Weyl curvature and the Euler characteristic in dimension four

We give lower bounds, in terms of the Euler characteristic, for the L²-norm of the Weyl curvature of closed Riemannian 4-manifolds. The same bounds were obtained by Gursky, in the case of positive scalar curvature metrics.     

Radiation-induced modifications of point defects in quartz crystals and their application in radiation dosimetry

Different types of impurity-related point defects in crystalline quartz are known to exhibit various spectroscopic signals. When exposed to ionizing radiations, these defect centers get modified and new species of point defects are formed. This paper presents a study and discussion of radiation-induced modification of point defects in natural as well as cultured quartz, with an emphasis to use this material for radiation dosimetry up to a range of a few Mrad.     

高效液相色谱－荧光检测法测定人血浆中匹伐他汀的含量

 Pitavastatin belongs to the class of coenzyme A reductase inhibitors. Very few methods of assaying pitavastatin from human plasma are available in literature. An analytical method is presented for the determination of the drug from human plasma making use of the fluorescent property of the drug. The drug is extracted from plasma using ethyl acetate under neutral condition and then analyzed by reversed-phase high performance liquid chromatography (HPLC) with fluorescence detection (λEx 245 nm; λEm 420 nm). Analysis of pitavastatin was carried out on a C18 HPLC column using a gradient flow of mobile phase (0.01 mol/L monobasic potassium phosphate (pH 3.20)-acetonitrile, 63∶37, v/v). Fluorescein isothiocyanate was used as internal standard. The dynamic range of assay was 3 to 50 ng/mL. The intraday precision was less than 10% and accuracy ranged from 95.2% to 112.6%. The same for interday check was less than 12% and 92.8% to 105.1%, respectively. The drug was found to be stable under the assay conditions. The developed method is simple, precise, accurate, and stable. This indicates that it can be applied to routine analysis of this drug in human subjects where there are large numbers of samples without the need of specialized instruments like column switching.     

LC–MS Determination of Gabapentin from Human Plasma

Gabapentin is an anticonvulsant drug used for the treatment of epilepsy. It is not bound to plasma protein and is not metabolized. A high performance liquid chromatography–mass spectrometric micro method is described in this report for its determination from human plasma. Chromatography was performed on a 50 × 4.6 mm, 4 μm nitrile column and the parent ion detected in the positive ionization mode on single quadrupole analyzer (Q1MI) with atmospheric pressure ionization source. Extraction was carried out on C₁₈, 100 mg/3cc cartridge using 10 μL sample volume. The mean extraction recovery was 97% and within batch and between batch coefficients of variation were <9%. Lack of interference from endogenous substances helped in achieving a highly sensitive method without the need for monitoring fragment ions. The lowest concentration injected on column for calibration curve was 195 pg (range 0.5–64 ng). The method was applied for analysis of samples from a cross-over bio-equivalence study comparing two formulations.

     

Design and synthesis of two armed molecular receptor for recognition of Gd3+ metal ion and its computational study

New receptor P henylene‐ B is‐ M ethylfuran‐yl‐2‐ M ethyele A cetohydrazide ( PBMMA ) has been synthesized by condensation of hydrazide and 5‐methyl furfural. Synthesized receptor has been fully characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopic and thermo gravimetric analysis. The receptor PBMMA shows selective recognition potential towards Gd³⁺ ion when tested with several metal ions such as Na⁺, K⁺, Mg²⁺, Cu²⁺, Cd²⁺, Hg²⁺, Y³⁺, La³⁺, Eu³⁺, Sm³⁺, Gd³⁺, Re⁶⁺ and Th⁴⁺ ion as their sulfates by UV–visible and fluorescence spectroscopic studies. Binding nature of PBMMA with Gd³⁺ ion was further studied by mass spectroscopic and cyclic voltammetric studies. The stoichiometry of PBMMA‐ Gd³⁺ ion has been established, 1:1 by Benesi‐Hildebrand plot method and method of continuous variation (Job's plot) with association affinity K = 6.491 × 10⁴ M^?1. In addition to these, molecular docking, molecular dynamic stimulation and binding energy of complex; through Density Function theory ?595.66 kcal/mol has also indication of strong binding. The electron transfer energy of Higher occupied molecular orbital (HOMO) to Lower unoccupied molecular orbital (LUMO) is about 4.186 eV and 295 nm for PBMMA‐Gd³⁺ Complex.     

