Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial.

<b>Objective</b>: It was hypothesized that the use of exercise limits prevents symptom increases and worsening of their health status following a walking exercise in people with Chronic Fatigue Syndrome (CFS). <b>Design</b>: An uncontrolled clinical trial (semi-experimental design). <b>Setting</b>: Outpatient clinic of a university department. <b>Subjects</b>: 24 patients with CFS. <b>Interventions</b>: Subjects undertook a walking test with the two concurrent exercise limits. Each subject walked at an <i>intensity</i> where the maximum heart rate was determined by heart rate corresponding to the respiratory exchange ratio =1.0 derived from a previous sub-maximal exercise test and for a duration calculated from how long each patient felt they were able to walk. <b>Main outcome measures</b>: The Short Form 36 Health Survey or SF-36, the CFS Symptom List, and the CFS-Activities and Participation Questionnaire were filled in prior to, immediately and 24 hours post-exercise. <b>Results</b>: The fatigue increase observed immediately post-exercise (p=0.006) returned to pre-exercise levels 24 hours post-exercise. The increase in pain observed immediately post-exercise was retained at 24 hours post-exercise (p=0.03). Fourteen of 24 subjects experienced a clinically meaningful change in bodily pain (change of SF-36 bodily pain score ³10). Six of 24 participants indicated that the exercise bout had slightly worsened their health status, and 2 of 24 had a clinically meaningful decrease in vitality (change of SF-36 vitality score ³20). There was no change in activity limitations/participation restrictions. <b>Conclusion</b>: It was shown that the use of exercise limits (limiting both the intensity and duration of exercise) prevents important health status changes following a walking exercise in people with CFS, but was unable to prevent short-term symptom increases

Planetary accretion and core formation inferred from Ni isotopes in enstatite meteorites

Nickel is a siderophile and near-refractory element, making its isotopes a potential tool for tracing planetary accretion and differentiation. However, the origin of the Ni stable isotope difference between bulk silicate Earth (BSE) and chondrites remains enigmatic. To address this problem, we report high precision Ni stable isotope data of enstatite chondrites and achondrites that possess similar mass independent O and Ni isotope compositions like the Earth-Moon system. Bulk enstatite chondrites have δ60/58Ni values of 0.24 ± 0.08 ‰ (2 s.d., n = 13). Enstatite achondrites, including main-group aubrites, Shallowater and Itqiy, show relatively large δ60/58Ni variations, ranging from 0.03 ± 0.02 ‰ to 0.57 ± 0.04 ‰. This could reflect fractionations between sulfide and metal phases, as is evidenced by correlation between their S/Ni ratios and δ60/58Ni values. In enstatite achondrites, Ni is mainly hosted in metal and to a lesser extent in sulfides, so δ60/58Ni values in enstatite achondrites may represent the Ni isotopic values of the cores of their parent bodies. The overlapping δ60/58Ni values between bulk enstatite achondrites and enstatite chondrites indicate limited Ni stable isotope fractionation during core formation processes on reduced, sulfur-rich parent bodies. The Ni stable isotope gap between chondrites and the BSE could be possibly explained by chondrule-rich accretion model

Signal Transmission Across Tile Assemblies: 3D Static Tiles Simulate Active Self-Assembly by 2D Signal-Passing Tiles

The 2-Handed Assembly Model (2HAM) is a tile-based self-assembly model in which, typically beginning from single tiles, arbitrarily large aggregations of static tiles combine in pairs to form structures. The Signal-passing Tile Assembly Model (STAM) is an extension of the 2HAM in which the tiles are dynamically changing components which are able to alter their binding domains as they bind together. For our first result, we demonstrate useful techniques and transformations for converting an arbitrarily complex STAM$^+$ tile set into an STAM$^+$ tile set where every tile has a constant, low amount of complexity, in terms of the number and types of ``signals'' they can send, with a trade off in scale factor. Using these simplifications, we prove that for each temperature $\tau>1$ there exists a 3D tile set in the 2HAM which is intrinsically universal for the class of all 2D STAM$^+$ systems at temperature $\tau$ (where the STAM$^+$ does not make use of the STAM's power of glue deactivation and assembly breaking, as the tile components of the 2HAM are static and unable to change or break bonds). This means that there is a single tile set $U$ in the 3D 2HAM which can, for an arbitrarily complex STAM$^+$ system $S$, be configured with a single input configuration which causes $U$ to exactly simulate $S$ at a scale factor dependent upon $S$. Furthermore, this simulation uses only two planes of the third dimension. This implies that there exists a 3D tile set at temperature $2$ in the 2HAM which is intrinsically universal for the class of all 2D STAM$^+$ systems at temperature $1$. Moreover, we show that for each temperature $\tau>1$ there exists an STAM$^+$ tile set which is intrinsically universal for the class of all 2D STAM$^+$ systems at temperature $\tau$, including the case where $\tau = 1$.Comment: A condensed version of this paper will appear in a special issue of Natural Computing for papers from DNA 19. This full version contains proofs not seen in the published versio

