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Abstract Focused ultrasound and microbubbles can non-invasively and locally deliver therapeutics and imaging agents across the blood–brain barrier. Uniform treatment and minimal adverse bioeffects are critical to achieve reliable doses and enable safe routine use of this technique. Towards these aims, we have previously designed a rapid short-pulse ultrasound sequence and used it to deliver a 3 kDa model agent to mouse brains. We observed a homogeneous distribution in delivery and blood–brain barrier closing within 10 min. However, many therapeutics and imaging agents are larger than 3 kDa, such as antibody fragments and antisense oligonucleotides. Here, we evaluate the feasibility of using rapid short-pulses to deliver higher-molecular-weight model agents. 3, 10 and 70 kDa dextrans were successfully delivered to mouse brains, with decreasing doses and more heterogeneous distributions with increasing agent size. Minimal extravasation of endogenous albumin (66.5 kDa) was observed, while immunoglobulin (~ 150 kDa) and PEGylated liposomes (97.9 nm) were not detected. This study indicates that rapid short-pulses are versatile and, at an acoustic pressure of 0.35 MPa, can deliver therapeutics and imaging agents of sizes up to a hydrodynamic diameter between 8 nm (70 kDa dextran) and 11 nm (immunoglobulin). Increasing the acoustic pressure can extend the use of rapid short-pulses to deliver agents beyond this threshold, with little compromise on safety. This study demonstrates the potential for deliveries of higher-molecular-weight therapeutics and imaging agents using rapid short-pulses.

To construct large-scale superconducting devices, it is critical to enhance the current carrying capability of superconducting coils. One practical approach is to utilise assembled cables, composed of multiple strands, for the winding. There have only been a few investigations of the dependence of current distribution among the strands on the AC losses of the cables and coils wound with these cables. In this work, we studied three types of cables; 1) 8/2 (eight 2 mm-wide strands) Roebel cable, 8/2 Roebel; 2) two parallel stacks (TPS) which have the same geometrical dimensions as the Roebel cable, 8/2 TPS; and 3) an equivalent four-conductor stack (ES) comprising four 4 mm-wide conductors, 4/4 ES. We proposed a new numerical approach that can achieve equal current sharing and free current sharing among the strands. We examined the loss behaviour of all three types of straight cables and two coil assemblies comprising two, and eight, stacks of double pancakes (DPCs) wound with these cables, respectively. 2D FEM analysis was carried out in COMSOL Multiphysics using the $H$ – formulation. The stacks were modelled in parallel connection, with the same electric field applied to all strands, so that current is distributed between the conductors. Simulated transport AC loss results in the straight 8/2 Roebel cable, 8/2 TPS and 4/4 ES were compared with previously measured results as well as each other. The numerical AC loss results in two coil windings 2-DPC and 8-DPC wound with the 8/2 Roebel cables were compared with the results in coil windings wound with the 8/2 TPS and 4/4 ES. No transposition was introduced at the connection between double pancakes, in order that current can be shared among the strands in the 8/2 TPS and 4/4 ES. The results indicate that AC loss in the straight 8/2 TPS and 4/4 ES is larger than that in the 8/2 Roebel cable. Current is more concentrated in the outer strands for the straight 8/2 TPS and 4/4 ES than the 8/2 Roebel cable and causes greater AC loss than the 8/2 Roebel cable. The 8-DPC coil winding wound with the 8/2 Roebel cable has the smallest loss and the coil winding wound with the 8/2 TPS has the greatest loss at two current amplitudes investigated. At 113 A, the AC loss value in the 8-DPC coil winding wound with the 8/2 TPS is 2.2 times of that wound with the 8/2 Roebel cable.

Iron cores are widely employed in high temperature superconducting (HTS) power devices to enhance the magnetic field and improve the power density. In spite of these benefits, the presence of iron cores leads to a substantial increase in AC loss within HTS coil windings. Therefore, it is necessary to estimate the AC loss of HTS coil windings coupled with iron cores to propose methods for loss reduction. An effective way to reduce AC loss is to apply flux diverters (FDs) near the HTS coil windings. In this work, the 3D $T$ - $A$ homogenization method is used to calculate AC losses of the 1DPC (double pancake coil)-, 2DPC-, 4DPC-, and 8DPC assemblies at different currents with four ferromagnetic combinations: with an iron core (IC), with an iron core and FDs (IC_FDs), with an air core (AirC), and with air core and FDs (AirC_FDs). To weaken the impact of the iron core, the enlarged distance between the iron core and coil assemblies is considered to investigate AC loss dependence on this distance. In addition, the influence of the positions of FDs on AC loss reduction is also analyzed. The simulation results demonstrate that FDs can reduce the AC loss in coil assemblies, even when the iron core is present, owing to the reduction of the perpendicular magnetic field component in the end discs. For the 4DPC and 8DPC assemblies with IC, increasing the distance while using FDs, or decreasing the vertical gap between the coil assemblies and FDs, are effective in reducing AC loss.

C-Met is a receptor tyrosine kinase that is overexpressed in a range of different cancer types, and has been identified as a potential biomarker for cancer imaging and therapy. Previously, a 68Ga-labelled peptide, [68Ga]Ga-EMP-100, has shown promise for imaging c-Met in renal cell carcinoma in humans. Herein, we report the synthesis and preliminary biological evaluation of an [18F]AlF-labelled analogue, [18F]AlF-EMP-105, for c-Met imaging by positron emission tomography. EMP-105 was radiolabelled using the aluminium-[18F]fluoride method with 46 ± 2% RCY and >95% RCP in 35–40 min. In vitro evaluation showed that [18F]AlF-EMP-105 has a high specificity for c-Met-expressing cells. Radioactive metabolite analysis at 5 and 30 min post-injection revealed that [18F]AlF-EMP-105 has good blood stability, but undergoes transformation—transchelation, defluorination or demetallation—in the liver and kidneys. PET imaging in non-tumour-bearing mice showed high radioactive accumulation in the kidneys, bladder and urine, demonstrating that the tracer is cleared predominantly as [18F]fluoride by the renal system. With its high specificity for c-Met expressing cells, [18F]AlF-EMP-105 shows promise as a potential diagnostic tool for imaging cancer.

Superconducting machine designs have historically focused on an isolated, cryogenic rotor and conventional (copper) stator due to unacceptable levels of AC loss in a superconducting stator. Thus, AC loss reduction in the armature windings is one of the key issues for achieving practical all-superconducting motors that could deliver an unprecedented power density and significantly reduce machine complexity. In this paper, a 100 kW, 1500 rpm, all - HTS motor operating at 65 K is designed and AC loss simulations in HTS armature windings wound with different types of (RE)BCO conductor arrangements are carried out by implementing the T-A formulation and a rotating mesh using commercial FEM software COMSOL Multiphysics. Either 4 mm-wide (RE)BCO conductors, 14/2 (14 strands, each strand is 2 mm wide) (RE)BCO Roebel cables, or striated (RE)BCO conductors with four 1 mm-wide filaments are considered in the armature windings. The simulation results show that armature windings wound with Roebel cables or striated conductors can significantly reduce the AC loss in the armature windings compared to windings wound with 4 mm-wide conductors. It is also shown that the AC loss in the armature winding wound with the 4 mm-wide (RE)BCO conductors decreases with decreasing operating temperature. The AC loss reduction can be attributed to the reduced magnetic field penetration associated with the increased $I_{\mathrm {c}}$ in the winding. Finally, a 2% AC loss reduction can be achieved in the armature winding wound with (RE)BCO conductors with asymmetric $I_{\mathrm {c}}(B$ , $\theta$ ) characteristics by simply flipping the direction of the conductors of the armature winding. The simulation results in this work have practical implications for designing all-HTS superconducting rotating machines. Such machines could be suitable for H2 powered electric vehicles like large interstate trucks, heavy machinery, or locomotives.

Gadolinium(III) complexes are strong enhancers of magnetic resonance imaging (MRI) signals, thus are widely used as contrast agents despite their potential toxicity. Here, the authors review ligand design approaches aimed at improving the stability of Gd(III)-based MRI contrast agents.

The C-X-C chemokine receptor 4 (CXCR4) is G protein-coupled receptor that upon binding to its cognate ligand, can lead to tumor progression. Several CXCR4-targeted therapies are currently under investigation, and with it comes the need for imaging agents capable of accurate depiction of CXCR4 for therapeutic stratification and monitoring. PET agents enjoy the most success, but more cost-effective and radiation-free approaches such as ultrasound (US) imaging could represent an attractive alternative. In this work, we developed a targeted microbubble (MB) for imaging of vascular CXCR4 expression in cancer. A CXCR4-targeted MB was developed through incorporation of the T140 peptide into the MB shell. Binding properties of the T140-MB and control, non-targeted MB (NT-MB) were evaluated in MDA-MB-231 cells where CXCR4 expression was knocked-down (via shRNA) through optical imaging, and in the lymphoma tumor models U2932 and SuDHL8 (high and low CXCR4 expression, respectively) by US imaging. PET imaging of [18F]MCFB, a tumor-penetrating CXCR4-targeted small molecule, was used to provide whole-tumor CXCR4 readouts. CXCR4 expression and microvessel density were performed by immunohistochemistry analysis and western blot. T140-MB were formed with similar properties to NT-MB and accumulated sensitively and specifically in cells according to their CXCR4 expression. In NOD SCID mice, T140-MB persisted longer in tumors than NT-MB, indicative of target interaction, but showed no difference between U2932 and SuDHL8. In contrast, PET imaging with [18F]MCFB showed a marked difference in tumor uptake at 40–60 min post-injection between the two tumor models (p

