F-waves could be occasionally recorded in some low-threshold MUs. However, during evoking F-wave, in contrast with the H-reflex, peri-stimulus time histograms revealed no statistically significant increase in MU discharge probability. Moreover, surprisingly, motoneurons appeared commonly incapable to fire a recurrent discharge within the most excitable part of a target interval. Thus, the F-wave, unlike the H-reflex, is the incorrect criterion of motoneuron excitability resulting in misleading conclusions. However, it does not exclude the validity of the F-wave as a clinical tool for other aims. It was concluded that the F-wave was first explored in low-threshold MUs during their natural firing. The findings may be useful at interpretations of changes in the motoneuron pool excitability in neuromuscular diseases.

  1. Shorter telomere length - A potential susceptibility factor for HIV-associated neurocognitive impairments in South African women [corrected].

    Directory of Open Access Journals (Sweden)

    Stefanie Malan-Müller

    Full Text Available The neuropathogenesis of the human immunodeficiency virus (HIV may manifest as various neurocognitive impairments (NCI. HIV-positive individuals also have significantly shorter telomere length (TL in peripheral blood mononuclear cells (PBMCs and CD8+ T cells compared to HIV-negative individuals. Additionally, reduced TL has been found to be associated with chronic psychological stress. This study focused on the effects of HIV-infection and chronic stress associated with childhood trauma on telomere length, and investigated whether leukocyte TL (LTL, in particular, represents a risk factor for NCI. Eighty-three HIV-positive and 45 HIV-negative women were assessed for childhood trauma and were subjected to detailed neurocognitive testing. Blood from each participant was used to extract Deoxyribonucleic acid (DNA. Relative LTL were determined by performing real time quantitative PCR reactions as described by Cawthon et al. (2002. As expected, relative LTL in the HIV-positive individuals was significantly shorter than that of HIV-negative individuals (F = 51.56, p = <0.01. Notably, a significant positive correlation was evident between relative LTL and learning performance in the HIV-positive group. In addition, a significant negative correlation was observed between relative LTL and verbal fluency, but this association was only evident in HIV-positive individuals who had experienced trauma. Our results suggest that reduced LTL is associated with worse learning performance in HIV-positive individuals, indicating that TL could act as a susceptibility factor in increasing neurocognitive decline in HIV-infected individuals.

  2. GM-CSF production from human airway smooth muscle cells is potentiated by human serum

    Directory of Open Access Journals (Sweden)

    Maria B. Sukkar

    2000-01-01

    Full Text Available Recent evidence suggests that airway smooth muscle cells (ASMC actively participate in the airway inflammatory process in asthma. Interleukin–1β (IL–1β and tumour necrosis factor–α (TNF–α induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1 allergic asthmatic serum (AAS modulates ASMC mediator release in response to IL–1β and TNF–α, and (2 IL–1β/TNF–α prime ASMC to release mediators in response to AAS. IL–5 and GMCSF were quantified by ELISA in culture supernatants of; (1 ASMC pre-incubated with either AAS, non-allergic non-asthmatic serum (NAS or MonomedTM (a serum substitute and subsequently stimulated with IL–1β and TNF–α and (2 ASMC stimulated with IL–1β/TNF–α and subsequently exposed to either AAS, NAS or MonomedTM. IL-1g and TNF–α induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pre-incubated with NAS or MonomedTM. IL–1β and TNF–α, however, primed ASMC to release GM-CSF in response to human serum. GM-CSF production following IL–1β/TNF–α and serum exposure (AAS or NAS was significantly greater than that following IL–1β /TNF–α and MonomedTM exposure or IL–1β/TNF–α exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage.

  3. Black holes as gases of punctures with a chemical potential: Bose-Einstein condensation and logarithmic corrections to the entropy

    CERN Document Server

    Asin, Olivier; Geiller, Marc; Noui, Karim; Perez, Alejandro

    2014-01-01

    We study the thermodynamical properties of black holes when described as gases of indistinguishable punctures with a chemical potential. In this picture, which arises from loop quantum gravity, the black hole microstates are defined by finite families of half-integers spins coloring the punctures, and the near-horizon energy measured by quasi-local stationary observers defines the various thermodynamical ensembles. The punctures carry excitations of quantum geometry in the form of quanta of area, and the total horizon area $a_\\text{H}$ is given by the sum of these microscopic contributions. We assume here that the system satisfies the Bose-Einstein statistics, and that each microstate is degenerate with a holographic degeneracy given by $\\exp\\big(\\lambda a_\\text{H}/\\ell_\\text{Pl}^2\\big)$ and $\\lambda>0$. We analyze in detail the thermodynamical properties resulting from these inputs, and in particular compute the grand canonical entropy. We explain why the requirements that the temperature be fixed to the Unr...

  4. The human oral metaproteome reveals potential biomarkers for caries disease

    DEFF Research Database (Denmark)

    Belda-Ferre, Pedro; Williamson, James; Simón-Soro, Áurea

    2015-01-01

    diversity. Healthy individuals appeared to have significantly higher amounts of L-lactate dehydrogenase and the arginine deiminase system, both implicated in pH buffering. Other proteins found to be at significantly higher levels in healthy individuals were involved in exopolysaccharide synthesis, iron...... metabolism and immune response. We applied multivariate analysis in order to find the minimum set of proteins that better allows discrimination of healthy and caries-affected dental plaque samples, detecting seven bacterial and five human protein functions that allow determining the health status...

  5. Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yung-Lin Chu

    2013-07-01

    Full Text Available Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic 大 蒜 Dà Suàn; Allium sativum, is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.

  6. Leptospirosis in Mexico: Epidemiology and Potential Distribution of Human Cases.

    Directory of Open Access Journals (Sweden)

    Sokani Sánchez-Montes

    Full Text Available Leptospirosis is widespread in Mexico, yet the potential distribution and risk of the disease remain unknown.We analysed morbidity and mortality according to age and gender based on three sources of data reported by the Ministry of Health and the National Institute of Geography and Statics of Mexico, for the decade 2000-2010. A total of 1,547 cases were reported in 27 states, the majority of which were registered during the rainy season, and the most affected age group was 25-44 years old. Although leptospirosis has been reported as an occupational disease of males, analysis of morbidity in Mexico showed no male preference. A total number of 198 deaths were registered in 21 states, mainly in urban settings. Mortality was higher in males (61.1% as compared to females (38.9%, and the case fatality ratio was also increased in males. The overall case fatality ratio in Mexico was elevated (12.8%, as compared to other countries. We additionally determined the potential disease distribution by examining the spatial epidemiology combined with spatial modeling using ecological niche modeling techniques. We identified regions where leptospirosis could be present and created a potential distribution map using bioclimatic variables derived from temperature and precipitation. Our data show that the distribution of the cases was more related to temperature (75% than to precipitation variables. Ecological niche modeling showed predictive areas that were widely distributed in central and southern Mexico, excluding areas characterized by extreme climates.In conclusion, an epidemiological surveillance of leptospirosis is recommended in Mexico, since 55.7% of the country has environmental conditions fulfilling the criteria that favor the presence of the disease.

  7. Amblyomma americanum: a potential vector of human ehrlichiosis.

    Science.gov (United States)

    Anderson, B E; Sims, K G; Olson, J G; Childs, J E; Piesman, J F; Happ, C M; Maupin, G O; Johnson, B J

    1993-08-01

    Polymerase chain reaction primers specific for Ehrlichia chaffeensis were used to amplify DNA from extracts of pooled ticks. Amplification was performed on extracts from 140 pools (1,579 total ticks) consisting of three tick genera collected from five states. The characteristic 389-basepair product was observed after amplification of extracts from seven different pools of adult Amblyomma americanum (117 pools, 1,462 ticks), but not from pools of nymphs. No specific product was observed after amplification of 20 pools (105 ticks) of Dermacentor variabilis and three pools of Ixodes scapularis (12 ticks). Ehrlichia chaffeensis was present in A. americanum at a minimum frequency of > or = 0.48%, suggesting that A. americanum may be a vector of human ehrlichiosis.

  8. Antibacterial potential of three seagrasses against human pathogens

    Institute of Scientific and Technical Information of China (English)

    Rajasekaran Arumugam; Perumal Anantharaman

    2010-01-01

    Objective:To evaluate the antibacterial activity ofHalophila stipulacea (H. stipulacea), Cymodocea serrulata (C. serrulata) andHalodule pinifolia (H. pinifolia) against seven human bacterial pathogens.Methods:The antibacterial activities of the extracts on the various test organisms using disc diffusion method and Minimum Inhibitory Concentraction(MIC).Results:Methanol and chloroform extracts of all the three seagrasses were active against all the tested pathogens, whereas the hexane extract of seagrasses was not active againstStaphylococcus aureus (S. aureus). Antibacterial activity of three seagrass screened, was in the order ofH. pinifolia >H. stipulacea>C. serrulata.Conclusions: This antibacterial studies can further investigated on seagrasses for purification of bioactive substance and its possible utility in disease control.

  9. Cocoa polyphenols and their potential benefits for human health.

    Science.gov (United States)

    Andújar, I; Recio, M C; Giner, R M; Ríos, J L

    2012-01-01

    This paper compiles the beneficial effects of cocoa polyphenols on human health, especially with regard to cardiovascular and inflammatory diseases, metabolic disorders, and cancer prevention. Their antioxidant properties may be responsible for many of their pharmacological effects, including the inhibition of lipid peroxidation and the protection of LDL-cholesterol against oxidation, and increase resistance to oxidative stress. The phenolics from cocoa also modify the glycemic response and the lipid profile, decreasing platelet function and inflammation along with diastolic and systolic arterial pressures, which, taken together, may reduce the risk of cardiovascular mortality. Cocoa polyphenols can also modulate intestinal inflammation through the reduction of neutrophil infiltration and expression of different transcription factors, which leads to decreases in the production of proinflammatory enzymes and cytokines. The phenolics from cocoa may thus protect against diseases in which oxidative stress is implicated as a causal or contributing factor, such as cancer. They also have antiproliferative, antimutagenic, and chemoprotective effects, in addition to their anticariogenic effects.

  10. The potential for new methods to assess human reproductive genotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, M.L.

    1987-09-01

    The immediate prospects are not good for practical methods for measuring the human heritable mutation rate. The methods discussed here range from speculative to impractical, and at best are sensitive enough only for large numbers of subjects. Given the rapid development of DNA methods and the current status of two-dimensional gel electrophoresis, there is some hope that the intermediate prospects may be better. In contrast, the prospects for useful cellular-based male germinal methods seem more promising and immediate. Effective specific locus methods for sperm are already conceivable and may be practical in a few years. Obviously such methods will not predict heritable effects definitively, but they will provide direct information on reproductive genotoxicity and should contribute significantly to many current medical and environmental situations where genetic damage is suspected. 22 refs.

  11. The human urinary exosome as a potential metabolic effector cargo.

    Science.gov (United States)

    Bruschi, Maurizio; Ravera, Silvia; Santucci, Laura; Candiano, Giovanni; Bartolucci, Martina; Calzia, Daniela; Lavarello, Chiara; Inglese, Elvira; Petretto, Andrea; Ghiggeri, Gianmarco; Panfoli, Isabella

    2015-08-01

    Exosomes are nanovesicles, derived from the endocytic pathway, released by most cell types and found in many body fluids, including urine. A variety of exosomal functions have been reported, including transfer of RNA, cell communication, control of apoptosis and protein lifespan. Exosomes from mesenchymal stem cells can rescue bioenergetics of injured cells. Here the urinary exosome proteome, non-urinary exosome proteome and urinome are compared. A consistent number of identified proteins cluster to metabolic functions. Cytoscape software analysis based on biological processes gene ontology database shows that metabolic pathways such as aerobic glycolysis and oxidative phosphorylation have a high probability (p ≤ 0.05) of being expressed and therefore functional. A metabolic function appears to be associated with human urinary exosomes, whose relevance experimental studies can assess.

  12. Potential presence of trihalomethanes in water intended for human consumption

    Directory of Open Access Journals (Sweden)

    C. Lasagna

    2011-01-01

    Full Text Available Since the 1970s it is well known that, though water for human consumption must generally be disinfected before being distributed along the network, the use of chemicals results in the formation of many different Disinfeection By-Products (DBPs. In the case of chlorine-based disinfectants, trihalomethanes (THMs are the most widely studied: the present work first compares some national and international regulations on this subject, then, in the experimental part, compares the results of a test carried out by disinfecting water of different origin collected in three different Italian regions with different amounts of chlorine. Samples were stored at ambient temperature for seven days, then the determination of THMs was carrried out by Purge and Trap extraction coupled with gas cromatography with Electron Capture Detection (ECD. The result obtained are finally compared and discussed.

  13. Technological Dangers and the Potential of Human-Robot Interaction

    DEFF Research Database (Denmark)

    2016-01-01

    watching a soccer game in which our child is one of the players. The question of which team we should cheer for never occurs to the parent. By changing the vantage point to a radical phenomenological perspective, informed by Eastern as well as Western thought, this chapter tests the basis for this type...... technological dangers and opportunities. Finally, aiming for the very limits of the theory, I discuss the contours of a praxis facilitating being-with-robots beyond conceptualization. Basically, this mode of being, pertaining to non-technological HRI, bypasses Heidegger’s warnings, and potentially facilitates...

  14. Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII.

    Science.gov (United States)

    Hu, Chuhong; Cela, Racel G; Suzuki, Masataka; Lee, Brendan; Lipshutz, Gerald S

    2011-02-01

    Neonatal gene therapy is a promising strategy for treating a number of congenital diseases diagnosed shortly after birth as expression of therapeutic proteins during postnatal life may limit the pathologic consequences and result in a potential "cure." Hemophilia A is often complicated by the development of antibodies to recombinant protein resulting in treatment failure. Neonatal administration of vectors may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immaturity. A helper-dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia A knockout mice. Three days later, mice produced high levels of FVIII. Levels declined rapidly with animal growth to 5 wk of age with stable factor VIII expression thereafter to >1 y of age. Decline in factor VIII expression was not related to cell-mediated or humoral responses with lack of development of antibodies to capsid or human factor VIII proteins. Subsequent readministration and augmentation of expression was possible as operational tolerance was established to factor VIII without development of inhibitors; however, protective immunity to adenovirus remained.

  15. Density-Functional Theory with Dispersion-Correcting Potentials for Methane: Bridging the Efficiency and Accuracy Gap between High-Level Wave Function and Classical Molecular Mechanics Methods.

    Science.gov (United States)

    Torres, Edmanuel; DiLabio, Gino A

    2013-08-13

    Large clusters of noncovalently bonded molecules can only be efficiently modeled by classical mechanics simulations. One prominent challenge associated with this approach is obtaining force-field parameters that accurately describe noncovalent interactions. High-level correlated wave function methods, such as CCSD(T), are capable of correctly predicting noncovalent interactions, and are widely used to produce reference data. However, high-level correlated methods are generally too computationally costly to generate the critical reference data required for good force-field parameter development. In this work we present an approach to generate Lennard-Jones force-field parameters to accurately account for noncovalent interactions. We propose the use of a computational step that is intermediate to CCSD(T) and classical molecular mechanics, that can bridge the accuracy and computational efficiency gap between them, and demonstrate the efficacy of our approach with methane clusters. On the basis of CCSD(T)-level binding energy data for a small set of methane clusters, we develop methane-specific, atom-centered, dispersion-correcting potentials (DCPs) for use with the PBE0 density-functional and 6-31+G(d,p) basis sets. We then use the PBE0-DCP approach to compute a detailed map of the interaction forces associated with the removal of a single methane molecule from a cluster of eight methane molecules and use this map to optimize the Lennard-Jones parameters for methane. The quality of the binding energies obtained by the Lennard-Jones parameters we obtained is assessed on a set of methane clusters containing from 2 to 40 molecules. Our Lennard-Jones parameters, used in combination with the intramolecular parameters of the CHARMM force field, are found to closely reproduce the results of our dispersion-corrected density-functional calculations. The approach outlined can be used to develop Lennard-Jones parameters for any kind of molecular system.

  16. Endocannabinoids measurement in human saliva as potential biomarker of obesity.

    Directory of Open Access Journals (Sweden)

    Isabelle Matias

    Full Text Available BACKGROUND: The discovery of the endocannabinoid system and of its role in the regulation of energy balance has significantly advanced our understanding of the physiopathological mechanisms leading to obesity and type 2 diabetes. New knowledge on the role of this system in humans has been acquired by measuring blood endocannabinoids. Here we explored endocannabinoids and related N-acylethanolamines in saliva and verified their changes in relation to body weight status and in response to a meal or to body weight loss. METHODOLOGY/PRINCIPAL FINDINGS: Fasting plasma and salivary endocannabinoids and N-acylethanolamines were measured through liquid mass spectrometry in 12 normal weight and 12 obese, insulin-resistant subjects. Salivary endocannabinoids and N-acylethanolamines were evaluated in the same cohort before and after the consumption of a meal. Changes in salivary endocannabinoids and N-acylethanolamines after body weight loss were investigated in a second group of 12 obese subjects following a 12-weeks lifestyle intervention program. The levels of mRNAs coding for enzymes regulating the metabolism of endocannabinoids, N-acylethanolamines and of cannabinoid type 1 (CB(1 receptor, alongside endocannabinoids and N-acylethanolamines content, were assessed in human salivary glands. The endocannabinoids 2-arachidonoylglycerol (2-AG, N-arachidonoylethanolamide (anandamide, AEA, and the N-acylethanolamines (oleoylethanolamide, OEA and palmitoylethanolamide, PEA were quantifiable in saliva and their levels were significantly higher in obese than in normal weight subjects. Fasting salivary AEA and OEA directly correlated with BMI, waist circumference and fasting insulin. Salivary endocannabinoids and N-acylethanolamines did not change in response to a meal. CB(1 receptors, ligands and enzymes were expressed in the salivary glands. Finally, a body weight loss of 5.3% obtained after a 12-weeks lifestyle program significantly decreased salivary AEA

  17. Mosquitoes as potential bridge vectors of malaria parasites from non-human primates to humans

    NARCIS (Netherlands)

    Verhulst, N.O.; Smallegange, R.C.; Takken, W.

    2012-01-01

    Malaria is caused by Plasmodium parasites which are transmitted by mosquitoes. Until recently, human malaria was considered to be caused by human-specific Plasmodium species. Studies on Plasmodium parasites in non-human primates (NHPs), however, have identified parasite species in gorillas and

  18. Paleopathology of Human Tuberculosis and the Potential Role of Climate

    Directory of Open Access Journals (Sweden)

    Andreas G. Nerlich

    2009-01-01

    Full Text Available Both origin and evolution of tuberculosis and its pathogens (Mycobacterium tuberculosis complex are not fully understood. The paleopathological investigation of human remains offers a unique insight into the molecular evolution and spread including correlative data of the environment. The molecular analysis of material from Egypt (3000–500 BC, Sudan (200–600 AD, Hungary (600–1700 AD, Latvia (1200–1600 AD, and South Germany (1400–1800 AD urprisingly revealed constantly high frequencies of tuberculosis in all different time periods excluding significant environmental influence on tuberculosis spread. The typing of various mycobacteria strains provides evidence for ancestral M. tuberculosis strains in Pre- to early Egyptian dynastic material (3500–2650 BC, while typical M. africanum signatures were detected in a Middle Kingdom tomb (2050–1650 BC. Samples from the New Kingdom to Late Period (1500–500 BC indicated modern M. tuberculosis strains. No evidence was seen for M. bovis in Egyptian material while M. bovis signatures were first identified in Siberian biomaterial dating 2000 years before present. These results contraindicates the theory that M. tuberculosis evolved from M. bovis during early domestication in the region of the “Fertile Crescent,” but supports the scenario that M. tuberculosis probably derived from an ancestral progenitor strain. The environmental influence of this evolutionary scenario deserves continuing intense evaluation.

  19. Human recombinant RNASET2: A potential anti-cancer drug

    Science.gov (United States)

    Roiz, Levava; Smirnoff, Patricia; Lewin, Iris; Shoseyov, Oded; Schwartz, Betty

    2016-01-01

    The roles of cell motility and angiogenetic processes in metastatic spread and tumor aggressiveness are well established and must be simultaneously targeted to maximize antitumor drug potency. This work evaluated the antitumorigenic capacities of human recombinant RNASET2 (hrRNASET2), a homologue of the Aspergillus niger T2RNase ACTIBIND, which has been shown to display both antitumorigenic and antiangiogenic activities. hrRNASET2 disrupted intracellular actin filament and actin-rich extracellular extrusion organization in both CT29 colon cancer and A375SM melanoma cells and induced a significant dose-dependent inhibition of A375SM cell migration. hrRNASET2 also induced full arrest of angiogenin-induced tube formation and brought to a three-fold lower relative HT29 colorectal and A375SM melanoma tumor volume, when compared to Avastin-treated animals. In parallel, mean blood vessel counts were 36.9% lower in hrRNASET2-vs. Avastin-treated mice and survival rates of hrRNASET2-treated mice were 50% at 73 days post-treatment, while the median survival time for untreated animals was 22 days. Moreover, a 60-day hrRNASET2 treatment period reduced mean A375SM lung metastasis foci counts by three-fold when compared to untreated animals. Taken together, the combined antiangiogenic and antitumorigenic capacities of hrRNASET2, seemingly arising from its direct interaction with intercellular and extracellular matrices, render it an attractive anticancer therapy candidate. PMID:27014725

  20. Cocoa Polyphenols and Their Potential Benefits for Human Health

    Directory of Open Access Journals (Sweden)

    I. Andújar

    2012-01-01

    Full Text Available This paper compiles the beneficial effects of cocoa polyphenols on human health, especially with regard to cardiovascular and inflammatory diseases, metabolic disorders, and cancer prevention. Their antioxidant properties may be responsible for many of their pharmacological effects, including the inhibition of lipid peroxidation and the protection of LDL-cholesterol against oxidation, and increase resistance to oxidative stress. The phenolics from cocoa also modify the glycemic response and the lipid profile, decreasing platelet function and inflammation along with diastolic and systolic arterial pressures, which, taken together, may reduce the risk of cardiovascular mortality. Cocoa polyphenols can also modulate intestinal inflammation through the reduction of neutrophil infiltration and expression of different transcription factors, which leads to decreases in the production of proinflammatory enzymes and cytokines. The phenolics from cocoa may thus protect against diseases in which oxidative stress is implicated as a causal or contributing factor, such as cancer. They also have antiproliferative, antimutagenic, and chemoprotective effects, in addition to their anticariogenic effects.

  1. Human recombinant RNASET2: A potential anti-cancer drug.

    Science.gov (United States)

    Roiz, Levava; Smirnoff, Patricia; Lewin, Iris; Shoseyov, Oded; Schwartz, Betty

    2016-01-01

    The roles of cell motility and angiogenetic processes in metastatic spread and tumor aggressiveness are well established and must be simultaneously targeted to maximize antitumor drug potency. This work evaluated the antitumorigenic capacities of human recombinant RNASET2 (hrRNASET2), a homologue of the Aspergillus niger T2RNase ACTIBIND, which has been shown to display both antitumorigenic and antiangiogenic activities. hrRNASET2 disrupted intracellular actin filament and actin-rich extracellular extrusion organization in both CT29 colon cancer and A375SM melanoma cells and induced a significant dose-dependent inhibition of A375SM cell migration. hrRNASET2 also induced full arrest of angiogenin-induced tube formation and brought to a three-fold lower relative HT29 colorectal and A375SM melanoma tumor volume, when compared to Avastin-treated animals. In parallel, mean blood vessel counts were 36.9% lower in hrRNASET2-vs. Avastin-treated mice and survival rates of hrRNASET2-treated mice were 50% at 73 days post-treatment, while the median survival time for untreated animals was 22 days. Moreover, a 60-day hrRNASET2 treatment period reduced mean A375SM lung metastasis foci counts by three-fold when compared to untreated animals. Taken together, the combined antiangiogenic and antitumorigenic capacities of hrRNASET2, seemingly arising from its direct interaction with intercellular and extracellular matrices, render it an attractive anticancer therapy candidate.

  2. MEETC2: Ocean Color Atmospheric Corrections in Coastal Complex Waters Using a Bayesian Latent Class Model and Potential for the Incoming Sentinel 3- OLCI Mission

    Science.gov (United States)

    Saulquin, Bertrand; Fablet, Ronan; Bourg, Ludovic; Mercier, Gregoire; Fanton d'Andon, Odile

    2016-08-01

    From top-of-atmosphere (TOA) observations, atmospheric correction for ocean color inversion aims at distinguishing atmosphere and water contributions. From a methodological point of view, our approach relies on a Bayesian inference using Gaussian Mixture Model prior distributions and reference spectra of aerosol and water reflectance [1].We evaluate our estimates of the sea surface reflectance from the MERIS TOA observations. Using the MERMAID radiometric in-situ dataset, we obtain significant improvements in the estimation of the sea surface reflectance, especially for the 412, 442, 490 and 510 nm bands, compared with the standard ESA MEGS algorithm and the a state-of- the-art neural network approach (C2R). The mean gain value on the relative error for the 13 bands between 412 and 885 nm is of 57% compared with MEGS algorithm and 10% compared with the C2R. We further discuss the potential of MEETC2 for new ESA OLCI / Sentinel 3 mission.

  3. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.

    Directory of Open Access Journals (Sweden)

    Francesca Oltolina

    Full Text Available A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM. We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.

  4. Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types

    Directory of Open Access Journals (Sweden)

    Sisti Stefano

    2008-07-01

    Full Text Available Abstract Background Human papillomavirus (HPV tests are crucial diagnostic tools for the prevention of neoplastic lesions of the uterine cervix. However most commercial methods are designed to detect high-risk (HR HPV types and a limited selection of low-risk ones, thus missing a fair number of intermediate/low-risk types. As a result, many HPV infections remain undiagnosed, generating distrust in virological diagnosis among gynaecologists, who continue to rely preferentially on cytological and colposcopic findings. Results In this study, we tested 6,335 consecutive clinical samples, most of them from Italian patients with cytological abnormalities. The samples, collected in 2000–2007, were analyzed using PCR amplification of a 173–206 bp (depending on HPV type conserved region in the L1 open reading frame, restriction endonuclease analysis and, where required, sequence analysis for type determination. Analysis of a smaller male sample and long term follow-up of a few female subjects was also performed. A total of 2,161 samples tested positive for HPV DNA (32.1%; 21.3% of them were mixed infections. Overall, 59 known and 2 unknown HPV types were detected. Their relative prevalence was calculated; notably, types not clearly identifiable using the most common commercial method accounted for 36% of infections. Clinical findings associated with the underdiagnosed types ranged from H-SIL to low-grade abnormalities, although none of these infections resulted in invasive cancer. Conclusion Given the high prevalence of some underdiagnosed HPV types in the population (principally HPV53, HPV66, HPV84, and HPV87 and their frequent association with cytological abnormalities, techniques capable of detecting and typing them would prove extremely useful.

  5. Dispersion-correcting potentials can significantly improve the bond dissociation enthalpies and noncovalent binding energies predicted by density-functional theory

    Energy Technology Data Exchange (ETDEWEB)

    DiLabio, Gino A., E-mail: Gino.DiLabio@nrc.ca [National Institute for Nanotechnology, National Research Council of Canada, 11421 Saskatchewan Drive, Edmonton, Alberta T6G 2M9 (Canada); Department of Chemistry, University of British Columbia, Okanagan, 3333 University Way, Kelowna, British Columbia V1V 1V7 (Canada); Koleini, Mohammad [National Institute for Nanotechnology, National Research Council of Canada, 11421 Saskatchewan Drive, Edmonton, Alberta T6G 2M9 (Canada); Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2V4 (Canada)

    2014-05-14

    Dispersion-correcting potentials (DCPs) are atom-centered Gaussian functions that are applied in a manner that is similar to effective core potentials. Previous work on DCPs has focussed on their use as a simple means of improving the ability of conventional density-functional theory methods to predict the binding energies of noncovalently bonded molecular dimers. We show in this work that DCPs developed for use with the LC-ωPBE functional along with 6-31+G(2d,2p) basis sets are capable of simultaneously improving predicted noncovalent binding energies of van der Waals dimer complexes and covalent bond dissociation enthalpies in molecules. Specifically, the DCPs developed herein for the C, H, N, and O atoms provide binding energies for a set of 66 noncovalently bonded molecular dimers (the “S66” set) with a mean absolute error (MAE) of 0.21 kcal/mol, which represents an improvement of more than a factor of 10 over unadorned LC-ωPBE/6-31+G(2d,2p) and almost a factor of two improvement over LC-ωPBE/6-31+G(2d,2p) used in conjunction with the “D3” pairwise dispersion energy corrections. In addition, the DCPs reduce the MAE of calculated X-H and X-Y (X,Y = C, H, N, O) bond dissociation enthalpies for a set of 40 species from 3.2 kcal/mol obtained with unadorned LC-ωPBE/6-31+G(2d,2p) to 1.6 kcal/mol. Our findings demonstrate that broad improvements to the performance of DFT methods may be achievable through the use of DCPs.

  6. The end of ignorance multiplying our human potential

    CERN Document Server

    Mighton, John

    2008-01-01

    A revolutionary call for a new understanding of how people learn. The End of Ignorance conceives of a world in which no child is left behind – a world based on the assumption that each child has the potential to be successful in every subject. John Mighton argues that by recognizing the barriers that we have experienced in our own educational development, by identifying the moment that we became disenchanted with a certain subject and forever closed ourselves off to it, we will be able to eliminate these same barriers from standing in the way of our children. A passionate examination of our present education system, The End of Ignorance shows how we all can work together to reinvent the way that we are taught. John Mighton, the author of The Myth of Ability, is the founder of JUMP Math, a system of learning based on the fostering of emergent intelligence. The program has proved so successful an entire class of Grade 3 students, including so-called slow learners, scored over 90% on a Grade 6 math test. A ...

  7. Physical dependence potential of daily tramadol dosing in humans

    Science.gov (United States)

    Lofwall, Michelle R.; Mintzer, Miriam Z.; Bigelow, George E.; Strain, Eric C.

    2011-01-01

    Rationale Tramadol is an atypical, mixed-mechanism analgesic involving both opioid and catecholamine processes that appears to have low abuse potential and may be useful as a treatment for opioid dependence. Objectives The current study assessed the level of physical dependence and opioid blockade efficacy produced by daily maintenance on oral tramadol. Methods Nine residential opioid-dependent adults were maintained on two doses of daily oral tramadol (200 and 800 mg) for approximately 4-week intervals in a randomized, double-blind, crossover design. The acute effects of intramuscular placebo, naloxone (0.25, 0.5, and 1.0 mg), and hydromorphone (1.5, 3.0, and 6.0 mg) were tested under double-blind, randomized conditions. Outcomes included observer- and subject-rated measures and physiologic indices. Results Challenge doses of naloxone resulted in significantly higher mean peak withdrawal scores compared to placebo. Withdrawal intensity from naloxone was generally greater during 800 versus 200 mg/day tramadol maintenance. Mean peak ratings of agonist effects were elevated at higher hydromorphone challenge doses, but did not differ significantly between tramadol doses. Physiologic measures were generally affected by challenge conditions in a dose-dependent manner, with few differences between tramadol maintenance dose conditions. Conclusions Chronic tramadol administration produces dose-related opioid physical dependence, without producing dose-related attenuation of agonist challenge effects. Tramadol may be a useful treatment for patients with low levels of opioid dependence or as a treatment for withdrawal during opioid detoxification, but does not appear to be effective as a maintenance medication due to a lack of opioid cross-tolerance. PMID:20589494

  8. Llama nanoantibodies with therapeutic potential against human norovirus diarrhea.

    Science.gov (United States)

    Garaicoechea, Lorena; Aguilar, Andrea; Parra, Gabriel I; Bok, Marina; Sosnovtsev, Stanislav V; Canziani, Gabriela; Green, Kim Y; Bok, Karin; Parreño, Viviana

    2015-01-01

    Noroviruses are a major cause of acute gastroenteritis, but no vaccines or therapeutic drugs are available. Llama-derived single chain antibody fragments (also called VHH) are small, recombinant monoclonal antibodies of 15 kDa with several advantages over conventional antibodies. The aim of this study was to generate recombinant monoclonal VHH specific for the two major norovirus (NoV) genogroups (GI and GII) in order to investigate their potential as immunotherapy for the treatment of NoV diarrhea. To accomplish this objective, two llamas were immunized with either GI.1 (Norwalk-1968) or GII.4 (MD2004) VLPs. After immunization, peripheral blood lymphocytes were collected and used to generate two VHH libraries. Using phage display technology, 10 VHH clones specific for GI.1, and 8 specific for GII.4 were selected for further characterization. All VHH recognized conformational epitopes in the P domain of the immunizing VP1 capsid protein, with the exception of one GII.4 VHH that recognized a linear P domain epitope. The GI.1 VHHs were highly specific for the immunizing GI.1 genotype, with only one VHH cross-reacting with GI.3 genotype. The GII.4 VHHs reacted with the immunizing GII.4 strain and showed a varying reactivity profile among different GII genotypes. One VHH specific for GI.1 and three specific for GII.4 could block the binding of homologous VLPs to synthetic HBGA carbohydrates, saliva, and pig gastric mucin, and in addition, could inhibit the hemagglutination of red blood cells by homologous VLPs. The ability of Nov-specific VHHs to perform well in these surrogate neutralization assays supports their further development as immunotherapy for NoV treatment and immunoprophylaxis.

  9. Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice.

    Science.gov (United States)

    Li, Xiaoguang; Wang, Zhihao; Tan, Lu; Wang, Yali; Lu, Chengbiao; Chen, Rongxiang; Zhang, Shujuan; Gao, Yuan; Liu, Yanchao; Yin, Yaling; Liu, Xinghua; Liu, Enjie; Yang, Ying; Hu, Yu; Xu, Zhipeng; Xu, Fuqiang; Wang, Jie; Liu, Gong-Ping; Wang, Jian-Zhi

    2017-01-04

    Patients with Alzheimer's disease (AD) commonly show anxiety behaviors, but the molecular mechanisms are not clear and no efficient intervention exists. Here, we found that overexpression of human wild-type, full-length tau (termed htau) in hippocampus significantly decreased the extracellular γ-aminobutyric acid (GABA) level with inhibition of γ oscillation and the evoked inhibitory postsynaptic potential (eIPSP). With tau accumulation, the mice show age-dependent anxiety behaviors. Among the factors responsible for GABA synthesis, release, uptake, and transport, we found that accumulation of htau selectively suppressed expression of the intracellular vesicular GABA transporter (vGAT). Tau accumulation increased miR92a, which targeted vGAT mRNA 3' UTR and inhibited vGAT translation. Importantly, we found that upregulating GABA tones by intraperitoneal injection of midazolam (a GABA agonist), ChR2-mediated photostimulating and overexpressing vGAT, or blocking miR92a by using specific antagomir or inhibitor efficiently rescued the htau-induced GABAergic dysfunctions with attenuation of anxiety. Finally, we also demonstrated that vGAT level decreased while the miR92a increased in the AD brains. These findings demonstrate that the AD-like tau accumulation induces anxiety through disrupting miR92a-vGAT-GABA signaling, which reveals molecular mechanisms underlying the anxiety behavior in AD patients and potentially leads to the development of new therapeutics for tauopathies. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  10. Reduction of coherence of the human brain electric potentials

    Science.gov (United States)

    Novik, Oleg; Smirnov, Fedor

    Plenty of technological processes are known to be damaged by magnetic storms. But technology is controlled by men and their functional systems may be damaged as well. We are going to consider the electro-neurophysiological aspect of the general problem: men surrounded by physical fields including ones of cosmic origination. Magnetic storms’ influence had been observed for a group of 13 students (practically healthy girls and boys from 18 to 23 years old, Moscow). To control the main functional systems of the examinees, their electroencephalograms (EEG) were being registered along with electrocardiograms, respiratory rhythms, arterial blood pressure and other characteristics during a year. All of these characteristics, save for the EEG, were within the normal range for all of the examinees during measurements. According to the EEG investigations by implementation of the computer proof-reading test in absence of magnetic storms, the values of the coherence function of time series of the theta-rhythm oscillations (f = 4 - 7.9 Hz, A = 20 μV) of electric potentials of the frontal-polar and occipital areas of the head belong to the interval [0.3, 0.8] for all of the students under investigation. (As the proof-reading test, it was necessary to choose given symbols from a random sequence of ones demonstrated at a monitor and to enter the number of the symbols discovered in a computer. Everyone was known that the time for determination of symbols is unlimited. On the other hand, nobody was known that the EEG and other registrations mentioned are connected with electromagnetic geophysical researches and geomagnetic storms). Let us formulate the main result: by implementation of the same test during a magnetic storm, 5 ≤ K ≤ 6, or no later then 24 hours after its beginning (different types of moderate magnetic storms occurred, the data of IZMIRAN were used), the values of the theta-rhythm frontal - occipital coherence function of all of the students of the group under

  11. Contemporary assumptions on human nature and work and approach to human potential managing

    Directory of Open Access Journals (Sweden)

    Vujić Dobrila

    2006-01-01

    Full Text Available A general problem of this research is to identify if there is a relationship between the assumption on human nature and work (Mcgregor, Argyris, Schein, Steers and Porter and a general organizational model preference, as well as a mechanism of human resource management? This research was carried out in 2005/2006. The sample consisted of 317 subjects (197 managers, 105 highly educated subordinates and 15 entrepreneurs in 7 big enterprises in a group of small business enterprises differentiating in terms of the entrepreneur’s structure and a type of activity. A general hypothesis "that assumptions on human nature and work are statistically significant in connection to the preference approach (models, of work motivation commitment", has been confirmed. A specific hypothesis have been also confirmed: ·The assumptions on a human as a rational economic being are statistically significant in correlation with only two mechanisms of traditional models, the mechanism of method work control and the working discipline mechanism. ·Statistically significant assumptions on a human as a social being are correlated with all mechanisms of engaging employees, which belong to the model of the human relations, except the mechanism introducing the adequate type of prizes for all employees independently of working results. ·The assumptions on a human as a creative being are statistically significant, positively correlating with preference of two mechanisms belonging to the human resource model by investing into education and training and making conditions for the application of knowledge and skills. The young with assumptions on a human as a creative being prefer much broader repertoire of mechanisms belonging to the human resources model from the remaining category of subjects in the pattern. The connection between the assumption on human nature and preference models of engaging appears especially in the sub-pattern of managers, in the category of young subjects

  12. Potential Human Health Risks of Tannery Waste-contaminated Poultry Feed

    Directory of Open Access Journals (Sweden)

    Mohammad Latiful Bari

    2015-01-01

    Conclusions. The estimated daily intake value, THQ, along with the aggregate hazard index value, indicated a potential risk to consumers through consumption of contaminated chicken. Therefore, the study results clearly demonstrate heavy metals accumulation in chicken due to feeding SCW-based feed. The contaminated chicken further transfers these heavy metals to humans through ingestion. Hence, there is a potential human health risk through consumption of contaminated chicken meat.

  13. High glucose-induced oxidative stress increases transient receptor potential channel expression in human monocytes

    DEFF Research Database (Denmark)

    Wuensch, Tilo; Thilo, Florian; Krueger, Katharina;

    2010-01-01

    Transient receptor potential (TRP) channel-induced cation influx activates human monocytes, which play an important role in the pathogenesis of atherosclerosis. In the present study, we investigated the effects of high glucose-induced oxidative stress on TRP channel expression in human monocytes....

  14. Transient receptor potential canonical type 3 channels and blood pressure in humans

    DEFF Research Database (Denmark)

    Thilo, Florian; Baumunk, Daniel; Krause, Hans;

    2009-01-01

    There is evidence that transient receptor potential canonical type 3 (TRPC3) cation channels are involved in the regulation of blood pressure, but this has not been studied using human renal tissue. We tested the hypothesis that the expression of TRPC3 in human renal tissue is associated with blood...