Structure-based design of oxygen-linked macrocyclic kinase inhibitors: discovery of SB1518 and SB1578, potent inhibitors of Janus kinase 2 (JAK2) and Fms-like tyrosine kinase-3 (FLT3)

Macrocycles from our Aurora project were screened in a kinase panel and were found to be active on other kinase targets, mainly JAKs, FLT3 and CDKs. Subsequently these compounds became leads in our JAK2 project. Macrocycles with a basic nitrogen in the linker form a salt bridge with Asp86 in CDK2 and Asp698 in FLT3. This residue is conserved in most CDKs resulting in potent pan CDK inhibition. One of the main project objectives was to achieve JAK2 potency with 100-fold selectivity against CDKs. Macrocycles with an ether linker have potent JAK2 activity with the ether oxygen forming a hydrogen bond to Ser936. A hydrogen bond to the equivalent residues of JAK3 and most CDKs cannot be formed resulting in good selectivity for JAK2 over JAK3 and CDKs. Further optimization of the macrocyclic linker and side chain increased JAK2 and FLT3 activity as well as improving DMPK properties. The selective JAK2/FLT3 inhibitor 11 (Pacritinib, SB1518) has successfully finished phase 2 clinical trials for myelofibrosis and lymphoma. Another selective JAK2/FLT3 inhibitor, 33 (SB1578), has entered phase 1 clinical development for the non-oncology indication rheumatoid arthritis.     

Well-defined ruthenium(II) carboxylate as catalyst for direct C-H/C-O bond arylations with phenols in water

The ruthenium(II) carboxylate complex [Ru(O(2)CMes)(2)(p-cymene)] enabled efficient direct arylations of unactivated C-H bonds with easily available, inexpensive phenols. Extraordinary chemoselectivity of the well-defined ruthenium catalyst set the stage for challenging C-H/C-O bond functionalizations to occur under solvent-free conditions as well as in water, and allowed first direct C-H bond arylations with user-friendly diaryl sulfates as electrophiles.     

Mechanistic insight into direct arylations with ruthenium(II) carboxylate catalysts

Mechanistic studies revealed ruthenium-catalyzed direct arylations to proceed through reversible C-H bond activation and subsequent rate-limiting oxidative addition with aryl halides, which led to the development of widely applicable well-defined ruthenium(II) carboxylate catalysts.     

Raman imaging on high‐quality graphene grown by hot‐filament chemical vapor deposition

We report the synthesis of high‐quality graphene on Cu foils using hot‐filament chemical vapor deposition technique and demonstrate that by suitably varying the CH₄ and H₂ flow rates, one can also obtain hydrogenated graphene. Micro‐Raman spectroscopy studies confirm the growth of monolayer graphene as inferred from the intensity ratio of 2D to G peak which is nearly four in unhydrogenated samples. Detailed Raman area mapping confirms the uniform coverage of monolayer graphene. The grown layer is also transferred onto a Si substrate over ~10 × 10 mm sq. area. The present results provide a leap in synthesis technology of high‐quality graphene and pave way for scaling up the process. Copyright © 2012 John Wiley & Sons, Ltd.     

Laser irradiation of AISI 316L stainless steel coated with Si3N4 and Ti

AISI 316L stainless steel was laser surface treated with different compositions of Si₃N₄ and Ti under various laser-processing parameters to improve its surface hardness through reinforcement of Ti-based silicides. The laser-treated regions exhibited improved surface hardness (250–1000 HV), variations in the surface morphology (smooth and bowl like) and presence of cracks and pores depending upon the Si₃N₄–Ti composition and laser-processing parameters. The study shows that when the Si₃N₄–Ti composition is 75–25 wt% and laser parameters are 1.5 kW laser power and 1.0 m min⁻¹ scan speed, a laser-treated region with high hardness of about 800 HV and smooth surface morphology as well as free from pores and cracks is observed. The X-ray diffractometer (XRD) and Energy-Dispersive Spectroscopy (EDS) analyses show that the laser surface-treated region has reinforced phase of Ti₅Si₃ and retained austenitic structure. The reinforced phase gives rise to very high hardness (or wear resistance) and also a corrosion resistance.