A Renormalizable Supersymmetric SU(5) Model

In the Supersymmetric SU(5) Model of Unification with the Missing Partner Mechanism, we present a renormalizable model using the Georgi-Jarlsog mechanism to describe the fermion masses and mixing. At the meantime the proton decay rates are also suppressed to satisfy the experimental data

Five Amino Acid Residues Responsible for the High Stability of Hydrogenobacter thermophilus Cytochrome c552

Five amino acid residues responsible for extreme stability have been identified in cytochrome c552 (HT c552) from a thermophilic bacterium, Hydrogenobacter thermophilus. The five residues, which are spatially distributed in three regions of HT c552, were replaced with the corresponding residues in the homologous but less stable cytochrome c551 (PA c551) from Pseudomonas aeruginosa. The quintuple HT c552 variant (A7F/M13V/Y34F/Y43E/I78V) showed the same stability against guanidine hydrochloride denaturation as that of PA c551, suggesting that the five residues in HT c552 necessarily and sufficiently contribute to the overall stability. In the three HT c552 variants carrying mutations in each of the three regions, the Y34F/Y43E mutations resulted in the greatest destabilization, by –13.3 kJ mol–1, followed by A7F/M13V (–3.3 kJ mol–1) and then I78V (–1.5 kJ mol–1). The order of destabilization in HT c552 was the same as that of stabilization in PA c551 with reverse mutations such as F34Y/E43Y, F7A/V13M, and V78I (13.4, 10.3, and 0.3 kJ mol–1, respectively). The results of guanidine hydrochloride denaturation were consistent with those of thermal denaturation for the same variants. The present study established a method for reciprocal mutation analysis. The effects of side-chain contacts were experimentally evaluated by swapping the residues between the two homologous proteins that differ in stability. A comparative study of the two proteins was a useful tool for assessing the amino acid contribution to the overall stability.This work was supported in part by grants from Hiroshima University, the Noda Institute for Scientific Research, and the Japanese Ministry of Education, Science and Culture (grants-in-aid for Scientific Research on Priority Areas)

Suppression of 1/f noise in one-qubit systems

We investigate the generation of quantum operations for one-qubit systems under classical noise with 1/f^\alpha power spectrum, where 2>\alpha > 0. We present an efficient way to approximate the noise with a discrete multi-state Markovian fluctuator. With this method, the average temporal evolution of the qubit density matrix under 1/f^\alpha noise can be feasibly determined from recently derived deterministic master equations. We obtain qubit operations such as quantum memory and the NOT}gate to high fidelity by a gradient based optimization algorithm. For the NOT gate, the computed fidelities are qualitatively similar to those obtained earlier for random telegraph noise. In the case of quantum memory however, we observe a nonmonotonic dependency of the fidelity on the operation time, yielding a natural access rate of the memory.Comment: 8 pages, 7 figure

Numerical simulations of shocks encountering clumpy regions

We present numerical simulations of the adiabatic interaction of a shock with a clumpy region containing many individual clouds. Our work incorporates a sub-grid turbulence model which for the first time makes this investigation feasible. We vary the Mach number of the shock, the density contrast of the clouds, and the ratio of total cloud mass to inter-cloud mass within the clumpy region. Cloud material becomes incorporated into the flow. This "mass-loading" reduces the Mach number of the shock, and leads to the formation of a dense shell. In cases in which the mass-loading is sufficient the flow slows enough that the shock degenerates into a wave. The interaction evolves through up to four stages: initially the shock decelerates; then its speed is nearly constant; next the shock accelerates as it leaves the clumpy region; finally it moves at a constant speed close to its initial speed. Turbulence is generated in the post-shock flow as the shock sweeps through the clumpy region. Clouds exposed to turbulence can be destroyed more rapidly than a similar cloud in an "isolated" environment. The lifetime of a downstream cloud decreases with increasing cloud-to-intercloud mass ratio. We briefly discuss the significance of these results for starburst superwinds and galaxy evolution.Comment: 17 pages, 19 figures, accepted for publication in MNRA

Imbalanced Base Excision Repair in Response to Folate Deficiency Is Accelerated by Polymerase β Haploinsufficiency

