Force Control: A Bird's Eye View

This paper summarizes the major conclusions of twenty years of research in robot force control, points out remaining problems, and introduces issues that need more attention. By looking at force control from a distance, a lot of common features among different control approaches are revealed; this allows us to put force control into a broader (e.g., differential-geometric) context. The paper starts with the basics of force control at an introductory level, by focusing at one or two degrees of freedom. Then the problems associated with the extension to the multidimensional case are described in a differential-geometric context. Finally, robustness and adaptive control are discussed. 1 Introduction The purpose of force control could be quite diverse, such as applying a controlled force needed for a manufacturing process (e.g., deburing or grinding), pushing an external object using a controlled force, or dealing with geometric uncertainty by establishing controlled contacts (e.g., in as..

Synthesis of new tetracyclic azaheteroaromatic cores via auto-tandem Pd-catalyzed and one-pot Pd- and Cu-catalyzed double C-N bond formation

Natural hot spring waters spouting from wellheads are essentially reductive in terms of oxidation-reduction potential (ORP); however, it was found that these ORP values increase over time due to oxidation after surfacing. Furthermore, it was revealed that, because its exposure upon bathing, the skin was the most susceptible to be affected. Therefore, it has been proposed that habitual bathing in fresh reductive hot spring water can suppress skin oxidation and contribute to prevent the aging process thereupon. In this study, as a facile evaluation method of the reductive ability of natural hot spring waters, instead of conducting ORP-pH measurements, the reductive ability of hot spring water was evaluated by redox titration with iodine contained in a well-known and commercially available gargling agent (Isodine®; povidone iodine). For didactic purposes, experiments evaluating the effects of fresh hot spring waters on preventing melanin formation were carried out by visualizing their effects on freshly peeled apples and potatoes that normally develop a brownish discoloration upon exposure to air, which is indicative of melanin formation. The second part of this study aims at a practical implementation of a simpler means for producing reductive hydrogen-rich bathwater. The effects of hydrogen produced by magnesium hydride (MgH2), a bath salt, on the skin were examined. Results from the present study revealed that home-use bathwater can be changed from an oxidative state to a reductive state by the production of reductive hydrogen from the reaction oMgH2 with water. Furthermore, it was found that natural hot spring water (alkaline, untreated hot spring water) in large-sized bathtubs of the spa facilities of Ashino Onsen can also be made more reductive by periodically adding MgH2thereto. The elasticity coefficients of the skin (flexural side of forearm) of volunteers in the habitual bathing experiments showed that a statistically significant improvement was observed in the group of in dividuals subjected to bathing in hydrogenated Ashino hot spring water. Finally, the present work proposes that the organoleptic evaluation of hot spring waters, such as the development of a smooth or soapy sensation on the skin, can be quantitatively estimated by a balance of concentrations between the alkaline components Ca and Mg

Active Robotic Sensing as Decision Making with Statistical Methods

status: publishe

Active robotic sensing as decision making with statistical methods

status: publishe

Building blocks for SLAM in autonomous compliant motion

This paper presents our research group's latest results in autonomous force-controlled manipulation tasks: (i) advanced non-linear estimators for simultaneous parameter estimation and contact formation "map building" for 6D contact tasks (with active sensing integrated into the task planner), and (ii) the application of these results to programming by human demonstration, for tasks involving contacts. © Springer-Verlag Berlin Heidelberg 2005.status: publishe

Commentaire bibliographique [Herman Van Impe, Het Belgisch Grondwettelijk Recht in kort bestek, Anvers, Kluwer rechtswetenschappen, 1982]