  15. Triangulation of the human, chimpanzee and Neanderthal genome sequences identifies potentially compensated mutations

    OpenAIRE

    Zhang, Guojie; Zhang,Pei; Krawczak, Michael; Ball, Edward V.; Mort, Matthew; Kehrer-Sawatzki, Hildegard; Cooper, David N.

    2010-01-01

    Abstract Triangulation of the human, chimpanzee and Neanderthal genome sequences with respect to 44,348 disease-causing or disease-associated missense mutations and 1,712 putative regulatory mutations listed in the Human Gene Mutation Database was employed to identify genetic variants that are apparently pathogenic in humans but which may represent a `compensated? wild-type state in at least one of the other two species. Of 122 such `potentially compensated mutations? (PCMs) identi...

  16. A Density Functional Theory Based Protocol to Compute the Redox Potential of Transition Metal Complex with the Correction of Pseudo-Counterion: General Theory and Applications.

    Science.gov (United States)

    Matsui, Toru; Kitagawa, Yasutaka; Shigeta, Yasuteru; Okumura, Mitsutaka

    2013-07-09

    We propose an accurate scheme to evaluate the redox potential of a wide variety of transition metal complexes by adding a charge-dependent correction term for a counterion around the charged complexes, which is based on Generalized Born theory, to the solvation energy. The mean absolute error (MAE) toward experimental redox potentials of charged complexes is considerably reduced from 0.81 V (maximum error 1.22 V) to 0.22 V (maximum error 0.50 V). We found a remarkable exchange-correlation functional dependence on the results rather than the basis set ones. The combination of Wachters+f (for metal) and 6-31++G(d,p) (for other atoms) with the B3LYP functional gives the least MAE 0.15 V for the test complexes. This scheme is applicable to other solvents, and heavier transition metal complexes such as M1(CO)5(pycn) (M1 = Cr, Mo, W), M2(mnt)2 (M2 = Ni, Pd, Pt), and M3(bpy)3 (M3 = Fe, Ru, Os) with the same quality.

  17. Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

    Energy Technology Data Exchange (ETDEWEB)

    Nozaki, Yumiko, E-mail: yumiko-nozaki@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Honda, Yayoi, E-mail: yayoi-honda@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Tsujimoto, Shinji, E-mail: shinji-tsujimoto@ds-pharma.co.jp [Regenerative and Cellular Medicine Office, Dainippon Sumitomo Pharma. Co., Ltd., Chuo-ku, Tokyo 104-0031 (Japan); Watanabe, Hitoshi, E-mail: hitoshi-1-watanabe@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Kunimatsu, Takeshi, E-mail: takeshi-kunimatsu@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Funabashi, Hitoshi, E-mail: hitoshi-funabashi@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan)

    2014-07-01

    Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.

  18. Mandatory Reporting of Human Trafficking: Potential Benefits and Risks of Harm.

    Science.gov (United States)

    English, Abigail

    2017-01-01

    Human trafficking, including both sex and labor trafficking, has profound consequences for the safety, health, and well-being of victims and survivors. Efforts to address human trafficking through prevention, protection, and prosecution are growing but remain insufficient. Mandatory reporting has the potential to bring victims and survivors to the attention of social service and law enforcement agencies but may discourage trafficked persons from seeking help, thereby limiting the ability of health care professionals to establish trust and provide needed care. States' experience in implementing child abuse laws can be useful in assessing the potential risks and benefits of mandatory reporting of human trafficking.

  19. Role of COX-2 in the regulation of the metastatic potential of human breast tumor cells

    Directory of Open Access Journals (Sweden)

    M. A. Taipov

    2014-01-01

    Full Text Available The expression of СOX-2, VEGF, VEGFR-1, VEGFR-2, VEGFR-3, EGFR, endoglin (СD105, and IL-6 was analyzed in the human breast tumor cells having a varying metastatic potential. The role of these factors in the regulation of the metastatic potential of breast cancer cells, as well as that of COX-2 in the regulation of metastatic processes at the cellular level were examined. The potential capacity of human breast tumor cells to elaborate factors that stimulate tumor growth, angiogenesis, and metastasis was evaluated.

  20. In vivo myogenic potential of human CD133+ muscle-derived stem cells: a quantitative study.

    Science.gov (United States)

    Negroni, Elisa; Riederer, Ingo; Chaouch, Soraya; Belicchi, Marzia; Razini, Paola; Di Santo, James; Torrente, Yvan; Butler-Browne, Gillian S; Mouly, Vincent

    2009-10-01

    In recent years, numerous reports have identified in mouse different sources of myogenic cells distinct from satellite cells that exhibited a variable myogenic potential in vivo. Myogenic stem cells have also been described in humans, although their regenerative potential has rarely been quantified. In this study, we have investigated the myogenic potential of human muscle-derived cells based on the expression of the stem cell marker CD133 as compared to bona fide satellite cells already used in clinical trials. The efficiency of these cells to participate in muscle regeneration and contribute to the renewal of the satellite cell pool, when injected intramuscularly, has been evaluated in the Rag2(-/-) gammaC(-/-) C5(-/-) mouse in which muscle degeneration is induced by cryoinjury. We demonstrate that human muscle-derived CD133+ cells showed a much greater regenerative capacity when compared to human myoblasts. The number of fibers expressing human proteins and the number of human cells in a satellite cell position are all dramatically increased when compared to those observed after injection of human myoblasts. In addition, CD133+/CD34+ cells exhibited a better dispersion in the host muscle when compared to human myoblasts. We propose that muscle-derived CD133+ cells could be an attractive candidate for cellular therapy.

  1. In Vivo Myogenic Potential of Human CD133+ Muscle-derived Stem Cells: A Quantitative Study

    Science.gov (United States)

    Negroni, Elisa; Riederer, Ingo; Chaouch, Soraya; Belicchi, Marzia; Razini, Paola; Di Santo, James; Torrente, Yvan; Butler-Browne, Gillian S; Mouly, Vincent

    2009-01-01

    In recent years, numerous reports have identified in mouse different sources of myogenic cells distinct from satellite cells that exhibited a variable myogenic potential in vivo. Myogenic stem cells have also been described in humans, although their regenerative potential has rarely been quantified. In this study, we have investigated the myogenic potential of human muscle–derived cells based on the expression of the stem cell marker CD133 as compared to bona fide satellite cells already used in clinical trials. The efficiency of these cells to participate in muscle regeneration and contribute to the renewal of the satellite cell pool, when injected intramuscularly, has been evaluated in the Rag2−/− γC−/− C5−/− mouse in which muscle degeneration is induced by cryoinjury. We demonstrate that human muscle–derived CD133+ cells showed a much greater regenerative capacity when compared to human myoblasts. The number of fibers expressing human proteins and the number of human cells in a satellite cell position are all dramatically increased when compared to those observed after injection of human myoblasts. In addition, CD133+/CD34+ cells exhibited a better dispersion in the host muscle when compared to human myoblasts. We propose that muscle-derived CD133+ cells could be an attractive candidate for cellular therapy. PMID:19623164

  2. 78 FR 34245 - Miscellaneous Corrections

    Science.gov (United States)

    2013-06-07

    ... Federal Regulations is sold by the Superintendent of Documents. #0;Prices of new books are listed in the... office, correcting and adding missing cross-references, correcting grammatical errors, revising language... the name of its human capital office, correcting and adding missing cross-references,...

  3. List-mode PET motion correction using markerless head tracking: proof-of-concept with scans of human subject.

    Science.gov (United States)

    Olesen, Oline V; Sullivan, Jenna M; Mulnix, Tim; Paulsen, Rasmus R; Højgaard, Liselotte; Roed, Bjarne; Carson, Richard E; Morris, Evan D; Larsen, Rasmus

    2013-02-01

    A custom designed markerless tracking system was demonstrated to be applicable for positron emission tomography (PET) brain imaging. Precise head motion registration is crucial for accurate motion correction (MC) in PET imaging. State-of-the-art tracking systems applied with PET brain imaging rely on markers attached to the patient's head. The marker attachment is the main weakness of these systems. A healthy volunteer participating in a cigarette smoking study to image dopamine release was scanned twice for 2 h with (11)C-racolopride on the high resolution research tomograph (HRRT) PET scanner. Head motion was independently measured, with a commercial marker-based device and the proposed vision-based system. A list-mode event-by-event reconstruction algorithm using the detected motion was applied. A phantom study with hand-controlled continuous random motion was obtained. Motion was time-varying with long drift motions of up to 18 mm and regular step-wise motion of 1-6 mm. The evaluated measures were significantly better for motion-corrected images compared to no MC. The demonstrated system agreed with a commercial integrated system. Motion-corrected images were improved in contrast recovery of small structures.

  4. Extension of the B3LYP - Dispersion-Correcting Potential Approach to the Accurate Treatment of both Inter- and Intramolecular Interactions

    CERN Document Server

    DiLabio, Gino A; Torres, Edmanuel

    2013-01-01

    We recently showed that dispersion-correcting potentials (DCPs), atom-centered Gaussian-type functions developed for use with B3LYP (J. Phys. Chem. Lett. 2012, 3, 1738-1744) greatly improved the ability of the underlying functional to predict non-covalent interactions. However, the application of B3LYP-DCP for the {\\beta}-scission of the cumyloxyl radical led a calculated barrier height that was over-estimated by ca. 8 kcal/mol. We show in the present work that the source of this error arises from the previously developed carbon atom DCPs, which erroneously alters the electron density in the C-C covalent-bonding region. In this work, we present a new C-DCP with a form that was expected to influence the electron density farther from the nucleus. Tests of the new C-DCP, with previously published H-, N- and O-DCPs, with B3LYP-DCP/6-31+G(2d,2p) on the S66, S22B, HSG-A, and HC12 databases of non-covalently interacting dimers showed that it is one of the most accurate methods available for treating intermolecular i...

  5. Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients.

    Science.gov (United States)

    Lagresle-Peyrou, Chantal; Benjelloun, Fatine; Hue, Christophe; Andre-Schmutz, Isabelle; Bonhomme, Delphine; Forveille, Monique; Beldjord, Kheira; Hacein-Bey-Abina, Salima; De Villartay, Jean-Pierre; Charneau, Pierre; Durandy, Anne; Fischer, Alain; Cavazzana-Calvo, Marina

    2008-02-01

    Severe combined immunodeficiency (SCID) caused by mutation of the recombination-activating gene 1 (RAG1) or Artemis gene lead to the absence of B- and T-cell differentiation. The only curative treatment is allogeneic bone marrow (BM) transplantation, which displays a high survival rate when an HLA compatible donor is available but has a poorer prognosis when the donor is partially compatible. Consequently, gene therapy may be a promising alternative strategy for these diseases. Here, we report that lentiviral gene-corrected BM CD34(+) cells (isolated from Artemis- or RAG1-deficient patients) sustain human B-cell differentiation following injection into non-obese diabetic/SCID (NOD-SCID) mice previously infused with anti-interleukin-2 receptor beta chain monoclonal antibody. In most of the mice BM, engrafted with Artemis-transduced cells, human B-cell differentiation occurred until the mature stage. The B cells were functional as human immunoglobulin M (IgM) was present in the serum. Following injection with RAG1-transduced cells, human engraftment occurred in vivo but B-cell differentiation until the mature stage was less frequent. However, when it occurred, it was always associated with human IgM production. This overall approach represents a useful tool for evaluating gene transfer efficiency in human SCID forms affecting B-cell development (such as Artemis deficiency) and for testing new vectors for improving in vivo RAG1 complementation.

  6. In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins.

    Science.gov (United States)

    Liu, Hua; Kim, Yonghak; Sharkis, Saul; Marchionni, Luigi; Jang, Yoon-Young

    2011-05-11

    Human induced pluripotent stem cells (iPSCs) are a potential source of hepatocytes for liver transplantation to treat end-stage liver disease. In vitro differentiation of human iPSCs into hepatic cells has been achieved using a multistage differentiation protocol, but whether these cells are functional and capable of engrafting and regenerating diseased liver tissue is not clear. We show that human iPSC-derived hepatic cells at various differentiation stages can engraft the liver in a mouse transplantation model. Using the same differentiation and transplantation protocols, we also assessed the ability of human iPSCs derived from each of the three developmental germ layer tissues (that is, ectoderm, mesoderm, and endoderm) to regenerate mouse liver. These iPSC lines, with similar but distinct global DNA methylation patterns, differentiated into multistage hepatic cells with an efficiency similar to that of human embryonic stem cells. Human hepatic cells at various differentiation stages derived from iPSC lines of different origins successfully repopulated the liver tissue of mice with liver cirrhosis. They also secreted human-specific liver proteins into mouse blood at concentrations comparable to that of proteins secreted by human primary hepatocytes. Our results demonstrate the engraftment and liver regenerative capabilities of human iPSC-derived multistage hepatic cells in vivo and suggest that human iPSCs of distinct origins and regardless of their parental epigenetic memory can efficiently differentiate along the hepatic lineage.

  7. Human immune system mice: current potential and limitations for translational research on human antibody responses.

    Science.gov (United States)

    Vuyyuru, Raja; Patton, John; Manser, Tim

    2011-12-01

    It has recently become possible to generate chimeric mice durably engrafted with many components of the human immune system (HIS mice). We have characterized the maturation and function of the B cell compartment of HIS mice. The antibody response of HIS mice to T cell-dependent B cell antigens is limited, and contributing factors may be the general immaturity of the B cell compartment, infrequent helper T cells selected on human MHC class II antigens, and incomplete reconstitution of secondary lymphoid organs and their microenvironments. In contrast, HIS mice generate protective antibody responses to the bacterium Borrelia hermsii, which acts as a T cell-independent antigen in mice, but do not respond to purified polysaccharide antigens (PPS). We speculate that the anti-B. hermsii response of HIS mice is derived from an abundant B cell subset that may be analogous to B1 B cells in mice. We suggest that failure of HIS mice to respond to PPS is due to the lack of a B cell subset that may originate from adult bone marrow and is highly dependent on human interleukin-7 for development.

  8. Dissecting the oncogenic and tumorigenic potential of differentiated human induced pluripotent stem cells and human embryonic stem cells.

    Science.gov (United States)

    Ghosh, Zhumur; Huang, Mei; Hu, Shijun; Wilson, Kitchener D; Dey, Devaveena; Wu, Joseph C

    2011-07-15

    Pluripotent stem cells, both human embryonic stem cells (hESC) and human-induced pluripotent stem cells (hiPSC), can give rise to multiple cell types and hence have tremendous potential for regenerative therapies. However, the tumorigenic potential of these cells remains a great concern, as reflected in the formation of teratomas by transplanted pluripotent cells. In clinical practice, most pluripotent cells will be differentiated into useful therapeutic cell types such as neuronal, cardiac, or endothelial cells prior to human transplantation, drastically reducing their tumorigenic potential. Our work investigated the extent to which these differentiated stem cell derivatives are truly devoid of oncogenic potential. In this study, we analyzed the gene expression patterns from three sets of hiPSC- and hESC-derivatives and the corresponding primary cells, and compared their transcriptomes with those of five different types of cancer. Our analysis revealed a significant gene expression overlap of the hiPSC- and hESC-derivatives with cancer, whereas the corresponding primary cells showed minimum overlap. Real-time quantitative PCR analysis of a set of cancer-related genes (selected on the basis of rigorous functional and pathway analyses) confirmed our results. Overall, our findings suggested that pluripotent stem cell derivatives may still bear oncogenic properties even after differentiation, and additional stringent functional assays to purify these cells should be done before they can be used for regenerative therapy.

  9. A sensitive RNase protection assay to detect transcripts from potentially functional human endogenous L1 retrotransposons

    DEFF Research Database (Denmark)

    Woodcock, D M; Williamson, M R; Doherty, J P

    1996-01-01

    A high background of read-through transcripts from degenerate human L1 retrotransposons is present in almost all human cell types. This prevents the detection of RNA transcripts from potentially functional elements. To overcome this, we have developed an RNase protection assay based on the recons...... transcripts from divergent L1 families but are either discrete shorter transcripts or specifically processed products from longer initial transcripts....

  10. Cellular development of the human cochlea and the regenerative potential of hair follicle bulge stem cells

    OpenAIRE

    2015-01-01

    The embryonic development of the human cochlea (the organ of hearing) has been investigated for over one hundred years. However, little is still known about the development on a cellular and protein level, which is important to better understand etiologies and pathologies of various types of sensorineural hearing loss. Knowledge of the normal gene expression patterns and cell fate specification in the human cochlea has therefore the potential to aid in the development of gene and cell-based t...

  11. Experimental repetitive quantum error correction.

    Science.gov (United States)

    Schindler, Philipp; Barreiro, Julio T; Monz, Thomas; Nebendahl, Volckmar; Nigg, Daniel; Chwalla, Michael; Hennrich, Markus; Blatt, Rainer

    2011-05-27

    The computational potential of a quantum processor can only be unleashed if errors during a quantum computation can be controlled and corrected for. Quantum error correction works if imperfections of quantum gate operations and measurements are below a certain threshold and corrections can be applied repeatedly. We implement multiple quantum error correction cycles for phase-flip errors on qubits encoded with trapped ions. Errors are corrected by a quantum-feedback algorithm using high-fidelity gate operations and a reset technique for the auxiliary qubits. Up to three consecutive correction cycles are realized, and the behavior of the algorithm for different noise environments is analyzed.

  12. A 2015 survey of established or potential epigenetic biomarkers for the accurate detection of human cancers.

    Science.gov (United States)

    Amacher, David E

    2016-07-01

    Context The silencing or activation of cancer-associated genes by epigenetic mechanisms can ultimately lead to the clonal expansion of cancer cells. Objective The aim of this review is to summarize all relevant epigenetic biomarkers that have been proposed to date for the diagnosis of some prevalent human cancers. Methods A Medline search for the terms epigenetic biomarkers, human cancers, DNA methylation, histone modifications and microRNAs was performed. Results One hundred fifty-seven relevant publications were found and reviewed. Conclusion To date, a significant number of potential epigenetic cancer biomarkers of human cancer have been investigated, and some have advanced to clinical implementation.

  13. Noise-driven activation in human intermittent control: a double-well potential model

    CERN Document Server

    Zgonnikov, Arkady

    2014-01-01

    In controlling unstable systems humans switch intermittently between the passive and active behavior instead of controlling the system in a continuous manner. The notion of noise-driven control activation provides a richer alternative to the conventional threshold-based models of intermittent motor control. The present study represents the control activation as a random walk in a continuously changing double-well potential. The match between the proposed model and the previous data on human balancing of virtual stick prompts that the double-well approach can aid in explaining complex dynamics of human behavior in control processes.

  14. Investigation of human body potential measured by a non-contact measuring system.

    Science.gov (United States)

    Ichikawa, Norimitsu

    2016-12-07

    A human body is occasionally electrified in a room. This charged object will be a source of electrostatic accidents, including the malfunction of electronic equipment. Hence, prevention of these accidents is required. Accidents occasionally occur, even though antistatic clothes and shoes are used. One of the causes for these accidents is that there is a lack of the preventive measures. This situation occurs when using, for example, unconductive wax. In this study, human body potential (voltage) is measured using a non-contact measuring system. An investigation of the human body's voltage when using this system is conducted. The result demonstrates that the voltage of a human body wearing antistatic clothes and shoes or light clothes and slippers exceeds a malfunctioning voltage of a microelectronics device when the body walks on floors. Thus, accidents may occur even if a human body wearing the antistatic clothes walks on flooring. These results will be useful in estimating determination whether electrostatic accidents occur or not.

  15. H7N9 avian influenza A virus and the perpetual challenge of potential human pandemicity.

    Science.gov (United States)

    Morens, David M; Taubenberger, Jeffery K; Fauci, Anthony S

    2013-07-09

    ABSTRACT The ongoing H7N9 influenza epizootic in China once again presents us questions about the origin of pandemics and how to recognize them in early stages of development. Over the past ~135 years, H7 influenza viruses have neither caused pandemics nor been recognized as having undergone human adaptation. Yet several unusual properties of these viruses, including their poultry epizootic potential, mammalian adaptation, and atypical clinical syndromes in rarely infected humans, suggest that they may be different from other avian influenza viruses, thus questioning any assurance that the likelihood of human adaptation is low. At the same time, the H7N9 epizootic provides an opportunity to learn more about the mammalian/human adaptational capabilities of avian influenza viruses and challenges us to integrate virologic and public health research and surveillance at the animal-human interface.

  16. [Psychophysiological correlates of increasing the work ability of human operator owing to the programmable correction of the functional status].

    Science.gov (United States)

    Tuzin, P S; Evdokimov, A V; Iznak, A F; Chaianov, N V

    1996-01-01

    There has been studied application of a complex approach to development of automated ways to gain contactless psychophysiological correction of functional status and improvement of performance of working up operators. The psychophysiological support of operator consisted in combined presentation of functional music, surf noise and pulsed dynamic green lighting under a special program built-up on the principle of biological feedback of heart and respiration rates. The individually adaptable audio and visual pulses on the programme showed a rather high efficiency as was confirmed by the change in the set of psychophysiological indices (heart rate, arterial pressure, cutaneogalvanic reaction, accommodation volume, critical rate of flicker fusion, electroencephalogram), and subjective SAM (self-feeling, activity, mood) estimates in the course of extended operator's activity.

  17. Restricting the above ground sink corrects the root/shoot ratio and substantially boosts the yield potential per panicle in field-grown rice (Oryza sativa L.).

    Science.gov (United States)

    Nada, Reham M; Abogadallah, Gaber M

    2016-04-01

    Rice has shallow, weak roots, but it is unknown how much increase in yield potential could be achieved if the root/shoot ratio is corrected. Removing all tillers except the main one, in a japonica (Sakha 101) and an indica (IR64) rice cultivar, instantly increased the root/shoot ratio from 0.21 to 1.16 in Sakha 101 and from 0.16 to 1.46 in IR64. Over 30 days after detillering, the root/shoot ratios of the detillered plants decreased to 0.49 in Sakha 101 and 0.46 in IR64 but remained significantly higher than in the controls. The detillered plants showed two- or fourfold increase in the main tiller fresh weight, as a consequence of more positive midday leaf relative water content (RWC), and consistently higher rates of stomatal conductance and photosynthesis, but not transpiration, compared with the controls. The enhanced photosynthesis in Sakha 101 after detillering resulted from both improved water status and higher Rubisco contents whereas in IR64, increasing the Rubisco content did not contribute to improving photosynthesis. Detillering did not increase the carbohydrate contents of leaves but prevented starch depletion at the end of grain filling. The leaf protein content during vegetative and reproductive stages, the grain filling rate, the number of filled grains per panicle were greatly improved, bringing about 38.3 and 35.9% increase in the harvested grain dry weight per panicle in Sakha 101 and IR64, respectively. We provide evidence that improving the root performance by increasing the root/shoot ratio would eliminate the current limitations to photosynthesis and growth in rice.

  18. Cocaine exposure impairs multilineage hematopoiesis of human hematopoietic progenitor cells mediated by the sigma-1 receptor [corrected].

    Science.gov (United States)

    Nixon, Christopher C; Schwartz, Brandon H; Dixit, Dhaval; Zack, Jerome A; Vatakis, Dimitrios N

    2015-03-02

    Prenatal exposure to cocaine is a significant source of fetal and neonatal developmental defects. While cocaine associated neurological and cardiac pathologies are well-documented, it is apparent that cocaine use has far more diverse physiological effects. It is known that in some cell types, the sigma-1 receptor mediates many of cocaine's cellular effects. Here we present a novel and concise investigation into the mechanism that underlies cocaine associated hematopoietic pathology. Indeed, this is the first examination of the effects of cocaine on hematopoiesis. We show that cocaine impairs multilineage hematopoiesis from human progenitors from multiple donors and tissue types. We go on to present the first demonstration of the expression of the sigma-1 receptor in human CD34 + human hematopoietic stem/progenitor cells. Furthermore, we demonstrate that these cocaine-induced hematopoietic defects can be reversed through sigma-1 receptor blockade.

  19. Potential of human twin embryos generated by embryo splitting in assisted reproduction and research.

    Science.gov (United States)

    Noli, Laila; Ogilvie, Caroline; Khalaf, Yacoub; Ilic, Dusko

    2017-03-01

    Embryo splitting or twinning has been widely used in veterinary medicine over 20 years to generate monozygotic twins with desirable genetic characteristics. The first human embryo splitting, reported in 1993, triggered fierce ethical debate on human embryo cloning. Since Dolly the sheep was born in 1997, the international community has acknowledged the complexity of the moral arguments related to this research and has expressed concerns about the potential for reproductive cloning in humans. A number of countries have formulated bans either through laws, decrees or official statements. However, in general, these laws specifically define cloning as an embryo that is generated via nuclear transfer (NT) and do not mention embryo splitting. Only the UK includes under cloning both embryo splitting and NT in the same legislation. On the contrary, the Ethics Committee of the American Society for Reproductive Medicine does not have a major ethical objection to transferring two or more artificially created embryos with the same genome with the aim of producing a single pregnancy, stating that 'since embryo splitting has the potential to improve the efficacy of IVF treatments for infertility, research to investigate the technique is ethically acceptable'. Embryo splitting has been introduced successfully to the veterinary medicine several decades ago and today is a part of standard practice. We present here an overview of embryo splitting experiments in humans and non-human primates and discuss the potential of this technology in assisted reproduction and research. A comprehensive literature search was carried out using PUBMED and Google Scholar databases to identify studies on embryo splitting in humans and non-human primates. 'Embryo splitting' and 'embryo twinning' were used as the keywords, alone or in combination with other search phrases relevant to the topics of biology of preimplantation embryos. A very limited number of studies have been conducted in humans and non-human

  20. Chapter 6: Ecotoxicology, Environmental Risk Assessment & Potential Impact on Human Health

    Science.gov (United States)

    This chapter examines potential risks posed by pharmaceuticals present in the aquatic environment to humans and aquatic life. We begin by describing the mechanisms by which pharmaceuticals enter the vertebrate body, produce effects and leave the body. Then we describe theoretical...

  1. Potential Predictors of Poor Visual Outcome in Human Leukocyte Antigen-B27-Associated Uveitis

    NARCIS (Netherlands)

    Verhagen, Fleurieke H; Brouwer, Anna H; Kuiper, Jonas J W|info:eu-repo/dai/nl/342171070; Ossewaarde-van Norel, Jeannette; ten Dam-van Loon, Ninette H|info:eu-repo/dai/nl/304816957; de Boer, Joke H|info:eu-repo/dai/nl/140201890

    2016-01-01

    PURPOSE: To identify potential predictors of permanent vision loss in patients with human leukocyte antigen (HLA)-B27-associated uveitis in a tertiary referral center. DESIGN: Retrospective case-control study. METHODS: The charts of 212 patients (338 eyes) with HLA-B27-associated uveitis that visite

  2. Snake scales, partial exposure, and the Snake Detection Theory: A human event-related potentials study

    NARCIS (Netherlands)

    J.W. van Strien (Jan); L.A. Isbell (Lynne A.)

    2017-01-01

    textabstractStudies of event-related potentials in humans have established larger early posterior negativity (EPN) in response to pictures depicting snakes than to pictures depicting other creatures. Ethological research has recently shown that macaques and wild vervet monkeys respond strongly to pa

  3. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH AND SCREENING

    Science.gov (United States)

    Molecular Analysis of Human Spermatozoa: Potential for Infertility Research and ScreeningDavid Miller1, David Dix2, Robert Reid3, Susan Wykes3 and Stephen Krawetz3 1Reproductive Biology Group, University of Leeds, UK2Reproductive Toxicology Division, U.S. Environmenta...

  4. Chapter 6: Ecotoxicology, Environmental Risk Assessment & Potential Impact on Human Health

    Science.gov (United States)

    This chapter examines potential risks posed by pharmaceuticals present in the aquatic environment to humans and aquatic life. We begin by describing the mechanisms by which pharmaceuticals enter the vertebrate body, produce effects and leave the body. Then we describe theoretical...

  5. An Evaluation of the Human Carcinogenic Potential of Ethylene Glycol Butyl Ether (Egbe)

    Science.gov (United States)

    This position paper, An Evaluation of the Human Carcinogenic Potential of Ethylene Glycol Butyl Ether, was developed in support of the EPA's evaluation of a petition from the American Chemistry Council requesting to delist EGBE per the Clean Air Act Amendments (CAAA), Titl...

  6. Evaluation of human skin tests for potential dermal irritant and contact sensitizing products: a position paper

    NARCIS (Netherlands)

    Loveren H van; Jong WH de; Garssen J; LPI

    1998-01-01

    Prediction of human cutaneous irritation and sensitization in view of hazard identification has primarily relied on the use of laboratory animals. Such studies in laboratory animals have been very instrumental in the detection of potential contact sensitizing agents. There are however many uncertain

  7. Potential Predictors of Poor Visual Outcome in Human Leukocyte Antigen-B27-Associated Uveitis

    NARCIS (Netherlands)

    Verhagen, Fleurieke H; Brouwer, Anna H; Kuiper, Jonas J W; Ossewaarde-van Norel, Jeannette; ten Dam-van Loon, Ninette H; de Boer, Joke H

    2016-01-01

    PURPOSE: To identify potential predictors of permanent vision loss in patients with human leukocyte antigen (HLA)-B27-associated uveitis in a tertiary referral center. DESIGN: Retrospective case-control study. METHODS: The charts of 212 patients (338 eyes) with HLA-B27-associated uveitis that visite

  8. Potential human pathogenic bacteria in a mixed urban watershed as revealed by pyrosequencing

    Science.gov (United States)

    Current microbial source tracking (MST) methods for water depend on testing for fecal indicator bacterial counts or specific marker gene sequences to identify fecal contamination where potential human pathogenic bacteria could be present. In this study, we applied 454 high-throughput pyrosequencing ...

  9. Probiotic Potential of Lactobacillus Strains with Antimicrobial Activity against Some Human Pathogenic Strains

    Directory of Open Access Journals (Sweden)

    Parisa Shokryazdan

    2014-01-01

    Full Text Available The objective of this study was to isolate, identify, and characterize some lactic acid bacterial strains from human milk, infant feces, and fermented grapes and dates, as potential probiotics with antimicrobial activity against some human pathogenic strains. One hundred and forty bacterial strains were isolated and, after initial identification and a preliminary screening for acid and bile tolerance, nine of the best isolates were selected and further identified using 16 S rRNA gene sequences. The nine selected isolates were then characterized in vitro for their probiotic characteristics and their antimicrobial activities against some human pathogens. Results showed that all nine isolates belonged to the genus Lactobacillus. They were able to tolerate pH 3 for 3 h, 0.3% bile salts for 4 h, and 1.9 mg/mL pancreatic enzymes for 3 h. They exhibited good ability to attach to intestinal epithelial cells and were not resistant to the tested antibiotics. They also showed good antimicrobial activities against the tested pathogenic strains of humans, and most of them exhibited stronger antimicrobial activity than the reference strain L. casei Shirota. Thus, the nine Lactobacillus strains could be considered as potential antimicrobial probiotic strains against human pathogens and should be further studied for their human health benefits.

  10. Effects of different contact lens correction on Zernike aberrations of human eye%不同角膜接触镜对人眼Zernike像差的影响

    Institute of Scientific and Technical Information of China (English)

    保金华; 贺极苍; 毛欣杰; 吕帆

    2013-01-01

    Background Even though the change in wavefront aberrations with correction modality is well documented in the literature,little is known about the underlying mechanism.Complete understanding of the causes responsible for the wavefront change in the combined lens-eye system is important since it provides basic knowledge for further improving the technique to correct refractive error by correcting lenses.Objective The aim of this study was to investigate the influence of refractive correction lens on optical property of the eye by analyzing Zernike aberrations in myopic eyes with contact lens correction.Methods This study was approved by the Ethic Committee of Wenzhou Medical College.Written informed consent was obtained from each subject before entering this study.Zernike aberrations of 52 myopic eyes of 26 subjects with the spherical equivalent-1.75 to-8.50 D were measured using a Hartmann-Shock wavefront sensor.The human eye aberrations were examined at the uncorrected condition,rigid-gas-permeable contact lens (RGP-CL) corrected condition and soft contact lens (Soft-CL) corrected condition.The differences of wavefront aberrations and Zernike coefficients were compared by repeated measurement of single factor variance analysis,and correlation of the aberration changes between uncorrected condition and RGP-CL corrected condition or Sofi-CL corrected condition,between the right eyes and left eyes in different conditions were analyzed by Pearson linear correlation.Results Mean total root-mean-square (tRMS) was (0.71 ± 0.30)μm,(0.54±0.19)μm and (0.74±0.32)μm in the uncorrected condition,RGP-CL corrected condition and Soft-CL corrected condition,with a significant difference (F =8.758,P<0.001),and tRMS was significant declined under the RGP-CL corrected condition compared with uncorrected condition (t =2.746,P =0.008),and tRMS in RGP-CL corrected condition was significantly lower than that in Soft-CL corrected condition (t =3.428,P =0.001).The high RMS (h

  11. Genesis & the Human Ribcage: An Opportunity to Correct a Misconception & Introduce an Evolution Lesson into the Anatomy Class

    Science.gov (United States)

    Senter, Phil

    2013-01-01

    Many anatomy students begin the course with a misconception that human males and females do not have the same number of ribs. At the root of that misconception is Genesis 2:21-22, in which God removes a rib from Adam to make Eve. Removal of a body part is a surgical procedure, and one does not pass on the results of surgery to one's offspring. The…

  12. Conduction velocity of the human spinothalamic tract as assessed by laser evoked potentials

    DEFF Research Database (Denmark)

    Cruccu, G.; Iannetti, G. D.; Agostino, R.

    2000-01-01

    To study the conduction velocity of the spinothalamic tract (STT) we delivered CO2 laser pulses, evoking pinprick sensations, to the skin overlying the vertebral spinous processes at different spinal levels from C5 to T10 and recorded evoked potentials (LEPs) in 15 healthy human subjects. These s......To study the conduction velocity of the spinothalamic tract (STT) we delivered CO2 laser pulses, evoking pinprick sensations, to the skin overlying the vertebral spinous processes at different spinal levels from C5 to T10 and recorded evoked potentials (LEPs) in 15 healthy human subjects....... These stimuli yielded large-amplitude vertex potentials consisting of a negative wave at a peak latency of about 200 ms followed by a positive wave at a peak latency of about 300 ms. The mean conduction velocity of the STT was 21 m/s, i.e. higher than the reported velocity of the corresponding primary sensory...

  13. ERRORS AND CORRECTION

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    To err is human . Since the 1960s, most second language teachers or language theorists have regarded errors as natural and inevitable in the language learning process . Instead of regarding them as terrible and disappointing, teachers have come to realize their value. This paper will consider these values, analyze some errors and propose some effective correction techniques.

  14. Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice.

    Science.gov (United States)

    Fortier, Mélanie; Soni, Krishnakant; Laurin, Nancy; Wang, Shu Pei; Mauriège, Pascale; Jirik, Frank R; Mitchell, Grant A

    2005-09-01

    In white adipose tissue (WAT), hormone-sensitive lipase (HSL) can mediate lipolysis, a central pathway in obesity and diabetes. Gene-targeted HSL-deficient (HSL-/-) mice with no detectable HSL peptide or activity (measured as cholesteryl esterase) have WAT abnormalities, including low mass, marked heterogeneity of cell diameter, increased diacylglycerol content, and low beta-adrenergic stimulation of adipocyte lipolysis. Three transgenic mouse strains preferentially expressing human HSL in WAT were bred to a HSL-/- background. One, HSL-/- N, expresses normal human HSL (41.3 +/- 9.1% of normal activity); two express a serine-to-alanine mutant (S554A) initially hypothesized to be constitutively active: HSL-/- ML, 50.3 +/- 12.3% of normal, and HSL-/- MH, 69.8 +/- 15.8% of normal. In WAT, HSL-/- N mice resembled HSL+/+ controls in WAT mass, histology, diacylglyceride content, and lipolytic response to beta-adrenergic agents. In contrast, HSL-/- ML and HSL-/- MH mice resembled nontransgenic HSL-/- mice, except that diacylglycerol content and perirenal and inguinal WAT masses approached normal in HSL-/- MH mice. Therefore, 1) WAT expression of normal human HSL markedly improves HSL-/- WAT biochemically, physiologically, and morphologically; 2) similar levels of S554A HSL have a low physiological effect despite being active in vitro; and 3) diacylglycerol accumulation is not essential for the development of the characteristic WAT pathology of HSL-/- mice.

  15. The N2-P3 complex of the evoked potential and human performance

    Science.gov (United States)

    Odonnell, Brian F.; Cohen, Ronald A.

    1988-01-01

    The N2-P3 complex and other endogenous components of human evoked potential provide a set of tools for the investigation of human perceptual and cognitive processes. These multidimensional measures of central nervous system bioelectrical activity respond to a variety of environmental and internal factors which have been experimentally characterized. Their application to the analysis of human performance in naturalistic task environments is just beginning. Converging evidence suggests that the N2-P3 complex reflects processes of stimulus evaluation, perceptual resource allocation, and decision making that proceed in parallel, rather than in series, with response generation. Utilization of these EP components may provide insights into the central nervous system mechanisms modulating task performance unavailable from behavioral measures alone. The sensitivity of the N2-P3 complex to neuropathology, psychopathology, and pharmacological manipulation suggests that these components might provide sensitive markers for the effects of environmental stressors on the human central nervous system.

  16. The potential role of inhibitor of differentiation-3 in human adipose tissue remodeling and metabolic health

    DEFF Research Database (Denmark)

    Svendstrup, Mathilde; Vestergaard, Henrik

    2014-01-01

    in the tissue. Regulation of angiogenesis in SAT and VAT in response to diet is therefore crucial for the metabolic outcome in obesity. Knowledge about the underlying genetic mechanisms determining metabolic health in obesity is very limited. We aimed to review the literature of the inhibitor of differentiation......-3 (ID3) gene in relation to adipose tissue and angiogenesis in humans in order to determine whether ID3 could be involved in the regulation of adipose tissue expansion and metabolic health in human obesity. We find evidence that ID3 is involved in regulatory mechanisms in adipose tissue...... literature suggest ID3 to play a potential role in the underlying regulatory mechanisms of metabolic health in human obesity. The literature is still sparse and further studies focusing on human ID3 in relation to the nature of obesity are warranted....

  17. Leptospira wolffii, a potential new pathogenic Leptospira species detected in human, sheep and dog.

    Science.gov (United States)

    Zakeri, Sedigheh; Khorami, Nargess; Ganji, Zahra F; Sepahian, Neda; Malmasi, Abdol-Ali; Gouya, Mohammad Mehdi; Djadid, Navid D

    2010-03-01

    Leptospirosis is the most common zoonotic disease, which is transmitted to humans through contaminated water or direct exposure to the urine of infected animals. In this study, the presence and prevalence of Leptospira species in the infected samples of human (n=369) and sheep (n=75) sera and also dogs' urine (n=150), collected from four provinces of Iran, were investigated by using nested-PCR/RFLP assay followed by sequencing analysis. Nested-PCR assay detected that 98/369 (26.5%) human, 13/75 (17.33%) of sheep's sera and 33/150 (22%) dogs' urine samples were positive for Leptospira DNA. RFLP assay detected that all positive cases had either pathogenic or intermediate Leptospira species. By sequence analysis, Leptospira interrogans was the most prevalent species among the examined samples of human (53/82, 64.6%) and sheep (11/13, 84.6%). However, in dog samples, Leptospira wolffii (27/29, 93.1%) was detected for the first time and was the dominant species. The presence of L. wolffii with 100% identity in clinical human samples and animals suspected with Leptospira may provide evidence for circulation of L. wolffii and its role in transmission cycle within human and animal hosts. In addition, this species can be potentially pathogenic to human and probably animal hosts. A large epidemiology survey would be needed to define the presence and the prevalence of this species in global endemic regions.

