Stability effects on results of diffusion tensor imaging analysis by reduction of the number of gradient directions due to motion artifacts: an application to presymptomatic Huntington's disease.

In diffusion tensor imaging (DTI), an improvement in the signal-to-noise ratio (SNR) of the fractional anisotropy (FA) maps can be obtained when the number of recorded gradient directions (GD) is increased. Vice versa, elimination of motion-corrupted or noisy GD leads to a more accurate characterization of the diffusion tensor. We previously suggest a slice-wise method for artifact detection in FA maps. This current study applies this approach to a cohort of 18 premanifest Huntington's disease (pHD) subjects and 23 controls. By 2-D voxelwise statistical comparison of original FA-maps and FA-maps with a reduced number of GD, the effect of eliminating GD that were affected by motion was demonstrated.We present an evaluation metric that allows to test if the computed FA-maps (with a reduced number of GD) still reflect a "true" FA-map, as defined by simulations in the control sample. Furthermore, we investigated if omitting data volumes affected by motion in the pHD cohort could lead to an increased SNR in the resulting FA-maps.A high agreement between original FA maps (with all GD) and corrected FA maps (i.e. without GD corrupted by motion) were observed even for numbers of eliminated GD up to 13. Even in one data set in which 46 GD had to be eliminated, the results showed a moderate agreement

Infection of the fishes with Ligula intestinalis and Bothriocephalus acheilognathi in Sattarkhan Dam, northwestern Iran

After an extensive fish mortality in Sattarkhan Dam, in East-Azarbaijan province during the year 2002, we collected 160 specimens of the fish Alburnus filippi and 5 specimens of the fish and Alburnoides bipunctatus to examine the cause of mortality. The samples measured biometrically an examined them for internal and external infections. We found that of the 160 specimens of Alburnus filippi, 131 (81.8%) were infected with Ligula intestinalis and 26 (16.25%) specimens were infected with Bothriocephalus acheilognathi. Of 5 specimens of Alburnoides bipunctatus, 4 (80%) were infected with Ligula intestinalis and no Bothriocephalus acheilognathi observed. This is the first report of the Ligula and Bothriocephalus parasites infecting fishes in the Sattarkhan Dam

Polyglutamine diseases

Polyglutamine diseases are a collection of nine CAG trinucleotide expansion disorders, presenting with a spectrum of neurological and clinical phenotypes. Recent human, mouse and cell studies of Huntington's disease have highlighted the role of DNA repair genes in somatic expansion of the CAG repeat region, modifying disease pathogenesis. Incomplete splicing of the HTT gene has also been shown to occur in humans, with the resulting exon 1 fragment most probably contributing to the Huntington's disease phenotype. In the spinocerebellar ataxias, studies have converged on transcriptional dysregulation of ion channels as a key disease modifier. In addition, advances have been made in understanding how increased levels of toxic, polyglutamine-expanded proteins can arise in the spinocerebellar ataxias through post-transcriptional and -translational modifications and autophagic mechanisms. Recent studies in spinal and bulbar muscular atrophy implicate similar pathogenic pathways to the more common polyglutamine diseases, highlighting autophagy stimulation as a potential therapeutic target. Finally, the therapeutic use of antisense oligonucleotides in several polyglutamine diseases has shown preclinical benefits and serves as potential future therapies in humans

Simultaneous conduction and valence band quantisation in ultra-shallow, high density doping profiles in semiconductors

We demonstrate simultaneous quantisation of conduction band (CB) and valence band (VB) states in silicon using ultra-shallow, high density, phosphorus doping profiles (so-called Si:P $\delta$-layers). We show that, in addition to the well known quantisation of CB states within the dopant plane, the confinement of VB-derived states between the sub-surface P dopant layer and the Si surface gives rise to a simultaneous quantisation of VB states in this narrow region. We also show that the VB quantisation can be explained using a simple particle-in-a-box model, and that the number and energy separation of the quantised VB states depend on the depth of the P dopant layer beneath the Si surface. Since the quantised CB states do not show a strong dependence on the dopant depth (but rather on the dopant density), it is straightforward to exhibit control over the properties of the quantised CB and VB states independently of each other by choosing the dopant density and depth accordingly, thus offering new possibilities for engineering quantum matter.Comment: 5 pages, 2 figures and supplementary materia

