Protease inhibitors prevent plasminogen-mediated, but not pemphigus vulgaris-induced, acantholysis in human epidermis

Pemphigus is an autoimmune blistering disease of the skin and mucous membranes. It is caused by autoantibodies directed against desmosomes, which are the principal adhesion structures between epidermal keratinocytes. Binding of autoantibodies leads to the destruction of desmosomes resulting in the loss of cell-cell adhesion (acantholysis) and epidermal blisters. The plasminogen activator system has been implicated as a proteolytic effector in pemphigus. We have tested inhibitors of the plasminogen activator system with regard to their potential to prevent pemphigus-induced cutaneous pathology. In a human split skin culture system, IgG preparations of sera from pemphigus vulgaris patients caused histopathologic changes (acantholysis) similar to those observed in the original pemphigus disease. All inhibitors that were tested (active site inhibitors directed against uPA, tPA, and/or plasmin; antibodies neutralizing the enzymatic activity of uPA or tPA; substances interfering with the binding of uPA to its specific cell surface receptor uPAR) failed to prevent pemphigus vulgaris IgG-mediated acantholysis. Plasminogen-mediated acantholysis, however, was effectively antagonized by the synthetic active site serine protease inhibitor WX-UK1 or by p-aminomethylbenzoic acid. Our data argue against applying anti-plasminogen activator/anti-plasmin strategies in the management of pemphigus

Towards a Precise Parton Luminosity Determination at the CERN LHC

A new approach to determine the LHC luminosity is investigated. Instead of employing the proton-proton luminosity measurement, we suggest to measure directly the parton-parton luminosity. It is shown that the electron and muon pseudorapidity distributions, originating from the decay of W+, W- and Z0 bosons produced at 14 TeV pp collisions (LHC), constrain the x distributions of sea and valence quarks and antiquarks in the range from about 3 x 10**-4 to about 10**-1 at a Q**2 of about 10**4 GeV**2. Furthermore, it is demonstrated that, once the quark and antiquark structure functions are constrained from the W+,W- and Z0 production dynamics, other quark-antiquark related scattering processes at the LHC like q-qbar --> W+W- can be predicted accurately. Thus, the lepton pseudorapidity distributions provide the key to a precise parton luminosity monitor at the LHC, with accuracies of about +-1% compared to the so far considered goal of +-5%.Comment: plain tex, 14 pages, 5 figure

Clinical Characteristics of Suicidal Youths and Adults: A One-Year Retrospective Study

Suicide is a major mental health problem, particularly during youth, when it is the second leading cause of death. Since young people at risk of suicide are often cared for by the adult health system, we sought to identify the specificities and similarities between suicidal youths and adults in order to further inform the potential need for adaptations in taking care of suicidal youths. For this study, we used the following data: mental disorders, treatments, previous hospitalization, and reasons for current hospitalization, that were collected from November 2016 to October 2017 among people hospitalized for a suicidal crisis in a specialized psychiatric unit. First, we compared the data from the youth group with those from the adult group, and then we tried to determine if there were any associations between variables. Analyses showed that youths were more similar to adults than expected. In particular, we found comparable rates of personality disorders (especially borderline) and relapse, and similar profiles of reasons for hospitalization in suicidal crisis. Remarkably, among youth, neuroleptics appeared to be associated with fewer hospitalizations for behavioral than ideational reasons, but with more relapses. Results of this study suggest that young people could benefit from brief psychotherapeutic interventions implemented for adult

Searching for a heavy Higgs boson via the H --> l nu jj decay mode at the CERN LHC

The discovery of a heavy Higgs boson with mass up to m_H = 1 TeV at the CERN LHC is possible in the H--> W^+W^- --> l nu jj decay mode. The weak boson scattering signal and backgrounds from t\bar tjj and from W+jets production are analyzed with parton level Monte Carlo programs which are built on full tree level amplitudes for all subprocesses. The use of double jet tagging and the reconstruction of the W invariant mass reduce the combined backgrounds to the same level as the Higgs signal. A central mini-jet veto, which distinguishes the different gluon radiation patterns of the hard processes, further improves the signal to background ratio to about 2.5:1, with a signal cross section of 1 fb. The jet energy asymmetry of the W --> jj decay will give a clear signature of the longitudinal polarization of the W's in the final event sample.Comment: 23 pages (with 7 embedded figures), Revtex, uses epsf.sty. Z-compressed postscript version also available at http://phenom.physics.wisc.edu/pub/preprints/1997/madph-97-1017.ps.Z or at ftp://phenom.physics.wisc.edu/pub/preprints/1997/madph-97-1017.ps.

In non-transformed cells Bak activates upon loss of anti-apoptotic Bcl-X-L and Mcl-1 but in the absence of active BH3-only proteins

Mitochondrial apoptosis is controlled by proteins of the B-cell lymphoma 2 (Bcl-2) family. Pro-apoptotic members of this family, known as BH3-only proteins, initiate activation of the effectors Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak),which is counteracted by anti-apoptotic family members. How the interactions of Bcl-2 proteins regulate cell death is still not entirely clear. Here, we show that in the absence of extrinsic apoptotic stimuli Bak activates without detectable contribution from BH3-only proteins, and cell survival depends on anti-apoptotic Bcl-2 molecules. All anti-apoptotic Bcl-2 proteins were targeted via RNA interference alone or in combinations of two in primary human fibroblasts. Simultaneous targeting of B-cell lymphoma-extra large and myeloid cell leukemia sequence 1 led to apoptosis in several cell types. Apoptosis depended on Bak whereas Bax was dispensable. Activator BH3-only proteins were not required for apoptosis induction as apoptosis was unaltered in the absence of all BH3-only proteins known to activate Bax or Bak directly, Bcl-2-interacting mediator of cell death, BH3-interacting domain death agonist and p53-upregulated modulator of apoptosis. These findings argue for auto-activation of Bak in the absence of anti-apoptotic Bcl-2 proteins and provide evidence of profound differences in the activation of Bax and Bak

