Support Vector Machine Implementations for Classification & Clustering

BACKGROUND: We describe Support Vector Machine (SVM) applications to classification and clustering of channel current data. SVMs are variational-calculus based methods that are constrained to have structural risk minimization (SRM), i.e., they provide noise tolerant solutions for pattern recognition. The SVM approach encapsulates a significant amount of model-fitting information in the choice of its kernel. In work thus far, novel, information-theoretic, kernels have been successfully employed for notably better performance over standard kernels. Currently there are two approaches for implementing multiclass SVMs. One is called external multi-class that arranges several binary classifiers as a decision tree such that they perform a single-class decision making function, with each leaf corresponding to a unique class. The second approach, namely internal-multiclass, involves solving a single optimization problem corresponding to the entire data set (with multiple hyperplanes). RESULTS: Each SVM approach encapsulates a significant amount of model-fitting information in its choice of kernel. In work thus far, novel, information-theoretic, kernels were successfully employed for notably better performance over standard kernels. Two SVM approaches to multiclass discrimination are described: (1) internal multiclass (with a single optimization), and (2) external multiclass (using an optimized decision tree). We describe benefits of the internal-SVM approach, along with further refinements to the internal-multiclass SVM algorithms that offer significant improvement in training time without sacrificing accuracy. In situations where the data isn't clearly separable, making for poor discrimination, signal clustering is used to provide robust and useful information – to this end, novel, SVM-based clustering methods are also described. As with the classification, there are Internal and External SVM Clustering algorithms, both of which are briefly described

Low dose cranial irradiation-induced cerebrovascular damage is reversible in mice

BACKGROUND: High-dose radiation-induced blood-brain barrier breakdown contributes to acute radiation toxicity syndrome and delayed brain injury, but there are few data on the effects of low dose cranial irradiation. Our goal was to measure blood-brain barrier changes after low (0.1 Gy), moderate (2 Gy) and high (10 Gy) dose irradiation under in vivo and in vitro conditions. METHODOLOGY: Cranial irradiation was performed on 10-day-old and 10-week-old mice. Blood-brain barrier permeability for Evans blue, body weight and number of peripheral mononuclear and circulating endothelial progenitor cells were evaluated 1, 4 and 26 weeks postirradiation. Barrier properties of primary mouse brain endothelial cells co-cultured with glial cells were determined by measurement of resistance and permeability for marker molecules and staining for interendothelial junctions. Endothelial senescence was determined by senescence associated β-galactosidase staining. PRINCIPLE FINDINGS: Extravasation of Evans blue increased in cerebrum and cerebellum in adult mice 1 week and in infant mice 4 weeks postirradiation at all treatment doses. Head irradiation with 10 Gy decreased body weight. The number of circulating endothelial progenitor cells in blood was decreased 1 day after irradiation with 0.1 and 2 Gy. Increase in the permeability of cultured brain endothelial monolayers for fluorescein and albumin was time- and radiation dose dependent and accompanied by changes in junctional immunostaining for claudin-5, ZO-1 and β-catenin. The number of cultured brain endothelial and glial cells decreased from third day of postirradiation and senescence in endothelial cells increased at 2 and 10 Gy. CONCLUSION: Not only high but low and moderate doses of cranial irradiation increase permeability of cerebral vessels in mice, but this effect is reversible by 6 months. In-vitro experiments suggest that irradiation changes junctional morphology, decreases cell number and causes senescence in brain endothelial cells

Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications

The ability to deliver drug molecules effectively across the blood–brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations, and to those with different pathologies or degrees of pathology, obviously demands caution. Nevertheless, microdialysis data can provide valuable guidelines for designing CNS therapies, and play an important role in small phase II clinical trials. In this review, we focus on the role of cerebral microdialysis in recent clinical studies of antimicrobial agents, drugs for tumour therapy, neuroprotective agents and anticonvulsants

Étude de la perméabilité de la barrière hémato-encéphalique par microdialyse après irradiation photonique monofractionnée chez le rat

The effects of total-body irradiation on the permeability of rat striatal blood-brain barrier (BBB) to [ 3H] aminoisobutyric acid (AIBA) and [ 14C] sucrose were investigated. Seven days, 6 weeks, 3 and 5 months after gamma exposure at the dose of 4.5 Gy, no modification of the permeability to both [ 3H] AIBA and [ 14C] sucrose was observed. A transient “opening" of the BBB to [ 14C] sucrose was noticed about 28 hours following irradiation. The transport of [3H] AIBA through BBB was decreased between the 33th and the 47th post-radiation hour

Quantitation of brain metabolites by HRMAS-NMR spectroscopy in rats exposed to sublethal irradiation.

Puropose : In the event of an acute total-body irradiation, whatever it is therapeutic or accidental, the physiopathology explaining the long-term neurological effects is unknown. We have developed a model of adult rats for which frequent behavioral assays were performed before and after a non-lethal whole-body ionizing radiation (60Co, 4,5 Gy). Learning and memory processing is an aspect of cognition involving mainly the hippocampus. We used high-resolution magic angle spinning (HRMAS) 1H NMR spectroscopy to characterize the biochemistry of four specific brain regions. The biological data for each animal will be compared to their behavioral performances, in order to underline any possible correlations. The best understanding of the physiopathological process in the Central Nervous System (CNS) will allow determining some prevention means or some enhancements for the radio-induced neurological late effects. Experimental procedures: Twenty male Wistar rats were experimented for each sample period, among which ten were gamma radiated (4.5 Gy). The cerebral structures (cortex, striata, anterior and posterior hippocampus, hypothalamus) were removed at three times: 48 hours, 8 days and 30 days after radiation. The HRMAS 1H NMR experiments were performed on a Brüker DRX Avance spectrometer at 9.4 T. Samples were spun at 4 kHz and the temperature maintained at 4°C. A spin-echo sequence with a 30ms total echo time was used. Eighteen metabolites were included in the basis. They were quantitated using the quest procedure of JMRUI software, and statistically analyzed. Moreover, another group of animals was radiated and tested in the same conditions. Then a immuno-histological study of apoptosis and neurogenesis events in the CNS was made at the same removal times. Results: NMR HRMAS results present significant differences (p<0.05) between the radiated group and the non-radiated one. GPC decreased at 48 hours post-radiation whereas Cho and PC increased, potentially with relation to a cerebral oedema. At Day-8, a decrease of Gly and Tau, and an increase in Gln, are observed in the posterior hippocampus. One month after total body irradiation, we observe an increase of GABA in cortex and striatum. Perspectives: The behavioral data, showing a significant difference in the cognitive capacities of the rats between the radiated group and the witnesses at one month, may suggest that relevant correlations are possible with biochemical and morphological modifications of the CNS. For example, the increase in GABA levels in cortex and striatum might explain the least performances of learning test