julilili42/papers huggingface dataset:
An Image-Based Model for Early Visual Processing
2016-09-01

Early spatial vision was explored extensively over several decades in many psychophysical detection and discrimination experiments, and thus a large body of data is available. Goris et al. (2013; Psych. Rev.) integrated this psychophysical literature and proposed a model based on maximum-likelihood decoding of a neurophysiologically inspired population of model neurons. Their neural population model (NPM) is able to predict several data sets simultaneously, using a single set of parameters. However, the NPM is only one-dimensional, operating on the activity of abstract spatial frequency channels. Thus it cannot be applied to arbitrary images as a generic front-end to explore the influence of early visual processing on mid- or high-level vision. Bradley et. al. (2014; JoV), on the other hand, presented a model operating on images. Their model is thus able to make predictions for arbitrary images. However, compared to the NPM, their model lacks in nonlinear processing, which is replaced by an effective masking contrast depending on the detection target. Thus while Bradley et al. fit a range of detection data they do not fit nonlinear aspects of early vision like the dipper function. Here we combine both approaches and present a model which includes nonlinear processing and operates on images. In addition, the model applies optical degradation and retinal processing to the image before it is passed to a spatial frequency and orientation decomposition followed by divisive inhibition. For the optical transfer function of the eye and the distribution of retinal midget ganglion cells we use the approximations of Watson (2013, 2014; JoV). We tested the predictions of our model against a broad range of early psychophysical literature and found it predicts some hallmarks of early visual processing like the contrast sensitivity function under different temporal conditions and the dipper function for contrast discrimination. Meeting abstract presented at VSS 2016
An integrated model for the shading and silhouette cues in the perception of biological motion.
2016-09-01

In absence of stereo and texture cues the perception of biological motion can show multistability, where different walking directions can be attributed to the same physical stimulus (Vangeneugden 2012, Vanrie 2004, 2006). This bistability disappears for walkers that consist of shaded volumetric elements, where the disambiguation depends on the light-source direction. No neural models exist that account for this multi-stability of biological motion perception, or its dependence on shading cues. METHODS: We extended an established neural model for biological motion perception (Giese & Poggio, 2013) by two essential mechanisms: (i) A two-dimensional neural field that consists of snapshot neurons that are selective for keyframes of actions with different preferred views. The dynamics of this recurrent neural networks reproduces the multi-stability of biological perception. (ii) A new hierarchical pathway that processes intrinsic shading cues, independent of contours generated by the silhouette of the walker. RESULTS: The model reproduces the observed bistability of biological motion perception, perceptual switching, and its dependence on adaptation. We are able to reproduce the disambiguation by additional shading cues, and demonstrate that the robustness of processing of such internal shading cues is improved by the novel shading pathway. CONCLUSION: Body motion perception integrates multiple cues, including surface shading. Straight-forward extensions of existing neural models can account for these effects. Meeting abstract presented at VSS 2016
Seeking summary statistics that match peripheral visual appearance using naturalistic textures generated by Deep Neural Networks
2016-09-01

An important hypothesis that emerged from crowding research is that the perception of image structure in the periphery is texture-like. We investigate this hypothesis by measuring perceptual properties of a family of naturalistic textures generated using Deep Neural Networks (DNNs), a class of algorithms that can identify objects in images with near-human performance. DNNs function by stacking repeated convolutional operations in a layered feedforward hierarchy. Our group has recently shown how to generate shift-invariant textures that reproduce the statistical structure of natural images increasingly well, by matching the DNN representation at an increasing number of layers. Here, observers discriminated original photographic images from DNN-synthesised images in a spatial oddity paradigm. In this paradigm, low psychophysical performance means that the model is good at matching the appearance of the original scenes. For photographs of natural textures (a subset of the MIT VisTex dataset), discrimination performance decreased as the DNN representations were matched to higher convolutional layers. For photographs of natural scenes (containing inhomogeneous structure), discrimination performance was nearly perfect until the highest layers were matched, whereby performance declined (but never to chance). Performance was only weakly related to retinal eccentricity (from 1.5 to 10 degrees) and strongly depended on individual source images (some images were always hard, others always easy). Surprisingly, performance showed little relationship to size: within a layer-matching condition, images further from the fovea were somewhat harder to discriminate but this result was invariant to a three-fold change in image size (changed via up/down sampling). The DNN stimuli we examine here can match texture appearance but are not yet sufficient to match the peripheral appearance of inhomogeneous scenes. In the future, we can leverage the flexibility of DNN texture synthesis for testing different sets of summary statistics to further refine what information can be discarded without affecting appearance. Meeting abstract presented at VSS 2016
Parallel Lives: Friedrich Max Müller and William Wright
2016-09-01

