Genomic organization and chromosomal localization of the murine 2 P domain potassium channel gene Kcnk8: conservation of gene structure in 2 P domain potassium channels.

A 2 P domain potassium channel expressed in eye, lung, and stomach, Kcnk8, has recently been identified. To initiate further biochemical and genetic studies of this channel, we assembled the murine Kcnk8 cDNA sequence, characterized the genomic structure of the Kcnk8 gene, determined its chromosomal localization, and analyzed its activity in a Xenopus laevis oocyte expression system. The composite cDNA has an open reading frame of 1029 bp and encodes a protein of 343 amino acids with a predicted molecular mass of 36 kDa. Structure analyses predict 2 P domains and four potential transmembrane helices with a potential single EF-hand motif and four potential SH3-binding motifs in the COOH-terminus. Cloning of the Kcnk8 chromosomal gene revealed that it is composed of three exons distributed over 4 kb of genomic DNA. Genome database searching revealed that one of the intron/exon boundaries identified in Kcnk8 is present in other mammalian 2 P domain potassium channels genes and many C. elegans 2P domain potassium channel genes, revealing evolutionary conservation of gene structure. Using fluorescence in situ hybridization, the murine Kcnk8 gene was mapped to chromosome 19, 2B, the locus of the murine dancer phenotype, and syntenic to 11q11-11q13, the location of the human homologue. No significant currents were generated in a Xenopus laevis oocyte expression system using the composite Kcnk8 cDNA sequence, suggesting, like many potassium channels, additional channel subunits, modulator substances, or cellular chaperones are required for channel function

Increase of Effective String Tension and Production of Strange Particles

The increase of effective string tension as a result of the hard gluon kinks on a string is investigated using a parametrization form. In this form the effective string tension increasing with energies in hadron-hadron collisions is due to the mini-jet (gluon) production in the collisions. The data of the energy dependence of the strange quark suppression factor in hh collisions are very well reproduced with this mechanism. Meanwhile, the experimental phenomena of approximate energy independence of the strange quark suppression factor in e$^+$e$^-$-annihilations are discussed.Comment: LaTeX, 2 figure

Monopoles and Holography

We present a holographic theory in AdS_4 whose zero temperature ground state develops a crystal structure, spontaneously breaking translational symmetry. The crystal is induced by a background magnetic field, but requires no chemical potential. This lattice arises from the existence of 't Hooft-Polyakov monopole solitons in the bulk which condense to form a classical object known as a monopole wall. In the infra-red, the magnetic field is screened and there is an emergent SU(2) global symmetry.Comment: 33 pages, 16 figures; v2: ref adde

In vitro synergy and enhanced murine brain penetration of saquinavir coadministered with mefloquine.

Highly active antiretroviral therapy has substantially improved prognosis in human immunodeficiency virus (HIV). However, the integration of proviral DNA, development of viral resistance, and lack of permeability of drugs into sanctuary sites (e.g., brain and lymphocyte) are major limitations to current regimens. Previous studies have indicated that the antimalarial drug chloroquine (CQ) has antiviral efficacy and a synergism with HIV protease inhibitors. We have screened a panel of antimalarial compounds for activity against HIV-1 in vitro. A limited efficacy was observed for CQ, mefloquine (MQ), and mepacrine (MC). However, marked synergy was observed between MQ and saquinavir (SQV), but not CQ in U937 cells. Furthermore, enhancement of the antiviral activity of SQV and four other protease inhibitors (PIs) by MQ was observed in MT4 cells, indicating a class specific rather than a drug-specific phenomenon. We demonstrate that these observations are a result of inhibition of multiple drug efflux proteins by MQ and that MQ also displaces SQV from orosomucoid in vitro. Finally, coadministration of MQ and SQV in CD-1 mice dramatically altered the tissue distribution of SQV, resulting in a >3-fold and >2-fold increase in the tissue/blood ratio for brain and testis, respectively. This pharmacological enhancement of in vitro antiviral activity of PIs by MQ now warrants further examination in vivo

A Qualitative Exploration of the Role of Vape Shop Environments in Supporting Smoking Abstinence

