Intention Tremor and Deficits of Sensory Feedback Control in Multiple Sclerosis: a Pilot Study

Background Intention tremor and dysmetria are leading causes of upper extremity disability in Multiple Sclerosis (MS). The development of effective therapies to reduce tremor and dysmetria is hampered by insufficient understanding of how the distributed, multi-focal lesions associated with MS impact sensorimotor control in the brain. Here we describe a systems-level approach to characterizing sensorimotor control and use this approach to examine how sensory and motor processes are differentially impacted by MS. Methods Eight subjects with MS and eight age- and gender-matched healthy control subjects performed visually-guided flexion/extension tasks about the elbow to characterize a sensory feedback control model that includes three sensory feedback pathways (one for vision, another for proprioception and a third providing an internal prediction of the sensory consequences of action). The model allows us to characterize impairments in sensory feedback control that contributed to each MS subject’s tremor. Results Models derived from MS subject performance differed from those obtained for control subjects in two ways. First, subjects with MS exhibited markedly increased visual feedback delays, which were uncompensated by internal adaptive mechanisms; stabilization performance in individuals with the longest delays differed most from control subject performance. Second, subjects with MS exhibited misestimates of arm dynamics in a way that was correlated with tremor power. Subject-specific models accurately predicted kinematic performance in a reach and hold task for neurologically-intact control subjects while simulated performance of MS patients had shorter movement intervals and larger endpoint errors than actual subject responses. This difference between simulated and actual performance is consistent with a strategic compensatory trade-off of movement speed for endpoint accuracy. Conclusions Our results suggest that tremor and dysmetria may be caused by limitations in the brain’s ability to adapt sensory feedback mechanisms to compensate for increases in visual information processing time, as well as by errors in compensatory adaptations of internal estimates of arm dynamics

Chandra Early-Type Galaxy Atlas

The hot ISM in early type galaxies (ETGs) plays a crucial role in understanding their formation and evolution. The structural features of the hot gas identified by Chandra observations point to key evolutionary mechanisms, (e.g., AGN and stellar feedback, merging history). In our Chandra Galaxy Atlas (CGA) project, taking full advantage of the Chandra capabilities, we systematically analyzed the archival Chandra data of 70 ETGs and produced uniform data products for the hot gas properties. The primary data products are spatially resolved 2D spectral maps of the hot gas from individual galaxies. We emphasize that new features can be identified in the spectral maps which are not readily visible in the surface brightness maps. The high-level images can be viewed at the dedicated CGA website, and the CGA data products can be downloaded to compare with data at other wavelengths and to perform further analyses. Utilizing our data products, we address a few focused science topics.Comment: 52 pages, 9 figures, accepted in ApJ Supp

Endovascular Therapy for Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis

Recent reports have emerged suggesting that multiple sclerosis (MS) may be due to abnormal venous outflow from the central nervous system, termed chronic cerebrospinal venous insufficiency (CCSVI). These reports have generated strong interest and controversy over the prospect of a treatable cause of this chronic debilitating disease. This review aims to describe the proposed association between CCSVI and MS, summarize the current data, and discuss the role of endovascular therapy and the need for rigorous randomized clinical trials to evaluate this association and treatment

DNA Origami Rotaxanes: Tailored Synthesis and Controlled Structure Switching

Mechanically interlocked supramolecular assemblies are appealing building blocks for creating functional nanodevices. Herein, we describe the multistep assembly of large DNA origami rotaxanes that are capable of programmable structural switching. We validated the topology and structural integrity of these rotaxanes by analyzing the intermediate and final products of various assembly routes by electrophoresis and electron microscopy. We further analyzed two structureâ switching behaviors of our rotaxanes, which are both mediated by DNA hybridization. In the first mechanism, the translational motion of the macrocycle can be triggered or halted at either terminus. In the second mechanism, the macrocycle can be elongated after completion of the rotaxane assembly, giving rise to a unique structure that is otherwise difficult to access.A new set of threads: Rotaxanes with a length of up to 200â nm were assembled by a DNA origami approach. The threaded macrocycles can be programmably docked at either dumbbell stopper, and the assemblies can be reconfigured to generate new, otherwise unfavorable rotaxane topologies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137326/1/anie201604621_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137326/2/anie201604621-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137326/3/anie201604621.pd

One-pot Synthesis of Lactams Using Domino Reactions: Combination of Schmidt Reaction with Sakuri and Aldol Reaction

A series of domino reactions in which the intramolecular Schmidt reaction is combined with either a Sakurai reaction, an aldol reaction, or both is reported. The Sakurai reaction of an allylsilane with an azido-containing enone under Lewis acidic conditions followed by protonation of the resulting titanium enolate species allowed for a subsequent intramolecular Schmidt reaction. Alternatively, the intermediate titanium enolate could undergo an aldol reaction, followed by the intramolecular Schmidt reaction to form lactam products with multiple stereogenic centers. The stereochemical features of the titanium enolate aldol reaction with several 3-azidoaldehyde substrates during this domino process is discussed

Determinants of low bone mineral density in people with multiple sclerosis: Role of physical activity

