Budd Revisited - Gambling in Great Britain 15 Years On

In 2000, Sir Alan Budd, the noted economist was asked by the British Government to chair a review of the nation’s gambling laws. The resulting ‘The Report of the Gambling Review Body’ (referred to here as ‘The Budd Report’ or ‘Budd’) was published a year later and provided a blueprint for how gaming and betting would subsequently be regulated under a major new piece of legislation - the Gambling Act 2005 (the ‘2005 Act’ or the ‘Gambling Act’). The work of the Gambling Review Body (the ‘Review Body’) was undertaken at considerable expense and effort – more than 200 submissions were evaluated, 20 evidence gathering sessions were held, a number of overseas jurisdictions were visited. In the end, a 201-page report was produced. The Review Body’s 176 recommendations for how gambling ought to be regulated were based upon a set of explicitly stated policy objectives designed to further the interests of the British consumer - balancing extended choice with enhanced protections. It was the last time that gambling was subjected to such intense scrutiny in Great Britain; the last time that such a wide variety of regulatory options were weighed with such consideration. It is to be lamented that in the 15 years since the publication of the Budd Report – a period of profound change in the British gambling market – there has been no systematic attempt to assess whether the ambitions of the Review Body have been achieved. The aim of this essay is to do precisely that – to examine how gambling in Great Britain has developed through the prism of Budd’s aspirations

Influencing FTO thin film growth with thin seeding layers: a route to microstructural modification

We report on the seeded growth of fluorine doped tin oxide (FTO) polycrystalline transparent conducting oxide (TCO) thin films on float glass using a novel two-step chemical vapour deposition (CVD) method. Aerosol-assisted CVD (AACVD) was used to grow a seed layer to direct and promote full film growth via an atmospheric pressure CVD (APCVD) overlay. The method allowed for reproducible control over morphology and denser, rougher, higher-performing TCO at a relatively low growth temperature (500 °C). Growth promotion depended on seeding time with an optimal seeding time being present, below which morphology control and conformal coverage was unavailable. The film properties and functional characteristics were characterised by SEM, AFM, XRD, XPS, UV-Vis-Near IR transmittance-reflectance and Hall Effect probe measurements. Highly transparent and electrically conductive films, comparable to commercial materials and with high roughness and low transmission haze values indicate the process yields high quality films with a controllable morphology that can be tuned to desired application. The versatile method provides a route towards the morphological control of high-quality FTO thin films with high optical clarity and low-emissivity properties and can be readily extended to a variety of different substrates and metal oxide materials

Pregnancy outcome following gestational exposure to azithromycin

BACKGROUND: Azithromycin is an azalide antibiotic with an extensive range of indications and has become a common treatment option due to its convenient dosing regimen and therapeutic advantages. Human studies addressing gestational use of azithromycin have primarily focused on antibiotic efficacy rather than fetal safety. Our primary objective was to evaluate the possibility of teratogenic risk following gestational exposure to azithromycin. METHODS: There were 3 groups of pregnant women enrolled in our study: 1) women who took azithromycin. 2) women exposed to non-teratogenic antibiotics for similar indications, and 3) women exposed to non-teratogenic agents. They were matched for gestational age at time of call, maternal age, cigarette and alcohol consumption. Rates of major malformations and other endpoints of interest were compared among the three groups. RESULTS: Pregnancy outcome of 123 women in each group was ascertained. There were no statistically significant differences among the three groups in the rates of major malformations; 3.4% (exposed) versus 2.3% (disease matched) and 3.4% (non teratogen) or any other endpoints that were examined. In the azithromycin group, 88 (71.6%) women took the drug during the first trimester CONCLUSION: Results suggest that gestational exposure to azithromycin is not associated with an increase in the rate of major malformations above the baseline of 1–3%. Our data adds to previous research showing that macrolide antibiotics, as a group, are generally safe in pregnancy and provides an evidence-based option for health professionals caring for populations with chlamydia

The novel Fh8 and H fusion partners for soluble protein expression in Escherichia coli : a comparison with the traditional gene fusion technology

The Escherichia coli host system is an advantageous choice for simple and inexpensive recombinant protein production but it still presents bottlenecks at expressing soluble proteins from other organisms. Several efforts have been taken to overcome E. coli limitations, including the use of fusion partners that improve protein expression and solubility. New fusion technologies are emerging to complement the traditional solutions. This work evaluates two novel fusion partners, the Fh8 tag (8 kDa) and the H tag (1 kDa), as solubility enhancing tags in E. coli and their comparison to commonly used fusion partners. A broad range comparison was conducted in a small-scale screening and subsequently scaled-up. Six difficult-to-express target proteins (RVS167, SPO14, YPK1, YPK2, Frutalin and CP12) were fused to eight fusion tags (His, Trx, GST, MBP, NusA, SUMO, H and Fh8). The resulting protein expression and solubility levels were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis before and after protein purification and after tag removal. The Fh8 partner improved protein expression and solubility as the well-known Trx, NusA or MBP fusion partners. The H partner did not function as a solubility tag. Cleaved proteins from Fh8 fusions were soluble and obtained in similar or higher amounts than proteins from the cleavage of other partners as Trx, NusA or MBP. The Fh8 fusion tag therefore acts as an effective solubility enhancer, and its low molecular weight potentially gives it an advantage over larger solubility tags by offering a more reliable assessment of the target protein solubility when expressed as a fusion protein.The financial support of the EMBL Heidelberg, Germany and Fundacao para a Ciencia e Tecnologia (FCT), Portugal, is acknowledged: the fellowship SFRH/BD/46482/2008 to Sofia J. Costa and the project PTDC/CVT/103081/2008. The authors wish to acknowledge Anne-Claude Gavin for providing four of the constructs for this study (RVS167, SPO14, YPK1, and YPK2) and Emmanuel Poilpre for the experimental help (both from the EMBL Heidelberg, Germany)

