Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation.

OBJECTIVE: This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. METHODS: Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. RESULTS: Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. CONCLUSIONS: High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms mediating a sustained 'perpetual cycle' of appetite enhancement were observed. The GlyR protein may constitute a novel treatment target for the reduction of central orexigenic signals in obesity.

Hopfield neural network implementation of the optimal CDMA multiuser detector.

We investigate the application of Hopfield neural networks (HNN's) to the problem of multiuser detection in spread spectrum/CDMA (code division multiple access) communication systems. It is shown that the NP-complete problem of minimizing the objective function of the optimal multiuser detector (OMD) can be translated into minimizing an HNN "energy" function, thus allowing to take advantage of the ability of HNN's to perform very fast gradient descent algorithms in analog hardware and produce in real-time suboptimal solutions to hard combinatorial optimization problems. The performance of the proposed HNN receiver is evaluated via computer simulations and compared to that of other suboptimal schemes as well as to that of the OMD for both the synchronous and the asynchronous CDMA transmission cases. It is shown that the HNN detector exhibits a number of attractive properties and that it provides a powerful generalization of a well-known and extensively studied suboptimal scheme, namely the multistage detector.

Analog neural network-based helicopter gearbox health monitoring system.

The development of a reliable helicopter gearbox health monitoring system (HMS) has been the subject of considerable research over the past 15 years. The deployment of such a system could lead to a significant saving in lives and vehicles as well as dramatically reduce the cost of helicopter maintenance. Recent research results indicate that a neural network-based system could provide a viable solution to the problem. This paper presents two neural network-based realizations of an HMS system. A hybrid (digital/analog) neural system is proposed as an extremely accurate off-line monitoring tool used to reduce helicopter gearbox maintenance costs. In addition, an all analog neural network is proposed as a real-time helicopter gearbox fault monitor that can exploit the ability of an analog neural network to directly compute the discrete Fourier transform (DFT) as a sum of weighted samples. Hardware performance results are obtained using the Integrated Neural Computing Architecture (INCA/1) analog neural network platform that was designed and developed at The Charles Stark Draper Laboratory. The results indicate that it is possible to achieve a 100% fault detection rate with 0% false alarm rate by performing a DFT directly on the first layer of INCA/1 followed by a small-size two-layer feed-forward neural network and a simple post-processing majority voting stage.

Using recurrent neural networks for adaptive communication channel equalization.

Nonlinear adaptive filters based on a variety of neural network models have been used successfully for system identification and noise-cancellation in a wide class of applications. An important problem in data communications is that of channel equalization, i.e., the removal of interferences introduced by linear or nonlinear message corrupting mechanisms, so that the originally transmitted symbols can be recovered correctly at the receiver. In this paper we introduce an adaptive recurrent neural network (RNN) based equalizer whose small size and high performance makes it suitable for high-speed channel equalization. We propose RNN based structures for both trained adaptation and blind equalization, and we evaluate their performance via extensive simulations for a variety of signal modulations and communication channel models. It is shown that the RNN equalizers have comparable performance with traditional linear filter based equalizers when the channel interferences are relatively mild, and that they outperform them by several orders of magnitude when either the channel's transfer function has spectral nulls or severe nonlinear distortion is present. In addition, the small-size RNN equalizers, being essentially generalized IIR filters, are shown to outperform multilayer perceptron equalizers of larger computational complexity in linear and nonlinear channel equalization cases.