This article compares and contrasts the life and career of Friedrich Max Müller (1823–1900) with those of the Semitic scholar William Wright (1830–1889), examining their relations with each other in the light of both scholarly publications and comments to be found in private letters of the period. From these it appears that tensions between Müller and some of his orientalist colleagues were due not only to different opinions in scholarly debates, but also to different conceptions of the role of scholars and the ways in which they should relate to the public.
Human neutrophils release bioactive inflammasome complexes; relevance for cystic fibrosis
2016-09-01

<b>Rationale.</b> Massive neutrophil recruitment and their secreted products are hallmarks of cystic fibrosis (CF) airway disease. We previously described that healthy neutrophils store key inflammasome components and release Il-1ß, found at high levels in CF airways (Bakele et al, 2014). Moreover, a recent study identified that inflammasomes, usually thought to be cytosolic multi-protein complexes, could be secreted and act as extracellular danger signal to amplify inflammation (Baroja-Mazo et al, 2014). <b>Aims.</b> We attempt to characterize neutrophil inflammasome components and their release to evaluate the potential impact in CF lung disease. <b>Methods.</b> We activated inflammasomes in isolated neutrophils and PBMCs (LPS +/- ATP or Nigericin) and also performed autocrine/paracrine stimulation to evaluate the impact on neutrophil/PBMC activity. Collected supernatants were analysed by western blot, enzymatic assays and ELISA to detect secreted inflammasome proteins and caspases9 activity and Il-1ß levels. Finally, we assessed inflammasome activity in CF neutrophils and fluids, which we compared to healthy control samples. <b>Results.</b> We demonstrated that human neutrophils release distinct oligomeric inflammasome-associated particles. These secreted complexes remained enzymatically active, interacted physically with caspase-1 and amplified the inflammatory response. In addition, we described inflammasome modulation in CF samples. <b>Conclusions.</b> These findings support a model where neutrophils release inflammasome components as an endogenous danger signal and therefore amplify the inflammatory response, suggesting potential anti-inflammatory therapeutic strategies in CF.
Screening eosinophil counts and risk of exacerbations after inhaled corticosteroid withdrawal in severe COPD
2016-09-01

<b>Introduction:</b> Blood eosinophil counts may predict response to inhaled corticosteroids (ICS) in patients with COPD with a history of exacerbations. <b>Aim:</b> To investigate if higher screening blood eosinophil counts were associated with more exacerbations after ICS withdrawal in the WISDOM study. <b>Methods:</b> In WISDOM (NCT00975195; 12-month, randomised, parallel-group study), patients with severe to very severe COPD and a history of exacerbations received 18 μg tiotropium, 100 μg salmeterol and 1000 μg fluticasone propionate daily for 6 weeks then continued or reduced ICS over the next 12 weeks. This <i>post hoc</i> analysis after complete ICS withdrawal compared exacerbation outcomes based on analysis of mutually exclusive blood eosinophil subgroups. <b>Results:</b> 2296 patients were followed post-ICS withdrawal. Moderate or severe exacerbation rate ratios were similar in patients with eosinophil counts &lt;2%, ≥2–&lt;3%, ≥3–&lt;4%, &lt;150 cells/μL or 150–&lt;300 cells/μL (Figure). Exacerbation rate increased in the ICS-withdrawal versus the ICS arm for blood eosinophil subgroups ≥4–&lt;5%, ≥5–&lt;6%, ≥6%, ≥300–&lt;400 cells/μL and ≥400 cells/μL, reaching statistical significance in the ≥5–&lt;6% and ≥400 cells/μL subgroups. <b>Conclusions:</b> In WISDOM, high screening blood eosinophil count (≥4% or ≥300 cells/μL) predicted an increased exacerbation risk in patients with severe to very severe COPD after ICS withdrawal. <b>Funding:</b> Boehringer Ingelheim.
L20 Olesoxime targets calpain overactivation in models of huntington’s disease
2016-09-01

