A Biomechanics-Aware Robot-Assisted Steerable Drilling Framework for Minimally Invasive Spinal Fixation Procedures.

In this paper, we propose a novel biomechanics-aware robot-assisted steerable drilling framework with the goal of addressing common complications of spinal fixation procedures occurring due to the rigidity of drilling instruments and implants. This framework is composed of two main unique modules to design a robotic system including (i) a Patient-Specific Biomechanics-aware Trajectory Selection Module used to analyze the stress and strain distribution along an implanted pedicle screw in a generic drilling trajectory (linear and/or curved) and obtain an optimal trajectory; and (ii) a complementary semi-autonomous robotic drilling module that consists of a novel Concentric Tube Steerable Drilling Robot (CT-SDR) integrated with a seven degree-of-freedom robotic manipulator. This semi-autonomous robot-assisted steerable drilling system follows a multi-step drilling procedure to accurately and reliably execute the optimal hybrid drilling trajectory (HDT) obtained by the Trajectory Selection Module.

A Concentric Tube Steerable Drilling Robot for Minimally Invasive Spinal Fixation of Osteoporotic Vertebrae.

Spinal fixation with rigid pedicle screws have shown to be an effective treatment for many patients. However, this surgical option has been proved to be insufficient and will eventually fail for patients experiencing osteoporosis. This failure is mainly attributed to the lack of dexterity in the existing rigid drilling instruments and the complex anatomy of vertebrae, forcing surgeons to implant rigid pedicle screws within the osteoporotic regions of anatomy.

Modeling of the growth hormone secretagogue receptor antagonistic activity using chemometric tools.

A quantitative structure-activity relationship (QSAR) study has been carried out on growth hormone secretagogue receptor antagonistic activity of the derivatives of 2,4-diaminopyrimidine. To obtain significant QSARs, the approaches involving the non-parametric such as Fujita-Ban, and the parametric based on physicochemical and DRAGON descriptors in Hansch type of analysis have been employed. The Fujita-Ban approach, however, was constrained to 18 compounds only due to a limited number of substituents appeared at varying positions.

Topological descriptors in modeling the agonistic activity of human A3 adenosine receptor ligands: the derivatives of 2-chloro-N(6)-substituted-4'-thioadenosine-5'-uronamide.

The human A(3) adenosine receptor agonistic activity of 2-chloro-N(6)-substituted-4'-thioadenosine-5'-uronamides has been analyzed through Combinatorial Protocol in Multiple Linear Regression (CP-MLR) using 488 topological descriptors obtained from DRAGON software for the energy minimized 3D-structures of these molecules. Among the various descriptor classes considered in the study, the human A(3) adenosine receptor agonistic activity is correlated with simple topological descriptors (TOPO), Modified Burden eigenvalues (BCUT) and functional group (FUNC) classes of descriptors. The average valence connectivity index of order zero, X0Av, the sum of topological distances between O and Cl, T (O.

Modeling of vascular endothelial growth factor receptor 2 (VEGFR2) kinase inhibitory activity of 2-anilino-5-aryloxazoles using chemometric tools.

The structure-activity models of the VEGFR2 kinase inhibitory activity of the derivatives of 2-anilino-5-aryloxazole have been investigated using Combinatorial Protocol in Multiple Linear Regression (CP-MLR) with nearly 500 topological descriptors which were calculated from DRAGON software. Among the descriptor classes considered collectively in the study, the inhibitory activity was, however, correlated with simple functional (FUN), topological (TOPO), atom centered fragments (ACF), molecular walk counts (MWC) and 2D-autocorrelation (2D-AUTO) descriptors. The developed models and participating descriptors in them have suggested that the substitutional modifications in the 2-anilino-5-aryloxazole moiety may have sufficient scope in optimization of prevailing inhibitory activity of these analogues.

Quantitative structure-activity relationship study on affinity profile of a series of 1,8-naphthyridine antagonists toward bovine adenosine receptors.