The glycoproteins of selected microbial pathogens often include highly modified carbohydrates such as 2,4-diacetamidobacillosamine (diNAcBac). These glycoconjugates are involved in host–cell interactions and may be associated with the virulence of medically significant Gram-negative bacteria. In light of genetic studies demonstrating the attenuated virulence of bacterial strains in which modified carbohydrate biosynthesis enzymes have been knocked out, we are developing small molecule inhibitors of selected enzymes as tools to evaluate whether such compounds modulate virulence. We performed fragment-based and high-throughput screens against an amino-sugar acetyltransferase enzyme, PglD, involved in biosynthesis of UDP-diNAcBac in Campylobacter jejuni. Herein we report optimization of the hits into potent small molecule inhibitors (IC₅₀ < 300 nM). Biophysical characterization shows that the best inhibitors are competitive with acetyl coenzyme A and an X-ray cocrystal structure reveals that binding is biased toward occupation of the adenine subpocket of the AcCoA binding site by an aromatic ring

Crystallographic and thermodynamic characterization of phenylaminopyridine bisphosphonates binding to human farnesyl pyrophosphate synthase

<div><p>Human farnesyl pyrophosphate synthase (hFPPS) catalyzes the production of the 15-carbon isoprenoid farnesyl pyrophosphate. The enzyme is a key regulator of the mevalonate pathway and a well-established drug target. Notably, it was elucidated as the molecular target of nitrogen-containing bisphosphonates, a class of drugs that have been widely successful against bone resorption disorders. More recently, research has focused on the anticancer effects of these inhibitors. In order to achieve increased non-skeletal tissue exposure, we created phenylaminopyridine bisphosphonates (P<i>N</i>P-BPs) that have bulky hydrophobic side chains through a structure-based approach. Some of these compounds have proven to be more potent than the current clinical drugs in a number of antiproliferation assays using multiple myeloma cell lines. In the present work, we characterized the binding of our most potent P<i>N</i>P-BPs to the target enzyme, hFPPS. Co-crystal structures demonstrate that the molecular interactions designed to elicit tighter binding are indeed established. We carried out thermodynamic studies as well; the newly introduced protein-ligand interactions are clearly reflected in the enthalpy of binding measured, which is more favorable for the new P<i>N</i>P-BPs than for the lead compound. These studies also indicate that the affinity of the P<i>N</i>P-BPs to hFPPS is comparable to that of the current drug risedronate. Risedronate forms additional polar interactions via its hydroxyl functional group and thus exhibits more favorable binding enthalpy; however, the entropy of binding is more favorable for the P<i>N</i>P-BPs, owing to the greater desolvation effects resulting from their large hydrophobic side chains. These results therefore confirm the overall validity of our drug design strategy. With a distinctly different molecular scaffold, the P<i>N</i>P-BPs described in this report represent an interesting new group of future drug candidates. Further investigation should follow to characterize the tissue distribution profile and assess the potential clinical benefits of these compounds.</p></div

Thienopyrimidine Bisphosphonate (ThPBP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase: Optimization and Characterization of the Mode of Inhibition

Human farnesyl pyrophosphate synthase (hFPPS) controls the post-translational prenylation of small GTPase proteins that are essential for cell signaling, cell proliferation, and osteoclast-mediated bone resorption. Inhibition of hFPPS is a clinically validated mechanism for the treatment of lytic bone diseases, including osteoporosis and cancer related bone metastases. A new series of thienopyrimidine-based bisphosphonates (ThP-BPs) were identified that inhibit hFPPS with low nanomolar potency. Crystallographic evidence revealed binding of ThP-BP inhibitors in the allylic subpocket of hFPPS. Simultaneous binding of inorganic pyrophosphate in the IPP subpocket leads to conformational closing of the active site cavity. The ThP-BP analogues are significantly less hydrophilic yet exhibit higher affinity for the bone mineral hydroxyapatite than the current <i>N</i>-BP drug risedronic acid. The antiproliferation properties of a potent ThB-BP analogue was assessed in a multiple myeloma cell line and found to be equipotent to the best current <i>N</i>-BP drugs. Consequently, these compounds represent a new structural class of hFPPS inhibitors and a novel scaffold for the development of human therapeutics