Improving Text Classification with Word Embedding

One challenge in text classification is that it is hard to make feature reduction basing upon the meaning of the features. An improper feature reduction may even worsen the classification accuracy. Word2Vec, a word embedding method, has recently been gaining popularity due to its high precision rate of analyzing the semantic similarity between words at relatively low computational cost. However, there are only a limited number of researchers focusing on feature reduction using Word2Vec. In this project, we developed a Word2Vec based method to reduce the feature size while increasing the classification accuracy. The feature reduction is achieved by loosely clustering the similar features using graph search techniques. The similarity thresholds above 0.5 are used in our method to pair and cluster the features. Finally, we utilize Multinomial Naïve Bayes classifier, Support Vector Machine, K-Nearest Neighbor and Random Forest classifier to evaluate the effect of our method. Four datasets with dimensions up to 100,000 feature size and 400,000 document size are used to evaluate the result of our method. The result shows that around 4-10% feature reduction is achieved with up to 1-4% improvement of classification accuracy in terms of different datasets and classifiers. Meanwhile, we also show success in improving feature reduction and classification accuracy by combining our method with other classic feature reduction techniques such as chi-square and mutual information

The serine/threonine kinase AKT switches between functional modes of the vesicle release machinery

Neurotransmitter release is a fundamental process in the nervous system by which neurons are enabled to communicate with postsynaptic cells in a highly controlled manner. This communication is mediated by three types of neurotransmitter release: synchronous, asynchronous and spontaneous vesicle releases, of which each has its own functional importance. A misbalance of these forms of transmitter release is therefore likely associated with improper information processing and may hence lead to network malfunction or even psychiatric conditions. While the fundamental principles of synaptic neurotransmission have been well clarified, questions remain whether for example the different release modes are based on distinct identities of vesicular release machineries or whether they reflect different functional states of the same vesicle release machinery. In this thesis we approached these and related questions at the larval (neuromuscular junction) NMJ of Drosophila melanogaster. We found that the membrane-associated serine/threonine kinase AKT, a nodal part of the phosphatidylinositol-3-kinase (PI3K) signaling pathway, is required to maintain the release machineries of presynaptic vesicles in a tightly clamped and calcium-sensitive status. In this status vesicle release can be evoked synchronously or asynchronously by action potentials and associated calcium influxes. Lost or reduced AKT activity switches the release machinery into a calcium-insensitive and fusogenic status resulting in spontaneous vesicle release that is independent of action potentials or the presence of calcium. AKT-mediated switching of the functional status of vesicle release machineries is a rapid process that acts acutely on readily releasable vesicles and hence can dynamically influence synaptic communication. Mechanistically, we show that the calcium sensor Synaptotagmin 1 that is also part of the release machineriesʼ fusion clamp mediates the AKT effects and hence may be a direct target of AKT phosphorylation. We further show that the clustered and functionally intact voltage gated calcium channel Cacophony is required for the AKT interaction with the release machinery, suggesting that only docked and primed vesicles are accessible to and regulated by AKT. These results demonstrate that AKT is an essential direct regulator of the mode by which synaptic vesicles can be released. In chapter II, with an attempt to identify potential synaptic regulators of AKT we assessed whether the recently identified ATP-dependent on-off switch of AKT might play a role in the regulation of its synaptic function. We found that treatment with oligomycin resulted in enhanced spontaneous vesicle release that was similar to that elicited by AKT blockade. Short trains of nerve stimulation during oligomycin incubation triggered an instantaneous increase in the rate of spontaneous vesicle release whereas a similar stimulation without oligomycin was without effect. These data indicate that nerve stimulation strongly enhances the ATP consumption in nerve terminals resulting in ATP-depletion and perhaps in AKT-inactivation. To test this hypothesis we made use of an alternative ATP-depletion strategy that allowed us to make postsynaptic recordings during periods of intense nerve stimulation. We found that stimulation-induced ATP-depletion triggered a strong enhancement of spontaneous vesicle release that was indeed AKT- and PI3K-dependent, which was mediated by Synaptotagmin 1 and depended on the functional presence of the Cacophony. These results confirmed the functional existence of a Cacophony/AKT/release machinery complex and they suggest that AKT is regulated by ATP. They further suggest that AKT may serve at vesicle release sites as a local energy sensor that depending on the availability of ATP switches individual vesicle release machinery either into a tightly clamped mode for evoked release or at low ATP levels into a loosely clamped mode generating spontaneous release. This novel and evolutionarily conserved synaptic role of AKT could shed new light onto the pathogenesis of Schizophrenia or Autism Spectrum Disorders in which AKT activities seem to be reduced. It also needs to be considered in recent approaches to treat several forms of cancer with AKT-inhibitors. In parallel to the above work, I was involved in a collaborative project that aimed at establishing a three-dimensional computational model of the glutamatergic synapses of larval NMJs. Chapter III summarizes the experimental data that formed the basis of the computational model and showed that high frequency nerve stimulation leads to a disproportional decay of evoked EJP amplitudes due to limited vesicle supply. The model is described in the discussion

