Supplementary Material: PREMATURE EXPRESSION OF AN AGE-ASSOCIATED MUSCLE SENESCENCE PATHWAY IN HIV INFECTION

Supplement online material

B Cell Activation in Insulin Resistance and Obesity

Our group has demonstrated that inflammatory diseases such as type 2 diabetes (DM), inflammatory bowel disease (IBD), and periodontal disease (PD) are associated with altered B cell function that may contribute to disease pathogenesis. B cells were found to be highly activated with characteristics of inflammatory cells. Obesity is a pre-disease state for cardiovascular disease and type 2 diabetes and is considered a state of chronic inflammation. Therefore, we sought to better characterize B cell function and phenotype in obese patients. We demonstrate that (Toll-like receptor) TLR4 and CD36 expression by B cells is elevated in obese subjects, suggesting increased sensing of lipopolysaccharide (LPS) and other TLR ligands. These ligands may be of microbial, from translocation from a leaky gut, or host origin. To better assess microbial ligand burden and host response in the bloodstream, we measured LPS binding protein (LBP), bacterial/permeability increasing protein (BPI), and high mobility group box 1 (HMGB1). Thus far, our data demonstrate an increase in LBP in DM and obesity indicating increased responses to TLR ligands in the blood. Interestingly, B cells responded to certain types of LPS by phosphorylating extracellular-signal-regulated kinases (ERK) 1/2. A better understanding of the immunological state of obesity and the microbial and endogenous TLR ligands that may be activating B cells will help identify novel therapeutics to reduce the risk of more dangerous conditions, such as cardiovascular disease.

Efficient Nearest Neighbor Classification Using a Cascade of Approximate Similarity Measures

Nearest neighbor classification using shape context can yield highly accurate results in a number of recognition problems. Unfortunately, the approach can be too slow for practical applications, and thus approximation strategies are needed to make shape context practical. This paper proposes a method for efficient and accurate nearest neighbor classification in non-Euclidean spaces, such as the space induced by the shape context measure. First, a method is introduced for constructing a Euclidean embedding that is optimized for nearest neighbor classification accuracy. Using that embedding, multiple approximations of the underlying non-Euclidean similarity measure are obtained, at different levels of accuracy and efficiency. The approximations are automatically combined to form a cascade classifier, which applies the slower approximations only to the hardest cases. Unlike typical cascade-of-classifiers approaches, that are applied to binary classification problems, our method constructs a cascade for a multiclass problem. Experiments with a standard shape data set indicate that a two-to-three order of magnitude speed up is gained over the standard shape context classifier, with minimal losses in classification accuracy.

Face Identification by a Cascade of Rejection Classifiers

Nearest neighbor search is commonly employed in face recognition but it does not scale well to large dataset sizes. A strategy to combine rejection classifiers into a cascade for face identification is proposed in this paper. A rejection classifier for a pair of classes is defined to reject at least one of the classes with high confidence. These rejection classifiers are able to share discriminants in feature space and at the same time have high confidence in the rejection decision. In the face identification problem, it is possible that a pair of known individual faces are very dissimilar. It is very unlikely that both of them are close to an unknown face in the feature space. Hence, only one of them needs to be considered. Using a cascade structure of rejection classifiers, the scope of nearest neighbor search can be reduced significantly. Experiments on Face Recognition Grand Challenge (FRGC) version 1 data demonstrate that the proposed method achieves significant speed up and an accuracy comparable with the brute force Nearest Neighbor method. In addition, a graph cut based clustering technique is employed to demonstrate that the pairwise separability of these rejection classifiers is capable of semantic grouping.

A Dopamine-Acetylcholine Cascade: Simulating Learned and Lesion-Induced Behavior ff Striatal Cholinergic Interneurons

The "teaching signal" that modulates reinforcement learning at cortico-striatal synapses may be a sequence composed of an adaptively scaled DA burst, a brief ACh burst, and a scaled ACh pause. Such an interpretation is consistent with recent data on cholinergic interneurons of the striatum are tonically active neurons (TANs) that respond with characteristic pauses to novel events and to appetitive and aversive conditioned stimuli. Fluctuations in acetylcholine release by TANs modulate performance- and learning- related dynamics in the striatum. Whereas tonic activity emerges from intrinsic properties of these neurons, glutamatergic inputs from thalamic centromedian-parafascicular nuclei, and dopaminergic inputs from midbrain are required for the generation of pause responses. No prior computational models encompass both intrinsic and synaptically-gated dynamics. We present a mathematical model that robustly accounts for behavior-related electrophysiological properties of TANs in terms of their intrinsic physiological properties and known afferents. In the model balanced intrinsic hyperpolarizing and depolarizing currents engender tonic firing, and glutamatergic inputs from thalamus (and cortex) both directly excite and indirectly inhibit TANs. If the latter inhibition, probably mediated by GABAergic NOS interneurons, exceeds a threshold, its effect is amplified by a KIR current to generate a prolongued pause. In the model, the intrinsic mechanisms and external inputs are both modulated by learning-dependent dopamine (DA) signals and our simulations revealed that many learning-dependent behaviors of TANs are explicable without recourse to learning-dependent changes in synapses onto TANs.