BACE1 Polymorphisms Do Not Influence Platelet Membrane β-secretase Activity or Genetic Susceptibility for Alzheimer’s Disease in the Northern Irish Population

ß-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a biological and positional candidate gene for Alzheimer’s disease (AD). BACE1 is a protease that catalyses APP cleavage at the ß-secretase site. We evaluated all common and putatively functional polymorphisms in the genomic region encompassing BACE1 for an association with AD, and for functional effects on platelet ß-secretase activity. Tag SNPs (n = 10) derived from phase II of the International HapMap Project, and a nonsynonymous variant, were successfully genotyped in 901 Caucasian individuals from Northern Ireland using Sequenom iPLEX and TaqMan technologies. APOE genotyping was performed by PCR-RFLP. Platelet membrane ß-secretase activity was assayed in a subset of individuals (n = 311). Hardy–Weinberg equilibrium was observed for all variants. Evidence for an association with AD was observed with multi-marker haplotype analyses (P = 0.01), and with rs676134 when stratified for APOE genotype (P = 0.02), however adjusting for multiple testing negated the evidence for association of this variant with AD. ?2 analysis of genotype and allele frequencies in cases versus controls for individual SNPs revealed no evidence for association (5% level). No genetic factors were observed that significantly influenced platelet membrane ß-secretase activity. We have selected an appropriate subset of variants suitable for comprehensive genetic investigation of the BACE1 gene. Our results suggest that common BACE1 polymorphisms and putatively functional variants have no significant influence on genetic susceptibility to AD, or platelet ß-secretase activity, in this Caucasian Northern Irish population.

In vitro study of the efficacy of acrylic bone cement loaded with supplementary amounts of gentamicin: Effect on mechanical properties, antibiotic release, and biofilm formation

Background: Infection remains a severe complication following a total hip replacement. If infection is suspected when revision surgery is being performed, additional gentamicin is often added to the cement on an ad hoc basis in an attempt to reduce the risk of recurrent infection.

Methods and results: In this in vitro study, we determined the effect of incorporating additional gentamicin on the mechanical properties of cement. We also determined the degree of gentamicin release from cement, and also the extent to which biofilms of clinical Staphylococcus spp. isolates form on cement in vitro. When gentamicin was added to unloaded cement (1–4 g), there was a significant reduction in the mechanical performance of the loaded cements compared to unloaded cement. A significant increase in gentamicin release from the cement over 72 h was apparent, with the amount of gentamicin released increasing significantly with each additional 1 g of gentamicin added. When overt infection was modeled, the incorporation of additional gentamicin did result in an initial reduction in bacterial colonization, but this beneficial effect was no longer apparent by 72 h, with the clinical strains forming biofilms on the cements despite the release of high levels of gentamicin.

Interpretation: Our findings indicate that the addition of large amounts of gentamicin to cement is unlikely to eradicate bacteria present as a result of an overt infection of an existing implant, and could result in failure of the prosthetic joint because of a reduction in mechanical performance of the bone cement.

Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene

Variations in the interleukin 4 receptor A (IL4RA) gene have been reported to be associated with atopy, asthma, and allergy, which may occur less frequently in subjects with type 1 diabetes (T1D). Since atopy shows a humoral immune reactivity pattern, and T1D results from a cellular (T lymphocyte) response, we hypothesised that alleles predisposing to atopy could be protective for T1D and transmitted less often than the expected 50% from heterozygous parents to offspring with T1D. We genotyped seven exonic single nucleotide polymorphisms (SNPs) and the -3223 C>T SNP in the putative promoter region of IL4RA in up to 3475 T1D families, including 1244 Finnish T1D families. Only the -3223 C>T SNP showed evidence of negative association (P=0.014). There was some evidence for an interaction between -3233 C>T and the T1D locus IDDM2 in the insulin gene region (P=0.001 in the combined and P=0.02 in the Finnish data set). We, therefore, cannot rule out a genetic effect of IL4RA in T1D, but it is not a major one.

The Secular Beyond: Free Religious Dissent and Debates over the Afterlife in Nineteenth-Century Germany

Toward the end of the first third of the nineteenth century, German writers began to favor a new metaphor for the afterlife: “das Jenseits” (“the Beyond”). At first glance, the emergence of such a term may appear to have little bearing on our understanding of the history of religious thought. However, as the late historian Reinhart Koselleck maintained, the study of semantic changes can betray tectonic shifts in the matrix of ideas that underpin the worlds of politics, learning, and religion. Drawing on Koselleck's method of conceptual history, the following essay takes the popularization of “the Beyond” as a point of departure for investigating secularization and secularism as two linked, yet distinct, sources of pressure on the fault lines of nineteenth-century German religious thought.

