B16-Test Beamline
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Abstract: Intense research activities have been made in the development of high-Z and wide-bandgap compound semiconductor pixel detectors for the next generation X-ray and gamma ray spectroscopic imagers. Cadmium telluride (CdTe) and cadmium–zinc–telluride (CdZnTe or CZT) pixel detectors have shown impressive performance in X-ray and gamma ray detection from energies of few keV up to 1 MeV. Charge sharing and cross-talk phenomena represent the typical drawbacks in sub-millimeter pixel detectors, with severe distortions in both energy and spatial resolution. In this chapter, we review the effects of these phenomena on the response of CZT/CdTe pixel detectors, with particular emphasis on the current state of the art of the discrimination/correction techniques. The results from original energy-recovery procedures of multiple charge sharing events, recently developed by our group, are also shown.
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Jan 2023
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Krios I-Titan Krios I at Diamond
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Yang
Yang
,
Wenjuan
Zhang
,
Alexey G.
Murzin
,
Manuel
Schweighauser
,
Melissa
Huang
,
Sofia
Lovestam
,
Sew Y.
Peak-Chew
,
Takashi
Saito
,
Takaomi C.
Saido
,
Jennifer
Macdonald
,
Isabelle
Lavenir
,
Bernardino
Ghetti
,
Caroline
Graff
,
Amit
Kumar
,
Agneta
Nordberg
,
Michel
Goedert
,
Sjors H. W.
Scheres
Diamond Proposal Number(s):
[23268]
Open Access
Abstract: The Arctic mutation, encoding E693G in the amyloid precursor protein (APP) gene [E22G in amyloid-β (Aβ)], causes dominantly inherited Alzheimer’s disease. Here, we report the high-resolution cryo-EM structures of Aβ filaments from the frontal cortex of a previously described case (AβPParc1) with the Arctic mutation. Most filaments consist of two pairs of non-identical protofilaments that comprise residues V12–V40 (human Arctic fold A) and E11–G37 (human Arctic fold B). They have a substructure (residues F20–G37) in common with the folds of type I and type II Aβ42. When compared to the structures of wild-type Aβ42 filaments, there are subtle conformational changes in the human Arctic folds, because of the lack of a side chain at G22, which may strengthen hydrogen bonding between mutant Aβ molecules and promote filament formation. A minority of Aβ42 filaments of type II was also present, as were tau paired helical filaments. In addition, we report the cryo-EM structures of Aβ filaments with the Arctic mutation from mouse knock-in line AppNL−G−F. Most filaments are made of two identical mutant protofilaments that extend from D1 to G37 (AppNL−G−F murine Arctic fold). In a minority of filaments, two dimeric folds pack against each other in an anti-parallel fashion. The AppNL−G−F murine Arctic fold differs from the human Arctic folds, but shares some substructure.
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Jan 2023
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I19-Small Molecule Single Crystal Diffraction
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Open Access
Abstract: Lithium-rich oxides are attracting intense interest as the next generation cathode materials for lithium-ion batteries due to their high theoretical capacity. Nevertheless, these materials suffer from a number of shortcomings, such as oxygen loss at high voltage, large hysteresis and poor rate capability. In this work, we show that through a dual cation doping strategy replacing Ti with Mo and Mg, the disordered rocksalt (DRS) Li1.2Ni0.4Ti0.4O2 is transformed into a new cation ordered layered phase Li1.2Ni0.4Mo0.2Mg0.2O2, with the high valence dopant Mo6+ on the (0,0,0) site. Li1.2Ni0.4Mo0.2Mg0.2O2 showed improved performance compared to that of the similarly prepared DRS Li1.2Ni0.4Ti0.4O2 material (~190 mAhg-1 vs ~105 mAhg-1 after 10 cycles, respectively). The characteristics of the electrochemical process were studied using ex situ XRD and XAS, which indicated the involvement of both Ni and Mo redox during the cycling as well as the electrochemical instability of the layered phase which changes to a disordered rocksalt phase on cycling.
