Softening the Supersymmetric Flavor Problem in Orbifold GUTs

The infra-red attractive force of the bulk gauge interactions is applied to soften the supersymmetric flavor problem in the orbifold SU(5) GUT of Kawamura. Then this force aligns in the infra-red regime the soft supersymmetry breaking terms out of their anarchical disorder at a fundamental scale, in such a way that flavor-changing neutral currents as well as dangerous CP-violating phases are suppressed at low energies. It is found that this dynamical alignment is sufficiently good compared with the current experimental bounds, as long as the diagonalization matrices of the Yukawa couplings are CKM-like.Comment: 15 pages,4 figure

CP Violation in a Supersymmetric SO(10) x U(2)_{F} Model

A model based on SUSY SO(10) combined with U(2) family symmetry constructed recently by the authors is generalized to include phases in the mass matrices leading to CP violation. In contrast with the commonly used effective operator approach, $\bar{126}$-dimensional Higgs fields are utilized to construct the Yukawa sector. R-parity symmetry is thus preserved at low energies. The symmetric mass textures arising from the left-right symmetry breaking chain of SO(10) give rise to very good predictions for quark and lepton masses and mixings. The prediction for $\sin 2\beta$ agrees with the average of current bounds from BaBar and Belle. In the neutrino sector, our predictions are in good agreement with results from atmospheric neutrino experiments. Our model favors both the LOW and QVO solutions to the solar neutrino anomaly; the matrix element for neutrinoless double beta decay is highly suppressed. The leptonic analog of the Jarlskog invariant, $J_{CP}^{l}$, is predicted to be of $O(10^{-2})$.Comment: RevTeX4; 7 pages; typos corrected; clarification remarks added; more references added. To appear in Physical Review

Four-fermion heavy quark operators and light current amplitudes in heavy flavor hadrons

We introduce and study the properties of the "color-straight" four-quark operators containing heavy and light quark fields. They are of the form (\bar b\Gamma_b b)(\bar q\Gamma_q q) where both brackets are color singlets. Their expectation values include the bulk of the nonfactorizable contributions to the nonleptonic decay widths of heavy hadrons. The expectation values of the color-straight operators in the heavy hadrons are related to the momentum integrals of the elastic light-quark formfactors of the respective heavy hadron. We calculate the asymptotic behavior of the light-current formfactors of heavy hadrons and show that the actual decrease is 1/(q^2)^3/2 rather than 1/q^4. The two-loop hybrid anomalous dimensions of the four-quark operators and their mixing (absent in the first loop) are obtained. Using plausible models for the elastic formfactors, we estimate the expectation values of the color-straight operators in the heavy mesons and baryons. Improved estimates will be possible in the future with new data on the radiative decays of heavy hadrons. We give the Wilson coefficients of the four-fermion operators in the 1/m_b expansion of the inclusive widths and discuss the numerical predictions. Estimates of the nonfactorizable expectation values are given.Comment: 51 pages. The case of flavor-singlet operators is added for the two-loop anomalous dimension

Finite Theories and the SUSY Flavor Problem

We study a finite SU(5) grand unified model based on the non-Abelian discrete symmetry A_4. This model leads to the democratic structure of the mass matrices for the quarks and leptons. In the soft supersymmetry breaking sector, the scalar trilinear couplings are aligned and the soft scalar masses are degenerate, thus solving the SUSY flavor problem.Comment: 17 pages, LaTeX, 1 figur

Dynamical Left-Right Symmetry Breaking

We study a left--right symmetric model which contains only elementary gauge boson and fermion fields and no scalars. The phenomenologically required symmetry breaking emerges dynamically leading to a composite Higgs sector with a renormalizable effective Lagrangian. We discuss the pattern of symmetry breaking and phenomenological consequences of this scenario. It is shown that a viable top quark mass can be achieved for the ratio of the VEVs of the bi--doublet $\tan\beta\equiv\kappa/\kappa'$ =~ 1.3--4. For a theoretically plausible choice of the parameters the right--handed scale can be as low as $\sim 20 TeV$; in this case one expects several intermediate and low--scale scalars in addition to the \SM Higgs boson. These may lead to observable lepton flavour violation effects including $\mu\to e\gamma$ decay with the rate close to its present experimental upper bound.Comment: 51 pages, LaTeX and uuencoded, packed Postscript figures. The complete paper, including figures, is also available via WWW at http://www.cip.physik.tu-muenchen.de/tumphy/d/T30d/PAPERS/ TUM-HEP-222-95.ps.g

Direct measurement of the rate of glutathione synthesis in 1-chloro-2,4-dinitrobenzene treated human erythrocytes.

Item does not contain fulltextCell glutathione scavenges free radicals, degrades peroxides, removes damaging electrophiles and maintains the redox state. The aim of this study was to develop an effective and efficient method to measure the rate of glutathione synthesis from its constituent amino acids in whole erythrocytes (RBCs). RBCs (10% haematocrit) were exposed to 0.3 mM 1-chloro-2,4-dinitrobenzene (CDNB) to lower their total glutathione content by 70% and then incubated with glucose, and N-acetylcysteine as a cysteine source. Over 3 h, glutathione levels increased at a constant rate of 1.2 micromol (L RBC)(-1)min(-1), almost 5 times faster than the rate of glutathione synthesis in RBCs with normal glutathione levels. Glutathione at concentrations normally found in RBCs is known to inhibit glutamate cysteine ligase (the major rate controlling enzyme for glutathione synthesis). The rate of glutathione recovery was substantially reduced in RBCs treated with buthionine sulfoximine, a specific inhibitor of glutamate cysteine ligase. Our results indicate that the measurement of glutathione recovery rate after CDNB treatment can be used to estimate de novo synthesis of glutathione. Application of this direct method for measuring glutathione synthesis will increase understanding of the interactions of effectors that determine glutathione levels in RBCs under various physiological and pathological conditions

A three base pair gene variation within the distal 5'-flanking region of the interleukin-10 (IL-10) gene is related to the in vitro IL-10 production capacity of lipopolysaccharide-stimulated peripheral blood mononuclear cells.

Item does not contain fulltextInterleukin-10 (IL-10) is an important multifunctional immunmodulator. There is evidence that IL-10 secretion is associated with certain genetic elements of the proximal IL-10 gene 5'-flanking region. The allelic and genotypic comparison of IL-10 expression by lipopolysaccharide (LPS)- stimulated leukocytes (PBMC) with a recently discovered distal "indel" DNA-sequence variation at - 7400 bp revealed significant inter-individual differences in the IL-10 in vitro production capacity. Homozygotes lacking the three base pairs "GGA" (- 7400del) at this gene locus are characterised by high expression of IL-10 with a median of 1690pg/ml (P <or=0.009). The allelic comparison supports this finding (P <or=0.002). Further analysis of the haplotype -7400/- 1087 showed that homozygotes for - 7400del/- 1087G may be classified as very strong IL-10 responders with a median IL-10 secretion of 2378 pg/ml (P <or=0.025). When leukocytes were stimulated in vitro by dibutyryl-cAMP or infected with Epstein-Barr virus no significant inter-individual differences between the - 7400indel alleles or genotypes and the IL-10 in vitro production capacity were observed. Our findings further the understanding of the complexity of IL-10 gene regulation in relation to defined regulatory gene variations

A second form of collagenous lectin from the tunicate, Styela plicata.