The affinity profiles for the bovine adenosine receptors, A(1) and A(2A), of a series of 1,8-naphthyridine derivatives were quantitatively analyzed using physicochemical and structural parameters of the substituents, present at varying positions of the molecules. The derived significant correlation, for bovine A(1) receptor, suggested that a R(1) substituent having a higher van der Waals volume, a R(2) substituent being a hydrogen-bond donor and a R(3) substituent able to transmit a higher field effect are helpful in augmenting the pK(i) of a compound. Similarly the study, pertaining to bovine A(2A) receptor, revealed that a less bulky substituent at R(2) and a strong electron-withdrawing substituent at R(3) are desirable in improving the binding affinity of a compound while substituents at R(1) remain insignificant to any interaction.

QSAR study about ATP-sensitive potassium channel activation of cromakalim analogues using CP-MLR approach.

The structure-activity models of the myorelaxant activity of the cromakalim analogues have been investigated with nearly 470 topological descriptors from DRAGON software using Combinatorial Protocol in Multiple Linear Regression (CP-MLR). Among the descriptor classes considered in the study, the binding affinity is correlated with simple functional (FUN), topological (TOPO), atom centered fragments (ACF), empirical (EMP), modified Burden eigenvalues (BCUT), Galvez topological charge indices (GVZ), 2D-autocorrelation (2D-AUTO) and constitutional (CONS) descriptors. The models developed, and the participating descriptors suggest that the substituent groups of 4,6-disubstituted-2,2-dimethylchromans hold scope for further modification in the optimization of activity.

A quantitative structure-activity relationship study of novel, potent, orally active, selective VEGFR-2 and PDGFRalpha tyrosine kinase inhibitors: derivatives of N-phenyl-N'-{4-(4-quinolyloxy)phenyl}urea as antitumor agents.

The tyrosine kinase inhibitory action of the derivatives of N-Phenyl-N'-{4-(4-quinolyloxy)phenyl}urea is quantitatively analyzed using multiple regression analysis. The analysis has helped to ascertain the role of different substituents in explaining the observed inhibitory actions of these compounds for two receptors, namely vascular endothelial growth factor receptor 2 (VEGFR-2) and platelet-derived growth factor receptor alpha (PDGFRalpha). From a derived significant correlation equation for inhibition of VEGFR-2, it was concluded that a less hydrophobic molecule with ortho-substituent(s), exerting less steric hindrance and para-substituent devoid of hydrogen-bond acceptor property augment the inhibition action.

Quantitative structure-activity relationship study of novel rhinacanthins and related naphthoquinone esters as anticancer agents.

The anticancer activity of rhinacanthins and related naphthoquinone esters is quantitatively analyzed through Fujita-Ban and Hansch approaches. The analyses have helped to ascertain the role of different substituents in explaining the observed inhibitory actions of these compounds. From both approaches it appeared that naphthalene ring instead of benzene ring, dimethyl substitution at R(1) and R(2), and hydrogen-bond acceptor substituents at R(3) (Figure 1) are advantageous to improve the activity of a compound against KB cell lines.

Quantitative structure-activity relationship study of ATP-sensitive potassium channel openers: derivatives of 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide.

The inhibitory activity of glucose-induced insulin secretion on isolated rat pancreatic islets and the contractile activity of KCl-depolarized rat aorta rings of the derivatives of 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide are quantitatively analyzed using multiple regression analysis. The study has helped to ascertain the role of different substituents in explaining these observed inhibitory activities. From a derived most significant correlation equation, it was concluded that a less hydrophobic 3-substituent and a less bulky 7-substituent in addition to a 3-aminoisopropyl and a 6-chloro substituent are advantageous to enhance the inhibitory action of a compound towards rat pancreatic islets.

Quantitative structure-activity relationship study of new potent and selective antagonists at the 5-HT(1A) and adrenergic alpha(1d) receptors: Derivatives of spiroethyl phenyl(substituted)piperazine.

The antagonistic activities of derivatives of spiroethyl phenyl(substituted)piperazine at the 5-HT(1A) and adrenergic alpha(1d) receptors is quantitatively analyzed employing physicochemical and structural parameters. The derived correlation equation revealed that a substituent, other than 2-CH3 in the phenyl ring, having higher molar refraction, MR, and a substituent producing higher positive field effect at the 3-position are beneficial in increasing the binding affinity at the 5-HT(1A) receptor. In addition, a less hydrophobic substituent at the 4-position is also helpful in augmenting the binding affinity.