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Jan 2023
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I24-Microfocus Macromolecular Crystallography
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Diamond Proposal Number(s):
[29990]
Open Access
Abstract: Since 2000, some thirteen quinolones and fluoroquinolones have been developed and have come to market. The quinolones, one of the most successful classes of antibacterial drugs, stabilize DNA cleavage complexes with DNA gyrase and topoisomerase IV (topo IV), the two bacterial type IIA topoisomerases. The dual targeting of gyrase and topo IV helps decrease the likelihood of resistance developing. Here, we report on a 2.8 Å X-ray crystal structure, which shows that zoliflodacin, a spiropyrimidinetrione antibiotic, binds in the same DNA cleavage site(s) as quinolones, sterically blocking DNA religation. The structure shows that zoliflodacin interacts with highly conserved residues on GyrB (and does not use the quinolone water–metal ion bridge to GyrA), suggesting it may be more difficult for bacteria to develop target mediated resistance. We show that zoliflodacin has an MIC of 4 µg/mL against Acinetobacter baumannii (A. baumannii), an improvement of four-fold over its progenitor QPT-1. The current phase III clinical trial of zoliflodacin for gonorrhea is due to be read out in 2023. Zoliflodacin, together with the unrelated novel bacterial topoisomerase inhibitor gepotidacin, is likely to become the first entirely novel chemical entities approved against Gram-negative bacteria in the 21st century. Zoliflodacin may also become the progenitor of a new safer class of antibacterial drugs against other problematic Gram-negative bacteria.
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Jan 2023
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I03-Macromolecular Crystallography
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Diamond Proposal Number(s):
[26794]
Open Access
Abstract: Hyperactive mutation V617F in the JAK2 regulatory pseudokinase domain (JH2) is prevalent in patients with myeloproliferative neoplasms. Here, we identified novel small molecules that target JH2 of JAK2 V617F and characterized binding via biochemical and structural approaches. Screening of 107,600 small molecules resulted in identification of 55 binders to the ATP-binding pocket of recombinant JAK2 JH2 V617F protein at a low hit rate of 0.05%, which indicates unique structural characteristics of the JAK2 JH2 ATP-binding pocket. Selected hits and structural analogs were further assessed for binding to JH2 and JH1 (kinase) domains of JAK family members (JAK1-3, TYK2) and for effects on MPN model cell viability. Crystal structures were determined with JAK2 JH2 wild-type and V617F. The JH2-selective binders were identified in diaminotriazole, diaminotriazine, and phenylpyrazolo-pyrimidone chemical entities, but they showed low-affinity, and no inhibition of MPN cells was detected, while compounds binding to both JAK2 JH1 and JH2 domains inhibited MPN cell viability. X-ray crystal structures of protein-ligand complexes indicated generally similar binding modes between the ligands and V617F or wild-type JAK2. Ligands of JAK2 JH2 V617F are applicable as probes in JAK-STAT research, and SAR optimization combined with structural insights may yield higher-affinity inhibitors with biological activity.
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Jan 2023
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[21497]
Abstract: Organic semiconductors are promising for efficient, printable optoelectronics. Yet, strong excited-state quenching due to uncontrolled aggregation limits their use in devices. We report on the self-assembly of a supramolecular pseudo-cube formed from six perylene diimides (PDIs). The rigid, shape-persistent cage sets the distance and orientation of the PDIs and suppresses intramolecular rotations and vibrations, leading to non-aggregated, monomer-like properties in solution and the solid state, in contrast to the fast fluorescence quenching in the free ligand. The stabilized excited state and electronic purity in the cage enables the observation of delayed fluorescence due to a bright excited multimer, acting as excited-state reservoir in a rare case of benign inter-chromophore interactions in the cage. We show that self-assembly provides a powerful tool for retaining and controlling the electronic properties of chromophores, and to bring molecular electronics devices within reach.
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Jan 2023
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I14-Hard X-ray Nanoprobe
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Ian
Byrnes
,
Lisa Magdalena
Rossbach
,
Jakub
Jaroszewicz
,
Daniel
Grolimund
,
Dario
Ferreira Sanchez
,
Miguel A.
Gomez-Gonzalez
,
Gert
Nuyts
,
Estela
Reinoso-Maset
,
Koen
Janssens
,
Brit
Salbu
,
Dag Anders
Brede
,
Ole Christian
Lind
Diamond Proposal Number(s):
[27615]
Open Access
Abstract: Micro- and nanoscopic X-ray techniques were used to investigate the relationship between uranium (U) tissue distributions and adverse effects to the digestive tract of aquatic model organism Daphnia magna following uranium nanoparticle (UNP) exposure. X-ray absorption computed tomography measurements of intact daphnids exposed to sublethal concentrations of UNPs or a U reference solution (URef) showed adverse morphological changes to the midgut and the hepatic ceca. Histological analyses of exposed organisms revealed a high proportion of abnormal and irregularly shaped intestinal epithelial cells. Disruption of the hepatic ceca and midgut epithelial tissues implied digestive functions and intestinal barriers were compromised. Synchrotron-based micro X-ray fluorescence (XRF) elemental mapping identified U co-localized with morphological changes, with substantial accumulation of U in the lumen as well as in the epithelial tissues. Utilizing high-resolution nano-XRF, 400–1000 nm sized U particulates could be identified throughout the midgut and within hepatic ceca cells, coinciding with tissue damages. The results highlight disruption of intestinal function as an important mode of action of acute U toxicity in D. magna and that midgut epithelial cells as well as the hepatic ceca are key target organs.
