Sparse Coding Predicts Optic Flow Specificities of Zebrafish Pretectal Neurons

Zebrafish pretectal neurons exhibit specificities for large-field optic flow patterns associated with rotatory or translatory body motion. We investigate the hypothesis that these specificities reflect the input statistics of natural optic flow. Realistic motion sequences were generated using computer graphics simulating self-motion in an underwater scene. Local retinal motion was estimated with a motion detector and encoded in four populations of directionally tuned retinal ganglion cells, represented as two signed input variables. This activity was then used as input into one of two learning networks: a sparse coding network (competitive learning) and backpropagation network (supervised learning). Both simulations develop specificities for optic flow which are comparable to those found in a neurophysiological study (Kubo et al. 2014), and relative frequencies of the various neuronal responses are best modeled by the sparse coding approach. We conclude that the optic flow neurons in the zebrafish pretectum do reflect the optic flow statistics. The predicted vectorial receptive fields show typical optic flow fields but also "Gabor" and dipole-shaped patterns that likely reflect difference fields needed for reconstruction by linear superposition.Comment: Published Conference Paper from ICANN 2018, Rhode

Combined sedation with midazolam/propofol for gastrointestinal endoscopy in elderly patients

<p>Abstract</p> <p>Background</p> <p>Although gastrointestinal endoscopy with sedation is increasingly performed in elderly patients, data on combined sedation with midazolam/propofol are very limited for this age group.</p> <p>Methods</p> <p>We retrospectively analyzed 454 endoscopic procedures in 347 hospitalized patients ≥ 70 years who had received combined sedation with midazolam/propofol. 513 endoscopic procedures in 397 hospitalized patients < 70 years during the observation period served as controls. Characteristics of endoscopic procedures, co-morbidity, complications and mortality were compared.</p> <p>Results</p> <p>Elderly patients had a higher level of co-morbidity and needed lower mean propofol doses for sedation. We observed no major complication and no difference in the number of minor complications. The procedure-associated mortality was 0%; the 28-day mortality was significantly higher in the elderly (2.9% vs. 1.0%).</p> <p>Conclusions</p> <p>In this study on elderly patients with high level co-morbidity, a favourable safety profile was observed for a combined sedation with midazolam/propofol with a higher sensitivity to propofol in the elderly.</p

Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

Two New Vortex Liquids

It is suggested that the observations of nonlinear susceptibility and Nernst effect in cuprate superconductors above Tc, and those of non-classical rotational inertia in solid He, are two manifestations of a state of matter we call a vortex liquid, distinct from a conventional liquid in that its properties are dominated by conserved supercurrents flowing around a thermally fluctuating tangle of vortices

Wide-Field Motion Integration in Fly VS Cells: Insights from an Inverse Approach

Fly lobula plate tangential cells are known to perform wide-field motion integration. It is assumed that the shape of these neurons, and in particular the shape of the subclass of VS cells, is responsible for this type of computation. We employed an inverse approach to investigate the morphology-function relationship underlying wide-field motion integration in VS cells. In the inverse approach detailed, model neurons are optimized to perform a predefined computation: here, wide-field motion integration. We embedded the model neurons to be optimized in a biologically plausible model of fly motion detection to provide realistic inputs, and subsequently optimized model neuron with and without active conductances (gNa, gK, gK(Na)) along their dendrites to perform this computation. We found that both passive and active optimized model neurons perform well as wide-field motion integrators. In addition, all optimized morphologies share the same blueprint as real VS cells. In addition, we also found a recurring blueprint for the distribution of gK and gNa in the active models. Moreover, we demonstrate how this morphology and distribution of conductances contribute to wide-field motion integration. As such, by using the inverse approach we can predict the still unknown distribution of gK and gNa and their role in motion integration in VS cells

MicroRNA expression profiles in human cancer cells after ionizing radiation

Introduction: MicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers. MicroRNAs also modulate responses to anti-cancer therapy. In the context of radiation oncology microRNAs were found to modulate cell death and proliferation after irradiation. However, changes in microRNA expression profiles in response to irradiation have not been comprehensively analyzed so far. The present study's intend is to present a broad screen of changes in microRNA expression following irradiation of different malignant cell lines. Materials and methods: 1100 microRNAs (Sanger miRBase release version 14.0) were analyzed in six malignant cell lines following irradiation with clinically relevant doses of 2.0 Gy. MicroRNA levels 6 hours after irradiation were compared to microRNA levels in non-irradiated cells using the "Geniom Biochip MPEA homo sapiens". Results: Hierarchical clustering analysis revealed a pattern, which significantly (p = 0.014) discerned irradiated from non-irradiated cells. The expression levels of a number of microRNAs known to be involved in the regulation of cellular processes like apoptosis, proliferation, invasion, local immune response and radioresistance (e. g. miR-1285, miR-24-1, miR-151-5p, let-7i) displayed 2 - 3-fold changes after irradiation. Moreover, several microRNAs previously not known to be radiation-responsive were discovered. Conclusion: Ionizing radiation induced significant changes in microRNA expression profiles in 3 glioma and 3 squamous cell carcinoma cell lines. The functional relevance of these changes is not addressed but should by analyzed by future work especially focusing on clinically relevant endpoints like radiation induced cell death, proliferation, migration and metastasis

CUL-2^LRR-1 and UBXN-3 drive replisome disassembly during DNA replication termination and mitosis