In non-transformed cells Bak activates upon loss of anti-apoptotic Bcl-X-L and Mcl-1 but in the absence of active BH3-only proteins

Mitochondrial apoptosis is controlled by proteins of the B-cell lymphoma 2 (Bcl-2) family. Pro-apoptotic members of this family, known as BH3-only proteins, initiate activation of the effectors Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak),which is counteracted by anti-apoptotic family members. How the interactions of Bcl-2 proteins regulate cell death is still not entirely clear. Here, we show that in the absence of extrinsic apoptotic stimuli Bak activates without detectable contribution from BH3-only proteins, and cell survival depends on anti-apoptotic Bcl-2 molecules. All anti-apoptotic Bcl-2 proteins were targeted via RNA interference alone or in combinations of two in primary human fibroblasts. Simultaneous targeting of B-cell lymphoma-extra large and myeloid cell leukemia sequence 1 led to apoptosis in several cell types. Apoptosis depended on Bak whereas Bax was dispensable. Activator BH3-only proteins were not required for apoptosis induction as apoptosis was unaltered in the absence of all BH3-only proteins known to activate Bax or Bak directly, Bcl-2-interacting mediator of cell death, BH3-interacting domain death agonist and p53-upregulated modulator of apoptosis. These findings argue for auto-activation of Bak in the absence of anti-apoptotic Bcl-2 proteins and provide evidence of profound differences in the activation of Bax and Bak

CERN West Area neutrino facility beam line alignment

This papers describes the alignment of the West Area Neutrino Beam Line at CERN to the two neutrino experiments CHORUS and NOMAD. The T9 neutrino (n) target position and the position of the magnetic horn were optimised using the secondary muon intensity profiles from the muon pits in the shielding. In the experiments the improved geometry provides a better centred beam (< 5 cm) and a measured increase in the n flux of 8%

Vector Meson Photoproduction with an Effective Lagrangian in the Quark Model

A quark model approach to the photoproduction of vector mesons off nucleons is proposed. Its starting point is an effective Lagrangian of the interaction between the vector meson and the quarks inside the baryon, which generates the non-diffractive s- and u- channel resonance contributions. Additional t-channel $\pi^0$ and $\sigma$ exchanges are included for the $\omega$ and $\rho^0$ production respectively to account for the large diffractive behavior in the small $t$ region as suggested by Friman and Soyeur. The numerical results are presented for the $\omega$ and $\rho$ productions in four isospin channels with the same set of parameters, and they are in good agreement with the available data not only in $\omega$ and $\rho^0$ productions but also in the charged $\rho$ productions where the additional t-channel $\sigma$ exchange does not contribute so that it provides an important test to this approach. The investigation is also extended to the $\phi$ photoproduction, and the initial results show that the non-diffractive behavior of the $\phi$ productions in the large $t$ region can be described by the s- and u- channel contributions with significantly smaller coupling constants, which is consistent with the findings in the similar studies in the QHD framework. The numerical investigation has also shown that polarization observables are essential for identifying so-called "missing resonances".Comment: 36 pages, 10 PS figures, extended version of nucl-th/9711061 and nucl-th/9803021, submitted to PR

Relating parton model and color dipole formulation of heavy quark hadroproduction

At high center of mass energies, hadroproduction of heavy quarks can be expressed in terms of the same color dipole cross section as low Bjorken-x deep inelastic scattering. We show analytically that at leading order, the dipole formulation is equivalent to the gluon-gluon fusion mechanism of the conventional parton model. In phenomenological application, we employ a parameterization of the dipole cross section which also includes higher order and saturation effects, thereby going beyond the parton model. Numerical calculations in the dipole approach agree well with experimental data on open charm production over a wide range of energy. Dipole approach and next to leading order parton model yield similar values for open charm production, but for open bottom production, the dipole approach tends to predict somewhat higher cross sections than the parton model.Comment: 16 pages, 4 figure

Probing color-singlet exchange in Z+2Z+2-jet events at the LHC

The purely electroweak process $qq\to qqZ$ (via $t$-channel $\gamma/Z$ or $W$ exchange) provides a copious and fairly clean source of color-singlet exchange events in $pp$ collisions at the LHC. A judicious choice of phase-space region allows the suppression of QCD backgrounds to the level of the signal. The color-singlet-exchange signal can be distinguished from QCD backgrounds by the radiation patterns of additional minijets in individual events. A rapidity-gap trigger at the minijet level substantially enhances the signal versus the background. Analogous features of weak boson scattering events make $Z+2$-jet events at the LHC an ideal laboratory for investigation of the soft-jet activity expected in weak-boson scattering events.Comment: 24 pages (with 7 embedded figures), Revtex, uses epsf.sty. Z-compressed postscript version also available at http://phenom.physics.wisc.edu/pub/preprints/1996/madph-96-943.ps.Z or at ftp://phenom.physics.wisc.edu/pub/preprints/1996/madph-96-943.ps.