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Jan 2023
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E02-JEM ARM 300CF
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Diamond Proposal Number(s):
[25787, 27541, 29157]
Open Access
Abstract: Single-atom catalysts (SACs) on hematite photoanodes are efficient cocatalysts to boost photoelectrochemical performance. They feature high atom utilization, remarkable activity, and distinct active sites. However, the specific role of SACs on hematite photoanodes is not fully understood yet: Do SACs behave as a catalytic site or as a spectator? By combining spectroscopic experiments and computer simulations, we demonstrate that single-atom iridium (sIr) catalysts on hematite (α-Fe2O3/sIr) photoanodes act as a true catalyst by trapping holes from hematite and providing active sites for the water oxidation reaction. In situ transient absorption spectroscopy showed a reduced number of holes and shortened hole lifetime in the presence of sIr. This was particularly evident on the second timescale, indicative of fast hole transfer and depletion toward water oxidation. Intensity-modulated photocurrent spectroscopy evidenced a faster hole transfer at the α-Fe2O3/sIr/electrolyte interface compared to that at bare α-Fe2O3. Density functional theory calculations revealed the mechanism for water oxidation using sIr as a catalytic center to be the preferred pathway as it displayed a lower onset potential than the Fe sites. X-ray photoelectron spectroscopy demonstrated that sIr introduced a mid-gap of 4d state, key to the fast hole transfer and hole depletion. These combined results provide new insights into the processes controlling solar water oxidation and the role of SACs in enhancing the catalytic performance of semiconductors in photo-assisted reactions.
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Jan 2023
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B23-Circular Dichroism
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Abstract: High-resolution calorimetry has played a significant role in providing detailed information on phase transitions in liquid crystals. In particular, adiabatic scanning calorimetry (ASC), capable of providing simultaneous information on the temperature dependence of the specific enthalpy
h
(
T
)
and on the specific heat capacity
c
p
(
T
)
, has proven to be an important tool to determine the order of transitions and render high-resolution information on pretransitional thermal behavior. Here we report on ASC results on the compound 2,3′,4′,5′-tetrafluoro[1,1′-biphenyl]-4-yl 2,6-difluoro-4-(5-propyl-1,3-dioxan-2-yl) benzoate (DIO) and on mixtures with 4-[(4-nitrophenoxy)carbonyl]phenyl 2,4-dimethoxybenzoate (RM734). Both compounds exhibit a low-temperature ferroelectric nematic phase (
N
F
) and a high-temperature paraelectric nematic phase
(
N
)
. However, in DIO these two phases are separated by an intermediate phase (
N
x
). From the detailed data of
h
(
T
)
and
c
p
(
T
)
, we found that the intermediate phase was present in all the mixtures over the complete composition range, albeit with strongly decreasing temperature width for that phase with decreasing mole fraction of DIO (
x
DIO
). The
x
DIO
dependence on the transition temperatures for both transitions could be well described by a quadratic function. Both these transitions were weakly first order. The true latent heat of the
N
x
−
N
transition of DIO was as low as
L
=
0.0075
±
0.0005
J
/
g
and
L
=
0.23
±
0.03
J
/
g
for the
N
F
−
N
x
transition, which is about twice the previously reported value of 0.115 J/g for the
N
F
−
N
transition in RM734. In the mixtures both transition latent heats decrease gradually with decreasing
x
DIO
. At all the
N
x
−
N
transitions pretransition fluctuation effects are absent and these transitions are purely but very weakly first order. As in RM734 the transition from the
N
F
to the higher-temperature phase exhibits substantial pretransitional behavior, in particular, in the high-temperature phase. Power-law analysis of
c
p
(
T
)
resulted in an effective critical exponent
α
=
0.88
±
0.1
for DIO and this value decreased in the mixtures with decreasing
x
DIO
toward
α
=
0.50
±
0.05
reported for RM734. Ideal mixture analysis of the phase diagram was consistent with ideal mixture behavior provided the total transition enthalpy change was used in the analysis.
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Jan 2023
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I19-Small Molecule Single Crystal Diffraction
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Open Access
Abstract: The synthesis, spectroelectrochemical and structural characteristics of highly electron-accepting diketopyrrrolopyrrole (DPP) molecules with adjoining pyridinium rings is reported, along with an assessment of their toxicity, which is apparently low. The compounds show reversible electrochemistry and in one subfamily a massive increase in molar extinction coefficient upon electrochemical reduction.
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Jan 2023
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