Geometric modeling and validation of twist drills with a generic point profile

Traditionally, twist drills with a few specific point geometry, such as planar, conical, cylindrical, ellipsoidal or hyperboloidal, have been designed and adapted for specific applications. Using CAD, the point geometry can be given a generic definition which will enhance the freedom to design drills with different point profiles and optimize them for multiple objectives. Such a definition can also be used for several downstream applications. This paper presents a methodology to model the twist drills with generic point geometry using NURBS. To begin with, a detailed basic model for a fluted twist drill with sectional geometry made up of arcs and straight lines has been presented in terms of bi-parametric surface patches. The coordinates of cutting lips and chisel edge of the drill have been obtained as solution to a surface-curve intersection problem using optimization algorithm. Subsequently, the model has been generalized by employing NURBS to represent the curves whereby the cutting edges and angles can be altered simply by changing the control points or their respective weights. Using this methodology, the generic definitions of the conventional angles on the drill point have been derived and presented. The proposed model has been illustrated in MATLAB environment and validated experimentally for a conical and an arbitrary point geometry. The experiments show a good conformity with the theoretical evaluations.     

A branch-and-cut method for 0-1 mixed convex programming

We generalize the disjunctive approach of Balas, Ceria, and Cornuéjols [2] and devevlop a branch-and-cut method for solving 0-1 convex programming problems. We show that cuts can be generated by solving a single convex program. We show how to construct regions similar to those of Sherali and Adams [20] and Lovász and Schrijver [12] for the convex case. Finally, we give some preliminary computational results for our method. Received January 16, 1996 / Revised version received April 23, 1999?Published online June 28, 1999     

Optimal Eighth Order Iterative Methods

We develop an eighth order family of methods, consisting of three steps and three parameters, for solving nonlinear equations. Per iteration the methods require four evaluations (three function evaluations and one evaluation of the first derivative). Convergence analysis shows that the family is eighth-order convergent which is also substantiated through the numerical work. Computational results ascertain that family of methods are efficient and demonstrate equal or better performance as compared with other well known methods.     

Monosaccharide-Directed Selective Internalization of Gold and Silver Nanoparticles in Hepatic Cancer Cells

The therapeutic success of nanomedicines requires nanomaterials to either adhere to the surface or internalize within the cytoplasm. The endocytosis phenomenon is controlled by the nanomaterial's shape, size, composition, charge, and capping molecules. The membrane potential-based non-specific internalization of therapeutic nanomedicines offers limited benefits than receptor-based specific delivery. Glut receptor-based internalization of glucose molecules is a well-known process in cancerous cells, which is one of the most exploited strategies to target cancer cells using nanoparticles. However, the internalization process of other structurally similar monosaccharides (D-Galactose, Mannose, and D-Fructose) conjugated nanoparticles remains to be unexplored. Herein, D-Glucose, D-Galactose, Mannose, and D-Fructose-coated AuNPs and AgNPs have been synthesized and studied the role of Glut receptors in their internalization in liver cancer cells, and compared them with non-cancerous cells. Results revealed that almost all monosaccharide-coated NPs exhibited high uptake in liver cancer cells than non-cancerous cells. Glut-1 receptor is observed to play a key role in the uptake and inhibition of Glut-1 receptors by genistein lead to a significant decrease in nanoparticle uptake. In conclusion, monosaccharide-conjugated nanoparticles can be used to direct the selective internalization of AuNPs and AgNPs in hepatic cancer cells to realize therapeutic and imaging applications.     

Nanostructured ZrO2 and Zr‐C‐N Coatings from Chemical Vapor Deposition of Metal‐Organic Precursors

Nanocrystalline zirconium carbonitride (Zr‐C‐N) and zirconium oxide (ZrO₂) films were deposited by chemical vapor deposition (CVD) of zirconium‐tetrakis‐diethylamide (Zr(NEt₂)₄) and ‐tert‐butyloxide (Zr(OBu^t)₄), respectively. The films were deposited on iron substrates and characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD) and X‐ray photoelectron spectroscopy (XPS). The Zr‐C‐N films show blue, golden brown or bronze colours, with colour stability depending upon the precursor composition (pure metal amide or mixed with Et₂NH). The deposition temperature showed no pronounced effect on the granular morphology of the Zr‐C‐N films. The XRD data of the films correspond to the formation of carbonitride phase whereas the XPS analyses revealed a strong surface oxidation and incorporation of oxygen in the film. The films deposited using a mixture of Zr(NEt₂)₄ and Et₂NH showed higher N content, better adhesion and scratch resistance when compared to films obtained from the CVD of pure Zr(NEt₂)₄. Subject to the precursor composition and deposition temperature (550‐750 °C), the microhardness values of Zr‐C‐N films were found to be in the range 2.11‐5.65 GPa. For ZrO₂ films, morphology and phase composition strongly depend on the deposition temperature. The CVD deposits obtained at 350 °C show tetragonal ZrO₂ to be the only crystalline phase. Upon increasing the deposition temperature to 450 °C, a mixture of tetragonal and monoclinic modifications was formed with morphology made up of interwoven elongated grains. At higher temperatures (550 and 650 °C), pure monoclinic phase was obtained with facetted grains and developed texture.     