Replisome disassembly is the final step of DNA replication in eukaryotes, involving the ubiquitylation and CDC48-dependent dissolution of the CMG helicase (CDC45-MCM-GINS). Using Caenorhabditis elegans early embryos and Xenopus laevis egg extracts, we show that the E3 ligase CUL-2(LRR-1) associates with the replisome and drives ubiquitylation and disassembly of CMG, together with the CDC-48 cofactors UFD-1 and NPL-4. Removal of CMG from chromatin in frog egg extracts requires CUL2 neddylation, and our data identify chromatin recruitment of CUL2(LRR1) as a key regulated step during DNA replication termination. Interestingly, however, CMG persists on chromatin until prophase in worms that lack CUL-2(LRR-1), but is then removed by a mitotic pathway that requires the CDC-48 cofactor UBXN-3, orthologous to the human tumour suppressor FAF1. Partial inactivation of lrr-1 and ubxn-3 leads to synthetic lethality, suggesting future approaches by which a deeper understanding of CMG disassembly in metazoa could be exploited therapeutically

Reexamining age, race, site, and thermometer type as variables affecting temperature measurement in adults – A comparison study

BACKGROUND: As a result of the recent international vigilance regarding disease assessment, accurate measurement of body temperature has become increasingly important. Yet, trusted low-tech, portable mercury glass thermometers are no longer available. Thus, comparing accuracy of mercury-free thermometers with mercury devices is essential. Study purposes were 1) to examine age, race, site as variables affecting temperature measurement in adults, and 2) to compare clinical accuracy of low-tech Galinstan-in-glass device to mercury-in-glass at oral, axillary, groin, and rectal sites in adults. METHODS: Setting 176 bed accredited healthcare facility, rural northwest US Participants Convenience sample (N = 120) of hospitalized persons ≥ 18 years old. Instruments Temperatures (°F) measured at oral, skin (simultaneous), immediately followed by rectal sites with four each mercury-glass (BD) and Galinstan-glass (Geratherm) thermometers; 10 minute dwell times. RESULTS: Participants averaged 61.6 years (SD 17.9), 188 pounds (SD 55.3); 61% female; race: 85% White, 8.3% Native Am., 4.2% Hispanic, 1.7 % Asian, 0.8% Black. For both mercury and Galinstan-glass thermometers, within-subject temperature readings were highest rectally; followed by oral, then skin sites. Galinstan assessments demonstrated rectal sites 0.91°F > oral and ≅ 1.3°F > skin sites. Devices strongly correlated between and across sites. Site difference scores between devices showed greatest variability at skin sites; least at rectal site. 95% confidence intervals of difference scores by site (°F): oral (0.142 – 0.265), axilla (0.167 – 0.339), groin (0.037 – 0.321), and rectal (-0.111 – 0.111). Race correlated with age, temperature readings each site and device. CONCLUSION: Temperature readings varied by age, race. Mercury readings correlated with Galinstan thermometer readings at all sites. Site mean differences between devices were considered clinically insignificant. Still considered the gold standard, mercury-glass thermometers may no longer be available worldwide. Therefore, mercury-free, environmentally safe low-tech Galinstan-in-glass may be an appropriate replacement. This is especially important as we face new, internationally transmitted diseases

Accurate Visuomotor Control below the Perceptual Threshold of Size Discrimination

Background: Human resolution for object size is typically determined by psychophysical methods that are based on conscious perception. In contrast, grasping of the same objects might be less conscious. It is suggested that grasping is mediated by mechanisms other than those mediating conscious perception. In this study, we compared the visual resolution for object size of the visuomotor and the perceptual system. Methodology/Principal Findings: In Experiment 1, participants discriminated the size of pairs of objects once through perceptual judgments and once by grasping movements toward the objects. Notably, the actual size differences were set below the Just Noticeable Difference (JND). We found that grasping trajectories reflected the actual size differences between the objects regardless of the JND. This pattern was observed even in trials in which the perceptual judgments were erroneous. The results of an additional control experiment showed that these findings were not confounded by task demands. Participants were not aware, therefore, that their size discrimination via grasp was veridical. Conclusions/Significance: We conclude that human resolution is not fully tapped by perceptually determined thresholds

An incremental approach to automated protein localisation

Tscherepanow M, Jensen N, Kummert F. An incremental approach to automated protein localisation. BMC Bioinformatics. 2008;9(1): 445.Background: The subcellular localisation of proteins in intact living cells is an important means for gaining information about protein functions. Even dynamic processes can be captured, which can barely be predicted based on amino acid sequences. Besides increasing our knowledge about intracellular processes, this information facilitates the development of innovative therapies and new diagnostic methods. In order to perform such a localisation, the proteins under analysis are usually fused with a fluorescent protein. So, they can be observed by means of a fluorescence microscope and analysed. In recent years, several automated methods have been proposed for performing such analyses. Here, two different types of approaches can be distinguished: techniques which enable the recognition of a fixed set of protein locations and methods that identify new ones. To our knowledge, a combination of both approaches – i.e. a technique, which enables supervised learning using a known set of protein locations and is able to identify and incorporate new protein locations afterwards – has not been presented yet. Furthermore, associated problems, e.g. the recognition of cells to be analysed, have usually been neglected. Results: We introduce a novel approach to automated protein localisation in living cells. In contrast to well-known techniques, the protein localisation technique presented in this article aims at combining the two types of approaches described above: After an automatic identification of unknown protein locations, a potential user is enabled to incorporate them into the pre-trained system. An incremental neural network allows the classification of a fixed set of protein location as well as the detection, clustering and incorporation of additional patterns that occur during an experiment. Here, the proposed technique achieves promising results with respect to both tasks. In addition, the protein localisation procedure has been adapted to an existing cell recognition approach. Therefore, it is especially well-suited for high-throughput investigations where user interactions have to be avoided. Conclusion: We have shown that several aspects required for developing an automatic protein localisation technique – namely the recognition of cells, the classification of protein distribution patterns into a set of learnt protein locations, and the detection and learning of new locations – can be combined successfully. So, the proposed method constitutes a crucial step to render image-based protein localisation techniques amenable to large-scale experiments