Unsupervised learning as a complement to convolutional neural network classification in the analysis of saccadic eye movement in spino-cerebellar ataxia type 2

IWANN es un congreso internacional que se celebra bienalmente desde 1991. Su campo de estudio se centra en la fundamentación y aplicación de las distintas técnicas de Inteligencia Computacional : Redes Neuronales Artificiales, Algoritmos Genéticos, Lógica Borrosa, Aprendizaje Automático. En esta edición han participado 150 investigadores.This paper aims at assessing spino-cerebellar type 2 ataxiaby classifying electrooculography records into registers corresponding to healthy, presymptomatic and ill individuals. The primary used technique is the convolutional neural network applied to the time series of eye movements, called saccades. The problem is exceptionally hard, though, because the recorded saccadic movements for presymptomatic cases often do not substantially di er from those of healthy individuals. Precisely this distinction is of the utmost clinical importance, since early intervention on presymptomatic patients can ameliorate symptoms or at least slow their progression. Yet, each register contains a number of saccades that, although not consistent with the current label, have not been considered indicative of another class by the examining physicians. As a consequence, an unsupervised learning mechanism may be more suitable to handle this form of misclassi cation. Thus, our proposal introduces the k-means approach and the SOM method, as complementary techniques to analyse the time series. The three techniques operating in tandem lead to a well performing solution to this diagnosis problem.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Universidad de Granada, Universitat Politècnica de Catalunya, Universidad de Las Palmas de Gran Canaria, Springe

Dynamic clustering of time series with Echo State Networks

In this paper we introduce a novel methodology for unsupervised analysis of time series, based upon the iterative implementation of a clustering algorithm embedded into the evolution of a recurrent Echo State Network. The main features of the temporal data are captured by the dynamical evolution of the network states, which are then subject to a clustering procedure. We apply the proposed algorithm to time series coming from records of eye movements, called saccades, which are recorded for diagnosis of a neurodegenerative form of ataxia. This is a hard classification problem, since saccades from patients at an early stage of the disease are practically indistinguishable from those coming from healthy subjects. The unsupervised clustering algorithm implanted within the recurrent network produces more compact clusters, compared to conventional clustering of static data, and provides a source of information that could aid diagnosis and assessment of the disease.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure

Gain of DNA methylation is enhanced in the absence of CTCF at the human retinoblastoma gene promoter

<p>Abstract</p> <p>Background</p> <p>Long-term gene silencing throughout cell division is generally achieved by DNA methylation and other epigenetic processes. Aberrant DNA methylation is now widely recognized to be associated with cancer and other human diseases. Here we addressed the contribution of the multifunctional nuclear factor CTCF to the epigenetic regulation of the human <it>retinoblastoma </it>(<it>Rb</it>) gene promoter in different tumoral cell lines.</p> <p>Methods</p> <p>To assess the DNA methylation status of the <it>Rb </it>promoter, genomic DNA from stably transfected human erythroleukemic K562 cells expressing a <it>GFP </it>reporter transgene was transformed with sodium bisulfite, and then PCR-amplified with modified primers and sequenced. Single- and multi-copy integrants with the CTCF binding site mutated were isolated and characterized by Southern blotting. Silenced transgenes were reactivated using 5-aza-2'-deoxycytidine and Trichostatin-A, and their expression was monitored by fluorescent cytometry. <it>Rb </it>gene expression and protein abundance were assessed by RT-PCR and Western blotting in three different glioma cell lines, and DNA methylation of the promoter region was determined by sodium bisulfite sequencing, together with CTCF dissociation and methyl-CpG-binding protein incorporation by chromatin immunoprecipitation assays.</p> <p>Results</p> <p>We found that the inability of CTCF to bind to the <it>Rb </it>promoter causes a dramatic loss of gene expression and a progressive gain of DNA methylation.</p> <p>Conclusions</p> <p>This study indicates that CTCF plays an important role in maintaining the <it>Rb </it>promoter in an optimal chromatin configuration. The absence of CTCF induces a rapid epigenetic silencing through a progressive gain of DNA methylation. Consequently, CTCF can now be seen as one of the epigenetic components that allows the proper configuration of tumor suppressor gene promoters. Its aberrant dissociation can then predispose key genes in cancer cells to acquire DNA methylation and epigenetic silencing.</p

