A Recognition-Based Alternative to Discrimination-Based Multi-layer Perceptrons

Though impressive classification accuracy is often obtained via discrimination-based learning techniques such as Multi-Layer Perceptrons (DMLP), these techniques often assume that the underlying training sets are optimally balanced (in terms of the number of positive and negative examples). Unfortunately, this is not always the case. In this paper, we look at a recognitionbased approach whose accuracy in such environments is superior to that obtained via more conventional mechanisms. At the heart of the new technique is a modified auto-encoder that allows for the incorporation of a recognition component into the conventional MLP mechanism. In short, rather than being associated with an output value of "1", positive examples are fully reconstructed at the network output layer while negative examples, rather than being associated with an output value of "0", have their inverse derived at the output layer. The result is an auto-encoder able to recognize positive examples while discriminating against negative ones by virtue of the fact that negative cases generate larger reconstruction errors. A simple technique is employed to exaggerate the impact of training with these negative examples so that reconstruction errors can be more reliably established. Preliminary testing on both seismic and sonar data sets has demonstrated that the new method produces lower error rates than standard connectionist systems in imbalanced settings. Our approach thus suggests a simple and more robust alternative to commonly used classification mechanisms

Estabelecimento de espécies florestais em substrato degradado.

O estabelecimento e o desenvolvimento inicial (ate um ano de idade) de quatro especies florestais foi verificando em um substrato oriundo de area de exploracao de xisto pirobetuminoso, no municipio de Sao Mateus do Sul, PR. As mudas cresceram em casa de vegetacao, sendo que ao final de um ano foram avaliados o peso seco aereo e de nodulos, altura das plantas, diametro do colo, comprimento de raiz, mortalidade e colonizacao micorrizica. Os dados foram analisados atraves de uma analise de Cluster. dentre as quatro especies testadas, Acacia longifolia foi a que apresentou a maior sobrevivencia (61%) e o maior peso seco de materia seca, tendo o melhor comportamento geral entre as especies testadas. De maneira oposta, Mimosa scabrella foi a que apresentou o menor preco de materia seca e a menor colonizacao micorrizica. Tipuana tipu apresentou a mais alta colonizacao por fungos micorrizicos arbusculares (66%), um bom peso seco de nodulos (0,18g) e um bom desenvolvimento global, apesar de possuir um sistema radicular pouco desenvolvido. Mimosa bimucronata apresentou um desenvolvimento medio sob todos os aspectos. De maneira geral, o substrato testado nao apresentou capacidade de suporte ao estabelecimento e desenvolvimento das especies estudadas. A analise dos dados sugere que as especies testadas podem se beneficiar da inoculacao com fungos micorrizicos e Rhizobium

Transgenic mouse lines for non-invasive ratiometric monitoring of intracellular chloride

Chloride is the most abundant physiological anion and participates in a variety of cellular processes including trans-epithelial transport, cell volume regulation, and regulation of electrical excitability. The development of tools to monitor intracellular chloride concentration ([Cli]) is therefore important for the evaluation of cellular function in normal and pathological conditions. Recently, several Cl-sensitive genetically encoded probes have been described which allow for non-invasive monitoring of [Cli]. Here we describe two mouse lines expressing a CFP-YFP-based Cl probe called Cl-Sensor. First, we generated transgenic mice expressing Cl-Sensor under the control of the mouse Thy1 mini promoter. Cl-Sensor exhibited good expression from postnatal day two (P2) in neurons of the hippocampus and cortex, and its level increased strongly during development. Using simultaneous whole-cell monitoring of ionic currents and Cl-dependent fluorescence, we determined that the apparent EC50 for Cli was 46 mM, indicating that this line is appropriate for measuring neuronal [Cli] in postnatal mice. We also describe a transgenic mouse reporter line for Cre-dependent conditional expression of Cl-Sensor, which was targeted to the Rosa26 locus and by incorporating a strong exogenous promoter induced robust expression upon Cre-mediated recombination. We demonstrate high levels of tissue-specific expression in two different Cre-driver lines targeting cells of the myeloid lineage and peripheral sensory neurons. Using these mice the apparent EC50 for Cli was estimated to be 61 and 54 mM in macrophages and DRG, respectively. Our data suggest that these mouse lines will be useful models for ratiometric monitoring of Cli in specific cell types in vivo. © 2013 Batti, Mukhtarov, Audero, Ivanov, Paolicelli, Zurborg, Gross, Bregestovski and Heppenstall