  18. Angiogenic Potential of Human Neonatal Foreskin Stromal Cells in the Chick Embryo Chorioallantoic Membrane Model

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Vishnubalaji

    2015-01-01

    Full Text Available Several studies have demonstrated the multipotentiality of human neonatal foreskin stromal cells (hNSSCs as being able to differentiate into adipocytes and osteoblasts and potentially other cell types. Recently, we demonstrated that hNSSCs play a role during in vitro angiogenesis and appear to possess a capacity to differentiate into endothelial-like cells; however, their angiogenic potential within an ex vivo environment remains unclear. Current study shows hNSSCs to display significant migration potential in the undifferentiated state and high responsiveness in the in vitro wound healing scratch assay. When hNSSCs were seeded onto the top of the CAM, human von Willebrand factor (hVWF, CD31, smooth muscle actin (SMA, and factor XIIIa positive cells were observed in the chick endothelium. CAMs transplanted with endothelial-differentiated hNSSCs displayed a higher number of blood vessels containing hNSSCs compared to CAMs transplanted with undifferentiated hNSSCs. Interestingly, undifferentiated hNSSCs showed a propensity to differentiate towards ectoderm with indication of epidermal formation with cells positive for CD1a, CK5/6, CK19, FXIIIa, and S-100 cells, which warrant further investigation. Our findings imply a potential angiogenic role for hNSSCs ex vivo in the differentiated and undifferentiated state, with potential contribution to blood vessel formation and potential application in tissue regeneration and vascularization.

  19. The Potential for Snow to Supply Human Water Demand in the Present and Future

    Science.gov (United States)

    Mankin, Justin S.; Viviroli, Daniel; Singh, Deepti; Hoekstra, Arjen Y.; Diffenbaugh, Noah S.

    2015-01-01

    Runoff from snowmelt is regarded as a vital water source for people and ecosystems throughout the Northern Hemisphere (NH). Numerous studies point to the threat global warming poses to the timing and magnitude of snow accumulation and melt. But analyses focused on snow supply do not show where changes to snowmelt runoff are likely to present the most pressing adaptation challenges, given sub-annual patterns of human water consumption and water availability from rainfall. We identify the NH basins where present spring and summer snowmelt has the greatest potential to supply the human water demand that would otherwise be unmet by instantaneous rainfall runoff. Using a multi-model ensemble of climate change projections, we find that these basins - which together have a present population of approx. 2 billion people - are exposed to a 67% risk of decreased snow supply this coming century. Further, in the multi-model mean, 68 basins (with a present population of more than 300 million people) transition from having sufficient rainfall runoff to meet all present human water demand to having insufficient rainfall runoff. However, internal climate variability creates irreducible uncertainty in the projected future trends in snow resource potential, with about 90% of snow-sensitive basins showing potential for either increases or decreases over the near-term decades. Our results emphasize the importance of snow for fulfilling human water demand in many NH basins, and highlight the need to account for the full range of internal climate variability in developing robust climate risk management decisions.

  20. The potential for snow to supply human water demand in the present and future

    Science.gov (United States)

    Mankin, Justin S.; Viviroli, Daniel; Singh, Deepti; Hoekstra, Arjen Y.; Diffenbaugh, Noah S.

    2015-11-01

    Runoff from snowmelt is regarded as a vital water source for people and ecosystems throughout the Northern Hemisphere (NH). Numerous studies point to the threat global warming poses to the timing and magnitude of snow accumulation and melt. But analyses focused on snow supply do not show where changes to snowmelt runoff are likely to present the most pressing adaptation challenges, given sub-annual patterns of human water consumption and water availability from rainfall. We identify the NH basins where present spring and summer snowmelt has the greatest potential to supply the human water demand that would otherwise be unmet by instantaneous rainfall runoff. Using a multi-model ensemble of climate change projections, we find that these basins—which together have a present population of ∼2 billion people—are exposed to a 67% risk of decreased snow supply this coming century. Further, in the multi-model mean, 68 basins (with a present population of >300 million people) transition from having sufficient rainfall runoff to meet all present human water demand to having insufficient rainfall runoff. However, internal climate variability creates irreducible uncertainty in the projected future trends in snow resource potential, with about 90% of snow-sensitive basins showing potential for either increases or decreases over the near-term decades. Our results emphasize the importance of snow for fulfilling human water demand in many NH basins, and highlight the need to account for the full range of internal climate variability in developing robust climate risk management decisions.

  1. Benzodiazepines have no effect on fear-potentiated startle in humans.

    Science.gov (United States)

    Baas, Johanna M P; Grillon, Christian; Böcker, Koen B E; Brack, Anouk A; Morgan, Charles A; Kenemans, J Leon; Verbaten, Marinus N

    2002-05-01

    Pre-clinical and clinical investigations have provided a great deal of evidence that the fear-potentiated startle paradigm represents a valid model for the objective assessment of emotional states of anxiety and fear. The four studies presented in this report sought to further validate the "threat of shock" paradigm as a human analogue to fear-potentiated startle in rats, by examining the effect of benzodiazepine administration on both baseline and fear-potentiated startle. Three studies, conducted at Utrecht University, evaluated the effects of oxazepam and of diazepam on baseline and fear-potentiated startle, whereas a fourth study, conducted at Yale University, evaluated the effect of diazepam on baseline, contextual and cue-specific fear-potentiated startle. The threat of shock paradigm consisted of verbal instruction about two visual cues (the threat cue predicted the possible administration of electric shock, the other predicted a safe period), followed by a series of presentations of these cues. During these conditions, acoustic startle stimuli were presented in order to elicit startle responses. The magnitude of the startle response was used to index the degree of fear or alarm experienced during the periods of threat and safety. The fourth study examined the effect of IV administration of diazepam in a similar threat of shock paradigm except that there were two additional context manipulations: electrode placement and darkness. None of the drug manipulations affected specific threat-cue potentiation of startle. However, reductions in baseline startle were observed. Further, startle potentiation by darkness was inhibited by diazepam. At least one type of fear-potentiated startle, i.e. potentiation by a cue-specific fear manipulation, is not susceptible to benzodiazepine treatment. In contrast, effects of manipulations more akin to anxiety (darkness, context) appear sensitive to benzodiazepines. Human experimental models differentiating between these cue

  2. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral

    Directory of Open Access Journals (Sweden)

    Claire M. Smith

    2016-08-01

    Full Text Available Defective interfering (DI viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8 was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1; it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral.

  3. Screening of Differently Expressed Genes in Human Prostate Cancer Cell Lines with Different Metastasis Potentials

    Institute of Scientific and Technical Information of China (English)

    SONG Anping; LIAO Guoning; WU Mingfu; LU Yunping; MA Ding

    2007-01-01

    In order to screen the genes differentially expressed in two human prostate cancer cells with different metastasis potentials, suppression subtractive hybridization (SSH) was done twice on human prostate cancer cell line with high potential of metastasis PC3M-1E8 and its synogenetic cell line PC3M-2B4 with low metastasis potential. In the first subtraction PC3M-2B4 was used as tester and PC3M-1E8 as driver and the forward subtractive library was constructed. In the second one the tester and driver were interchanged and the reverse subtractive library was constructed. The screened clones of both libraries were sequenced and Gene Bank homology search was performed. Some clones were confirmed by quantitative real-time PCR. The results showed that two subtrac-tive libraries containing 238 positive clones were constructed. Analysis of 16 sequenced clones ran-domly picked from two libraries showed that 4 differentially expressed gene fragments were identi-fied as new EST with unknown functions. It was concluded that two subtractive libraries of human prostate cancer cell lines with different metastasis potentials were constructed successfully.

  4. In-Space Assembly Capability Assessment for Potential Human Exploration and Science Applications

    Science.gov (United States)

    Jefferies, Sharon A.; Jones, Christopher A.; Arney, Dale C.; Stillwagen, Frederic H.; Chai, Patrick R.; Hutchinson, Craig D.; Stafford, Matthew A.; Moses, Robert W.; Dempsey, James A.; Rodgers, Erica M.; hide

    2017-01-01

    Human missions to Mars present several major challenges that must be overcome, including delivering multiple large mass and volume elements, keeping the crew safe and productive, meeting cost constraints, and ensuring a sustainable campaign. Traditional methods for executing human Mars missions minimize or eliminate in-space assembly, which provides a narrow range of options for addressing these challenges and limits the types of missions that can be performed. This paper discusses recent work to evaluate how the inclusion of in-space assembly in space mission architectural concepts could provide novel solutions to address these challenges by increasing operational flexibility, robustness, risk reduction, crew health and safety, and sustainability. A hierarchical framework is presented to characterize assembly strategies, assembly tasks, and the required capabilities to assemble mission systems in space. The framework is used to identify general mission system design considerations and assembly system characteristics by assembly strategy. These general approaches are then applied to identify potential in-space assembly applications to address each challenge. Through this process, several focus areas were identified where applications of in-space assembly could affect multiple challenges. Each focus area was developed to identify functions, potential assembly solutions and operations, key architectural trades, and potential considerations and implications of implementation. This paper helps to identify key areas to investigate were potentially significant gains in addressing the challenges with human missions to Mars may be realized, and creates a foundation on which to further develop and analyze in-space assembly concepts and assembly-based architectures.

  5. PKC-mediated potentiation of morphine analgesia by St. John's Wort in rodents and humans.

    Science.gov (United States)

    Galeotti, Nicoletta; Farzad, Mersedeh; Bianchi, Enrica; Ghelardini, Carla

    2014-01-01

    Our purpose was to combine the use of morphine with clinically available inhibitors of protein kinase C (PKC), finally potentiating morphine analgesia in humans. Thermal tests were performed in rodents and humans previously administered with acute or chronic morphine combined or not with increasing doses of the PKC-blocker St. John's Wort (SJW) or its main component hypericin. Phosphorylation of the γ subunit of PKC enzyme was assayed by western blotting in the periaqueductal grey matter (PAG) from rodents co-administered with morphine and hypericin and was prevented in rodent PAG by SJW or hypericin co-administration with morphine, inducing a potentiation of morphine analgesia in thermal pain. The score of pain assessment in healthy volunteers were decreased by 40% when morphine was co-administered with SJW at a dose largely below those used to obtain an antidepressant or analgesic effect in both rodents and humans. The SJW/hypericin potentiating effect lasted in time and preserved morphine analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW could reduce the dose of morphine obtaining the same analgesic effect. Therefore, SJW and one of its main components, hypericin, appear ideal to potentiate morphine-induced analgesia.

  6. Polybrominated diphenyl ether (PBDE) flame retardants: environmental contamination, human body burden and potential adverse health effects.

    Science.gov (United States)

    Costa, Lucio G; Giordano, Gennaro; Tagliaferri, Sara; Caglieri, Andrea; Mutti, Antonio

    2008-12-01

    Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants, widely used in a variety of consumer products. In the past several years, PBDEs have become widespread environmental pollutants, and have been detected in water, soil, air, animals and human tissues. Exposure occurs in particular through the diet and the indoor environment. Infants and toddlers have the highest body burden, due to exposure via maternal milk and through house dust. Tetra-, penta- and hexa-BDEs are the congeners most commonly found in humans. Recent concerns on possible adverse health effects of PBDEs are focusing on their potential endocrine disrupting effects and on developmental neurotoxicity.

  7. Human health risk assessment of potentially toxic elements (PTEs) from environmental matrices

    OpenAIRE

    Elom, Nwabueze

    2012-01-01

    In assessing human health risk of potentially toxic elements (PTEs), it is not the concentration of PTEs in the environmental matrices that is of greatest concern but the fraction that is absorbed into the body via the exposure pathways. The determination of this fraction (i.e. the bioaccessible fraction) through the application of bioaccessibility protocols is the focus of this work. The study investigated human health risk of PTEs (As, Cd, Cr, Cu, Pb, Mn, Ni and Zn) from oral ingestion of s...

  8. The liver partition coefficient-corrected inhibitory quotient and the pharmacokinetic-pharmacodynamic relationship of directly acting anti-hepatitis C virus agents in humans.

    Science.gov (United States)

    Duan, Jianmin; Bolger, Gordon; Garneau, Michel; Amad, Ma'an; Batonga, Joëlle; Montpetit, Hélène; Otis, François; Jutras, Martin; Lapeyre, Nicole; Rhéaume, Manon; Kukolj, George; White, Peter W; Bethell, Richard C; Cordingley, Michael G

    2012-10-01

    Pharmacokinetic-pharmacodynamic (PK-PD) data analyses from early hepatitis C virus (HCV) clinical trials failed to show a good correlation between the plasma inhibitory quotient (IQ) and antiviral activity of different classes of directly acting antiviral agents (DAAs). The present study explored whether use of the liver partition coefficient-corrected IQ (LCIQ) could improve the PK-PD relationship. Animal liver partition coefficients (Kp(liver)) were calculated from liver to plasma exposure ratios. In vitro hepatocyte partition coefficients (Kp(hep)) were determined by the ratio of cellular to medium drug concentrations. Human Kp(liver) was predicted using an in vitro-in vivo proportionality method: the species-averaged animal Kp(liver) multiplied by the ratio of human Kp(hep) over those in animals. LCIQ was calculated using the IQ multiplied by the predicted human Kp(liver). Our results demonstrated that the in vitro-in vivo proportionality approach provided the best human Kp(liver) prediction, with prediction errors of <45% for all 5 benchmark drugs evaluated (doxorubicin, verapamil, digoxin, quinidine, and imipramine). Plasma IQ values correlated poorly (r(2) of 0.48) with maximum viral load reduction and led to a corresponding 50% effective dose (ED(50)) IQ of 42, with a 95% confidence interval (CI) of 0.1 to 148534. In contrast, the LCIQ-maximum VLR relationship fit into a typical sigmoidal curve with an r(2) value of 0.95 and an ED(50) LCIQ of 121, with a 95% CI of 83 to 177. The present study provides a novel human Kp(liver) prediction model, and the LCIQ correlated well with the viral load reductions observed in short-term HCV monotherapy of different DAAs and provides a valuable tool to guide HCV drug discovery.

  9. Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Anita Rózsás

    Full Text Available Recombinant human erythropoietins (rHuEPOs are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR signaling in human non-small cell lung cancer (NSCLC also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.

  10. Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

    Institute of Scientific and Technical Information of China (English)

    Zhao-You Tang; Lun-Xiu Qin; Hui-Chuan Sun; Lu Wang; Jian Zhou; Yah Li; Zeng-Chen Ma; Xin-Da Zhou; Zhi-Quan Wu; Zhi-Ying Lin; Bing-Hui Yang; Fan-Xian Sun; Jian Tian; Sheng-Long Ye; Yin-Kun Liu; Kang-Da Liu; Qiong Xue; Jie Chen; Jing-Lin Xia

    2001-01-01

    Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.``

  11. Correction of Murine Diabetic Hyperglycaemia With A Single Systemic Administration of An AAV2/8 Vector Containing A Novel Codon Optimized Human Insulin Gene.

    Science.gov (United States)

    Gan, Shu Uin; Notaridou, Maria; Fu, Zhen Ying; Lee, Kok Onn; Sia, Kian Chuan; Nathwani, Amit Chunilal; Della Peruta, Marco; Calne, Roy Yorke

    2016-01-01

    We report the correction of hyperglycemia of STZ induced diabetic mice using one intravenous systemic administration of a single stranded serotype 8 pseudotyped adeno-associated virus (ssAAV2/8) vector encoding the human proinsulin gene under a constitutive liver specific promoter. In vivo dose titration experiments were carried out and we identified an optimal range that achieved maintenance of euglycaemia or a mild diabetic condition for at least 9 months and ongoing to beyond 1 year for some animals, accompanied by human C-peptide secretion and weight gain. Further DNA codon optimization of the insulin gene construct resulted in approximately 3-10 times more human C-peptide secreted in the blood of codon optimized treated animals thereby reducing the number of vector particles required to achieve the same extent of reduction in blood glucose levels as the non-codon optimized vector. The constitutive secretion of insulin achieved with a single administration of the vector could be of therapeutic value for some diabetic patients.

  12. "Using recruitment source timing and diagnosticity to enhance applicants' occupation-specific human capital": Correction to Campion, Ployhart, and Campion (2017).

    Science.gov (United States)

    2017-05-01

    Reports an error in "Using Recruitment Source Timing and Diagnosticity to Enhance Applicants' Occupation-Specific Human Capital" by Michael C. Campion, Robert E. Ployhart and Michael A. Campion (Journal of Applied Psychology, Advanced Online Publication, Feb 02, 2017, np). In the article, the following headings were inadvertently set at the wrong level: Method, Participants and Procedure, Measures, Occupation specific human capital, Symbolic jobs, Relevant majors, Occupation-specific capital hotspots, Source timing, Source diagnosticity, Results, and Discussion. All versions of this article have been corrected. (The following abstract of the original article appeared in record 2017-04566-001.) This study proposes that reaching applicants through more diagnostic recruitment sources earlier in their educational development (e.g., in high school) can lead them to invest more in their occupation-specific human capital (OSHC), thereby making them higher quality candidates. Using a sample of 78,157 applicants applying for jobs within a desirable professional occupation in the public sector, results indicate that applicants who report hearing about the occupation earlier, and applicants who report hearing about the occupation through more diagnostic sources, have higher levels of OSHC upon application. Additionally, source timing and diagnosticity affect the likelihood of candidates applying for jobs symbolic of the occupation, selecting relevant majors, and attending educational institutions with top programs related to the occupation. These findings suggest a firm's recruiting efforts may influence applicants' OSHC investment strategies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  13. Constancy and characteristics of the anterior cutaneous branch of the first intercostal nerve: correcting the descriptions in human anatomy texts.

    Science.gov (United States)

    Miyawaki, Makoto

    2006-12-01

    Human anatomy texts state that the anterior cutaneous branch of the first intercostal nerve (Rca-Th1) does not exist or that, even if it does, it is poorly developed. However, an anterior cutaneous branch in the first intercostal space (Rca-1) was observed in 74.8% of cases examined (104/139 sides) and was not poorly developed at all. Some of the observed Rca-I were even larger than the anterior cutaneous branches in the second intercostal space (Rca-ll). The segment of origin of the Rca-I was analyzed in 37 sides and 66.2% (49/74 branches) were confirmed to be from Th1. As a result, in contrast with traditional beliefs, it was shown that Rca-Th1 exists. The Rca-I was classified into two types according to the course and distribution: (i) an anterior cutaneous branch that appeared at the anterior end of the first intercostal space (ICS), ran through the pectoralis major muscle and extended in the first ICS (Rca-1); and (ii) another branch that appeared at the same place but ran downward along the anterior surface of the second costal cartilage, deep to the pectoralis major muscle, to reach the inferior edge of the second costal cartilage or the second ICS, passed through the pectoralis major muscle and extended to the second rib or the second ICS (pseudo Rca-2). It was found that 77.8% (35/45 branches) of Rca-1 and 48.3% (14/29 branches) of pseudo Rca-2 were derived from Th1. Accordingly, the author suggests that the description in human anatomy texts should be revised to read, '... the Rca-Th1 exists quite constantly and some of appear at a position resembling Rca-Th2'.

  14. Optimal humanization of 1B4, an anti-CD18 murine monoclonal antibody, is achieved by correct choice of human V-region framework sequences.

    Science.gov (United States)

    Singer, I I; Kawka, D W; DeMartino, J A; Daugherty, B L; Elliston, K O; Alves, K; Bush, B L; Cameron, P M; Cuca, G C; Davies, P

    1993-04-01

    The murine anti-CD18 mAb 1B4 has been humanized using CDR grafting. Three VH (Gal, Jon, and New) and two VL (Rei and Len) human frameworks, whose selection was based exclusively on their sequence identity with m1B4, were used to construct five human gamma 4/kappa recombinant antibodies: Gal/Rei, Gal/Len, Jon/Rei, and New/Rei, and a "hemichimeric" antibody pairing the VH of m1B4 with grafted Rei. Each of these h1B4 constructs completely inhibited the binding of m1B4 to activated human leukocytes with avidities (IC50) ranging from 1.5 to 8.0 nM, compared to 0.5 nM for m1B4. Replacement of three VH residues in the best VH framework, Gal, with the corresponding m1B4 "packing" (nonsolvent exposed) residues gave an h1B4 (mutant Gal/Rei) with the same avidity as m1B4. Avidity correlated with overall percent identity between the human and murine VH frameworks and, in particular, with conservation of "packing" residues. Rei and Len VL frameworks proved to be interchangeable. Further characterization showed that the Gal/Rei prototype was equipotent to m1B4 in blocking adhesion of polymorphonuclear leukocytes and monocytes to human vascular endothelium in vitro, and polymorphonuclear leukocyte extravasation into C5a-injected rabbit or monkey skin sites. Dual-label immunofluorescence microscopy of bone marrow cells with Gal/Rei h1B4 and m1B4 demonstrated that the fine specificity of the combining sites had not been altered by humanization. Reduced immunogenicity was demonstrated in rhesus monkeys that tolerated weekly treatment with h1B4 for 6 wk, whereas m1B4 induced profound anaphylaxis at 3 wk. Anti-1B4 titers in h1B4-treated rhesus were 50 to 66% lower and developed 1 wk later than in m1B4-treated monkeys. Crucially, the anti-h1B4 antibodies were anti-idiotypic while the anti-m1B4 antibodies were directed against constant and framework regions. We conclude that sequence identity searches are sufficient to identify suitable human frameworks for CDR-grafting of m1B4

  15. Influence of Physical Activity on Human Sensory Long-Term Potentiation.

    Science.gov (United States)

    Smallwood, Nicola; Spriggs, Meg J; Thompson, Christopher S; Wu, Carolyn C; Hamm, Jeff P; Moreau, David; Kirk, Ian J

    2015-11-01

    A growing body of literature has explored the influence of physical activity on brain structure and function. While the mechanisms of this relationship remain largely speculative, recent research suggests that one of the effects of physical exercise is an increase in synaptic long-term potentiation (LTP). This has not yet been explored directly in humans due to the difficulty of measuring LTP non-invasively. However, we have previously established that LTP-like changes in visual-evoked potentials (VEPs) can be measured in humans. Here, we investigated whether physical fitness status affects the degree of visual sensory LTP. Using a self-report measure of physical activity, participants were split into two groups: a high-activity group, and a low-activity group. LTP was measured and compared between the two groups using the previously established electroencephalography-LTP paradigm, which assesses the degree to which the N1b component of the VEP elicited by a sine grating is potentiated (enhanced) following a rapid "tetanic" presentation of that grating. Both groups demonstrated increased negativity in the amplitude of the N1b component of the VEP immediately after presentation of the visual "tetanus," indicating potentiation. However, after a 30-min rest period, the N1b for the high-activity group remained potentiated while the N1b for the low-activity group returned to baseline. This study presents the first evidence for the impact of self-reported levels of physical activity on LTP in humans, and sheds light on potential neurological mechanisms underlying the relationship between physical fitness and cognition.

  16. Event-related potential study on image-symmetry discrimination in the human brain.

    Science.gov (United States)

    Sambul, Alwin Melkie; Murayama, Nobuki; Igasaki, Tomohiko

    2013-01-01

    The human visual system seems to have a highly perceptual sensitivity to symmetry. However, where and when the discrimination of symmetrical properties begins in the context of visual information processing is largely unclear. This study investigates event-related potential (ERP) patterns in humans when perceiving symmetry-varied complex object images. ERP responses were derived from electroencephalography (EEG) data recorded from eight healthy subjects using 128-channel scalp electrodes. Visual stimulation was provided using gray-scaled photographs of a car with six different viewpoints, hence disrupting the vertical symmetry, where one of the stimuli was intentionally made symmetric by mirroring the image about its center vertical axis. The results show that discrimination of image symmetry is revealed by potential deflection in early ERP components recorded at occipito-temporal sites and can be significantly observed around 220 ms after stimulus onset.

  17. Prevalence and pathogenic potential of campylobacter isolates from free-living, human-commensal american crows.

    Science.gov (United States)

    Weis, Allison M; Miller, Woutrina A; Byrne, Barbara A; Chouicha, Nadira; Boyce, Walter M; Townsend, Andrea K

    2014-03-01

    Recent studies have suggested a potential role for wild birds in zoonotic transmission of Campylobacter jejuni, the leading cause of gastroenteritis in humans worldwide. In this study, we detected Campylobacter spp. in 66.9% (85/127) of free-ranging American crows (Corvus brachyrhyncos) sampled in the Sacramento Valley of California in 2012 and 2013. Biochemical testing and sequence analysis of 16S rRNA revealed that 93% of isolates (n = 70) were C. jejuni, with cytolethal distending toxin (CDT) and flagellin A genes detected by PCR in 20% and 46% of the C. jejuni isolates (n = 59), respectively. The high prevalence of C. jejuni, coupled with the occurrence of known virulence markers CDT and flagellin A, demonstrates that crows shed Campylobacter spp. in their feces that are potentially pathogenic to humans. Crows are abundant in urban, suburban, and agricultural settings, and thus further study to determine their role in zoonotic transmission of Campylobacter will inform public health.

  18. Refraction corrections for surveying

    Science.gov (United States)

    Lear, W. M.

    1980-01-01

    Optical measurements of range and elevation angles are distorted by refraction of Earth's atmosphere. Theoretical discussion of effect, along with equations for determining exact range and elevation corrections, is presented in report. Potentially useful in optical site surveying and related applications, analysis is easily programmed on pocket calculator. Input to equation is measured range and measured elevation; output is true range and true elevation.

  19. Potential use of mesenchymal stem cells in human meniscal repair: current insights

    Science.gov (United States)

    Pak, Jaewoo; Lee, Jung Hun; Park, Kwang Seung; Jeon, Jeong Ho; Lee, Sang Hee

    2017-01-01

    The menisci of the human knee play an important role in maintaining normal functions to provide stability and nutrition to the articular cartilage, and to absorb shock. Once injured, these important structures have very limited natural healing potential. Unfortunately, the traditional arthroscopic meniscectomy performed on these damaged menisci may predispose the joint toward early development of osteoarthritis. Although a very limited number of studies are available, mesenchymal stem cells (MSCs) have been investigated as an alternative therapeutic modality to repair human knee meniscal tears. This review summarizes the results of published applications of MSCs in human patients, which showed that the patients who received MSCs (autologous adipose tissue-derived stem cells or culture-expanded bone marrow-derived stem cells) presented symptomatic improvements, along with magnetic resonance imaging evidences of the meniscal repair. PMID:28356779

  20. Characterization and angiogenic potential of human neonatal and infant thymus mesenchymal stromal cells.

    Science.gov (United States)

    Wang, Shuyun; Mundada, Lakshmi; Johnson, Sean; Wong, Joshua; Witt, Russell; Ohye, Richard G; Si, Ming-Sing

    2015-04-01

    Resident mesenchymal stromal cells (MSCs) are involved in angiogenesis during thymus regeneration. We have previously shown that MSCs can be isolated from enzymatically digested human neonatal and infant thymus tissue that is normally discarded during pediatric cardiac surgical procedures. In this paper, we demonstrate that thymus MSCs can also be isolated by explant culture of discarded thymus tissue and that these cells share many of the characteristics of bone marrow MSCs. Human neonatal thymus MSCs are clonogenic, demonstrate exponential growth in nearly 30 population doublings, have a characteristic surface marker profile, and express pluripotency genes. Furthermore, thymus MSCs have potent proangiogenic behavior in vitro with sprout formation and angiogenic growth factor production. Thymus MSCs promote neoangiogenesis and cooperate with endothelial cells to form functional human blood vessels in vivo. These characteristics make thymus MSCs a potential candidate for use as an angiogenic cell therapeutic agent and for vascularizing engineered tissues in vitro.

  1. The Concept and Use of Human Security: A Critical Analysis of its Potentialities and Risks

    Directory of Open Access Journals (Sweden)

    Karlos Pérez de Armiño

    2007-02-01

    Full Text Available Bearing in mind the existence of different approaches to human security (the broad one and the restricted one, this article analyses the scope of this new paradigm based on a study of its contributions and potentialities, as well as the risks entailed in applying it. Among the positive contributions, it must be highlighted that: it focuses on the person as the subject of security, and not on the State; it is linked to human development and human rights; and it underscores the need for public policies and so-called ‘humanitarianinterventions’. On the other hand, the risks have grown following 9/11, with the paradigm being used more in its security dimension and less in its development-related aspect.

  2. Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid-derived stem cells.

    Science.gov (United States)

    Kang, N-H; Hwang, K-A; Kim, S U; Kim, Y-B; Hyun, S-H; Jeung, E-B; Choi, K-C

    2012-08-01

    As stem cells are capable of self-renewal and can generate differentiated progenies for organ development, they are considered as potential source for regenerative medicine and tissue replacement after injury or disease. Along with this capacity, stem cells have the therapeutic potential for treating human diseases including cancers. According to the origins, stem cells are broadly classified into two types: embryonic stem cells (ESCs) and adult stem cells. In terms of differentiation potential, ESCs are pluripotent and adult stem cells are multipotent. Amnion, which is a membranous sac that contains the fetus and amniotic fluid and functions in protecting the developing embryo during gestation, is another stem cell source. Amnion-derived stem cells are classified as human amniotic membrane-derived epithelial stem cells, human amniotic membrane-derived mesenchymal stem cells and human amniotic fluid-derived stem cells. They are in an intermediate stage between pluripotent ESCs and lineage-restricted adult stem cells, non-tumorigenic, and contribute to low immunogenicity and anti-inflammation. Furthermore, they are easily available and do not cause any controversial issues in their recovery and applications. Not only are amnion-derived stem cells applicable in regenerative medicine, they have anticancer capacity. In non-engineered stem cells transplantation strategies, amnion-derived stem cells effectively target the tumor and suppressed the tumor growth by expressing cytotoxic cytokines. Additionally, they also have a potential as novel delivery vehicles transferring therapeutic genes to the cancer formation sites in gene-directed enzyme/prodrug combination therapy. Owing to their own advantageous properties, amnion-derived stem cells are emerging as a new candidate in anticancer therapy.

  3. Enhancement of the amplitude of somatosensory evoked potentials following magnetic pulse stimulation of the human brain.

    Science.gov (United States)

    Seyal, M; Browne, J K; Masuoka, L K; Gabor, A J

    1993-01-01

    In this study we have demonstrated an enhancement of cortically generated wave forms of the somatosensory evoked potential (SEP) following magnetic pulse stimulation of the human brain. Subcortically generated activity was unaltered. The enhancement of SEP amplitude was greatest when the median nerve was stimulated 30-70 msec following magnetic pulse stimulation over the contralateral parietal scalp. We posit that the enhancement of the SEP is the result of synchronization of pyramidal cells in the sensorimotor cortex resulting from the magnetic pulse.

  4. Psychiatry and human rights: a difficult relationship, but with a growing potential.

    Science.gov (United States)

    Jarab, Jan

    2015-01-01

    Persons with psychosocial disabilities (mental health problems) are under the protection of the new United Nations Convention on Rights of Persons with Disabilities (CRPD). The CRPD brings a human rights-based approach to disability: it challenges paternalistic views by emphasizing the person as a rights-holder, an active subject, and not just a passive object of care. It also represents a challenge to mainstream human rights movements and mechanisms who have long paid insufficient attention to human rights of persons with (psychosocial) disabilities. It is increasingly understood that human rights of persons with psychosocial disabilities (mental health problems) should not be seen in the narrow perspective, as if the only issue was the most controversial one, that is, deprivation of liberty. In many areas, reform-minded psychiatrists have themselves initiated human rights-friendly reforms. For instance, efforts to implement article 19 of the CRPD—independent living and inclusion in the community—are increasingly becoming part of the mainstream in mental health care. There is potential for further synergy between mental health professionals and human rights activists in looking at the whole range of civil, political, economic, and social rights listed in the Universal Declaration of Human Rights—realizing that all these rights apply also to persons with psychosocial disabilities, and working together towards removing real-life obstacles to their enjoyment.The building of bridges between the two different types of expertise should be encouraged. In this regard, psychiatry would benefit from more cooperation across borders as well as with international human rights bodies, non-governmental organizations and persons with psychosocial disabilities themselves

  5. A Cas9 Variant for Efficient Generation of Indel-Free Knockin or Gene-Corrected Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Sara E. Howden

    2016-09-01

    Full Text Available While Cas9 nucleases permit rapid and efficient generation of gene-edited cell lines, the CRISPR-Cas9 system can introduce undesirable “on-target” mutations within the second allele of successfully modified cells via non-homologous end joining (NHEJ. To address this, we fused the Streptococcus pyogenes Cas9 (SpCas9 nuclease to a peptide derived from the human Geminin protein (SpCas9-Gem to facilitate its degradation during the G1 phase of the cell cycle, when DNA repair by NHEJ predominates. We also use mRNA transfection to facilitate low and transient expression of modified and unmodified versions of Cas9. Although the frequency of homologous recombination was similar for SpCas9-Gem and SpCas9, we observed a marked reduction in the capacity for SpCas9-Gem to induce NHEJ-mediated indels at the target locus. Moreover, in contrast to native SpCas9, we demonstrate that transient SpCas9-Gem expression enables reliable generation of both knockin reporter cell lines and genetically repaired patient-specific induced pluripotent stem cell lines free of unwanted mutations at the targeted locus.

  6. Intranasal "painless" human Nerve Growth Factor [corrected] slows amyloid neurodegeneration and prevents memory deficits in App X PS1 mice.

    Directory of Open Access Journals (Sweden)

    Simona Capsoni

    Full Text Available Nerve Growth Factor (NGF is being considered as a therapeutic candidate for Alzheimer's disease (AD treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V, which would allow increasing the dose of NGF without triggering pain. We show that "painless" hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8, hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of "painless" hNGF variants as a new generation of therapeutics for neurodegenerative diseases.

  7. The Food and Beverage Occurrence of Furfuryl Alcohol and Myrcene—Two Emerging Potential Human Carcinogens?

    Directory of Open Access Journals (Sweden)

    Alex O. Okaru

    2017-03-01

    Full Text Available For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The World Health Organization (WHO International Agency for Research on Cancer (IARC continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene are potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages, while β-myrcene occurs naturally as a constituent of the essential oils of plants such as hops, lemongrass, and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using literature review data. Additionally, results of furfuryl alcohol occurrence from our own nuclear magnetic resonance (NMR analysis are included. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg and in some fish products (about 10 mg/kg, while among beverages, wines contained between 1 and 10 mg/L, with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

  8. Upregulated and prolonged differentiation potential of the ependymal cells lining the ventriculus terminalis in human fetuses.

    Science.gov (United States)

    Song, Dae Yong; Cho, Byung Pil; Choi, Byoung Young; Yang, Young Chul; Lee, Bong Hee; Lim, Chang Kyo; Kang, Ho Suck

    2005-09-23

    The ventriculus terminalis (VT) is a dilated cavity within the conus medullaris of the spinal cord. Although the VT was discovered in the mid-nineteenth century, little is known about its characteristics during development in human fetuses. Ependymal cells lining the cavities within the CNS retain high differentiation potential, and are believed to be responsible for the postnatal neurogenesis. To evaluate the differentiation capacity of the ependymal cells lining the VT during development, we examined glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA) expression in the spinal cord of 18-24-week-old human fetuses. GFAP is a marker for the degree of ependymal cell differentiation in the human fetus, and PCNA is a well-known marker for cell division. Morphological characteristics of the VT were also examined. At the lower portion of the conus medullaris, the central canal abruptly expands dorsally to become the VT. Then the VT widens bilaterally while its anteroposterior diameter reduces gradually in a caudal direction. Finally, the VT becomes a narrow, transverse slit at the level of the lowermost conus medullaris. Compared with those lining the central canal, more numerous ependymal cells lining the VT showed more intensive GFAP and PCNA expression throughout all gestational ages examined. This suggests that, in the developing human spinal cord, ependymal cells lining the VT retain their differentiation potential, including a higher proliferative capacity, until a later stage of development than those lining the central canal.

  9. Potential Role of Pet Cats As a Sentinel Species for Human Exposure to Flame Retardants

    Directory of Open Access Journals (Sweden)

    Luis A. Henríquez-Hernández

    2017-05-01

    Full Text Available Flame retardants are a wide group of chemicals used by the industry to avoid combustion of materials. These substances are commonly found in plastics, electronic equipment, fabrics, and in many other everyday articles. Subsequently, ubiquitous environmental contamination by these common chemical is frequently reported. In the present study, we have evaluated the level of exposure to polychlorinated biphenyls (PCBs, brominated diphenyl ethers (BDEs, and organophosphorous flame retardants (OPFRs in pet cats through the analysis of their serum. We also analyzed the level exposure to such chemicals in a series of 20 cat owners, trying to disclose the role of pet cats as sentinel species of human exposure to FRs. Our results showed that PCBs, banned 40 years ago, showed the lowest levels of exposure, followed by BDEs—banned recently. Congeners PCB-138 and PCB-180 were detected in ≥50% of the series, while BDE-47 was detected in near 90% of the pet cats. On the other hand, the highest levels were that of OPFRs, whose pattern of detection was similar to that observed in humans, thus suggesting a potential role of cats as a sentinel species for human exposure to these currently used FRs. Six out of 11 OPFRs determined [2-ethylhexyldiphenyl phosphate, tributylphosphate, triisobutylphosphate, triphenylphosphate, tris (2-chloroethyl phosphate, and tris (2-chloroisopropyl phosphate] were detected in 100% of the samples. It will be interesting to perform future studied aimed to elucidating the potential toxicological effects of these highly detected chemicals both, in cats and humans.

  10. Periodontitis promotes the proliferation and suppresses the differentiation potential of human periodontal ligament stem cells.

    Science.gov (United States)

    Zheng, Wei; Wang, Shi; Wang, Jianguo; Jin, Fang

    2015-10-01

    The aim of the present study was to investigate the periodontitis-associated changes in the number, proliferation and differentiation potential of human periodontal ligament stem cells (PDLSCs). Cultures of human periodontal ligament cells (PDLCs) were established from healthy donors and donors with periodontitis. The numbers of stem cell were characterized using flow cytometry. PDLSCs were isolated from the PDLCs by immunomagnetic bead selection. Colony‑forming abilities, osteogenic and adipogenic potential, gene expression of cementoblast phenotype, alkaline phosphatase activity and in vivo differentiation capacities were then evaluated. Periodontitis caused an increase in the proliferation of PDLSCs and a decrease in the commitment to the osteoblast lineage. This is reflected by changes in the expression of osteoblast markers. When transplanted into immunocompromised mice, PDLSCs from the healthy donors exhibited the capacity to produce cementum PDL‑like structures, whereas, the inflammatory PDLSCs transplants predominantly formed connective tissues. In conclusion, the data from the present study suggest that periodontitis affects the proliferation and differentiation potential of human PDLSCs in vitro and in vivo.

  11. Tissue engineering potential of human dermis-isolated adult stem cells from multiple anatomical locations.

    Science.gov (United States)

    Kwon, Heenam; Haudenschild, Anne K; Brown, Wendy E; Vapniarsky, Natalia; Paschos, Nikolaos K; Arzi, Boaz; Hu, Jerry C; Athanasiou, Kyriacos A

    2017-01-01

    Abundance and accessibility render skin-derived stem cells an attractive cell source for tissue engineering applications. Toward assessing their utility, the variability of constructs engineered from human dermis-isolated adult stem (hDIAS) cells was examined with respect to different anatomical locations (foreskin, breast, and abdominal skin), both in vitro and in a subcutaneous, athymic mouse model. All anatomical locations yielded hDIAS cells with multi-lineage differentiation potentials, though adipogenesis was not seen for foreskin-derived hDIAS cells. Using engineered cartilage as a model, tissue engineered constructs from hDIAS cells were compared. Construct morphology differed by location. The mechanical properties of human foreskin- and abdominal skin-derived constructs were similar at implantation, remaining comparable after 4 additional weeks of culture in vivo. Breast skin-derived constructs were not mechanically testable. For all groups, no signs of abnormality were observed in the host. Addition of aggregate redifferentiation culture prior to construct formation improved chondrogenic differentiation of foreskin-derived hDIAS cells, as evident by increases in glycosaminoglycan and collagen contents. More robust Alcian blue staining and homogeneous cell populations were also observed compared to controls. Human DIAS cells elicited no adverse host responses, reacted positively to chondrogenic regimens, and possessed multi-lineage differentiation potential with the caveat that efficacy may differ by anatomical origin of the skin. Taken together, these results suggest that hDIAS cells hold promise as a potential cell source for a number of tissue engineering applications.

