High-content analysis of kinase activity in cells

High-content analysis (HCA) is a term used to describe techniques involving multiplexed analysis of fluorescent markers to measure multiple cellular responses to biological stimuli or drug treatment. HCA is usually based on automated microscopy or related technologies, and its value lies in providing multiparametric information on single cells within a population. During the last decade, several HCA approaches have been developed and applied to assess cellular mechanism of action of pharmacologically relevant compounds identified through biochemical screening or similar in vitro methods. With automation and instrument development, these approaches have evolved to the extent that the technique is now routinely used in screening applications, including primary HTS on compound collections. Here, we review the field and discuss in particular the application of HCA to the discovery of small molecule inhibitors targeting kinases which are implicated in Oncology.     

Phase-coherent frequency combs in the vacuum ultraviolet via high-harmonic generation inside a femtosecond enhancement cavity

We demonstrate the generation of phase-coherent frequency combs in the vacuum utraviolet spectral region. The output from a mode-locked laser is stabilized to a femtosecond enhancement cavity with a gas jet at the intracavity focus. The resulting high-peak power of the intracavity pulse enables efficient high-harmonic generation by utilizing the full repetition rate of the laser. Optical-heterodyne-based measurements reveal that the coherent frequency comb structure of the original laser is fully preserved in the high-harmonic generation process. These results open the door for precision frequency metrology at extreme ultraviolet wavelengths and permit the efficient generation of phase-coherent high-order harmonics using only a standard laser oscillator without active amplification of single pulses.     

Cc （X） Spaces with X Locally Compact

In this paper, we show, among other results, that if X is a [separable] locally compact space X [satisfying the first countability axiom] then the space Cc （X） has countable tightness [if and only if it has bounding tightness] if and only if it is Frechet-Urysohn, if and only if Cc （X） contains a dense （LM） subspace and if and only if X is a-compact.     

On quasi-Souslin C c (X) spaces

We prove that the space C _c (X) of the real-valued continuous functions with the compact-open topology is quasi-Souslin iff it is K-analytic. This implies that C _c (X) is K-analytic iff it is dominated by the irrationals. Partially supported by the project MTM2005-01182 of the Spanish Ministry of Education and Science, co-financed by the European Community (Feder projects).     

The evaluation of a quartic integral via Schwinger, Schur and Bessel

We provide additional methods for the evaluation of the integral

Temperature responsive complex coacervate core micelles with a PEO and PNIPAAm corona

In aqueous solutions at room temperature, poly( N-methyl-2-vinyl pyridinium iodide)- block-poly(ethylene oxide), P2MVP 38- b-PEO 211 and poly(acrylic acid)- block-poly(isopropyl acrylamide), PAA 55- b-PNIPAAm 88 spontaneously coassemble into micelles, consisting of a mixed P2MVP/PAA polyelectrolyte core and a PEO/PNIPAAm corona. These so-called complex coacervate core micelles (C3Ms), also known as polyion complex (PIC) micelles, block ionomer complexes (BIC), and interpolyelectrolyte complexes (IPEC), respond to changes in solution pH and ionic strength as their micellization is electrostatically driven. Furthermore, the PNIPAAm segments ensure temperature responsiveness as they exhibit lower critical solution temperature (LCST) behavior. Light scattering, two-dimensional 1H NMR nuclear Overhauser effect spectrometry, and cryogenic transmission electron microscopy experiments were carried out to investigate micellar structure and solution behavior at 1 mM NaNO 3, T = 25, and 60 degrees C, that is, below and above the LCST of approximately 32 degrees C. At T = 25 degrees C, C3Ms were observed for 7 < pH < 12 and NaNO 3 concentrations below approximately 105 mM. The PEO and PNIPAAm chains appear to be (randomly) mixed within the micellar corona. At T = 60 degrees C, onion-like complexes are formed, consisting of a PNIPAAm inner core, a mixed P2MVP/PAA complex coacervate shell, and a PEO corona.     

The evaluation of Tornheim double sums. Part 2

We provide an explicit formula for the Tornheim double series T(a,0,c) in terms of an integral involving the Hurwitz zeta function. For integer values of the parameters, a=m, c=n, we show that in the most interesting case of even weight N:=m+n the Tornheim sum T(m,0,n) can be expressed in terms of zeta values and the family of integrals

The Energetic Nitrocarbamate O2NN(H)CO[OCH2C(NO2)3] Derived from Phosgene

A new simple synthesis route for 2,2,2‐trinitroethyl chloroformate ( 1 ), from easily available starting materials 2,2,2‐trinitroethanol and phosgene is presented. 2,2,2‐Trinitroethyl carbamate ( 2 ) was obtained by the reaction of 1 with aqueous ammonia. The nitration of 2 with anhydrous nitric acid and sulfuric acid yields 2,2,2‐trinitroethyl nitrocarbamate ( 3 ), which has potential as a perchlorate free high energetic dense oxidizer with a high oxygen balance of Ω(CO₂) = +14.9 %. The thermal stability was studied using differential scanning calorimetry and the energies of formation were calculated on the CBS‐4M level of theory, as well as several detonation parameters and propulsion properties were determined. In addition to full spectroscopic characterization, X‐ray diffraction studies were performed for 2 and 3 .