DNA repair in the trinucleotide repeat disorders

Background Inherited diseases caused by unstable repeated DNA sequences are rare, but together represent a substantial cause of morbidity. Trinucleotide repeat disorders are severe, usually life-shortening, neurological disorders caused by nucleotide expansions, and most have no disease-modifying treatments. Longer repeat expansions are associated with genetic anticipation (ie, earlier disease onset in successive generations), although the differences in age at onset are not entirely accounted for by repeat length. Such phenotypic variation within disorders implies the existence of additional modifying factors in pathways that can potentially be modulated to treat disease. Recent developments A genome-wide association study detected genetic modifiers of age at onset in Huntington's disease. Similar findings were seen in the spinocerebellar ataxias, indicating an association between DNA damage-response and repair pathways and the age at onset of disease. These studies also suggest that a common genetic mechanism modulates age at onset across polyglutamine diseases and could extend to other repeat expansion disorders. Genetic defects in DNA repair underlie other neurodegenerative disorders (eg, ataxia-telangiectasia), and DNA double-strand breaks are crucial to the modulation of early gene expression, which provides a mechanistic link between DNA repair and neurodegeneration. Mismatch and base-excision repair are important in the somatic expansion of repeated sequences in mouse models of trinucleotide repeat disorders, and somatic expansion of the expanded CAG tract in HTT correlates with age at onset of Huntington's disease and other trinucleotide repeat disorders. Where next? To understand the common genetic architecture of trinucleotide repeat disorders and any further genetic susceptibilities in individual disorders, genetic analysis with increased numbers of variants and sample sizes is needed, followed by sequencing approaches to define the phenotype-modifying variants. The findings must then be translated into cell biology analyses to elucidate the mechanisms through which the genetic variants operate. Genes that have roles in the DNA damage response could underpin a common DNA repeat-based mechanism and provide new therapeutic targets (and hence therapeutics) in multiple trinucleotide repeat disorders

Huntington's Disease Clinical Trials Corner: November 2022

In this edition of the Huntington's Disease Clinical Trials Corner, we expand on the PIVOT HD (PTC518), and SIGNAL (pepinemab) trials, and list all currently registered and ongoing clinical trials in Huntington's disease.We also introduce a 'breaking news' section highlighting recent updates about the SELECT HD, uniQure AMT-130, and VIBRANT HD clinical trials

Huntington's Disease Clinical Trials Corner: July 2023

In this edition of the Huntington's Disease Clinical Trials Corner, we expand on the GENERATION HD2 (tominersen) and on the Asklepios Biopharmaceutical/BrainVectis trial with AB-1001. We also comment on the recent findings from the PROOF-HD trial, and list all currently registered and ongoing clinical trials in Huntington's disease

Rooftop wind monitoring campaigns for small wind turbine applications: Effect of sampling rate and averaging period

Small wind turbines are often sited in more complex environments than the open terrain sites assumed in relevant installation guidelines or in the international small wind turbine design standard IEC61400-2. The built environment is an example of such a complex environment and installation of small wind turbines on the rooftops of high buildings has been suggested by architects and project developers as a potential means of incorporating sustainable energy generation into building design. In the absence of guidelines for installing wind turbines in the built environment, two key wind measurement parameters are the rate at which a data acquisition system (DAQ) samples the sensor, and the period over which the sampled data is averaged.This paper presents the results of the effect of sampling rate and averaging period on turbulence measurements from a monitoring system on a building rooftop, in order to inform the process of developing guidelines. The results will inform the development of a Recommended Practice of wind resource assessment in the built environment, via the International Energy Agency Task 27. The key finding of the paper is that, in general, 10Hz sampling and 10min averaging period give upper estimates for turbulence intensity and maximum values of the turbulence power spectra. Using these conservative values in the design of the turbine may be the best approach to ensure that the turbine can handle both the fatigue loads and resonance due to gusts

Modelling the structural loading of a small wind turbine at a highly turbulent site via modifications to the Kaimal turbulence spectra

Although, wind turbines have traditionally been sited in open terrain, there is a growing trend of installing turbines in non-homogeneous terrain, such as urban areas. Recorded urban turbine failures suggest that turbine design has been inadequate for the turbulence experienced at these sites and hence a better understanding of the turbine-loading issues in the built environment is required. This paper compares turbine blade load statistics for inflow turbulence fields based on the open terrain standard Kaimal spectra, as suggested in the standard IEC61400-2 that covers the design and safety standard of small wind turbines, and measured turbulence spectra from a built environment site. The findings show that for extreme, high turbulent intensity winds, the measured spectra predict isolated loading events around twice the magnitude of loads predicted by use of the standard spectra. The work suggests the need for improvements to the standard in order to model the non-Gaussian wind statistics that occur in extreme events such as sudden strong gusts