Crystal structures of the pyrazinamide–p‐aminobenzoic acid (1/1) cocrystal and the transamidation reaction product 4‐(pyrazine‐2‐carboxamido)benzoic acid in the molten state

The synthesis of pharmaceutical cocrystals is a strategy to enhance the performance of active pharmaceutical ingredients (APIs) without affecting their therapeutic efficiency. The 1:1 pharmaceutical cocrystal of the antituberculosis drug pyrazinamide (PZA) and the cocrystal former p‐aminobenzoic acid (p‐ABA), C₇H₇NO₂·C₅H₅N₃O, (1), was synthesized successfully and characterized by relevant solid‐state characterization methods. The cocrystal crystallizes in the monoclinic space group P2₁/n containing one molecule of each component. Both molecules associate via intermolecular O—H...O and N—H...O hydrogen bonds [O...O = 2.6102 (15) Å and O—H...O = 168.3 (19)°; N...O = 2.9259 (18) Å and N—H...O = 167.7 (16)°] to generate a dimeric acid–amide synthon. Neighbouring dimers are linked centrosymmetrically through N—H...O interactions [N...O = 3.1201 (18) Å and N—H...O = 136.9 (14)°] to form a tetrameric assembly supplemented by C—H...N interactions [C...N = 3.5277 (19) Å and C—H...N = 147°]. Linking of these tetrameric assemblies through N—H...O [N...O = 3.3026 (19) Å and N—H...O = 143.1 (17)°], N—H...N [N...N = 3.221 (2) Å and N—H...N = 177.9 (17)°] and C—H...O [C...O = 3.5354 (18) Å and C—H...O = 152°] interactions creates the two‐dimensional packing. Recrystallization of the cocrystals from the molten state revealed the formation of 4‐(pyrazine‐2‐carboxamido)benzoic acid, C₁₂H₉N₃O₃, (2), through a transamidation reaction between PZA and p‐ABA. Carboxamide (2) crystallizes in the triclinic space group P with one molecule in the asymmetric unit. Molecules of (2) form a centrosymmetric dimeric homosynthon through an acid–acid O—H...O hydrogen bond [O...O = 2.666 (3) Å and O—H...O = 178 (4)°]. Neighbouring assemblies are connected centrosymmetrically via a C—H...N interaction [C...N = 3.365 (3) Å and C—H...N = 142°] engaging the pyrazine groups to generate a linear chain. Adjacent chains are connected loosely via C—H...O interactions [C...O = 3.212 (3) Å and C—H...O = 149°] to generate a two‐dimensional sheet structure. Closely associated two‐dimensional sheets in both compounds are stacked via aromatic π‐stacking interactions engaging the pyrazine and benzene rings to create a three‐dimensional multi‐stack structure.     

Spherically symmetric, self-similar spacetimes

In this paper, we show that self-similarity with respect to the existence of a (purely radial) homothetic Killing vector field for spherically symmetric spacetimes implies the separability of the spacetime metric in terms of the co-moving coordinates (and vice versa) and that the metric is, uniquely, the one recently reported in (Class. Quantam Grav. 18: 2147–2162; 2001). This spacetime, in general, has non-vanishing energy flux and shear. An interesting feature of this spacetime, in contrast to other self-similar spherically symmetric spacetimes (not reducible to our form) is that it has an arbitrary radial distribution of matter.     

Ensuring robustness in the quality of antibiotic susceptibility test discs for four novel antibiotics

Antibiotic susceptibility test (AST) discs are used as an in-vitro diagnostic tool to select the appropriate antibiotic to treat an infection. Generally, the concentration of the drug loaded on to the AST discs is measured by studying its activity against quality control organisms. This methodology has several limitations—it is time consuming, requires trained manpower, has a wider acceptance criteria of zone of inhibitions—causing ambiguity in judging smaller variations in drug concentration. To overcome these issues, we have developed and validated high-performance liquid chromatographic (HPLC) methods for the determination of strength of AST discs for in-house researched antibiotics, namely Levonadifloxacin/WCK 771, Nafithromycin/WCK 4873, Cefepime-Tazobactam/WCK 4282, and Cefepime-Zidebactam/WCK 5222. The drugs were extracted from the AST discs using an appropriate solvent. The developed methods are simple, accurate, precise, reproducible, rugged, and robust. They are efficient in terms of time, and can be easily conducted in a quality control laboratory during release as well as stability evaluation of AST disc. Application of HPLC methods for the determination of strength of AST discs ensures flawless quality and, consequently, a better selection of drugs to treat bacterial infections in clinics.     

Development of a bioanalytical method for the quantification of sinococuline in human plasma and its application in phase I clinical pharmacokinetic study

A selective, highly sensitive, precise, and novel bioanalytical method has been developed and validated to quantify sinococuline, an active constituent present in the phytopharmaceutical drug product containing Cocculus hirsutus plant extract, in vivo. Chromatographic separation was achieved on a Luna Omega Polar-C18 bonded analytical column maintained at 45°C. The isocratic mobile phase consisted of methanol and ammonium formate buffer (60:40, v/v) at acidic pH with a low flow rate of 0.250 mL/min. Detection was performed on an API 4000 mass spectrometer using electrospray ionization in positive polarity and multiple reaction monitoring mode to achieve a lower limit of quantification of 1.50 ng/mL. Excellent accuracy and precision were obtained after extracting the analyte from plasma samples using a chemical analogue as an internal standard in the absence of an isotope-labeled compound. The extraction efficacy was evidenced from recovery study, and the analyte was found to be stable in plasma. Validation study demonstrated linearity with coefficient of correlation, r ≥ 0.99, and minimal matrix effect. This bioanalytical method was successfully applied to evaluate pharmacokinetic parameters of sinococuline from a phase I clinical trial of an aqueous extract of C. hirsutus in healthy human volunteers.