Performance of the EUDET-type beam telescopes

Test beam measurements at the test beam facilities of DESY have been conducted to characterise the performance of the EUDET-type beam telescopes originally developed within the EUDET project. The beam telescopes are equipped with six sensor planes using MIMOSA26 monolithic active pixel devices. A programmable Trigger Logic Unit provides trigger logic and time stamp information on particle passage. Both data acquisition framework and offline reconstruction software packages are available. User devices are easily integrable into the data acquisition framework via predefined interfaces. The biased residual distribution is studied as a function of the beam energy, plane spacing and sensor threshold. Its standard deviation at the two centre pixel planes using all six planes for tracking in a 6\,GeV electron/positron-beam is measured to be (2.88\,\pm\,0.08)\,\upmu\meter.Iterative track fits using the formalism of General Broken Lines are performed to estimate the intrinsic resolution of the individual pixel planes. The mean intrinsic resolution over the six sensors used is found to be (3.24\,\pm\,0.09)\,\upmu\meter.With a 5\,GeV electron/positron beam, the track resolution halfway between the two inner pixel planes using an equidistant plane spacing of 20\,mm is estimated to (1.83\,\pm\,0.03)\,\upmu\meter assuming the measured intrinsic resolution. Towards lower beam energies the track resolution deteriorates due to increasing multiple scattering. Threshold studies show an optimal working point of the MIMOSA26 sensors at a sensor threshold of between five and six times their RMS noise. Measurements at different plane spacings are used to calibrate the amount of multiple scattering in the material traversed and allow for corrections to the predicted angular scattering for electron beams

Mechanistic basis of the Cu(OAc)2 catalyzed azide-ynamine (3 + 2) cycloaddition reaction

R.P.B. and G.A.B. thank GSK and the Engineering and Physical Sciences Research Council (EPSRC) for an industrial CASE studentship (EP/P51066X/1). G.A.B., F.P., and A.J.B.W. thank the Leverhulme Trust (RP-2020-380). A.T.S. and G.A.B. thank the Biotechnology and Biological Research Council (BBSRC) for its support (BB/V017586/1; BB/T000627/1). A.J.B.W. and M.J.A. thank the EPSRC for its support (EP/R025754/1). A.J.B.W. thanks the Leverhulme Trust for a Research Fellowship (RF-2022-014).The Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction is used as a ligation tool throughout chemical and biological sciences. Despite the pervasiveness of CuAAC, there is a need to develop more efficient methods to form 1,4-triazole ligated products with low loadings of Cu. In this paper, we disclose a mechanistic model for the ynamine-azide (3 + 2) cycloadditions catalyzed by copper(II) acetate. Using multinuclear nuclear magnetic resonance spectroscopy, electron paramagnetic resonance spectroscopy, and high-performance liquid chromatography analyses, a dual catalytic cycle is identified. First, the formation of a diyne species via Glaser–Hay coupling of a terminal ynamine forms a Cu(I) species competent to catalyze an ynamine-azide (3 + 2) cycloaddition. Second, the benzimidazole unit of the ynamine structure has multiple roles: assisting C–H activation, Cu coordination, and the formation of a postreaction resting state Cu complex after completion of the (3 + 2) cycloaddition. Finally, reactivation of the Cu resting state complex is shown by the addition of isotopically labeled ynamine and azide substrates to form a labeled 1,4-triazole product. This work provides a mechanistic basis for the use of mixed valency binuclear catalytic Cu species in conjunction with Cu-coordinating alkynes to afford superior reactivity in CuAAC reactions. Additionally, these data show how the CuAAC reaction kinetics can be modulated by changes to the alkyne substrate, which then has a predictable effect on the reaction mechanism.Peer reviewe

