Evolutionary analysis of the TPP-dependent enzyme family

The evolutionary relationships of the thiamine pyrophosphate (TPP)-dependent family of enzymes was investigated by generation of a neighbor joining phylogenetic tree using sequences from the conserved pyrophosphate (PP) and pyrimidine (Pyr) binding domains of 17 TPP-dependent enzymes. This represents the most comprehensive analysis of TPP-dependent enzyme evolution to date. The phylogeny was shown to be robust by comparison with maximum likelihood trees generated for each individual enzyme and also broadly confirms the evolutionary history proposed recently from structural comparisons alone (Duggleby 2006). The phylogeny is most parsimonious with the TPP enzymes having arisen from a homotetramer which subsequently diverged into an α2β2 heterotetramer. The relationship between the PP- and Pyr-domains and the recruitment of additional protein domains was examined using the transketolase C-terminal (TKC)-domain as an example. This domain has been recruited by several members of the family and yet forms no part of the active site and has unknown function. Removal of the TKC-domain was found to increase activity toward β-hydroxypyruvate and glycolaldehyde. Further truncations of the Pyr-domain yielded several variants with retained activity. This suggests that the influence of TKC-domain recruitment on the evolution of the mechanism and specificity of transketolase (TK) has been minor, and that the smallest functioning unit of TK comprises the PP- and Pyr-domains, whose evolutionary histories extend to all TPP-dependent enzymes

Case studies of outdoor testing and analysis of building components

The construction and development of the PASSYS/PASLINK outdoor test cells were funded by the European Commission, with the objective of providing high-quality test environments for quantifying the performance of passive solar building components. Over the years since the original test cells were commissioned, the initial concept for outdoor testing has been extended to include other test cell types. Significant improvements have been made to the experimental procedures and analysis techniques, and a broad range of components has been tested. This paper describes representative experiments that have been conducted using these highly controlled outdoor test environments, indicates some of the related analysis, and shows the type of information that can be obtained from such tests. It demonstrates the way in which component performance can be ascertained in the realistic external environment. The case studies chosen range from building component tests within EC research projects to commercial tests, and from conventional building components to novel integrated facade systems. They also include a large range of passive and active components. Each case study summarises the test component, the purpose of the test, details of the test configuration (period of test, instrumentation, etc.), results and analysis, and associated modelling and monitoring where appropriate. The paper concludes with an appraisal of the advantages and limitations of the test cells for the various component types

Practical ultrasonographic technique to precisely identify and differentiate tendons and ligaments of the elbow at the level of the humeral epicondyles: anatomical study.

To develop a practical step-by-step technique to precisely identify and differentiate tendons and ligaments attaching to the humeral epicondyles, to confirm through gross anatomical study the accurate structure identification provided by this technique and to determine the frequency at which each structure can be identified in healthy volunteers. First, ten fresh frozen cadavers (6 men, age at death = 58-92 years) were examined by two musculoskeletal radiologists and a step-by-step technique for the identification of tendons and ligaments at the level of humeral epicondyles was developed. Second, the accurate identification of structures was confirmed through gross anatomical study including anatomical sections on five specimens and layer-by-layer dissection technique on five others. Finally, 12 healthy volunteers (6 men, average age = 36, range = 28-52) were scanned by two radiologists following the same technique. An ultrasonographic technique based on the recognition of bony landmarks and the use of ultrasonographic signs to differentiate overlapping structures was developed and validated through gross anatomical study. In healthy volunteers, most tendons and ligaments were identified and well-defined in ≥ 80% of cases, except for the extensor carpi radialis brevis and extensor digiti minimi tendons on the lateral epicondyle (having common attachments with the extensor digitorum communis) and the palmaris longus tendon on the medial epicondyle (absent, or common attachment with the flexor carpi radialis). A step-by-step approach to the ultrasonographic assessment of tendons and ligaments at the humeral epicondyles allowed accurate identification of and differentiation among these structures, in particular those relevant to pathological conditions

Suppression of human papillomavirus gene expression in vitro and in vivo by herpes simplex virus type 2 infection

AbstractRecent epidemiological studies have found that women infected with both herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) type 16 or HPV-18 are at greater risk of developing cervical carcinoma compared to women infected with only one virus. However, it remains unclear if HSV-2 is a cofactor for cervical cancer or if HPV and HSV-2 interact in any way. We have studied the effect of HSV-2 infection on HPV-11 gene expression in an in vitro double-infection assay. HPV transcripts were down-regulated in response to HSV-2 infection. Two HSV-2 vhs mutants failed to reduce HPV-16 E1^E4 transcripts. We also studied the effect of HSV-2 infection on preexisting experimental papillomas in a vaginal epithelial xenograft model. Doubly infected grafts demonstrated papillomatous transformation and the classical cytopathic effect from HSV-2 infection. HPV and HSV DNA signals were mutually exclusive. These studies may have therapeutic applications for HPV infections and related neoplasms

Construction of the Pauli-Villars-regulated Dirac vacuum in electromagnetic fields