  12. Evolution of the clonogenic potential of human epidermal stem/progenitor cells with age.

    Science.gov (United States)

    Zobiri, Olivia; Deshayes, Nathalie; Rathman-Josserand, Michelle

    2012-01-01

    A number of clinical observations have indicated that the regenerative potential and overall function of the epidermis is modified with age. The epidermis becomes thinner, repairs itself less efficiently after wounding, and presents modified barrier function recovery. In addition, the dermal papillae fatten out with increasing age, suggesting a modification in the interaction between epidermal and dermal compartments. As the epidermal regenerative capacity is dependent upon stem and progenitor cell function, it is naturally of interest to identify and understand age-related changes in these particular keratinocyte populations. Previous studies have indicated that the number of stem cells does not decrease with age in mouse models but little solid evidence is currently available concerning human skin. The objective of this study was to evaluate the clonogenic potential of keratinocyte populations isolated from the epidermis of over 50 human donors ranging from 18 to 71 years old. The data indicate that the number of epidermal cells presenting high regenerative potential does not dramatically decline with age in human skin. The authors believe that changes in the microenvironment controlling epidermal basal cell activity are more likely to explain the differences in epidermal function observed with increasing age.

  13. Evolution of the clonogenic potential of human epidermal stem/progenitor cells with age

    Directory of Open Access Journals (Sweden)

    Zobiri O

    2012-02-01

    Full Text Available Olivia Zobiri, Nathalie Deshayes, Michelle Rathman-JosserandDepartment of Biological Research, L'Oréal Advanced Research, Clichy Cedex, FranceAbstract: A number of clinical observations have indicated that the regenerative potential and overall function of the epidermis is modified with age. The epidermis becomes thinner, repairs itself less efficiently after wounding, and presents modified barrier function recovery. In addition, the dermal papillae flatten out with increasing age, suggesting a modification in the interaction between epidermal and dermal compartments. As the epidermal regenerative capacity is dependent upon stem and progenitor cell function, it is naturally of interest to identify and understand age-related changes in these particular keratinocyte populations. Previous studies have indicated that the number of stem cells does not decrease with age in mouse models but little solid evidence is currently available concerning human skin. The objective of this study was to evaluate the clonogenic potential of keratinocyte populations isolated from the epidermis of over 50 human donors ranging from 18 to 71 years old. The data indicate that the number of epidermal cells presenting high regenerative potential does not dramatically decline with age in human skin. The authors believe that changes in the microenvironment controlling epidermal basal cell activity are more likely to explain the differences in epidermal function observed with increasing age.Keywords: skin, epidermal stem cells, aging, colony-forming efficiency test

  14. Robotic Reconnaissance Missions to Small Bodies and Their Potential Contributions to Human Exploration

    Science.gov (United States)

    Abell, P. A.; Rivkin, A. S.

    2015-01-01

    Introduction: Robotic reconnaissance missions to small bodies will directly address aspects of NASA's Asteroid Initiative and will contribute to future human exploration. The NASA Asteroid Initiative is comprised of two major components: the Grand Challenge and the Asteroid Mission. The first component, the Grand Challenge, focuses on protecting Earth's population from asteroid impacts by detecting potentially hazardous objects with enough warning time to either prevent them from impacting the planet, or to implement civil defense procedures. The Asteroid Mission involves sending astronauts to study and sample a near- Earth asteroid (NEA) prior to conducting exploration missions of the Martian system, which includes Phobos and Deimos. The science and technical data obtained from robotic precursor missions that investigate the surface and interior physical characteristics of an object will help identify the pertinent physical properties that will maximize operational efficiency and reduce mission risk for both robotic assets and crew operating in close proximity to, or at the surface of, a small body. These data will help fill crucial strategic knowledge gaps (SKGs) concerning asteroid physical characteristics that are relevant for human exploration considerations at similar small body destinations. Small Body Strategic Knowledge Gaps: For the past several years NASA has been interested in identifying the key SKGs related to future human destinations. These SKGs highlight the various unknowns and/or data gaps of targets that the science and engineering communities would like to have filled in prior to committing crews to explore the Solar System. An action team from the Small Bodies Assessment Group (SBAG) was formed specifically to identify the small body SKGs under the direction of the Human Exploration and Operations Missions Directorate (HEOMD), given NASA's recent interest in NEAs and the Martian moons as potential human destinations [1]. The action team

  15. The potential utility of animal poisoning data to identify human exposure to environmental toxins.

    Science.gov (United States)

    Hungerford, L L; Trammel, H L; Clark, J M

    1995-04-01

    The database of the National Animal Poison Control Center (NAPCC) was evaluated as a source for animal poison data indicating human health hazards in indoor and outdoor environments. From 14,150 calls in the 1985 database, 259 cases were identified with histories suggesting human exposure. A subgroup of 25 cases with known human exposure was found. Dogs were the most common sentinel animal, but bird cases represented the highest proportional selection from the total 1985 call list. Indoor exposures represented 43.2% of cases; the most common toxicants were insecticides, lead and toxic fumes. Exposures associated with lawns were mainly due to insecticides and herbicides and constituted 25.5% of cases. Other outdoor exposures composed the remaining 31.7% of cases, with insecticides, herbicides and unidentified toxins the leading categories. Many of the specific agents identified, such as organophosphate insecticides, lead, gas and fume toxins, and phenoxy herbicides are also risk factors in human diseases. This study indicates that databases such as NAPCC could serve as sources of sentinel animal intoxications for followup studies to evaluate known and potential human health hazards.

  16. Transient receptor potential vanilloid-1 signaling as a regulator of human sebocyte biology.

    Science.gov (United States)

    Tóth, Balázs I; Géczy, Tamás; Griger, Zoltán; Dózsa, Anikó; Seltmann, Holger; Kovács, László; Nagy, László; Zouboulis, Christos C; Paus, Ralf; Bíró, Tamás

    2009-02-01

    Transient receptor potential vanilloid-1 (TRPV1), originally described as a central integrator of nociception, is expressed on human epidermal and hair follicle keratinocytes and is involved in regulation of cell growth and death. In human pilosebaceous units, we had shown that TRPV1 stimulation inhibits hair shaft elongation and matrix keratinocyte proliferation, and induces premature hair follicle regression and keratinocyte apoptosis. In the current study, we have explored the role of TRPV1-mediated signaling in sebaceous gland (SG) biology, using a human sebocyte cell culture model (SZ95 sebocytes). Demonstrating that human skin SG in situ and SZ95 sebocytes in vitro express TRPV1, we show that the prototypic TRPV1 agonist, capsaicin, selectively inhibits basal and arachidonic acid-induced lipid synthesis in a dose-, time-, and extracellular calcium-dependent and a TRPV1-specific manner. Low-dose capsaicin stimulates cellular proliferation via TRPV1, whereas higher concentrations inhibit sebocyte growth and induce cell death independent of TRPV1. Moreover, capsaicin suppresses the expression of genes involved in lipid homeostasis and of selected proinflammatory cytokines. Collectively, these findings support the concept that TRPV1 signaling is a significant, previously unreported player in human sebocyte biology and identify TRPV1 as a promising target in the clinical management of inflammatory SG disorders (for example, acne vulgaris).

  17. The pertinence and potential of surgery to correct presbyopia%老视矫正手术的临床应用与展望

    Institute of Scientific and Technical Information of China (English)

    李莹

    2015-01-01

    With changing times and advancing technology, presbyopia has gradually attracted more and more focus and concern.Laser treatment to correct presbyopia, like that to correct ametropia, has been advancing fast in both research and the development of devices as well as in clinical practice, with techniques such as corneal laser, corneal inlay, corneal thermal remodeling and scleral gasification.However, presbyopia is different from ametropia (myopia, hyperopia and astigmatism) in that refractive error in ametropia remains relatively stable when people reach a certain age.Presbyopia, on the other hand, is closely related to age.At present we are faced with a large population with presbyopia, and more and more people are looking forward to a surgical technique for correcting presbyopia that is safe, effective, highly predictable, and with a range that corrects for distance, intermediate and near vision.%随着人们对生活质量的需求提高,老视问题越来越受到关注.像屈光不正矫正手术一样,老视的激光矫正治疗无论是设备开发还是临床手术的应用都逐年增多,如角膜的激光、角膜板层间镶嵌、角膜热重塑、巩膜气化等.但是老视又与屈光不正(近视、远视和散光)不同,到了一定年龄屈光度会相对稳定,而老视则与年龄有紧密的相关性.目前老视人群庞大,因此有许多人期待着安全、有效、可预测性强、远中近视力都能兼顾的老视矫治手术.

  18. Maximum diastolic potential of human induced pluripotent stem cell-derived cardiomyocytes depends critically on I(Kr).

    Science.gov (United States)

    Doss, Michael Xavier; Di Diego, José M; Goodrow, Robert J; Wu, Yuesheng; Cordeiro, Jonathan M; Nesterenko, Vladislav V; Barajas-Martínez, Héctor; Hu, Dan; Urrutia, Janire; Desai, Mayurika; Treat, Jacqueline A; Sachinidis, Agapios; Antzelevitch, Charles

    2012-01-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) hold promise for therapeutic applications. To serve these functions, the hiPSC-CM must recapitulate the electrophysiologic properties of native adult cardiomyocytes. This study examines the electrophysiologic characteristics of hiPSC-CM between 11 and 121 days of maturity. Embryoid bodies (EBs) were generated from hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record action potentials (AP) from spontaneously beating clusters (BC) micro-dissected from the EBs (n = 103; 37°C) and to examine the response to 5 µM E-4031 (n = 21) or BaCl(2) (n = 22). Patch-clamp techniques were used to record I(Kr) and I(K1) from cells enzymatically dissociated from BC (n = 49; 36°C). Spontaneous cycle length (CL) and AP characteristics varied widely among the 103 preparations. E-4031 (5 µM; n = 21) increased Bazett-corrected AP duration from 291.8±81.2 to 426.4±120.2 msec (pKr) in all (11/11). Consistent with the electrophysiological data, RT-PCR and immunohistochemistry studies showed relatively poor mRNA and protein expression of I(K1) in the majority of cells, but robust expression of I(Kr.) In contrast to recently reported studies, our data point to major deficiencies of hiPSC-CM, with remarkable diversity of electrophysiologic phenotypes as well as pharmacologic responsiveness among beating clusters and cells up to 121 days post-differentiation (dpd). The vast majority have a maximum diastolic potential that depends critically on I(Kr) due to the absence of I(K1). Thus, efforts should be directed at producing more specialized and mature hiPSC-CM for future therapeutic applications.

  19. Potential environmental and human health impacts of rechargeable lithium batteries in electronic waste.

    Science.gov (United States)

    Kang, Daniel Hsing Po; Chen, Mengjun; Ogunseitan, Oladele A

    2013-05-21

    Rechargeable lithium-ion (Li-ion) and lithium-polymer (Li-poly) batteries have recently become dominant in consumer electronic products because of advantages associated with energy density and product longevity. However, the small size of these batteries, the high rate of disposal of consumer products in which they are used, and the lack of uniform regulatory policy on their disposal means that lithium batteries may contribute substantially to environmental pollution and adverse human health impacts due to potentially toxic materials. In this research, we used standardized leaching tests, life-cycle impact assessment (LCIA), and hazard assessment models to evaluate hazardous waste classification, resource depletion potential, and toxicity potentials of lithium batteries used in cellphones. Our results demonstrate that according to U.S. federal regulations, defunct Li-ion batteries are classified hazardous due to their lead (Pb) content (average 6.29 mg/L; σ = 11.1; limit 5). However, according to California regulations, all lithium batteries tested are classified hazardous due to excessive levels of cobalt (average 163,544 mg/kg; σ = 62,897; limit 8000), copper (average 98,694 mg/kg; σ = 28,734; limit 2500), and nickel (average 9525 mg/kg; σ = 11,438; limit 2000). In some of the Li-ion batteries, the leached concentrations of chromium, lead, and thallium exceeded the California regulation limits. The environmental impact associated with resource depletion and human toxicity is mainly associated with cobalt, copper, nickel, thallium, and silver, whereas the ecotoxicity potential is primarily associated with cobalt, copper, nickel, thallium, and silver. However, the relative contribution of aluminum and lithium to human toxicity and ecotoxicity could not be estimated due to insufficient toxicity data in the models. These findings support the need for stronger government policy at the local, national, and international levels to encourage recovery, recycling, and

  20. Pleasant and unpleasant odors influence hedonic evaluations of human faces: an event-related potential study.

    Directory of Open Access Journals (Sweden)

    Stephanie Jane Cook

    2015-12-01

    Full Text Available Odors can alter hedonic evaluations of human faces, but the neural mechanisms of such effects are poorly understood. The present study aimed to analyze the neural underpinning of odor-induced changes in evaluations of human faces in an odor-priming paradigm, using event-related potentials (ERPs. Healthy, young participants (N = 20 rated neutral faces presented after a three second pulse of a pleasant odor (jasmine, unpleasant odor (methylmercaptan, or no-odor control (clean air. Neutral faces presented in the pleasant odor condition were rated more pleasant than the same faces presented in the no-odor control condition, which in turn were rated more pleasant than faces in the unpleasant odor condition. Analysis of face-related potentials revealed four clusters of electrodes significantly affected by odor condition at specific time points during long-latency epochs (600−950 ms. In the 620−640 ms interval, two scalp-time clusters showed greater negative potential in the right parietal electrodes in response to faces in the pleasant odor condition, compared to those in the no-odor and unpleasant odor conditions. At 926 ms, face-related potentials showed greater positivity in response to faces in the pleasant and unpleasant odor conditions at the left and right lateral frontal-temporal electrodes, respectively. Our data shows that odor-induced shifts in evaluations of faces were associated with amplitude changes in the late (> 600 and ultra-late (> 900 ms latency epochs. The observed amplitude changes during the ultra-late epoch are consistent with a left/right hemisphere bias towards pleasant/unpleasant odor effects. Odors alter evaluations of human faces, even when there is a temporal lag between presentation of odors and faces. Our results provide an initial understanding of the neural mechanisms underlying effects of odors on hedonic evaluations.

  1. Pleasant and Unpleasant Odors Influence Hedonic Evaluations of Human Faces: An Event-Related Potential Study

    Science.gov (United States)

    Cook, Stephanie; Fallon, Nicholas; Wright, Hazel; Thomas, Anna; Giesbrecht, Timo; Field, Matt; Stancak, Andrej

    2015-01-01

    Odors can alter hedonic evaluations of human faces, but the neural mechanisms of such effects are poorly understood. The present study aimed to analyze the neural underpinning of odor-induced changes in evaluations of human faces in an odor-priming paradigm, using event-related potentials (ERPs). Healthy, young participants (N = 20) rated neutral faces presented after a 3 s pulse of a pleasant odor (jasmine), unpleasant odor (methylmercaptan), or no-odor control (clean air). Neutral faces presented in the pleasant odor condition were rated more pleasant than the same faces presented in the no-odor control condition, which in turn were rated more pleasant than faces in the unpleasant odor condition. Analysis of face-related potentials revealed four clusters of electrodes significantly affected by odor condition at specific time points during long-latency epochs (600−950 ms). In the 620−640 ms interval, two scalp-time clusters showed greater negative potential in the right parietal electrodes in response to faces in the pleasant odor condition, compared to those in the no-odor and unpleasant odor conditions. At 926 ms, face-related potentials showed greater positivity in response to faces in the pleasant and unpleasant odor conditions at the left and right lateral frontal-temporal electrodes, respectively. Our data shows that odor-induced shifts in evaluations of faces were associated with amplitude changes in the late (>600) and ultra-late (>900 ms) latency epochs. The observed amplitude changes during the ultra-late epoch are consistent with a left/right hemisphere bias towards pleasant/unpleasant odor effects. Odors alter evaluations of human faces, even when there is a temporal lag between presentation of odors and faces. Our results provide an initial understanding of the neural mechanisms underlying effects of odors on hedonic evaluations. PMID:26733843

  2. Methods for Motion Correction Evaluation Using 18F-FDG Human Brain Scans on a High-Resolution PET Scanner

    DEFF Research Database (Denmark)

    Keller, Sune H.; Sibomana, Merence; Olesen, Oline Vinter

    2012-01-01

    Many authors have reported the importance of motion correction (MC) for PET. Patient motion during scanning disturbs kinetic analysis and degrades resolution. In addition, using misaligned transmission for attenuation and scatter correction may produce regional quantification bias in the reconstr...

  3. Correction: Cecotti, H. and Rivet, B. Subject Combination and Electrode Selection in Cooperative Brain-Computer Interface Based on Event Related Potentials. Brain Sci. 2014, 4, 335–355

    Directory of Open Access Journals (Sweden)

    Hubert Cecotti

    2014-09-01

    Full Text Available The authors wish to make the following correction to this paper (Cecotti, H.; Rivet, B. Subject Combination and Electrode Selection in Cooperative Brain-Computer Interface Based on Event Related Potentials. Brain Sci. 2014, 4, 335–355: Due to an internal error, the reference numbers in the original published paper were not shown, and the error was not due to the authors. The former main text should be replaced as below.

  4. ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus [corrected].

    Directory of Open Access Journals (Sweden)

    John C Castle

    Full Text Available Acetyl-CoA carboxylases ACC1 and ACC2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA, regulating fatty-acid synthesis and oxidation, and are potential targets for treatment of metabolic syndrome. Expression of ACC1 in rodent lipogenic tissues and ACC2 in rodent oxidative tissues, coupled with the predicted localization of ACC2 to the mitochondrial membrane, have suggested separate functional roles for ACC1 in lipogenesis and ACC2 in fatty acid oxidation. We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. Human adipose, along with human liver, expresses more ACC2 than ACC1. Using RT-PCR, real-time PCR, and immunoprecipitation we report a novel isoform of ACC2 (ACC2.v2 that is expressed at significant levels in human adipose. The protein generated by this isoform has enzymatic activity, is endogenously expressed in adipose, and lacks the N-terminal sequence. Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis. The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors.

  5. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.

    Science.gov (United States)

    Menachery, Vineet D; Yount, Boyd L; Debbink, Kari; Agnihothram, Sudhakar; Gralinski, Lisa E; Plante, Jessica A; Graham, Rachel L; Scobey, Trevor; Ge, Xing-Yi; Donaldson, Eric F; Randell, Scott H; Lanzavecchia, Antonio; Marasco, Wayne A; Shi, Zhengli-Li; Baric, Ralph S

    2015-12-01

    The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.

  6. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dong; Li, Yang; Song, Gaojie; Zhang, David; Shaw, Neil; Liu, Zhi-Jie; (Chinese Aca. Sci.)

    2009-07-10

    Retinoblastoma (RB), a carcinoma of the retina, is caused by mutations in the long arm of chromosome 13, band 13q14. The esterase D (ESD) gene maps at a similar location as the RB gene locus and therefore serves as a potential marker for the prognosis of retinoblastoma. Because very little is known about the structure and function of ESD, we determined the 3-dimensional structure of the enzyme at 1.5 {angstrom} resolution using X-ray crystallography. ESD shows a single domain with an {alpha}/{beta}-hydrolase fold. A number of insertions are observed in the canonical {alpha}/{beta}-hydrolase fold. The active site is located in a positively charged, shallow cleft on the surface lined by a number of aromatic residues. Superimposition studies helped identify the typical catalytic triad residues -- Ser-153, His264, and Asp230 -- involved in catalysis. Mutagenesis of any of the catalytic triad residues to alanine abolished the enzyme activity. Backbone amides of Leu54 and Met150 are involved in the formation of the oxyanion hole. Interestingly, a M150A mutation increased the enzyme activity by 62%. The structure of human ESD determined in this study will aid the elucidation of the physiological role of the enzyme in the human body and will assist in the early diagnosis of retinoblastoma. Wu, D., Li, Y., Song, G., Zhang, D., Shaw, N., Liu, Z. J. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma.

  7. Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

    Directory of Open Access Journals (Sweden)

    Teresa de Souza Fernandez

    2013-01-01

    Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

  8. Assessment of Pulmonary Fibrogenic Potential of Multiwalled Carbon Nanotubes in Human Lung Cells

    Directory of Open Access Journals (Sweden)

    Anurag Mishra

    2012-01-01

    Full Text Available Multiwalled carbon nanotubes have been shown to possess unusual fibrogenic activity in vivo and are currently the focus of intense toxicological investigations. This study further determines the fibrogenic potential of well-dispersed MWCNT in human lung cell culture models and to develop a novel platform for understanding the cellular mechanisms of MWCNT-induced lung fibrosis. Survanta, a natural lung surfactant, showed effectiveness in dispersing agglomerates of MWCNT to fine structures similar in size to aerosolized one. At relevant low doses (0.002–0.2 μg/cm2, MWCNT exhibited a dose-dependent bio-effect on the human lung epithelial cells which is more pronounced in dispersed-MWCNT compared to non-dispersed form. Significantly elevated levels of fibrogenic mediators, such as transforming growth factor-β1 and matrix metalloprotienases-9 were observed in the dispersed-MWCNT treated lung epithelial cells. Based on previous in vivo studies showing that dispersed-MWCNT penetrated the interstitium and caused rapid interstitial fibrosis, we evaluated the potential direct interaction between lung fibroblasts and MWCNT. Direct stimulation of human lung fibroblast cell proliferation, collagen expression and fibroblast growth factor-2 were observed which suggests novel mechanisms of MWCNT-induced lung fibrosis. Our results indicate that the dispersion status of MWCNT determines their fibrogenic activity which is consistent with in vivo findings.

  9. Assessing the Biohazard Potential of Putative Martian Organisms for Exploration Class Human Space Missions

    Science.gov (United States)

    Warmflash, David; Larios-Sanz, Maia; Jones, Jeffrey; Fox, George E.; McKay, David S.

    2007-01-01

    Exploration Class missions to Mars will require precautions against potential contamination by any native microorganisms that may be incidentally pathogenic to humans. While the results of NASA's Viking biology experiments of 1976 have been generally interpreted as inconclusive for surface organisms, the possibility of native surface life has never been ruled out and more recent studies suggest that the case for biological interpretation of the Viking Labeled Release data may now be stronger than it was when the experiments were originally conducted. It is possible that, prior to the first human landing on Mars, robotic craft and sample return missions will provide enough data to know with certainty whether or not future human landing sites harbor extant life forms. However, if native life is confirmed, it will be problematic to determine whether any of its species may present a medical risk to astronauts. Therefore, it will become necessary to assess empirically the risk that the planet contains pathogens based on terrestrial examples of pathogenicity and to take a reasonably cautious approach to bio-hazard protection. A survey of terrestrial pathogens was conducted with special emphasis on those pathogens whose evolution has not depended on the presence of animal hosts. The history of the development and implementation of Apollo anticontamination protocol and recent recommendations of the NRC Space Studies Board regarding Mars were reviewed. Organisms can emerge in nature in the absence of indigenous animal hosts and both infectious and non-infectious human pathogens are theoretically possible on Mars. The prospect of Martian surface life, together with the existence of a diversity of routes by which pathogenicity has emerged on Earth, suggests that the possibility of human pathogens on Mars, while low, is not zero. Since the discovery and study of Martian life can have long-term benefits for humanity, the risk that Martian life might include pathogens should not

  10. Caring potentials in the shadows of power, correction, and discipline - Forensic psychiatric care in the light of the work of Michel Foucault.

    Science.gov (United States)

    Hörberg, Ulrica; Dahlberg, Karin

    2015-01-01

    The aim of this article is to shed light on contemporary forensic psychiatric care through a philosophical examination of the empirical results from two lifeworld phenomenological studies from the perspective of patients and carers, by using the French philosopher Michel Foucault's historical-philosophical work. Both empirical studies were conducted in a forensic psychiatric setting. The essential results of the two empirical studies were reexamined in a phenomenological meaning analysis to form a new general structure in accordance with the methodological principles of Reflective Lifeworld Research. This general structure shows how the caring on the forensic psychiatric wards appears to be contradictory, in that it is characterized by an unreflective (non-)caring attitude and contributes to an inconsistent and insecure existence. The caring appears to have a corrective approach and thus lacks a clear caring structure, a basic caring approach that patients in forensic psychiatric services have a great need of. To gain a greater understanding of forensic psychiatric caring, the new empirical results were further examined in the light of Foucault's historical-philosophical work. The philosophical examination is presented in terms of the three meaning constituents: Caring as correction and discipline, The existence of power, and Structures and culture in care. The philosophical examination illustrates new meaning nuances of the corrective and disciplinary nature of forensic psychiatric care, its power, and how this is materialized in caring, and what this does to the patients. The examination reveals embedded difficulties in forensic psychiatric care and highlights a need to revisit the aim of such care.

  11. Caring potentials in the shadows of power, correction, and discipline—Forensic psychiatric care in the light of the work of Michel Foucault

    Directory of Open Access Journals (Sweden)

    Ulrica Hörberg

    2015-08-01

    Full Text Available The aim of this article is to shed light on contemporary forensic psychiatric care through a philosophical examination of the empirical results from two lifeworld phenomenological studies from the perspective of patients and carers, by using the French philosopher Michel Foucault's historical–philosophical work. Both empirical studies were conducted in a forensic psychiatric setting. The essential results of the two empirical studies were reexamined in a phenomenological meaning analysis to form a new general structure in accordance with the methodological principles of Reflective Lifeworld Research. This general structure shows how the caring on the forensic psychiatric wards appears to be contradictory, in that it is characterized by an unreflective (non-caring attitude and contributes to an inconsistent and insecure existence. The caring appears to have a corrective approach and thus lacks a clear caring structure, a basic caring approach that patients in forensic psychiatric services have a great need of. To gain a greater understanding of forensic psychiatric caring, the new empirical results were further examined in the light of Foucault's historical–philosophical work. The philosophical examination is presented in terms of the three meaning constituents: Caring as correction and discipline, The existence of power, and Structures and culture in care. The philosophical examination illustrates new meaning nuances of the corrective and disciplinary nature of forensic psychiatric care, its power, and how this is materialized in caring, and what this does to the patients. The examination reveals embedded difficulties in forensic psychiatric care and highlights a need to revisit the aim of such care.

  12. Caring potentials in the shadows of power, correction, and discipline—Forensic psychiatric care in the light of the work of Michel Foucault

    Science.gov (United States)

    Hörberg, Ulrica; Dahlberg, Karin

    2015-01-01

    The aim of this article is to shed light on contemporary forensic psychiatric care through a philosophical examination of the empirical results from two lifeworld phenomenological studies from the perspective of patients and carers, by using the French philosopher Michel Foucault's historical–philosophical work. Both empirical studies were conducted in a forensic psychiatric setting. The essential results of the two empirical studies were reexamined in a phenomenological meaning analysis to form a new general structure in accordance with the methodological principles of Reflective Lifeworld Research. This general structure shows how the caring on the forensic psychiatric wards appears to be contradictory, in that it is characterized by an unreflective (non-)caring attitude and contributes to an inconsistent and insecure existence. The caring appears to have a corrective approach and thus lacks a clear caring structure, a basic caring approach that patients in forensic psychiatric services have a great need of. To gain a greater understanding of forensic psychiatric caring, the new empirical results were further examined in the light of Foucault's historical–philosophical work. The philosophical examination is presented in terms of the three meaning constituents: Caring as correction and discipline, The existence of power, and Structures and culture in care. The philosophical examination illustrates new meaning nuances of the corrective and disciplinary nature of forensic psychiatric care, its power, and how this is materialized in caring, and what this does to the patients. The examination reveals embedded difficulties in forensic psychiatric care and highlights a need to revisit the aim of such care. PMID:26319100

  13. PBDE levels in human milk: the situation in Germany and potential influencing factors - a controlled study

    Energy Technology Data Exchange (ETDEWEB)

    Vieth, B.; Mielke, H.; Ostermann, B.; Ruediger, T. [Federal Inst. for Risk Assessment, Berlin (Germany); Herrmann, T.; Paepke, O. [ERGO Forschungsgesellschaft mbH, Hamburg (Germany)

    2004-09-15

    An exponential increase of PBDE levels in breast milk from Sweden between 1972 and 1997 has been reported, which is in contrast to the continuous decline of other chlorinated POPs in breast milk. Also in blood samples from Germany, an increasing trend has been observed during the period from 1985 to 1999. The knowledge about human exposure pathways, which contribute to the PBDE body burden, is very limited. Consumption of food of animal origin, inhalation or ingestion of dust and further factors possibly influencing the PBDE levels in human matrices, like age, breast-feeding or smoking are under discussion. Only a few data on PBDE levels in breast milk from Germany have been published. To fill the data gaps, a controlled study was started in 2001 to characterise the PBDE levels in human milk from Germany with special efforts to identify and quantify deca-BDE-209. Furthermore, it was intended to verify potential factors possibly influencing PBDE levels. Two main hypotheses were proposed: (1) Are PBDE levels in breast milk from mothers consuming traditional food (omnivores) higher than those found in breast milk from mothers consuming vegetarian or vegan food? and (2) Are the PBDE levels found in human milk after a three-months period of breast-feeding lower than those detected at the beginning or does breast feeding result in a lower body burden, respectively? This paper summarises preliminary results. Further analytical data and results of data evaluation will be presented at the conference.

  14. Sorghum (Sorghum bicolor L.): Nutrients, bioactive compounds, and potential impact on human health.

    Science.gov (United States)

    de Morais Cardoso, Leandro; Pinheiro, Soraia Silva; Martino, Hércia Stampini Duarte; Pinheiro-Sant'Ana, Helena Maria

    2017-01-22

    Sorghum is the fifth most produced cereal in the world and is a source of nutrients and bioactive compounds for the human diet. We summarize the recent findings concerning the nutrients and bioactive compounds of sorghum and its potential impact on human health, analyzing the limitations and positive points of the studies and proposing directions for future research. Sorghum is basically composed of starch, which is more slowly digested than that of other cereals, has low digestibility proteins and unsaturated lipids, and is a source of some minerals and vitamins. Furthermore, most sorghum varieties are rich in phenolic compounds, especially 3-deoxyanthocyanidins and tannins. The results obtained in vitro and in animals have shown that phenolics compounds and fat soluble compounds (polycosanols) isolated from sorghum benefit the gut microbiota and parameters related to obesity, oxidative stress, inflammation, diabetes, dyslipidemia, cancer, and hypertension. The effects of whole sorghum and its fractions on human health need to be evaluated. In conclusion, sorghum is a source of nutrients and bioactive compounds, especially 3-deoxyanthocyanidins, tannins, and polycosanols, which beneficially modulate, in vitro and in animals, parameters related to noncommunicable diseases. Studies should be conducted to evaluate the effects of different processing on protein and starch digestibility of sorghum as well as on the profile and bioavailability of its bioactive compounds, especially 3-deoxyanthocyanidins and tannins. Furthermore, the benefits resulting from the interaction of bioactive compounds in sorghum and human microbiota should be studied.

  15. Regenerative potential of human airway stem cells in lung epithelial engineering.

    Science.gov (United States)

    Gilpin, Sarah E; Charest, Jonathan M; Ren, Xi; Tapias, Luis F; Wu, Tong; Evangelista-Leite, Daniele; Mathisen, Douglas J; Ott, Harald C

    2016-11-01

    Bio-engineered organs for transplantation may ultimately provide a personalized solution for end-stage organ failure, without the risk of rejection. Building upon the process of whole organ perfusion decellularization, we aimed to develop novel, translational methods for the recellularization and regeneration of transplantable lung constructs. We first isolated a proliferative KRT5(+)TP63(+) basal epithelial stem cell population from human lung tissue and demonstrated expansion capacity in conventional 2D culture. We then repopulated acellular rat scaffolds in ex vivo whole organ culture and observed continued cell proliferation, in combination with primary pulmonary endothelial cells. To show clinical scalability, and to test the regenerative capacity of the basal cell population in a human context, we then recellularized and cultured isolated human lung scaffolds under biomimetic conditions. Analysis of the regenerated tissue constructs confirmed cell viability and sustained metabolic activity over 7 days of culture. Tissue analysis revealed extensive recellularization with organized tissue architecture and morphology, and preserved basal epithelial cell phenotype. The recellularized lung constructs displayed dynamic compliance and rudimentary gas exchange capacity. Our results underline the regenerative potential of patient-derived human airway stem cells in lung tissue engineering. We anticipate these advances to have clinically relevant implications for whole lung bioengineering and ex vivo organ repair.

  16. Small heat shock proteins potentiate amyloid dissolution by protein disaggregases from yeast and humans.

    Directory of Open Access Journals (Sweden)

    Martin L Duennwald

    Full Text Available How small heat shock proteins (sHsps might empower proteostasis networks to control beneficial prions or disassemble pathological amyloid is unknown. Here, we establish that yeast sHsps, Hsp26 and Hsp42, inhibit prionogenesis by the [PSI+] prion protein, Sup35, via distinct and synergistic mechanisms. Hsp42 prevents conformational rearrangements within molten oligomers that enable de novo prionogenesis and collaborates with Hsp70 to attenuate self-templating. By contrast, Hsp26 inhibits self-templating upon binding assembled prions. sHsp binding destabilizes Sup35 prions and promotes their disaggregation by Hsp104, Hsp70, and Hsp40. In yeast, Hsp26 or Hsp42 overexpression prevents [PSI+] induction, cures [PSI+], and potentiates [PSI+]-curing by Hsp104 overexpression. In vitro, sHsps enhance Hsp104-catalyzed disaggregation of pathological amyloid forms of α-synuclein and polyglutamine. Unexpectedly, in the absence of Hsp104, sHsps promote an unprecedented, gradual depolymerization of Sup35 prions by Hsp110, Hsp70, and Hsp40. This unanticipated amyloid-depolymerase activity is conserved from yeast to humans, which lack Hsp104 orthologues. A human sHsp, HspB5, stimulates depolymerization of α-synuclein amyloid by human Hsp110, Hsp70, and Hsp40. Thus, we elucidate a heretofore-unrecognized human amyloid-depolymerase system that could have applications in various neurodegenerative disorders.

  17. Nrf2 activators as potential modulators of injury in human kidney cells

    Directory of Open Access Journals (Sweden)

    Amandla Atilano-Roque

    2016-01-01

    Full Text Available Cisplatin is a chemotherapeutic agent used in the treatment of solid tumors, with clinical use often complicated by kidney toxicity. Nuclear factor (erythroid-derived-2-like 2 (Nrf2 is a transcription factor involved in kidney protectant effects. The purpose of this study was to determine whether the Nrf2 activators oltipraz, sulforaphane, and oleanolic acid could protect human kidney cells against cisplatin-induced injury and to compare the protective effects between three Nrf2 activators. Human proximal tubule cells (hPTC and human embryonic kidney 293 cells (HEK293 were exposed to cisplatin doses in the absence and presence of Nrf2 activators. Pre- and delayed-cisplatin and Nrf2 activator exposures were also assessed. Cell viability was enhanced with Nrf2 activator exposures, with differences detected between pre- and delayed-treatments. Both sulforaphane and oltipraz increased the expression of anti-oxidant genes GCLC and NQO1. These findings suggest potential human kidney protective benefits of Nrf2 activators with planned exposures to cisplatin.

  18. Probiotic lactobacilli: a potential prophylactic treatment for reducing pesticide absorption in humans and wildlife.

    Science.gov (United States)

    Trinder, M; Bisanz, J E; Burton, J P; Reid, G

    2015-01-01

    Numerous pesticides are used in agriculture, gardening, and wildlife-control. Despite their intended toxicity to pests, these compounds can also cause harm to wildlife and humans due to their ability to potentially bioaccumulate, leach into soils, and persist in the environment. Humans and animals are commonly exposed to these compounds through agricultural practices and consumption of contaminated foods and water. Pesticides can cause a range of adverse effects in humans ranging from minor irritation, to endocrine or nervous system disruption, cancer, or even death. A convenient and cost-effective method to reduce unavoidable pesticide absorption in humans and wildlife could be the use of probiotic lactobacilli. Lactobacillus is a genus of Gram-positive gut commensal bacteria used in the production of functional foods, such as yoghurt, cheese, sauerkraut and pickles, as well as silage for animal feed. Preliminary in vitro experiments suggested that lactobacilli are able to degrade some pesticides. Probiotic Lactobacillus rhamnosus GR-1-supplemented yoghurt reduced the bioaccumulation of mercury and arsenic in pregnant women and children. A similar study is warranted to test if this approach can reduce pesticide absorption in vivo, given that the lactobacilli can also attenuate reactive oxygen production, enhance gastrointestinal barrier function, reduce inflammation, and modulate host xenobiotic metabolism.

  19. The natural antibody repertoire of sharks and humans recognizes the potential universe of antigens.

    Science.gov (United States)

    Adelman, Miranda K; Schluter, Samuel F; Marchalonis, John J

    2004-02-01

    In ancestral sharks, a rapid emergence in the evolution of the immune system occurred, giving jawed-vertebrates the necessary components for the combinatorial immune response (CIR). To compare the natural antibody (NAb) repertoires of the most divergent vertebrates with the capacity to produce antibodies, we isolated NAbs to the same set of antigens by affinity chromatography from two species of Carcharhine sharks and from human polyclonal IgG and IgM antibody preparations. The activities of the affinity-purified anti-T-cell receptor (anti-TCR) NAbs were compared with those of monoclonal anti-TCR NAbs that were generated from a systemic lupus erythematosus patient. We report that sharks and humans, representing the evolutionary extremes of vertebrate species sharing the CIR, have NAbs to human TCRs, Igs, the human senescent cell antigen, and to numerous retroviral antigens, indicating that essential features of the combinatorial repertoire and the capacity to recognize the potential universe of antigens is shared among all jawed-vertebrates.

  20. Identification of a novel population of human cord blood cells with hematopoietic and chondrocytic potential

    Institute of Scientific and Technical Information of China (English)

    Karen E JAY; Anne ROULEAU; T Michael UNDERHILL; Mickie BHATIA

    2004-01-01

    With the exception of mature erythrocytes, cells within the human hematopoietic system are characterized by the cell surface expression of the pan-leukocyte receptor CD45. Here, we identify a novel subset among mononuclear cord blood cells depleted of lineage commitment markers (Lin-) that are devoid of CD45 expression. Surprisingly, functional examination of Lin-CD45- cells also lacking cell surface CD34 revealed they were capable of multipotential hematopoietic progenitor capacity. Co-culture with mouse embryonic limb bud cells demonstrated that Lin-CD45-CD34- cells were capable of contributing to cartilage nodules and differentiating into human chondrocytes. BMP-4, a mesodermal factor known to promote chondrogenesis, significantly augmented Lin-CD45-CD34- differentiation into chondrocytes.Moreover, unlike CD34+ human hematopoietic stem cells, Lin-CD45-CD34- cells were unable to proliferate or survive in liquid cultures, whereas single Lin-CD45-CD34- cells were able to chimerize the inner cell mass (ICM) of murine blastocysts and proliferate in this embryonic environment. Our study identifies a novel population of Lin-CD45-CD34-cells capable of commitment into both hematopoietic and chondrocytic lineages, suggesting that human cord blood may provide a more ubiquitous source of tissue with broader developmental potential than previously appreciated.

