A gauge model for quantum mechanics on a stratified space

In the Hamiltonian approach on a single spatial plaquette, we construct a quantum (lattice) gauge theory which incorporates the classical singularities. The reduced phase space is a stratified K\"ahler space, and we make explicit the requisite singular holomorphic quantization procedure on this space. On the quantum level, this procedure furnishes a costratified Hilbert space, that is, a Hilbert space together with a system which consists of the subspaces associated with the strata of the reduced phase space and of the corresponding orthoprojectors. The costratified Hilbert space structure reflects the stratification of the reduced phase space. For the special case where the structure group is $\mathrm{SU}(2)$, we discuss the tunneling probabilities between the strata, determine the energy eigenstates and study the corresponding expectation values of the orthoprojectors onto the subspaces associated with the strata in the strong and weak coupling approximations.Comment: 38 pages, 9 figures. Changes: comments on the heat kernel and coherent states have been adde

Genetic Mosaicism in Calmodulinopathy.

CaM (calmodulin) mutations are associated with congenital arrhythmia susceptibility (calmodulinopathy) and are most often de novo. In this report, we sought to broaden the genotype-phenotype spectrum of calmodulinopathies with 2 novel calmodulin mutations and to investigate mosaicism in 2 affected families. CaM mutations were identified in 4 independent cases by DNA sequencing. Biochemical and electrophysiological studies were performed to determine functional consequences of each mutation. Genetic studies identified 2 novel CaM variants (CALM3-E141K in 2 cases; CALM1-E141V) and one previously reported CaM pathogenic variant (CALM3-D130G) among 4 probands with shared clinical features of prolonged QTc interval (range 505-725 ms) and documented ventricular arrhythmia. A fatal outcome occurred for 2 of the cases. The parents of all probands were asymptomatic with normal QTc duration. However, 2 of the families had multiple affected offspring or multiple occurrences of intrauterine fetal demise. The mother from the family with recurrent intrauterine fetal demise exhibited the CALM3-E141K mutant allele in 25% of next-generation sequencing reads indicating somatic mosaicism, whereas CALM3-D130G was present in 6% of captured molecules of the paternal DNA sample, also indicating mosaicism. Two novel mutations (E141K and E141V) impaired Ca <sup>2+</sup> binding affinity to the C-domain of CaM. Human-induced pluripotent stem cell-derived cardiomyocytes overexpressing mutant or wild-type CaM showed that both mutants impaired Ca <sup>2+</sup> -dependent inactivation of L-type Ca <sup>2+</sup> channels and prolonged action potential duration. We report 2 families with somatic mosaicism associated with arrhythmogenic calmodulinopathy, and demonstrate dysregulation of L-type Ca <sup>2+</sup> channels by 2 novel CaM mutations affecting the same residue. Parental mosaicism should be suspected in families with unexplained fetal arrhythmia or fetal demise combined with a documented CaM mutation

Emergence and global spread of epidemic healthcare-associated Clostridium difficile

Epidemic C. difficile (027/BI/NAP1) has rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key events in evolutionary history leading to its emergence and the subsequent patterns of global spread remain unknown. Here, we define the global population structure of C. difficile 027/BI/NAP1 using whole-genome sequencing and phylogenetic analysis. We show that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance-conferring mutation and a highly related conjugative transposon. The two epidemic lineages showed distinct patterns of global spread, and the FQR2 lineage spread more widely, leading to healthcare-associated outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid transcontinental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system

Communicating culture: a reinforcement process model

In this article, after laying the conceptual foundations of communication and corporate culture, we revise the disagreement on whether their role in their mutual relationship is a minor or a fundamental one. Then, we define “communication in corporate culture”, as the foundation of the communication-culture system. Building on this idea, we suggest a model for organizational reinforcement. Finally, we define the basic patterns in order to strengthen and reinforce the proposed cycle