The mechanism by which folate deficiency influences carcinogenesis is not well established, but a phenotype of DNA strand breaks, mutations, and chromosomal instability suggests an inability to repair DNA damage. To elucidate the mechanism by which folate deficiency influences carcinogenicity, we have analyzed the effect of folate deficiency on base excision repair (BER), the pathway responsible for repairing uracil in DNA. We observe an up-regulation in initiation of BER in liver of the folate-deficient mice, as evidenced by an increase in uracil DNA glycosylase protein (30%, p < 0.01) and activity (31%, p < 0.05). However, no up-regulation in either BER or its rate-determining enzyme, DNA polymerase beta (beta-pol) is observed in response to folate deficiency. Accordingly, an accumulation of repair intermediates in the form of DNA single strand breaks (37% increase, p < 0.03) is observed. These data indicate that folate deficiency alters the balance and coordination of BER by stimulating initiation without subsequently stimulating the completion of repair, resulting in a functional BER deficiency. In directly establishing that the inability to induce beta-pol and mount a BER response when folate is deficient is causative in the accumulation of toxic repair intermediates, beta-pol-haploinsufficient mice subjected to folate deficiency displayed additional increases in DNA single strand breaks (52% increase, p < 0.05) as well as accumulation in aldehydic DNA lesions (38% increase, p < 0.01). Since young beta-polhaploinsufficient mice do not spontaneously exhibit increased levels of these repair intermediates, these data demonstrate that folate deficiency and beta-pol haploinsufficiency interact to increase the accumulation of DNA damage. In addition to establishing a direct role for beta-pol in the phenotype expressed by folate deficiency, these data are also consistent with the concept that repair of uracil and abasic sites is more efficient than repair of oxidized bases

Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage

Adefective response to DNA damage is observed in several human autosomal recessive ataxias with oculomotor apraxia, including ataxia-telangiectasia. We report that senataxin, defective in ataxia oculomotor apraxia (AOA) type 2, is a nuclear protein involved in the DNA damage response. AOA2 cells are sensitive to H2O2, camptothecin, and mitomycin C, but not to ionizing radiation, and sensitivity was rescued with full-length SETX cDNA. AOA2 cells exhibited constitutive oxidative DNA damage and enhanced chromosomal instability in response to H2O2. Rejoining of H2O2-induced DNA double-strand breaks (DSBs) was significantly reduced in AOA2 cells compared to controls, and there was no evidence for a defect in DNA single-strand break repair. This defect in DSB repair was corrected by full-length SETX cDNA. These results provide evidence that an additional member of the autosomal recessive AOA is also characterized by a defective response to DNA damage, which may contribute to the neurodegeneration seen in this syndrome

Exploration of hyperfine interaction between constituent quarks via eta productions

In this work, the different exchange freedom, one gluon, one pion or Goldstone boson, in constituent quark model is investigated, which is responsible to the hyperfine interaction between constituent quarks, via the combined analysis of the eta production processes, $\pi^{-}p\rightarrow\eta n$ and $\gamma p\rightarrow\eta p$. With the Goldstone-boson exchange, as well as the one-gluon or one-pion exchange, both the spectrum and observables, such as, the differential cross section and polarized beam asymmetry, are fitted to the suggested values of Particle Data Group and the experimental data. The first two types of exchange freedoms give acceptable description of the spectrum and observables while the one pion exchange can not describe the observables and spectrum simultaneously, so can be excluded. The experimental data for the two processes considered here strongly support the mixing angles for two lowest S11 sates and D13 states as about -30 and 6 degree respectively.Comment: 7 pages, 4 figures, 4 table

Apurinic/Apyrimidinic Endonuclease (APE/REF-1) Haploinsufficient Mice Display Tissue-specific Differences in DNA Polymerase β-Dependent Base Excision Repair

Apurinic/apyrimidinic (AP) endonuclease (APE) is a multifunctional protein possessing both DNA repair and redox regulatory activities. In base excision repair (BER), APE is responsible for processing spontaneous, chemical, or monofunctional DNA glycosylase-initiated AP sites via its 5'-endonuclease activity and 3'-"end-trimming" activity when processing residues produced as a consequence of bifunctional DNA glycosylases. In this study, we have fully characterized a mammalian model of APE haploinsufficiency by using a mouse containing a heterozygous gene-targeted deletion of the APE gene (Apex(+/-)). Our data indicate that Apex(+/-) mice are indeed APE-haploinsufficient, as exhibited by a 40-50% reduction (p < 0.05) in APE mRNA, protein, and 5'-endonuclease activity in all tissues studied. Based on gene dosage, we expected to see a concomitant reduction in BER activity; however, by using an in vitro G:U mismatch BER assay, we observed tissue-specific alterations in monofunctional glycosylase-initiated BER activity, e.g. liver (35% decrease, p < 0.05), testes (55% increase, p < 0.05), and brain (no significant difference). The observed changes in BER activity correlated tightly with changes in DNA polymerase beta and AP site DNA binding levels. We propose a mechanism of BER that may be influenced by the redox regulatory activity of APE, and we suggest that reduced APE may render a cell/tissue more susceptible to dysregulation of the polymerase beta-dependent BER response to cellular stress