Large cross-effect dynamic nuclear polarisation enhancements with kilowatt inverting chirped pulses at 94 GHz

This work was supported by UK Research Council EPSRC research grant EP/R13705/1 and Wellcome Trust 099149/Z/12/Z.Dynamic nuclear polarisation (DNP) is a process that transfers electron spin polarisation to nuclei by applying resonant microwave radiation, and has been widely used to improve the sensitivity of nuclear magnetic resonance (NMR). Here we demonstrate new levels of performance for static cross-effect proton DNP using high peak power chirped inversion pulses at 94 GHz to create a strong polarisation gradient across the inhomogeneously broadened line of the mono-radical 4-amino TEMPO. Enhancements of up to 340 are achieved at an average power of a few hundred mW, with fast build-up times (3 s). Experiments are performed using a home-built wideband kW pulsed electron paramagnetic resonance (EPR) spectrometer operating at 94 GHz, integrated with an NMR detection system. Simultaneous DNP and EPR characterisation of other mono-radicals and biradicals, as a function of temperature, leads to additional insights into limiting relaxation mechanisms and give further motivation for the development of wideband pulsed amplifiers for DNP at higher frequencies.Publisher PDFPeer reviewe

Compact corrugated feedhorns with high Gaussian coupling efficiency and -60 dB sidelobes

We demonstrate that very high performance, extremely compact, scalar corrugated feedhorns can be designed and constructed by optimizing the excitation and phasing of the HE11, HE12 and HE13 modes near the throat of the horn whilst limiting excitation of higher order modes. We present the design and measurement of two families of dual-profiled horn, both with a directivity of 20 dBi that couple with very high efficiency to a fundamental Gaussian mode. The first was optimized for sidelobe performance and features sidelobes approaching -60 dB for a horn length of only 15.6λ. The second was designed to minimize horn length and achieves sidelobe levels below -35 dB for a horn which is only 4.8λ long. The horns exhibit excellent coupling to the fundamental free-space Gaussian mode, with LG00 power coupling of 99.92% and 99.75% respectively. We demonstrate excellent agreement between simulation and experiment at 94 GHz and simulate the performance over a 20% bandwidth. High performance compact scalar horns are of interest because they reduce manufacturing risk at high frequencies, and reduce size and weight at lower frequencies, which can be important in horn arrays and space applications, where horn arrays often have serious weight and size restrictions.PostprintPeer reviewe

Shape dependent conformable holographic metasurfaces

Funding: European Research Council - 819346; Engineering and Physical Sciences Research Council - EP/V029975/1; Royal Society - URF\R\211033.In this paper, the design, fabrication, and experimental demonstration of conformable holographic metasurfaces are reported. Here, it is shown that the produced holographic image changes as the metasurface is applied to targets with different shapes. The demonstration is based on a reflective type metasurface, where the reflected polarization is perpendicular to that of the incident light. In addition, how the parameters of the metasurface determine the quality of the images produced and the ability to produce independent images are discussed critically.Publisher PDFPeer reviewe

An output coupler for a W-band high power wideband gyro-amplifier

This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) U.K. under Research Grant EP/K029746/1, and Science and Technology Facilities Council (STFC) U.K. under Research Grants ST/K006673/1 & ST/K006703/1, ST/N002326/1 & ST/N002318/1.An output coupler for a W-band high power wideband gyro-amplifier has been designed, manufactured and experimentally measured. It consists of a high performance sin2-parallel corrugated horn integrated with a broadband multi-layer window. The major design requirements are that the horn/window combination must have an input return loss lower than -30 dB over a 10 GHz bandwidth, provide a high quality output beam pattern, and operate under ultra-high vacuum conditions. The coupler converts a circular wave guide TE11 mode into the free space Laguerre Gaussian LG00 mode over the frequency band of 90–100 GHz with a measured return loss of between -30 and -40 dB and a simulated Gaussian coupling efficiency of over 99% at 94 GHz.PostprintPeer reviewe

Selective Expression and Functions of Interleukin 18 Receptor on T Helper (Th) Type 1 but not Th2 Cells

Interleukin (IL)-18 induces interferon (IFN)-γ synthesis and synergizes with IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells. IL-18R mRNA was expressed constitutively and consistently in long-term cultured clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the expression of IL-12Rβ2 mRNA, indicating that IL-18R transmits signals that maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated IL-18R mRNA. Antibody against an IL-18R–derived peptide bound Th1 but not Th2 clones. It also labeled polarized Th1 but not Th2 cells derived from naive ovalbumin–T cell antigen receptor-αβ transgenic mice (D011.10). Anti–IL-18R antibody inhibited IL-18– induced IFN-γ production by Th1 clones in vitro. In vivo, anti–IL-18R antibody reduced local inflammation and lipopolysaccharide-induced mortality in mice. This was accompanied by shifting the balance from Th1 to Th2 responses, manifest as decreased IFN-γ and proinflammatory cytokine production and increased IL-4 and IL-5 synthesis. Therefore, these data provide a direct mechanism for the selective effect of IL-18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12 and IL-18 on Th1 development may be due to the reciprocal upregulation of their receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from Th2 cells and may be a therapeutic target

Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy

Acknowledgements The authors are grateful to Nils Lindstrom and members of the Gillingwater laboratory for advice and assistance with this study and helpful comments on the manuscript; Neil Cashman for the NSC-34 cell line; and Ji-Long Liu for the DrosophilasmnA and smnB lines. This work was supported by grants from the SMA Trust (to T.H. Gillingwater, P.J. Young, and R. Morse), BDF Newlife (to T.H. Gillingwater and S.H. Parson), the Anatomical Society (to T.H. Gillingwater and S.H. Parson), the Muscular Dystrophy Campaign (to T.H. Gillingwater), the Jennifer Trust for Spinal Muscular Atrophy (to H.R. Fuller), the Muscular Dystrophy Association (to G.E. Morris), the Vandervell Foundation (to P.J. Young), the Medical Research Council (GO82208 to I.M. Robinson), Roslin Institute Strategic Grant funding from the BBSRC (to T.M. Wishart), the BBSRC (to C.G. Becker), the Deutsche Forschungsgemeinschaft and EU FP7/2007-2013 (grant no. 2012-305121, NeurOmics, to B. Wirth), the Center for Molecular Medicine Cologne (to B. Wirth and M. Hammerschmidt), and SMA Europe (to M.M. Reissland). We would also like to acknowledge financial support to the Gillingwater lab generated through donations to the SMASHSMA campaign.Peer reviewedPublisher PD

The re-discovery of contemplation through science : with Tom McLeish, “The Re-Discovery of Contemplation through Science: Boyle Lecture 2021”; Rowan Williams, “The Re-Discovery of Contemplation through Science: A Response to Tom McLeish”; Fraser Watts, “Discussion of the Boyle Lecture 2021”; and Tom McLeish, “Response to Boyle Lecture 2021 Panel and Participant Discussion.”

Some of the early-modern changes in the social framing of science, while often believed to be essential, are shown to be contingent. They contribute to the flawed public narrative around science today, and especially to the misconceptions around science and religion. Four are examined in detail, each of which contributes to the demise of the contemplative stance that science both requires and offers. They are: (1) a turn from an immersed subject to the pretense of a pure objectivity, (2) a turn from imagination as a legitimate pathway to knowledge, (3) a turn from shared and participative science to a restricted professionalism, and (4) an overprosaic reading of the metaphor of the “Book of Nature.” All four, but especially the imperative to consider reading nature as poetry, and a deeper examination of the entanglements between poetry and theoretical science, draw unavoidably on theological ideas, and contribute to a developing “theology of science.”