A20-Deficient Mast Cells Exacerbate Inflammatory Responses In Vivo

Mast cells are implicated in the pathogenesis of inflammatory and autoimmune diseases. However, this notion based on studies in mast cell-deficient mice is controversial. We therefore established an in vivo model for hyperactive mast cells by specifically ablating the NF-kappa B negative feedback regulator A20. While A20 deficiency did not affect mast cell degranulation, it resulted in amplified pro-inflammatory responses downstream of IgE/Fc epsilon RI, TLRs, IL-1R, and IL-33R. As a consequence house dust mite- and IL-33-driven lung inflammation, late phase cutaneous anaphylaxis, and collagen-induced arthritis were aggravated, in contrast to experimental autoimmune encephalomyelitis and immediate anaphylaxis. Our results provide in vivo evidence that hyperactive mast cells can exacerbate inflammatory disorders and define diseases that might benefit from therapeutic intervention with mast cell function

An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice

AIMS/HYPOTHESIS: Loss of circadian clocks from all tissues causes defective glucose homeostasis as well as loss of feeding and activity rhythms. Little is known about peripheral tissue clocks, so we tested the hypothesis that an intrinsic circadian clock of the pancreas is important for glucose homeostasis. METHODS: We monitored real-time bioluminescence of pancreas explants from circadian reporter mice and examined clock gene expression in beta cells by immunohistochemistry and in situ hybridisation. We generated mice selectively lacking the essential clock gene Bmal1 (also known as Arntl) in the pancreas and tested mutant mice and littermate controls for glucose and insulin tolerance, insulin production and behaviour. We examined islets isolated from mutants and littermate controls for glucose-stimulated insulin secretion and total insulin content. RESULTS: Pancreas explants exhibited robust circadian rhythms. Clock genes Bmal1 and Per1 were expressed in beta cells. Despite normal activity and feeding behaviour, mutant mice lacking clock function in the pancreas had severe glucose intolerance and defective insulin production; their isolated pancreatic islets had defective glucose-stimulated insulin secretion, but normal total insulin content. CONCLUSIONS/INTERPRETATION: The mouse pancreas has an autonomous clock function and beta cells are very likely to be one of the pancreatic cell types possessing an intrinsic clock. The Bmal1 circadian clock gene is required in the pancreas, probably in beta cells, for normal insulin secretion and glucose homeostasis. Our results provide evidence for a previously unrecognised molecular regulator of pancreatic glucose-sensing and/or insulin secretion

Population Physiology: Leveraging Electronic Health Record Data to Understand Human Endocrine Dynamics

Studying physiology and pathophysiology over a broad population for long periods of time is difficult primarily because collecting human physiologic data can be intrusive, dangerous, and expensive. One solution is to use data that have been collected for a different purpose. Electronic health record (EHR) data promise to support the development and testing of mechanistic physiologic models on diverse populations and allow correlation with clinical outcomes, but limitations in the data have thus far thwarted such use. For example, using uncontrolled population-scale EHR data to verify the outcome of time dependent behavior of mechanistic, constructive models can be difficult because: (i) aggregation of the population can obscure or generate a signal, (ii) there is often no control population with a well understood health state, and (iii) diversity in how the population is measured can make the data difficult to fit into conventional analysis techniques. This paper shows that it is possible to use EHR data to test a physiological model for a population and over long time scales. Specifically, a methodology is developed and demonstrated for testing a mechanistic, time-dependent, physiological model of serum glucose dynamics with uncontrolled, population-scale, physiological patient data extracted from an EHR repository. It is shown that there is no observable daily variation the normalized mean glucose for any EHR subpopulations. In contrast, a derived value, daily variation in nonlinear correlation quantified by the time-delayed mutual information (TDMI), did reveal the intuitively expected diurnal variation in glucose levels amongst a random population of humans. Moreover, in a population of continuously (tube) fed patients, there was no observable TDMI-based diurnal signal. These TDMI-based signals, via a glucose insulin model, were then connected with human feeding patterns. In particular, a constructive physiological model was shown to correctly predict the difference between the general uncontrolled population and a subpopulation whose feeding was controlled

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured