The s ---> d gamma decay in and beyond the Standard Model

The New Physics sensitivity of the s ---> d gamma transition and its accessibility through hadronic processes are thoroughly investigated. Firstly, the Standard Model predictions for the direct CP-violating observables in radiative K decays are systematically improved. Besides, the magnetic contribution to epsilon prime is estimated and found subleading, even in the presence of New Physics, and a new strategy to resolve its electroweak versus QCD penguin fraction is identified. Secondly, the signatures of a series of New Physics scenarios, characterized as model-independently as possible in terms of their underlying dynamics, are investigated by combining the information from all the FCNC transitions in the s ---> d sector.Comment: 54 pages, 14 eps figure

Electronic correlations in the iron pnictides

In correlated metals derived from Mott insulators, the motion of an electron is impeded by Coulomb repulsion due to other electrons. This phenomenon causes a substantial reduction in the electron's kinetic energy leading to remarkable experimental manifestations in optical spectroscopy. The high-Tc superconducting cuprates are perhaps the most studied examples of such correlated metals. The occurrence of high-Tc superconductivity in the iron pnictides puts a spotlight on the relevance of correlation effects in these materials. Here we present an infrared and optical study on single crystals of the iron pnictide superconductor LaFePO. We find clear evidence of electronic correlations in metallic LaFePO with the kinetic energy of the electrons reduced to half of that predicted by band theory of nearly free electrons. Hallmarks of strong electronic many-body effects reported here are important because the iron pnictides expose a new pathway towards a correlated electron state that does not explicitly involve the Mott transition.Comment: 10 page

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Human Computation and Convergence

Humans are the most effective integrators and producers of information, directly and through the use of information-processing inventions. As these inventions become increasingly sophisticated, the substantive role of humans in processing information will tend toward capabilities that derive from our most complex cognitive processes, e.g., abstraction, creativity, and applied world knowledge. Through the advancement of human computation - methods that leverage the respective strengths of humans and machines in distributed information-processing systems - formerly discrete processes will combine synergistically into increasingly integrated and complex information processing systems. These new, collective systems will exhibit an unprecedented degree of predictive accuracy in modeling physical and techno-social processes, and may ultimately coalesce into a single unified predictive organism, with the capacity to address societies most wicked problems and achieve planetary homeostasis.Comment: Pre-publication draft of chapter. 24 pages, 3 figures; added references to page 1 and 3, and corrected typ

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Genotype‐phenotype analysis of LMNA‐related diseases predicts phenotype‐selective alterations in lamin phosphorylation

Laminopathies are rare diseases associated with mutations in LMNA, which encodes nuclear lamin A/C. LMNA variants lead to diverse tissue‐specific phenotypes including cardiomyopathy, lipodystrophy, myopathy, neuropathy, progeria, bone/skin disorders, and overlap syndromes. The mechanisms underlying these heterogeneous phenotypes remain poorly understood, although post‐translational modifications, including phosphorylation, are postulated as regulators of lamin function. We catalogued all known lamin A/C human mutations and their associated phenotypes, and systematically examined the putative role of phosphorylation in laminopathies. In silico prediction of specific LMNA mutant‐driven changes to lamin A phosphorylation and protein structure was performed using machine learning methods. Some of the predictions we generated were validated via assessment of ectopically expressed wild‐type and mutant LMNA. Our findings indicate phenotype‐ and mutant‐specific alterations in lamin phosphorylation, and that some changes in phosphorylation may occur independently of predicted changes in lamin protein structure. Therefore, therapeutic targeting of phosphorylation in the context of laminopathies will likely require mutant‐ and kinase‐specific approaches.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155891/1/fsb220571.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155891/2/fsb220571_am.pd