  1. Differential proteomics of human seminal plasma: A potential target for searching male infertility marker proteins.

    Science.gov (United States)

    Tomar, Anil Kumar; Sooch, Balwinder Singh; Singh, Sarman; Yadav, Savita

    2012-04-01

    The clinical fertility tests, available in the market, fail to define the exact cause of male infertility in almost half of the cases and point toward a crucial need of developing better ways of infertility investigations. The protein biomarkers may help us toward better understanding of unknown cases of male infertility that, in turn, can guide us to find better therapeutic solutions. Many clinical attempts have been made to identify biomarkers of male infertility in sperm proteome but only few studies have targeted seminal plasma. Human seminal plasma is a rich source of proteins that are essentially required for development of sperm and successful fertilization. This viewpoint article highlights the importance of human seminal plasma proteome in reproductive physiology and suggests that differential proteomics integrated with functional analysis may help us in searching potential biomarkers of male infertility.

  2. Potential Use of Bacterial Community Succession in Decaying Human Bone for Estimating Postmortem Interval.

    Science.gov (United States)

    Damann, Franklin E; Williams, Daniel E; Layton, Alice C

    2015-07-01

    Bacteria are taphonomic agents of human decomposition, potentially useful for estimating postmortem interval (PMI) in late-stage decomposition. Bone samples from 12 individuals and three soil samples were analyzed to assess the effects of decomposition and advancing time on bacterial communities. Results indicated that partially skeletonized remains maintained a presence of bacteria associated with the human gut, whereas bacterial composition of dry skeletal remains maintained a community profile similar to soil communities. Variation in the UniFrac distances was significantly greater between groups than within groups (p < 0.001) for the unweighted metric and not the weighted metric. The members of the bacterial communities were more similar within than between decomposition stages. The oligotrophic environment of bone relative to soft tissue and the physical protection of organic substrates may preclude bacterial blooms during the first years of skeletonization. Therefore, community membership (unweighted) may be better for estimating PMI from skeletonized remains than community structure (weighted).

  3. Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies

    Directory of Open Access Journals (Sweden)

    Elena Maria Varoni

    2013-07-01

    Full Text Available Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.

  4. Carbon Monoxide Effects onHuman Ventricle Action PotentialAssessed by Mathematical Simulations

    Directory of Open Access Journals (Sweden)

    Beatriz eTrenor

    2013-10-01

    Full Text Available Carbon monoxide (CO that is produced in a number of different mammalian tissues is now known to have significant effects on the cardiovascular system. These include: i vasodilation, ii changes in heart rate and strength of contractions and iii modulation of autonomic nervous system input to both the pacemaker and the working myocardium. Excessive CO in the environment is toxic and can initiate or mediate life threatening cardiac rhythm disturbances. Recent reports link these ventricular arrhythmias to an increase in the slowly inactivating, or ‘late’ component of the Na+ current in the mammalian heart.The main goal of this paper is to explore the basis of this pro-arrhythmic capability of CO by incorporating recently reported changes in CO-induced ion channel activity and intracellular signalling pathways in the mammalian heart. To do this, a quite well-documented mathematical model of the action potential and intracellular calcium transient in the human ventricular myocyte has been employed. In silico iterations based on this model provide a useful first step in illustrating the cellular electrophysiological consequences of CO that have been reported from mammalian heart experiments. Specifically, when the Grandi et al. model of the human ventricular action potential is utilized, and after the Na+ and Ca2+ currents in a single myocyte are modified based on the experimental literature, early after-depolarization (EAD rhythm disturbances appear, and important elements of the underlying causes of these EADs are revealed/illustrated. Our modified mathematical model of the human ventricular action potential also provides a convenient digital platform for designing future experimental work and relating these changes in cellular cardiac electrophysiology to emerging clinical and epidemiological data on CO toxicity.

  5. A matter of identity — Phenotype and differentiation potential of human somatic stem cells

    Directory of Open Access Journals (Sweden)

    S.E.P. New

    2015-07-01

    Full Text Available Human somatic stem cells with neural differentiation potential can be valuable for developing cell-based therapies, including treatment of birth-related defects, while avoiding issues associated with cell reprogramming. Precisely defining the “identity” and differentiation potential of somatic stem cells from different sources, has proven difficult, given differences in sets of specific markers, protocols used and lack of side-by-side characterization of these cells in different studies. Therefore, we set to compare expression of mesenchymal and neural markers in human umbilical cord-derived mesenchymal stem cells (UC-MSCs, pediatric adipose-derived stem cells (p-ADSCs in parallel with human neural stem cells (NSCs. We show that UC-MSCs at a basal level express mesenchymal and so-called “neural” markers, similar to that we previously reported for the p-ADSCs. All somatic stem cell populations studied, independently from tissue and patient of origin, displayed a remarkably similar expression of surface markers, with the main difference being the restricted expression of CD133 and CD34 to NSCs. Expression of certain surface and neural markers was affected by the expansion medium used. As predicted, UC-MSCs and p-ADSCs demonstrated tri-mesenchymal lineage differentiation potential, though p-ADSCs display superior chondrogenic differentiation capability. UC-MSCs and p-ADSCs responded also to neurogenic induction by up-regulating neuronal markers, but crucially they appeared morphologically immature when compared with differentiated NSCs. This highlights the need for further investigation into the use of these cells for neural therapies. Crucially, this study demonstrates the lack of simple means to distinguish between different cell types and the effect of culture conditions on their phenotype, and indicates that a more extensive set of markers should be used for somatic stem cell characterization, especially when developing therapeutic

  6. Three-dimensional CT might be a potential evaluation modality in correction of asymmetrical masseter muscle hypertrophy by botulinum toxin injection.

    Science.gov (United States)

    No, Yeon A; Ahn, Byeong Heon; Kim, Beom Joon; Kim, Myeung Nam; Hong, Chang Kwon

    2016-01-01

    For correction of this asymmetrical hypertrophy, botulinum toxin type A (BTxA) injection is one of convenient treatment modalities. Unfortunately, physical examination of masseter muscle is not enough to estimate the exact volume of muscle hypertrophy difference. Two Koreans, male and female, of bilateral masseter hypertrophy with asymmetricity were evaluated. BTxA (NABOTA(®), Daewoong, Co. Ltd., Seoul, Korea) was injected at master muscle site with total 50 U (25 U at each side) and volume change was evaluated with three-dimensional (3D) CT image analysis. Maximum reduction of masseter hypertrophy was recognized at 2-month follow-up and reduced muscle size started to restore after 3 months. Mean reduction of masseter muscle volume was 36% compared with baseline. More hypertrophied side of masseter muscle presented 42% of volume reduction at 2-month follow-up but less hypertrophied side of masseter muscle showed 30% of volume shrinkage. In conclusion, 3D CT image analysis might be the exact evaluation tool for correction of asymmetrical masseter hypertrophy by botulinum toxin injection.

  7. Potential, pH, and arachidonate gate hydrogen ion currents in human neutrophils.

    OpenAIRE

    DeCoursey, T E; Cherny, V V

    1993-01-01

    Indirect evidence indicates that a proton-selective conductance is activated during the respiratory burst in neutrophils. A voltage- and time-dependent H(+)-selective conductance, gH, in human neutrophils is demonstrated here directly by the whole-cell patch-clamp technique. The gH is extremely low at large negative potentials, increases slowly upon membrane depolarization, and does not inactivate. It is enhanced at high external pH or low internal pH and is inhibited by Cd2+ and Zn2+. Arachi...

  8. Establishment and characterization of cell sublines with high and low metastatic potential derived from human osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-bing; CHEN An-ming; CAI Xian-hua; GUO Fen-jing; LIAO Guo-ning; MA Ding

    2005-01-01

    @@ The most frequent cause of death of patients with osteosarcoma is the metastasis of tumour cells. In spite of successful control of the primary tumour, the mortality of the patients due to metastatic spread is more than 30% within 5 years.1 Recent studies about osteosarcoma metastatic mechanism are based on osteosarcoma matrilineal cell lines.2 For further studies of metastatic mechanism of osteosarcoma the establishment of a better metastatic experimental model of osteosarcoma is needed. We isolated and established two cell sublines, with high and low metastatic potentials, respectively, derived from human osteosarcoma MG-63 cell line by cloning in vitro and transplantation in vivo, then analysed and identified their biological characteristics.

  9. Review of the role of potential teratogens in the origin of human nonsyndromic oral clefts.

    Science.gov (United States)

    Wyszynski, D F; Beaty, T H

    1996-05-01

    Oral clefts are common birth defects affecting approximately 1 every 1,000 caucasian newborns. While many syndromes with cleft lip with or without cleft palate (CL/P) or with cleft palate (CP) are recognized, the majority of oral clefts fall into the category of "nonsyndromic oral clefts" and the etiology of this group remains incompletely understood. Investigators agree that oral clefts are multifactorial in origin, with both genetic and environmental factors in their etiology. While animal models have identified several teratogens for oral clefts, their precise relevance for humans remains unclear. The goal of this work is to review literature on environmental exposures potentially associated with non-syndromic oral clefts.

  10. [ASSESSMENT OF POTENTIAL RISK FOR CONTAMINATION OF SURFACE WATER RESERVOIRS BY PATHOGENS OF HUMAN PARASITIC DISEASES].

    Science.gov (United States)

    Khromenkova, E P; Dimidova, L L; Dumbadze, O S; Aidinov, G T; Shendo, G L; Agirov, A Kh; Batchaev, Kh Kh

    2015-01-01

    Sanitary and parasitological studies of the waste effluents and surface reservoir waters were conducted in the south of Russia. The efficiency of purification of waste effluents from the pathogens of parasitic diseases was investigated in the region's sewage-purification facilities. The water of the surface water reservoirs was found to contain helminthic eggs and larvae and intestinal protozoan cysts because of the poor purification and disinfection of service fecal sewage waters. The poor purification and disinvasion of waste effluents in the region determine the potential risk of contamination of the surface water reservoirs and infection of the population with the pathogens of human parasitic diseases.

  11. Spatially resolved streaming potentials of human intervertebral disk motion segments under dynamic axial compression.

    Science.gov (United States)

    Iatridis, James C; Furukawa, Masaru; Stokes, Ian A F; Gardner-Morse, Mack G; Laible, Jeffrey P

    2009-03-01

    Intervertebral disk degeneration results in alterations in the mechanical, chemical, and electrical properties of the disk tissue. The purpose of this study is to record spatially resolved streaming potential measurements across intervertebral disks exposed to cyclic compressive loading. We hypothesize that the streaming potential profile across the disk will vary with radial position and frequency and is proportional to applied load amplitude, according to the presumed fluid-solid relative velocity and measured glycosaminoglycan content. Needle electrodes were fabricated using a linear array of AgAgCl micro-electrodes and inserted into human motion segments in the midline from anterior to posterior. They were connected to an amplifier to measure electrode potentials relative to the saline bath ground. Motion segments were loaded in axial compression under a preload of 500 N, sinusoidal amplitudes of +/-200 N and +/-400 N, and frequencies of 0.01 Hz, 0.1 Hz, and 1 Hz. Streaming potential data were normalized by applied force amplitude, and also compared with paired experimental measurements of glycosaminoglycans in each disk. Normalized streaming potentials varied significantly with sagittal position and there was a significant location difference at the different frequencies. Normalized streaming potential was largest in the central nucleus region at frequencies of 0.1 Hz and 1.0 Hz with values of approximately 3.5 microVN. Under 0.01 Hz loading, normalized streaming potential was largest in the outer annulus regions with a maximum value of 3.0 microVN. Correlations between streaming potential and glycosaminoglycan content were significant, with R(2) ranging from 0.5 to 0.8. Phasic relationships between applied force and electrical potential did not differ significantly by disk region or frequency, although the largest phase angles were observed at the outermost electrodes. Normalized streaming potentials were associated with glycosaminoglycan content, fluid, and

  12. Differential redox potential between the human cytosolic and mitochondrial branched-chain aminotransferase

    Institute of Scientific and Technical Information of China (English)

    Steven J. Coles; John T. Hancock; Myra E. Conway

    2012-01-01

    The human branched-chain aminotransferase (hBCAT) isoenzymes are CXXC motif redox sensitive homodimers central to glutamate metabolism in the central nervous system.These proteins respond differently to oxidation by H2O2,NO,and S-glutathionylation,suggesting that the redox potential is distinct between isoenzymes.Using various reduced to oxidized glutathione ratios (GSH:GSSG) to alter the redox environment,we demonstrate that hBCATc (cytosolic) has an overall redox potential that is 30 mV lower than hBCATm (mitochondrial).Furthermore,the CXXC motif of hBCATc was estimated to be 80 mV lower,suggesting that hBCATm is more oxidizing in nature.Western blot analysis revealed close correlations between hBCAT S-glutathionylation and the redox status of the assay environment,offering the hBCAT isoenzymes as novel biomarkers for cytosolic and mitochondrial oxidative stress.

  13. Closely spaced multiple mutations as potential signatures of transient hypermutability in human genes.

    Science.gov (United States)

    Chen, Jian-Min; Férec, Claude; Cooper, David N

    2009-10-01

    Data from diverse organisms suggests that transient hypermutability is a general mutational mechanism with the potential to generate multiple synchronous mutations, a phenomenon probably best exemplified by closely spaced multiple mutations (CSMMs). Here we have attempted to extend the concept of transient hypermutability from somatic cells to the germline, using human inherited disease-causing multiple mutations as a model system. Employing stringent criteria for data inclusion, we have retrospectively identified numerous potential examples of pathogenic CSMMs that exhibit marked similarities to the CSMMs reported in other systems. These examples include (1) eight multiple mutations, each comprising three or more components within a sequence tract of mutation showers"; and (3) numerous highly informative "homocoordinate" mutations. Using the proportion of CpG substitution as a crude indicator of the relative likelihood of transient hypermutability, we present evidence to suggest that CSMMs comprising at least one pair of mutations separated by mutation screening.

  14. Robotic Missions to Small Bodies and Their Potential Contributions to Human Exploration and Planetary Defense

    Science.gov (United States)

    Abell, Paul A.; Rivkin, Andrew S.

    2015-01-01

    Introduction: Robotic missions to small bodies will directly address aspects of NASA's Asteroid Initiative and will contribute to future human exploration and planetary defense. The NASA Asteroid Initiative is comprised of two major components: the Grand Challenge and the Asteroid Mission. The first component, the Grand Challenge, focuses on protecting Earth's population from asteroid impacts by detecting potentially hazardous objects with enough warning time to either prevent them from impacting the planet, or to implement civil defense procedures. The Asteroid Mission involves sending astronauts to study and sample a near-Earth asteroid (NEA) prior to conducting exploration missions of the Martian system, which includes Phobos and Deimos. The science and technical data obtained from robotic precursor missions that investigate the surface and interior physical characteristics of an object will help identify the pertinent physical properties that will maximize operational efficiency and reduce mission risk for both robotic assets and crew operating in close proximity to, or at the surface of, a small body. These data will help fill crucial strategic knowledge gaps (SKGs) concerning asteroid physical characteristics that are relevant for human exploration considerations at similar small body destinations. These data can also be applied for gaining an understanding of pertinent small body physical characteristics that would also be beneficial for formulating future impact mitigation procedures. Small Body Strategic Knowledge Gaps: For the past several years NASA has been interested in identifying the key SKGs related to future human destinations. These SKGs highlight the various unknowns and/or data gaps of targets that the science and engineering communities would like to have filled in prior to committing crews to explore the Solar System. An action team from the Small Bodies Assessment Group (SBAG) was formed specifically to identify the small body SKGs under the

  15. Membrane potential gradient is carbon monoxide-dependent in mouse and human small intestine.

    Science.gov (United States)

    Sha, Lei; Farrugia, Gianrico; Harmsen, W Scott; Szurszewski, Joseph H

    2007-08-01

    The aims of this study were to quantify the change in resting membrane potential (RMP) across the thickness of the circular muscle layer in the mouse and human small intestine and to determine whether the gradient in RMP is dependent on the endogenous production of carbon monoxide (CO). Conventional sharp glass microelectrodes were used to record the RMPs of circular smooth muscle cells at different depths in the human small intestine and in wild-type, HO2-KO, and W/W(V) mutant mouse small intestine. In the wild-type mouse and human intestine, the RMP of circular smooth muscle cells near the myenteric plexus was -65.3 +/- 2 mV and -58.4 +/- 2 mV, respectively, and -60.1 +/- 2 mV and -49.1 +/- 1 mV, respectively, in circular smooth muscle cells at the submucosal border. Oxyhemoglobin (20 microM), a trapping agent for CO, and chromium mesoporphyrin IX, an inhibitor of heme oxygenase, abolished the transwall gradient. The RMP gradients in mouse and human small intestine were not altered by N(G)-nitro-l-arginine (200 microM). No transwall RMP gradient was found in HO2-KO mice and W/W(V) mutant mice. TTX (1 microM) and 1H-[1,2,4-]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM) had no effect on the RMP gradient. These data suggest that the gradient in RMP across the thickness of the circular muscle layer of mouse and human small intestine is CO dependent.

  16. In Vitro Differentiation Potential of Human Placenta Derived Cells into Skin Cells

    Directory of Open Access Journals (Sweden)

    Ruhma Mahmood

    2015-01-01

    Full Text Available Skin autografting is the most viable and aesthetic technique for treatment of extensive burns; however, this practice has potential limitations. Harvesting cells from neonatal sources (such as placental tissue is a simple, inexpensive, and noninvasive procedure. In the current study authors sought to evaluate in vitro potential of human placenta derived stem cells to develop into skin-like cells. After extensive washing, amniotic membrane and umbilical cord tissue were separated to harvest amniotic epithelial cells (AECs and umbilical cord mesenchymal stem cells (UC-MSCs, respectively. Both types of cells were characterized for the expression of embryonic lineage markers and their growth characteristics were determined. AECs and UC-MSCs were induced to differentiate into keratinocytes-like and dermal fibroblasts-like cells, respectively. After induction, morphological changes were detected by microscopy. The differentiation potential was further assessed using immunostaining and RT-PCR analyses. AECs were positive for cytokeratins and E-Cadherin while UC-MSCs were positive for fibroblast specific makers. AECs differentiated into keratinocytes-like cells showed positive expression of keratinocyte specific cytokeratins, involucrin, and loricrin. UC-MSCs differentiated into dermal fibroblast-like cells indicated expression of collagen type 3, desmin, FGF-7, fibroblast activation protein alpha, procollagen-1, and vimentin. In conclusion, placenta is a potential source of cells to develop into skin-like cells.

  17. The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis

    Directory of Open Access Journals (Sweden)

    Danilo Cimadomo

    2016-01-01

    Full Text Available Preimplantation Genetic Diagnosis and Screening (PGD/PGS for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential.

  18. The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis

    Science.gov (United States)

    Cimadomo, Danilo; Capalbo, Antonio; Ubaldi, Filippo Maria; Scarica, Catello; Palagiano, Antonio; Canipari, Rita; Rienzi, Laura

    2016-01-01

    Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential. PMID:26942198

  19. Human toxicity potentials for life-cycle assessment and toxics release inventory risk screening.

    Science.gov (United States)

    Hertwich, E G; Mateles, S F; Pease, W S; McKone, T E

    2001-04-01

    The human toxicity potential (HTP), a calculated index that reflects the potential harm of a unit of chemical released into the environment, is based on both the inherent toxicity of a compound and its potential dose. It is used to weight emissions inventoried as part of a life-cycle assessment (LCA) or in the toxics release inventory (TRI) and to aggregate emissions in terms of a reference compound. Total emissions can be evaluated in terms of benzene equivalence (carcinogens) and toluene equivalents (noncarcinogens). The potential dose is calculated using a generic fate and exposure model, CalTOX, which determines the distribution of a chemical in a model environment and accounts for a number of exposure routes, including inhalation, ingestion of produce, fish, and meat, and dermal contact with water and soil. Toxicity is represented by the cancer potency q1* for carcinogens and the safe dose (RfD, RfC) for noncarcinogens. This article presents cancer and noncancer HTP values for air and surface-water emissions of 330 compounds. This list covers 258 chemicals listed in U.S. Environmental Protection Agency TRI, or 79 weight-% of the TRI releases to air reported in 1997.

  20. Isolation and Multiple Differentiation Potential Assessment of Human Gingival Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2014-11-01

    Full Text Available The aim of this study was to isolate human mesenchymal stem cells (MSCs from the gingiva (GMSCs and confirm their multiple differentiation potentials, including the odontogenic lineage. GMSCs, periodontal ligament stem cells (PDLSCs and dermal stem cells (DSCs cultures were analyzed for cell shape, cell cycle, colony-forming unit-fibroblast (CFU-F and stem cell markers. Cells were then induced for osteogenic and adipogenic differentiation and analyzed for differentiation markers (alkaline phosphatase (ALP activity, mineralization nodule formation and Runx2, ALP, osteocalcin (OCN and collagen I expressions for the osteogenic differentiation, and lipid vacuole formation and PPARγ-2 expression for the adipogenic differentiation. Besides, the odontogenic differentiation potential of GMSCs induced with embryonic tooth germ cell-conditioned medium (ETGC-CM was observed. GMSCs, PDLSCs and DSCs were all stromal origin. PDLSCs showed much higher osteogenic differentiation ability but lower adipogenic differentiation potential than DSCs. GMSCs showed the medial osteogenic and adipogenic differentiation potentials between those of PDLSCs and DSCs. GMSCs were capable of expressing the odontogenic genes after ETGC-CM induction. This study provides evidence that GMSCs can be used in tissue engineering/regeneration protocols as an approachable stem cell source.

  1. Pericyte plasticity - comparative investigation of the angiogenic and multilineage potential of pericytes from different human tissues.

    Science.gov (United States)

    Herrmann, M; Bara, J J; Sprecher, C M; Menzel, U; Jalowiec, J M; Osinga, R; Scherberich, A; Alini, M; Verrier, S

    2016-04-10

    Pericyte recruitment is essential for the stability of newly formed vessels. It was also suggested that pericytes represent common ancestor cells giving rise to mesenchymal stem cells (MSCs) in the adult. Here, we systematically investigated pericytes and MSCs from different human tissues in terms of their angiogenic and multilineage differentiation potential in vitro in order to assess the suitability of the different cell types for the regeneration of vascularised tissues. Magnetic-activated cell sorting (MACS®) was used to enrich CD34-CD146+ pericytes from adipose tissue (AT) and bone marrow (BM). The multilineage potential of pericytes was assessed by testing their capability to differentiate towards osteogenic, adipogenic and chondrogenic lineage in vitro. Pericytes and endothelial cells were co-seeded on Matrigel™ and the formation of tube-like structures was examined to study the angiogenic potential of pericytes. MSCs from AT and BM were used as controls. CD34-CD146+ cells were successfully enriched from AT and BM. Only BM-derived cells exhibited trilineage differentiation potential. AT-derived cells displayed poor chondrogenic differentiation upon stimulation with transforming growth factor-β1. Interestingly, osteogenic differentiation was more efficient in AT-PC and BM-PC compared to the respective full MSC population. Matrigel™ assays revealed that pericytes from all tissues integrated into tube-like structures. We show that MACS®-enriched pericytes from BM and AT have the potential to regenerate tissues of different mesenchymal lineages and support neovascularisation. MACS® represents a simple enrichment strategy of cells, which is of particular interest for clinical application. Finally, our results suggest that the regenerative potential of pericytes depends on their tissue origin, which is an important consideration for future studies.

  2. The Impact of Employee Satisfaction on the Release of Human Creative Potential

    Directory of Open Access Journals (Sweden)

    Damjana Dragman

    2014-09-01

    Full Text Available Research Question (RQ: Does employee satisfaction in the workplace affect the release of human creative potential? Purpose: Based on interviews conducted in the context of a particular department, the purpose was to determine whether employee satisfaction affects creativity and efficiency of employees. Method: A qualitative method was used as the research method, where interviews were used to obtain data. Results: The results showed that employee satisfaction in the workplace strongly affects their motivation at work and their effectiveness. Also personal praise from leaders influences employee satisfaction, which in turn also affect the release of human creative potential. Organization: Several factors affect employee satisfaction that is typical for the entire company. A special role is played by those who are responsible for creating a positive atmosphere within their working environment and encouraging employees towards increased creativity and efficiency. Society: Research shows that employee satisfaction significantly affects their performance. For this reason employees should create a pleasant working environment within the entire company and for good relationships with co-workers. Originality: The first such study conducted in the context of a particular department. Limitations/further research: The research study was carried out in only one department of one organization.

  3. Comparative analysis of the potential probiotic abilities of lactobacilli of human origin and from fermented vegetables

    Directory of Open Access Journals (Sweden)

    Petrović Tanja

    2012-01-01

    Full Text Available In this study, twelve strains of Lactobacillus plantarum derived from spontaneously fermented vegetables (carrots and beetroot and traditionally prepared sauerkraut were compared for their potential probiotic abilities with seven Lactobacillus rhamnosus strains of human origin. The tested strains were investigated for some technological properties and in vitro functional characteristics for potential probiotic strains. Selection probiotic criteria included the ability of the strains to withstand conditions similar to the digestive tract, antimicrobial activity against a wide range of intestinal pathogens and sensitivity to antibiotics. The total acidity in milk was generally higher in intestinal strains in relation to plant strains. The ability of the tested strains to survive simulated gastric conditions showed a greater resistance of the human strains at a low pH 2.5 and the presence of pepsin, while in the presence of bile salts and pancreatin, some intestinal strains were more sensitive compared to plant strains. A wide spectrum of antimicrobial activities was observed in all tested strains. Most of the plant strains were resistant to aminoglycosides and vancomycin but sensitive to ampicillin and penicillin, while only some intestinal strains were resistant to these drugs. [Projekat Ministarstva nauke Republike Srbije, br. 46010

  4. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential.

    Science.gov (United States)

    Ishii, Tetsuya

    2014-10-13

    Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS) cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART) that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

  5. Establishment of human cell type-specific iPS cells with enhanced chondrogenic potential.

    Science.gov (United States)

    Guzzo, Rosa M; Scanlon, Vanessa; Sanjay, Archana; Xu, Ren-He; Drissi, Hicham

    2014-12-01

    The propensity of induced pluripotent stem (iPS) cells to differentiate into specific lineages may be influenced by a number of factors, including the selection of the somatic cell type used for reprogramming. Herein we report the generation of new iPS cells, which we derived from human articular chondrocytes and from cord blood mononucleocytes via lentiviral-mediated delivery of Oct4, Klf4, Sox2, and cMyc. Molecular, cytochemical, and cytogenic analyses confirmed the acquisition of hallmark features of pluripotency, as well as the retention of normal karyotypes following reprogramming of both the human articular chondrocytes (AC) and the cord blood (CB) cells. In vitro and in vivo functional analyses formally established the pluripotent differentiation capacity of all cell lines. Chondrogenic differentiation assays comparing iPS cells derived from AC, CB, and a well established dermal fibroblast cell line (HDFa-Yk26) identified enhanced proteoglycan-rich matrix formation and cartilage-associated gene expression from AC-derived iPS cells. These findings suggest that the tissue of origin may impact the fate potential of iPS cells for differentiating into specialized cell types, such as chondrocytes. Thus, we generated new cellular tools for the identification of inherent features driving high chondrogenic potential of reprogrammed cells.

  6. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

    Directory of Open Access Journals (Sweden)

    Tetsuya Ishii

    2014-10-01

    Full Text Available Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

  7. New evidence for the therapeutic potential of curcumin to treat nonalcoholic fatty liver disease in humans

    Science.gov (United States)

    Inzaugarat, María Eugenia; De Matteo, Elena; Baz, Placida; Lucero, Diego; García, Cecilia Claudia; Gonzalez Ballerga, Esteban; Daruich, Jorge; Sorda, Juan Antonio; Wald, Miriam Ruth

    2017-01-01

    Introduction The immune system acts on different metabolic tissues that are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Leptin and linoleic acid have the ability to potentially affect immune cells, whereas curcumin is a known natural polyphenol with antioxidant and anti-inflammatory properties. Aims This study was designed to evaluate the pro-inflammatory and pro-oxidant effects of leptin and linoleic acid on immune cells from patients with NAFLD and to corroborate the modulatory effects of curcumin and its preventive properties against the progression of NAFLD using a high-fat diet (HFD)-induced NAFLD/nonalcoholic steatohepatitis mouse model. Results The ex vivo experiments showed that linoleic acid increased the production of reactive oxygen species in monocytes and liver macrophages, whereas leptin enhanced tumor necrosis factor-α (TNF-α) production in monocytes and interferon-γ production in circulating CD4+ cells. Conversely, oral administration of curcumin prevented HFD-induced liver injury, metabolic alterations, intrahepatic CD4+ cell accumulation and the linoleic acid- and leptin- induced pro-inflammatory and pro-oxidant effects on mouse liver macrophages. Conclusion Our findings provide new evidence for the therapeutic potential of curcumin to treat human NAFLD. However, the development of a preventive treatment targeting human circulating monocytes and liver macrophages as well as peripheral and hepatic CD4+ cells requires additional research. PMID:28257515

  8. Human health risk assessment of nitrosamines and nitramines for potential application in CO2 capture.

    Science.gov (United States)

    Ravnum, S; Rundén-Pran, E; Fjellsbø, L M; Dusinska, M

    2014-07-01

    Emission and accumulation of carbon dioxide (CO2) in the atmosphere exert an environmental and climate change challenge. An attempt to deal with this challenge is made at Mongstad by application of amines for CO2 capture and storage (CO2 capture Mongstad (CCM) project). As part of the CO2 capture process, nitrosamines and nitramines may be emitted. Toxicological testing of nitrosamines and nitramines indicate a genotoxic potential of these substances. Here we present a risk characterization and assessment for five nitrosamines (N-Nitrosodi-methylamine (NDMA) N-Nitrosodi-ethylamine (NDEA), N-Nitroso-morpholine (NNM), N-Nitroso-piperidine (NPIP), and Dinitroso-piperazine (DNP)) and two nitramines (N-Methyl-nitramine (NTMA), Dimethyl-nitramine (NDTMA)), which are potentially emitted from the CO2 capture plant (CCP). Human health risk assessment of genotoxic non-threshold substances is a heavily debated topic, and no consensus methodology exists internationally. Extrapolation modeling from high-dose animal exposures to low-dose human exposures can be crucial for the final risk calculation. In the work presented here, different extrapolation models are discussed, and suggestions on applications are given. Then, preferred methods for calculating derived minimal effect level (DMEL) are presented with the selected nitrosamines and nitramines.

  9. Gravitational Correction to Vacuum Polarization

    CERN Document Server

    Jentschura, U D

    2015-01-01

    We consider the gravitational correction to (electronic) vacuum polarization in the presence of a gravitational background field. The Dirac propagators for the virtual fermions are modified to include the leading gravitational correction (potential term) which corresponds to a coordinate-dependent fermion mass. The mass term is assumed to be uniform over a length scale commensurate with the virtual electron-positron pair. The on-mass shell renormalization condition ensures that the gravitational correction vanishes on the mass shell of the photon, i.e., the speed of light is unaffected by the quantum field theoretical loop correction, in full agreement with the equivalence principle. Nontrivial corrections are obtained for off-shell, virtual photons. We compare our findings to other works on generalized Lorentz transformations and combined quantum-electrodynamic gravitational corrections to the speed of light which have recently appeared in the literature.

  10. The Real Problem (Humans) and Some Potentially Effective Alternatives and New Tools

    Energy Technology Data Exchange (ETDEWEB)

    Hanlon, Edward; Capece, John

    2011-01-07

    The presentation offers a wider perspective, where on the example of Everglades’ restoration efforts, the real problem – humans – is exposed. Some potentially effective alternatives and new tools are offered and discussed. Everglades’s problems are primarily caused to human activity, whether these are related to poor water quality, land use changes or cheap short-sighted fixes. Ground rules need to be set in order to have a real discussion and seek real solutions to such problems. The difference between facts and opinions is explained, so is the difference between interests and positions. These terms are often partly coinciding in human minds, thus causing further misunderstandings in pursuing real solutions. Some confounding factors in the Everglades restoration efforts are listed, with one of the main examples being the assignment of a monetary value to all factors. Some of these factors are priceless, but not being valued easily and properly (such as water). The proposed alternative to monetary value is assigning energy as the unit of measurement. The two main methods for such alternate approach are (1) Embodied energy (Emergy) and (2) Life Cycle Analysis. Agriculturally-based ecosystems services are different from natural ecosystems services. Pursuing agriculturally-based ecosystems services (such as e.g. water storage on farms, reducing nutrients in water, using flood-tolerant crops cultivars, etc.) can develop eco-services into agricultural operations and systems, addressing everyone’s interest and benefiting the society.

  11. Invasive Lionfish (Pterois volitans: A Potential Human Health Threat for Ciguatera Fish Poisoning in Tropical Waters

    Directory of Open Access Journals (Sweden)

    Alison Robertson

    2013-12-01

    Full Text Available Invasive Indo-Pacific lionfish (Pterois volitans have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP. More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas.

  12. Invasive lionfish (Pterois volitans): a potential human health threat for ciguatera fish poisoning in tropical waters.

    Science.gov (United States)

    Robertson, Alison; Garcia, Ana C; Quintana, Harold A Flores; Smith, Tyler B; Castillo, Bernard F; Reale-Munroe, Kynoch; Gulli, Joseph A; Olsen, David A; Hooe-Rollman, Jennifer I; Jester, Edward L E; Klimek, Brian J; Plakas, Steven M

    2013-12-27

    Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas.

  13. Human BK Polyomavirus—The Potential for Head and Neck Malignancy and Disease

    Directory of Open Access Journals (Sweden)

    Raquel Burger-Calderon

    2015-07-01

    Full Text Available Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV has conclusively been linked to human cancer, all members of the polyomavirus (PyV family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD. HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future.

  14. Human recombinant truncated RNASET2, devoid of RNase activity; A potential cancer therapeutic agent

    Science.gov (United States)

    Nesiel-Nuttman, Liron; Schwartz, Betty; Shoseyov, Oded

    2014-01-01

    Human RNASET2 has been implicated in antitumorigenic and antiangiogenic activities, independent of its ribonuclease capacities. We constructed a truncated version of human RNASET2, starting at E50 (trT2-50) and devoid of ribonuclease activity. trT2-50 maintained its ability to bind actin and to inhibit angiogenesis and tumorigenesis. trT2-50 binds to cell surface actin and formed a complex with actin in vitro. The antiangiogenic effect of this protein was demonstrated in human umbilical vein endothelial cells (HUVECs) by its ability to arrest tube formation on Matrigel, induced by angiogenic factors. Immunofluorescence staining of HUVECs showed nuclear and cytosolic RNASET2 protein that was no longer detectable inside the cell following trT2-50 treatment. This effect was associated with disruption of the intracellular actin network. trT2-50 co-localized with angiogenin, suggesting that both molecules bind (or compete) for similar cellular epitopes. Moreover, trT2-50 led to a significant inhibition of tumor development. Histological analysis demonstrated abundant necrotic tissue and a substantial loss of endothelial structure in trT2-50-treated tumors. Collectively, the present results indicate that trT2-50, a molecule engineered to be deficient of its catalytic activity, still maintained its actin binding and anticancer-related biological activities. We therefore suggest that trT2-50 may serve as a potential cancer therapeutic agent. PMID:25426551

  15. Arctic stratospheric ozone depletion and increased UVB radiation: potential impacts to human health.

    Science.gov (United States)

    De Fabo, Edward C

    2005-12-01

    Contrary to popular belief, stratospheric ozone depletion, and the resultant increase in solar UV-B (280-320 nm), are unlikely to fully recover soon. Notwithstanding the success of the Montreal Protocol in reducing the amount of ozone destroying chemicals into the stratosphere, the life-times of these compounds are such that even with full compliance with the Protocol by all countries, it will be decades before stratospheric ozone could return to pre-1980 levels. This raises the question, therefore, of what will happen to biological processes essential to the maintenance of life on earth which are sensitive to damage by increased UV-B radiation, particularly those involved with human health? The polar regions, because of the vagaries of climate and weather, are the bellwether for stratospheric ozone depletion and will, therefore, be the first to experience impacts due to increases in solar UV-B radiation. The impacts of these are incompletely understood and cannot be predicted with certainty. While some UV-B impacts on human health are recognized, much is unknown, unclear and uncertain. Thus, this paper attempts, as a first approximation, to point out potential impacts to the health and welfare of human inhabitants of the Arctic due to increased solar UV-B radiation associated with stratospheric ozone depletion. As will be seen, much more data is critically needed before adequate risk assessment can occur.

  16. Potential uses of human salivary protein and peptide analysis in the diagnosis of disease.

    Science.gov (United States)

    Al Kawas, Sausan; Rahim, Zubaidah H A; Ferguson, David B

    2012-01-01

    Saliva is an important body fluid containing a complex mixture of proteins, peptides and other substances. These are not only important in maintaining the health of the oral cavity but also may yield information about oral and systemic disease. Comprehensive analysis and identification of the proteomic content of human saliva may contribute to the understanding of oral pathophysiology and provide a foundation for the recognition of potential biomarkers of human disease. The collection of saliva samples is non-invasive, safe, and inexpensive. It seems likely that testing methods can be developed which can be used in general medical or dental practice. However, it is important to realize that the collection of saliva must be carefully controlled. In this paper we review the progress in the analysis of the human salivary proteome and summarise the diagnostic possibilities that have been explored. The precautions in collecting saliva, and some of the factors which would have to be considered if a diagnostic test were to be generally adopted are discussed.

  17. What is the potential of oligodendrocyte progenitor cells to successfully treat human spinal cord injury?

    Directory of Open Access Journals (Sweden)

    Yeung Trevor M

    2011-09-01

    Full Text Available Abstract Background Spinal cord injury is a serious and debilitating condition, affecting millions of people worldwide. Long seen as a permanent injury, recent advances in stem cell research have brought closer the possibility of repairing the spinal cord. One such approach involves injecting oligodendrocyte progenitor cells, derived from human embryonic stem cells, into the injured spinal cord in the hope that they will initiate repair. A phase I clinical trial of this therapy was started in mid 2010 and is currently underway. Discussion The theory underlying this approach is that these myelinating progenitors will phenotypically replace myelin lost during injury whilst helping to promote a repair environment in the lesion. However, the importance of demyelination in the pathogenesis of human spinal cord injury is a contentious issue and a body of literature suggests that it is only a minor factor in the overall injury process. Summary This review examines the validity of the theory underpinning the on-going clinical trial as well as analysing published data from animal models and finally discussing issues surrounding safety and purity in order to assess the potential of this approach to successfully treat acute human spinal cord injury.

  18. Calpains are required for invasive and metastatic potentials of human HCC cells.

    Science.gov (United States)

    Chen, Bo; Tang, Juan; Guo, Yun-Shan; Li, Yong; Chen, Zhi-Nan; Jiang, Jian-Li

    2013-07-01

    Calpains are a conserved family of calcium-dependent cysteine proteinases involved in various cellular functions. Two ubiquitous isoforms, µ- and m-calpain, are key members of the calpain family that play essential roles in regulating cell migration and invasion. However, it remains unclear whether they are involved in the progression of hepatocellular carcinoma (HCC). Here, we investigated the functions of µ- and m-calpain in the invasive and metastatic processes of human hepatoma cells. Our results indicated that the expression levels of calpains were elevated in HCC cells compared with those in normal hepatic cells. Our results indicated that small interfering RNA (siRNA)-mediated silencing of µ- and m-calpain expressions significantly suppressed the adhesive, migrative and invasive potentials of human hepatoma cells. The matrix metalloproteinases (MMPs) are key regulators of malignant tumour invasion and metastasis. siRNA-mediated down-regulation of µ- and m-calpain expressions also significantly attenuated MMP-2 and MMP-9 secretion. Thus µ- and m-calpain may play important roles in the invasion and metastasis of human hepatoma cells, and calpains may be drug targets for preventing HCC metastasis.