Updated parameters for the transiting exoplanet WASP-3b using RISE, a new fast camera for the Liverpool Telescope

Some of the first results are reported from RISE - a new fast camera mounted on the Liverpool Telescope primarily designed to obtain high time-resolution light curves of transiting extrasolar planets for the purpose of transit timing. A full and partial transit of WASP-3 are presented, and a Markov-Chain Monte Carlo analysis is used to update the parameters from the discovery paper. This results in a planetary radius of 1.29(-0.12)(+0.05) R-J and therefore a density of 0.82(-0.09)(+0.14) rho(J), consistent with previous results. The inclination is 85.06(-0.15)(+0.16) deg, in agreement (but with a significant improvement in the precision) with the previously determined value. Central transit times are found to be consistent with the ephemeris given in the discovery paper; however, a new ephemeris calculated using the longer baseline results in T-c(0) = 2 454 605.55915 +/- 0.00023 HJD and P = 1.846835 +/- 0.000002 days.

The 0.5M(J) transiting exoplanet WASP-13b

We report the discovery of WASP-13b, a low-mass M-p = 0.46(-0.05)(+0.06) M-J transiting exoplanet with an orbital period of 4.35298 +/- 0.00004 days. The transit has a depth of 9 mmag, and although our follow-up photometry does not allow us to constrain the impact parameter well (0 <b <0.46), with radius in the range R-p similar to 1.06-1.21 R-J the location of WASP-13b in the mass-radius plane is nevertheless consistent with H/He-dominated, irradiated, low core mass and core-free theoretical models. The G1V host star is similar to the Sun in mass (M-* = 1.03(-0.09)(+0.11) M-circle dot) and metallicity ([M/H] = 0.0 +/- 0.2), but is possibly older (8.5(-4.9)(+5.5) Gyr).

A Transit Timing Analysis of Mine RISE Light Curves of the Exoplanet System TrES-3

We present nine newly observed transits of TrES-3, taken as part of a transit timing program using the RISE instrument on the Liverpool Telescope. A Markov-Chain Monte Carlo analysis was used to determine the planet star radius ratio and inclination of the system, which were found to be R-p/R-star = 0.1664(-0.0018)(+0.0011) and i = 81.73(-0.04)(+0.13), respectively, consistent with previous results. The central transit times and uncertainties were also calculated, using a residual-permutation algorithm as an independent check on the errors. A re-analysis of eight previously published TrES-3 light curves was conducted to determine the transit times and uncertainties using consistent techniques. Whilst the transit times were not found to be in agreement with a linear ephemeris, giving chi(2) = 35.07 for 15 degrees of freedom, we interpret this to be the result of systematics in the light curves rather than a real transit timing variation. This is because the light curves that show the largest deviation from a constant period either have relatively little out-of-transit coverage or have clear systematics. A new ephemeris was calculated using the transit times and was found to be T-c(0) = 2454632.62610 +/- 0.00006 HJD and P = 1.3061864 +/- 0.0000005 days. The transit times were then used to place upper mass limits as a function of the period ratio of a potential perturbing planet, showing that our data are sufficiently sensitive to have probed sub-Earth mass planets in both interior and exterior 2:1 resonances, assuming that the additional planet is in an initially circular orbit.

WASP-14b: 7.3 M-J transiting planet in an eccentric orbit

We report the discovery of a 7.3 M-J exoplanet WASP-14b, one of the most massive transiting exoplanets observed to date. The planet orbits the 10th-magnitude F5V star USNO-B1 11118-0262485 with a period of 2.243 752 d and orbital eccentricity e = 0.09. A simultaneous fit of the transit light curve and radial velocity measurements yields a planetary mass of 7.3 +/- 0.5 M-J and a radius of 1.28 +/- 0.08 R-J. This leads to a mean density of about 4.6 g cm(-3) making it the densest transiting exoplanets yet found at an orbital period less than 3 d. We estimate this system to be at a distance of 160 +/- 20 pc. Spectral analysis of the host star reveals a temperature of 6475 +/- 100 K, log g = 4.07 cm s(-2) and v sin i = 4.9 +/- 1.0 km s(-1), and also a high lithium abundance, log N(Li) = 2.84 +/- 0.05. The stellar density, effective temperature and rotation rate suggest an age for the system of about 0.5-1.0 Gyr.

