The membrane-permeable calmodulin inhibitors (W-7/W-13) bind to membranes changing the electrostatic surface potential. Dual effect of W-13 on EGFR activation

Membrane-permeable calmodulin inhibitors, such as the napthalenesulfonamide derivatives W-7/W-13, trifluoperazine, and calmidazolium, are used widely to investigate the role of calcium/calmodulin (Ca2+/CaM) in living cells. If two chemically different inhibitors (e.g. W-7 and trifluoperazine) produce similar effects, investigators often assume the effects are due to CaM inhibition. Zeta potential measurements, however, show that these amphipathic weak bases bind to phospholipid vesicles at the same concentrations as they inhibit Ca 2 /CaM; this suggests that they also bind to the inner leaflet of the plasma membrane, reducing its negative electrostatic surface potential. This change will cause electrostatically bound clusters of basic residues on peripheral (e.g. Src and K-Ras4B) and integral (e.g. epidermal growth factor receptor (EGFR)) proteins to translocate from the membrane to the cytoplasm. We measured inhibitor-mediated translocation of a simple basic peptide corresponding to the calmodulin-binding juxtamembrane region of the EGFR on model membranes; W-7/W-13 causes translocation of this peptide from membrane to solution, suggesting that caution must be exercised when interpreting the results obtained with these inhibitors in living cells. We present evidence that they exert dual effects on autophosphorylation of EGFR;W-13 inhibits epidermal growth factordependent EGFR autophosphorylation under different experimental conditions, but in the absence of epidermal growth factor, W-13 stimulates autophosphorylation of the receptor in four different cell types. Our interpretation is that the former effect is due toW-13inhibition of Ca 2 /CaM, but thelatter results could be due to binding of W-13 to the plasma membrane.

Suomen maatiede : [Alexander Gustaf Julius Hallstén] ; suomentanut G. C.

Second revised edition.

Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma

It is well established that interleukin-6 (IL-6) is an essential growth factor for multiple myeloma (MM) and patients with increased IL-6 levels have a poor prognosis. In healthy subjects, the presence of the C allele at a polymorphic site (-174 G/C) of the IL-6 gene is related to low IL-6 levels. In view of the potential association of this particular polymorphism with IL-6 concentration, and the relevance of IL-6 in MM pathogenesis, the objective of the present study was to investigate the prevalence of IL-6 (-174 G/C) promoter polymorphism and its association with development of MM in Brazilian individuals. We investigated the prevalence of these alleles in 52 patients and 60 healthy subjects (matched by age, sex, and race) of a Brazilian population. Thirty patients were male (42.4%), 24 (46.2%) were white and the median age at diagnosis was 58.5 years (range: 28 to 84 years). To determine the IL-6 (-174 G/C) polymorphism, molecular analysis was performed by polymerase chain reaction followed by endonuclease restriction digestion. The genotype distributions observed in the group of patients were 4% CC, 42% GC and 54% GG. The C allele frequency was 0.25. These results were similar to the control group, suggesting no impact of this polymorphism on the susceptibility to MM.

Förteckning öfver böcker tillgänglige vid A. W. Edgrens och J. E. Reuters lånbibliothek i Åbo

Imprimatur: L. Heimbürger.

Suomalainen laina-kirjasto Uudessakaupungissa, perustettu w. 1861

Sisältää myös kirjaston käyttösäännöt.

Estudio comparativo de identidad universitaria de dos instituciones de educación superior en Colombia

Este trabajo es un análisis de carácter investigativo que busca explorar los principales rasgos que describen y constituyen la identidad de dos instituciones de Educación Superior en Colombia. Se busca identificar las características de convergencia y divergencia entre ambas, así como indagar acerca del impacto que tienen los procesos de cambio en la conformación de una identidad sólida que les permita ser perdurables en el tiempo.

G band atmospheric radars: new frontiers in cloud physics

Clouds and associated precipitation are the largest source of uncertainty in current weather and future climate simulations. Observations of the microphysical, dynamical and radiative processes that act at cloud scales are needed to improve our understanding of clouds. The rapid expansion of ground-based super-sites and the availability of continuous profiling and scanning multi-frequency radar observations at 35 and 94 GHz have significantly improved our ability to probe the internal structure of clouds in high temporal-spatial resolution, and to retrieve quantitative cloud and precipitation properties. However, there are still gaps in our ability to probe clouds due to large uncertainties in the retrievals. The present work discusses the potential of G band (frequency between 110 and 300 GHz) Doppler radars in combination with lower frequencies to further improve the retrievals of microphysical properties. Our results show that, thanks to a larger dynamic range in dual-wavelength reflectivity, dual-wavelength attenuation and dual-wavelength Doppler velocity (with respect to a Rayleigh reference), the inclusion of frequencies in the G band can significantly improve current profiling capabilities in three key areas: boundary layer clouds, cirrus and mid-level ice clouds, and precipitating snow.

Search for right-handed W bosons in top quark decay

We present a measurement of the fraction f(+) of right-handed W bosons produced in top quark decays, based on a candidate sample of t (t) over bar events in the lepton+jets decay mode. These data correspond to an integrated luminosity of 230 pb(-1), collected by the D0 detector at the Fermilab Tevatron p (p) over bar Collider at root s=1.96 TeV. We use a constrained fit to reconstruct the kinematics of the t (t) over bar and decay products, which allows for the measurement of the leptonic decay angle theta(*) for each event. By comparing the cos theta(*) distribution from the data with those for the expected background and signal for various values of f(+), we find f(+)=0.00 +/- 0.13(stat)+/- 0.07(syst). This measurement is consistent with the standard model prediction of f(+)=3.6 x 10(-4).

Search for anomalous heavy-flavor quark production in association with W bosons

We search for anomalous production of heavy-flavor quark jets in association with W bosons at the Fermilab Tevatron p(p) over bar Collider in final states in which the heavy-flavor quark content is enhanced by requiring at least one tagged jet in an event. Jets are tagged using one algorithm based on semileptonic decays of b/c hadrons, and another on their lifetimes. We compare e+jets (164 pb(-1)) and mu+jets (145 pb(-1)) channels collected with the D0 detector at root s = 1.96 TeV to expectations from the standard model and set upper limits on anomalous production of such events.

Measurement of the W boson helicity in top quark decays at D0

We present a measurement of the fraction f(+) of right-handed W bosons produced in top quark decays, based on a candidate sample of tt events in the l + jets and dilepton decay channels corresponding to an integrated luminosity of 370 pb(-1) collected by the D0 detector at the Fermilab Tevatron pp Collider at root s = 1.96 TeV. We reconstruct the decay angle theta* for each lepton. By comparing the cos theta* distribution from the data with that for the expected background and signal for various values of f(+) (where we assume that the fraction of longitudinally-polarized W bosons has the standard model value of 0.70), we find f(+) = 0.056 +/- 0.080 (stat) +/- 0.057 (syst) (f(+) < 0.23 at 95% C. L.), consistent with the standard model prediction of f(+) = 3.6 X 10(-4).

Search for W ' boson production in the W ' -> t(b)over-bar decay channel

We present a search for the production of a new heavy gauge boson W' that decays to a top quark and a bottom quark. We have analyzed 230 pb(-1) of data collected with the DO detector at the Fermilab Tevatron collider at a center-of-mass energy of 1.96 TeV. No significant excess of events above the standard model expectation is found in any region of the final state invariant mass distribution. We set upper limits on the production cross section of W' bosons times branching ratio to top quarks at the 95% confidence level for several different W, boson masses. We exclude masses between 200 and 610 GeV for a W' boson with standard-model-like couplings, between 200 and 630 GeV for a W, boson with right-handed couplings that is allowed to decay to both leptons and quarks, and between 200 and 670 GeV for a W' boson with right-handed couplings that is only allowed to decay to quarks. (c) 2006 Elsevier B.V. All rights reserved.

Measurement of the pp(-)-> W gamma plus X cross section at root s=1.96 TeV and WW gamma anomalous coupling limits

The WW gamma triple gauge boson coupling parameters are studied using p (p) over bar -> l nu gamma + X(l = e, mu) events at root s = 1.96 TeV. The data were collected with the D0 detector from an integrated luminosity of 162 pb(-1) delivered by the Fermilab Tevatron Collider. The cross section times branching fraction for p (p) over bar -> W(gamma) + X -> l nu gamma + X with E-T(gamma) > 8 GeV and Delta R-l gamma > 0.7 is 14.8 +/- 1.6(stat) +/- 1.0(syst) +/- 1.0(lum) pb. The one-dimensional 95% confidence level limits on anomalous couplings are -0.88 < Delta kappa(gamma) < 0.96 and -0.20 < lambda(gamma) < 0.20.

Search for W H associated production in 5.3 fb(-1) of p(p)over-bar collisions at the Fermilab Tevatron

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Measurement of the ratio of the p(p)over-bar -> W + c-jet cross section to the inclusive p(p)over-bar -> W + jets cross section

We present a measurement of the fraction of inclusive W +jets events produced with net charm quantum number 11, denoted W + c-jet, in p collisions at root s = 1.96 TeV using approximately 1 fb(-1) of data collected by the do detector at the Fermilab Tevatron Collider. We identify the W +jets events via the leptonic W boson decays. Candidate W + c-jet events are selected by requiring a jet containing a muon in association with a reconstructed W boson and exploiting the charge correlation between this muon and W boson decay lepton to perform a nearly model-independent background subtraction. We measure the fraction of W + c-jet events in the inclusive W +jets sample for jet PT > 20 GeV and pseudorapidity |eta| < 2.5 to be 0.074 +/- 0.019(stat.) +/-(0.012)(0.014) (syst.), in agreement with theoretical predictions. The probability that background fluctuations could produce the observed fraction of W + c-jet events is estimated to be 2.5 x 10(-4), which corresponds to a 3.5 sigma statistical significance. Published by Elsevier B.V.

Measurements of inclusive W plus jets production rates as a function of jet transverse momentum in p(p)over-bar collisions root s=1.96 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)