An end-to-end framework for real-time automatic sleep stage classification.

Sleep staging is a fundamental but time consuming process in any sleep laboratory. To greatly speed up sleep staging without compromising accuracy, we developed a novel framework for performing real-time automatic sleep stage classification. The client-server architecture adopted here provides an end-to-end solution for anonymizing and efficiently transporting polysomnography data from the client to the server and for receiving sleep stages in an interoperable fashion. The framework intelligently partitions the sleep staging task between the client and server in a way that multiple low-end clients can work with one server, and can be deployed both locally as well as over the cloud. The framework was tested on four datasets comprising ≈1700 polysomnography records (≈12000 hr of recordings) collected from adolescents, young, and old adults, involving healthy persons as well as those with medical conditions. We used two independent validation datasets: one comprising patients from a sleep disorders clinic and the other incorporating patients with Parkinson's disease. Using this system, an entire night's sleep was staged with an accuracy on par with expert human scorers but much faster (≈5 s compared with 30-60 min). To illustrate the utility of such real-time sleep staging, we used it to facilitate the automatic delivery of acoustic stimuli at targeted phase of slow-sleep oscillations to enhance slow-wave sleep

Crystallization and preliminary X-ray diffraction studies of FHA domains of Dun1 and Rad53 protein kinases

Forkhead-associated (FHA) domains are modular protein–protein interaction domains of ~130 amino acids present in numerous signalling proteins. FHA-domain-dependent protein interactions are regulated by phosphorylation of target proteins and FHA domains may be multifunctional phosphopeptide-recognition modules. FHA domains of the budding yeast cell-cycle checkpoint protein kinases Dun1p and Rad53p have been crystallized. Crystals of the Dun1-FHA domain exhibit the symmetry of the space group P6122 or P6522, with unit-cell parameters a = b = 127.3, c = 386.3 Å; diffraction data have been collected to 3.1 Å resolution on a synchrotron source. Crystals of the N-terminal FHA domain (FHA1) of Rad53p diffract to 4.0 Å resolution on a laboratory X-ray source and have Laue-group symmetry 4/mmm, with unit-cell parameters a = b = 61.7, c = 104.3 Å

Changes in the Circadian Rhythm in Patients with Primary Glaucoma

Purpose The current study was undertaken to investigate whether glaucoma affects the sleep quality and whether there is any difference between patients with primary glaucoma (primary open angle glaucoma, POAG and primary angle-closure glaucoma, PACG) and healthy subjects, using a validated self-rated questionnaire, the Pittsburgh Sleep Quality Index (PSQI). Methods The sleep quality of patients with POAG and PACG was tested against normal controls. Subjects were divided into three sub-groups according to age. Differences in the frequency of sleep disturbances (PSQI score >7) were assessed. The differences of sleep quality within the three groups and within the POAG group depending on the patients’ intraocular pressure (IOP) and impairment of visual field (VF) were also studied. Results 92 POAG patients, 48 PACG patients and 199 controls were included. Sleep quality declined with age in control and POAG group (tendency chi-square, P0.05). No significant differences were found in POAG group between patients with a highest IOP in daytime and at nighttime (χ2-test, P>0.05). Conclusions The prevalence of sleep disorders was higher in patients with POAG and PACG than in controls. PACG patients seemed to have a more serious problem of sleep disorders than POAG patients between 61 to 80 years old. No correlation was found between the prevalence of sleep disorders and impairment of VF or the time when POAG patients showed a highest IOP

Testing the Behavioral Responses of West Virginia Turtles to Roads and Vehicles

Road mortality has been identified as a major threat to many turtle species; however, response to passing vehicles, crossing speed, and general behavior while crossing roads has never been investigated in turtles. To investigate these factors, Midland Painted Turtles (Chrysemys picta marginata), Eastern Box Turtles (Terrapene c. carolina), and Stinkpots (Sternotherus odoratus) were collected and placed in a release box on the side of a closed road with an active road running parallel to it 26 m away. Turtles were released via a pulley-operated door facing the road, and their actions videotaped by an observer in a nearby blind. A vehicle was driven past crossing turtles on the closed road to simulate passing traffic in the adjoining lane. Resulting videos were used to determine the frequency of responses and length of stops due to passing vehicles, effective crossing speed, and other on-road behavior. Following trials, turtles were released at the original point of capture. Eastern Box Turtles stopped due to the stimulus of active road vehicles more than either Stinkpots or Midland Painted Turtles (87.50%, 33.33%, and 22.22%, respectively), and when stopped, they remained stationary for a greater time. All species reacted to a passing closed road vehicle by stopping on the road; however, Stinkpots had a greater mean stop time than Eastern Box Turtles or Midland Painted Turtles, although differences between Stinkpots and Eastern Box Turtles were not statistically significant. Eastern Box Turtles averaged slower effective crossing speeds than Midland Painted Turtles or Stinkpots. These results indicate that Eastern Box Turtles are at greater risk of mortality when crossing divided highways than either Stinkpots or Midland Painted Turtles due to slower effective crossing speeds and a higher stop response rate to opposing lane vehicles

