Exponential Krylov time integration for modeling multi-frequency optical response with monochromatic sources

Light incident on a layer of scattering material such as a piece of sugar or white paper forms a characteristic speckle pattern in transmission and reflection. The information hidden in the correlations of the speckle pattern with varying frequency, polarization and angle of the incident light can be exploited for applications such as biomedical imaging and high-resolution microscopy. Conventional computational models for multi-frequency optical response involve multiple solution runs of Maxwell's equations with monochromatic sources. Exponential Krylov subspace time solvers are promising candidates for improving efficiency of such models, as single monochromatic solution can be reused for the other frequencies without performing full time-domain computations at each frequency. However, we show that the straightforward implementation appears to have serious limitations. We further propose alternative ways for efficient solution through Krylov subspace methods. Our methods are based on two different splittings of the unknown solution into different parts, each of which can be computed efficiently. Experiments demonstrate a significant gain in computation time with respect to the standard solvers.Comment: 22 pages, 4 figure

Ion concentrations in cerebrospinal fluid in wakefulness, sleep and sleep deprivation in healthy humans

Sleep is controlled by a circadian rhythmicity, via a reduction of arousal-promoting neuromodulatory activity, and by accumulation of somnogenic factors in the interstitial fluid of the brain. Recent experiments in mice suggest that a reduced neuronal excitability caused by a reduced concentration of potassium in the brain, concomitant with an increased concentration of calcium and magnesium, constitutes an important mediator of sleep. In the present study, we examined whether such changes in ion concentrations could be detected in the cerebrospinal fluid of healthy humans. Each subject underwent cerebrospinal fluid collection at three occasions in a randomized order: at 15:00 hours–17:00 hours during waking, at 06:00 hours–07:00 hours immediately following 1 night of sleep, and at 06:00 hours–07:00 hours following 1 night of sleep deprivation. When compared with wakefulness, both sleep and sleep deprivation produced the same effect of a small (0.1 mm, about 3%), but robust and highly significant, reduction in potassium concentration. Calcium and magnesium concentrations were unchanged. Our results support a circadian modulation of neuronal excitability in the brain mediated via changes of the interstitial potassium concentration

Astrocyte-mediated short-term synaptic depression in the rat hippocampal CA1 area: two modes of decreasing release probability

<p>Abstract</p> <p>Background</p> <p>Synaptic burst activation feeds back as a short-term depression of release probability at hippocampal CA3-CA1 synapses. This short-term synaptic plasticity requires functional astrocytes and it affects both the recently active (< 1 s) synapses (post-burst depression) as well as inactive neighboring synapses (transient heterosynaptic depression). The aim of this study was to investigate and compare the components contributing to the depression of release probability in these two different scenarios.</p> <p>Results</p> <p>When tested using paired-pulses, following a period of inactivity, the transient heterosynaptic depression was expressed as a reduction in the response to only the first pulse, whereas the response to the second pulse was unaffected. This selective depression of only the first response in a high-frequency burst was shared by the homosynaptic post-burst depression, but it was partially counteracted by augmentation at these recently active synapses. In addition, the expression of the homosynaptic post-burst depression included an astrocyte-mediated reduction of the pool of release-ready primed vesicles.</p> <p>Conclusions</p> <p>Our results suggest that activated astrocytes depress the release probability via two different mechanisms; by depression of vesicular release probability only at inactive synapses and by imposing a delay in the recovery of the primed pool of vesicles following depletion. These mechanisms restrict the expression of the astrocyte-mediated depression to temporal windows that are typical for synaptic burst activity.</p

A pilot randomized controlled trial of exercise to improve cognitive performance in patients with stable glioma:A proof of concept

BACKGROUND: Patients with glioma often suffer from cognitive deficits. Physical exercise has been effective in ameliorating cognitive deficits in older adults and neurological patients. This pilot randomized controlled trial (RCT) explored the possible impact of an exercise intervention, designed to improve cognitive functioning in glioma patients, regarding cognitive test performance and patient-reported outcomes (PROs). METHODS: Thirty-four clinically stable patients with World Health Organization grades II/III glioma were randomized to a home-based remotely coached exercise group or an active control group. Patients exercised 3 times per week for 20-45 minutes, with moderate to vigorous intensity, during 6 months. At baseline and immediate follow-up, cognitive performance and PROs were assessed with neuropsychological tests and questionnaires, respectively. Linear regression analyses were used to estimate effect sizes of potential between-group differences in cognitive performance and PROs at 6 months. RESULTS: The exercise group (n = 21) had small- to medium-sized better follow-up scores than the control group (n = 11) on several measures of attention and information processing speed, verbal memory, and executive function, whereas the control group showed a slightly better score on a measure of sustained selective attention. The exercise group also demonstrated small- to medium-sized better outcomes on measures of self-reported cognitive symptoms, fatigue, sleep, mood, and mental health-related quality of life. CONCLUSIONS: This small exploratory RCT in glioma patients provides a proof of concept with respect to improvement of cognitive functioning and PROs after aerobic exercise, and warrants larger exercise trials in brain tumor patients

