Superconducting magnet protection must address two main areas of the magnet and circuit performance, namely conductor hot-spot temperatures and circuit voltages. The maximum hot-spot temperatures and ...voltages occur during the superconductor's transition called a quench and the subsequent energy extraction. As has been previously demonstrated, by using a varistor more energy can be extracted from the coil for the same maximum voltage, or the peak voltage can be reduced compared to a resistor for comparable extraction times. The principles of operation and theory behind the varistor are covered and three case studies are presented. Case 1 presents experimental data on energy extraction with varistors for the CERN Hi-Lumi MCBRD magnets under test at IMPCAS. Case 2 presents experimental data on the FECR sextupole magnet, also under test at IMPCAS. Case 3 covers simulated data for the CERN Hi-Lumi MBXF magnets, under test at KEK.
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Bacterial biofilms are a huge burden on our healthcare systems worldwide. The lack of specificity in diagnostic and treatment possibilities result in difficult-to-treat and persistent ...infections. The aim of this in vitro study was to investigate if microbubbles targeted specifically to bacteria in biofilms could be used both for diagnosis as well for sonobactericide treatment and demonstrate their theranostic potential for biofilm infection management. The antibiotic vancomycin was chemically coupled to the lipid shell of microbubbles and validated using mass spectrometry and high-axial resolution 4Pi confocal microscopy. Theranostic proof-of-principle was investigated by demonstrating the specific binding of vancomycin-decorated microbubbles (vMB) to statically and flow grown Staphylococcus aureus (S. aureus) biofilms under increasing shear stress flow conditions (0–12 dyn/cm2), as well as confirmation of microbubble oscillation and biofilm disruption upon ultrasound exposure (2 MHz, 250 kPa, and 5,000 or 10,000 cycles) during flow shear stress of 5 dyn/cm2 using time-lapse confocal microscopy combined with the Brandaris 128 ultra-high-speed camera. Vancomycin was successfully incorporated into the microbubble lipid shell. vMB bound significantly more often than control microbubbles to biofilms, also in the presence of free vancomycin (up to 1000 µg/mL) and remained bound under increasing shear stress flow conditions (up to 12 dyn/cm2). Upon ultrasound insonification biofilm area was reduced of up to 28%, as confirmed by confocal microscopy. Our results confirm the successful production of vMB and support their potential as a new theranostic tool for S. aureus biofilm infections by allowing for specific bacterial detection and biofilm disruption.
We describe the design and data analysis of the DEEP2 Galaxy Redshift Survey, the densest and largest high-precision redshift survey of galaxies at z approx. 1 completed to date. The survey was ...designed to conduct a comprehensive census of massive galaxies, their properties, environments, and large-scale structure down to absolute magnitude MB = −20 at z approx. 1 via approx.90 nights of observation on the Keck telescope. The survey covers an area of 2.8 Sq. deg divided into four separate fields observed to a limiting apparent magnitude of R(sub AB) = 24.1. Objects with z approx. < 0.7 are readily identifiable using BRI photometry and rejected in three of the four DEEP2 fields, allowing galaxies with z > 0.7 to be targeted approx. 2.5 times more efficiently than in a purely magnitude-limited sample. Approximately 60% of eligible targets are chosen for spectroscopy, yielding nearly 53,000 spectra and more than 38,000 reliable redshift measurements. Most of the targets that fail to yield secure redshifts are blue objects that lie beyond z approx. 1.45, where the O ii 3727 Ang. doublet lies in the infrared. The DEIMOS 1200 line mm(exp −1) grating used for the survey delivers high spectral resolution (R approx. 6000), accurate and secure redshifts, and unique internal kinematic information. Extensive ancillary data are available in the DEEP2 fields, particularly in the Extended Groth Strip, which has evolved into one of the richest multiwavelength regions on the sky. This paper is intended as a handbook for users of the DEEP2 Data Release 4, which includes all DEEP2 spectra and redshifts, as well as for the DEEP2 DEIMOS data reduction pipelines. Extensive details are provided on object selection, mask design, biases in target selection and redshift measurements, the spec2d two-dimensional data-reduction pipeline, the spec1d automated redshift pipeline, and the zspec visual redshift verification process, along with examples of instrumental signatures or other artifacts that in some cases remain after data reduction. Redshift errors and catastrophic failure rates are assessed through more than 2000 objects with duplicate observations. Sky subtraction is essentially photon-limited even under bright OH sky lines; we describe the strategies that permitted this, based on high image stability, accurate wavelength solutions, and powerful B-spline modeling methods. We also investigate the impact of targets that appear to be single objects in ground-based targeting imaging but prove to be composite in Hubble Space Telescope data; they constitute several percent of targets at z approx. 1, approaching approx. 5%-10% at z > 1.5. Summary data are given that demonstrate the superiority of DEEP2 over other deep high-precision redshift surveys at z approx. 1 in terms of redshift accuracy, sample number density, and amount of spectral information. We also provide an overview of the scientific highlights of the DEEP2 survey thus far.