The stochastic nature of single-molecule charge transport measurements requires collection of large data sets to capture their full complexity. Here, the authors adopt strategies from machine learning for the unsupervised classification of single-molecule charge transport data without a prioriassumptions.

Maximum entropy inference can be used to find equations for the critical currents (Jc) in a type II superconductor as a function of temperature, applied magnetic field, and angle of the applied field, θ or φ . This approach provides an understanding of how the macroscopic critical currents arise from averaging over different sources of vortex pinning. The dependence of critical currents on temperature and magnetic field can be derived with logarithmic constraints and accord with expressions which have been widely used with empirical justification since the first development of technical superconductors. In this paper we provide a physical interpretation of the constraints leading to the distributions for Jc(T) and Jc(B), and discuss the implications for experimental data analysis. We expand the maximum entropy analysis of angular Jc data to encompass samples which have correlated defects at arbitrary angles to the crystal axes giving both symmetric and asymmetric peaks and samples which show vortex channeling behavior. The distributions for angular data are derived using combinations of first, second or fourth order constraints on cot θ or cot φ . We discuss why these distributions apply whether or not correlated defects are aligned with the crystal axes and thereby provide a unified description of critical currents in superconductors. For J//B we discuss what the maximum entropy equations imply about the vortex geometry.

Ferrocenediyl systems offer a motif that incorporates multiple functionality and redox-active centers, enabling these units to be used as molecular scaffolds in linear and cyclic compounds. Herein, we discuss a new modular methodology for the synthesis and incorporation of ferrocenediyl motifs within extended conjugated systems. We have synthesized a family of compounds featuring ferrocenediyl-ethynyl units with various para-substituted aromatic linkages. Extended linear, open-chain species have been isolated and understanding towards the analogous cyclic compounds gained. The new compounds have been probed using NMR, mass spectrometry, cyclic voltammetry and X-ray crystallography to gain further understanding of their structural and electronic properties.

New unsymmetrical hydroxyferrocenes were synthesised from dibromoferrocene. The oxygen heteroatom was introduced vialithiation and quenching with bis-trimethylsilylperoxide followed by hydrolysis to unmask the hydroxyl functionality. The coordination chemistry of 1′-(diphenylphosphino)-1-hydroxyferrocene 2was explored with palladium and rhodium precursors. A dinuclear palladium methyl complex with bridging ferrocenyloxo groups was obtained from the reaction between 2and (cyclooctadiene)methylchloropalladium(ii). With tetracarbonyldichlorodirhodium(i), two complexes were isolated. The major product was a bis ligand cisphosphine ligated complex with one ligand bound in a chelating mode and one with a pendant hydroxyl group. A minor product was crystallographically characterised as a dinuclear ferrocenyloxo-bridged rhodium carbonyl complex. The coordination chemistry of 2and the corresponding phosphine oxide 3was examined with group 4 metals and the resulting complexes examined as ethylene polymerisation catalysts. The ligands were found to bind in either a chelating fashion or with pendant phosphine donors. In all cases, low to moderately active ethylene polymerisation catalysts were found. The catalysts were very unstable and catalyst residues were observed in the isolated polymer indicating a short catalyst lifetime. [ABSTRACT FROM AUTHOR]

Molecular or personalised medicine is the future of patient management and healthcare, and molecular imaging plays a key role towards this goal. However, amongst molecular imaging techniques, no single modality is perfect and sufficient to gain all the necessary information. For instance, optical fluorescence imaging is difficult to quantify—especially in tissue more than a few millimetres in depth within a subject; magnetic resonance imaging (MRI) has superb resolution but low sensitivity and positron emission tomography (PET) has very high sensitivity but poor resolution. The combination of multiple molecular imaging techniques can therefore offer synergistic advantages over any modality alone. However, the problem cannot be solved by simply adding two different classes of imaging probes together, unless they happen to have identical pharmacodynamic properties. Therefore, multi-modal contrast agents or imaging probes have been developed to solve this problem. Despite the great wealth of information that such probes can provide, their development is far from trivial and represents an important challenge to synthetic chemists. In this feature article, we provide an overview of recent findings in the synthesis, evaluation and application of dual-modality molecular imaging probes. [ABSTRACT FROM AUTHOR]

The deprotection of phosphonium chloride salts [PR2(CH2OH)2]+Cl− and subsequent condensation reaction with N-methyl-2-aminopyridine has been carried out to give a series of ligands of the form PR2CH2N(CH3)C5H4N (R = Ph 6, Cy 7, t-Bu 8) which have been fully characterised either as the pure ligand (6) or the air stable borane adducts (R = Cy 7a, t-Bu 8a). The 1 : 1 reactions of 6, 7 and 8 with PdCl2(COD) gave the N,P chelate complexes [Pd{PR2CH2N(CH3)C5H4N}Cl2]; the Cy (10) and t-Bu (11) complexes were characterised by X-ray crystallography. The bisligated species [Pd{PCy2CH2N(CH3)C5H4N}2Cl2] (12) was obtained when the reaction was carried out at higher temperatures and the ligands were found to be coordinated to the metal in a trans configuration through the phosphorus donors. Abstraction of the chlorides from the bis-ligated species 12, using silver salts, resulted in the coordination of the pyridine ring forming the bis-chelate complex [Pd{PCy2CH2N(CH3)C5H4N}2]2+13. In comparison, the palladium bis-chelate complex of ligand 5 [Pd{PPh2CH2N(CH3)C5H4N}2]2+ (14) was shown to form in a cis configuration and was fully characterised by X-ray crystallography. [ABSTRACT FROM AUTHOR]

Complexes of the ligand 2,3-dioxo-1,4,8,11-tetraaza-cyclotetradecane (exoO2-cyclam) have been prepared of formula [M1{M2(exoO2-cyclam)}2][BPh4]2 where M1M2 = CoCo (3), ZnZn (4), MnCu (5), FeCu (6), CoCu (7), NiCu (8), ZnCu (9), and [(bipy)2Ru{Cu(exoO2-cyclam)}][NO3]2 (10). Complex 10 crystallised in the space group C2/c and shows Jahn–Teller distorted Cu(ii) with axial nitrate ligands. The {Cu(exoO2-cyclam)} moiety chelates to the Ru with Ru–O distances of 2.082(5) Å. Complexes 5–10 show a Cu(ii)/Cu(iii) redox process and additional metal-centred (6, 8, 10) processes and ligand-centred (10) processes. The electrochemical and UV-Vis spectroelectrochemical study of 10 suggested two closely-spaced oxidations based on the Cu and Ru centres which suggests that substituted derivatives of 10 will be of interest for enhanced charge separation in dye-sensitised solar cells. Magnetic susceptibility measurements revealed dominant antiferromagnetic coupling within the trinuclear species 3, 5–8. Complex 10 showed Curie–Weiss behaviour with weak intermolecular interactions. [ABSTRACT FROM AUTHOR]

Three bidentate, mixed-donor ligands based on a triphenylphosphine unit bearing a pyrazole group in the ortho-position of one phenyl ring have been synthesised; the N,P ligand [2-(3-pyrazolyl)phenyl]diphenylphosphine pzphos has been synthesised and transformed into new N,P(O) and N,P(S) derivatives, [2-(3-pyrazolyl)phenyl]diphenylphosphine oxide pzphos(O) and [2-(3-pyrazolyl)phenyl]diphenylphosphine sulfide pzphos(S), respectively. The coordination chemistry of pzphos and pzphos(O) towards palladium(ii) has been investigated. Depending on the ligand to metal molar ratio employed in the reactions of palladium(ii) with pzphos , either the 1 : 1 chelate [Pd(pzphos)Cl2] 1a or the 2 : 1 N,P chelate [Pd(pzphos)2]Cl21b was obtained. 1b contains two six-membered chelate rings in which the chlorides have been displaced from the inner coordination sphere of palladium. Exchange of the chloride anions in 1b for perchlorate anions was achieved using AgClO4 to give [Pd(pzphos)2][ClO4]21c. Reaction of pzphos(O) under the same conditions forms the 2 : 1 adduct [Pd(pzphos(O))2Cl2] 2b regardless of the metal to ligand ratio or the order of addition of reactants. Unlike the N,P chelate 1b, the N,P(O) ligands in complex 2b bind in a monodentate fashion through the N-donor atoms of the pyrazole rings. Abstraction of the chloro ligands in compound 2b using AgClO4 gave the 2 : 1 N,P(O) chelate [Pd{pzphos(O)}2][ClO4]22c, in which entropically unfavourable 7-membered chelate rings are formed. X-Ray diffraction has been used to confirm the solid-state structures of the pzphos(O) ligand and the complexes 1b, 1c, 2b and 2c. [ABSTRACT FROM AUTHOR]

