Porous graphitic carbon chromatography/tandem mass spectrometric determination of cytarabine in mouse plasma

A high-performance liquid chromatography (HPLC) system using a porous graphitic carbon (PGC) stationary phase interfaced with an electrospray ionization (ESI) source and a tandem mass spectrometer (MS/MS) for the analysis of cytarabine (ara-C) in mouse plasma samples has been developed in support of a pharmacodynamic study. The graphitized carbon column was adopted for the separation of ara-C and endogenous peaks from mouse plasma samples under the reversed-phase phase mode in liquid chromatography. The retention characteristics of the PGC column and the ionization efficiencies of all analytes based on the experimental factors such as the composition of mobile phases were investigated. The potential of ionization suppression resulting from the endogenous biological matrices on the PGC column during HPLC/ESI-MS/MS was investigated using post-column infusion. The concentrations of ara-C in mouse plasma obtained by using PGC-HPLC/MS/MS and ion-pairing HPLC/MS/MS were found to be in good agreement in terms of analytical accuracy.     

Energy transfer to analyse membrane-integrated mitoxantrone in BCRP-overexpressed cells

The binding and the diffusion of mitoxantrone (MTX) through the plasma membrane was performed by F?rster resonance energy transfer (FRET) from the membrane fluorescent donor (4Di-10ASP) to the co-localized acceptor MTX. The MTX addition to living 4Di-10ASP-tagged cells resulted in the rapid quenching of the probe emission (1s), revealing the MTX binding to the outer leaflet. Then, a slower quenching (about 90s) occurred which corresponded to the MTX flip-flop into the inner leaflet. Changes of MTX integration into the plasma membrane were described in BCRP-overexpressed cells (HCT-116R) treated with (i) the BCRP inhibitor fumitremorgin C (FTC), (ii) cyclosporin A (CSA) and (iii) benzyl alcohol (BA). Treatments with FTC or CSA showed 80% and 40% higher flip-flop of MTX from the outer to the inner leaflet of HCT-116R cells. The addition of BA clearly increased the MTX integration into both outer and inner leaflets. Confocal fluorescence microscopy displayed that FTC, CSA and BA enhanced MTX accumulation in HCT-116R. In conclusion, Fumitremorgin C and agents modulating MTX accumulation resulted in higher MTX integration in the resistant cell membrane and could disrupt the membrane cohesion. This energy transfer method appears well-adapted to describe the drug diffusion through the plasma membrane of living cells.     

Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling

In this report, inhibitors of the gamma-secretase enzyme have been exploited to characterize the antiproliferative relationship between target inhibition and cellular responses in Notch-dependent human T cell acute lymphoblastic leukemia (T-ALL) cell lines. Inhibition of gamma-secretase led to decreased Notch signaling, measured by endogenous NOTCH intracellular domain (NICD) formation, and was associated with decreased cell viability. Flow cytometry revealed that decreased cell viability resulted from a G(0)/G(1) cell cycle block, which correlated strongly to the induction of apoptosis. These effects associated with inhibitor treatment were rescued by exogenous expression of NICD and were not mirrored when a markedly less active enantiomer was used, demonstrating the gamma-secretase dependency and specificity of these responses. Together, these data strengthen the rationale for using gamma-secretase inhibitors therapeutically and suggest that programmed cell death may contribute to reduction of tumor burden in the clinic.     

Description of carbo-oxocarbons and assessment of exchange-correlation functionals for the DFT description of carbo-mers

Mono- and polycyclic valence isomers of carbo-[3]oxocarbon C(9)O(3) and carbo-[5]oxocarbon C(15)O(5) have been characterized on the singlet spin state potential energy surface. By contrast to their geometry, their relative stability is highly sensitive to the calculation level. The performance of LDA, GGA, meta-GGA, and hybrid functionals is compared to that of HF, post-HF, and multiconfigurational calculations. The results obtained for C(9)O(3) are compared to those obtained for hydrocarbon analogues such as &[3]pericyclyne C9(H2)3 and carbo-[3]radialene C9(CH2)3 and are analyzed on the basis of an energy decomposition scheme. The respective role of the exchange and correlation counterparts of the functional in the discrepancy of the results is discussed.     

