Studies on the impact of small vessel disease (SVD) on cognition generally focus on white matter hyperintensity (WMH) volume. The extent to which WMH location relates to cognitive performance has ...received less attention, but is likely to be functionally important. We examined the relation between WMH location and cognition in a memory clinic cohort of patients with sporadic SVD.
A total of 167 patients with SVD were recruited from memory clinics. Assumption-free region of interest-based analyses based on major white matter tracts and voxel-wise analyses were used to determine the association between WMH location and executive functioning, visuomotor speed and memory.
Region of interest-based analyses showed that WMHs located particularly within the anterior thalamic radiation and forceps minor were inversely associated with both executive functioning and visuomotor speed, independent of total WMH volume. Memory was significantly associated with WMH volume in the forceps minor, independent of total WMH volume. An independent assumption-free voxel-wise analysis identified strategic voxels in these same tracts. Region of interest-based analyses showed that WMH volume within the anterior thalamic radiation explained 6.8% of variance in executive functioning, compared to 3.9% for total WMH volume; WMH volume within the forceps minor explained 4.6% of variance in visuomotor speed and 4.2% of variance in memory, compared to 1.8% and 1.3% respectively for total WMH volume.
Our findings identify the anterior thalamic radiation and forceps minor as strategic white matter tracts in which WMHs are most strongly associated with cognitive impairment in memory clinic patients with SVD. WMH volumes in individual tracts explained more variance in cognition than total WMH burden, emphasizing the importance of lesion location when addressing the functional consequences of WMHs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The ultracold neutron (UCN) source at Los Alamos National Laboratory (LANL), which uses solid deuterium as the UCN converter and is driven by accelerator spallation neutrons, has been successfully ...operated for over 10 years, providing UCN to various experiments, as the first production UCN source based on the superthermal process. It has recently undergone a major upgrade. This paper describes the design and performance of the upgraded LANL UCN source. Measurements of the cold neutron spectrum and UCN density are presented and compared to Monte Carlo predictions. The source is shown to perform as modeled. The UCN density measured at the exit of the biological shield was 184(32) UCN/cm3, a fourfold increase from the highest previously reported. The polarized UCN density stored in an external chamber was measured to be 39(7) UCN/cm3, which is sufficient to perform an experiment to search for the nonzero neutron electric dipole moment with a one-standard-deviation sensitivity of σ(dn)=3×10-27ecm.
We present a thorough analysis of soliton solutions to the quasi-one-dimensional (quasi-1D) nonlinear Dirac equation (NLDE) for a Bose-Einstein condensate in a honeycomb lattice with armchair ...geometry. Our NLDE corresponds to a quasi-1D reduction of the honeycomb lattice along the zigzag direction, in direct analogy to graphene nanoribbons. Excitations in the remaining large direction of the lattice correspond to the linear subbands in the armchair nanoribbon spectrum. Analytical as well as numerical soliton Dirac spinor solutions are obtained. We analyze the solution space of the quasi-1D NLDE by finding fixed points, delineating the various regions in solution space, and through an invariance relation which we obtain as a first integral of the NLDE. We obtain spatially oscillating multi-soliton solutions as well as asymptotically flat single soliton solutions using five different methods: by direct integration; an invariance relation; parametric transformation; a series expansion; and by numerical shooting. By tuning the ratio of the chemical potential to the nonlinearity for a fixed value of the energy-momentum tensor, we can obtain both bright and dark solitons over a nonzero density background.
Cortico-cortical evoked potentials (CCEPs) are a common tool for probing effective connectivity in intracranial human electrophysiology. As with all human electrophysiology data, CCEP data are highly ...susceptible to noise. To address noise, filters and re-referencing are often applied to CCEP data, but different processing strategies are used from study to study.
We systematically compare how common average re-referencing and filtering CCEP data impacts quantification.
We show that common average re-referencing and filters, particularly filters that cut out more frequencies, can significantly impact the quantification of CCEP magnitude and morphology. We identify that high cutoff high pass filters (> 0.5 Hz), low cutoff low pass filters (< 200 Hz), and common average re-referencing impact quantification across subjects. However, we also demonstrate that the presence of noise may impact CCEP quantification, and preprocessing is necessary to mitigate this. We show that filtering is more effective than re-referencing or averaging across trials for reducing most common types of noise.