Summary
Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate ...stable tolDC by pharmacological modulation of human monocyte‐derived DC. These tolDC exert potent pro‐tolerogenic actions on CD4+ T cells. Lack of interleukin (IL)−12p70 production is a key immunoregulatory attribute of tolDC but does not explain their action fully. Here we show that tolDC express transforming growth factor (TGF)‐β1 at both mRNA and protein levels, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte‐derived DC. By inhibiting TGF‐β1 signalling we demonstrate that tolDC regulate CD4+ T cell responses in a manner that is at least partly dependent upon this cytokine. Crucially, we also show that while there is no significant difference in expression of TGF‐βRII on CD4+ T cells from RA patients and healthy controls, RA patient CD4+ T cells are measurably less responsive to TGF‐β1 than healthy control CD4+ T cells reduced TGF‐β‐induced mothers against decapentaplegic homologue (Smad)2/3 phosphorylation, forkhead box protein 3 (FoxP3) expression and suppression of (IFN)‐γ secretion. However, CD4+ T cells from RA patients can, nonetheless, be regulated efficiently by tolDC in a TGF‐β1‐dependent manner. This work is important for the design and development of future studies investigating the potential use of tolDC as a novel immunotherapy for the treatment of RA.
We report that tolerogenic dendritic cells generated with dexamethasone and vitamin D3 express the immunoregulatory cytokine TGF‐β1. Despite CD4+ T‐cells from rheumatoid arthritis patients being measurably less responsive to TGF‐β1 they can nonetheless be efficiently regulated by tolDC in a TGF‐β1‐dependent manner.
Future high-energy accelerators will need very high magnetic fields in the range of 20 T. The Enhanced European Coordination for Accelerator Research and Development (EuCARD-2) Work Package 10 is a ...collaborative push to take high-temperature superconductor (HTS) materials into an accelerator-quality demonstrator magnet. The demonstrator will produce 5 T stand alone and between 17 and 20 T when inserted into the 100-mm aperture of a Fresca-2 high-field outsert magnet. The HTS magnet will demonstrate the field strength and the field quality that can be achieved. An effective quench detection and protection system will have to be developed to operate with the HTS superconducting materials. This paper presents a ReBCO magnet design using a multistrand Roebel cable that develops a stand-alone field of 5 T in a 40-mm clear aperture and discusses the challenges associated with a good field quality using this type of material. A selection of magnet designs is presented as the result of the first phase of development.
We present an analysis of MicroBooNE data with a signature of one muon, no pions, and at least one proton above a momentum threshold of 300 MeV/c(CC0πNp). This is the first differential cross-section ...measurement of this topology in neutrino-argon interactions. We achieve a significantly lower proton momentum threshold than previous carbon and scintillator-based experiments. Using data collected from a total of approximately 1.6 × 1020 protons on target, we measure the muon neutrino cross section for the CC0πNp interaction channel in argon at MicroBooNE in the Booster Neutrino Beam which has a mean energy of around 800 MeV. We present the results from a data sample with estimated efficiency of 29% and purity of 76% as differential cross sections in five reconstructed variables: the muon momentum and polar angle, the leading proton momentum and polar angle, and the muon-proton opening angle. We include smearing matrices that can be used to "forward fold" theoretical predictions for comparison with these data. We compare the measured differential cross sections to a number of recent theory predictions demonstrating largely good agreement with this first-ever dataset on argon.
Responsive hybrid nanomaterials with well-defined properties are of significant interest for the development of biosensors with additional applications in tissue engineering and drug delivery. Here, ...we present a detailed characterization using UV–vis spectroscopy and small angle X-ray scattering of a hybrid material comprised of polypeptide-decorated gold nanoparticles with highly controllable assembly properties. The assembly is triggered by a folding-dependent bridging of the particles mediated by the heteroassociation of immobilized helix–loop–helix polypeptides and a complementary nonlinear polypeptide present in solution. The polypeptides are de novo designed to associate and fold into a heterotrimeric complex comprised of two disulfide-linked four-helix bundles. The particles form structured assemblies with a highly defined interparticle gap (4.8 ± 0.4 nm) that correlates to the size of the folded polypeptides. Transitions in particle aggregation dynamics, mass-fractal dimensions and ordering, as a function of particle size and the concentration of the bridging polypeptide, are observed; these have significant effects on the optical properties of the assemblies. The assembly and ordering of the particles are highly complex processes that are affected by a large number of variables including the number of polypeptides bridging the particles and the particle mobility within the aggregates. A fundamental understanding of these processes is of paramount interest for the development of novel hybrid nanomaterials with tunable structural and optical properties and for the optimization of nanoparticle-based colorimetric biodetection strategies.
Abstract
Aims
To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity.
Methods and results
We followed the European ...Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy.
Conclusion
We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.
Abstract
Various initiatives in Europe have been launched to study superconducting magnets for a rotatable gantry suitable to deliver up to 440 MeV/A carbon ions for hadron therapy. One initiative is ...led by INFN inside an agreement with CERN, CNAO, and MedAustron aiming at designing and manufacturing a strongly curved cos θ dipole rated for 4 T central field and with a ramp rate of 0.15-0.4 T/s. Here we explore the suitability of dipole technology derived from HEP collider for a rotatable gantry that poses severe conditions on the thermal design (indirectly cooled coils). A second one is in the frame of the European program H2020-HITRIplus-WP8, aimed at exploring the feasibility of using the novel Canted Cosine Theta (CCT) concept to produce a superconducting dipole with similar characteristics. The scope is to design and built one or two prototypes with Nb-Ti rope, to see if this route could be a viable alternative. Finally in the European collaboration H2020-I. FAST-WP8 we are exploring both CCT in combined function design (dipole + quadrupole, in Nb-Ti) and the use of HTS (REBCO tapes) with CCT dipole layout, pursuing the design manufacture of small prototypes with European Industry. If HTS will be found successful, it will be a great benefit for the cryogenic design of the magnet system.
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