645 research outputs found
Spin gating electrical current
We use an aluminium single electron transistor with a magnetic gate to
directly quantify the chemical potential anisotropy of GaMnAs materials.
Uniaxial and cubic contributions to the chemical potential anisotropy are
determined from field rotation experiments. In performing magnetic field sweeps
we observe additional isotropic magnetic field dependence of the chemical
potential which shows a non-monotonic behavior. The observed effects are
explained by calculations based on the kinetic
exchange model of ferromagnetism in GaMnAs. Our device inverts the conventional
approach for constructing spin transistors: instead of spin-transport
controlled by ordinary gates we spin-gate ordinary charge transport.Comment: 5 pages, 4 figure
Reconfigurable Boolean Logic using Magnetic Single-Electron Transistors
We propose a novel hybrid single-electron device for reprogrammable low-power
logic operations, the magnetic single-electron transistor (MSET). The device
consists of an aluminium single-electron transistors with a GaMnAs magnetic
back-gate. Changing between different logic gate functions is realized by
reorienting the magnetic moments of the magnetic layer which induce a voltage
shift on the Coulomb blockade oscillations of the MSET. We show that we can
arbitrarily reprogram the function of the device from an n-type SET for
in-plane magnetization of the GaMnAs layer to p-type SET for out-of-plane
magnetization orientation. Moreover, we demonstrate a set of reprogrammable
Boolean gates and its logical complement at the single device level. Finally,
we propose two sets of reconfigurable binary gates using combinations of two
MSETs in a pull-down network
Ongoing microstructural changes in the cervical cord underpin disability progression in early primary progressive multiple sclerosis
Background: Pathology in the spinal cord of patients with primary progressive multiple sclerosis (PPMS) contributes to disability progression. We previously reported abnormal Q-space imaging (QSI)-derived indices in the spinal cord at baseline in patients with early PPMS, suggesting early neurodegeneration. /
Objective: The aim was to investigate whether changes in spinal cord QSI over 3 years in the same cohort are associated with disability progression and if baseline QSI metrics predict clinical outcome. /
Methods: Twenty-three PPMS patients and 23 healthy controls recruited at baseline were invited for follow-up cervical cord 3T magnetic resonance imaging (MRI) and clinical assessment after 1 year and 3 years. Cord cross-sectional area (CSA) and QSI measures were obtained, together with standard brain MRI measures. Mixed-effect models assessed MRI changes over time and their association with clinical changes. Linear regression identified baseline MRI indices associated with disability at 3 years. /
Results: Over time, patients deteriorated clinically and showed an increase in cord QSI indices of perpendicular diffusivity that was associated with disability worsening, independently of the decrease in CSA. Higher perpendicular diffusivity and lower CSA at baseline predicted worse disability at 3 years.
Conclusion:
Increasing spinal cord perpendicular diffusivity may indicate ongoing neurodegeneration, which underpins disability progression in PPMS, independently of the development of spinal cord atrophy
Fuzzy Fibers: Uncertainty in dMRI Tractography
Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI)
allows for noninvasive reconstruction of fiber bundles in the human brain. In
this chapter, we discuss sources of error and uncertainty in this technique,
and review strategies that afford a more reliable interpretation of the
results. This includes methods for computing and rendering probabilistic
tractograms, which estimate precision in the face of measurement noise and
artifacts. However, we also address aspects that have received less attention
so far, such as model selection, partial voluming, and the impact of
parameters, both in preprocessing and in fiber tracking itself. We conclude by
giving impulses for future research
Facing the urgency of therapies for progressive MS — a Progressive MS Alliance proposal
Therapies for infiltrative inflammation in multiple sclerosis (MS) have advanced greatly, but neurodegeneration and compartmentalized inflammation remain virtually untargeted as in other diseases of the nervous system. Consequently, many therapies are available for the relapsing–remitting form of MS, but the progressive forms remain essentially untreated. The objective of the International Progressive MS Alliance is to expedite the development of effective therapies for progressive MS through new initiatives that foster innovative thinking and concrete advancements. Based on these principles, the Alliance is developing a new funding programme that will focus on experimental medicine trials. Here, we discuss the reasons behind the focus on experimental medicine trials, the strengths and weaknesses of these approaches and of the programme, and why we hope to advance therapies while improving the understanding of progression in MS. We are soliciting public and academic feedback, which will help shape the programme and future strategies of the Alliance
Combining tractography and cortical measures to test system-specific hypotheses in multiple sclerosis
The objective was to test three motor system-specific hypotheses in multiple sclerosis patients: (i) corticospinal tract and primary motor cortex imaging measures differ between multiple sclerosis patients and controls; (ii) in patients, these measures correlate with disability; (iii) in patients, corticospinal tract measures correlate with measures of the ipsilateral primary motor cortex
Spatial patterns of brain lesions assessed through covariance estimations of lesional voxels in multiple Sclerosis: The SPACE-MS technique