These results suggest that existing CCEP processing methods must be applied with care to maximize noise reduction and minimize changes to the data. We do not test every available processing strategy; rather we demonstrate that processing can influence the results of CCEP studies. We emphasize the importance of reporting all processing methods, particularly re-referencing methods.
We propose a general framework for choosing an appropriate processing pipeline for CCEP data, taking into consideration the noise levels of a specific dataset. We suggest that minimal gentle filtering is preferable.
•CCEP processing strategies vary widely across the literature.•Processing can significantly impact the results of CCEP quantification.•The amount of noise in data should be considered when choosing processing methods.•It is critical that studies reporting CCEP results document signal processing steps.
White matter hyperintensities (WMH) are associated with cognitive dysfunction after ischemic stroke. Yet, uncertainty remains about affected domains, the role of other preexisting brain injury, and ...infarct types in the relation between WMH burden and poststroke cognition. We aimed to disentangle these factors in a large sample of patients with ischemic stroke from different cohorts.
We pooled and harmonized individual patient data (n=1568) from 9 cohorts, through the Meta VCI Map consortium (www.metavcimap.org). Included cohorts comprised patients with available magnetic resonance imaging and multidomain cognitive assessment <15 months poststroke. In this individual patient data meta-analysis, linear mixed models were used to determine the association between WMH volume and domain-specific cognitive functioning (
scores; attention and executive functioning, processing speed, language and verbal memory) for the total sample and stratified by infarct type. Preexisting brain injury was accounted for in the multivariable models and all analyses were corrected for the study site as a random effect.
In the total sample (67 years SD, 11.5, 40% female), we found a dose-dependent inverse relationship between WMH volume and poststroke cognitive functioning across all 4 cognitive domains (coefficients ranging from -0.09 SE, 0.04,
=0.01 for verbal memory to -0.19 SE, 0.03,
<0.001 for attention and executive functioning). This relation was independent of acute infarct volume and the presence of lacunes and old infarcts. In stratified analyses, the relation between WMH volume and domain-specific functioning was also largely independent of infarct type.
In patients with ischemic stroke, increasing WMH volume is independently associated with worse cognitive functioning across all major domains, regardless of old ischemic lesions and infarct type.
A 73-year-old man was referred for surgical excision of a massive mediastinal and cervical liposarcoma following neoadjuvant chemotherapy. Surgery was performed via a cervical incision, sternotomy ...and right posterolateral thoracotomy. The tumour arose from the oesophagus, which underwent extensive dissection and was oversewn with pleura after tumour resection. Histology confirmed a completely excised grade 2 de-differentiated liposarcoma with complete macroscopic excision. The patient made an excellent recovery. Oesophageal liposarcomas are rare and, unlike in this case, often extend intraluminally, necessitating oesophagectomy. To our knowledge, this is the largest such tumour found in the literature.
Astronomical data reveals that approximately 3.5 terawatts (TW) of tidal energy is dissipated in the ocean. Tidal models and satellite altimetry suggest that 1 TW of this energy is converted from the ...barotropic to internal tides in the deep ocean, predominantly around regions of rough topography such as mid-ocean ridges. A global tidal model is used to compute turbulent energy levels associated with the dissipation of internal tides, and the diapycnal mixing supported by this energy flux is computed using a simple parameterization.
The mixing parameterization has been incorporated into a coarse resolution numerical model of the global ocean. This parameterization offers an energetically consistent and practical means of improving the representation of ocean mixing processes in climate models. Novel features of this implementation are that the model explicitly accounts for the tidal energy source for mixing, and that the mixing evolves both spatially and temporally with the model state. At equilibrium, the globally averaged diffusivity profile ranges from 0.3 cm
2
s
−1 at thermocline depths to 7.7 cm
2
s
−1 in the abyss with a depth average of 0.9 cm
2
s
−1, in close agreement with inferences from global balances. Water properties are strongly influenced by the combination of weak mixing in the main thermocline and enhanced mixing in the deep ocean. Climatological comparisons show that the parameterized mixing scheme results in a substantial reduction of temperature/salinity bias relative to model solutions with either a uniform vertical diffusivity of 0.9 cm
2
s
−1 or a horizontally uniform bottom-intensified arctangent mixing profile. This suggests that spatially varying bottom intensified mixing is an essential component of the balances required for the maintenance of the ocean’s abyssal stratification.