Synaptic boutons sizes are tuned to best fit their physiological performances

To truly appreciate the myriad of events which relate synaptic function and vesicle dynamics, simulations should be done in a spatially realistic environment. This holds true in particular in order to explain as well the rather astonishing motor patterns which we observed within in vivo recordings which underlie peristaltic contractionsas well as the shape of the EPSPs at different forms of long-term stimulation, presented both here, at a well characterized synapse, the neuromuscular junction (NMJ) of the Drosophila larva (c.f. Figure 1). To this end, we have employed a reductionist approach and generated three dimensional models of single presynaptic boutons at the Drosophila larval NMJ. Vesicle dynamics are described by diffusion-like partial differential equations which are solved numerically on unstructured grids using the uG platform. In our model we varied parameters such as bouton-size, vesicle output probability (Po), stimulation frequency and number of synapses, to observe how altering these parameters effected bouton function. Hence we demonstrate that the morphologic and physiologic specialization maybe a convergent evolutionary adaptation to regulate the trade off between sustained, low output, and short term, high output, synaptic signals. There seems to be a biologically meaningful explanation for the co-existence of the two different bouton types as previously observed at the NMJ (characterized especially by the relation between size and Po), the assigning of two different tasks with respect to short- and long-time behaviour could allow for an optimized interplay of different synapse types. We can present astonishing similar results of experimental and simulation data which could be gained in particular without any data fitting, however based only on biophysical values which could be taken from different experimental results. As a side product, we demonstrate how advanced methods from numerical mathematics could help in future to resolve also other difficult experimental neurobiological issues

Research advances on the molecular biological mechanism of purple vegetables colorization

Anthocyanins are water-soluble pigments,and they play vital roles in many biological functions such as oxidation resistance,preventing and curing many diseases.The purple vegetables accumulate abundant anthocyanins.Its value of scientific research and economic and social benefits of the purple vegetables have become more obvious.In this review,we focused on recent advances regarding the colour related genes and breeding,and proposed a regulation model of anthocyanins biosynthesis in purple vegetables.It will be provide theoretic foundation to further research on anthocyanins biosynthesis and acaumulation,metabolic regulation and control,and genetic improvement of special vegetables

Synaptic bouton properties are tuned to best fit the prevailing firing pattern

The morphology of presynaptic specializations can vary greatly ranging from classical single-release-site boutons in the central nervous system to boutons of various sizes harboring multiple vesicle release sites. Multi-release-site boutons can be found in several neural contexts, for example at the neuromuscular junction (NMJ) of body wall muscles of Drosophila larvae. These NMJs are built by two motor neurons forming two types of glutamatergic multi-release-site boutons with two typical diameters. However, it is unknown why these distinct nerve terminal configurations are used on the same postsynaptic muscle fiber. To systematically dissect the biophysical properties of these boutons we developed a full three-dimensional model of such boutons, their release sites and transmitter-harboring vesicles and analyzed the local vesicle dynamics of various configurations during stimulation. Here we show that the rate of transmission of a bouton is primarily limited by diffusion-based vesicle movements and that the probability of vesicle release and the size of a bouton affect bouton-performance in distinct temporal domains allowing for an optimal transmission of the neural signals at different time scales. A comparison of our in silico simulations with in vivo recordings of the natural motor pattern of both neurons revealed that the bouton properties resemble a well-tuned cooperation of the parameters release probability and bouton size, enabling a reliable transmission of the prevailing firing-pattern at diffusion-limited boutons. Our findings indicate that the prevailing firing-pattern of a neuron may determine the physiological and morphological parameters required for its synaptic terminals

Ratios of peripheral blood mononuclear cells to lncRNA steroid receptor RNA activator as new indicators of metabolic syndrome

Introduction: Metabolic syndrome (MetS) is a clinical syndrome with several characteristics. Steroid receptor RNA activator (SRA) is a long non-coding RNA (lncRNA), which can increase the expression of steroid receptor-dependent gene. This study aimed to explore the changes in metabolic parameters and the predictive value of the peripheral blood mononuclear cells (PBMCs) to SRA ratios as new indicators in subjects with and without MetS in southern China. Material and methods: There were 81 participants (39 with MetS and 42 without MetS) in this cross-sectional study. The expression of lncRNAs in PBMCs was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The risks of SRA and PBMCs to SRA ratios contributing to the presence of MetS were estimated by univariate and multivariate logistic regression models. The area under the receiver (AUC) operating characteristic curve was employed to evaluate diagnostic accuracy. Results: MetS was positively correlated with cortisol, interleukin 6 (IL-6), white blood cell to SRA ratio (WTSR),  lymphocyte to SRA ratio (LTSR), monocyte to SRA ratio (MTSR), and PBMC to SRA ratio (PTSR). A receiver operating characteristic (ROC) curve analysis was performed to assess the value of LTSR (OR: 0.722; p < 0.001) for predicting MetS. The area under the curve yielded a cut-off value of 0.483, with a sensitivity of 76.9% and a specificity of 71.4% (p < 0.001). Conclusion: In summary, SRA in PBMCs may be an important biomarker of stress reaction and may play a role in vulnerability to MetS. Also, the lymphocyte to SRA ratio demonstrated high accuracy in the diagnosis of MetS

Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine actions

The function and pharmacology of γ-aminobutyric acid type A receptors (GABAARs) are of great physiological and clinical importance and have long been thought to be determined by the channel pore-forming subunits. We discovered that Shisa7, a single-passing transmembrane protein, localizes at GABAergic inhibitory synapses and interacts with GABAARs. Shisa7 controls receptor abundance at synapses and speeds up the channel deactivation kinetics. Shisa7 also potently enhances the action of diazepam, a classic benzodiazepine, on GABAARs. Genetic deletion of Shisa7 selectively impairs GABAergic transmission and diminishes the effects of diazepam in mice. Our data indicate that Shisa7 regulates GABAAR trafficking, function, and pharmacology and reveal a previously unknown molecular interaction that modulates benzodiazepine action in the brain