<h3>Background</h3> A long-term treatment study of BACHD rats with olesoxime, a mitochondria-targeting drug, revealed beneficial effects on specific behavioural and neuropathological phenotypes. On the molecular level, olesoxime suppressed the activation of calpains, calcium-dependent cysteine proteases which were associated with cleavage of mutant huntingtin, through a yet unknown mechanism. <h3>Aims</h3> As calcium dyshomeostasis represents a hallmark of affected neurons in Huntington’s disease and mitochondrial function is essential for the maintenance of calcium levels, olesoxime might exert its calpain suppression by stabilising mitochondrial calcium buffering. By analysing olesoxime’s effects on calpains and calcium homeostasis in further cell and animal models, we sought to elucidate its underlying molecular mode of action. <h3>Methods</h3> To reproduce the observations made in our BACHD rats, we treated a second animal model of Huntington’s disease, the <i>Hdh</i><sup>Q111</sup> knock-in mouse, with olesoxime. For a more precise investigation of olesoxime’s molecular function, we utilised cell models and examined cell viability, calpain activation and calcium buffering capacity after drug treatment. <h3>Results</h3> We validated the decrease of calpain activation and huntingtin fragmentation by olesoxime treatment in <i>Hdh</i><sup>Q111</sup> knock-in mice. Furthermore, cell models showed beneficial effects of olesoxime on cell viability and calcium buffering capacity. <h3>Conclusions</h3> Our improved understanding of olesoxime’s mode of action can help us to optimise its application as a drug not only in Huntington’s disease but also in other disorders involving calpain overactivation.
C7 The bachd rat model of huntington’s disease shows signs of fronto-striatal dysfunction in two skinner box-based tests of short-term memory
2016-09-01

<h3>Background</h3> The BACHD rat is a recently established animal model of Huntington’s disease (HD), which expresses the full-length HD-causing gene. The rats are currently being characterised in order to investigate to what extent they model HD pathology. <h3>Aims</h3> To assess BACHD rats’ performance in Skinner box-based delayed alternation and delayed non-matching to position tests. <h3>Methods</h3> Both tests evaluate short-term memory. During test sessions, levers are available during discrete trials and rats are trained to respond to them in either an alternating or a non-matching to position-based fashion. Delays are then introduced to investigate how long the rats remember which lever to push. Two separate cohorts of male rats were used, one for each test. Rats were initially trained at 2–4 months of age and then retested at 7–9, 12–14 and 17–19 months of age. Performance baselines for wild type (WT) rats were established for two different food restriction protocols at each age, to evaluate if any parameters were affected by motivational changes. <h3>Results</h3> The BACHD rats had problems learning the alternation task, but not the non-matching to position task. During baseline performance BACHD rats still performed worse than WT rats in both tests. Specifically, BACHD rats showed generally lower success rates compared to WT rats, but showed similar drops in success rate with delay duration. Both genotypes appeared to use specific and identical behaviours during the delays to guide their lever choices. Still, BACHD rats showed a higher frequency of performing these mediating behaviours. The phenotypes did not appear to change with age or be affected by motivational factors. <h3>Conclusions</h3> The results indicate that BACHD rats have general problems with performing both tests, while not showing an impaired short-term memory function. Similar phenotypes have been found in other transgenic HD models, in animals with lesions to fronto-striatal circuits, and in HD patients. The BACHD rats’ frequent use of mediating behaviours might indicate that they are more dependent on these compared to WT rats, but it could also indicate a change in inhibitory control.
B48 DNA repair pathways as a common genetic mechanism modulating the age at onset in polyglutamine diseases
2016-09-01

<h3>Background</h3> Over 30 human diseases are caused by expansion of unstable microsatellite sequences. Nine of these are caused by expanded CAG tracts encoding polyglutamines in different genes. This subgroup of diseases, usually referred to as the polyglutamine diseases which include Huntington’s disease (HD), several spinocerebellar ataxias (SCAs), and spinal and bulbar muscular atrophy, are amongst the commonest hereditary neurodegenerative diseases. Longer CAG repeat tracts are associated with earlier ages at onset (AAO), but this does not account for all the variance, suggesting the existence of additional modifying factors. DNA repair pathways have been recently associated with the HD motor AAO in a recent HD GWAS. We therefore aimed to confirm the association between HD motor AAO and DNA repair pathways; and to investigate whether these modifying effects of variants in DNA repair genes can be extended to other polyglutamine diseases. <h3>Methods</h3> We collected an independent cohort of 1462 subjects with HD and polyglutamine SCAs, and genotyped SNPs selected from the most significant hits in the HD study. <h3>Results</h3> In an overall analysis of DNA repair pathway, we found the most significant association with AAO when grouping all polyglutamine diseases (HD+SCAs, p = 1.43 × 10<sup>−5</sup>). Significant associations were also found for HD (p = 0.00194), all SCAs (p = 0.00107), SCA2 (p = 0.0035), and SCA6 (p = 0.00162). Testing individual SNPs, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10<sup>−5</sup>) and all SCAs (p = 2.22 × 10<sup>−4</sup>), and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10<sup>−5</sup>). All these associations follow the same direction as in the HD GWAS. <h3>Conclusions</h3> We show that DNA repair genes significantly modify the AAO not only in HD, but also in polyglutamine SCAs. This suggests a common pathogenic mechanism for these diseases, which could operate through the observed somatic expansion of repeats. Manipulation of DNA repair pathways may offer novel therapeutic opportunities in multiple diseases.
C8 Metabolic properties of hypothalamic primary neuron cultures from bachd rats
2016-09-01

<h3>Background</h3> The BACHD rat overexpresses a bacterial artificial chromosome (BAC) with the full length human mutant huntingtin (mHTT) with 97 alternating CAA/CAG repeats, which are the sole cause of disease onset. BACHD rats display mHTT aggregates and nuclear accumulation of mHTT throughout the brain and develop behavioural and neuropathological- and metabolic abnormalities, growth deficits, mitochondrial dysfunction as well as obesity and a lack of body weight loss that are not typical for human HD. <h3>Aims</h3> The aim of this study was to investigate different metabolic properties and possible mitochondrial deficits in primary neurons of BACHD rats. <h3>Methods</h3> BACHD rat pups were dissected at embryonic day 19 and primary neurons of the hypothalamus, striatum and cortex were cultivated and used for following assays: MTT- and LDH-assays and IGF-1 levels for general health and growth. MitoTracker measurements and JC-1-assay to assess the mitochondrial membrane potential YO-PRO-1-Assay for the rate of mitochondrial apoptosis <h3>Results</h3> Hypothalamic neuron cultures had a lower overall metabolic activity than primary neurons of WT controls. These cells also showed an increased survival rate compared to control cells. The same effects were observed in the striatum, whereas cells from the cortex showed no significant reduction of the metabolic activity, but a decreased survival rate. Since the experiments are still onging at the date of the abstract submission no further results can be shown. <h3>Conclusion</h3> Our preliminary data and upcoming results will establish BACHD primary neurons as a valuable tool for the investigation of metabolic dysfunction in HD.
C3 Reduced cell size and enhanced cell proliferation are characteristics of sthdhq111/111 cells and should be considered as possible confounding factors
2016-09-01