The Cold Classical Kuiper Belt, a class of small bodies in undisturbed orbits beyond Neptune, is composed of primitive objects preserving information about Solar System formation. In January 2019, ...the New Horizons spacecraft flew past one of these objects, the 36-kilometer-long contact binary (486958) Arrokoth (provisional designation 2014 MU
). Images from the flyby show that Arrokoth has no detectable rings, and no satellites (larger than 180 meters in diameter) within a radius of 8000 kilometers. Arrokoth has a lightly cratered, smooth surface with complex geological features, unlike those on previously visited Solar System bodies. The density of impact craters indicates the surface dates from the formation of the Solar System. The two lobes of the contact binary have closely aligned poles and equators, constraining their accretion mechanism.
Background:l-Arginine is a nutritional supplement that may be useful for promoting intestinal repair. Arginine is metabolised by the oxidative deiminase pathway to form nitric oxide (NO) and by the ...arginase pathway to yield ornithine and polyamines. Aims: To determine if arginine stimulates restitution via activation of NO synthesis and/or polyamine synthesis. Methods: We determined the effects of arginine on cultured intestinal cell migration, NO production, polyamine levels, and activation of focal adhesion kinase, a key mediator of cell migration. Results: Arginine increased the rate of cell migration in a dose dependent biphasic manner, and was additive with bovine serum concentrate (BSC). Arginine and an NO donor activated focal adhesion kinase (a tyrosine kinase which localises to cell matrix contacts and mediates β1 integrin signalling) after wounding. Arginine stimulated cell migration was dependent on focal adhesion kinase (FAK) signalling, as demonstrated using adenovirus mediated transfection with a kinase negative mutant of FAK. Arginine stimulated migration was dependent on NO production and was blocked by NO synthase inhibitors. Arginine dependent migration required synthesis of polyamines but elevating extracellular arginine concentration above 0.4 mM did not enhance cellular polyamine levels. Conclusions: These results showed that l-arginine stimulates cell migration through NO and FAK dependent pathways and that combination therapy with arginine and BSC may enhance intestinal restitution via separate and convergent pathways.
BirA catalyzes the adenylation and subsequent covalent attachment of biotin to the biotin carboxyl carrier protein (BCCP). In the absence of apo-BCCP, biotin-5′-AMP acts as a co-repressor that ...induces BirA dimerization and binding to the
bio operator to repress biotin biosynthesis. The crystal structures of apo-BirA, and BirA in complex with biotin have been reported. We here describe the 2.8
Å resolution crystal structure of BirA in complex with the co-repressor analog biotinol-5′-AMP. It was previously shown that the structure of apo-BirA is monomeric and that binding of biotin weakly induces a dimeric structure in which three disordered surface loops become organized to form the dimer interface. The structure of the co-repressor complex is also a dimer, clearly related to the BirA·biotin structure, but with several significant conformational changes. A hitherto disordered “adenylate binding loop” forms a well-defined structure covering the co-repressor. The co-repressor buttresses the dimer interface, resulting in improved packing and a 12° change in the hinge-bending angle along the dimer interface relative to the BirA·biotin structure. This helps explain why the binding of the co-repressor is necessary to optimize the binding of BirA to the bioO operator. The structure reveals an unexpected use of the nucleotide-binding motif GXGXXG in binding adenylate and controlling the repressor function. Finally, based on structural analysis we propose that the class of adenylating enzymes represented by BirA, lipoate protein ligase and class II tRNA synthetases diverged early and were selected based on their ability to sequester co-factors or amino acid residues, and adenylation activity arose independently through functional convergence.
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