Predicting disability in progressive multiple sclerosis (MS) is extremely challenging. Although there is some evidence that the spatial distribution of white matter (WM) lesions may play a role in disability accumulation, the lack of well-established quantitative metrics that characterise these aspects of MS pathology makes it difficult to assess their relevance for clinical progression. This study introduces a novel approach, called SPACE-MS, to quantitatively characterise spatial distributional features of brain MS lesions, so that these can be assessed as predictors of disability accumulation. In SPACE-MS, the covariance matrix of the spatial positions of each patient's lesional voxels is computed and its eigenvalues extracted. These are combined to derive rotationally-invariant metrics known to be common and robust descriptors of ellipsoid shape such as anisotropy, planarity and sphericity. Additionally, SPACE-MS metrics include a neuraxis caudality index, which we defined for the whole-brain lesion mask as well as for the most caudal brain lesion. These indicate how distant from the supplementary motor cortex (along the neuraxis) the whole-brain mask or the most caudal brain lesions are. We applied SPACE-MS to data from 515 patients involved in three studies: the MS-SMART (NCT01910259) and MS-STAT1 (NCT00647348) secondary progressive MS trials, and an observational study of primary and secondary progressive MS. Patients were assessed on motor and cognitive disability scales and underwent structural brain MRI (1.5/3.0Â T), at baseline and after 2Â years. The MRI protocol included 3DT1-weighted (1x1x1mm3) and 2DT2-weighted (1x1x3mm3) anatomical imaging. WM lesions were semiautomatically segmented on the T2-weighted scans, deriving whole-brain lesion masks. After co-registering the masks to the T1 images, SPACE-MS metrics were calculated and analysed through a series of multiple linear regression models, which were built to assess the ability of spatial distributional metrics to explain concurrent and future disability after adjusting for confounders. Patients whose WM lesions laid more caudally along the neuraxis or were more isotropically distributed in the brain (i.e. with whole-brain lesion masks displaying a high sphericity index) at baseline had greater motor and/or cognitive disability at baseline and over time, independently of brain lesion load and atrophy measures. In conclusion, here we introduced the SPACE-MS approach, which we showed is able to capture clinically relevant spatial distributional features of MS lesions independently of the sheer amount of lesions and brain tissue loss. Location of lesions in lower parts of the brain, where neurite density is particularly high, such as in the cerebellum and brainstem, and greater spatial spreading of lesions (i.e. more isotropic whole-brain lesion masks), possibly reflecting a higher number of WM tracts involved, are associated with clinical deterioration in progressive MS. The usefulness of the SPACE-MS approach, here demonstrated in MS, may be explored in other conditions also characterised by the presence of brain WM lesions
Reduced neurite density in the brain and cervical spinal cord in relapsing–remitting multiple sclerosis: A NODDI study
Background:
Multiple sclerosis (MS) affects both brain and spinal cord. However, studies of the neuraxis with advanced magnetic resonance imaging (MRI) are rare because of long acquisition times. We investigated neurodegeneration in MS brain and cervical spinal cord using neurite orientation dispersion and density imaging (NODDI).
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Objective:
The aim of this study was to investigate possible alterations, and their clinical relevance, in neurite morphology along the brain and cervical spinal cord of relapsing–remitting MS (RRMS) patients.
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Methods:
In total, 28 RRMS patients and 20 healthy controls (HCs) underwent brain and spinal cord NODDI at 3T. Physical and cognitive disability was assessed. Individual maps of orientation dispersion index (ODI) and neurite density index (NDI) in brain and spinal cord were obtained. We examined differences in NODDI measures between groups and the relationships between NODDI metrics and clinical scores using linear regression models adjusted for age, sex and brain tissue volumes or cord cross-sectional area (CSA).
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Results:
Patients showed lower NDI in the brain normal-appearing white matter (WM) and spinal cord WM than HCs. In patients, a lower NDI in the spinal cord WM was associated with higher disability.
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Conclusion:
Reduced neurite density occurs in the neuraxis but, especially when affecting the spinal cord, it may represent a mechanism of disability in MS
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Loss of the xeroderma pigmentosum group B protein binding site impairs p210 BCR/ABL1 leukemogenic activity
Previous studies have demonstrated that p210 BCR/ABL1 interacts directly with the xeroderma pigmentosum group B (XPB) protein, and that XPB is phosphorylated on tyrosine in cells that express p210 BCR/ABL1. In the current study, we have constructed a p210 BCR/ABL1 mutant that can no longer bind to XPB. The mutant has normal kinase activity and interacts with GRB2, but can no longer phosphorylate XPB. Loss of XPB binding is associated with reduced expression of c-MYC and reduced transforming potential in ex-vivo clonogenicity assays, but does not affect nucleotide excision repair in lymphoid or myeloid cells. When examined in a bone marrow transplantation (BMT) model for chronic myelogenous leukemia, mice that express the mutant exhibit attenuated myeloproliferation and lymphoproliferation when compared with mice that express unmodified p210 BCR/ABL1. Thus, the mutant-transplanted mice show predominantly neutrophilic expansion and altered progenitor expansion, and have significantly extended lifespans. This was confirmed in a BMT model for B-cell acute lymphoblastic leukemia, wherein the majority of the mutant-transplanted mice remain disease free. These results suggest that the interaction between p210 BCR/ABL1 and XPB can contribute to disease progression by influencing the lineage commitment of lymphoid and myeloid progenitors
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