New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Terror and terrorism Pleasure, violence and the aesthetic, 1757-1854

Available from British Library Document Supply Centre-DSC:D217188 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Optical Kerr-effect study of trans- and cis-1,2-dichloroethene: liquid-liquid transition or super-Arrhenius relaxation

The evidence that a molecular liquid in its thermodynamically-stable state can undergo a liquid-liquid transition (LLT) is still uncertain. Therefore, trans-1,2-dichloroethene is of interest due to reports of a LLT above the melting point [S. Kawanishi, T. Sasuga and M. Takehisa, J. Phys. Soc. Jpn., 1982, 51, 1579-1583; S. Rzoska, J. Ziolo, A. Drozd-Rzoska, J. L. Tamarit and N. Veglio, J. Phys.: Condens. Matter, 2008, 20, 244124; K. Merkel, A. Kocot, R. Wrzalik and J. Ziolo, J. Chem. Phys., 2008, 129, 074503-074508]. Ultrafast optical Kerr-effect (OKE) spectroscopy enables accurate measurement of the low-frequency modes arising from interactions in liquids and therefore should be sensitive to the change in liquid structure inherent in such a transition. In the OKE data presented here, no sharp transitions are discernible, nor are there any in calorimetry data. However, the same data do reveal that neither trans- nor cis-1,2-dichloroethene is a simple liquid: in each case, a non-Arrhenius temperature dependence (with a Debye lineshape) is observed for the α relaxation. This dependence can be fitted by the Vogel-Fulcher-Tammann (VFT) law over the measurable temperature range suggesting that at low temperature, cooperative relaxation, due to the formation of clusters or structure, is present. Accurate analysis of the OKE spectrum in the terahertz region is generally limited by approximations inherent in the models. Here the diffusional modes are convoluted with librational modes to give a more physically meaningful approximation to the inertial response

200 ns pulse high-voltage supply for terahertz field emission

We present a method of generating 200 ns high-voltage (up to 40 kV) pulses operating at repetition rates of up to 100 kHz, which may be synchronized with laser pulses. These supplies are simple to make and were developed for ultrafast terahertz pulse generation from GaAs photoconductive antennas using a high-repetition-rate regeneratively amplified laser. We also show an improvement in signal-to-noise ratio over a continuous dc bias field and application of the supply to terahertz pulse generation

Moving the Maasai

This dissertation examines the two major forced moves of the Maasai in British East Africa in the 1900s, through which the 'northern' sections lost the greater part of their land, and non-violent resistance to these events which culminated in a landmark court case in 1913. The Maasai lost this action, the so-called Maasai Case, on a technicality. The dissertation amis to compare the parallel and contested narratives of the British and the Maasai about these events and related issues, drawing on original oral testimony and archival sources in Kenya and Britain. It attempts to address major omissions in the historiography which include a failure to examine these events from a Maasai perspective and include Maasai voices, to fully analyse their significance and effects, and to place Maasai responses to the moves within the context of contemporary African resistance. It focuses as much on people's perspectives as it does on events, and on a metaphysical as well as material realm. The immediate frame of reference is 1904 to 1918, with the broader frame c. 1896 to the 1930s. The two leading characters around whom the story revolves are Dr Norman Leys, a colonial dissident who orchestrated support for the Maasai in Britain, and Parsaloi Ole Gilisho, an important age-set spokesman of the Purko section who launched the legal action against the British. New evidence reveals the full extent of their actions, motivation and influence, and casts light upon the activities of other European colonial critics inside British East Africa. Secondary themes include the legal implications of the Maasai Case and Agreements; the relative powers of Maasai leaders and a critique of 'anthrohistorical' models; the complex relationship between Maasai leaders and prominent settlers; labour relations on highland farms; the post-war return of Maasai to their former northern territories; the role of East Coast fever in relation to the second move; disease as a social metaphor; and a reinterpretation of the causes of rebellions in 1918, 1922 and 1935 which may be connected to the earlier land alienation.</p

The structure and terahertz dynamics of water confined in nanoscale pools in salt solutions

The behaviour of liquid water below its melting point is of great interest as it may hold clues to the properties of normal liquid water and of water in and on the surfaces of biomolecules. A second critical point, giving rise to a polyamorphic transition between high and low density water, may be hidden in the supercooled region but cannot be observed directly. Here it is shown that water can be locked up in nano-pools or worm-like structures using aqueous LiCl salt solutions and can be studied with terahertz spectroscopies. Very high dynamic range ultrafast femtosecond optical Kerr effect (OKE) spectroscopy is used to study the temperature-dependent behaviour of water in these nano-pools on timescales from 10 fs to 4 ns. These experiments are complemented by temperature-dependent nuclear magnetic resonance (NMR) diffusion measurements, concentration-dependent Fourier-transform infrared (FTIR) measurements, and temperature-dependent rheology. It is found that liquid water in the nanoscale pools undergoes a fragile-to-strong transition at about 220 K associated with a sharp increase in the inhomogeneity of translational dynamics

Is the ionic liquid ethylammonium nitrate like water?

The protic ionic liquid ethylammonium nitrate [EtNH3+][NO3–] (EAN) can in some ways be considered as an archetypal IL. Certainly, since its first investigation 100 years ago by Walden, it is one of the best known. The study of the dynamics of EAN, with its relatively simple structure, provides an opportunity to better understand the behaviour of more complex ILs. However, there is another reason why EAN warrants special attention: this is because it has been proposed as an analogue of that truly mysterious but very important substance dihydrogen monoxide (aka water). The basis for this claim is an apparent similarity between various H-bonding modes that are observed in the far-infrared (THz) region of both substances. However, such spectra are difficult to measure and even more difficult to interpret without detailed knowledge of other possible modes that might exist in this spectral region. This talk will describe the dynamics of EAN and some closely-related compounds over the extraordinarily wide frequency range from 200 MHz to 10 THz (~350 cm–1) obtained by using a combination of dielectric relaxation and optical Kerr-effect spectroscopies. Detailed analysis of these spectra shows that the observed intensities are actually a complex combination of overlapping and probably coupled modes, including H-bond vibrations, cation and anion librations and possibly other cooperative effects; the relationships between EAN and water are not clear-cut