Automating the Satellite Range Scheduling Process

Satellite range scheduling is a complex problem that involves scheduling satellite supports in which a satellite and a specific remote tracking station are assigned a time window during which they communicate with each other. As the number and complexity of satellite supports continue to increase, more pressure is placed on the current manual system to efficiently generate a schedule. The objective of this research was to develop a methodology that will automate the generation of the initial 24 hour schedule. The goal of the algorithm developed was to schedule as many conflict free supports as possible. A two phased approach was developed to schedule the supports. The first phase scheduled as many low altitude satellite supports as possible, while the second phase scheduled as many additional high altitude satellite supports as possible. For both phases, schedule generation and schedule improvement algorithms were developed. The schedule generation algorithms are a mixed integer program linking procedure and an insertion procedure. The schedule improvement algorithms are a two satellite interchange procedure and a three satellite interchange procedure. A schedule was generated for six representative data sets with encouraging results. At least 91% of all satellite support requests were scheduled for each day. These results were comparable to results of the current range schedulers and a previous automation study. Based on the results reported, the methodology presented in this research effort seems to be a valid approach for automating the initial 24 hour schedule

Effects of Exposure to Intermittent versus Continuous Red Light on Human Circadian Rhythms, Melatonin Suppression, and Pupillary Constriction

Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21–28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm−2 s−1), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light

Optimisation of NMR dynamic models II. A new methodology for the dual optimisation of the model-free parameters and the Brownian rotational diffusion tensor.

Finding the dynamics of an entire macromolecule is a complex problem as the model-free parameter values are intricately linked to the Brownian rotational diffusion of the molecule, mathematically through the autocorrelation function of the motion and statistically through model selection. The solution to this problem was formulated using set theory as an element of the universal set [formula: see text]-the union of all model-free spaces (d'Auvergne EJ and Gooley PR (2007) Mol BioSyst 3(7), 483-494). The current procedure commonly used to find the universal solution is to initially estimate the diffusion tensor parameters, to optimise the model-free parameters of numerous models, and then to choose the best model via model selection. The global model is then optimised and the procedure repeated until convergence. In this paper a new methodology is presented which takes a different approach to this diffusion seeded model-free paradigm. Rather than starting with the diffusion tensor this iterative protocol begins by optimising the model-free parameters in the absence of any global model parameters, selecting between all the model-free models, and finally optimising the diffusion tensor. The new model-free optimisation protocol will be validated using synthetic data from Schurr JM et al. (1994) J Magn Reson B 105(3), 211-224 and the relaxation data of the bacteriorhodopsin (1-36)BR fragment from Orekhov VY (1999) J Biomol NMR 14(4), 345-356. To demonstrate the importance of this new procedure the NMR relaxation data of the Olfactory Marker Protein (OMP) of Gitti R et al. (2005) Biochem 44(28), 9673-9679 is reanalysed. The result is that the dynamics for certain secondary structural elements is very different from those originally reported

A Case Report of Delayed, Severe, Paroxysmal Muscle Cramping after Chilean Rose Tarantula (Grammostola rosea) Envenomation

Introduction: Grammostola rosea (Chilean rose tarantula) is a common exotic pet belonging to the Theraphosidae (tarantula) family. Case reports of theraphosid bites in adults commonly describe local tissue damage and local pain. Muscle spasms have also been described as a result of the bites but are rarer. We present a case of severe and persistent muscle spasms after a G rosea bite, which is uncommonly reported in the literature. Case Report: A 42-year-old woman was holding a G rosea tarantula when she was bit on the forearm. Within hours, severe local muscle cramping occurred. Due to worsening cramping, she initially presented to the emergency department the day after the bite, and again on the following day. She was admitted on her second visit and treated with diazepam, cephalexin, diphenhydramine, baclofen, cefpodoxime, doxycycline, prednisone, and topical hydrocortisone. Her laboratory testing was unremarkable, and while medical management may have mildly improved her symptoms, painful cramping persisted. After discharge, her paroxysmal muscle cramping continued for four weeks before completely resolving. Conclusion: While local tissue damage and pain are common, G rosea bites may lead to severe muscle cramping that persists for weeks. Standard laboratory testing may be completely normal in these cases. Muscle cramps may be persistent and are difficult to manage

The allosteric mechanism of G-protein-coupled receptors is induced fit, not conformational selection

The allosteric mechanism of G-protein-coupled receptors (GPCRs) involves a population shift from inactive to active receptor conformations in response to the binding of ligand agonists. Two possible kinetic mechanisms for this population shift are induced fit and conformational selection. The two mechanisms differ in the temporal sequence of binding events and conformational changes: Ligand bindings occurs prior to the change from the inactive to the active receptor conformation in the induced-fit mechanism, and after the conformational change in the conformational-selection mechanism. In this article, we discuss the current evidence from experiments that probe the binding kinetics of GPCRs to identify the allosteric mechanism. For the peptide-activated neurotensin receptor 1, the modeling of kinetic data from stopped-flow mixing experiments indicates an induced-fit mechanism. The conformational exchange rates of the induced-fit mechanism obtained from this modeling agree with rates measured by saturation transfer difference NMR experiments of the peptide-receptor complex, which corroborates the mechanism. For the small-molecule-activated β2-andrenergic receptor, an induced-fit mechanism has been inferred from a comparison of ligand-association rates for the inactive and the active receptor conformation. A stabilization of the active receptor conformation by G proteins or nanobodies leads to a decrease of ligand association rates, which indicates that ligand binding occurs in the inactive conformation and, thus, prior to the change from the inactive to the active conformation as in the induced-fit mechanism. A structural explanation for the induced-fit mechanism of the β2-andrenergic receptor is a closed lid over the binding site that blocks ligand entry in the active conformation. Since constriction and closing of the ligand-binding site in the active conformation is rather common for small-molecule-activated and peptide-activated GPCRs, induced fit likely is shared as allosteric mechanism by these GPCRs