E-cigarettes are the most popular method of quitting smoking in England and most are purchased in specialist vape shops. This qualitative study explores how the vape shop environment is experienced by quitters to support smoking abstinence. Semi-structured qualitative interviews were conducted to elicit experiences of e-cigarette use, including experiences of vape shops, in 40 people who had used e-cigarettes in a quit attempt. Observations of six shops in a range of locations were also undertaken. Interview and observation data were analysed using inductive thematic analysis and triangulated. At an individual level, smoking abstinence was supported through shop assistants’ attempts to understand customers’ smoking preferences in order to: (i) tailor advice about the most appropriate product; and (ii) offer an ongoing point of contact for practical help. At an interpersonal level, shops offered opportunity to socialise and reinforce a vaping identity, although the environment was perceived as intimidating for some (e.g., new and female users). At a structural level, shops ensured easy access to products perceived to be good value by customers and had adapted to legislative changes. Vape shops can provide effective behavioural support to quitters to maintain smoking abstinence. Health professionals could capitalise on this through partnership working with shops, to ensure best outcomes for clients wanting to use e-cigarettes to quit smoking

Contact Manifolds, Contact Instantons, and Twistor Geometry

Recently, Kallen and Zabzine computed the partition function of a twisted supersymmetric Yang-Mills theory on the five-dimensional sphere using localisation techniques. Key to their construction is a five-dimensional generalisation of the instanton equation to which they refer as the contact instanton equation. Subject of this article is the twistor construction of this equation when formulated on K-contact manifolds and the discussion of its integrability properties. We also present certain extensions to higher dimensions and supersymmetric generalisations.Comment: v3: 28 pages, clarifications and references added, version to appear in JHE

The potential role of Antarctic krill faecal pellets in efficient carbon export at the marginal ice zone of the South Orkney Islands in spring

Antarctic krill (Euphausia superba) play a central role in the food web of the Southern Ocean, forming a link between primary production and large predators. Krill produce large, faecal pellets (FP) which can form a large component of mesopelagic particulate organic carbon (POC) fluxes. However, the patchy distribution of krill swarms, highly variable pellet composition, and variable sinking and attenuation rates means that these episodic, but potentially large, carbon fluxes are difficult to sample or model. We measured particle flux and type using Marine Snow Catchers (MSC) in the marginal ice zone near the South Orkneys, Antarctica. Krill FP were the dominant component of the POC flux in the upper 200 m (typically 60–85%). FP sinking velocities measured onboard were highly variable (15–507 m d− 1) but overall high, with mean equivalent velocities of 172, 267, and 161 m d− 1 at our three stations. The high numbers of krill FP sinking through the mesopelagic suggest that krill FP can be transferred efficiently and/or that rates of krill FP production are high. We compared our direct MSC-derived estimates of krill FP POC flux (33–154 mg C m− 2 d− 1) and attenuation to estimates of krill FP production based on previous measurements of krill density and literature FP egestion rates, and estimated net krill FP attenuation rates in the upper mesopelagic. Calculated attenuation rates are sensitive to krill densities in the overlying water column but suggest that krill FP could be transferred efficiently through the upper mesopelagic, and, in agreement with our MSC attenuation estimates, could make large contributions to bathypelagic POC fluxes. Our study contrasts with some others which suggest rapid FP attenuation, highlighting the need for further work to constrain attenuation rates and assess how important the contribution of Antarctic krill FP could be to the Southern Ocean biological carbon pump

Exercise intolerance at high altitude (5050 m): critical power and W'

The relationship between work rate (WR) and its tolerable duration (t(LIM)) has not been investigated at high altitude (HA). At HA (5050 m) and at sea level (SL), six subjects therefore performed symptom-limited cycle-ergometry: an incremental test (IET) and three constant-WR tests (% of IET WR(max), HA and SL respectively: WR(1) 70±8%, 74±7%; WR(2) 86±14%, 88±10%; WR(3) 105±13%, 104±9%). The power asymptote (CP) and curvature constant (W') of the hyperbolic WR-t(LIM) relationship were reduced at HA compared to SL (CP: 81±21 vs. 123±38 W; W': 7.2±2.9 vs. 13.1±4.3 kJ). HA breathing reserve (estimated maximum voluntary ventilation minus end-exercise ventilation) was also compromised (WR(1): 25±25 vs. 50±18 l min(-1); WR(2): 4±23 vs. 38±23 l min(-1); WR(3): -3±18 vs. 32±24 l min(-1)) with near-maximal dyspnea levels (Borg) (WR(1): 7.2±1.2 vs. 4.8±1.3; WR(2): 8.8±0.8 vs. 5.3±1.2; WR(3): 9.3±1.0 vs. 5.3±1.5). The CP reduction is consistent with a reduced O(2) availability; that of W' with reduced muscle-venous O(2) storage, exacerbated by ventilatory limitation and dyspnea. Copyright © 2011 Elsevier B.V. All rights reserved

Can HRCT be used as a marker of airway remodelling in children with difficult asthma?

BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with D