D-brane anomaly inflow revisited

Axial and gravitational anomaly of field theories, when embedded in string theory, must be accompanied by canceling inflow. We give a self-contained overview for various world-volume theories, and clarify the role of smeared magnetic sources in I-brane/D-brane cases. The proper anomaly descent of the source, as demanded by regularity of RR field strengths H's, turns out to be an essential ingredient. We show how this allows correct inflow to be generated for all such theories, including self-dual cases, and also that the mechanism is now insensitive to the choice between the two related but inequivalent forms of D-brane Chern-Simons couplings. In particular, SO(6)_R axial anomaly of d=4 maximal SYM is canceled by the inflow onto D3-branes via the standard minimal coupling to C_4. We also propose how, for the anomaly cancelation, the four types of Orientifold planes should be coupled to the spacetime curvatures, of which conflicting claims existed previously.Comment: 41 pages, references updated; version to appear in JHE

Therapeutic strategies for spinal muscular atrophy: SMN and beyond

Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder characterized by loss of motor neurons and muscle atrophy, generally presenting in childhood. SMA is caused by low levels of the survival motor neuron protein (SMN) due to inactivating mutations in the encoding gene SMN1 A second duplicated gene, SMN2, produces very little but sufficient functional protein for survival. Therapeutic strategies to increase SMN are in clinical trials, and the first SMN2-directed antisense oligonucleotide (ASO) therapy has recently been licensed. However, several factors suggest that complementary strategies may be needed for the long-term maintenance of neuromuscular and other functions in SMA patients. Pre-clinical SMA models demonstrate that the requirement for SMN protein is highest when the structural connections of the neuromuscular system are being established, from late fetal life throughout infancy. Augmenting SMN may not address the slow neurodegenerative process underlying progressive functional decline beyond childhood in less severe types of SMA. Furthermore, individuals receiving SMN-based treatments may be vulnerable to delayed symptoms if rescue of the neuromuscular system is incomplete. Finally, a large number of older patients living with SMA do not fulfill the present criteria for inclusion in gene therapy and ASO clinical trials, and may not benefit from SMN-inducing treatments. Therefore, a comprehensive whole-lifespan approach to SMA therapy is required that includes both SMN-dependent and SMN-independent strategies that treat the CNS and periphery. Here, we review the range of non-SMN pathways implicated in SMA pathophysiology and discuss how various model systems can serve as valuable tools for SMA drug discovery

The Foraging Tunnel System of the Namibian Desert Termite, Baucaliotermes hainesi

The harvester termite, Baucaliotermes hainesi (Fuller) (Termitidae: Nasutitermitinae), is an endemic in southern Namibia, where it collects and eats dry grass. At the eastern, landward edge of the Namib Desert, the nests of these termites are sometimes visible above ground surface, and extend at least 60 cm below ground. The termites gain access to foraging areas through underground foraging tunnels that emanate from the nest. The looseness of the desert sand, combined with the hardness of the cemented sand tunnels allowed the use of a gasolinepowered blower and soft brushes to expose tunnels lying 5 to 15 cm below the surface. The tunnels form a complex system that radiates at least 10 to 15 m from the nest with crossconnections between major tunnels. At 50 to 75 cm intervals, the tunnels are connected to the surface by vertical risers that can be opened to gain foraging access to the surrounding area. Foraging termites rarely need to travel more than a meter on the ground surface. The tunnels swoop up and down forming high points at riser locations, and they have a complex architecture. In the center runs a smooth, raised walkway along which termites travel, and along the sides lie pockets that act as depots where foragers deposit grass pieces harvested from the surface. Presumably, these pieces are transported to the nest by a second group of termites. There are also several structures that seem to act as vertical highways to greater depths, possibly even to moist soil. A census of a single nest revealed about 45,000 termites, of which 71% were workers, 9% soldiers and 6% neotenic supplementary reproductives. The nest consisted of a hard outer “carapace” of cemented sand, with a central living space of smooth, sweeping arches and surfaces. A second species of termite, Promirotermes sp. nested in the outer carapace

Oscillations and interactions of dark and dark-bright solitons in Bose-Einstein condensates

Solitons are among the most distinguishing fundamental excitations in a wide range of non-linear systems such as water in narrow channels, high speed optical communication, molecular biology and astrophysics. Stabilized by a balance between spreading and focusing, solitons are wavepackets, which share some exceptional generic features like form-stability and particle-like properties. Ultra-cold quantum gases represent very pure and well-controlled non-linear systems, therefore offering unique possibilities to study soliton dynamics. Here we report on the first observation of long-lived dark and dark-bright solitons with lifetimes of up to several seconds as well as their dynamics in highly stable optically trapped $^{87}$Rb Bose-Einstein condensates. In particular, our detailed studies of dark and dark-bright soliton oscillations reveal the particle-like nature of these collective excitations for the first time. In addition, we discuss the collision between these two types of solitary excitations in Bose-Einstein condensates.Comment: 9 pages, 4 figure

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Genome-Wide Association Study of Smoking Trajectory and Meta-Analysis of Smoking Status in 842,000 Individuals

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (Ntotal = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior