Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry

Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography – tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. In a pooled (CSF) sample used for internal quality control, absolute quantification was performed on 10 sterols, semi-quantification on 9 sterols and approximate quantification on a further three partially identified sterols. The value of the method is illustrated by confirming the sterol phenotype of a patient suffering from ACOX2 deficiency, a rare disorder of bile acid biosynthesis, and in a plasma sample from a patient suffering from cerebrotendinous xanthomatosis, where cholesterol 27-hydroxylase is deficient

Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3

GATA-3 is essential for T cell development from the earliest stages. However, abundant GATA-3 can drive T lineage precursors to a non–T cell fate, depending on Notch signaling and developmental stage. Here, overexpression of GATA-3 blocked the survival of pro–T cells when Notch-Delta signals were present but enhanced viability in their absence. In fetal thymocytes at the double-negative 1 (DN1) stage and DN2 stage but not those at the DN3 stage, overexpression of GATA-3 rapidly induced respecification to the mast cell lineage with high frequency by direct transcriptional 'reprogramming'. Normal DN2 thymocytes also showed mast cell potential when interleukin 3 and stem cell factor were added in the absence of Notch signaling. Our results suggest a close relationship between the pro–T cell and mast cell programs and a previously unknown function for Notch in T lineage fidelity

Reputation for technological innovation: Does it actually cohere with innovative activity?

Firms strategically promote, foster and pursue a reputation for technological innovation. Yet, present research did not examine whether such perception actually coheres with innovative activity itself. Previous studies in this field often relied solely on tangible products/product introductions, hence we apply multiple proxies based on a firm's intangible innovative performance to examine the influences on reputation for technological innovation. Using patent, financial and consumer data our Poisson regression analyzes 65 international firms which have been nominated by 231 consumers. We apply time-series and likewise cross-sectional data for our interdisciplinary analysis. Our findings demonstrate that innovative performance (citation intensity) is linked to reputation for technological innovation. Counter-intuitively, our results provide evidence that marketing intensity negatively influences a reputation for technological innovation. From the results, we conclude that innovative performance may be associated with a reputation for technological innovation. Actual technological advancement attracts attention from consumers that cannot be purchased with greater marketing investments. This implies that consumers appreciate the costly and uncertain R&D efforts and value those firms that constantly offer innovation. As a theoretical implication, the consideration of intangible inputs for reputation research is an important contribution for a holistic understanding. The results represent essential strategic information for innovation and marketing functions, where both divisions need to align their activities and investments

PbS(Se) quantum dot doped glass applications as laser passive Q-Switches

Nonlinear optical properties of phosphate and silicate glasses doped with PbS and PbSe quantum dots of different sizes were studied. Absorption saturation intensity in the range of the first and second excitonic transitions was estimated. Passive Q-switch operation of glasses doped with PbS- and PbSe-quantum dots as saturable absorbers for 1.067 mum Nd3+:KGd(WO4)(2), 1.54 mum Er:glass and 2.1 mum Ho3-:Cr3+:Tm3+: Y3Al5O12 diode- and flashlamp-pumped lasers was demonstrated