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

Labour politics and society in South Yorkshire.

This doctoral thesis looks at Labour politics and society in South Yorkshire between the start of the Second World War in September 1939 and the fall from office of the Attlee Labour Government in October 1951. While it accepts the predominating effects of national and international factors in providing challenges which Labour councils and local Labour Parties had to find solutions to - such as the effects of the Sheffield Blitz in 1940 and the need to re-plan Sheffield and the maintaining of the organisational existence of Labour Parties during the Second World War - it nevertheless examines those 'micro-historical' factors which made for the local diversity of the party in South Yorkshire. It tries to create a holistic and rounded portrait of the local Labour movement based mainly on fragmentary archival and newspaper evidence and examines current historical debates for local relevance such as whether a post-war consensus actually existed, whether popular political attitudes were radical or conservative and, whether such popular attitudes favoured or disfavoured Labour. It also looks at Marxist debates over the concept of 'Labourism' and whether Labour was narrowly culturally determined or whether other factors were equally important. Chapter One introduces the thesis. Chapter Two examines the fears over the post-war industrial future of Sheffield which took place during the Second World War within the City Council and between it and organisations like the trade unions and the Chamber of Commerce. It also looks at City Council debates over the proposed post-war regionalisation of local government and how that was prevented by a united council. This shows that the centralising tendencies of the London government could be resisted by the peripheries and that such tendencies were not inevitable. Chapter Three examines town planning in Sheffield during the Second World War after the Blitz in December 1940 provided an opportunity to create a more modem, better planned and less ugly city. The planning process is examined and the secrecy of the City Council noted at a time when the country was fighting to defend an open and democratic society from the Nazis. Chapter Three also looks at the wartime context of the acute post-war housing crisis. Chapter Four looks at the wartime Labour Party in South Yorkshire, its ebb in membership prior to 1942 and its resurgence after that date ending with an examination of the 1945 General Election in Sheffield. Chapter Five looks at local government between 1945 and 1951, examining the factors which prevented the reform of the local structure of local government, the effect on Sheffield and Rotherham Councils of the nationalisation of electricity, gas and local authority hospitals, and the attempts to implement the Butler Education Act of 1944 in South Yorkshire. Chapter Six looks at the attempts to implement the 1945 Collie town plan for Sheffield and the reasons for the lack of progress as well as at the contrasting housing records of Sheffield and Rotherham Councils. It attempts to account for the latter's better record when compared with the former. Chapter Seven looks the ideology and cultural determinants of the Labour Party in South Yorkshire between 1945 and 1951. It also examines Labour organisation noting the essential role of women as unpaid voluntary labour and contrasting it with their limited entry to local political office. Finally it looks at and comments on the municipal and general election results in Sheffield of the Labour Party between 1945 and 1951. Chapter Eight provides a conclusion

Global Law as Intercontextuality and as Interlegality

Since the 1990s the effects of globalization on law and legal developments has been a central topic of scholarly debate. To date, the debate is however marked by three substantial deficiencies which this chapter seeks to remedy through a reconceptualization of global law as a law of inter-contextuality expressed through inter-legality and materialized through a particular body of legal norms which can be characterized as connectivity norms. The first deficiency is a historical and empirical one. Both critics as well as advocates of ‘non-state law’ share the assumption that ‘law beyond the state’ and related legal norms have gained in centrality when compared with previous historical times. While global law, including both public and private global governance law as well as regional occurrences such as EU law, has undergone profound transformations since the structural transformations which followed the de-colonialization processes of the mid-twentieth century, we do not have more global law relatively to other types of law today than in previous historical times. The second deficiency is a methodological one. The vast majority of scholarship on global law is either of an analytical nature, drawing on insights from philosophy, or empirically observing the existence of global law and the degree of compliance with global legal norms at a given moment in time. While both approaches bring something to the table they remain static approaches incapable of explaining and evaluating the transformation of global law over time. The third deficiency is a conceptual-theoretical one. In most instances, global law is understood as a unitary law producing singular legal norms with a planetary reach, or, alternatively, a radical pluralist perspective is adopted dismissing the existence of singular global norms. Both of these approaches however misapprehend the structural characteristics, function and societal effects of global law. Instead a third positon between unitary and radical pluralist perspectives can be adopted through an understanding of global law and its related legal norms as a de-centred kind of inter-contextual law characterised by inter-legality

Model-independent search for CP violation in D0→K−K+π−π+ and D0→π−π+π+π− decays

A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states K−K+π−π+ and π−π+π+π− is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fb−1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the K−K+π−π+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the π−π+π+π− final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity

Search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓

A search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓ is performed with a data sample, corresponding to an integrated luminosity of 1.0  fb-1 of pp collisions at √s=7  TeV, collected by the LHCb experiment. The observed number of Bs0→e±μ∓ and B0→e±μ∓ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0→e±μ∓)101  TeV/c2 and MLQ(B0→e±μ∓)>126  TeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds

Measurement of B meson production cross-sections in proton-proton collisions at √s= 7 TeV

The production cross-sections of B mesons are measured in pp collisions at a centre-of-mass energy of 7 TeV using data collected with the LHCb detector corresponding to a integrated luminosity of 0.36fb−1. The B+, B0 and B0s mesons are reconstructed in the exclusive decays B+→J/ψK+, B0→J/ψK∗0 and B0s→J/ψϕ, with J/ψ→μ+μ−, K∗0→K+π− and ϕ→K+K−. The differential cross-sections are measured as functions of B meson transverse momentum pT and rapidity y, in the range 0 < pT<40GeV/c2 and 2.0<y<4.5. The integrated cross-sections in the same pT and y ranges, including charge-conjugate states, are measured to be σ(pp→B++X)=38.9±0.3(stat.)±2.5(syst.)±1.3(norm.)μb, σ(pp→B0+X)=38.1±0.6(stat.)±3.7(syst.)±4.7(norm.)μb, σ(pp→B0s+X)=10.5±0.2(stat.)±0.8(syst.)±1.0(norm.)μb, where the third uncertainty arises from the pre-existing branching fraction measurements

Study of DJ meson decays to D+π−, D0π+ and D∗+π− final states in pp collisions

A study of D+π−, D0π+ and D∗+π− final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fb−1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D1(2420)0 resonance is observed in the D∗+π− final state and the D∗2(2460) resonance is observed in the D+π−, D0π+ and D∗+π− final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the D∗+π−, D+π− and D0π+ final states

Searches for B0(s)→J/ψppˉ and B+→J/ψppˉπ+ decays

The results of searches for B0(s)→J/ψ pp¯ and B + → J/ψ p p¯ π+ decays are reported. The analysis is based on a data sample, corresponding to an integrated luminosity of 1.0 fb−1 of pp collisions, collected with the LHCb detector. An excess with 2.8 σ significance is seen for the decay B0s→J/ψ pp¯ and an upper limit on the branching fraction is set at the 90 % confidence level: B(B0s→J/ψ pp¯) < 4.8 × 10−6, which is the first such limit. No significant signals are seen for B0 → J/ψ pp¯ and B+ → J/ψ pp¯ π + decays, for which the corresponding limits are set: B(B0→J/ψ pp¯) < 5.2 × 10−7, which significantly improves the existing limit; and B(B+→J/ψ pp¯π+) < 5.0 × 10−7, which is the first limit on this branching fraction