WASP-10b: a 3M(J), gas-giant planet transiting a late-type K star

We report the discovery of WASP-10b, a new transiting extrasolar planet (ESP) discovered by the Wide Angle Search for Planets ( WASP) Consortium and confirmed using Nordic Optical Telescope FIbre-fed Echelle Spectrograph and SOPHIE radial velocity data. A 3.09-d period, 29 mmag transit depth and 2.36 h duration are derived for WASP-10b using WASP and high-precision photometric observations. Simultaneous fitting to the photometric and radial velocity data using a Markov Chain Monte Carlo procedure leads to a planet radius of 1.28R(J), a mass of 2.96M(J) and eccentricity of approximate to 0.06. WASP-10b is one of the more massive transiting ESPs, and we compare its characteristics to the current sample of transiting ESP, where there is currently little information for masses greater than approximate to 2M(J) and non-zero eccentricities. WASP-10's host star, GSC 2752-00114 (USNO-B1.0 1214-0586164) is among the fainter stars in the WASP sample, with V = 12.7 and a spectral type of K5. This result shows promise for future late-type dwarf star surveys.

Simple heuristics: From one infinite regress to another?

Gigerenzer, Todd, and the ABC Research Group argue that optimisation under constraints leads to an infinite regress due to decisions about how much information to consider when deciding. In certain cases, however, their fast and frugal heuristics lead instead to an endless series of decisions about how best to decide.

Wasp-7: A Bright Transiting-Exoplanet System in the Southern Hemisphere

We report that a Jupiter-mass planet, WASP-7b, transits the V = 9.5 star HD 197286 every 4.95 d. This is the brightest discovery from the WASP-South transit survey so far and is currently the brightest transiting-exoplanet system in the southern hemisphere. WASP-7b is among the densest of the known Jupiter-mass planets, suggesting that it has a massive core. The planet mass is 0.96+0.12 -0.18 M Jup, the radius is 0.915+0.046 -0.040 R Jup, and the density is 1.26+0.25 -0.21 ?Jup (1.67+0.33 -0.28 g cm-3).

Between Colonial Violence and Socialist Worldview: The Conversions of Ernst Daumig

In 1900, Ernst Däumig (1866–1922) wrote to Karl Kautsky of his ‘bitter experiences’ of violence in the French Foreign Legion and then in the Prussian military that had led to his recent ‘conversion’ to the socialist worldview. This article takes up Däumig's letters, articles and travelogues, and a drama, to explore how he recast his experiences of colonial and military violence twice, first as a writer for a German soldiers’ journal and then as an aspiring socialist journalist. As well as a burden that pushed him to critique his past, Däumig's military and colonial experiences are shown to have been his starting capital in the world of journalism and politics. The article gives particular attention to the process of conversion, through which Däumig forged a new life narrative out of the moral tales offered by the adopted worldview and the events of his own past. In addition to providing a case study of worldview conversion, this article demonstrates how biographical research can challenge assumptions about the impact of colonial violence on German metropolitan culture. At the same time, this biographical analysis sheds light on the early career of one of the key figures in the German Revolution of 1918 to 1921. As co-chairman of the Independent Social Democratic Party (USPD), Däumig led the USPD into union with the Communist Party in 1920.

A transit timing analysis of seven RISE light curves of the exoplanet system HAT-P-3

We present seven light curves of the exoplanet system HAT-P-3, taken as part of a transit timing programme using the rapid imager to search for exoplanets instrument on the Liverpool Telescope. The light curves are analysed using a Markov chain Monte Carlo algorithm to update the parameters of the system. The inclination is found to be i = 86.75+0.22-0.21°, the planet-star radius ratio to be Rp/R* = 0.1098+0.0010-0.0012 and the stellar radius to be R* = 0.834+0.018-0.026Rsolar, consistent with previous results but with a significant improvement in the precision. Central transit times and uncertainties for each light curve are also determined, and a residual permutation algorithm is used as an independent check on the errors. The transit times are found to be consistent with a linear ephemeris, and a new ephemeris is calculated as Tc(0) = 2454856.70118 +/- 0.00018 HJD and P = 2.899738 +/- 0.000007 d. Model timing residuals are fitted to the measured timing residuals to place upper mass limits for a hypothetical perturbing planet as a function of the period ratio. These show that we have probed for planets with masses as low as 0.33 and 1.81 M? in the interior and exterior 2:1 resonances, respectively, assuming the planets are initially in circular orbits.