  19. Potential Applications for Radioisotope Power Systems in Support of Human Exploration Missions

    Science.gov (United States)

    Cataldo, Robert L.; Colozza, Anthony J.; Schmitz, Paul C.

    2013-01-01

    Radioisotope power systems (RPS) for space applications have powered over 27 U.S. space systems, starting with Transit 4A and 4B in 1961, and more recently with the successful landing of the Mars Science Laboratory rover Curiosity in August 2012. RPS enable missions with destinations far from the Sun with faint solar flux, on planetary surfaces with dense or dusty atmospheres, and at places with long eclipse periods where solar array sizes and energy storage mass become impractical. RPS could also provide an enabling capability in support of human exploration activities. It is envisioned that with the higher power needs of most human mission concepts, a high efficiency thermal-to-electric technology would be required such as the Advanced Stirling Radioisotope generator (ASRG). The ASRG should be capable of a four-fold improvement in efficiency over traditional thermoelectric RPS. While it may be impractical to use RPS as a main power source, many other applications could be considered, such as crewed pressurized rovers, in-situ resource production of propellants, back-up habitat power, drilling, any mobile or remote activity from the main base habitat, etc. This paper will identify potential applications and provide concepts that could be a practical extension of the current ASRG design in providing for robust and flexible use of RPS on human exploration missions.

  20. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    Science.gov (United States)

    Ryan, James; Curran, Catherine E; Hennessy, Emer; Newell, John; Morris, John C; Kerin, Michael J; Dwyer, Roisin M

    2011-01-19

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log(10) Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log(10)RQ, phuman NIS and ERα (r = 0.22, pfibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones.

  1. A fibrolytic potential in the human ileum mucosal microbiota revealed by functional metagenomic

    Science.gov (United States)

    Patrascu, Orlane; Béguet-Crespel, Fabienne; Marinelli, Ludovica; Le Chatelier, Emmanuelle; Abraham, Anne-Laure; Leclerc, Marion; Klopp, Christophe; Terrapon, Nicolas; Henrissat, Bernard; Blottière, Hervé M.; Doré, Joël; Béra-Maillet, Christel

    2017-01-01

    The digestion of dietary fibers is a major function of the human intestinal microbiota. So far this function has been attributed to the microorganisms inhabiting the colon, and many studies have focused on this distal part of the gastrointestinal tract using easily accessible fecal material. However, microbial fermentations, supported by the presence of short-chain fatty acids, are suspected to occur in the upper small intestine, particularly in the ileum. Using a fosmid library from the human ileal mucosa, we screened 20,000 clones for their activities against carboxymethylcellulose and xylans chosen as models of the major plant cell wall (PCW) polysaccharides from dietary fibres. Eleven positive clones revealed a broad range of CAZyme encoding genes from Bacteroides and Clostridiales species, as well as Polysaccharide Utilization Loci (PULs). The functional glycoside hydrolase genes were identified, and oligosaccharide break-down products examined from different polysaccharides including mixed-linkage β-glucans. CAZymes and PULs were also examined for their prevalence in human gut microbiome. Several clusters of genes of low prevalence in fecal microbiome suggested they belong to unidentified strains rather specifically established upstream the colon, in the ileum. Thus, the ileal mucosa-associated microbiota encompasses the enzymatic potential for PCW polysaccharide degradation in the small intestine. PMID:28091525

  2. Conserved B-cell epitopes among human bocavirus species indicate potential diagnostic targets.

    Directory of Open Access Journals (Sweden)

    Zhuo Zhou

    Full Text Available BACKGROUND: Human bocavirus species 1-4 (HBoV1-4 have been associated with respiratory and enteric infections in children. However, the immunological mechanisms in response to HBoV infections are not fully understood. Though previous studies have shown cross-reactivities between HBoV species, the epitopes responsible for this phenomenon remain unknown. In this study, we used genomic and immunologic approaches to identify the reactive epitopes conserved across multiple HBoV species and explored their potential as the basis of a novel diagnostic test for HBoVs. METHODOLOGY/PRINCIPAL FINDINGS: We generated HBoV1-3 VP2 gene fragment phage display libraries (GFPDLs and used these libraries to analyze mouse antisera against VP2 protein of HBoV1, 2, and 3, and human sera positive for HBoVs. Using this approach, we mapped four epitope clusters of HBoVs and identified two immunodominant peptides--P1 (¹MSDTDIQDQQPDTVDAPQNT²⁰, and P2 (¹⁶²EHAYPNASHPWDEDVMPDL¹⁸⁰--that are conserved among HBoV1-4. To confirm epitope immunogenicity, we immunized mice with the immunodominant P1 and P2 peptides identified in our screen and found that they elicited high titer antibodies in mice. These two antibodies could only recognize the VP2 of HBoV 1-4 in Western blot assays, rather than those of the two other parvoviruses human parvovirus B19 and human parvovirus 4 (PARV4. Based on our findings, we evaluated epitope-based peptide-IgM ELISAs as potential diagnostic tools for HBoVs IgM antibodies. We found that the P1+P2-IgM ELISA showed a higher sensitivity and specificity in HBoVs IgM detection than the assays using a single peptide. CONCLUSIONS/SIGNIFICANCE: The identification of the conserved B-cell epitopes among human bocavirus species contributes to our understanding of immunological cross-reactivities of HBoVs, and provides important insights for the development of HBoV diagnostic tools.

  3. Human papillomavirus type 16 variant analysis of E6, E7, and L1 [corrected] genes and long control region in [corrected] cervical carcinomas in patients in northeast China.

    Science.gov (United States)

    Shang, Qinglong; Wang, Yan; Fang, Yong; Wei, Lanlan; Chen, Sijia; Sun, Yuhui; Li, Baoxin; Zhang, Fengmin; Gu, Hongxi

    2011-07-01

    Human papillomavirus type 16 (HPV 16) plays a cardinal role in the pathogenesis of cervical cancer. HPV 16 has intratypic variants which show different geographical distributions and different oncogenic potentials. To analyze the presence of sequence variations of HPV 16 variants in northeast China, 71 cervical carcinomas were identified by HPV typing. HPV 16-positive specimens were analyzed by PCR-directed sequencing in the E6, E7, and L1 genes and the LCR (long control region). The variation data were compared with those of neighboring districts. In this hospital-based study, HPV 16 was the most common type (73.24%). In HPV 16-positive specimens, 67.31% belonged to the European (E) lineage, while 32.69% were Asian (As) variants. The Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and northern American (NA) lineages were not detected. The most frequently observed variation sites were T178G (32.69%) in E6; A647G (34.62%), G666A (38.46%), and T846C (32.69%) in E7; C6826T (36.17%) and G7060A (61.70%) in L1; and G7521A (98.08%) in the LCR. The most prevalent amino acid variations were D25E in E6 and N29S in E7. In addition, 28 novel variations of HPV 16 were reported. Some covariations between different genes were obtained. In this study, HPV 16 variants belonged to the European lineage and the Asian lineage. Compared with neighboring districts, the distribution of HPV 16 variants in northeast China had a typical pattern. As the first report on HPV 16 variants in northeast China, it should be helpful for designing a HPV vaccine and HPV vaccination program in China.

  4. Radiative corrections to Bose condensation

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, A. (Academia de Ciencias de Cuba, La Habana. Inst. de Matematica, Cibernetica y Computacion)

    1985-04-01

    The Bose condensation of the scalar field in a theory behaving in the Coleman-Weinberg mode is considered. The effective potential of the model is computed within the semiclassical approximation in a dimensional regularization scheme. Radiative corrections are shown to introduce certain ..mu..-dependent ultraviolet divergences in the effective potential coming from the Many-Particle theory. The weight of radiative corrections in the dynamics of the system is strongly modified by the charge density.

  5. Virtual impact: visualizing the potential effects of cosmic impact in human history

    Energy Technology Data Exchange (ETDEWEB)

    Masse, W Bruce [Los Alamos National Laboratory; Janecky, David R [Los Alamos National Laboratory; Forte, Maurizio [UC MERCED; Barrientos, Gustavo [UNIV OF LA PLATA, ARG.

    2009-01-01

    Current models indicate that catastrophic impacts by asteroids and comets capable of killing more than one quarter of Earth's human population have occurred on average once every million years; smaller impacts, such the 1908 Tunguska impact that leveled more than 2,000 square km of Siberian forest, occur every 200-300 years. Therefore, cosmic impact likely significantly affected hominine evolution and conceivably played a role in Holocene period human culture history. Regrettably, few archaeologists are trained to appreciate the nature and potential effects of cosmic impact. We have developed a conceptual model for an extensible set of educational and research tools based on virtual reality collaborative environments to engage archaeologists and the general public on the topic of the role of cosmic impact in human history. Our initial focus is on two documented asteroid impacts in Argentina during the period of 4000 to 1000 B.C. Campo del Cicio resulted in an energy release of around 2-3 megatons (100-150 times the Hiroshima atomic weapon), and left several craters and a strewn field covering 493 km{sup 2} in northeastern Argentina. Rio Cuarto was likely more than 1000 megatons and may have devastated an area greater than 50,000 km{sup 2} in central Argentina. We are focusing on reconstructions of these events and their potential effects on contemporary hunter and gatherers. Our vinual reality tools also introduce interactive variables (e.g., impactor physical properties, climate, vegetation, topography, and social complexity) to allow researchers and students to better investigate and evaluate the factors that significantly influence cosmic impact effects.

  6. Identification of an anti-inflammatory potential of Eriodictyon angustifolium compounds in human gingival fibroblasts.

    Science.gov (United States)

    Walker, Jessica; Reichelt, Katharina V; Obst, Katja; Widder, Sabine; Hans, Joachim; Krammer, Gerhard E; Ley, Jakob P; Somoza, Veronika

    2016-07-13

    Polyphenol-rich plant extracts have been shown to possess anti-inflammatory activity against oral pathogen-induced cytokine release in model systems of inflammation. Here, it was hypothesized that a flavanone-rich extract of E. angustifolium exhibits an anti-inflammatory potential against endotoxin-induced inflammatory response in human gingival fibroblasts (HGF-1). HGF-1 cells were stimulated with lipopolysaccharide from Porphyromonas gingivalis (pg-LPS) to release pro-inflammatory cytokines. Concentrations of interleukins IL-6 and IL-8 and macrophage chemoattractant protein-1 in the incubation media upon stimulation were determined by means of magnetic bead analysis. A crude ethanol/water extract of E. angustifolium (EE) was fractionated via gel permeation chromatography into a flavanone-rich fraction (FF) and an erionic acid-rich fraction (EF). Individual flavanones and erionic acids as well as EE, EF and FF were tested in the pg-LPS-stimulated HGF-1 cells for their anti-inflammatory potential. The E. angustifolium extract possessed anti-inflammatory potential in this model system, attenuating the pg-LPS-induced release of IL-6 by up to 52.0 ± 15.5%. Of the individual flavanones, eriodictyol and naringenin had the most pronounced effect. However, a mixture of the flavanones did not possess the same effect as the entire flavanoid fraction, indicating that other compounds may contribute to the anti-inflammatory potential of E. angustifolium. For the first time, an anti-inflammatory potential of E. angustifolium and containing erionic acids has been determined.

  7. Electromechanical Assessment of Human Knee Articular Cartilage with Compression-Induced Streaming Potentials.

    Science.gov (United States)

    Becher, Christoph; Ricklefs, Marcel; Willbold, Elmar; Hurschler, Christof; Abedian, Reza

    2016-01-01

    To assess the electromechanical properties of human knee articular cartilage with compression-induced streaming potentials for reliability among users and correlation with macroscopic and histological evaluation tools and sulfated glycosaminoglycan (sGAG) content. Streaming potentials are induced in cartilage in response to loading when mobile positive ions in the interstitial fluid temporarily move away from negatively charged proteoglycans. Streaming potential integrals (SPIs) were measured with an indentation probe on femoral condyles of 10 human knee specimens according to a standardized location scheme. Interobserver reliability was measured using an interclass correlation coefficient (ICC). The learning curves of 3 observers were evaluated by regression analysis. At each SPI measurement location the degradation level of the tissue was determined by means of the International Cartilage Repair Society (ICRS) score, Mankin score, and sGAG content. The computed ICC was 0.77 (0.70-0.83) indicating good to excellent linear agreement of SPI values among the 3 users. A significant positive linear correlation of the learning index values was observed for 2 of the 3 users. Statistically significant negative correlations between SPI and both ICRS and Mankin scores were observed (r = 0.502, P < 0.001, and r = 0.255, P = 0.02, respectively). No correlation was observed between SPI and sGAG content (r = 0.004, P = 0.973). SPI values may be used as a quantitative means of cartilage evaluation with sufficient reliability among users. Due to the significant learning curve, adequate training should be absolved before routine use of the technique.

  8. Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses*

    Science.gov (United States)

    Yu, Ying; Lasanajak, Yi; Song, Xuezheng; Hu, Liya; Ramani, Sasirekha; Mickum, Megan L.; Ashline, David J.; Prasad, B. V. Venkataram; Estes, Mary K.; Reinhold, Vernon N.; Cummings, Richard D.; Smith, David F.

    2014-01-01

    Human milk contains a rich set of soluble, reducing glycans whose functions and bioactivities are not well understood. Because human milk glycans (HMGs) have been implicated as receptors for various pathogens, we explored the functional glycome of human milk using shotgun glycomics. The free glycans from pooled milk samples of donors with mixed Lewis and Secretor phenotypes were labeled with a fluorescent tag and separated via multidimensional HPLC to generate a tagged glycan library containing 247 HMG targets that were printed to generate the HMG shotgun glycan microarray (SGM). To investigate the potential role of HMGs as decoy receptors for rotavirus (RV), a leading cause of severe gastroenteritis in children, we interrogated the HMG SGM with recombinant forms of VP8* domains of the RV outer capsid spike protein VP4 from human neonatal strains N155(G10P[11]) and RV3(G3P[6]) and a bovine strain, B223(G10P[11]). Glycans that were bound by RV attachment proteins were selected for detailed structural analyses using metadata-assisted glycan sequencing, which compiles data on each glycan based on its binding by antibodies and lectins before and after exo- and endo-glycosidase digestion of the SGM, coupled with independent MSn analyses. These complementary structural approaches resulted in the identification of 32 glycans based on RV VP8* binding, many of which are novel HMGs, whose detailed structural assignments by MSn are described in a companion report. Although sialic acid has been thought to be important as a surface receptor for RVs, our studies indicated that sialic acid is not required for binding of glycans to individual VP8* domains. Remarkably, each VP8* recognized specific glycan determinants within a unique subset of related glycan structures where specificity differences arise from subtle differences in glycan structures. PMID:25048705

  9. A critical role for the transient receptor potential channel type 6 in human platelet activation.

    Directory of Open Access Journals (Sweden)

    Hari Priya Vemana

    Full Text Available While calcium signaling is known to play vital roles in platelet function, the mechanisms underlying its receptor-operated calcium entry component (ROCE remain poorly understood. It has been proposed, but never proven in platelets, that the canonical transient receptor potential channel-6 (TRPC6 mediates ROCE. Nonetheless, we have previously shown that the mouse TRPC6 regulates hemostasis, thrombogenesis by regulating platelet aggregation. In the present studies, we used a pharmacological approach to characterize the role of TRPC6 in human platelet biology. Thus, interestingly, we observed that a TRPC6 inhibitor exerted significant inhibitory effects on human platelet aggregation in a thromboxane receptor (TPR-selective manner; no additional inhibition was observed in the presence of the calcium chelator BAPTA. This inhibitor also significantly inhibited human platelet secretion (dense and alpha granules, integrin IIb-IIIa, Akt and ERK phosphorylation, again, in a TPR-selective manner; no effects were observed in response to ADP receptor stimulation. Furthermore, there was a causal relationship between these inhibitory effects, and the capacity of the TRPC6 inhibitor to abrogate elevation in intracellular calcium, that was again found to be TPR-specific. This effect was not found to be due to antagonism of TPR, as the TRPC6 inhibitor did not displace the radiolabeled antagonist [3H]SQ29,548 from its binding sites. Finally, our studies also revealed that TRPC6 regulates human clot retraction, as well as physiological hemostasis and thrombus formation, in mice. Taken together, our findings demonstrate, for the first time, that TRPC6 directly regulates TPR-dependent ROCE and platelet function. Moreover, these data highlight TRPC6 as a novel promising therapeutic strategy for managing thrombotic disorders.

  10. Cholesterol-lowering potential in human subjects of fat from pigs fed rapeseed oil.

    Science.gov (United States)

    Sandström, B; Bügel, S; Lauridsen, C; Nielsen, F; Jensen, C; Skibsted, L H

    2000-08-01

    The possibility of achieving blood-lipid-lowering characteristics of pig fat by increasing the content of unsaturated fat in pig feed was evaluated. Three pig feeding regimens were applied: basal feed (no added fat or vitamin E), basal feed + rapeseed oil (60 g/kg feed), and basal feed + rapeseed oil (60 g/kg) + vitamin E (200 mg/kg). Meat and meat products from the three pig groups were incorporated into diets providing 86 g pig fat/10 MJ. The diets were served to twelve healthy human male subjects for 3 weeks each in a randomised crossover design. The diets prepared from pigs fed rapeseed oil had a lower content of saturated fatty acids (approximately 9 v. 11% of energy) and a higher content of polyunsaturated fatty acids (approximately 6 v. 4% of energy) than the diet prepared from pigs fed the basal feed. Diets based on fat from pigs fed the rapeseed oil resulted in significantly lower (approximately 4%, P = 0.019) total serum cholesterol concentration compared with the diet from pigs fed the basal feed. No differences were observed in LDL-, HDL- or VLDL-cholesterol, or in triacylglycerol or VLDL-triacylglycerol concentrations. Addition of vitamin E to the pig feed resulted in only a minor increase in vitamin E content in the human subjects' diet and the vitamin E content was low in all three pig diets. Plasma vitamin E concentration in the human subjects at the end of the period with diets from pigs fed rapeseed oil without vitamin E was significantly lower (P = 0.04) than in the other two diet periods. In conclusion, an increased content of rapeseed oil in pig feed changes the fatty acid composition of the pig fat in a way that has a potential to reduce blood cholesterol concentrations in human subjects. However, intake of pig fat with a higher content of unsaturated fatty acids needs to be matched by a higher dietary intake of vitamin E.

  11. The Metastatic Potential and Chemoresistance of Human Pancreatic Cancer Stem Cells.

    Directory of Open Access Journals (Sweden)

    Vikash J Bhagwandin

    Full Text Available Cancer stem cells (CSCs typically have the capacity to evade chemotherapy and may be the principal source of metastases. CSCs for human pancreatic ductal carcinoma (PDAC have been identified, but neither the metastatic potential nor the chemoresistance of these cells has been adequately evaluated. We have addressed these issues by examining side-population (SP cells isolated from the Panc-1 and BxPC3 lines of human PDAC cells, the oncogenotypes of which differ. SP cells could be isolated from monolayers of Panc-1, but only from spheroids of BxPC3. Using orthotopic xenografts into the severely immunocompromised NSG mouse, we found that SP cells isolated from both cell lines produced tumors that were highly metastatic, in contrast to previous experience with PDAC cell lines. SP cells derived from both cell lines expressed the ABCG2 transporter, which was demonstrably responsible for the SP phenotype. SP cells gave rise to non-SP (NSP cells in vitro and in vivo, a transition that was apparently due to posttranslational inhibition of the ABCG2 transporter. Twenty-two other lines of PDAC cells also expressed ABCG2. The sensitivity of PDAC SP cells to the vinca alkaloid vincristine could be greatly increased by verapamil, a general inhibitor of transporters. In contrast, verapamil had no effect on the killing of PDAC cells by gemcitabine, the current first-line therapeutic for PDAC. We conclude that the isolation of SP cells can be a convenient and effective tool for the study of PDAC CSCs; that CSCs may be the principal progenitors of metastasis by human PDAC; that the ABCG2 transporter is responsible for the SP phenotype in human PDAC cells, and may be a ubiquitous source of drug-resistance in PDAC, but does not confer resistance to gemcitabine; and that inhibition of ABCG2 might offer a useful adjunct in a therapeutic attack on the CSCs of PDAC.

  12. Radioactivity contents in dicalcium phosphate and the potential radiological risk to human populations.

    Science.gov (United States)

    Casacuberta, N; Masqué, P; Garcia-Orellana, J; Bruach, J M; Anguita, M; Gasa, J; Villa, M; Hurtado, S; Garcia-Tenorio, R

    2009-10-30

    Potentially harmful phosphate-based products derived from the wet acid digestion of phosphate rock represent one of the most serious problems facing the phosphate industry. This is particularly true for dicalcium phosphate (DCP), a food additive produced from either sulphuric acid or hydrochloric acid digestion of raw rock material. This study determined the natural occurring radionuclide concentrations of 12 DCP samples and 4 tricalcium phosphate (TCP) samples used for animal and human consumption, respectively. Metal concentrations (Al, Fe, Zn, Cd, Cr, As, Hg, Pb and Mg) were also determined. Samples were grouped into three different clusters (A, B, C) based on their radionuclide content. Whereas group A is characterized by high activities of 238U, 234U (approximately 10(3) Bq kg(-1)), 210Pb (2 x 10(3) Bq kg(-1)) and (210)Po ( approximately 800 Bq kg(-1)); group B presents high activities of (238)U, (234)U and (230)Th (approximately 10(3) Bq kg(-1)). Group C was characterized by very low activities of all radionuclides (DCP samples for animal consumption (groups A and B) were related to the wet acid digestion method used, with group A samples produced from hydrochloric acid digestion, and group B samples produced using sulphuric acid. Group C includes more purified samples required for human consumption. High radionuclide concentrations in some DCP samples (reaching 2 x 10(3) and 10(3) Bq kg(-1) of 210Pb and 210Po, respectively) may be of concern due to direct or indirect radiological exposure via ingestion. Our experimental results based on 210Pb and 210Po within poultry consumed by humans, suggest that the maximum radiological doses are 11 +/- 2 microSv y(-1). While these results suggest that human health risks are small, additional testing should be conducted.

  13. Real and potential mercury accumulation in human scalp of adolescents: a case study.

    Science.gov (United States)

    Vieira, H C; Morgado, F; Soares, A M V M; Abreu, S N

    2015-02-01

    Mercury (Hg) concentration in human hair is used to estimate methylmercury (MeHg) exposure and establish a reference dose for MeHg intake. In this study, Hg accumulation and MeHg intake were evaluated in relation to fish consumption habits in adolescents from two coastal areas: Angra do Heroísmo (Azores archipelago) and Murtosa (Portuguese mainland). Results showed that Hg concentration and MeHg intake increased with increasing fish consumption. In spite of that, Hg concentrations remained relatively low when compared with World Health Organization "no observed adversary effect level"; therefore, risk for mercury exposure should not be considered. Adolescents revealed a similar range of Hg concentrations (0.03-2.60 μg g(-1)) in scalp hair, apart from being exposed to natural or anthropogenic Hg source (Azores and Mainland, respectively). Nevertheless, Mainland volunteers generally exhibited higher values of Hg accumulation, being approximately 50 % of the results above 1 μg g(-1). Hg concentrations increased in both adolescent groups according to the weekly rate of fish meals, however, not linearly in the highest fish consumption rates. In fact, considering the adolescents' group having over one fish meal per week, the Hg bioaccumulation pattern found in the respective scalp hair suggests the ability of the human body to induce a self-protection response, probably mitigating Hg levels in the blood when experiencing increasing Hg exposure due to fish uptake. Actual and potential mercury levels in human scalp of adolescents probably diverge as fish consumption increases, the effective Hg uptake being lower than the expected, reducing risk to human health.

  14. The sodium iodide symporter (NIS and potential regulators in normal, benign and malignant human breast tissue.

    Directory of Open Access Journals (Sweden)

    James Ryan

    Full Text Available INTRODUCTION: The presence, relevance and regulation of the Sodium Iodide Symporter (NIS in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. METHODS: Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10 were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ, oestrogen (ERα, thyroid hormones (THRα, THRβ, and also phosphoinositide-3-kinase (PI3K. Breast cancer cells were treated with Retinoic acid (ATRA, Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. RESULTS: The lowest levels of NIS were detected in normal tissue (Mean(SEM 0.70(0.12 Log(10 Relative Quantity (RQ with significantly higher levels observed in fibroadenoma (1.69(0.21 Log(10RQ, p<0.005 and malignant breast tissue (1.18(0.07 Log(10RQ, p<0.05. Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05 and RARα (r = 0.29, p<0.005, with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001. An inverse relationship between NIS and PI3K expression was also observed (r =  0.21, p<0.05. In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6-16 fold, while ATRA and Thyroxine combined caused the greatest increase (range 16-26 fold. CONCLUSION: Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones.

  15. The Metastatic Potential and Chemoresistance of Human Pancreatic Cancer Stem Cells.

    Science.gov (United States)

    Bhagwandin, Vikash J; Bishop, J Michael; Wright, Woodring E; Shay, Jerry W

    2016-01-01

    Cancer stem cells (CSCs) typically have the capacity to evade chemotherapy and may be the principal source of metastases. CSCs for human pancreatic ductal carcinoma (PDAC) have been identified, but neither the metastatic potential nor the chemoresistance of these cells has been adequately evaluated. We have addressed these issues by examining side-population (SP) cells isolated from the Panc-1 and BxPC3 lines of human PDAC cells, the oncogenotypes of which differ. SP cells could be isolated from monolayers of Panc-1, but only from spheroids of BxPC3. Using orthotopic xenografts into the severely immunocompromised NSG mouse, we found that SP cells isolated from both cell lines produced tumors that were highly metastatic, in contrast to previous experience with PDAC cell lines. SP cells derived from both cell lines expressed the ABCG2 transporter, which was demonstrably responsible for the SP phenotype. SP cells gave rise to non-SP (NSP) cells in vitro and in vivo, a transition that was apparently due to posttranslational inhibition of the ABCG2 transporter. Twenty-two other lines of PDAC cells also expressed ABCG2. The sensitivity of PDAC SP cells to the vinca alkaloid vincristine could be greatly increased by verapamil, a general inhibitor of transporters. In contrast, verapamil had no effect on the killing of PDAC cells by gemcitabine, the current first-line therapeutic for PDAC. We conclude that the isolation of SP cells can be a convenient and effective tool for the study of PDAC CSCs; that CSCs may be the principal progenitors of metastasis by human PDAC; that the ABCG2 transporter is responsible for the SP phenotype in human PDAC cells, and may be a ubiquitous source of drug-resistance in PDAC, but does not confer resistance to gemcitabine; and that inhibition of ABCG2 might offer a useful adjunct in a therapeutic attack on the CSCs of PDAC.

  16. MicroRNA-138 is a potential regulator of memory performance in humans

    Directory of Open Access Journals (Sweden)

    Julia eSchröder

    2014-07-01

    Full Text Available Genetic factors underlie a substantial proportion of individual differences in cognitive functions in humans, including processes related to episodic and working memory. While genetic association studies have proposed several candidate memory genes, these currently explain only a minor fraction of the phenotypic variance. Here, we performed genome-wide screening on 13 episodic and working memory phenotypes in 1,318 participants of the Berlin Aging Study II aged 60 years or older. The analyses highlight a number of novel single nucleotide polymorphisms (SNPs associated with memory performance, including one located in a putative regulatory region of microRNA (miRNA hsa-mir-138-5p (rs9882688, P-value = 7.8x10-9. Expression quantitative trait locus analyses on next-generation RNA-sequencing data revealed that rs9882688 genotypes show a significant correlation with the expression levels of this miRNA in 309 human lymphoblastoid cell lines (P-value = 5x10-4. In silico modeling of other top-ranking GWAS signals identified an additional memory-associated SNP in the 3' untranslated region (3'UTR of DCP1B, a gene encoding a core component of the mRNA decapping complex in humans, predicted to interfere with hsa-mir-138-5p binding. This prediction was confirmed in vitro by luciferase assays showing differential binding of hsa-mir-138-5p to 3'UTR reporter constructs in two human cell lines (HEK293: P-value = 0.0470; SH-SY5Y: P-value = 0.0866. Finally, expression profiling of hsa-mir-138-5p and DCP1B mRNA in human post-mortem brain tissue revealed that both molecules are expressed simultaneously in frontal cortex and hippocampus, suggesting that the proposed interaction between hsa-mir-138-5p and DCP1B may also take place in vivo. In summary, by combining unbiased genome-wide screening with extensive in silico modeling, in vitro functional assays, and gene expression profiling, our study identified miRNA-138 as a potential molecular regulator of human memory

  17. MicroRNA-138 is a potential regulator of memory performance in humans

    Science.gov (United States)

    Schröder, Julia; Ansaloni, Sara; Schilling, Marcel; Liu, Tian; Radke, Josefine; Jaedicke, Marian; Schjeide, Brit-Maren M.; Mashychev, Andriy; Tegeler, Christina; Radbruch, Helena; Papenberg, Goran; Düzel, Sandra; Demuth, Ilja; Bucholtz, Nina; Lindenberger, Ulman; Li, Shu-Chen; Steinhagen-Thiessen, Elisabeth; Lill, Christina M.; Bertram, Lars

    2014-01-01

    Genetic factors underlie a substantial proportion of individual differences in cognitive functions in humans, including processes related to episodic and working memory. While genetic association studies have proposed several candidate “memory genes,” these currently explain only a minor fraction of the phenotypic variance. Here, we performed genome-wide screening on 13 episodic and working memory phenotypes in 1318 participants of the Berlin Aging Study II aged 60 years or older. The analyses highlight a number of novel single nucleotide polymorphisms (SNPs) associated with memory performance, including one located in a putative regulatory region of microRNA (miRNA) hsa-mir-138-5p (rs9882688, P-value = 7.8 × 10−9). Expression quantitative trait locus analyses on next-generation RNA-sequencing data revealed that rs9882688 genotypes show a significant correlation with the expression levels of this miRNA in 309 human lymphoblastoid cell lines (P-value = 5 × 10−4). In silico modeling of other top-ranking GWAS signals identified an additional memory-associated SNP in the 3′ untranslated region (3′ UTR) of DCP1B, a gene encoding a core component of the mRNA decapping complex in humans, predicted to interfere with hsa-mir-138-5p binding. This prediction was confirmed in vitro by luciferase assays showing differential binding of hsa-mir-138-5p to 3′ UTR reporter constructs in two human cell lines (HEK293: P-value = 0.0470; SH-SY5Y: P-value = 0.0866). Finally, expression profiling of hsa-mir-138-5p and DCP1B mRNA in human post-mortem brain tissue revealed that both molecules are expressed simultaneously in frontal cortex and hippocampus, suggesting that the proposed interaction between hsa-mir-138-5p and DCP1B may also take place in vivo. In summary, by combining unbiased genome-wide screening with extensive in silico modeling, in vitro functional assays, and gene expression profiling, our study identified miRNA-138 as a potential molecular regulator of

  18. Fibrogenic potential of human multipotent mesenchymal stromal cells in injured liver.

    Directory of Open Access Journals (Sweden)

    Reto M Baertschiger

    Full Text Available Multipotent mesenchymal stromal cells (MSC are currently investigated clinically as cellular therapy for a variety of diseases. Differentiation of MSC toward endodermal lineages, including hepatocytes and their therapeutic effect on fibrosis has been described but remains controversial. Recent evidence attributed a fibrotic potential to MSC. As differentiation potential might be dependent of donor age, we studied MSC derived from adult and pediatric human bone marrow and their potential to differentiate into hepatocytes or myofibroblasts in vitro and in vivo. Following characterization, expanded adult and pediatric MSC were co-cultured with a human hepatoma cell line, Huh-7, in a hepatogenic differentiation medium containing Hepatocyte growth factor, Fibroblast growth factor 4 and oncostatin M. In vivo, MSC were transplanted into spleen or liver of NOD/SCID mice undergoing partial hepatectomy and retrorsine treatment. Expression of mesenchymal and hepatic markers was analyzed by RT-PCR, Western blot and immunohistochemistry. In vitro, adult and pediatric MSC expressed characteristic surface antigens of MSC. Expansion capacity of pediatric MSC was significantly higher when compared to adult MSC. In co-culture with Huh-7 cells in hepatogenic differentiation medium, albumin expression was more frequently detected in pediatric MSC (5/8 experiments when compared to adult MSC (2/10 experiments. However, in such condition pediatric MSC expressed alpha smooth muscle more strongly than adult MSC. Stable engraftment in the liver was not achieved after intrasplenic injection of pediatric or adult MSC. After intrahepatic injection, MSC permanently remained in liver tissue, kept a mesenchymal morphology and expressed vimentin and alpha smooth muscle actin, but no hepatic markers. Further, MSC localization merges with collagen deposition in transplanted liver and no difference was observed using adult or pediatric MSC. In conclusion, when transplanted into an

  19. La correction et la révision de l’écrit en français langue seconde: médiation humaine, médiation informatique Correcting and editing texts written by FSL students: human mediation vs. computer-assisted mediation

    Directory of Open Access Journals (Sweden)

    Chantal Dion

    2003-06-01

    Full Text Available L’apprentissage de la correction / révision de l’écrit par les apprenants de français langue seconde peut-elle tirer profit des correcteurs orthographiques et grammaticaux des traitements de texte ou des correcticiels spécialisés ? La nature de la médiation informatique permet-elle aux apprenants de corriger de façon efficace leurs textes et comment se compare-t-elle avec la correction humaine ? Qu’est-ce qui différencie ces deux médiations ? Des textes rédigés par des anglophones ont été soumis aux deux types de corrections, humaine et informatique, soit deux enseignantes ayant vingt ans d’expérience et la correction informatique effectuée par le correcteur orthographique et grammatical de Word et les deux correcticiels canadiens, Le correcteur 101 et Antidote. Les résultats montrent que la nature de ces médiations n’est pas comparable et que la médiation informatique, pour être efficace, nécessite la participation active, intelligente et instruite de l’utilisateur et que les correcticiels ne peuvent pas corriger efficacement des textes d’étudiants de niveau intermédiaire.Can spellcheckers or grammar correctors, be they part of a word processor or stand-alone programs, help FSL students become more adept at correcting or editing the written texts they produce? Does computer-assisted mediation enable learners to correct their work efficiently and how does it compare with human mediation? What differentiates them? Texts written by anglophone students were corrected using both methods, i.e., on the one hand, by two teachers with 20 years experience and, on the other hand, using the specialized tools available with MSWord as well as two Canadian text correction programs, Le Correcteur 101 and Antidote. It turns out that the two methods are of very different natures ; computer-based correction can only give some positive results if the users have received appropriate training enabling them to actively and

  20. Bioaccumulation of heavy metals in mollusca species and assessment of potential risks to human health.

    Science.gov (United States)

    Abdallah, Maha Ahmed Mohamed

    2013-05-01

    Along the Alexandria coast of the Egyptian Mediterranean Sea, five edible species of bivalve molluscs and one gastropoda species (Mactra coralline, Ruditapes decussates, Paphia undulate, Venerupis rhomboids, Crista pectinata and Coralliophila meyendorffi) were analyzed for content of metals (Cadmium, Chromium, Lead, Cobalt and Nickel) in the muscle and in the sediments where they live. The potential health risks of metals to humans via consumption of seafood were assessed by estimated daily intake and target hazard quotient. Significant positive correlations (p < 0.05) were obtained between tissue concentrations for all pairs of metals, with the exception of Cadmium. Significant positive correlations were also obtained for the concentrations of Cd and Ni in tissues of all studied species relative to their concentrations in surface sediments. However, correlations between tissue and sediment concentrations for Chromium, Lead and Cobalt were negative. Ruditapes decussates and C. meyendorffi had the highest values for the summed target hazard quotient and may pose a potential risk to local inhabitants through their consumption in the diet. The potential risk would arise from exposure to high tissue concentrations of Cd and Pb, which exceeded published guidelines for safety of seafood products in some cases. Chromium contributed a considerable fraction of the total target hazard quotient for all metals combined, but did not exceed the published guidelines. Cobalt and Ni did not contribute greatly overall to the target hazard quotient, except in the case of Ni in V. rhomboids.

  1. The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease.

    Science.gov (United States)

    Lee, Hyun Ju; Lee, Jong Kil; Lee, Hyun; Shin, Ji-woong; Carter, Janet E; Sakamoto, Toshiro; Jin, Hee Kyung; Bae, Jae-sung

    2010-08-30

    The neuropathological hallmarks of Alzheimer's disease (AD) include the presence of extracellular amyloid-beta peptide (Abeta) in the form of amyloid plaques in the brain parenchyma and neuronal loss. The mechanism associated with neuronal death by amyloid plaques is unclear but oxidative stress and glial activation has been implicated. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are being scrutinized as a potential therapeutic tool to prevent various neurodegenerative diseases including AD. However, the therapeutic impact of hUCB-MSCs in AD has not yet been reported. Here we undertook in vitro work to examine the potential impact of hUCB-MSCs treatment on neuronal loss using a paradigm of cultured hippocampal neurons treated with Abeta. We confirmed that hUCB-MSCs co-culture reduced the hippocampal apoptosis induced by Abeta treatment. Moreover, in an acute AD mouse model to directly test the efficacy of hUCB-MSCs treatment on AD-related cognitive and neuropathological outcomes, we demonstrated that markers of glial activation, oxidative stress and apoptosis levels were decreased in AD mouse brain. Interestingly, hUCB-MSCs treated AD mice demonstrated cognitive rescue with restoration of learning/memory function. These data suggest that hUCB-MSCs warrant further investigation as a potential therapeutic agent in AD.

  2. Potentials-attract or likes-attract in human mate choice in China.

    Science.gov (United States)

    He, Qiao-Qiao; Zhang, Zhen; Zhang, Jian-Xin; Wang, Zhi-Guo; Tu, Ying; Ji, Ting; Tao, Yi

    2013-01-01

    To explain how individuals' self-perceived long-term mate value influences their mate preference and mate choice, two hypotheses have been presented, which are "potentials-attract" and "likes-attract", respectively. The potentials-attract means that people choose mates matched with their sex-specific traits indicating reproductive potentials; and the likes-attract means that people choose mates matched with their own conditions. However, the debate about these two hypotheses still remains unsolved. In this paper, we tested these two hypotheses using a human's actual mate choice data from a Chinese online dating system (called the Baihe website), where 27,183 users of Baihe website are included, in which there are 590 paired couples (1180 individuals) who met each other via the website. Our main results show that not only the relationship between individuals' own attributes and their self-stated mate preference but also that between individuals' own attributes and their actual mate choice are more consistent with the likes-attract hypothesis, i.e., people tend to choose mates who are similar to themselves in a variety of attributes.

  3. Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review.

    Science.gov (United States)

    Kollins, S H; MacDonald, E K; Rush, C R

    2001-03-01

    Methylphenidate (MPH) is widely used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children, adolescents, and adults. Methylphenidate is clearly effective for the treatment of ADHD, but there is controversy as to whether it has significant abuse potential like other psychostimulants (e.g., D-amphetamine and cocaine). In general, the drug is believed to be abused at rates much lower than those for other stimulants. The present review examines studies that investigated the behavioral pharmacological profile of methylphenidate and discusses how results from these studies address its abuse liability. Using MEDLINE search terms methylphenidate, drug discrimination, reinforcement, self-administration, subjective effects, subject-rated effects, abuse potential, and abuse liability, along with a review of the references from identified articles, 60 studies were located in which the reinforcing, discriminative-stimulus, or subjective effects of methylphenidate were directly assessed in nonhumans or humans. Forty-eight (80.0%) of the studies reviewed indicate that methylphenidate either functions in a manner similar to D-amphetamine or cocaine (e.g., functions as a reinforcer, substitutes fully in drug discrimination experiments), or produces a pattern of subjective effects suggestive of abuse potential. The results are discussed as they pertain to factors that may account for the apparent discrepancy in abuse rates between methylphenidate and other stimulants, including characterization of actual abuse rates, defining abuse and misuse, pharmacokinetic factors, and validity of abuse liability assays.

  4. Potentials-attract or likes-attract in human mate choice in China.

    Directory of Open Access Journals (Sweden)

    Qiao-Qiao He

    Full Text Available To explain how individuals' self-perceived long-term mate value influences their mate preference and mate choice, two hypotheses have been presented, which are "potentials-attract" and "likes-attract", respectively. The potentials-attract means that people choose mates matched with their sex-specific traits indicating reproductive potentials; and the likes-attract means that people choose mates matched with their own conditions. However, the debate about these two hypotheses still remains unsolved. In this paper, we tested these two hypotheses using a human's actual mate choice data from a Chinese online dating system (called the Baihe website, where 27,183 users of Baihe website are included, in which there are 590 paired couples (1180 individuals who met each other via the website. Our main results show that not only the relationship between individuals' own attributes and their self-stated mate preference but also that between individuals' own attributes and their actual mate choice are more consistent with the likes-attract hypothesis, i.e., people tend to choose mates who are similar to themselves in a variety of attributes.

  5. Introducing the potential of antimicrobial materials for human and robotic spaceflight activities

    Science.gov (United States)

    Hahn, Claudia; Reitz, Guenther; Moeller, Ralf; Rettberg, Petra; Hans, Michael; Muecklich, Frank

    One major goal of space research is to discover past or present life on foreign planets such as Mars (Horneck et al., 2010). To detect extraterrestrial life on other planets it is important to prevent microbial contamination imported from the Earth, also known as forward contamination. Until now missions to Mars are solely progressed by robots like the Mars Science Laboratory mission with the Curiosity lander. The assembly of spacecraft components is performed in special bioburden controlled clean rooms. Nevertheless, the microbial diversity in these clean rooms is enormous (Vaishampayan et al., 2013). The propagation of microorganisms and in particular the spread of environmental and human-associated species can be facilitated through numerous exposure routes (e.g., air, personal contact, water, excretions, etc.). Besides robotic missions, on-board the International Space Station (ISS) and in (future) space vehicles for long-term journeys to special targets of astrobiological interests in the solar system, astronauts will have the unique opportunity for scientific exploration. The manned exploration of new environments (e.g. asteroids, Mars) require long-term residence in confined stations and habitats (e.g. space stations, spacecraft, vehicles). During these missions, the health of the crew members has to be protected, and the integrity of the materials and facilities should be carefully monitored (van Houdt et al., 2012). A major concern is the microbiological burden in enclosed environments, where human inhabitants are continuously exposed to potential harmful microorganisms over a long-duration, which may affect the health and performance of the human subjects (Horneck et al., 2010) in addition to potential risks by biofilm formation and biocorrosion of materials. In both scenarios, the application of antimicrobial surfaces is an encouraging approach to reduce microorganisms in a straightforward way. Antimicrobial agents and materials are characterized by

  6. [Correction of five different types of errors of model REFSEQs appeared in NCBI human gene database only by using two novel human genes C17orf32 and ZNF362].

    Science.gov (United States)

    Zhang, De-Li; Li, Yan-Da; Ji, Liang

    2004-04-01

    to the 208 aa protein encoded by C17orf32, with matching percentage of 50% in 48% of total window over the full-length protein, especially 23 approximately 104 aa of XP_097165 is just the same as 96 approximately 177 aa of C17orf32 protein. Both flanking regions of LOC147007 outside the same ORF central part are wrong assembly of non-relative cDNA. In addition, we have in silico cloned a novel mouse gene, ORF32 (open reading frame 32) with TPA accession number of BK000258, which is the mouse ortholog of human C17orf32. Our strategy is helpful in both finding out more novel human genes and correcting the mistakes in the REFSEQs issued by NCBI genome annnotation project. For example, we adopted the gene anticipating method, through automatic calculation and analysis, anticipated two modes reference sequences (LOC124919 and LOC147007) from NCBI contig NT_ 010808. Both of them should be C17orf32, but the fact is that both of them are various wrong forms of C17orf32, respectively are the first type and second type of mistakes. Another example, we adopted gene anticipation method, through automatic calculation and analysis, anticipated three modes reference sequences (LOC14907, LOC200084 and LOC91126) from NCBI contig NT_004511 which really are one type of gene of ZNF362, but submitted three different wrong forms of ZNF362, respectively are: the fourth, fifth, and seventh type of mistakes. We can correct or avoid the currently wrong human genome coding sequence by using in silico clone and combining experimental verification. People should be cautious in treating the computer's annotation which may exist all type of wrong human genome coding sequences. The correct identification and annotation of the novel human genes still remain to be a long and arduous task.

  7. Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes.

    Science.gov (United States)

    Arufe, M C; De la Fuente, A; Fuentes, I; de Toro, F J; Blanco, F J

    2010-11-01

    In this study we analyzed the chondrogenic potential of subpopulations of mesenchymal stem cells (MSCs) derived from human synovial membranes enriched for CD73, CD106, and CD271 markers. Subpopulations of human synovial membrane MSCs enriched for CD73, CD106, and CD271 markers were isolated using a cytometry sorter and characterized by flow cytometry for MSC markers. The expression of Sox9, Nanog, and Runx2 genes by these cells was measured by reverse transcriptase-polymerase chain reaction. The chondrogenesis of each subpopulation was assessed by culturing the cells in a defined medium to produce spontaneous spheroid formation and differentiation towards chondrocyte-like cells. The examination of the spheroids by histological and immunohistochemical analyses for collagen type II (COL2), aggrecan, collagen type I (COL1), metalloprotease 13 (MMP13), and collagen type X (COLX) levels were performed to assess their chondrogenesis capacity. The adipogenesis and osteogenesis potential of each subpopulation was determined using commercial media; the resulting cells were stained with oil red O or red alizarin to test the degree of differentiation. The subpopulations had different profiles of cells positive for the MSC markers CD44, CD69, CD73, CD90, and CD105 and showed different expression levels of the genes Sox9, Nanog, and Runx2 involved in chondrogenesis, undifferentiation, and osteoblastogenesis, respectively. Immunohistochemical analysis demonstrated that COL1, COL2, COLX, MMP13, and aggrecan were expressed in the spheroids as soon as 14 days of culture. The CD271(+) subpopulation expressed the highest levels of COL2 staining compared to the other subpopulations. CD105 and Runx2 were shown by immunohistochemistry and genetic analysis to have significantly higher expression CD271(+) subpopulation than the other subpopulations. Spheroids formed from CD271-enriched and CD73-enriched MSCs from normal human synovial membranes mimic the native cartilage extracellular

  8. Generation of future potential scenarios in an Alpine Catchment by applying bias-correction techniques, delta-change approaches and stochastic Weather Generators at different spatial scale. Analysis of their influence on basic and drought statistics.

    Science.gov (United States)

    Collados-Lara, Antonio-Juan; Pulido-Velazquez, David; Pardo-Iguzquiza, Eulogio

    2017-04-01

    Assessing impacts of potential future climate change scenarios in precipitation and temperature is essential to design adaptive strategies in water resources systems. The objective of this work is to analyze the possibilities of different statistical downscaling methods to generate future potential scenarios in an Alpine Catchment from historical data and the available climate models simulations performed in the frame of the CORDEX EU project. The initial information employed to define these downscaling approaches are the historical climatic data (taken from the Spain02 project for the period 1971-2000 with a spatial resolution of 12.5 Km) and the future series provided by climatic models in the horizon period 2071-2100 . We have used information coming from nine climate model simulations (obtained from five different Regional climate models (RCM) nested to four different Global Climate Models (GCM)) from the European CORDEX project. In our application we have focused on the Representative Concentration Pathways (RCP) 8.5 emissions scenario, which is the most unfavorable scenario considered in the fifth Assessment Report (AR5) by the Intergovernmental Panel on Climate Change (IPCC). For each RCM we have generated future climate series for the period 2071-2100 by applying two different approaches, bias correction and delta change, and five different transformation techniques (first moment correction, first and second moment correction, regression functions, quantile mapping using distribution derived transformation and quantile mapping using empirical quantiles) for both of them. Ensembles of the obtained series were proposed to obtain more representative potential future climate scenarios to be employed to study potential impacts. In this work we propose a non-equifeaseble combination of the future series giving more weight to those coming from models (delta change approaches) or combination of models and techniques that provides better approximation to the basic

  9. In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell-Derived Osteoprogenitors

    Directory of Open Access Journals (Sweden)

    Intekhab Islam

    2016-01-01

    Full Text Available Cellular therapy using stem cells in bone regeneration has gained increasing interest. Various studies suggest the clinical utility of osteoprogenitors-like mesenchymal stem cells in bone regeneration. However, limited availability of mesenchymal stem cells and conflicting evidence on their therapeutic efficacy limit their clinical application. Human embryonic stem cells (hESCs are potentially an unlimited source of healthy and functional osteoprogenitors (OPs that could be utilized for bone regenerative applications. However, limited ability to track hESC-derived progenies in vivo greatly hinders translational studies. Hence, in this study, we aimed to establish hESC-derived OPs (hESC-OPs expressing green fluorescent protein (GFP and to investigate their osteogenic differentiation potential in vitro. We fluorescently labelled H9-hESCs using a plasmid vector encoding GFP. The GFP-expressing hESCs were differentiated into hESC-OPs. The hESC-OPsGFP+ stably expressed high levels of GFP, CD73, CD90, and CD105. They possessed osteogenic differentiation potential in vitro as demonstrated by increased expression of COL1A1, RUNX2, OSTERIX, and OPG transcripts and mineralized nodules positive for Alizarin Red and immunocytochemical expression of osteocalcin, alkaline phosphatase, and collagen-I. In conclusion, we have demonstrated that fluorescently labelled hESC-OPs can maintain their GFP expression for the long term and their potential for osteogenic differentiation in vitro. In future, these fluorescently labelled hESC-OPs could be used for noninvasive assessment of bone regeneration, safety, and therapeutic efficacy.

  10. Multipotency and cardiomyogenic potential of human adipose-derived stem cells from epicardium, pericardium, and omentum.

    Science.gov (United States)

    Wystrychowski, Wojciech; Patlolla, Bhagat; Zhuge, Yan; Neofytou, Evgenios; Robbins, Robert C; Beygui, Ramin E

    2016-06-13

    Acute myocardial infarction (MI) leads to an irreversible loss of proper cardiac function. Application of stem cell therapy is an attractive option for MI treatment. Adipose tissue has proven to serve as a rich source of stem cells (ADSCs). Taking into account the different morphogenesis, anatomy, and physiology of adipose tissue, we hypothesized that ADSCs from different adipose tissue depots may exert a diverse multipotency and cardiogenic potential. The omental, pericardial, and epicardial adipose tissue samples were obtained from organ donors and patients undergoing heart transplantation at our institution. Human foreskin fibroblasts were used as the control group. Isolated ADSCs were analyzed for adipogenic and osteogenic differentiation capacity and proliferation potential. The immunophenotype and constitutive gene expression of alkaline phosphatase (ALP), GATA4, Nanog, and OCT4 were analyzed. DNA methylation inhibitor 5-azacytidine was exposed to the cells to stimulate the cardiogenesis. Finally, reprogramming towards cardiomyocytes was initiated with exogenous overexpression of seven transcription factors (ESRRG, GATA4, MEF2C, MESP1, MYOCD, TBX5, ZFPM2) previously applied successfully for fibroblast transdifferentiation toward cardiomyocytes. Expression of cardiac troponin T (cTNT) and alpha-actinin (Actn2) was analyzed 3 weeks after initiation of the cardiac differentiation. The multipotent properties of isolated plastic adherent cells were confirmed with expression of CD29, CD44, CD90, and CD105, as well as successful differentiation toward adipocytes and osteocytes; with the highest osteogenic and adipogenic potential for the epicardial and omental ADSCs, respectively. Epicardial ADSCs demonstrated a lower doubling time as compared with the pericardium and omentum-derived cells. Furthermore, epicardial ADSCs revealed higher constitutive expression of ALP and GATA4. Increased Actn2 and cTNT expression was observed after the transduction of seven

  11. Radioiodine therapy of benign non-toxic goitre. Potential role of recombinant human TSH

    DEFF Research Database (Denmark)

    Fast, S; Bonnema, S J; Hegedüs, L

    2011-01-01

    This review provides an update on recombinant human TSH (rh-TSH) augmented radioiodine (¹³¹I) therapy and outlines its potential role in the treatment of symptomatic benign multinodular non-toxic goitre. In some countries, ¹³¹I has been used for three decades to reduce the size of nodular goitres......-56% amplification of goitre reduction at one-year post radioiodine compared to conventional (without rh-TSH) ¹³¹I therapy. Although patient satisfaction is not improved at one-year, this approach facilitates tracheal decompression and is particularly promising in large goitres. The majority of multinodular non......-toxic goitre patients may not require amplified goitre reduction. But as an alternative strategy, rh-TSH allows up to 80% reduction of the therapeutic ¹³¹I activity while still achieving goitre reduction comparable to that of conventional ¹³¹I therapy and maintaining high patient satisfaction. The dose...

  12. Pulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells

    DEFF Research Database (Denmark)

    Thilo, Florian; Vorderwülbecke, Bernd J; Marki, Alex

    2012-01-01

    as measured by quantitative real-time RT-PCR and normalized to GAPDH expression. Thereby, TRPC6 and TRPV1 mRNA expressions were significantly increased after 24 hours of exposure to an atheroprone flow profile compared with an atheroprotective flow profile. Furthermore, the expression of transcription factors......The goal of the study was to assess whether pulsatile atheroprone shear stress modulates the expression of transient receptor potential (TRP) channels, TRPC3, TRPC6, TRPM7, and TRPV1 mRNA, in human umbilical vascular endothelial cells. Exposure of cultured vascular endothelial cells to defined...... shear stress, producing a constant laminar flow (generating a shear stress of 6 dyne/cm(2)), laminar pulsatile atheroprotective flow (with a mean shear stress of 20 dyne/cm(2)), or laminar atheroprone bidirectional flow (with a mean shear stress of 0 dyne/cm(2)) differentially induced TRPC6 and TRPV1 mRNA...

  13. Difference, adapted physical activity and human development: potential contribution of capabilities approach.

    Science.gov (United States)

    Silva, Carla Filomena; Howe, P David

    2012-01-01

    This paper is a call to Adapted Physical Activity (APA) professionals to increase the reflexive nature of their practice. Drawing upon Foucault's concept of governmentality (1977) APA action may work against its own publicized goals of empowerment and self-determination. To highlight these inconsistencies, we will draw upon historical and social factors that explain the implicit dangers of practice not following policy. We propose that APA practitioners work according to ethical guidelines, based upon a capabilities approach (Nussbaum, 2006, 2011; Sen, 2009) to counteract possible adverse effects of APA practitioner action. A capabilities approach is conducive to the development of each individual's human potential, by holistically considering the consequences of physical activity (i.e., biological, cultural, social, and psychological dimensions). To conclude, this paper will offer suggestions that may lead to an ethical reflection aligned with the best interest of APA's users.

  14. Electroencephalography (EEG) and event-related potentials (ERPs) with human participants.

    Science.gov (United States)

    Light, Gregory A; Williams, Lisa E; Minow, Falk; Sprock, Joyce; Rissling, Anthony; Sharp, Richard; Swerdlow, Neal R; Braff, David L

    2010-07-01

    Understanding the basic neural processes that underlie complex higher-order cognitive operations and functional domains is a fundamental goal of cognitive neuroscience. Electroencephalography (EEG) is a non-invasive and relatively inexpensive method for assessing neurophysiological function that can be used to achieve this goal. EEG measures the electrical activity of large, synchronously firing populations of neurons in the brain with electrodes placed on the scalp. This unit outlines the basics of setting up an EEG experiment with human participants, including equipment, and a step-by-step guide to applying and preparing an electrode cap. Also included are support protocols for two event-related potential (ERP) paradigms, P50 suppression, and mismatch negativity (MMN), which are measures of early sensory processing. These paradigms can be used to assess the integrity of early sensory processing in normal individuals and clinical populations, such as individuals with schizophrenia.

  15. The insecticide DDT decreases membrane potential and cell input resistance of cultured human liver cells.

    Science.gov (United States)

    Schefczik, K; Buff, K

    1984-10-03

    The resting membrane potential, Em, and the cell input resistance, Rinp, of cultured human Chang liver cells were measured using the single electrode 'double-pulse' current clamp technique, following exposure of the cells to the insecticide DDT (20 microM). In control (unexposed) cells, the mean Em was -24 mV, and the mean Rinp was 30 M omega. Neither parameter was significantly impaired after 1 h of cell exposure to DDT. But after 7 and 48 h, the Em was depolarized by 15 and 25 mV, respectively, in parallel with a decrease of the cell input resistance. The strongly time-delayed effect of DDT on Chang liver cell membranes may indicate a mode of interaction different from excitable membranes.

  16. Oncogenic potential of Human Papillomavirus (HPV and its relation with cervical cancer

    Directory of Open Access Journals (Sweden)

    Idrees Muhammad

    2011-06-01

    Full Text Available Abstract Human Papillomavirus (HPV is the most common cause of cervical cancer. Cervical cancer being the second most common cancer after lung cancer, affecting women of different age groups; has a prevalence of about 20% in young sexually active women. Among different types of HPV, HPV16 the major strain causing this cancer and is sexually transmitted had been unnoticed for decades. Keeping in mind the multiple risk factors related with cervical cancer such as early age sexual activities, teenage pregnancies, smoking, use of oral contraceptives, having multiple sex partners, hormone replacement therapies and various other unknown factors lead to the onset of the disease. Awareness for various diagnostic procedures such as Pap smears screening prove to be an effective way in eradicating the oncogenic potential of HPV.

  17. Neural correlates of mental state decoding in human adults: an event-related potential study.

    Science.gov (United States)

    Sabbagh, Mark A; Moulson, Margaret C; Harkness, Kate L

    2004-04-01

    Successful negotiation of human social interactions rests on having a theory of mind - an understanding of how others' behaviors can be understood in terms of internal mental states, such as beliefs, desires, intentions, and emotions. A core theory-of-mind skill is the ability to decode others' mental states on the basis of observable information, such as facial expressions. Although several recent studies have focused on the neural correlates of reasoning about mental states, no research has addressed the question of what neural systems underlie mental state decoding. We used dense-array event-related potentials (ERP) to show that decoding mental states from pictures of eyes is associated with an N270-400 component over inferior frontal and anterior temporal regions of the right hemisphere. Source estimation procedures suggest that orbitofrontal and medial temporal regions may underlie this ERP effect. These findings suggest that different components of everyday theory-of-mind skills may rely on dissociable neural mechanisms.

  18. Investigation on a Potential Targeting Drug Delivery System Consisting of Folate, Mitoxantrone and Human Serum Albumin

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qiu-Jua; BI Ya-Jing; XIANG Jun-Feng; TANG Ya-Lin; YANG Qian-Fan; XU Guang-Zhi

    2008-01-01

    A potential targeting drug delivery system consisting of folate (FA), the targeting molecule, human serum al- bumin (HSA), the carrier, and mitoxantrone (MTO), the medicine, has been designed. Data obtained by UV absorp-tion, fluorescence, and NMR techniques indicated the formation of ternary complexes and possible application to building a targeting drug delivery system by using FA, MTO and HSA. Furthermore, cytotoxicity assay indicated that the toxicity of the FA-HSA-MTO against PC-3 cell line was 79.95%, which was much higher than that of free MTO tested in totally the same conditions. About 30% increase of the toxicity should be owed to the targeting ef-fect of FA. Thus, the feasibility and validity of a novel targeting drug delivery system, FA-HSA-MTO, was con-firmed.

  19. NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A.

    Science.gov (United States)

    Shelby, Michael D

    2008-09-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans. The CERHR Expert Panel on Bisphenol A completed its evaluation in August 2007. CERHR selected bisphenol A for evaluation because of the: widespread human exposure; public concern for possible health effects from human exposures; high production volume; evidence of reproductive and developmental toxicity in laboratory animal studies Bisphenol A (CAS RN: 80-05-7) is a high production volume chemical used primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics are used in some food and drink containers; the resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. To a lesser extent bisphenol A is used in the production of polyester resins, polysulfone resins, polyacrylate resins, and flame retardants. In addition, bisphenol A is used in the processing of polyvinyl chloride plastic and in the recycling of thermal paper. Some polymers used in dental sealants and tooth coatings contain bisphenol A. The primary source of exposure to bisphenol A for most people is assumed to occur through the diet. While air, dust, and water (including skin contact during bathing and swimming) are other possible sources of exposure, bisphenol A in food and beverages accounts for the majority of daily human exposure. The highest estimated daily intakes of bisphenol A in the general population occur in infants and children. The results of this bisphenol A evaluation are published in an NTP-CERHR Monograph that includes the (1) NTP Brief and (2) Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A. Additional information related to the evaluation process, including the peer review report for the NTP Brief and public comments received on the draft NTP

  20. Maximum diastolic potential of human induced pluripotent stem cell-derived cardiomyocytes depends critically on I(Kr.

    Directory of Open Access Journals (Sweden)

    Michael Xavier Doss

    Full Text Available Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM hold promise for therapeutic applications. To serve these functions, the hiPSC-CM must recapitulate the electrophysiologic properties of native adult cardiomyocytes. This study examines the electrophysiologic characteristics of hiPSC-CM between 11 and 121 days of maturity. Embryoid bodies (EBs were generated from hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record action potentials (AP from spontaneously beating clusters (BC micro-dissected from the EBs (n = 103; 37°C and to examine the response to 5 µM E-4031 (n = 21 or BaCl(2 (n = 22. Patch-clamp techniques were used to record I(Kr and I(K1 from cells enzymatically dissociated from BC (n = 49; 36°C. Spontaneous cycle length (CL and AP characteristics varied widely among the 103 preparations. E-4031 (5 µM; n = 21 increased Bazett-corrected AP duration from 291.8±81.2 to 426.4±120.2 msec (p<0.001 and generated early afterdepolarizations in 8/21 preparations. In 13/21 BC, E-4031 rapidly depolarized the clusters leading to inexcitability. BaCl(2, at concentrations that selectively block I(K1 (50-100 µM, failed to depolarize the majority of clusters (13/22. Patch-clamp experiments revealed very low or negligible I(K1 in 53% (20/38 of the cells studied, but presence of I(Kr in all (11/11. Consistent with the electrophysiological data, RT-PCR and immunohistochemistry studies showed relatively poor mRNA and protein expression of I(K1 in the majority of cells, but robust expression of I(Kr. In contrast to recently reported studies, our data point to major deficiencies of hiPSC-CM, with remarkable diversity of electrophysiologic phenotypes as well as pharmacologic responsiveness among beating clusters and cells up to 121 days post-differentiation (dpd. The vast majority have a maximum diastolic potential that depends critically on I(Kr due to the absence of

  1. Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

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    Jakubowski Ann A

    2009-12-01

    Full Text Available Abstract We have described a severe combined immunodeficiency (SCID mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL and 66 acute myeloid leukemia (AML in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8% displayed an aggressive growth pattern, 14 (10.5% displayed an indolent growth pattern and 74 (55.6% did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

  2. Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor

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    Patil, Rajreddy; Kumar, B. Mohana; Lee, Won-Jae; Jeon, Ryoung-Hoon; Jang, Si-Jung; Lee, Yeon-Mi [Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Park, Bong-Wook; Byun, June-Ho [Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju 660-702 (Korea, Republic of); Ahn, Chun-Seob; Kim, Jae-Won [Department of Microbiology, Division of Life Sciences, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Rho, Gyu-Jin, E-mail: jinrho@gnu.ac.kr [Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Research Institute of Life Sciences, Gyeongsang National University, Jinju 660-701 (Korea, Republic of)

    2014-01-01

    Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression of surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dental MSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and call therapy. - Highlights: • Isolated and characterized three types of human dental MSCs from a single donor. • MSCs of dental follicle, pulp and papilla had largely similar biological properties. • All MSCs were capable of transdifferentiating into functional hepatocyte-like cells. • 2DE proteomics with MALDI-TOF/MS identified 19 proteins in three types of MSCs. • Similar proteomic profiles suggest interchangeable applications of dental MSCs.

  3. Glioblastoma-dependent differentiation and angiogenic potential of human mesenchymal stem cells in vitro.

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    Birnbaum, Tobias; Hildebrandt, Jenna; Nuebling, Georg; Sostak, Petra; Straube, Andreas

    2011-10-01

    Tumor angiogenesis is of central importance in the malignancy of glioblastoma multiforme (GBM). As previously shown, human mesenchymal stem cells (hMSC) migrate towards GBM and are incorporated into tumor microvessels. However, phenotype and function of recruited hMSC remain unclear. We evaluated the differentiation and angiogenic potential of hMSC after stimulation with glioblastoma-conditioned medium in vitro. Immunostaining with endothelial, smooth muscle cell and pericyte markers was used to analyze hMSC differentiation in different concentrations of tumor-conditioned medium (CM), and the angiogenic potential was evaluated by matrigel-based tube-formation assay (TFA). Immunofluorescence staining revealed that tumor-conditioned hMSC (CM-hMSC) expressed CD 151, VE-cadherin, desmin, α-smooth muscle actin, nestin, and nerval/glial antigen 2 (NG2) in a CM concentration-dependent manner, whereas no expression of von-Willebrand factor (vWF) and smooth myosin could be detected. These findings are indicative of GBM-dependent differentiation of hMSC into pericyte-like cells, rather than endothelial or smooth muscle cells. Furthermore, TFA of hMSC and CM-hMSC revealed CM-dependent formation of capillary-like networks, which differed substantially from those formed by human endothelial cells (HUVEC), also implying pericyte-like tube formation. These results are indicative of GBM-derived differentiation of hMSC into pericyte-like mural cells, which might contribute to the neovascularization and stabilization of tumor vessels.

  4. 'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells.

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    Okamoto, Kazuma; Miyoshi, Shunichiro; Toyoda, Masashi; Hida, Naoko; Ikegami, Yukinori; Makino, Hatsune; Nishiyama, Nobuhiro; Tsuji, Hiroko; Cui, Chang-Hao; Segawa, Kaoru; Uyama, Taro; Kami, Daisuke; Miyado, Kenji; Asada, Hironori; Matsumoto, Kenji; Saito, Hirohisa; Yoshimura, Yasunori; Ogawa, Satoshi; Aeba, Ryo; Yozu, Ryohei; Umezawa, Akihiro

    2007-07-15

    The clinical application of cell transplantation for severe heart failure is a promising strategy to improve impaired cardiac function. Recently, an array of cell types, including bone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and embryonic stem cells, have become important candidates for cell sources for cardiac repair. In the present study, we focused on the placenta as a cell source. Cells from the chorionic plate in the fetal portion of the human placenta were obtained after delivery by the primary culture method, and the cells generated in this study had the Y sex chromosome, indicating that the cells were derived from the fetus. The cells potentially expressed 'working' cardiomyocyte-specific genes such as cardiac myosin heavy chain 7beta, atrial myosin light chain, cardiac alpha-actin by gene chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin 43 by immunohistochemistry. These cells were able to differentiate into cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous pattern of localization at intercellular contact sites after cardiomyogenic differentiation, suggesting that the chorionic mesoderm contained a large number of cells with cardiomyogenic potential. The cells began spontaneously beating 3 days after co-cultivation with murine fetal cardiomyocytes and the frequency of beating cells reached a maximum on day 10. The contraction of the cardiomyocytes was rhythmical and synchronous, suggesting the presence of electrical communication between the cells. Placenta-derived human fetal cells may be useful for patients who cannot supply bone marrow cells but want to receive stem cell-based cardiac therapy.

  5. Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study

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    Weinans Harrie

    2007-02-01

    Full Text Available Abstract Background Tendinosis lesions show an increase of glycosaminoglycan amount, calcifications, and lipid accumulation. Therefore, altered cellular differentiation might play a role in the etiology of tendinosis. This study investigates whether adolescent human tendon tissue contains a population of cells with intrinsic differentiation potential. Methods Cells derived from adolescent non-degenerative hamstring tendons were characterized by immunohistochemistry and FACS-analysis. Cells were cultured for 21 days in osteogenic, adipogenic, and chondrogenic medium and phenotypical evaluation was carried out by immunohistochemical and qPCR analysis. The results were compared with the results of similar experiments on adult bone marrow-derived stromal cells (BMSCs. Results Tendon-derived cells stained D7-FIB (fibroblast-marker positive, but α-SMA (marker for smooth muscle cells and pericytes negative. Tendon-derived cells were 99% negative for CD34 (endothelial cell marker, and 73% positive for CD105 (mesenchymal progenitor-cell marker. In adipogenic medium, intracellular lipid vacuoles were visible and tendon-derived fibroblasts showed upregulation of adipogenic markers FABP4 (fatty-acid binding protein 4 and PPARG (peroxisome proliferative activated receptor γ. In chondrogenic medium, some cells stained positive for collagen 2 and tendon-derived fibroblasts showed upregulation of collagen 2 and collagen 10. In osteogenic medium Von Kossa staining showed calcium deposition although osteogenic markers remained unaltered. Tendon-derived cells and BMCSs behaved largely comparable, although some distinct differences were present between the two cell populations. Conclusion This study suggests that our population of explanted human tendon cells has an intrinsic differentiation potential. These results support the hypothesis that there might be a role for altered tendon-cell differentiation in the pathophysiology of tendinosis.

  6. SLAM family predicting the initiation potential of human acute lymphoblastic leukemia in NOD/SCID mice

    Institute of Scientific and Technical Information of China (English)

    WANG Na; ZHOU Jian-feng; HUANG Liang; XIAO Fei; LIU Jin-ping; WANG Di; GENG Zhe; WANG Jin; MA Shu-yan; SHU Li-li; CHEN Tai-ping

    2011-01-01

    Background The SLAM family recently has been reported to show an important biological role in lymphocyte development and immunological function, and it is efficient to highly purify hematopoietic stem cells using a simple combination of SLAM family members. To elucidate the presence of this family on acute lymphoblastic leukemia (ALL),as well as its relationship with the leukemia-initiating potential, we analyzed the expression pattern of this family members on human ALL progenitor cells, combined with serial xenotransplantation assay.Methods Expression analysis was carried out by flow cytometry. We combined the expression pattern of human CD150,CD244 and CD48 with serial xenotransplantation of B-ALL progenitor cells to indicate their relationship.Results CD48 and CD244 were expressed on most B-ALL progenitor cells, the percentage being (93.08±6.46)% and (63.37±29.31)%, respectively. Interestingly, the proportion of CD150+ cells declined obviously in engrafted cases ((24.94±7.32)%) compared with non-engrafted cases ((77.54±5.93)%, P <0.01), which indicated that only blast cells with low percentage of CD150+ population were able to reconstitute leukemia into primary, secondary and tertiary NOD/SCID mice.Conclusions SLAM family members are present on B-ALL progenitor cells and the leukemia-initiating potential of leukemic blasts is correlated negatively with the proportion of CD150+ cells, the percentage of which can serve as a useful predictor for engraftment success of B-ALL to immune deficient mice.

  7. Neutralization potential of the plasma of HIV-1 infected Indian patients in the context of anti-V3 antibody content and antiretroviral therapy. [corrected].

    Science.gov (United States)

    Choudhary, Alok Kumar; Andrabi, Raiees; Prakash, Somi Sankaran; Kumar, Rajesh; Choudhury, Shubhasree Dutta; Wig, Naveet; Biswas, Ashutosh; Hazarika, Anjali; Luthra, Kalpana

    2012-02-01

    We assessed the anti-V3 antibody content and viral neutralization potential of the plasma of 63 HIV-1-infected patients (antiretroviral naïve=39, treated=24) against four primary isolates (PIs) of clade C and a tier 1 clade B isolate SF162. Depletion and inhibition of anti-V3 antibodies in the plasma of five patients with high titers of anti-V3 antibodies led to modest change in the neutralization percentage against two PIs (range 0-21%). The plasma of antiretroviral-treated patients exhibited higher neutralization potential than that of the drug-naïve plasmas against the four PIs tested which was further evidenced by a follow-up study.

  8. Biocompatibility and Inflammatory Potential of Titanium Alloys Cultivated with Human Osteoblasts, Fibroblasts and Macrophages

    Directory of Open Access Journals (Sweden)

    Jana Markhoff

    2017-01-01

    Full Text Available The biomaterials used to maintain or replace functions in the human body consist mainly of metals, ceramics or polymers. In orthopedic surgery, metallic materials, especially titanium and its alloys, are the most common, due to their excellent mechanical properties, corrosion resistance, and biocompatibility. Aside from the established Ti6Al4V alloy, shape memory materials such as nickel-titanium (NiTi have risen in importance, but are also discussed because of the adverse effects of nickel ions. These might be reduced by specific surface modifications. In the present in vitro study, the osteoblastic cell line MG-63 as well as primary human osteoblasts, fibroblasts, and macrophages were cultured on titanium alloys (forged Ti6Al4V, additive manufactured Ti6Al4V, NiTi, and Diamond-Like-Carbon (DLC-coated NiTi to verify their specific biocompatibility and inflammatory potential. Additive manufactured Ti6Al4V and NiTi revealed the highest levels of metabolic cell activity. DLC-coated NiTi appeared as a suitable surface for cell growth, showing the highest collagen production. None of the implant materials caused a strong inflammatory response. In general, no distinct cell-specific response could be observed for the materials and surface coating used. In summary, all tested titanium alloys seem to be biologically appropriate for application in orthopedic surgery.

  9. Snake scales, partial exposure, and the Snake Detection Theory: A human event-related potentials study.

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    Van Strien, Jan W; Isbell, Lynne A

    2017-04-07

    Studies of event-related potentials in humans have established larger early posterior negativity (EPN) in response to pictures depicting snakes than to pictures depicting other creatures. Ethological research has recently shown that macaques and wild vervet monkeys respond strongly to partially exposed snake models and scale patterns on the snake skin. Here, we examined whether snake skin patterns and partially exposed snakes elicit a larger EPN in humans. In Task 1, we employed pictures with close-ups of snake skins, lizard skins, and bird plumage. In task 2, we employed pictures of partially exposed snakes, lizards, and birds. Participants watched a random rapid serial visual presentation of these pictures. The EPN was scored as the mean activity (225-300 ms after picture onset) at occipital and parieto-occipital electrodes. Consistent with previous studies, and with the Snake Detection Theory, the EPN was significantly larger for snake skin pictures than for lizard skin and bird plumage pictures, and for lizard skin pictures than for bird plumage pictures. Likewise, the EPN was larger for partially exposed snakes than for partially exposed lizards and birds. The results suggest that the EPN snake effect is partly driven by snake skin scale patterns which are otherwise rare in nature.

  10. Characterization of a ligand binding site in the human transient receptor potential ankyrin 1 pore.

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    Klement, Göran; Eisele, Lina; Malinowsky, David; Nolting, Andreas; Svensson, Mats; Terp, Gitte; Weigelt, Dirk; Dabrowski, Michael

    2013-02-19

    The pharmacology and regulation of Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel activity is intricate due to the physiological function as an integrator of multiple chemical, mechanical, and temperature stimuli as well as differences in species pharmacology. In this study, we describe and compare the current inhibition efficacy of human TRPA1 on three different TRPA1 antagonists. We used a homology model of TRPA1 based on Kv1.2 to select pore vestibule residues available for interaction with ligands entering the vestibule. Site-directed mutation constructs were expressed in Xenopus oocytes and their functionality and pharmacology assessed to support and improve our homology model. Based on the functional pharmacology results we propose an antagonist-binding site in the vestibule of the TRPA1 ion channel. We use the results to describe the proposed intravestibular ligand-binding site in TRPA1 in detail. Based on the single site substitutions, we designed a human TRPA1 receptor by substituting several residues in the vestibule and adjacent regions from the rat receptor to address and explain observed species pharmacology differences. In parallel, the lack of effect on HC-030031 inhibition by the vestibule substitutions suggests that this molecule interacts with TRPA1 via a binding site not situated in the vestibule.

  11. In vitro differentiation potential of human haematopoietic CD34(+) cells towards pancreatic β-cells.

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    Sunitha, Manne Mudhu; Srikanth, Lokanathan; Santhosh Kumar, Pasupuleti; Chandrasekhar, Chodimella; Sarma, Potukuchi Venkata Gurunadha Krishna

    2016-10-01

    Haematopoietic stem cells (HSCs) possess multipotent ability to differentiate into various types of cells on providing appropriate niche. In the present study, the differentiating potential of human HSCs into β-cells of islets of langerhans was explored. Human HSCs were apheretically isolated from a donor and cultured. Phenotypic characterization of CD34 glycoprotein in the growing monolayer HSCs was confirmed by immunocytochemistry and flow cytometry techniques. HSCs were induced by selection with beta cell differentiating medium (BDM), which consists of epidermal growth factor (EGF), fibroblast growth factor (FGF), transferrin, Triiodo-l-Tyronine, nicotinamide and activin A. Distinct morphological changes of differentiated cells were observed on staining with dithizone (DTZ) and expression of PDX1, insulin and synaptophysin was confirmed by immunocytochemistry. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed distinct expression of specific β-cell markers, pancreatic and duodenal homeobox-1 (PDX1), glucose transporter-2 (GLUT-2), synaptophysin (SYP) and insulin (INS) in these differentiated cells compared to HSCs. Further, these cells exhibited elevated expression of INS gene at 10 mM glucose upon inducing with different glucose concentrations. The prominent feature of the obtained β-cells was the presence of glucose sensors, which was determined by glucokinase activity and high glucokinase activity compared with CD34(+) stem cells. These findings illustrate the differentiation of CD34(+) HSCs into β-cells of islets of langerhans.

  12. Interpenetrated Si-HPMC/alginate hydrogels as a potential scaffold for human tissue regeneration.

    Science.gov (United States)

    Viguier, Alexia; Boyer, Cecile; Chassenieux, Christophe; Benyahia, Lazhar; Guicheux, Jérôme; Weiss, Pierre; Rethore, Gildas; Nicolai, Taco

    2016-05-01

    Interpenetrated gels of biocompatible polysaccharides alginate and silanized hydroxypropyl methyl cellulose (Si-HPMC) have been studied in order to assess their potential as scaffolds for the regeneration of human tissues. Si-HPMC networks were formed by reduction of the pH to neutral and alginate networks were formed by progressive in situ release of Ca(2+). Linear and non-linear mechanical properties of the mixed gels at different polymer and calcium concentrations were compared with those of the corresponding single gels. The alginate/Si-HPMC gels were found to be stiffer than pure Si-HPMC gels, but weaker and more deformable than pure alginate gels. No significant difference was found for the maximum stress at rupture measured during compression for all these gels. The degrees of swelling or contraction in excess water at pH 7 as well as the release of Ca(2+) was measured as a function of time. Pure alginate gels contracted by as much as 50 % and showed syneresis, which was much reduced or even eliminated for mixed gels. The important release of Ca(2+) upon ageing for pure alginate gels was much reduced for the mixed gels. Furthermore, results of cytocompatibility assays indicated that there was no cytotoxicity of Si-HPMC/alginate hydrogels in 2D and 3D culture of human SW1353 cells. The results show that using interpenetrated Si-HPMC/alginate gels has clear advantages over the use of single gels for application in tissue regeneration.

  13. Local field potentials primarily reflect inhibitory neuron activity in human and monkey cortex

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    Teleńczuk, Bartosz; Dehghani, Nima; Le Van Quyen, Michel; Cash, Sydney S.; Halgren, Eric; Hatsopoulos, Nicholas G.; Destexhe, Alain

    2017-01-01

    The local field potential (LFP) is generated by large populations of neurons, but unitary contribution of spiking neurons to LFP is not well characterised. We investigated this contribution in multi-electrode array recordings from human and monkey neocortex by examining the spike-triggered LFP average (st-LFP). The resulting st-LFPs were dominated by broad spatio-temporal components due to ongoing activity, synaptic inputs and recurrent connectivity. To reduce the spatial reach of the st-LFP and observe the local field related to a single spike we applied a spatial filter, whose weights were adapted to the covariance of ongoing LFP. The filtered st-LFPs were limited to the perimeter of 800 μm around the neuron, and propagated at axonal speed, which is consistent with their unitary nature. In addition, we discriminated between putative inhibitory and excitatory neurons and found that the inhibitory st-LFP peaked at shorter latencies, consistently with previous findings in hippocampal slices. Thus, in human and monkey neocortex, the LFP reflects primarily inhibitory neuron activity. PMID:28074856

  14. Potential toxicity of sulfanilamide antibiotic: Binding of sulfamethazine to human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiabin [State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092 (China); Zhou, Xuefei [Key Laboratory of Yangtze River Water Environment for Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092 (China); Zhang, Yalei, E-mail: zhangyalei2003@163.com [State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092 (China); Gao, Haiping [Key Laboratory of Yangtze River Water Environment for Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092 (China)

    2012-08-15

    Antibiotics are widely used in daily life but their abuse has posed a potential threat to human health. The interaction between human serum albumin (HSA) and sulfamethazine (SMZ) was investigated by capillary electrophoresis, fluorescence spectrometry, and circular dichroism. The binding constant and site were determined to be 1.09 Multiplication-Sign 10{sup 4} M{sup -1} and 1.14 at 309.5 K. The thermodynamic determination indicated that the interaction was driven by enthalpy change, where the electrostatic interaction and hydrogen bond were the dominant binding force. The binding distance between SMZ and tryptophan residue of HSA was obtained to be 3.07 nm according to Foerster non-radioactive energy transfer theory. The site marker competition revealed that SMZ bound into subdomain IIA of HSA. The binding of SMZ induced the unfolding of the polypeptides of HSA and transferred the secondary conformation of HSA. The equilibrium dialysis showed that only 0.13 mM SMZ decreased vitamin B{sub 2} by 38% transported on the HSA. This work provides a new quantitative evaluation method for antibiotics to cause the protein damage. -- Highlights: Black-Right-Pointing-Pointer Various techniques characterized the interactions between SMZ and HSA. Black-Right-Pointing-Pointer The electrostatic interaction and hydrogen bond dominated in the interaction. Black-Right-Pointing-Pointer SMZ induced the conformation change of HSA. Black-Right-Pointing-Pointer SMZ affected the transportation function of HSA.

  15. Zinc finger protein 278, a potential oncogene in human colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoqing Tian; Danfeng Sun; Yanjie Zhang; Shuliang Zhao; Hua Xiong; Jingyuan Fang

    2008-01-01

    Zinc finger protein 278 (ZNF278) is a novel Krueppel Cys2-His2-type zinc finger protein that is ubiquitously distributed in human tissues. Whether ZNF278 is related to the development of colorectal cancer is still unclear. The transcriptional level of ZNF278 was studied in colorectal cancer by real-time polymerase chain reaction. The results showed that ZNF278 expression was increased in 53% of colorectal cancer tissues compared to corresponding non-cancerous tissues. The transcriptional down-regulation of ZNF278 was detected in only three (6%) human colorectal cancer tissues compared to corresponding non-cancer tissues. No significant difference was detected in 19 (41%) pairs of samples.However, we failed to find a significant association between the up-regulation of ZNF278 transcription and age, sex, the degree of infiltration, or the tumor size of colorectal cancer.To study the function of ZNF278 in colorectal carcinogenesis,the colon cancer cell line SW1116 was stably transfected with a wild-type ZNF278 plasmid to construct an overexpression system, and was transiently transfected with the small interfering RNA of ZNF278 to construct a ZNF278 knockdown system. Cell proliferation was assessed with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide dye and a cell counter. The results show that ZNF278 promotes cell growth, and its knockdown suppresses cell proliferation. ZNF278 could be a potential proto-oncogene in colorectal cancer.

  16. New phytochemicals as potential human anti-aging compounds: Reality, promise, and challenges.

    Science.gov (United States)

    Corrêa, Rúbia C G; Peralta, Rosane M; Haminiuk, Charles W I; Maciel, Giselle Maria; Bracht, Adelar; Ferreira, Isabel C F R

    2016-09-13

    Aging is an inevitable process influenced by genetic, lifestyle, and environmental factors. Indirect evidence shows that several phytochemicals can have anti-aging capabilities, although direct evidence in this field is still limited. This report aims to provide a critical review on aspects related to the use of novel phytochemicals as anti-aging agents, to discuss the obstacles found when performing most anti-aging study protocols in humans, and to analyze future perspectives. In addition to the extensively studied resveratrol, epicatechin, quercetin, and curcumin, new phytochemicals have been reported to act as anti-aging agents, such as the amino acid L-theanine isolated from green tea, and the lignans arctigenin and matairesinol isolated from Arctium lappa seeds. Furthermore, this review discusses the application of several new extracts rich in phytochemicals with potential use in anti-aging therapies. Finally, this review also discusses the most important biomarkers to test anti-aging interventions, the necessity of conducting epidemiological studies and the need of clinical trials with adequate study protocols for humans.

  17. An immunohistochemical study and review of potential markers of human intestinal M cells

    Directory of Open Access Journals (Sweden)

    NACS Wong

    2009-06-01

    Full Text Available M cells are found in intestinal follicle associated epithelium. Studies into the physiological and pathological roles of human M cells have been hampered by the lack of well-substantiated, specific markers for these cells. A critical literature review suggests the following molecules may potentially serve as such markers: CK7, FcaR (CD89, S100, CD1a, CD21, CD23, sialyl Lewis A, and cathepsin E. Normal ileum, appendix and colorectum were studied using paraffinembedded, formalin-fixed tissue and immunohistochemistry for these 8 markers. Cathepsin E immunohistochemistry was also performed on cases of colorectal adenocarcinoma, colorectal adenoma, colorectal hyperplastic/metaplastic polyp, lymphocytic colitis, collagenous colitis, pseudomembranous colitis and active ulcerative colitis. Of the 8 markers tested, only cathepsin E appeared to be specific to follicle associated epithelium (expressed by cells with and without M cell morphology and follicular crypt epithelium; this specificity was limited to the colorectum. Focal epithelial expression of cathepsin E was seen in adenocarcinoma, adenoma, hyperplastic/metaplastic polyp, ulcerative colitis and pseudomembranous colitis. In conclusion, cathepsin E is a specific marker of normal colorectal follicle associated epithelium and follicular crypt epithelium though is not specific to M cells within these compartments. None of the other 7 markers studied is exclusively expressed by human M cells.

  18. The human cathelicidin antimicrobial peptide LL-37 and mimics are potential anticancer drugs

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    Kengo eKuroda

    2015-06-01

    Full Text Available Antimicrobial peptides (AMPs play a critical role in innate host defense against microbial pathogens in many organisms. The human cathelicidin LL-37 has a net positive charge and is amphiphilic, and can eliminate pathogenic microbes directly via electrostatic attraction toward negatively charged bacterial membranes. A number of studies have shown that LL-37 participates in various host immune systems, such as inflammatory responses and tissue repair, in addition to its antibacterial properties. Moreover, recent evidence suggests that it is also involved in the regulation of cancer. Indeed, previous studies have suggested that human LL-37 is involved in carcinogenesis via multiple reporters such as FPR2 (FPRL1, EGFR, and ERBb2, although LL-37 and its fragments and analogues also show anticancer effects in various cancer cell lines. This discrepancy can be attributed to peptide-based factors, host membrane-based factors, and signal regulation. Here, we describe the association between AMPs and cancer with a focus on anticancer peptide functions and selectivity in an effort to understand potential therapeutic implications.

  19. Potentials and limitations for human control over historic fire regimes in the boreal forest.

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    Granström, Anders; Niklasson, Mats

    2008-07-12

    Fire, being both a natural and cultural phenomenon, presents problems in disentangling the historical effect of humans from that of climate change. Here, we investigate the potential impact of humans on boreal fire regimes from a perspective of fuels, ignitions and culture. Two ways for a low technology culture to impact the fire regime are as follows: (i) by altering the number of ignitions and their spatial distribution and timing and (ii) by hindering fire spread. Different cultures should be expected to have quite different impacts on the fire regimes. In northern Fennoscandia, there is evidence for fire regime changes associated with the following: a reindeer herding culture associated with few ignitions above the natural; an era of cattle husbandry with dramatically increased ignitions and somewhat higher fire frequency; and a timber exploitation era with decreasing fire sizes and diminishing fire frequency. In other regions of the boreal zone, such schemes can look quite different, but we suggest that a close look at the resource extraction and land use of different cultures should be part of any analysis of past fire regimes.

  20. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

    Science.gov (United States)

    Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  1. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder

    Directory of Open Access Journals (Sweden)

    Ubadah Sabbagh

    2016-01-01

    Full Text Available The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES. A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  2. Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex

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    Wang Lily

    2005-07-01

    Full Text Available Abstract There is evidence that the kynurenine pathway (KP and particularly one of its end products, quinolinic acid (QUIN play a role in the pathogenesis of several major neuroinflammatory diseases, and more particularly AIDS dementia complex (ADC. We hypothesized that QUIN may be involved in astrocyte apoptosis because: 1 apoptotic astrocytes have been observed in the brains of ADC patients, 2 ADC patients have elevated cerebrospinal fluid QUIN concentrations, and 3 QUIN can induce astrocyte death. Primary cultures of human fetal astrocytes were treated with three pathophysiological concentrations of QUIN. Numeration of apoptotic cells was assessed using double immunocytochemistry for expression of active caspase 3 and for nucleus condensation. We found that treatment of human astrocytes with QUIN induced morphological (cell body shrinking and biochemical changes (nucleus condensation and over-expression of active caspase 3 of apoptosis. After 24 hours of treatment with QUIN 500 nM and 1200 nM respectively 10 and 14% of astrocytes were undergoing apoptosis. This would be expected to lead to a relative lack of trophic support factors with consequent neuronal dysfunction and possibly death. Astroglial apoptosis induced by QUIN provides another potential mechanism for the neurotoxicity of QUIN during ADC.

  3. Early visual evoked potentials are modulated by eye position in humans induced by whole body rotations

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    Petit Laurent

    2004-09-01

    Full Text Available Abstract Background To reach and grasp an object in space on the basis of its image cast on the retina requires different coordinate transformations that take into account gaze and limb positioning. Eye position in the orbit influences the image's conversion from retinotopic (eye-centered coordinates to an egocentric frame necessary for guiding action. Neuroimaging studies have revealed eye position-dependent activity in extrastriate visual, parietal and frontal areas that is along the visuo-motor pathway. At the earliest vision stage, the role of the primary visual area (V1 in this process remains unclear. We used an experimental design based on pattern-onset visual evoked potentials (VEP recordings to study the effect of eye position on V1 activity in humans. Results We showed that the amplitude of the initial C1 component of VEP, acknowledged to originate in V1, was modulated by the eye position. We also established that putative spontaneous small saccades related to eccentric fixation, as well as retinal disparity cannot explain the effects of changing C1 amplitude of VEP in the present study. Conclusions The present modulation of the early component of VEP suggests an eye position-dependent activity of the human primary visual area. Our findings also evidence that cortical processes combine information about the position of the stimulus on the retinae with information about the location of the eyes in their orbit as early as the stage of primary visual area.

  4. EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

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    Rossella Terragni

    Full Text Available Epidermal growth factor receptor (EGFR or HER-1 and its analog c-erbB-2 (HER-2 are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7% carcinomas were classified as intestinal-type and 9 (64.3% as diffuse-type. EGFR was overexpressed (≥ 1+ in 8 (42.1% cases and HER-2 (3+ in 11 (57.9% cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80% than in the diffuse-type (11.1%, p = 0.023. KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R. EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.

  5. Potentiation and tolerance of toll-like receptor priming in human endothelial cells.

    Science.gov (United States)

    Koch, Stephen R; Lamb, Fred S; Hellman, Judith; Sherwood, Edward R; Stark, Ryan J

    2017-02-01

    Repeated challenge of lipopolysaccharide (LPS) alters the response to subsequent LPS exposures via modulation of toll-like receptor 4 (TLR4). Whether activation of other TLRs can modulate TLR4 responses, and vice versa, remains unclear. Specifically with regards to endothelial cells, a key component of innate immunity, the impact of TLR cross-modulation is unknown. We postulated that TLR2 priming (via Pam3Csk4) would inhibit TLR4-mediated responses while TLR3 priming (via Poly I:C) would enhance subsequent TLR4-inflammatory signaling. We studied human umbilical vein endothelial cells (HUVECs) and neonatal human dermal microvascular endothelial cells (HMVECs). Cells were primed with a combination of Poly I:C (10 μg/ml), Pam3Csk4 (10 μg/ml), or LPS (100 ng/ml), then washed and allowed to rest. They were then rechallenged with either Poly I:C, Pam3Csk4 or LPS. Endothelial cells showed significant tolerance to repeated LPS challenge. Priming with Pam3Csk4 also reduced the response to secondary LPS challenge in both cell types, despite a reduced proinflammatory response to Pam3Csk4 in HMVECs compared to HUVECs. Poly I:C priming enhanced inflammatory and interferon producing signals upon Poly I:C or LPS rechallenge, respectively. Poly I:C priming induced interferon regulatory factor 7, leading to enhancement of interferon production. Finally, both Poly I:C and LPS priming induced significant changes in receptor-interacting serine/threonine-protein kinase 1 activity. Pharmacological inhibition of receptor-interacting serine/threonine-protein kinase 1 or interferon regulatory factor 7 reduced the potentiated phenotype of TLR3 priming on TLR4 rechallenge. These results demonstrate that in human endothelial cells, prior activation of TLRs can have a significant impact on subsequent exposures and may contribute to the severity of the host response.

  6. Human enteric viruses–potential indicators for enhanced monitoring of recreational water quality

    Institute of Scientific and Technical Information of China (English)

    Erin; Allmann; Updyke; Zi; Wang; Si; Sun; Christina; Connell; Marek; Kirs; Mayee; Wong; Yuanan; Lu

    2015-01-01

    Recreational waters contaminated with human fecal pollution are a public health concern, and ensuring the safety of recreational waters for public use is a priority of both the Environmental Protection Agency(EPA) and the Centers for Disease Control and Prevention(CDC). Current recreational water standards rely on fecal indicator bacteria(FIB) levels as indicators of human disease risk. However present evidence indicates that levels of FIB do not always correspond to the presence of other potentially harmful organisms, such as viruses. Thus, enteric viruses are currently tested as water quality indicators, but have yet to be successfully implemented in routine monitoring of water quality. This study utilized enteric viruses as possible alternative indicators of water quality to examine 18 different fresh and offshore recreational waters on O‘ahu, Hawai‘i, by using newly established laboratory techniques including highly optimized PCR, real time PCR, and viral infectivity assays. All sample sites were detected positive for human enteric viruses by PCR including enterovirus, norovirus genogroups I and II, and male specific FRNA coliphage. A six time-point seasonal study of enteric virus presence indicated significant variation in virus detection between the rainy and dry seasons. Quantitative PCR detected the presence of norovirus genogroup II at levels at which disease risk may occur, and there was no correlation found between enteric virus presence and FIB counts. Under the present laboratory conditions, no infectious viruses were detected from the samples PCR-positive for enteric viruses. These data emphasize both the need for additional indicators for improved monitoring of water quality, and the feasibility of using enteric viruses as these indicators.

  7. Protective potential [correction of potencial] of Euphorbia hirta against cytotoxicity induced in hepatocytes and a HepG2 cell line.

    Science.gov (United States)

    Brindha, D; Saroja, S; Jeyanthi, G P

    2010-01-01

    Medicinal plants play a key role in human health care. Frustration over the side effects of allopathic drugs has driven the medical world to take asylum in the plant kingdom for the treatment of various ailments. Euphorbia hirta belonging to the family of Euphorbiacae has been reported to possess antibacterial, antiviral, and anticancer activity. The aim of the present study was to investigate the protective effect of E. hirta against antitubercular drug-induced cytotoxicity in freshly isolated hepatocytes. The extent of cytotoxicity of the plant extracts was also analyzed using human liver derived HepG2 cell line by estimating the viability of cells (MTT assay). The alcoholic plant extract normalized the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), triacylglycerol (TAG), cholesterol, total protein, albumin, total and direct bilirubin, which were altered due to antitubercular drug intoxication. A dose-dependent increase in percent viability was observed when antitubercular drug exposed HepG2 cells were treated with different concentrations of plant extracts (125, 250, 500 and 1000 microg/mL) which were compared with a standard hepatoprotective drug silymarin. The highest percentage viability of HepG2 was observed at a concentration of 1000 microg/mL. The results suggest that E. hirta exerts protection against antitubercular drug-induced cytotoxicity in this vitro model system.

  8. Evaluating Potential Human Health Risks Associated with the Development of Utility-Scale Solar Energy Facilities on Contaminated Sites

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, J. -J. [Argonne National Lab. (ANL), Argonne, IL (United States); Chang, Y. -S. [Argonne National Lab. (ANL), Argonne, IL (United States); Hartmann, H. [Argonne National Lab. (ANL), Argonne, IL (United States); Wescott, K. [Argonne National Lab. (ANL), Argonne, IL (United States); Kygeris, C. [Indiana Univ. of Pennsylvania, PA (United States)

    2013-09-01

    This report presents a general methodology for obtaining preliminary estimates of the potential human health risks associated with developing a utility-scale solar energy facility on a contaminated site, based on potential exposures to contaminants in soils (including transport of those contaminants into the air).

  9. Human health risk assessment for potentially toxic metals (PTEs) in Acerra' s area (Campanian Region, Italy)

    Science.gov (United States)

    Rezza, Carmela; Sorvari, Jaana; Albanese, Stefano; Matar, Thiombane; Lima, Annamaria; De Vivo, Benedetto

    2017-04-01

    Acerra's territory is situated in the Agro Aversano area. It is characterized by considerable anthropogenic pollution, caused by the illegal dumping and burning of waste since the 1990s. This area has also become highly urbanized and it is undergoing continuous changes in land-use patterns. Altogether 60 % of the total area is dedicated to agriculture, cereals, potato, tobacco and vegetables being the main crops, while 20 % of the area is urban and peri-urban. The remaining part is devoted to industrial use. The waste treatment plant, which incinerates mixed municipal solid waste from most of the municipalities around the city of Naples since 2009, is a potential major source of industrial pollution in the area. The aim of this study was to investigate the level of environmental contamination in Acerra and assess the consequential health risks. 178 topsoil samples and 10 food samples (corn and Chicorium endive) were taken within the whole study area. All samples were analysed for 15 elements (As, Be, Cd, Co, Cr, Cu, Hg, Ni, Pb, Sb, Se, Sn, Tl, V and Zn) at Bureau Veritas Analytical Laboratories (Vancouver, Canada) by ICP-MS and ICP-ES after an aqua-regia digestion. We calculated enrichment factors and pollution indexes of the PTEs in soil and vegetables by comparing their concentrations with the regional background level and trigger and action values for residential/recreational and industrial/commercial land use set in the Italian Environmental Law (152/06). We also calculated the soil-to-plant bio-concentration factor for critical PTEs. In the human health risk assessment, we focused on Be, Cu, Pb, and Zn since they were identified as the most critical elements based on the pollution indexes. We drew up a conceptual model to describe the formation of human health risks in the study area and divided it into agricultural, urban and industrial subareas. Considering the land use and environmental conditions, the following exposure routes are relevant in the formation

  10. Human thermal comfort antithesis in the context of the Mediterranean tourism potential

    Science.gov (United States)

    Nastos, Panagiotis T.; Zerefos, Christos S.; Kapsomenakis, Ioannis N.; Eleftheratos, Kostas; Polychroni, Iliana

    2016-04-01

    Weather and climate information are determinative factors in the decision of a touristic destination. The evaluation of the thermal, aesthetical and physical components of the climate is considered an issue of high importance in order to assess the climatic tourism potential. Mediterranean is an endowed region with respect to its temperate climate and impressive landscapes over the coastal environment and numerous islands. However, the harmony of the natural beauty is interrupted by extreme weather phenomena, such as heat and cold waves, heavy rains and stormy conditions. Thus, it is very important to know the seasonal behavior of the climate for touristic activities and recreation. Towards this objective we evaluated the antithesis in the human thermal perception as well as the sultriness, stormy, foggy, sunny and rainy days recorded in specific Greek touristic destinations against respective competitive Mediterranean resorts. Daily meteorological parameters, such as air temperature, relative humidity, wind speed, cloudiness and precipitation, were acquired from the most well-known touristic sites over the Mediterranean for the period 1970 to present. These variables were used on one hand to estimate the human thermal burden, by means of the thermal index of Physiologically Equivalent temperature (PET) and on the other hand to interpret the physical and aesthetic components of the tourism potential, by utilizing specific thresholds of the initial and derived variables in order to quantify in a simple and friendly way the environmental footprint on desired touristic destinations. The findings of this research shed light on the climate information for tourism in Greece against Mediterranean destinations. Greek resorts, especially in the Aegean Islands appear to be more ideal with respect to thermal comfort against resorts at the western and central Mediterranean, where the heat stress within the summer season seems to be an intolerable pressure on humans. This could

  11. The evaluation of the link between talent and potential of human resources

    Directory of Open Access Journals (Sweden)

    Daniel Daneci-Patrau

    2010-12-01

    Full Text Available The term “talent”, assigned to distinctive employees was certainly the past years leitmotif. Nowadays, the organizations need performance and for this reason they turn their attention towards the instruments which help them discover and explore the potential in people. In a context in which the crisis affects directly the labor market and the employees are more and more afraid of the possibility of losing their jobs, the incertitude and the insecurity appear more often. Especially, in these times, the need for continuous feedback, particularly connected to the decisions taken by the management, to the results of the company, to the adopted strategy and the way in which it reflects itself in the employees’ activity, is felt by all employees, no matter their role or their position. In this article, I presented the personal profile of the successful manager and the execution stages with the related conclusions in an evaluation program for the potential of the human resources in a sales company.

  12. The human milk microbiota: origin and potential roles in health and disease.

    Science.gov (United States)

    Fernández, Leónides; Langa, Susana; Martín, Virginia; Maldonado, Antonio; Jiménez, Esther; Martín, Rocío; Rodríguez, Juan M

    2013-03-01

    Human milk has been traditionally considered sterile; however, recent studies have shown that it represents a continuous supply of commensal, mutualistic and/or potentially probiotic bacteria to the infant gut. Culture-dependent and -independent techniques have revealed the dominance of staphylococci, streptococci, lactic acid bacteria and bifidobacteria in this biological fluid, and their role on the colonization of the infant gut. These bacteria could protect the infant against infections and contribute to the maturation of the immune system, among other functions. Different studies suggest that some bacteria present in the maternal gut could reach the mammary gland during late pregnancy and lactation through a mechanism involving gut monocytes. Thus, modulation of maternal gut microbiota during pregnancy and lactation could have a direct effect on infant health. On the other hand, mammary dysbiosis may lead to mastitis, a condition that represents the first medical cause for undesired weaning. Selected strains isolated from breast milk can be good candidates for use as probiotics. In this review, their potential uses for the treatment of mastitis and to inhibit mother-to-infant transfer of HIV are discussed.

  13. Therapeutic potentials of human adipose-derived stem cells on the mouse model of Parkinson's disease.

    Science.gov (United States)

    Choi, Hee Soon; Kim, Hee Jin; Oh, Jin-Hwan; Park, Hyeong-Geun; Ra, Jeong Chan; Chang, Keun-A; Suh, Yoo-Hun

    2015-10-01

    The treatment of Parkinson's disease (PD) using stem cells has long been the focus of many researchers, but the ideal therapeutic strategy has not yet been developed. The consistency and high reliability of the experimental results confirmed by animal models are considered to be a critical factor in the stability of stem cell transplantation for PD. Therefore, the aim of this study was to investigate the preventive and therapeutic potential of human adipose-derived stem cells (hASC) for PD and was to identify the related factors to this therapeutic effect. The hASC were intravenously injected into the tail vein of a PD mouse model induced by 6-hydroxydopamine. Consequently, the behavioral performances were significantly improved at 3 weeks after the injection of hASC. Additionally, dopaminergic neurons were rescued, the number of structure-modified mitochondria was decreased, and mitochondrial complex I activity was restored in the brains of the hASC-injected PD mouse model. Overall, this study underscores that intravenously transplanted hASC may have therapeutic potential for PD by recovering mitochondrial functions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Human parthenogenetic embryonic stem cells:one potential resource for cell therapy

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Pluripotent stem cells derived from somatic cells through such processes as nuclear transfer or induced pluripotent stem(iPS) cells present an important model for biomedical research and provide potential resources for cell replacement therapies.However,the overall efficiency of the conversional nuclear transfer is very low and the safety issue remains a major concern for iPS cells.Embryonic stem cells(ESCs) generated from parthenogenetic embryos are one attractive alternative as a source of histocompatible cells and tissues for cell therapy.Recent studies on human parthenogenetic embryonic stem cells(hPG ESCs) have revealed that these ESCs are very similar to the hESCs derived from IVF or in vivo produced blastocysts in gene expression and other characteristics,but full differentiation and development potential of these hPG ESCs have to be further investigated before clinical research and therapeutic interventions.To generate various pluripotent stem cells,diverse reprogramming techniques and approaches will be developed and integrated.This may help elucidate the fundamental mechanisms underlying reprogramming and stem cell biology,and ultimately benefit cell therapy and regenerative medicine.

  15. Differential DNA Methylation Regions in Adult Human Sperm following Adolescent Chemotherapy: Potential for Epigenetic Inheritance

    Science.gov (United States)

    Shnorhavorian, Margarett; Schwartz, Stephen M.; Stansfeld, Barbara; Sadler-Riggleman, Ingrid; Beck, Daniel

    2017-01-01

    Background The potential that adolescent chemotherapy can impact the epigenetic programming of the germ line to influence later life adult fertility and promote epigenetic inheritance was investigated. Previous studies have demonstrated a number of environmental exposures such as abnormal nutrition and toxicants can promote sperm epigenetic changes that impact offspring. Methods Adult males approximately ten years after pubertal exposure to chemotherapy were compared to adult males with no previous exposure. Sperm were collected to examine differential DNA methylation regions (DMRs) between the exposed and control populations. Gene associations and correlations to genetic mutations (copy number variation) were also investigated. Methods and Findings A signature of statistically significant DMRs was identified in the chemotherapy exposed male sperm. The DMRs, termed epimutations, were found in CpG desert regions of primarily 1 kilobase size. Observations indicate adolescent chemotherapy exposure can promote epigenetic alterations that persist in later life. Conclusions This is the first observation in humans that an early life chemical exposure can permanently reprogram the spermatogenic stem cell epigenome. The germline (i.e., sperm) epimutations identified suggest chemotherapy has the potential to promote epigenetic inheritance to the next generation. PMID:28146567

  16. Dynamics of the Transcriptome during Human Spermatogenesis: Predicting the Potential Key Genes Regulating Male Gametes Generation.

    Science.gov (United States)

    Zhu, Zijue; Li, Chong; Yang, Shi; Tian, Ruhui; Wang, Junlong; Yuan, Qingqing; Dong, Hui; He, Zuping; Wang, Shengyue; Li, Zheng

    2016-01-12

    Many infertile men are the victims of spermatogenesis disorder. However, conventional clinical test could not provide efficient information on the causes of spermatogenesis disorder and guide the doctor how to treat it. More effective diagnosis and treating methods could be developed if the key genes that regulate spermatogenesis were determined. Many works have been done on animal models, while there are few works on human beings due to the limited sample resources. In current work, testis tissues were obtained from 27 patients with obstructive azoospermia via surgery. The combination of Fluorescence Activated Cell Sorting and Magnetic Activated Cell Sorting was chosen as the efficient method to sort typical germ cells during spermatogenesis. RNA Sequencing was carried out to screen the change of transcriptomic profile of the germ cells during spermatogenesis. Differential expressed genes were clustered according to their expression patterns. Gene Ontology annotation, pathway analysis, and Gene Set Enrichment Analysis were carried out on genes with specific expression patterns and the potential key genes such as HOXs, JUN, SP1, and TCF3 which were involved in the regulation of spermatogenesis, with the potential value serve as molecular tools for clinical purpose, were predicted.

  17. Human parthenogenetic embryonic stem cells: one potential resource for cell therapy

    Institute of Scientific and Technical Information of China (English)

    HAO Jie; HU WanWan; SHENG Chao; YU Yang; ZHOU Qi

    2009-01-01

    Pluripotent stem cells derived from somatic cells through such processes as nuclear transfer or in duced pluripotent stem (iPS) cells present an important model for biomedical research and provide potential resources for cell replacement therapies. However, the overall efficiency of the conversional nuclear transfer is very low and the safety issue remains a major concern for iPS cells. Embryonic stem cells (ESCs) generated from parthenogenetic embryos are one attractive alternative as a source of histocompatible cells and tissues for cell therapy. Recent studies on human parthenogenetic embryonic stem cells (hPG ESCs) have revealed that these ESCs are very similar to the hESCs derived from IVF or in vivo produced blastocysts in gene expression and other characteristics, but full differentiation and development potential of these hPG ESCs have to be further investigated before clinical research and therapeutic interventions. To generate various pluripotent stem cells, diverse reprogramming techniques and approaches will be developed and integrated. This may help elucidate the fundamental mechanisms underlying reprogramming and stem cell biology, and ultimately benefit cell therapy and regenerative medicine.

  18. Docking-based virtual screening of potential human P2Y12 receptor antagonists

    Institute of Scientific and Technical Information of China (English)

    Hua Chen; Xianchi Dong; Minyun Zhou; Haiming Shi; Xinping Luo

    2011-01-01

    Platelet plays essential roles in hemostasis and its dysregulation can lead to arterial thrombosis. P2Y12 is an important platelet membrane adenosine diphosphate receptor,and its antagonists have been widely developed as anticoagulation agents. The current P2Y12 inhibitors available in clinical practice have not fully achieved saOsfactory antithrombotic effects, leaving room for further improvement To identify new chemical compounds as potential anticoagulation inhibitors, we constructed a three-dimensional structure model of human P2Y12 by homology modeling based on the recently reported G-protein coupled receptor Meleagris gallopavo βl adrenergic receptor. Virtual screening of the modeled P2Y12 against three subsets of small molecules from the ZINC database, namely lead-like, fragment-like, and drug-like, identified a number of compounds tbat might have high binding affinity to P2Y12.Detailed analyses of the top three compounds from each subset with the highest scores indicated that all of these compounds beard a hydrophobic bulk supplemented with a few polar atoms which bound at the ligand binding site via largely hydrophobic interactions with the receptor. This study not only provides a structure model of P2Y12 for rational design of anti-platelet inhibitors, but also identifies some potential chemicals for further development.

  19. Adaptive potential of genomic structural variation in human and mammalian evolution.

    Science.gov (United States)

    Radke, David W; Lee, Charles

    2015-09-01

    Because phenotypic innovations must be genetically heritable for biological evolution to proceed, it is natural to consider new mutation events as well as standing genetic variation as sources for their birth. Previous research has identified a number of single-nucleotide polymorphisms that underlie a subset of adaptive traits in organisms. However, another well-known class of variation, genomic structural variation, could have even greater potential to produce adaptive phenotypes, due to the variety of possible types of alterations (deletions, insertions, duplications, among others) at different genomic positions and with variable lengths. It is from these dramatic genomic alterations, and selection on their phenotypic consequences, that adaptations leading to biological diversification could be derived. In this review, using studies in humans and other mammals, we highlight examples of how phenotypic variation from structural variants might become adaptive in populations and potentially enable biological diversification. Phenotypic change arising from structural variants will be described according to their immediate effect on organismal metabolic processes, immunological response and physical features. Study of population dynamics of segregating structural variation can therefore provide a window into understanding current and historical biological diversification.

  20. Antileukemic Potential of Momordica charantia Seed Extracts on Human Myeloid Leukemic HL60 Cells

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    Ramani Soundararajan

    2012-01-01

    Full Text Available Momordica charantia (bitter gourd has been used in the traditional system of medicine for the treatment of various diseases. Anticancer activity of M. charantia extracts has been demonstrated by numerous in vitro and in vivo studies. In the present study, we investigated the differentiation inducing potential of fractionated M. charantia seed extracts in human myeloid HL60 cells. We found that the HL60 cells treated with the fractionated seed extracts differentiated into granulocytic lineage as characterized by NBT staining, CD11b expression, and specific esterase activity. The differentiation inducing principle was found to be heat-stable, and organic in nature. The differentiation was accompanied by a downregulation of c-myc transcript, indicating the involvement of c-myc pathway, at least in part, in differentiation. Taken together these results indicate that fractionated extracts of M. charantia seeds possess differentiation inducing activity and therefore can be evaluated for their potential use in differentiation therapy for leukemia in combination with other inducers of differentiation.

  1. Identification of potentially hazardous human gene products in GMO risk assessment.

    Science.gov (United States)

    Bergmans, Hans; Logie, Colin; Van Maanen, Kees; Hermsen, Harm; Meredyth, Michelle; Van Der Vlugt, Cécile

    2008-01-01

    Genetically modified organisms (GMOs), e.g. viral vectors, could threaten the environment if by their release they spread hazardous gene products. Even in contained use, to prevent adverse consequences, viral vectors carrying genes from mammals or humans should be especially scrutinized as to whether gene products that they synthesize could be hazardous in their new context. Examples of such potentially hazardous gene products (PHGPs) are: protein toxins, products of dominant alleles that have a role in hereditary diseases, gene products and sequences involved in genome rearrangements, gene products involved in immunomodulation or with an endocrine function, gene products involved in apoptosis, activated proto-oncogenes. For contained use of a GMO that carries a construct encoding a PHGP, the precautionary principle dictates that safety measures should be applied on a "worst case" basis, until the risks of the specific case have been assessed. The potential hazard of cloned genes can be estimated before empirical data on the actual GMO become available. Preliminary data may be used to focus hazard identification and risk assessment. Both predictive and empirical data may also help to identify what further information is needed to assess the risk of the GMO. A two-step approach, whereby a PHGP is evaluated for its conceptual dangers, then checked by data bank searches, is delineated here.

  2. Withania somnifera water extract as a potential candidate for differentiation based therapy of human neuroblastomas.

    Directory of Open Access Journals (Sweden)

    Hardeep Kataria

    Full Text Available Neuroblastoma is an aggressive childhood disease of the sympathetic nervous system. Treatments are often ineffective and have serious side effects. Conventional therapy of neuroblastoma includes the differentiation agents. Unlike chemo-radiotherapy, differentiation therapy shows minimal side effects on normal cells, because normal non-malignant cells are already differentiated. Keeping in view the limited toxicity of Withania somnifera (Ashwagandha, the current study was aimed to investigate the efficacy of Ashwagandha water extract (ASH-WEX for anti-proliferative potential in neuroblastoma and its underlying signalling mechanisms. ASH-WEX significantly reduced cell proliferation and induced cell differentiation as indicated by morphological changes and NF200 expression in human IMR-32 neuroblastoma cells. The induction of differentiation was accompanied by HSP70 and mortalin induction as well as pancytoplasmic translocation of the mortalin in ASH-WEX treated cells. Furthermore, the ASH-WEX treatment lead to induction of neural cell adhesion molecule (NCAM expression and reduction in its polysialylation, thus elucidating its anti-migratory potential, which was also supported by downregulation of MMP 2 and 9 activity. ASH-WEX treatment led to cell cycle arrest at G0/G1 phase and increase in early apoptotic population. Modulation of cell cycle marker Cyclin D1, anti-apoptotic marker bcl-xl and Akt-P provide evidence that ASH-WEX may prove to be a promising phytotherapeutic intervention in neuroblatoma related malignancies.

  3. Broader prevalence of Wolbachia in insects including potential human disease vectors.

    Science.gov (United States)

    de Oliveira, C D; Gonçalves, D S; Baton, L A; Shimabukuro, P H F; Carvalho, F D; Moreira, L A

    2015-06-01

    Wolbachia are intracellular, maternally transmitted bacteria considered the most abundant endosymbionts found in arthropods. They reproductively manipulate their host in order to increase their chances of being transmitted to the offspring, and currently are being used as a tool to control vector-borne diseases. Studies on distribution of Wolbachia among its arthropod hosts are important both for better understanding why this bacterium is so common, as well as for its potential use as a biological control agent. Here, we studied the incidence of Wolbachia in a broad range of insect species, collected from different regions of Brazil, using three genetic markers (16S rRNA, wsp and ftsZ), which varied in terms of their sensitivity to detect this bacterium. The overall incidence of Wolbachia among species belonging to 58 families and 14 orders was 61.9%. The most common positive insect orders were Coleoptera, Diptera, Hemiptera and Hymenoptera, with Diptera and Hemiptera having the highest numbers of Wolbachia-positive families. They included potential human disease vectors whose infection status has never been reported before. Our study further shows the importance of using quantitative polymerase chain reaction for high-throughput and sensitive Wolbachia screening.

  4. Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

    2017-04-01

    Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

  5. Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency

    Institute of Scientific and Technical Information of China (English)

    R David Hawkins; Zhen Ye; Samantha Kuan; Pengzhi Yu; Hui Liu; Xinmin Zhang; Roland D Green; Victor V Lobanenkov; Ron Stewart; James A Thomson; Bing Ren; Gary C Hon; Chuhu Yang; Jessica E Antosiewicz-Bourget; LeonardKLee; Que-Minh Ngo; Sarit Klugman; Keith A Ching; Lee E Edsall

    2011-01-01

    Pluripotency,the ability of a cell to differentiate and give rise to all embryonic lineages,defines a small number of mammalian cell types such as embryonic stem (ES) cells.While it has been generally held that pluripotency is the product of a transcriptional regulatory network that activates and maintains the expression of key stem cell genes,accumulating evidence is pointing to a critical role for epigenetic processes in establishing and safeguarding the pluripotency of ES cells,as well as maintaining the identity of differentiated cell types.In order to better understand the role of epigenetic mechanisms in pluripotency,we have examined the dynamics of chromatin modifications genomewide in human ES cells (hESCs) undergoing differentiation into a mesendodermal lineage.We found that chromatin modifications at promoters remain largely invariant during differentiation,except at a small number of promoters where a dynamic switch between acetylation and methylation at H3K27 marks the transition between activation and silencing of gene expression,suggesting a hierarchy in cell fate commitment over most differentially expressed genes.We also mapped over 50 000 potential enhancers,and observed much greater dynamics in chromatin modifications,especially H3K4mel and H3K27ac,which correlate with expression of their potential target genes.Further analysis of these enhancers revealed potentially key transcriptional regulators of pluripotency and a chromatin signature indicative of a poised state that may confer developmental competence in hESCs.Our results provide new evidence supporting the role of chromatin modifications in defining enhancers and pluripotency.

  6. Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins

    Directory of Open Access Journals (Sweden)

    Katarzyna eBozek

    2012-06-01

    Full Text Available Human immunodeficiency virus type 2 (HIV-2 and simian immunodeficiency virus isolated from a macaque monkey (SIVmac are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm. Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239 is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5. As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

  7. Partial Correction of Psoriasis upon Genetic Knock-Down of Human TNF-α by Lentivirus-Encoded shRNAs in a Xenograft Mouse Model

    DEFF Research Database (Denmark)

    Jakobsen, Maria; Stenderup, Karin; Rosada, Cecilia

    with lentiviral vectors encoding an irrelevant shRNA. In conclusion, our results demonstrate that lentiviral vector-encoded TNF- shRNAs have the potential to down-regulate TNF- production both in vitro and in vivo. Phenotypic changes in shRNA-treated psoriatic skin suggest that TNF- -encoding RNA is a valid......The proinfla