A genetically encoded reporter of synaptic activity in vivo

To image synaptic activity within neural circuits, we tethered the genetically encoded calcium indicator (GECI) GCaMP2 to synaptic vesicles by fusion to synaptophysin. The resulting reporter, SyGCaMP2, detected the electrical activity of neurons with two advantages over existing cytoplasmic GECIs: it identified the locations of synapses and had a linear response over a wider range of spike frequencies. Simulations and experimental measurements indicated that linearity arises because SyGCaMP2 samples the brief calcium transient passing through the presynaptic compartment close to voltage-sensitive calcium channels rather than changes in bulk calcium concentration. In vivo imaging in zebrafish demonstrated that SyGCaMP2 can assess electrical activity in conventional synapses of spiking neurons in the optic tectum and graded voltage signals transmitted by ribbon synapses of retinal bipolar cells. Localizing a GECI to synaptic terminals provides a strategy for monitoring activity across large groups of neurons at the level of individual synapses

Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is associated with deposition of amyloid β (Aβ) in the brain, which is reflected by low concentration of the Aβ1-42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional Aβ peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of Aβ. Here, we test the hypothesis that AD is characterized by a specific CSF Aβ isoform pattern that is distinct when comparing sporadic AD (SAD) and familial AD (FAD) due to different mechanisms underlying brain amyloid pathology in the two disease groups.</p> <p>Results</p> <p>We measured Aβ isoform concentrations in CSF from 18 patients with SAD, 7 carriers of the FAD-associated presenilin 1 (<it>PSEN1</it>) A431E mutation, 17 healthy controls and 6 patients with depression using immunoprecipitation-mass spectrometry. Low CSF levels of Aβ1-42 and high levels of Aβ1-16 distinguished SAD patients and FAD mutation carriers from healthy controls and depressed patients. SAD and FAD were characterized by similar changes in Aβ1-42 and Aβ1-16, but FAD mutation carriers exhibited very low levels of Aβ1-37, Aβ1-38 and Aβ1-39.</p> <p>Conclusion</p> <p>SAD patients and <it>PSEN1 </it>A431E mutation carriers are characterized by aberrant CSF Aβ isoform patterns that hold clinically relevant diagnostic information. <it>PSEN1 </it>A431E mutation carriers exhibit low levels of Aβ1-37, Aβ1-38 and Aβ1-39; fragments that are normally produced by γ-secretase, suggesting that the <it>PSEN1 </it>A431E mutation modulates γ-secretase cleavage site preference in a disease-promoting manner.</p

Optical to near-infrared transit observations of super-Earth GJ1214b: water-world or mini-Neptune?

GJ1214b is thought to be either a mini-Neptune with a thick, hydrogen-rich atmosphere, or a planet with a composition dominated by water. In the case of a hydrogen-rich atmosphere, molecular absorption and scattering processes may result in detectable radius variations as a function of wavelength. The aim of this paper is to measure these variations. We have obtained observations of the transit of GJ1214b in the r- and I-band with the INT, in the g, r, i and z bands with the 2.2 meter MPI/ESO telescope, in the Ks-band with the NOT, and in the Kc-band with the WHT. By comparing the transit depth between the the different bands, which is a measure for the planet-to-star size ratio, the atmosphere is investigated. We do not detect clearly significant variations in the planet-to-star size ratio as function of wavelength. Although the ratio at the shortest measured wavelength, in g-band, is 2sigma larger than in the other bands. The uncertainties in the Ks and Kc bands are large, due to systematic features in the light curves. The tentative increase in the planet-to-star size ratio at the shortest wavelength could be a sign of an increase in the effective planet-size due to Rayleigh scattering, which would require GJ1214b to have a hydrogen-rich atmosphere. If true, then the atmosphere has to have both clouds, to suppress planet-size variations at red optical wavelengths, as well as a sub-solar metallicity, to suppress strong molecular features in the near- and mid-infrared. However, star spots, which are known to be present on the hoststar's surface, can (partly) cancel out the expected variations in planet-to-star size ratio, due to the lower surface temperature of the spots . A hypothetical spot-fraction of 10% would be able to raise the infrared points sufficiently with respect to the optical measurements to be inconsistent with a water-dominated atmosphere. [abridged]Comment: 13 pages, 8 figures. Accepted for publication in A&

EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection

Ischemic preconditioning is the phenomenon whereby brief periods of sublethal ischemia protect against a subsequent, more prolonged, ischemic insult. In remote ischemic preconditioning (RIPC), ischemia to one organ protects others organs at a distance. We created mouse models to ask if inhibition of the alpha-ketoglutarate (αKG)-dependent dioxygenase Egln1, which senses oxygen and regulates the hypoxia-inducible factor (HIF) transcription factor, could suffice to mediate local and remote ischemic preconditioning. Using somatic gene deletion and a pharmacological inhibitor, we found that inhibiting Egln1 systemically or in skeletal muscles protects mice against myocardial ischemia-reperfusion (I/R) injury. Parabiosis experiments confirmed that RIPC in this latter model was mediated by a secreted factor. Egln1 loss causes accumulation of circulating αKG, which drives hepatic production and secretion of kynurenic acid (KYNA) that is necessary and sufficient to mediate cardiac ischemic protection in this setting.Broad Institute of MIT and Harvard. SPARC ProgramBurroughs Wellcome Fun