Production of alkenes and novel secondary products by P450 OleT JE using novel H2O2-generating fusion protein systems

Jeotgalicoccus sp. 8456 OleTJE (CYP152L1) is a fatty acid decarboxylase cytochrome P450 that uses hydrogen peroxide (H2O2) to catalyse production of terminal alkenes, which are industrially important chemicals with biofuel applications. We report enzyme fusion systems in which Streptomyces coelicolor alditol oxidase (AldO) is linked to OleTJE. AldO oxidizes polyols (including glycerol), generating H2O2 as a co-product and facilitating its use for efficient OleTJE-dependent fatty acid decarboxylation. AldO activity is regulatable by polyol substrate titration, enabling control over H2O2 supply to minimise oxidative inactivation of OleTJE and prolong activity for increased alkene production. We also use these fusion systems to generate novel products from secondary turnover of 2-OH and 3-OH myristic acid primary products, expanding the catalytic repertoire of OleTJE

Asymptotically cylindrical 7-manifolds of holonomy G_2 with applications to compact irreducible G_2-manifolds

We construct examples of exponentially asymptotically cylindrical Riemannian 7-manifolds with holonomy group equal to G_2. To our knowledge, these are the first such examples. We also obtain exponentially asymptotically cylindrical coassociative calibrated submanifolds. Finally, we apply our results to show that one of the compact G_2-manifolds constructed by Joyce by desingularisation of a flat orbifold T^7/\Gamma can be deformed to one of the compact G_2-manifolds obtainable as a generalized connected sum of two exponentially asymptotically cylindrical SU(3)-manifolds via the method given by the first author (math.DG/0012189).Comment: 36 pages; v2: corrected trivial typos; v3: some arguments corrected and improved; v4: a number of improvements on presentation, paritularly in sections 4 and 6, including an added picture

D6-branes and torsion

The D6-brane spectrum of type IIA vacua based on twisted tori and RR background fluxes is analyzed. In particular, we compute the torsion factors of the (co)homology groups H_n and describe the effect that they have on D6-brane physics. For instance, the fact that H_3 contains Z_N subgroups explains why RR tadpole conditions are affected by geometric fluxes. In addition, the presence of torsional (co)homology shows why some D6-brane moduli are lifted, and it suggests how the D-brane discretum appears in type IIA flux compactifications. Finally, we give a clear, geometrical understanding of the Freed-Witten anomaly in the present type IIA setup, and discuss its consequences for the construction of semi-realistic flux vacua.Comment: 35 pages, 1 figure. One reference adde

A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia

Introduction Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. We conducted gene-expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure, such as bacterial pneumonia, and noninfective systemic inflammatory response syndrome. Methods Whole-blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene-expression beadarrays. Differentially expressed genes were determined by linear mixed-model analysis and overrepresented biological pathways determined by using GeneGo MetaCore. Results The gene-expression profile of H1N1 influenza A pneumonia was distinctly different from those of bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene-expression profile is characterized by upregulation of genes from cell-cycle regulation, apoptosis, and DNA-damage-response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene-expression profile of influenza infection persisted through 5 days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection in whom bacterial co-infection subsequently developed, the influenza gene-expression signature remained unaltered, despite the presence of a superimposed bacterial infection. Conclusions The whole-blood expression-profiling data indicate that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed the identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly

A Conformally Invariant Holographic Two-Point Function on the Berger Sphere

We apply our previous work on Green's functions for the four-dimensional quaternionic Taub-NUT manifold to obtain a scalar two-point function on the homogeneously squashed three-sphere (otherwise known as the Berger sphere), which lies at its conformal infinity. Using basic notions from conformal geometry and the theory of boundary value problems, in particular the Dirichlet-to-Robin operator, we establish that our two-point correlation function is conformally invariant and corresponds to a boundary operator of conformal dimension one. It is plausible that the methods we use could have more general applications in an AdS/CFT context.Comment: 1+49 pages, no figures. v2: Several typos correcte

Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function

BACKGROUND: Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain. There are several important HPE mutational target genes, including the transcription factor SIX3, which encodes an early regulator of Shh, Wnt, Bmp and Nodal signalling expressed in the developing forebrain and eyes of all vertebrates. OBJECTIVE: To characterise genetic and clinical findings in patients with SIX3 mutations. METHODS: Patients with HPE and their family members were tested for mutations in HPE-associated genes and the genetic and clinical findings, including those for additional cases found in the literature, were analysed. The results were correlated with a mutation-specific functional assay in zebrafish. RESULTS: In a cohort of patients (n = 800) with HPE, SIX3 mutations were found in 4.7% of probands and additional cases were found through testing of relatives. In total, 138 cases of HPE were identified, 59 of whom had not previously been clinically presented. Mutations in SIX3 result in more severe HPE than in other cases of non-chromosomal, non-syndromic HPE. An over-representation of severe HPE was found in patients whose mutations confer greater loss of function, as measured by the functional zebrafish assay. The gender ratio in this combined set of patients was 1.5:1 (F:M) and maternal inheritance was almost twice as common as paternal. About 14% of SIX3 mutations in probands occur de novo. There is a wide intrafamilial clinical range of features and classical penetrance is estimated to be at least 62%. CONCLUSIONS: Our data suggest that SIX3 mutations result in relatively severe HPE and that there is a genotype-phenotype correlation, as shown by functional studies using animal models

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

Peer reviewe