The JAK inhibitor AZD1480 regulates proliferation and immunity in Hodgkin lymphoma

Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been reported to promote proliferation and survival of Hodgkin and Reed–Sternberg cells of Hodgkin lymphoma (HL). We investigated the activity of the JAK inhibitor AZD1480 in HL-derived cell lines and determined its mechanisms of action. AZD1480 at low doses (0.1–1 μ) potently inhibited STATs phosphorylation, but did not predictably result in antiproliferative effects, as it activated a negative-feedback loop causing phosphorylation of JAK2 and extracellular signal-regulated kinases 1 and 2 (ERK1/2), and increased IP-10, RANTES and interleukin (IL)-8 concentrations in the supernatants. Inhibition of the ERK activity by mitogen-activated extracellular signal regulated kinase (MEK) inhibitors (UO126 and PD98059) enhanced the cytotoxic activity of AZD1480. Interestingly, submicromolar concentrations of AZD1480 demonstrated significant immunoregulatory effects by downregulating T-helper 2 cytokines and chemokines, including IL-13 and thymus- and activation-regulated chemokine, and the surface expression of the immunosuppressive programmed death ligands 1 and 2. Higher concentrations of AZD1480 (5 μ) induced G2/M arrest and cell death by inhibiting Aurora kinases. Our study demonstrates that AZD1480 regulates proliferation and immunity in HL cell lines and provides mechanistic rationale for evaluating AZD1480 alone or in combination with MEK inhibitors in HL

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

Structural Basis for GTP-Dependent Dimerization of Hydrogenase Maturation Factor HypB

Maturation of [NiFe]-hydrogenase requires the insertion of iron, cyanide and carbon monoxide, followed by nickel, to the catalytic core of the enzyme. Hydrogenase maturation factor HypB is a metal-binding GTPase that is essential for the nickel delivery to the hydrogenase. Here we report the crystal structure of Archeoglobus fulgidus HypB (AfHypB) in apo-form. We showed that AfHypB recognizes guanine nucleotide using Asp-194 on the G5 loop despite having a non-canonical NKxA G4-motif. Structural comparison with the GTPγS-bound Methanocaldococcus jannaschii HypB identifies conformational changes in the switch I region, which bring an invariant Asp-72 to form an intermolecular salt-bridge with another invariant residue Lys-148 upon GTP binding. Substitution of K148A abolished GTP-dependent dimerization of AfHypB, but had no significant effect on the guanine nucleotide binding and on the intrinsic GTPase activity. In vivo complementation study in Escherichia coli showed that the invariant lysine residue is required for in vivo maturation of hydrogenase. Taken together, our results suggest that GTP-dependent dimerization of HypB is essential for hydrogenase maturation. It is likely that a nickel ion is loaded to an extra metal binding site at the dimeric interface of GTP-bound HypB and transferred to the hydrogenase upon GTP hydrolysis

Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse

Interaction between Hydrogenase Maturation Factors HypA and HypB Is Required for [NiFe]-Hydrogenase Maturation

The active site of [NiFe]-hydrogenase contains nickel and iron coordinated by cysteine residues, cyanide and carbon monoxide. Metal chaperone proteins HypA and HypB are required for the nickel insertion step of [NiFe]-hydrogenase maturation. How HypA and HypB work together to deliver nickel to the catalytic core remains elusive. Here we demonstrated that HypA and HypB from Archaeoglobus fulgidus form 1∶1 heterodimer in solution and HypA does not interact with HypB dimer preloaded with GMPPNP and Ni. Based on the crystal structure of A. fulgidus HypB, mutants were designed to map the HypA binding site on HypB. Our results showed that two conserved residues, Tyr-4 and Leu-6, of A. fulgidus HypB are required for the interaction with HypA. Consistent with this observation, we demonstrated that the corresponding residues, Leu-78 and Val-80, located at the N-terminus of the GTPase domain of Escherichia coli HypB were required for HypA/HypB interaction. We further showed that L78A and V80A mutants of HypB failed to reactivate hydrogenase in an E. coli ΔhypB strain. Our results suggest that the formation of the HypA/HypB complex is essential to the maturation process of hydrogenase. The HypA binding site is in proximity to the metal binding site of HypB, suggesting that the HypA/HypB interaction may facilitate nickel transfer between the two proteins

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration