In Vivo Imaging of the Tumor‐Associated Enzyme NCEH1 with a Covalent PET Probe

Herein, we report the development of an ¹⁸F‐labeled, activity‐based small‐molecule probe targeting the cancer‐associated serine hydrolase NCEH1. We undertook a focused medicinal chemistry campaign to simultaneously preserve potent and specific NCEH1 labeling in live cells and animals, while permitting facile ¹⁸F radionuclide incorporation required for PET imaging. The resulting molecule, [¹⁸F]JW199, labels active NCEH1 in live cells at nanomolar concentrations and greater than 1000‐fold selectivity relative to other serine hydrolases. [¹⁸F]JW199 displays rapid, NCEH1‐dependent accumulation in mouse tissues. Finally, we demonstrate that [¹⁸F]JW199 labels aggressive cancer tumor cells in vivo, which uncovered localized NCEH1 activity at the leading edge of triple‐negative breast cancer tumors, suggesting roles for NCEH1 in tumor aggressiveness and metastasis.     

Two new zinc(II) and mercury(II) complexes based on N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide): synthesis,crystal structures and antibacterial activities

Reaction of N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide), C₂₀H₁₈F₂N₄O₂, ( L^F ), with zinc chloride and mercury(II) chloride produced different types and shapes of neutral coordination complexes, namely, dichlorido[N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide)‐κ²N,O]zinc(II), [ZnCl₂(C₂₀H₁₈F₂N₄O₂)], ( 1 ), and dichlorido[N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide)‐κ⁴O,N,N′,O′]mercury(II), [HgCl₂(C₂₀H₁₈F₂N₄O₂)], ( 2 ). The organic ligand and its metal complexes are characterized using various techniques: IR, UV–Vis and nuclear magnetic resonance (NMR) spectroscopies, in addition to powder X‐ray diffraction (PXRD), single‐crystal X‐ray crystallography and microelemental analysis. Depending upon the data from these analyses and measurements, a typical tetrahedral geometry was confirmed for zinc complex ( 1 ), in which the Zn^II atom is located outside the bis(benzhydrazone) core. The Hg^II atom in ( 2 ) is found within the core and has a common octahedral structure. The in vitro antibacterial activities of the prepared compounds were evaluated against two different bacterial strains, i.e. gram positive Bacillus subtilis and gram negative Pseudomonas aeruginosa bacteria. The prepared compounds exhibited differentiated growth‐inhibitory activities against these two bacterial strains based on the difference in their lipophilic nature and structural features.     

Emodin,A Naturally Occuring Anthraquinone: Its Isolation and Spectrophotometric Determination in Rumex Cyprius Plant

A new method for isolation and specrophotometric determination of emodin is presented. Emodin was isolated by thin layer chromatography (tlc) and column chromatography (cc) techniques, as an orange long crystalline substance. Emodin exhibits two absorption maxima, at 420 and 520 nm. Stability of the color and the effect of pH were studied. Beer's law is obeyed in the range 2–30 ppm.

The method is applied to the determination of emodin in roots, stems, and leaves of Rumex cyprius plant.     

Large sample prediction intervals for future geometric mean a comparative study

This paper provides simulation comparisons among the performance of 11 possible prediction intervals for the geometric.mean of a Pareto distribution with parameters (αB, ). Six different procedures were used to obtain these intervals , namely; true inter -val , pivotal interval , maximum likelihood estimation interval, centrallimit teorem interval, variance stabilizing interval and a mixture of the above intervals . Some of these intervals are valid if the observed sample size m,are large , others are valid if both, n and the future sample size m, are large. Some of these intervals require a knowledge of α or B, while others do not. The simulation validation and efficiency study shows that intervals depending on the MLE's are the best. The second best intervalsare those obtained through pivotal methods or variance stabilization transformation. The third group of intervals is that which depends on the central limit theorem when λ is known. There are two intervals which proved to be unacceptable under any criterion.     

Large displacement analysis of shear deformable composite beams with interlayer slips

This paper presents a novel geometric non-linear finite element formulation for the analysis of shear deformable two-layer beams with interlayer slips. We adopt the co-rotational approach where the motion of the element is decomposed into two parts: a rigid body motion which defines a local coordinate system and a small deformational motion of the element relative to this local coordinate system. The main advantage of this approach is that the transformation matrices relating local and global quantities are independent to the choice of the geometrical linear local element. The effect of transverse shear deformation of the layers is taken into account by assuming that each layer behaves as a Timoshenko beam element. The layers are assumed to be continuously connected and partial interaction is considered by considering a continuous relationship between the interface shear flow and the corresponding slip. In order to avoid curvature and shear locking phenomena, the local linear element is formulated using “exact” displacement shape functions derived from the closed-form solution of the governing equations of a two-layer beam element. Finally, three numerical applications are presented in order to assess the performance of the proposed formulation.     

Simultaneous determination of ofloxacin,tetrahydrozoline hydrochloride,and prednisolone acetate by high-performance liquid chromatography

A simple, specific, and precise high-performance liquid chromatographic method has been developed for the simultaneous determination of ofloxacin (OFX), tetrahydrozoline hydrochloride (THC), and prednisolone acetate (PAC) in ophthalmic suspension using propylparaben (POP) as the internal standard. The mobile phase consists of 0.05 M phosphate buffer-acetonitrile (65:35, v/v), and the pH is adjusted to 2.7 with orthophosphoric acid. A column containing octadecyl silane chemically bonded to porous silica particles (Waters Spherisorb, 5 microm ODS 1, 4.6 x 150 mm) is used as the stationary phase. The detection is carried out using a variable wavelength UV-vis detector set at 210 nm for OFX and THC and 254 nm for POP (internal standard) and PAC. The solutions are chromatographed at a constant flow rate of 1.2 mL/min. Retention times for OFX, THC, POP, and PAC are approximately 2.5, 4.5, 7.8, and 9.5 min, respectively. The relative retention times are approximately 0.14 min for OFX, 0.35 min for THC, 1.00 min for POP, and 1.22 min for PAC. The linearity range and percent recoveries for OFX, THC, and PAC are 24-120, 4-16, and 16-80 microg/mL and 100.48%, 100.34%, and 100.21%, respectively.     

Second-order subgradients of convex integral functionals

The purpose of this work is twofold: on the one hand, we study the second-order behaviour of a nonsmooth convex function defined over a reflexive Banach space . We establish several equivalent characterizations of the set , known as the second-order subdifferential of at relative to . On the other hand, we examine the case in which is the functional integral associated to a normal convex integrand . We extend a result of Chi Ngoc Do from the space to a possible nonreflexive Banach space . We also establish a formula for computing the second-order subdifferential .