<h3>Background</h3> The ST<i>Hdh</i> cell lines are immortalised striatal precursor cells from wild type and <i>Hdh</i><sup>Q111</sup> knock-in mice and are commonly used to study the molecular aspects of HD. Morphological differences between the wild type and mutant cell lines exist, but are rarely described or clearly considered in published reports. <h3>Aims</h3> The aim was to characterise cell size and proliferation differences in the ST<i>Hdh</i> cells, to investigate the importance of these phenotypes for HD and their possible confounding nature. <h3>Methods</h3> Cell size, cell proliferation, mTOR-related cell signalling and chromosome content were assessed in wild type ST<i>Hdh</i><sup>Q7/7</sup> and HD mutant ST<i>Hdh</i><sup>Q111/111</sup> cell lines as well as in primary cultures of mouse embryonic fibroblasts (MEF) established from the same mouse model (MEF<i>Hdh</i><sup>Q7/7</sup> and MEF<i>Hdh</i><sup>Q111/111</sup> cells). Cell viability and cell death were measured in ST<i>Hdh</i> cells using standard fluorometric assays and flow cytometry. <h3>Results</h3> ST<i>Hdh</i><sup>Q111/111</sup> as well as MEF<i>Hdh</i><sup>Q111/111</sup> cells were smaller, showed higher proliferation rates and higher levels of phosphorylated mTOR pathway components compared to their wild type counterpart. Both ST<i>Hdh</i> cell lines displayed chromosome multiplications already at early passages, although the phenotype was more severe in ST<i>Hdh</i><sup>Q7/7</sup> cells. No marked chromosome abnormalities were found in the MEF cells. Results from fluorometric cell viability assays indicated that ST<i>Hdh</i><sup>Q111/111</sup> cells had reduced cell viability and increased cell mortality. This was not supported by the results from flow cytometry, the readouts of which are likely to be unaffected by cell size and proliferation. <h3>Conclusions</h3> Differences in cell size and proliferation are characteristics of ST<i>Hdh</i><sup>Q111/111</sup> cells and might be caused by altered mTOR-related signalling. These phenotypes appear to be a general feature of HD, as they are also found in the second cell model. The different degree of genomic instability in wild type and mutant ST<i>Hdh</i> cells puts the usefulness of the wild type cells as controls in question. Furthermore, cell size and proliferation phenotypes are likely to confound test results and lead to inaccurate conclusions. Thus, our observations suggest that careful experimental design and well-considered data analysis are crucial when using this cell model.
C6 Novel behavioural readouts of the bachd rat in the reeperbahn and barnes maze tests
2016-09-01

<h3>Background</h3> Huntington’s disease (HD) is an inherited, autosomal, neurodegenerative disease. Symptoms of HD patients often include motor, emotional and cognitive deficits. BACHD rats overexpress the full length human mutant huntingtin gene with 97 alternating CAA/CAG repeats under control of the human HD promoter and are considered to be a valid option to gather novel insights on behavioural level. <h3>Aims</h3> We investigated wild type and transgenic male rats, with 7–15 months of age, for possible cognitive, social and motor impairments by performing the Reeperbahn test and Barnes maze. <h3>Methods/technique</h3> In the Reeperbahn test male rats had to learn the location of a sexually active wild type female in a dry-land apparatus. Males could freely explore the arena during learning/reversal learning, whereas in the recall sessions the female was removed. Additionally to automated behaviour measurements, the ultrasound vocalisation of males was recorded. The Barnes maze test investigates the possible spatial learning/reversal learning deficits in BACHD rats. The animals were challenged to use either proximal (egocentric) or distal (allocentric) visual cues to locate and remember the target zone. <h3>Results/outcome</h3> The Reeperbahn test data show that BACHD rats have a decreased exploration time when the female’s location is reversed. Furthermore, BACHD rats exhibit a deficit in reversal learning as well as decreased locomotor activity. Ultrasonic vocalisations and Barnes maze data are currently analysed. <h3>Conclusions</h3> All together, these newly established behavioural tests provide further evidence of cognitive and motor deficits in BACHD rats.