Holonomy and parallel transport for Abelian gerbes

In this paper we establish a one-to-one correspondence between $S^1$-gerbes with connections, on the one hand, and their holonomies, for simply connected manifolds, or their parallel transports, in the general case, on the other hand. This result is a higher-order analogue of the familiar equivalence between bundles with connections and their holonomies for connected manifolds. The holonomy of a gerbe with group $S^1$ on a simply connected manifold $M$ is a group morphism from the thin second homotopy group to $S^1$, satisfying a smoothness condition, where a homotopy between maps from $[0,1]^2$ to $M$ is thin when its derivative is of rank $\leq 2$. For the non-simply connected case, holonomy is replaced by a parallel transport functor between two monoidal Lie groupoids. The reconstruction of the gerbe and connection from its holonomy is carried out in detail for the simply connected case. Our approach to abelian gerbes with connections holds out prospects for generalizing to the non-abelian case via the theory of double Lie groupoids.Comment: Final version. Improved readibility (hopefully). LaTeX, 60 pages, 14 figures. To appear in Advances in Mathematic

Intra-dance variation among waggle runs and the design of efficient protocols for honey bee dance decoding

Noise is universal in information transfer. In animal communication, this presents a challenge not only for intended signal receivers, but also to biologists studying the system. In honey bees, a forager communicates to nestmates the location of an important resource via the waggle dance. This vibrational signal is composed of repeating units (waggle runs) that are then averaged by nestmates to derive a single vector. Manual dance decoding is a powerful tool for studying bee foraging ecology, although the process is time-consuming: a forager may repeat the waggle run 1- >100 times within a dance. It is impractical to decode all of these to obtain the vector; however, intra-dance waggle runs vary, so it is important to decode enough to obtain a good average. Here we examine the variation among waggle runs made by foraging bees to devise a method of dance decoding. The first and last waggle runs within a dance are significantly more variable than the middle run. There was no trend in variation for the middle waggle runs. We recommend that any four consecutive waggle runs, not including the first and last runs, may be decoded, and we show that this methodology is suitable by demonstrating the goodness-of-fit between the decoded vectors from our subsamples with the vectors from the entire dances

Evidence of Titan's Climate History from Evaporite Distribution

Water-ice-poor, 5-$\mu$m-bright material on Saturn's moon Titan has previously been geomorphologically identified as evaporitic. Here we present a global distribution of the occurrences of the 5-$\mu$m-bright spectral unit, identified with Cassini's Visual Infrared Mapping Spectrometer (VIMS) and examined with RADAR when possible. We explore the possibility that each of these occurrences are evaporite deposits. The 5-$\mu$m-bright material covers 1\% of Titan's surface and is not limited to the poles (the only regions with extensive, long-lived surface liquid). We find the greatest areal concentration to be in the equatorial basins Tui Regio and Hotei Regio. Our interpretations, based on the correlation between 5-$\mu$m-bright material and lakebeds, imply that there was enough liquid present at some time to create the observed 5-$\mu$m-bright material. We address the climate implications surrounding a lack of evaporitic material at the south polar basins: if the south pole basins were filled at some point in the past, then where is the evaporite

Conformational Analysis by Nuclear Magnetic Resonance Spectroscopy

Nuclear magnetic resonance spectroscopy is a powerful and versatile spectroscopic technique and novel applications are continually being devised for it. This thesis concerns the application of nmr spectroscopy to the study and definition of both the time dependent and the time independent three dimensional geometries of organic molecules in solution. The purposes of this thesis are: (a) to establish the conceptual background to both nmr spectroscopy and conformational analysis and hence to relate the two fields, (b) to review in varying depth the published results in those areas of chemistry which have been ventured upon in the current research and (c) to present the results and conclus: :ions of the current studies. To these ends, nmr spectroscopy is first briefly reviewed and the areas of major topical interest touched upon. As nmr spectroscopy is a precisely mathematical subject, the theoretical applications later employed are briefly outlined. The thermodynamic considerations relevent to conformational analysis are then reviewed and this is followed by a discussion of the application of nmr spectroscopy to detailed conformational analysis. The current studies involve reviewing two discrete fields of conformational analysis. Firstly, nmr studies of conformations in medium ring compounds are reviewed in depth. The results of a study of syn-3,7-dibromo-cis,cis-cycloocta-1,5-diene are recorded in which a definitive statement of the solution conformation (in chloroform) of this molecule is possible. The consistency of the data from other techniques relating to this conformation is remarked upon and the similarity to the solid state conformation determined (F. B. Wilson, Ph. D. thesis, University of Glasgow, September 1971) by an X-ray study is deduced. Secondly, the vast field of nmr studies in conjugated systems is sketched relatively briefly before the few results relating to aromatic systems are detailed. Work on 9-nitroso, and 9-formyljulolidine rotation; :al barriers for the '9' group are then presented. Extensive electron delocalisation is observed from the nitrogen atom of the quinolizidine unit in these compounds to the '9' group and this is comparable to, or in excess of, that observed in para-substituted dimethylanilines. The rotational barriers for the dimethylamino function in three para-substituted N,N-dimethylanilines are then reported and a Hammett correlation between them is suggested. In this manner, an estimate of the rotational barrier for the dimethylamino function in N,N-dimethylaniline itself is presented. Upon this basis and upon results published for studies of aziridine inversion barriers, an estimate of the resonance energy in dimethylaniline is suggested at 10+/-1 kcal./mole. The necessary practical details of this work are then outlined. The importance of computing facilities in this work is made in the appendices and an original coding of a least squares method due to W. E. Wentworth (J. Chem. Ed. , 1965,42,96) is included. Published papers on this work are then appended

Improving arteriovenous fistula patency : transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation

Creation of an autologous arteriovenous fistula (AVF) for vascular access in haemodialysis is the modality of choice. However neointimal hyperplasia and loss of the luminal compartment result in AVF patency rates of ~60% at 12months. The exact cause of neointimal hyperplasia in the AVF is poorly understood. Vascular trauma has long been associated with hyperplasia. With this in mind in our rabbit model of AVF we simulated cannulation autologous to that undertaken in vascular access procedures and observed significant neointimal hyperplasia as a direct consequence of cannulation. The neointimal hyperplasia was completely inhibited by topical transdermal delivery of the non-steroidal anti-inflammatory (NSAID) diclofenac. In addition to the well documented anti-inflammatory properties we have identified novel anti-proliferative mechanisms demonstrating diclofenac increases AMPK-dependent signalling and reduced expression of the cell cycle protein cyclin D1. In summary prophylactic transdermal delivery of diclofenac to the sight of AVF cannulation prevents adverse neointimal hyperplasic remodelling and potentially offers a novel treatment option that may help prolong AVF patency and flow rates

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Counter and Complicit Masculine Discourse Among Men’s Shed Members

Men’s Sheds is a growing international movement aimed at providing men with places and activities that facilitate social connectedness. Despite Men’s Sheds’ focus on males, little attention has been paid to masculinities within the specific context of these settings. The current study used a gender relations framework to explore the ways in which attendees discussed Men’s Sheds, with particular attention to discussions that were complicit and counter to traditional, hegemonic views of masculinity, and diverse positions in between these binaries. The data consisted of transcripts and field notes from four focus groups comprised of mostly older, White, retired male members of a Canadian shed (N = 22). The analysis revealed three overall themes: (1) focus on work, (2) independence, and (3) need for male-focused spaces. These themes and associated subthemes suggest that shed members ascribe to dominant masculine values and ideals, but also support more fluid and flexible views of masculinity. Implications are discussed for how working with an array of masculinities within the Men’s Sheds movement will be helpful with respect to their future growth in Canada and internationally

The Binding of a Glycoprotein 120 V3 Loop Peptide to HIV-1 Neutralizing Antibodies STRUCTURAL IMPLICATIONS

Abstract The structural and antigenic properties of a peptide ("CRK") derived from the V3 loop of HIV-1 gp120 protein were studied using NMR and SPR techniques. The sequence of CRK corresponds to the central portion of the V3 loop containing the highly conserved "GPGR" residue sequence. Although the biological significance of this conserved sequence is unknown, the adoption of conserved secondary structure (type II β-turn) in this region has been proposed. The tendency of CRK (while free or conjugated to protein), to adopt such structure and the influence of such structure upon CRK antigenicity were investigated by NMR and SPR, respectively. Regardless of conjugation, CRK is conformationally averaged in solution but a weak tendency of the CRK "GPGR" residues to adopt a β-turn conformation was observed after conjugation. The influence of GPGR structure upon CRK antigenicity was investigated by measuring the affinities of two cognate antibodies: "5023A" and "5025A," for CRK, protein-conjugated CRK and gp120 protein. Each antibody bound to all the antigens with nearly the same affinity. From these data, it appears that: (a) antibody binding most likely involves an induced fit of the peptide and (b) the gp120 V3 loop is probably conformationally heterogeneous. Since 5023A and 5025A are HIV-1 neutralizing antibodies, neutralization in these cases appears to be independent of adopted GPGR β-turn structure