Development of a novel, multifunctional, membrane-interactive pyridinium salt with potent anticancer activity

The synthesis and biological evaluation of a novel pyridinium salt is reported. Initial membrane interaction with isolated phospholipid monolayers was obtained with the pyridinium salt, and two neutral analogues for comparison, and the anticancer effects of the best compound established using a cytotoxicity screening assay against glioma cells using both an established cell line and three short-term cell cultures – one of which has been largely resistant to all chemotherapeutic drugs tested to date. The results indicate that the pyridinium salt exhibits potent anticancer activity (EC50s = 9.8-312.5 μM) on all cell types, including the resistant one, for a continuous treatment of 72 hours. Microscopic examination of the treated cells using a trypan blue exclusion assay showed membrane lysis had occurred. Therefore, this letter highlights the potential for a new class of pyridinium salt to be developed as a much needed alternative treatment for glioma chemotherapy

Haptics Aided Kinematic Assembly Modeling and Efficient Determination of Joint Ranges of Motion

Abstract This paper presents the development of a tool for the assembly and kinematic modeling of the tessellated objects. The tool addresses the issue of reducing the effort required to generate the kinematic models. The tool is capable of automatically ascertaining the type of kinematic pairing between two part models represented in STL format by detecting the compatible combination of features and determining the joint range of motion (ROM). The haptic interface is used to realistically simulate the assembly process and to determine the range of motion in 3D. The feature extraction algorithm uses a mix of curvature and surface normal based segmentation of the tessellated surfaces. The computation necessary for the geometry extraction and joint recognition has been decoupled from the complexity of the models by "Region of Interest" identification. A novel method for the determination of the ROM is proposed, wherein the recognized joint type information is used to restrict the computation necessary to the physically allowed degrees of freedom (DOF), unlike in the methods like configuration space, where, the computation needs to be done in 6-DOF space. Also, an efficient haptic rendering scheme for the simulation of the ROM has been proposed, which eliminates the need for the computationally intensive collision detection between the two parts

Magnetic Resonance Cholangiopancreatography in 3 Tesla: 2D MRCP versus 3D MRCP in Diagnostic Evaluation with Special Reference to Different Acquisition and Reconstruction Planes

Purpose: Magnetic resonance cholangiopancreatography (MRCP) is an established technique for the evaluation of intra- and extrahepatic bile ducts in patients with known or suspected hepatobiliary disease. However, the ideal acquisition and reconstruction plane for optimal bile duct evaluation with 3D technique has not been evaluated.The purpose of our study was to compare different acquisition and reconstruction planes of 3D MRCP for bile duct assessment. Methods: 51 consecutive adult patients suspected to have pancreatico-biliary disease were examined with 3 Tesla (Philips 3 T Ingenia) system both a multi thin slice (3D) and a breath-hold (Single Shot) MRCP technique were performed. In the multi thin slice technique both source images and maximum intensity projections were examined. Two radiologists blinded to clinical information viewed both MRCP techniques independantly. Measure of correlation between each of the techniques and the inter observer agreement were computed. Coronal and axial MIP were reconstructed based on each dataset (resulting in two coronal and two axial MIP, respectively) and assessed the MIP, regarding visualization of bile ducts and image quality.Results were compared (Wilcoxon test). Intra- and interobserver variability were calculated (kappa-statistic). Results: In case of coronal data acquisition, visualization of bile duct segments was significantly better on coronal reconstructed MIP images as compared to axial reconstructed MIP (p \u3c 0.05). Regarding visualization, coronal MIP of the coronal acquisition were equal to coronal MIP of the axial acquisition (p \u3e 0.05). Image quality of coronal and axial datasets did not differ significantly. Obstruction due to tumor was shown in 30% of patients, and calculi in the common bile duct were shown also in 30% of patients employing the 3D MRCP technique. Obstruction due to tumor and calculi were shown in 30% and 21% of patients, respectively, using the SS 2D MRCP technique. Sensitivity and specificity in distinguishing calculi in the common bile duct by 3D MRCP and SS MRCP were 100%, 100%, 70% and 100% respectively. Conclusions: Although the 3D MRCP multislice technique is more time consuming than the SS MRCP breath-hold technique at a 3 Tesla (Philips 3 T Ingenia) system it is advisable to use thin slice 3D MRCP in order not to misdiagnose calculi in the common bile duct.The results of our study suggest that for visualization and evaluation of intra- and extrahepatic bile duct segments reconstructed images in coronal orientation are preferable

Our experience of the management of severe bone defects in primary total knee arthroplasty with cement and screws with undersizing of tibia