A comparative DNA scission activity study of azaferrocene, N-methyl-azaferrocene iodide and 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene (featuring iron in a oxidation state), along with ferrocene (iron ) and ferrocenium (iron ) cation is described. Experiments indicate a high cleavage activity of azaferrocene and its N-methyl derivative in DMSO. DNA cleavage activity can be slowed down by addition of a free radical scavenger (thiourea) or triggered by addition of a reductive agent (dithiothreitol, DTT). The X-ray crystal structure of the N-methyl-2,5-dimethylazaferrocene cation (iron ) with hexafluorophosphate as counter anion is also reported. [ABSTRACT FROM AUTHOR]

A new potentially hexadentate P2N4ligand has been prepared and its coordination chemistry to Pd(II) and Pt(II) investigated. The ligand bonds in a chelating fashion viathe diphosphine backbone to PdCl2and PtCl2while the appended pyridyl groups remain non-bonding. Abstraction of the chloride ions from the platinum complex results in fluxional exchange of the pyridyl groups in solution at room temperature on the NMR timescale. X-ray crystallographic analysis of this platinum complex revealed a tetracoordinate complex with two bound and two free pyridyl arms. [ABSTRACT FROM AUTHOR]

A new tris(pyrazolyl)borate ligand bearing phosphine donor groups appended to the 3-position of the pyrazolyl rings is reported, and the hemilabile behaviour of this tris-N,P ligand in coordination with K+, Tl+ and Cu+ ions is investigated. [ABSTRACT FROM AUTHOR]

Both AC loss and wire cost in coil windings are critical factors for high temperature superconductor (HTS) AC machinery applications. We present AC loss measurement results in three HTS coil assemblies at 77 K and 65 K which have a hybrid coil structure comprising one central winding (CW) and two end windings (EWs) wound with ReBCO and BSCCO wires with different self-field Ic values at 77 K. All AC loss results in the coil assemblies are hysteretic and the normalized AC losses in the coil assemblies at different temperatures can be scaled with the Ic value of the coil assemblies. The normalised results show that AC loss in a coil assembly with BSCCO CW can be reduced by using EWs wound with high Ic ReBCO wires, whilst further AC loss reduction can be achieved by replacing the BSCCO CW with ReBCO CW. The results imply that a flexible hybrid coil structure is possible which considers both AC loss and wire cost in coil assemblies. [ABSTRACT FROM AUTHOR]

HTS flux pumps enable superconducting currents to be directly injected into a magnet coil without the requirement for thermally inefficient current leads. Here, we present results from an experimental mechanically rotating HTS flux pump employing a coated-conductor stator and operated at 77 K. We show the effect of varying the size of the flux gap between the rotor magnets and coated conductor stator from 1 to 7.5 mm. This leads to a corresponding change in the peak applied perpendicular magnetic field at the stator from approximately 350 to 50 mT. We observe that our experimental device ceases to maintain a measurable output at flux gaps above 7.5 mm, which we attribute to the presence of screening currents in the stator wire. We show that our mechanically rotating flux pump is well described by a simple circuit model which enables the output performance to be described using two simple parameters, the open-circuit voltage Voc and the internal resistance, Rd. Both of these parameters are found to be directly proportional to magnet-crossing frequency and decrease with increasing flux gap. We show that the trend in Rd can be understood by considering the dynamic resistance experienced at the stator due to the oscillating amplitude of the applied rotor field. We adopt a literature model for the dynamic resistance within our coated-conductor stator and show that this gives good agreement with the experimentally measured internal resistance of our flux pump. [ABSTRACT FROM AUTHOR]

Dealing with excess death in the context of the COVID-19 pandemic has thrown the question of a ‘good or bad death’ into sharp relief as countries across the globe have grappled with multiple peaks of cases and mortality; and communities mourn those lost. In the UK, these challenges have included the fact that mortality has adversely affected minority communities. Corpse disposal and social distancing guidelines do not allow a process of mourning in which families and communities can be involved in the dying process. This study aimed to examine the main concerns of faith and non-faith communities across the UK in relation to death in the context of the COVID-19 pandemic. The research team used rapid ethnographic methods to examine the adaptations to the dying process prior to hospital admission, during admission, during the disposal and release of the body, during funerals and mourning. The study revealed that communities were experiencing collective loss, were making necessary adaptations to rituals that surrounded death, dying and mourning and would benefit from clear and compassionate communication and consultation with authorities.