Modulating basal ganglia and cerebellar activity to suppress parkinsonian tremor

Despite extensive research, the detailed pathophysiology of the parkinsonian tremor is still unknown. It has been hypothesized that the generation of parkinsonian tremor is related to abnormal activity within the basal ganglia. The cerebello-thalamic-cortical loop has been suggested to indirectly contribute to the expression of parkinsonian tremor. However, the observed tremor-related hyperactivity in the cerebellar loop may have a compensatory rather than a causal role in Parkinson's disease (PD) by preventing tremor from spilling over into voluntary movement. Furthermore, observed overactivation in cerebellar loops has also been associated with a higher ability of PD patients to perform repetitive movements that are cued by auditory or visual stimuli, suggesting that rhythmic synchronization with an auditory timekeeper can be achieved in the absence of intact basal ganglia function. Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is currently an accepted treatment for advanced PD that may significantly improve motor complications and reduce tremor. While DBS directly influences neuronal activity patterns in basal ganglia loops, it may be expected that modulation of the cerebellar loops have an additional effect on parkinsonian tremor if both loops are involved in tremor generation and expression.\ud The aim of this pilot study is to test whether the combination of DBS and auditory cueing has an enhanced effect on tremor reduction. Therefore, in a group of seven PD patients receiving STN-DBS, tremor occurrence in both hands and both feet was sequentially tested while performing repetitive movements cued by an auditory signal. The frequency of the auditory cues ranged from 1.6 Hz, which is within the range of frequencies that can be found during normal movements, and 4.8 Hz, which is near the average PD tremor frequency. Movements and tremor were registered by inertial sensors attached to the hands and feet. The Chi-square test was used to compare the occurrence of tremor in any of the extremities for the different cueing frequencies and DBS “on” and “off”.\ud Compared to the resting condition and the performance of self-paced hand or foot movements, the number of extremities showing tremor was significantly reduced under external cueing conditions when stimulation was “on”. With DBS “off”, only the lower cueing frequencies (1.6 and 3.2 Hz) provided a beneficial effect.\ud From the results it may be hypothesized that modulation of the pathological patterns in basal ganglia (by DBS) and cerebellar activity (by auditory cueing) provides enhanced suppression of action tremor in PD

It support for mass customization

Many authors have written about Mass Customization and its features and categories. Literature on the implementation of Mass Customization, and in particular the supporting information technology, is scant. This paper attempts to fill this gap by focusing on this subject. We determine the key functional requirements and identify possible implementations to show the existence of enabling information technologies for Mass Customization

Quantum Critical Dynamics of A Qubit Coupled to An Isotropic Lipkin-Meshkov-Glick Bath

We explore a dynamic signature of quantum phase transition (QPT) in an isotropic Lipkin-Meshkov-Glick (LMG) model by studying the time evolution of a central qubit coupled to it. We evaluate exactly the time-dependent purity, which can be used to measure quantum coherence, of the central qubit. It is found that distinctly different behaviors of the purity as a function of the parameter reveal clearly the QPT point in the system. It is also clarified that the present model is equivalent to an anti Jaynes-Cummings model under certain conditions.Comment: 8 pages, 4 figure

Pressure tuning of competing magnetic interactions in intermetallic CeFe_2

We use high-pressure magnetic x-ray diffraction and numerical simulation to determine the low-temperature magnetic phase diagram of stoichiometric CeFe_2. Near 1.5 GPa we find a transition from ferromagnetism to antiferromagnetism, accompanied by a rhombohedral distortion of the cubic Laves crystal lattice. By comparing pressure and chemical substitution we find that the phase transition is controlled by a shift of magnetic frustration from the Ce-Ce to the Fe-Fe sublattice. Notably the dominant Ce-Fe magnetic interaction, which sets the temperature scale for the onset of long-range order, remains satisfied throughout the phase diagram but does not determine the magnetic ground state. Our results illustrate the complexity of a system with multiple competing magnetic energy scales and lead to a general model for magnetism in cubic Laves phase intermetallic compounds

Electronic structure of the candidate 2D Dirac semimetal SrMnSb2: a combined experimental and theoretical study

SrMnSb$_2$ is suggested to be a magnetic topological semimetal. It contains square, 2D Sb planes with non-symmorphic crystal symmetries that could protect band crossings, offering the possibility of a quasi-2D, robust Dirac semi-metal in the form of a stable, bulk (3D) crystal. Here, we report a combined and comprehensive experimental and theoretical investigation of the electronic structure of SrMnSb$_2$, including the first ARPES data on this compound. SrMnSb$_2$ possesses a small Fermi surface originating from highly 2D, sharp and linearly dispersing bands (the Y-states) around the (0,$\pi$/a)-point in $k$-space. The ARPES Fermi surface agrees perfectly with that from bulk-sensitive Shubnikov de Haas data from the same crystals, proving the Y$-$states to be responsible for electrical conductivity in SrMnSb$_2$. DFT and tight binding (TB) methods are used to model the electronic states, and both show good agreement with the ARPES data. Despite the great promise of the latter, both theory approaches show the Y-states to be gapped above E$_F$, suggesting trivial topology. Subsequent analysis within both theory approaches shows the Berry phase to be zero, indicating the non-topological character of the transport in SrMnSb$_2$, a conclusion backed up by the analysis of the quantum oscillation data from our crystals.Comment: 26 pages, 10 figures, revised submission to SciPost after including changes requested by referees. All referee reports are open and can be viewed here: https://scipost.org/submissions/1711.07165v2

