The Smoothened receptor (Smo) mediates hedgehog (Hh) signaling critical for development, cell growth, and migration, as well as stem cell maintenance. Aberrant Hh signaling pathway activation has been implicated in a variety of cancers, and small-molecule antagonists of Smo have entered human clinical trials for the treatment of cancer. Here, we report the biochemical characterization of allost...

AB STRACT: Smoking pa tients show re duc tion of in flam ma tory clin i cal signs that might be as so ci ated with lo cal vasoconstriction and an in creased gingival ep i the lial thick ness. The pur pose of this work was to eval u ate the thick ness of the mar ginal gingival oral ep i the lium in smok ers and non-smok ers, with clin i cally healthy gingivae or with gin gi vi tis. Twenty bi op ...

The sequential minimal optimization (SMO) algorithm and variants thereof are the de facto standard method for solving large quadratic programs for support vector machine (SVM) training. In this paper we propose a simple yet powerful modification. The main emphasis is on an algorithm improving the SMO step size by planning-ahead. The theoretical analysis ensures its convergence to the optimum. E...

Developing axons are guided to their targets by attractive and repulsive guidance cues. In the embryonic spinal cord, the floor plate chemoattractant Netrin-1 is required to guide commissural neuron axons to the midline. However, genetic evidence suggests that other chemoattractant(s) are also involved. We show that the morphogen Sonic hedgehog (Shh) can mimic the additional chemoattractant act...

Abstract: In order to solve chattering problem of conventional sliding mode observer (SMO), this paper proposes a exponential reaching law sliding mode observer (ERL-SMO) for a permanent magnet synchronous motor (PMSM) which substitutes exponential reaching law for constant reaching law. The ERL-SMO estimates the rotor position and the angular velocity from the back electromotive force (EMF) ba...

Aberrant Shh signaling promotes tumor growth in diverse cancers. The importance of Shh signaling is particularly evident in medulloblastoma and basal cell carcinoma (BCC), where inhibitors targeting the Shh pathway component Smoothened (Smo) show great therapeutic promise. However, the emergence of drug resistance limits long-term efficacy, and the mechanisms of resistance remain poorly underst...

Training a support vector machine (SVM) is usually done by mapping the underlying optimization problem into a quadratic programming (QP) problem. Unfortunately, high quality QP solvers are not readily available, which makes research into the area of SVMs difficult for the those without a QP solver. Recently, the Sequential Minimal Optimization algorithm (SMO) was introduced [1, 2]. SMO reduces ...

We investigated a role for Hedgehog signalling in glioblastoma, neuroblastoma and medulloblastoma by studying the transcription of PTCH, SMO, GLI1 and GLI3 in a total of 25 cell lines by standard RT-PCR and qRT-PCR, before and after 5-aza-2'-deoxycytidine and trichostatin A (TSA) treatments. Also 25 glioblastoma samples were tested by qRT-PCR. We also performed real-time methylated specific PCR...

In the recent years support vector machines (SVMs) have been successfully applied to solve a large number of classification problems. Training an SVM, usually posed as a quadratic programming (QP) problem, often becomes a challenging task for the large data sets due to the high memory requirements and slow convergence. We propose to apply boosting to Platt’s Sequential Minimal Optimization (SMO...

Diabetes, obesity, and cancer affect upward of 15% of the world's population. Interestingly, all three diseases juxtapose dysregulated intracellular signaling with altered metabolic state. Exactly which genetic factors define stable metabolic set points in vivo remains poorly understood. Here, we show that hedgehog signaling rewires cellular metabolism. We identify a cilium-dependent Smo-Ca(2+)...