Support Vector Machines (SVM) is a practical algorithm that has been widely used in many areas. To guarantee its satisfying performance, it is important to set appropriate parameters of SVM algorithm. Sequential Minimal Optimization (SMO) is an effective training algorithm belonging to SVM, i.e.LS_SVM. Therefore, on the basis of the SMO algorithm and LS_SVM, which integrates SMO algorithm and L...

Secreted proteins of the Hedgehog (Hh) family have diverse organizing roles in animal development. Recently, a serpentine protein Smoothened (Smo) has been proposed as a Hh receptor. Here, we present evidence that implicates another multiple-pass transmembrane protein, Patched (Ptc), in Hh reception and suggests a novel signal transduction mechanism in which Hh binds to Ptc, or a Ptc-Smo comple...

BACKGROUND Hemorrhage is a major cause of soldier death; it must be quickly identified and appropriately treated. We developed a prototype patient monitor that noninvasively and continuously determines muscle oxygen saturation (SmO₂), muscle pH (pHm), and a regional assessment of blood volume (HbT) using near-infrared spectroscopy. Previous demonstration in a model of progressive, central hypov...

Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the ...

The ciliary localization of odorant receptors (ORs) is evolutionary conserved and essential for olfactory transduction. However, how the transport of ORs is regulated in mammalian olfactory sensory neurons is poorly understood. Here we demonstrate that odorant responsiveness and OR transport is regulated by the Hedgehog pathway. OR transport is inhibited by conditional gene inactivation of the ...

tion organelle. Primary cilia, immotile organelles found on most cells, have been implicated in several signaling pathways and we have observed direct binding of Hh protein to them. We find that the Ptc receptor protein is localized in cilia, where it prevents the accumulation of the Smo seven-transmembrane domain protein. Binding of Hh to Ptc causes departure of both from the cilium, allowing ...

The Hedgehog (Hh) signaling pathway plays important roles in the tumorigenesis of multiple cancers and is a key target for drug discovery. In a screen of natural products extracted from Chinese herbs, we identified eight ent-Kaurane diterpenoids and two triterpene dilactones as novel Hh pathway antagonists. Epistatic analyses suggest that these compounds likely act at the level or downstream of...

tion organelle. Primary cilia, immotile organelles found on most cells, have been implicated in several signaling pathways and we have observed direct binding of Hh protein to them. We find that the Ptc receptor protein is localized in cilia, where it prevents the accumulation of the Smo seven-transmembrane domain protein. Binding of Hh to Ptc causes departure of both from the cilium, allowing ...

5. What did the investigators conclude? Over the past decade, the hedgehog (HH) pathway has been found to be altered in patients with both syndromic and sporadic basal cell carcinoma (BCC) (Rohatgi and Scott, 2007). This pathway, when regulated, controls cell growth; however, alteration of the pathway results in cancer due to failure of patched 1, a component of the HH pathway, to suppress the ...

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and is divided into two major histological subgroups, i.e., embryonal (ERMS) and alveolar RMS (ARMS). RMS can show HEDGEHOG/SMOOTHENED (HH/SMO) signaling activity and several clinical trials using HH inhibitors for therapy of RMS have been launched. We here compared the antitumoral effects of the SMO inhibitors GDC-0449, ...