Mass Hierarchy, Mixing, CP-Violation and Higgs Decay---or Why Rotation is Good for Us

The idea of a rank-one rotating mass matrix (R2M2) is reviewed detailing how it leads to ready explanations both for the fermion mass hierarchy and for the distinctive mixing patterns between up and down fermion states, which can be and have been tested against experiment and shown to be fully consistent with existing data. Further, R2M2 is seen to offer, as by-products: (i) a new solution of the strong CP problem in QCD by linking the theta-angle there to the Kobayashi-Maskawa CP-violating phase in the CKM matrix, and (ii) some novel predictions of possible anomalies in Higgs decay observable in principle at the LHC. A special effort is made to answer some questions raised.Comment: 47 pages, 9 figure

A Comprehensive Mechanism Reproducing the Mass and Mixing Parameters of Quarks and Leptons

It is shown that if, from the starting point of a universal rank-one mass matrix long favoured by phenomenologists, one adds the assumption that it rotates (changes its orientation in generation space) with changing scale, one can reproduce, in terms of only 6 real parameters, all the 16 mass ratios and mixing parameters of quarks and leptons. Of these 16 quantities so reproduced, 10 for which data exist for direct comparison (i.e. the CKM elements including the CP-violating phase, the angles $\theta_{12}, \theta_{13}, \theta_{23}$ in $\nu$-oscillation, and the masses $m_c, m_\mu, m_e$) agree well with experiment, mostly to within experimental errors; 4 others ($m_s, m_u, m_d, m_{\nu_2}$), the experimental values for which can only be inferred, agree reasonably well; while 2 others ($m_{\nu_1}, \delta_{CP}$ for leptons), not yet measured experimentally, remain as predictions. In addition, one gets as bonuses, estimates for (i) the right-handed neutrino mass $m_{\nu_R}$ and (ii) the strong CP angle $\theta$ inherent in QCD. One notes in particular that the output value for $\sin^2 2 \theta_{13}$ from the fit agrees very well with recent experiments. By inputting the current experimental value with its error, one obtains further from the fit 2 new testable constraints: (i) that $\theta_{23}$ must depart from its "maximal" value: $\sin^2 2 \theta_{23} \sim 0.935 \pm 0.021$, (ii) that the CP-violating (Dirac) phase in the PMNS would be smaller than in the CKM matrix: of order only $|\sin \delta_{CP}| \leq 0.31$ if not vanishing altogether.Comment: 37 pages, 1 figur

Rapid detection of BRCA1/2 recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels.

BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS). BRCA mutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novel BRCA2 mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC

Developing the Framed Standard Model

The framed standard model (FSM) suggested earlier, which incorporates the Higgs field and 3 fermion generations as part of the framed gauge theory structure, is here developed further to show that it gives both quarks and leptons hierarchical masses and mixing matrices akin to what is experimentally observed. Among its many distinguishing features which lead to the above results are (i) the vacuum is degenerate under a global $su(3)$ symmetry which plays the role of fermion generations, (ii) the fermion mass matrix is "universal", rank-one and rotates (changes its orientation in generation space) with changing scale $\mu$, (iii) the metric in generation space is scale-dependent too, and in general non-flat, (iv) the theta-angle term in the QCD action of topological origin gets transformed into the CP-violating phase of the CKM matrix for quarks, thus offering at the same time a solution to the strong CP problem.Comment: 53 Page

A Nonabelian Yang-Mills Analogue of Classical Electromagnetic Duality

The classic question of a nonabelian Yang-Mills analogue to electromagnetic duality is here examined in a minimalist fashion at the strictly 4-dimensional, classical field and point charge level. A generalisation of the abelian Hodge star duality is found which, though not yet known to give dual symmetry, reproduces analogues to many dual properties of the abelian theory. For example, there is a dual potential, but it is a 2-indexed tensor $T_{\mu\nu}$ of the Freedman-Townsend type. Though not itself functioning as such, $T_{\mu\nu}$ gives rise to a dual parallel transport, $\tilde{A}_\mu$, for the phase of the wave function of the colour magnetic charge, this last being a monopole of the Yang-Mills field but a source of the dual field. The standard colour (electric) charge itself is found to be a monopole of $\tilde{A}_\mu$. At the same time, the gauge symmetry is found doubled from say $SU(N)$ to $SU(N) \times SU(N)$. A novel feature is that all equations of motion, including the standard Yang-Mills and Wong equations, are here derived from a `universal' principle, namely the Wu-Yang (1976) criterion for monopoles, where interactions arise purely as a consequence of the topological definition of the monopole charge. The technique used is the loop space formulation of Polyakov (1980).Comment: We regret that, due to a technical hitch, parts of the reference list were mixed up. This is the corrected version. We apologize to the authors whose papers were misquote

Mutations of PIK3CA in gastric adenocarcinoma

BACKGROUND: Activation of the phosphatidylinositol 3-kinase (PI3K) through mutational inactivation of PTEN tumour suppressor gene is common in diverse cancer types, but rarely reported in gastric cancer. Recently, mutations in PIK3CA, which encodes the p110α catalytic subunit of PI3K, have been identified in various human cancers, including 3 of 12 gastric cancers. Eighty percent of these reported mutations clustered within 2 regions involving the helical and kinase domains. In vitro study on one of the "hot-spot" mutants has demonstrated it as an activating mutation. METHODS: Based on these data, we initiated PIK3CA mutation screening in 94 human gastric cancers by direct sequencing of the gene regions in which 80% of all the known PIK3CA mutations were found. We also examined PIK3CA expression level by extracting data from the previous large-scale gene expression profiling study. Using Significance Analysis of Microarrays (SAM), we further searched for genes that show correlating expression with PIK3CA. RESULTS: We have identified PIK3CA mutations in 4 cases (4.3%), all involving the previously reported hotspots. Among these 4 cases, 3 tumours demonstrated microsatellite instability and 2 tumours harboured concurrent KRAS mutation. Data extracted from microarray studies showed an increased expression of PIK3CA in gastric cancers when compared with the non-neoplastic gastric mucosae (p < 0.001). SAM further identified 2910 genes whose expression levels were positively associated with that of PIK3CA. CONCLUSION: Our data suggested that activation of the PI3K signalling pathway in gastric cancer may be achieved through up-regulation or mutation of PIK3CA, in which the latter may be a consequence of mismatch repair deficiency

Characterizing Emerging Canine H3 Influenza Viruses.

The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer

Background: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA). Results: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.016 and &lt; 0.001, respectively) and in 15 out of 22 TCGA studies. Methylation loss correlated with immunohistochemically staining for TREX2 (p &lt; 0.0001) in laryngeal tumors and improved overall survival of laryngeal cancer patients (p = 0.045). Chromatin immunoprecipitation, demethylation experiments, and reporter gene assays revealed that the region of methylation loss can function as a CCAAT/enhancer binding protein alpha (CEBPA)-responsive enhancer element regulating TREX2 expression. Conclusions: The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Altered TREX2 protein levels in tumors may affect drug-induced DNA damage repair and provide new tailored therapies

Polygenic risk scores for prediction of breast cancer risk in Asian populations.

PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry