LEICA: a low energy ion composition analyzer for the study of solarand magnetospheric heavy ions

The SAMPEX (Solar, Anomalous, and Magnetospheric Particle Explorer) LEICA instrument is designed to measure ~0.5-5-MeV/nucleon solar and magnetospheric ions over the range from He-Ni. The instrument is a time-of-flight (TOF) mass spectrometer, which measures particle TOF over an ~0.5-m path and the residual energy deposited in an array of Si solid state detectors. Large-area microchannel plates are used, resulting in a large geometrical factor for the instrument (0.6 cm² sr), which is essential for accurate compositional measurements in small solar flares and in studies of precipitating magnetospheric heavy ions     

Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE

Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, and with clinical and serologic disease parameters of SLE. Compared to healthy controls (HC), CD38 expression levels in SLE were significantly increased on circulating plasmacytoid dendritic cells, CD14⁺⁺CD16⁺ monocytes, CD56⁺ CD16^dim natural killer cells, marginal zone-like IgD⁺CD27⁺ B cells, and on CD4⁺ and CD8⁺ memory T cells. Correlation analyses revealed coordinated CD38 expression between individual innate and memory T cell subsets in SLE but not HC. However, CD38 expression levels were heterogeneous across patients, and no correlation was found between CD38 expression on immune cell subsets and the disease activity index SLEDAI-2K or established serologic and immunological markers of disease activity. In conclusion, we identified widespread changes in CD38 expression on SLE immune cells that highly correlated over different leukocyte subsets within individual patients, but was heterogenous within the population of SLE patients, regardless of disease severity or clinical manifestations. As anti-CD38 treatment is being investigated in SLE, our results may have important implications for the personalized targeting of pathogenic leukocytes by anti-CD38 monoclonal antibodies.     

Torrefied agro-industrial residue as filler in natural rubber compounds

This study explored the feasibility of using torrefied biomass as a reinforcing filler in natural rubber compounds. Carbon black was then replaced with the torrefied biomass in elastomer formulations for concentrations varying from 0% to 100% (60 parts per hundred rubber or phr total). Their influence on the curing process, dynamic properties, and mechanical properties was investigated. Results were compared with the properties of vulcanizates containing solely carbon black fillers. Time to cure (t₉₀) for compounds with torrefied biomass fillers increased, while filler-filler interactions (ΔG') decreased, compared to carbon black controls. At low strains, the tan δ values of the torrefied fillers vulcanizates were similar to the controls. Incorporation of torrefied biomass into natural rubber decreased compound tensile strength and modulus but increased elongation. Replacement with torrefied fillers resulted in a weaker filler network in the matrix. Still, results showed that moderate substitution concentrations (~20 phr) could be feasible for some natural rubber applications.     

A study on using hierarchical basis error estimates in anisotropic mesh adaptation for the finite element method

A common approach for generating an anisotropic mesh is the M-uniform mesh approach where an adaptive mesh is generated as a uniform one in the metric specified by a given tensor M. A key component is the determination of an appropriate metric, which is often based on some type of Hessian recovery. Recently, the use of a global hierarchical basis error estimator was proposed for the development of an anisotropic metric tensor for the adaptive finite element solution. This study discusses the use of this method for a selection of different applications. Numerical results show that the method performs well and is comparable with existing metric tensors based on Hessian recovery. Also, it can provide even better adaptation to the solution if applied to problems with gradient jumps and steep boundary layers. For the Poisson problem in a domain with a corner singularity, the new method provides meshes that are fully comparable to the theoretically optimal meshes.     

Bivalent EGFR-Targeting DARPin-MMAE Conjugates

Epidermal growth factor receptor (EGFR) is a validated tumor marker overexpressed in various cancers such as squamous cell carcinoma (SSC) of the head and neck and gliomas. We constructed protein-drug conjugates based on the anti-EGFR Designed Ankyrin Repeat Protein (DARPin) E01, and compared the bivalent DARPin dimer (DD1) and a DARPin-Fc (DFc) to the monomeric DARPin (DM) and the antibody derived scFv425-Fc (scFvFc) in cell culture and a mouse model. The modular conjugation system, which was successfully applied for the preparation of protein-drug and -dye conjugates, uses bio-orthogonal protein-aldehyde generation by the formylglycine-generating enzyme (FGE). The generated carbonyl moiety is addressed by a bifunctional linker with a pyrazolone for a tandem Knoevenagel reaction and an azide for strain-promoted azide-alkyne cycloaddition (SPAAC). The latter reaction with a PEGylated linker containing a dibenzocyclooctyne (DBCO) for SPAAC and monomethyl auristatin E (MMAE) as the toxin provided the stable conjugates DD1-MMAE (drug-antibody ratio, DAR = 2.0) and DFc-MMAE (DAR = 4.0) with sub-nanomolar cytotoxicity against the human squamous carcinoma derived A431 cells. In vivo imaging of Alexa Fluor 647-dye conjugates in A431-xenografted mice bearing subcutaneous tumors as the SCC model revealed unspecific binding of bivalent DARPins to the ubiquitously expressed EGFR. Tumor-targeting was verified 6 h post-injection solely for DD1 and scFvFc. The total of four administrations of 6.5 mg/kg DD1-MMAE or DFc-MMAE twice weekly did not cause any sequela in mice. MMAE conjugates showed no significant anti-tumor efficacy in vivo, but a trend towards increased necrotic areas (p = 0.2213) was observed for the DD1-MMAE (n = 5).     

Characterization of silicon oxynitride films using ion beam analysis techniques

Heavy-ion elastic recoil detection analysis (HIERDA) is the ideal technique for quantitative analysis of silicon oxynitride films on silicon because of its unique ability to measure simultaneously all elements of interest (i.e., H, C, N, O and Si), thereby permitting key parameters such as the O/N-ratio to be determined in a single measurement. However, high-energy accelerators suitable for such HIERDA measurements are becoming much less readily available. Hence, the present paper investigates and calibrates an alternative IBA technique for simultaneous O, N and C analysis – namely, the use of (d,p) and (d,) nuclear reactions. Under optimum analysis conditions (850 keV deuterons and 150° detector angle), the Si background level sets a lower detection limit of 1×10¹⁶ nitrogen atoms/cm² and 3×10¹⁵ oxygen atoms/cm². H analysis is carried out separately, using low-energy ERDA and a 2 MeV ⁴He beam. Absolute cross-sections have been obtained for each of the (d,p) and (d,) groups. Comparison with data in the recent Handbook of Modern Ion Beam Materials Analysis shows reasonable agreement (10–15%) for the (d,p) reactions on oxygen and carbon. However, in the case of nitrogen, the measured cross-section values are 70% larger than the Handbook data. Several silicon oxynitride samples have been analyzed, first at UWO using 850 keV deuterons, and subsequently at ANU using HIERDA and a 200 MeV Au beam. The resulting O/N-ratios agree to within 10%. The relative importance of radiation damage effects is briefly discussed.     

The Influence of System Pressure on Bubble Coalescence in Nucleate Boiling

Boiling is one of the most effective heat transfer mechanisms. In spite of a long time of research, the physical fundamentals are still not sufficiently understood. Pursuing the objective to predict heat transfer based on physical and geometrical properties, experimental and numerical investigations are conducted at the institute of the authors. The focus of the presented research is the coalescence of two single bubbles under varying pressure conditions. In the experiment a thin stainless-steel foil is used as a Joule heater. The experiments were performed in a pressure range of 300–1000 mbar using FC72 as working fluid. Two types of heaters with a distance between two artificial nucleation sites of 300 μm (type 3) and 500 μm (type 5) were used. The experimental results indicate a strong dependence of the occurrence of bubble coalescence on pressure. For the type 5 heater, a Gaussian distribution for the coalescence frequency when plotted over pressure is observed. Experimental results with the type 3 heater show a similar distribution of the frequency with a shifted maximum. Further, it is shown that during bubble coalescence a small droplet can remain inside the bubble and enhance the heat transfer, which is attributed to an additional thin film region. The formation of this remaining droplet is sensitive to system pressure. Numerical investigations of bubble coalescence were conducted with the computational fluid dynamics (CFD) software OpenFOAM. In OpenFOAM, dynamic mesh handling allows high spatial resolution at the phase boundary, which is captured with the volume-of fluid method. Evaporation and a subgrid microscale model were implemented in the flow solver to account for evaporation at the phase boundary and the three-phase contact line. The results show a strong dependence of bubble dynamics and coalescence on contact angle and bubble growth rate. Although it was possible to observe the creation of the residual droplet, more effort needs to be put into finding appropriate initial conditions.     

Close encounter processes in Monte Carlo simulations of ion channeling

The backscattering yield is analyzed in terms of the depth-dependent distribution of ion trajectories, characterized by instantaneous values of such parameters as the ion energy, the scattering angle, the angle between the ion direction and the surface normal, and the impact parameter with respect to the equilibrium site of the nearest lattice atom. The normalized nuclear encounter probability (NEP) is reformulated as the expected value of the normalized NEP for a single trajectory, and the definition is extended for directions tilted by a large angle with respect to a major axis. It is shown that the normalized NEP cannot be defined to correspond to a physically measurable quantity if the energy and angular spreads of the beam in the crystal are taken into account. The scattering yield measured in the energy spectrum — to be used in comparisons of simulations with experiment — is also expressed as the expected value of the respective yield associated with a single trajectory. Examples of the distribution of trajectories are given for 1.5 MeV ⁴He ions traversing a Si(100) single crystal.