BRAF mutation-specific promoter methylation of FOX genes in colorectal cancer

Background: Cancer-specific hypermethylation of (promoter) CpG islands is common during the tumorigenesis of colon cancer. Although associations between certain genetic aberrations, such as BRAF mutation and microsatellite instability, and the CpG island methylator phenotype (CIMP), have been found, the mechanisms by which these associations are established are still unclear. We studied genome-wide DNA methylation differences between

Incommensurate antiferromagnetism in a pure spin system via cooperative organization of local and itinerant moments

Materials with strong correlations are prone to spin and charge instabilities, driven by Coulomb, magnetic, and lattice interactions. In materials that have significant localized and itinerant spins, it is not obvious which will induce order. We combine electrical transport, X-ray magnetic diffraction, and photoemission studies with band structure calculations to characterize successive anti-ferromagnetic transitions in GdSi. GdSi has both sizable local moments and a partially nested Fermi surface, without confounding contributions from orbital effects. We identify a route to incommensurate order where neither type of moment dominates, but is rooted in cooperative feedback between them. The nested Fermi surface of the itinerant electrons induces strong interactions between local moments at the nesting vector, whereas the ordered local moments in turn provide the necessary coupling for a spin-density wave to form among the itinerant electrons. This mechanism echoes the cooperative interactions between electrons and ions in charge-density-wave materials, and should be germane across a spectrum of transition-metal and rare-earth intermetallic compounds

MLPAinter for MLPA interpretation: An integrated approach for the analysis, visualisation and data management of Multiplex Ligation-dependent Probe Amplification

Background: Multiplex Ligation-Dependent Probe Amplification (MLPA) is an application that can be used for the detection of multiple chromosomal aberrations in a single experiment. In one reaction, up to 50 different genomic sequences can be analysed. For a reliable work-flow, tools are needed for administrative support, data management, normalisation, visualisation, reporting and interpretation.Results: Here, we developed a data management system, MLPAInter for MLPA interpretation, that is windows executable and has a stand-alone database for monitoring and interpreting the MLPA data stream that is generated from the experimental setup to analysis, quality control and visualisation. A statistical approach is applied for the normalisation and analysis of large series of MLPA traces, making use of multiple control samples and internal controls.Conclusions: MLPAinter visualises MLPA data in plots with information about sample replicates, normalisation settings, and sample characteristics. This integrated approach helps in the automated handling of large series of MLPA data and guarantees a quick and streamlined dataflow from the beginning of an experiment to an authorised report

The homeobox gene MEIS1 is methylated in BRAFp.V600E mutated colon tumors

Development of colorectal cancer (CRC) can occur both via gene mutations in tumor suppressor genes and oncogenes, as well as via epigenetic changes, including DNA methylation. Site-specific methylation in CRC regulates expression of tumor-associated genes. Right-sided colon tumors more frequently have BRAFp.V600E mutations and have higher methylation grades when compared to left-sided malignancies. The aim of this study was to identify DNA methylation changes associated with BRAFp.V600E mutation status. We performed methylation profiling of colon tumor DNA, isolated from frozen sections enriched for epithelial cells by macro-dissection, and from paired healthy tissue. Single gene analyses comparing BRAFp.V600E with BRAF wild type revealed MEIS1 as the most significant differentially methylated gene (log2 fold change: 0.89, false discovery rate-adjusted P-value 2.8*10-9). This finding was validated by methylation-specific PCR that was concordant with the microarray data. Additionally, validation in an independent cohort (n=228) showed a significant association between BRAF p.V600E and MEIS1 methylation (OR: 13.0, 95% CI: 5.2 - 33.0, P<0.0001). MEIS1 methylation was associated with decreased MEIS1 gene expression in both patient samples and CRC cell lines. The same was true for gene expression of a truncated form of MEIS1, MEIS1D27, which misses exon 8 and has a proposed tumor suppression function. To trace the origin of MEIS1 promoter methylation, 14 colorectal tumors were flow-sorted. Four out of eight BRAFp.V600E tumor epithelial fractions (50%) showed MEIS1 promoter methylation, as well as three out of eight BRAFp.V600E stromal fractions (38%). Only one out of six BRAF wild type showed MEIS1 promoter methylation in both the epithelial tumor and stromal fractions (17%). In conclusion, BRAFp.V600E colon tumors showed significant MEIS1 promoter methylation, which was associated with decreased MEIS1 gene expression. Copyright

Effective theory for deformed nuclei

Techniques from effective field theory are applied to nuclear rotation. This approach exploits the spontaneous breaking of rotational symmetry and the separation of scale between low-energy Nambu-Goldstone rotational modes and high-energy vibrational and nucleonic degrees of freedom. A power counting is established and the Hamiltonian is constructed at next-to-leading order