Bimetallic Pd/Sn-based Nanoparticles and their Catalytic Properties in the Semihydrogenation of Diphenylacetylene

Multimetallic nanoparticles often enhance the catalytic performance of their monometallic counterparts by increasing reaction rates, catalyst selectivity, and/or stability. A prerequisite for understanding structure- and composition-associated properties, however, is the careful design of multimetallic nanoparticles with various structures and compositions. Here, bimetallic Pd/Sn-based nanoparticles are prepared with a tunable composition and structure exploiting ionic liquids (ILs) as reaction medium (i. e., methyltrioctylammonium bis(trifluoromethylsulfonyl)imide). The nanoparticles are obtained in a one-pot synthetic procedure by reducing the metal salt precursors with triethylborohydride in the IL. The results show that the reaction parameters, in particular the nature and ratio of the Pd²⁺/Sn²⁺ precursors as well as the reaction temperature, influence NP formation and composition. X-ray diffraction with Rietveld analysis and transmission electron microscopy are employed to determine NP size and phase composition. Under optimized reaction conditions Pd₂Sn or PdSn nanocrystals are formed as single-phase products after introducing an additional annealing step at 200 °C. Nanocrystals with intermetallic composition reveal enhanced catalytic properties in the semihydrogenation of diphenylacetylene which was used as a model reaction.     

Enhancing Light Absorption and Charge Transfer Efficiency in Carbon Dots through Graphitization and Core Nitrogen Doping

Single-source precursor syntheses have been devised for the preparation of structurally similar graphitic carbon dots (CDs), with (g-N-CD) and without (g-CD) core nitrogen doping for artificial photosynthesis. An order of magnitude improvement has been realized in the rate of solar (AM1.5G) H₂ evolution using g-N-CD (7950 μmol_H2 (g_CD)⁻¹ h⁻¹) compared to undoped CDs. All graphitized CDs show significantly enhanced light absorption compared to amorphous CDs (a-CD) yet undoped g-CD display limited photosensitizer ability due to low extraction of photogenerated charges. Transient absorption spectroscopy showed that nitrogen doping in g-N-CD increases the efficiency of hole scavenging by the electron donor and thereby significantly extends the lifetime of the photogenerated electrons. Thus, nitrogen doping allows the high absorption coefficient of graphitic CDs to be translated into high charge extraction for efficient photocatalysis.     

Stationary analysis of the shortest queue problem

In this paper, we derive an approximation for throughput of TCP Compound connections under random losses. Throughput expressions for TCP Compound under a deterministic loss model exist in the literature. These are obtained assuming that the window sizes are continuous, i.e., a fluid behavior is assumed. We validate this model theoretically. We show that under the deterministic loss model, the TCP window evolution for TCP Compound is asymptotically periodic and is independent of the initial window size. We then consider the case when packets are lost randomly and independently of each other. We discuss Markov chain models to analyze performance of TCP in this scenario. We use insights from the deterministic loss model to get an appropriate scaling for the window size process and show that these scaled processes, indexed by p, the packet error rate, converge to a limit Markov chain process as p goes to 0. We show the existence and uniqueness of the stationary distribution for this limit process. Using the stationary distribution for the limit process, we obtain approximations for throughput, under random losses, for TCP Compound when packet error rates are small. We compare our results with ns2 simulations which show a good match and a better approximation than the fluid model at low p.     

Loading polyelectrolytes onto porous microspheres: impact of molecular and electrochemical parameters

The impact of macromolecule constitution and electrostatic dimensions on the adsorption of cationic model polyelectrolytes (PELs) onto oppositely charged porous microspheres (MSs) suspended in aqueous media is demonstrated. The contour length (L) of the PEL, the chemical structure of the substituents at the ionic group, the ionic strength of the solution (I), and the average pore radius of the microspheres (R) are considered as variable. Adsorption isotherms quantitatively reveal how PEL parameters, MS geometry, and medium characteristics affect the adsorbed amount and surface coverage. Electrostatic exclusion from pores was proved as long as the Debye length (lD) exceeded R, even if L was considerably smaller than the pore diameter. Two charge parameters (CRcalc and CRexp) and the ratio thereof (CR) were derived and served to evaluate the loading process. All three parameters are applicable to two limiting cases, first, adsorption only on the outer surface of the MS and, second, additional adsorption inside the pores. The findings are seen as valuable contributions to basic research in the field of PELs. Precise data, which were not available before, are provided for comparison with theoretical models and simulations. Overall, conclusions from this model system may be useful for technical applications such as surface modification, chromatographic processes, or materials development.     

The optical rotatory power of water

Ab initio molecular orbital calculations of the optical rotatory response of a single oriented water molecule are described. The unique tensor element g(xy) was computed to be -0.047 bohr(3) with CCSD/6-311+G(d,p). A value of -0.033 was obtained with the minimal valence basis that was better suited to parsing the rotatory response among a limited number of excited states. Transition moments were calculated ab initio and qualitatively derived from the wave functions. Rotations were reckoned from the relative dispositions of the transition moments with respect to the wavevectors. In this way, it was possible to intuitively reckon the form of the optical rotation tensor consistent with that from higher levels of theory and to establish which excitations make the most significant contributions.