Item does not contain fulltextThis study characterised a 90 kDa lectin from an invertebrate chordate, the tunicate Styela plicata. One- and two-dimensional electrophoresis showed that the apparent molecular weight of this protein is maintained under both reducing and non-reducing conditions, suggesting that its native form is a monomer. The 90 kDa lectin was localised within a single type of hemocyte (morula cells), but was secreted from those cells when tunicates were challenged with the inflammatory elicitor, zymosan. Functional studies showed that the 90 kDa protein binds to galactose-based sugars in a divalent cation-dependent manner. Amino acid composition analysis and N-terminal amino acid sequencing indicated that the 90 kDa lectin is related to a previously characterised, collagenous lectin from S. plicata, splic43. However, peptide mass fingerprinting identified numerous differences between the two proteins. This suggests that the 90 kDa molecule represents a novel protein that is involved in host defence

Antibodies to rifin: a component of naturally acquired responses to Plasmodium falciparum variant surface antigens on infected erythrocytes.

Item does not contain fulltextWe used a pool of recombinant rifin proteins to pre-adsorb antibodies to rifin in the plasma of semi-immune African (Gabonese) adults and showed that this results in a reduction in the level of IgG antibody reactivity to variant surface antigens (VSA) measured in a standardized flow cytometric assay with a panel of heterologous parasite isolates. The same methods demonstrated a similar but less-marked contribution of antibodies to the duffy binding-like 1alpha (DBL-1alpha ) domain to the overall anti-VSA response. Thus, we conclude that both antibodies to rifin and, to a lesser extent, antibodies directed to conserved regions of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) DBL-1alpha domain contribute to the overall antibody response to VSA. We also assessed the associations between these different antibody responses in a cohort of Gabonese children. We found marked differences related to the childrens' history of presentation with either mild or severe malaria, but no consistent pattern that would indicate a specific role or influence of antibody responses to rifin

Iron chelators: correlation between effects on Plasmodium spp. and immune functions.

Item does not contain fulltextIron chelating agents, which permeate through erythrocytic and parasite membranes, are effective against Plasmodium falciparum in vitro. However, the protective effect in humans is transient. We examined the antiplasmodial capacity of several iron chelators in vitro and in vivo. The chelators 3/3hb/2m and 3/2hb/b (together, MoB) were more effective against P. falciparum in vitro than desferrioxamine (DFO) and Salicylaldehyde isonicotinoyl hydrazone (SIH) (together, DoS). Despite similar pharmacokinetics of all iron chelators, mice infected with Plasmodium vinckei and treated with MoB succumbed to malaria, whereas DoS-treated mice survived. However, even in the surviving mice, peak parasitemias were above 30%. These results indicate that the direct effects of the drugs on the parasites were not responsible alone for the complete recovery of the mice. We suggest that the recovery is related to differential effects of the drugs on various immune functions. We concentrated on the effect of the iron chelators on B cell and T cell proliferation and on allogeneic stimulation (MLR), interleukin-10 (IL-10), gamma-interferon (gamma-IFN), tumor necrosis factor-alpha (TNF-alpha), and radical production. All the iron chelators examined inhibited the in vitro proliferation of B cells and T cells, and MLR. This may explain why iron chelators are only slightly efficient in treating human malaria. However, the inhibitory effects of MoB on B cell and T cell proliferation and on MLR were more pronounced than those of DoS. In addition, the release of free radicals by effector cells was inhibited to a greater extent by MoB than by DoS. These results may explain why MoB, which was more efficient in vitro, was not effective in vivo. The DoS effects on the in vitro secretion of cytokines correlate with their in vivo effect; there was a decrease of IL-10 and a parallel increase in gamma-IFN and TNF-alpha production by human mononuclear cells. MoB, which could not rescue the animals from malaria, did not affect IL-10 and TNF-alpha, but reduced gamma-IFN levels. Identical results were obtained when using monocytes instead of mononuclear cells (except for gamma-IFN, which is not produced by monocytes). Our results indicate that an iron chelator, or any antiparasitic drug that kills the parasites in vitro, should also be selected for further evaluation on the basis of its reaction with immune components; it should not interfere with crucial protective immunological processes, but it may still alleviate parasitemia by positive immune modulation