Background: There are several options for dealing with tibial bone defects during total knee arthroplasty in severe primary osteoarthritis. The aim of this study was to report the midterm results of TKA with screw and cement augmentation of moderate-sized tibial bone defects.Methods: Patients with osteoarthritis who had posterior stabilised TKA with screw and cement augmentation of the tibia were reviewed retrospectively. Patients were assessed preoperatively and at follow-up using the International knee society knee score and function score, and radiographic analysis of alignment and signs of loosening.Results: 60 knee in 60 patients were included in the study. The mean age was 71 years; mean follow-up was 58 months. KS improved from 46 to 76 and FS from 51 to 92. The femorotibial mechanical angle changed from 174 to 178. There were no signs of osteolysis or loosening, and no revisions. Radiolucent lines at the cement bone interface were common but non- progressive.Conclusions: Midterm clinical and radiographic results of TKA with screw and cement augmentation for moderate tibial defects were satisfactory

Scaling properties of composite information measures and shape complexity for hydrogenic atoms in parallel magnetic and electric fields

The scaling properties of various composite information-theoretic measures (Shannon and R\'enyi entropy sums, Fisher and Onicescu information products, Tsallis entropy ratio, Fisher-Shannon product and shape complexity) are studied in position and momentum spaces for the non-relativistic hydrogenic atoms in the presence of parallel magnetic and electric fields. Such measures are found to be invariant at the fixed values of the scaling parameters given by $s_1 = B \hbar^3(4\pi\epsilon_0)^2 / (Z^2m^2e^3)$ and $s_2 = F \hbar^4(4\pi\epsilon_0)^3 / (Z^3e^5m^2)$. Numerical results which support the validity of the scaling properties are shown by choosing the representative example of the position space shape complexity. Physical significance of the resulting scaling behaviour is discussed.Comment: 10 pages, 2 figure

Biocompatible superparamagnetic core-shell nanoparticles for potential use in hyperthermia-enabled drug release and as an enhanced contrast agent

Superparamagnetic iron oxide nanoparticles (SPIONs) and core-shell type nanoparticles, consisting of SPIONs coated with mesoporous silica and/or lipid, were synthesized and tested for their potential theranostic applications in drug delivery, magnetic hyperthermia and as a contrast agent. Transmission Electron Microscopy (TEM) confirmed the size of bare and coated SPIONs was in the range of 5-20 nm and 100-200 nm respectively. The superparamagnetic nature of all the prepared nanomaterials as indicated by Vibrating Sample Magnetometry (VSM) and their heating properties under an AC field confirm their potential for hyperthermia applications. Scanning Column Magnetometry (SCM) data showed that extrusion of bare-SPION (b-SPION) dispersions through a 100 nm polycarbonate membrane significantly improved the dispersion stability of the sample. No sedimentation was apparent after 18 hours compared to a pre-extrusion estimate of 43% settled at the bottom of the tube over the same time. Lipid coating also enhanced dispersion stability. Transversal relaxation time (T2) measurements for the nanoparticles, using a bench-top relaxometer, displayed a significantly lower value of 46 ms, with a narrow relaxation time distribution, for lipid silica coated SPIONs (Lip-SiSPIONs) as compared to that of 1316 ms for the b-SPIONs. Entrapment efficiency of the anticancer drug, Doxorubicin (DOX) for Lip-SPIONs was observed to be 35% which increased to 58% for Lip-SiSPIONs. Moreover, in-vitro cytotoxicity studies against human breast adenocarcinoma, MCF-7 cells showed that % cell viability increased from 57% for bSPIONs to 82% for Lip-SPIONs and to 87% for Lip-SiSPIONs. This suggests that silica and lipid coatings improve the biocompatibility of bSPIONs significantly and enhance the suitability of these particles as drug carriers. Hence, the magnetic nanomaterials prepared in this work have potential theranostic properties as a drug carrier for hyperthermia cancer therapy and also offer enhancement of contrast agent efficacy and a route to a significant increase in dispersion stability

Ground state study of simple atoms within a nano-scale box

Ground state energies for confined hydrogen (H) and helium (He) atoms, inside a penetrable/impenetrable compartment have been calculated using Diffusion Monte Carlo (DMC) method. Specifically, we have investigated spherical and ellipsoidal encompassing compartments of a few nanometer size. The potential is held fixed at a constant value on the surface of the compartment and beyond. The dependence of ground state energy on the geometrical characteristics of the compartment as well as the potential value on its surface has been thoroughly explored. In addition, we have investigated the cases where the nucleus location is off the geometrical centre of the compartment.Comment: 9 pages, 5 eps figures, Revte

A Processing in Memory Realization Using Quantum Dot Cellular Automata (QCA): Proposal and Implementation

Processing in Memory (PIM) is a computing paradigm that promises enormous gain in processing speed by eradicating latencies in the typical von Neumann architecture. It has gained popularity owing to its throughput by embedding storage and computation of data in a single unit. We portray implementation of Akers array architecture endowed with PIM computation using Quantum-dot Cellular Automata (QCA). We present the proof of concept of PIM with its realization in the QCA designer paradigm. We illustrate implementation of Ex-OR gate with the help of QCA based Akers Array and put forth many interesting potential possibilities