The Dimroth rearrangement as a probable cause for structural misassignments in imidazo[1,2-a]pyrimidines: A 15N-labelling study and an easy method for the determination of regiochemistry

Structural misassignments are often seen for complex natural products, but this can also be an issue with seemingly simpler structures. In this paper, we describe how, using a15N-labelled analogue, we established that the Dimroth rearrangement can occur in imidazo[1,2-a]pyrimidines and result in an incorrect regiochemical assignment of such compounds. These studies supported a rearrangement mechanism involving addition of hydroxide ion followed by ring opening. It was also observed that C(2) and C(3) substituted regioisomers could be readily distinguished using1H NMR spectroscopy

Trust in Nanotechnology? On Trust as Analytical Tool in Social Research on Emerging Technologies

Trust has become an important aspect of evaluating the relationship between lay public and technology implementation. Experiences have shown that a focus on trust provides a richer understanding of reasons for backlashes of technology in society than a mere focus of public understanding of risks and science communication. Therefore, trust is also widely used as a key concept for understanding and predicting trust or distrust in emerging technologies. But whereas trust broadens the scope for understanding established technologies with well-defined questions and controversies, it easily fails to do so with emerging technologies, where there are no shared questions, a lack of public familiarity with the technology in question, and a restricted understanding amongst social researchers as to where distrust is likely to arise and how and under which form the technology will actually be implemented. Rather contrary, ‘trust’ might sometimes even direct social research into fixed structures that makes it even more difficult for social research to provide socially robust knowledge. This article therefore suggests that if trust is to maintain its important role in evaluating emerging technologies, the approach has to be widened and initially focus not on people’s motivations for trust, but rather the object of trust it self, as to predicting how and where distrust might appear, how the object is established as an object of trust, and how it is established in relation with the public

Phenotypic screening identifies a trisubstituted imidazo[1,2-a]pyridine series that induces differentiation in multiple AML cell lines

Acute myeloid leukaemia (AML) is an aggressive type of leukaemia with low rates of long-term survival. While the current standard of care is based on cytotoxic chemotherapy, a promising emerging approach is differentiation therapy. However, most current differentiating agents target specific mutations and are effective only in certain patient subtypes. To identify agents which may be effective in wider population cohorts, we performed a phenotypic screen with the myeloid marker CD11b and identified a compound series that was able to differentiate AML cell lines in vitro regardless of their mutation status. Structure-activity relationship studies revealed that replacing the formamide and catechol methyl ether groups with sulfonamide and indazole respectively improved the in vitro metabolic profile of the series while maintaining the differentiation profile in multiple cell lines. This optimisation exercise enabled progression of a lead compound to in vivo efficacy testing. Our work supports the promise of phenotypic screening to identify novel small molecules that induce differentiation in a wide range of AML subtypes

An interdisciplinary cruise dedicated to understanding ocean eddies upstream of the Prince Edward Islands

A DETAILED HYDROGRAPHIC AND BIOLOGical survey was carried out in the region of the South-West Indian Ridge during April 2004. Altimetry and hydrographic data have identified this region as an area of high flow variability. Hydrographic data revealed that here the Subantarctic Polar Front (SAF) and Antarctic Polar Front (APF) converge toform a highly intense frontal system. Water masses identified during the survey showed a distinct separation in properties between the northwestern and southeastern corners. In the north-west, water masses were distinctly Subantarctic (>8.5°C, salinity >34.2), suggesting that the SAF lay extremely far to the south. In the southeast corner water masses were typical of the Antarctic zone, showing a distinct subsurface temperature minimum of <2.5°C. Total integrated chl-a concentration during the survey ranged from 4.15 to 22.81mgchl-am–2,with the highest concentrations recorded at stations occupied in the frontal region. These data suggest that the region of the South-West Indian Ridge represents not only an area of elevated biological activity but also acts as a strong biogeographic barrier to the spatial distribution of zooplankton

Search for the Higgs boson in events with missing transverse energy and b quark jets produced in proton-antiproton collisions at s**(1/2)=1.96 TeV

We search for the standard model Higgs boson produced in association with an electroweak vector boson in events with no identified charged leptons, large imbalance in transverse momentum, and two jets where at least one contains a secondary vertex consistent with the decay of b hadrons. We use ~1 fb-1 integrated luminosity of proton-antiproton collisions at s**(1/2)=1.96 TeV recorded by the CDF II experiment at the Tevatron. We find 268 (16) single (double) b-tagged candidate events, where 248 +/- 43 (14.4 +/- 2.7) are expected from standard model background processes. We place 95% confidence level upper limits on the Higgs boson production cross section for several Higgs boson masses ranging from 110 GeV/c2 to 140 GeV/c2. For a mass of 115 GeV/c2 the observed (expected) limit is 20.4 (14.2) times the standard model prediction.Comment: 8 pages, 2 figures, submitted to Phys. Rev. Let

An interdisciplinary cruise dedicated to understanding ocean eddies upstream of the Prince Edward Islands

A detailed hydrographic and biological survey was carried out in the region of the South-West Indian Ridge during April 2004. Altimetry and hydrographic data have identified this region as an area of high flow variability. Hydrographic data revealed that here the Subantarctic Polar Front (SAF) and Antarctic Polar Front (APF) converge to form a highly intense frontal system. Water masses identified during the survey showed a distinct separation in properties between the northwestern and southeastern corners. In the north-west, water masses were distinctly Subantarctic (>8.5°C, salinity >34.2), suggesting that the SAF lay extremely far to the south. In the southeast corner water masses were typical of the Antarctic zone, showing a distinct subsurface temperature minimum of <2.5°C. Total integrated chl-a concentration during the survey ranged from 4.15 to 22.81 mg chl-a m[superscript (-2)], with the highest concentrations recorded at stations occupied in the frontal region. These data suggest that the region of the South-West Indian Ridge represents not only an area of elevated biological activity but also acts as a strong biogeographic barrier to the spatial distribution of zooplankton

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Search for Pair Production of Scalar Top Quarks Decaying to a tau Lepton and a b Quark in ppbar Collisions at sqrt{s}=1.96 TeV

We search for pair production of supersymmetric top quarks (~t_1), followed by R-parity violating decay ~t_1 -> tau b with a branching ratio beta, using 322 pb^-1 of ppbar collisions at sqrt{s}=1.96 TeV collected by the CDF II detector at Fermilab. Two candidate events pass our final selection criteria, consistent with the standard model expectation. We set upper limits on the cross section sigma(~t_1 ~tbar_1)*beta^2 as a function of the stop mass m(~t_1). Assuming beta=1, we set a 95% confidence level limit m(~t_1)>153 GeV/c^2. The limits are also applicable to the case of a third generation scalar leptoquark (LQ_3) decaying LQ_3 -> tau b.Comment: 7 pages, 2 eps figure