Background People with multiple sclerosis (PwMS) have reduced bone mineral density (BMD), but the causes are unclear. Some factors that may cause reduced BMD in PwMS have been understudied, including physical activity, inflammation, cortisol, symptomatic fatigue, and depression. The aim of this study was to investigate factors that may uniquely contribute to reduced BMD in PwMS as compared to people without MS. We hypothesized that physical activity would be the primary determinant of low BMD in PwMS, with additional contributions from inflammation and sympathetic nervous system activation. Methods We tested 23 PwMS (16 women; median EDSS: 2) and 22 control participants (16 women). BMD was measured from the femoral neck and lumbar spine with dual x-ray absorptiometry. Disability was measured with the Expanded Disability Status Scale, and functional capacity was measured with the Multiple Sclerosis Functional Composite. Questionnaires measured symptomatic fatigue and depression. A blood draw was used to measure calcium, phosphate, vitamin D, N-terminal telopeptide, osteopontin, and cytokine markers of inflammation. Physical activity was measured with accelerometry. Salivary cortisol and cardiac heart rate variability also were obtained. All outcome variables were compared between groups with independent samples t-tests. Variables that were different between groups and significantly correlated (Pearson product-moment) with femoral neck BMD, were included in a theoretical model to explain femoral neck BMD. The expected direction of relations in the theoretical model were developed based upon the results of previous research. A Bayesian path analysis was used to test the relations of predictive variables with femoral neck BMD and interrelations among predictive variables, as detailed in the theoretical model. Results PwMS had lower BMD at the femoral neck than controls (p = =0.04; mean difference: -0.09; 95% CI: -0.2, -0.004; Cohen\u27s d = =0.65), and there was a smaller, statistically non-significant difference in BMD at the lumbar spine (p = =0.07; mean difference: -0.08; 95% CI: -0.17, 0.007; Cohen\u27s d = =0.59). PwMS also had lower functional capacity (p ≤ 0.001; Cohen\u27s d = =1.50), greater fatigue (pd = =1.88), greater depression (pd = =1.31), and decreased physical activity (p = =0.03; Cohen\u27s d = =0.62). Using path analysis to test our theoretical model, we found that disability (standardized estimate= -0.17), physical activity (standardized estimate=0.39), symptomatic fatigue (standardized estimate= -0.36), depression (standardized estimate= -0.30), and inflammatory markers (standardized estimate=0.27) explained 51% of the variance in femoral neck BMD. Inflammatory markers were also predictive of disability (standardized estimate=0.44) and physical activity (standardized estimate= -0.40). Symptomatic fatigue and depression were correlated (r = =0.64). Conclusion Physical activity, symptomatic fatigue, depression, disability, and inflammation all contributed independently to decreased femoral neck BMD in PWMS. Bone metabolism in PwMS is complex. Efforts to increase physical activity and address symptomatic fatigue and depression may improve bone mineral density in PwMS. Future research should investigate the mechanisms through which symptomatic fatigue and depression contribute to reduced BMD in PwMS

Filaments of The Slime Mold Cosmic Web And How They Affect Galaxy Evolution

We present a novel method for identifying cosmic web filaments using the IllustrisTNG (TNG100) cosmological simulations and investigate the impact of filaments on galaxies. We compare the use of cosmic density field estimates from the Delaunay Tessellation Field Estimator (DTFE) and the Monte Carlo Physarum Machine (MCPM), which is inspired by the slime mold organism, in the DisPerSE structure identification framework. The MCPM-based reconstruction identifies filaments with higher fidelity, finding more low-prominence/diffuse filaments and better tracing the true underlying matter distribution than the DTFE-based reconstruction. Using our new filament catalogs, we find that most galaxies are located within 1.5-2.5 Mpc of a filamentary spine, with little change in the median specific star formation rate and the median galactic gas fraction with distance to the nearest filament. Instead, we introduce the filament line density, {\Sigma}fil(MCPM), as the total MCPM overdensity per unit length of a local filament segment, and find that this parameter is a superior predictor of galactic gas supply and quenching. Our results indicate that most galaxies are quenched and gas-poor near high-line density filaments at z10.5 galaxies is mainly driven by mass, while lower-mass galaxies are significantly affected by the filament line density. In high-line density filaments, satellites are strongly quenched, whereas centrals have reduced star formation, but not gas fraction, at z<=0.5. We discuss the prospect of applying our new filament identification method to galaxy surveys with SDSS, DESI, Subaru PFS, etc. to elucidate the effect of large-scale structure on galaxy formation.Comment: Submitted to ApJ, comments welcome. Data available at https://github.com/farhantasy/CosmicWeb-Galaxies

FIRST-based survey of Compact Steep Spectrum sources, II. MERLIN and VLA observations of Medium-sized Symmetric Objects

A new sample of candidate Compact Steep Spectrum (CSS) sources that are much weaker than the CSS source prototypes has been selected from the VLA FIRST catalogue. MERLIN `snapshot' observations of the sources at 5 GHz indicate that six of them have an FR II-like morphology, but are not edge-brightened as is normal for Medium-sized Symmetric Objects (MSOs) and FR IIs. Further observations of these six sources with the VLA at 4.9 GHz and MERLIN at 1.7 GHz, as well as subsequent full-track observations with MERLIN at 5 GHz of what appeared to be the two sources of greatest interest are presented. The results are discussed with reference to the established evolutionary model of CSS sources being young but in which not all of them evolve to become old objects with extended radio structures. A lack of stable fuelling in some of them may result in an early transition to a so-called coasting phase so that they fade away instead of growing to become large-scale objects. It is possible that one of the six sources (1542+323) could be labelled as a prematurely `dying' MSO or a `fader'.Comment: 13 pages, matches the version printed in Astronomy & Astrophysic