Using the Pauli-Villars regularization and arguments from convex analysis, we construct solutions to the classical time-independent Maxwell equations in Dirac's vacuum, in the presence of small external electromagnetic sources. The vacuum is not an empty space, but rather a quantum fluctuating medium which behaves as a nonlinear polarizable material. Its behavior is described by a Dirac equation involving infinitely many particles. The quantum corrections to the usual Maxwell equations are nonlinear and nonlocal. Even if photons are described by a purely classical electromagnetic field, the resulting vacuum polarization coincides to first order with that of full Quantum Electrodynamics.Comment: Final version to appear in Arch. Rat. Mech. Analysi

Lack of association between KIR and HLA-C type and susceptibility to idiopathic bronchiectasis

SummaryIntroductionIdiopathic bronchiectasis is a poorly defined disease characterised by persistent inflammation, infection and progressive lung damage. Natural killer (NK) cells provide a major defense against infection, through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIR), and human leukocyte antigens (HLA) class I molecules. Homozygosity for HLA-C has been shown in a single study to confer increased genetic susceptibility to idiopathic bronchiectasis. We aimed to assess whether the KIR and HLA repertoire, alone or in combination, may influence the risk of developing idiopathic bronchiectasis, in an independent replication study.MethodsIn this prospective, observational, case-control association study, 79 idiopathic bronchiectasis patients diagnosed following extensive aetiological investigation were compared with 98 anonymous, healthy, age, sex and ethnically-matched controls attending blood donor sessions in the same geographical location. DNA extraction was performed according to standardised techniques. Determination of presence or absence of KIR genes was performed by a sequence specific oligonucleotide probe method. Allele frequencies for the proposed KIR, HLA-B and HLA-C risk alleles both individually and in combinations were compared.ResultsWe found no significant differences in allele frequency between the idiopathic bronchiectasis and control samples, whether considering HLA-C group homozygosity alone or in combination with the KIR type.DiscussionOur results do not show an association between HLA-C and KIR and therefore do not confirm previous positive findings. This may be explained by the lower frequency of HLA-C1 group homozygosity in the control population of the previous study (27.2%), compared to 42.3% in our study, which is consistent with the genetic profiling of control groups across the UK. The previous positive association study may therefore have been driven by an anomalous control group. Further larger prospective multicentre replication studies are needed to determine if an association exists

Evaluation of the potential for virus dispersal during hand drying: a comparison of three methods

Aims To use a MS2 bacteriophage model to compare three hand-drying methods, paper towels (PT), a warm air dryer (WAD) and a jet air dryer (JAD), for their potential to disperse viruses and contaminate the immediate environment during use. Methods and Results Participants washed their gloved hands with a suspension of MS2 bacteriophage and hands were dried with one of the three hand-drying devices. The quantity of MS2 present in the areas around each device was determined using a plaque assay. Samples were collected from plates containing the indicator strain, placed at varying heights and distances and also from the air. Over a height range of 0.15-1.65 m, the JAD dispersed an average of >60 and >1300-fold more plaque-forming units (pfu) compared to the WAD and PT (P 20 and >190-fold more pfu in total compared to WAD and PT at all distances tested up to 3 m (P 50 and >100-fold more pfu compared to the WAD and PT (P <0.001), respectively. Conclusions Use of the JAD lead to significantly greater and further dispersal of MS2 bacteriophage from artificially contaminated hands when compared to the WAD and PT. Significance and Impact of Study The choice of hand drying device should be considered carefully in areas where infection prevention concerns are paramount, such as healthcare settings and the food industry

More on scattering of Chern-Simons vortices

I derive a general formalism for finding kinetic terms of the effective Lagrangian for slowly moving Chern-Simons vortices. Deformations of fields linear in velocities are taken into account. From the equations they must satisfy I extract the kinetic term in the limit of coincident vortices. For vortices passing one over the other there is locally the right-angle scattering. The method is based on analysis of field equations instead of action functional so it may be useful also for nonvariational equations in nonrelativistic models of Condensed Matter Physics.Comment: discussion around Eq.(45) is generalised, one more condition for the local right-angle scattering is adde

Twistors and Black Holes

Motivated by black hole physics in N=2, D=4 supergravity, we study the geometry of quaternionic-Kahler manifolds M obtained by the c-map construction from projective special Kahler manifolds M_s. Improving on earlier treatments, we compute the Kahler potentials on the twistor space Z and Swann space S in the complex coordinates adapted to the Heisenberg symmetries. The results bear a simple relation to the Hesse potential \Sigma of the special Kahler manifold M_s, and hence to the Bekenstein-Hawking entropy for BPS black holes. We explicitly construct the ``covariant c-map'' and the ``twistor map'', which relate real coordinates on M x CP^1 (resp. M x R^4/Z_2) to complex coordinates on Z (resp. S). As applications, we solve for the general BPS geodesic motion on M, and provide explicit integral formulae for the quaternionic Penrose transform relating elements of H^1(Z,O(-k)) to massless fields on M annihilated by first or second order differential operators. Finally, we compute the exact radial wave function (in the supergravity approximation) for BPS black holes with fixed electric and magnetic charges.Comment: 47 pages, v2: typos corrected, reference added, v3: minor change