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Abstract: Since March 2013, the Diamond storage ring has been operated with a target vertical emittance of 8 pm.rad. This condition is achieved by first applying a LOCO* optics correction with IDs set to their typical gaps, then offsetting the skew quadrupole magnets in order to increase the vertical emittance again to the desired value. Whilst a feedback application** is able to stabilise the vertical emittance during ID gap and phase changes in the short to medium term, regular applications of LOCO are still required to maintain good coupling control in the longer term. In this paper we describe measures taken to speed up the optics correction procedure, including a fast orbit response matrix measurement, a reduction of the number of magnets used to measure the data, and a distribution of the LOCO calculations to run in parallel.

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Abstract: In the most common version of an oscillometric blood pressure monitor, the output from the pressure transducer, Y(t), is split into two parts, and used for separate determinations of the pressure inside the pneumatic cuff and its fluc-tuating part; the latter is derived by sending Y(t) to a high-pass filter (HPF) and amplifying the fil-tered part to obtain the oscillometric signal O(t). Using a typical HPF-amplifier combination, we show that if p(t), the pulsatile part of the cuff pressure, is defined to be a train of positive-going pulses, O(t) turns out to be rather close but not identical to dp/dt, and to demonstrate that one can easily retrieve p(t) from a record of O(t). This means that, with a small modification, the instrument can provide both p(t) and dp/dt; the practical advantages of this demonstration are pointed out.

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Abstract: High-reflectivity multilayers are required in many soft X-ray researches, from nowadays Synchrotron Radiation (SR) to future Free Electron Laser (FEL) optics. These synthetic reflectors are capable of working at near-normal incidence covering the lower X energy range not accessible by crystal diffraction. Recently, the deposition of such devices has progressed at INFN Legnaro Laboratories (LNL), giving robust Si/Mo mirror devices and first Ni/Ti and Ni/TiO2 multilayers. To test these new optics, at INFN Frascati Laboratories (LNF) a new vacuum compatible reflectometer has been assembled and commissioned in 2005. The final system is a θ-2θ diffractometer in vacuum environment, endowed with high angular resolution and repeatability and absolute detectors. A direct characterization of multilayer performances have been accomplished by SR from a wiggler source at DAΦNE. Results on characterization of the vacuum reflectometer and on the new Ni-Ti based multilayers are presented.

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Abstract: In fragment-based drug discovery, hundreds or often thousands of compounds smaller than ~300 Da are tested against the protein of interest to identify chemical entities that can be developed into potent drug candidates. Since the compounds are small, interactions are weak, and the screening method must therefore be highly sensitive; moreover, structural information tends to be crucial for elaborating these hits into lead-like compounds. Therefore, protein crystallography has always been a gold-standard technique, yet historically too challenging to find widespread use as a primary screen. Initial XChem experiments were demonstrated in 2014 and then trialed with academic and industrial collaborators to validate the process. Since then, a large research effort and significant beamtime have streamlined sample preparation, developed a fragment library with rapid follow-up possibilities, automated and improved the capability of I04-1 beamline for unattended data collection, and implemented new tools for data management, analysis and hit identification. XChem is now a facility for large-scale crystallographic fragment screening, supporting the entire crystals-to-deposition process, and accessible to academic and industrial users worldwide. The peer-reviewed academic user program has been actively developed since 2016, to accommodate projects from as broad a scientific scope as possible, including well-validated as well as exploratory projects. Academic access is allocated through biannual calls for peer-reviewed proposals, and proprietary work is arranged by Diamond's Industrial Liaison group. This workflow has already been routinely applied to over a hundred targets from diverse therapeutic areas, and effectively identifies weak binders (1%-30% hit rate), which both serve as high-quality starting points for compound design and provide extensive structural information on binding sites. The resilience of the process was demonstrated by continued screening of SARS-CoV-2 targets during the COVID-19 pandemic, including a 3-week turn-around for the main protease.

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Abstract: Crystallization of eukaryotic membrane proteins is a challenging, iterative process. The protein of interest is often modified in an attempt to improve crystallization and diffraction results. To accelerate this process, we took advantage of a GFP-fusion yeast expression system that uses PCR to direct homologous recombination and gene cloning. We explored the possibility of employing more than one PCR fragment to introduce various mutations in a single step, and found that when up to five PCR fragments were co-transformed into yeast, the recombination frequency was maintained as the number of fragments was increased. All transformants expressed the model membrane protein, while the resulting plasmid from each clone contained the designed mutations only. Thus, we have demonstrated a technique allowing the expression of mutant membrane proteins within 5 days, combining a GFP-fusion expression system and yeast homologous recombination.