Root traits explain plant species distributions along climatic gradients yet challenge the nature of ecological trade-offs

Ecological theory is built on trade-offs, where trait differences among species evolved as adaptations to different environments. Trade-offs are often assumed to be bidirectional, where opposite ends of a gradient in trait values confer advantages in different environments. However, unidirectional benefits could be widespread if extreme trait values confer advantages at one end of an environmental gradient, whereas a wide range of trait values are equally beneficial at the other end. Here, we show that root traits explain species occurrences along broad gradients of temperature and water availability, but model predictions only resembled trade-offs in two out of 24 models. Forest species with low specific root length and high root tissue density (RTD) were more likely to occur in warm climates but species with high specific root length and low RTD were more likely to occur in cold climates. Unidirectional benefits were more prevalent than trade-offs: for example, species with large-diameter roots and high RTD were more commonly associated with dry climates, but species with the opposite trait values were not associated with wet climates. Directional selection for traits consistently occurred in cold or dry climates, whereas a diversity of root trait values were equally viable in warm or wet climates. Explicit integration of unidirectional benefits into ecological theory is needed to advance our understanding of the consequences of trait variation on species responses to environmental change.</p

Rationally Designed Interfacial Peptides Are Efficient In Vitro Inhibitors of HIV-1 Capsid Assembly with Antiviral Activity

Virus capsid assembly constitutes an attractive target for the development of antiviral therapies; a few experimental inhibitors of this process for HIV-1 and other viruses have been identified by screening compounds or by selection from chemical libraries. As a different, novel approach we have undertaken the rational design of peptides that could act as competitive assembly inhibitors by mimicking capsid structural elements involved in intersubunit interfaces. Several discrete interfaces involved in formation of the mature HIV-1 capsid through polymerization of the capsid protein CA were targeted. We had previously designed a peptide, CAC1, that represents CA helix 9 (a major part of the dimerization interface) and binds the CA C-terminal domain in solution. Here we have mapped the binding site of CAC1, and shown that it substantially overlaps with the CA dimerization interface. We have also rationally modified CAC1 to increase its solubility and CA-binding affinity, and designed four additional peptides that represent CA helical segments involved in other CA interfaces. We found that peptides CAC1, its derivative CAC1M, and H8 (representing CA helix 8) were able to efficiently inhibit the in vitro assembly of the mature HIV-1 capsid. Cocktails of several peptides, including CAC1 or CAC1M plus H8 or CAI (a previously discovered inhibitor of CA polymerization), or CAC1M+H8+CAI, also abolished capsid assembly, even when every peptide was used at lower, sub-inhibitory doses. To provide a preliminary proof that these designed capsid assembly inhibitors could eventually serve as lead compounds for development of anti-HIV-1 agents, they were transported into cultured cells using a cell-penetrating peptide, and tested for antiviral activity. Peptide cocktails that drastically inhibited capsid assembly in vitro were also able to efficiently inhibit HIV-1 infection ex vivo. This study validates a novel, entirely rational approach for the design of capsid assembly interfacial inhibitors that show antiviral activity

Macrocheles species (Acari: Macrochelidae) associated with human corpses in Europe

The biology of macrochelid mites might offer new venues for the interpretation of the environmental conditions surrounding human death and decomposition. Three human corpses, one from Sweden and two from Spain, have been analysed for the occurrence of Macrochelidae species. Macrocheles muscaedomesticae females were associated with a corpse that was found in a popular beach area of southeast Spain. Their arrival coincides with the occurrence of one of their major carrier species, the filth fly Fannia scalaris, the activity of which peaks during mid-summer. M. glaber specimens were collected from a corpse in a shallow grave in a forest in Sweden at the end of summer, concurrent with the arrival of beetles attracted by odours from the corpse. M. perglaber adults were sampled from a corpse found indoors in the rural surroundings of Granada city, Spain. The phoretic behaviour of this species is similar to that of M. glaber, but being more specific to Scarabaeidae and Geotrupidae dung beetles, most of which favour human faeces. M. muscaedomesticae is known from urban and rural areas and poultry farms; M. glaber from outdoors, particularly the countryside; while M. perglaber from outdoor, rural, and remote, potentially mountainous locations. M. muscaedomesticae and M. perglaber are reported for the first time from the Iberian Peninsula. This is the first record of M. perglaber from human remains