Duchenne muscular dystrophy: disease mechanism and therapeutic strategies

Duchenne muscular dystrophy (DMD) is a severe, progressive, and ultimately fatal disease of skeletal muscle wasting, respiratory insufficiency, and cardiomyopathy. The identification of the dystrophin gene as central to DMD pathogenesis has led to the understanding of the muscle membrane and the proteins involved in membrane stability as the focal point of the disease. The lessons learned from decades of research in human genetics, biochemistry, and physiology have culminated in establishing the myriad functionalities of dystrophin in striated muscle biology. Here, we review the pathophysiological basis of DMD and discuss recent progress toward the development of therapeutic strategies for DMD that are currently close to or are in human clinical trials. The first section of the review focuses on DMD and the mechanisms contributing to membrane instability, inflammation, and fibrosis. The second section discusses therapeutic strategies currently used to treat DMD. This includes a focus on outlining the strengths and limitations of approaches directed at correcting the genetic defect through dystrophin gene replacement, modification, repair, and/or a range of dystrophin-independent approaches. The final section highlights the different therapeutic strategies for DMD currently in clinical trials

Differential transcriptional profiling of damaged and intact adjacent dorsal root ganglia neurons in neuropathic pain

Neuropathic pain, caused by a lesion in the somatosensory system, is a severely impairing mostly chronic disease. While its underlying molecular mechanisms are not thoroughly understood, neuroimmune interactions as well as changes in the pain pathway such as sensitization of nociceptors have been implicated. It has been shown that not only are different cell types involved in generation and maintenance of neuropathic pain, like neurons, immune and glial cells, but, also, intact adjacent neurons are relevant to the process. Here, we describe an experimental approach to discriminate damaged from intact adjacent neurons in the same dorsal root ganglion (DRG) using differential fluorescent neuronal labelling and fluorescence-activated cell sorting (FACS). Two fluorescent tracers, Fluoroemerald (FE) and 1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI), were used, whose properties allow us to distinguish between damaged and intact neurons. Subsequent sorting permitted transcriptional analysis of both groups. Results and qPCR validation show a strong regulation in damaged neurons versus contralateral controls as well as a moderate regulation in adjacent neurons. Data for damaged neurons reveal an mRNA expression pattern consistent with established upregulated genes like galanin, which supports our approach. Moreover, novel genes were found strongly regulated such as corticotropinreleasing hormone (CRH), providing novel targets for further research. Differential fluorescent neuronal labelling and sorting allows for a clear distinction between primarily damaged neuropathic neurons and "bystanders," thereby facilitating a more detailed understanding of their respective roles in neuropathic processes in the DRG

Secondary Endoleak Management Following TEVAR and EVAR.

Endovascular abdominal and thoracic aortic aneurysm repair and are widely used to treat increasingly complex aneurysms. Secondary endoleaks, defined as those detected more than 30 days after the procedure and after previous negative imaging, remain a challenge for aortic specialists, conferring a need for long-term surveillance and reintervention. Endoleaks are classified on the basis of their anatomic site and aetiology. Type 1 and type 2 endoleaks (EL1 and EL2) are the most common endoleaks necessitating intervention. The management of these requires an understanding of their mechanics, and the risk of sac enlargement and rupture due to increased sac pressure. Endovascular techniques are the main treatment approach to manage secondary endoleaks. However, surgery should be considered where endovascular treatments fail to arrest aneurysm growth. This chapter reviews the aetiology, significance, management strategy and techniques for different endoleak types

A French comparative monocentric study of stent-grafts for abdominal aortic aneurysms

BACKGROUND: Endovascular treatment of abdominal aortic aneurysms (AAA) has become more common and is expected to fit best for high risk patients even if it displays an increased number of secondary reintervention when compared to open surgery. METHODS: Cohort study of 311 consecutive patients with AAAs treated by endovascular repair from 2004 to 2015 in a single University Hospital were analyzed and included in the study. We computed Kaplan-Meier life tables to estimate all-cause survival at 30 days and 1 year as well as to estimate rate of endovascular and global (endovascular + surgical) reintervention, incidence of endoleaks and of aneurysm progression at 1 month, 3 months, 6 months and 1 year. Patients were observed from the date of intervention. RESULTS: Sixty-eight patients were lost to follow-up. No statistically significant differences emerged from the comparison of 30 days mortality between the 6 endograft groups (overall rate 1.7%, P=0.787). No significant differences of mean aneurysm diameter reduction recorded within 1 year from intervention were observed between the groups. Overall diameter stability, regression and progression occurred in 82.5%, 12.5% and 4.5%, respectively. Cook device displayed the highest incidence of type I endoleak within the 1st postoperative year (11.5% vs. 2.4%; HR=3.75, 95% CI: 0.95-14.73, P=0.059) while Gore and Anaconda devices of type II endoleaks within the same period (49.5% vs. 26.0%; HR=1.79, 95% CI: 0.95-3.40, P=0.073). Endovascular aneurysm repair treatment failed in 16 patients (5.1%) who were thus converted to open surgery. CONCLUSIONS: Gore and Cook devices resulted those with the highest incidence of type II endoleaks and of global reintervention while AFX resulted the device with the lowest incidence of both the events mentioned. In conclusion, regular follow-up of patients is mandatory for the effectiveness of endovascular treatment and to detect early complications and when EVAR fails, open surgical repair is still a reasonable surgical alternative