Longitudinal Serum Protein Analysis of Women with a High Risk of Developing Breast Cancer Reveals Large Interpatient Versus Small Intrapatient Variations: First Results from the TESTBREAST Study

The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities. To this end, protein cluster patterns were evaluated to form a conceptual basis for further clinical analyses. Using a mass spectrometry-based bottom-up proteomics strategy, the protein abundance of 30 samples was analyzed: five sequential serum samples from six high-risk women; three who developed a breast malignancy (cases) and three who did not (controls). Serum samples were chromatographically fractionated and an in-depth serum proteome was acquired. Cluster analyses were applied to indicate differences between and within protein levels in serum samples of individuals. Statistical analyses were performed using ANOVA to select proteins with a high level of clustering. Cluster analyses on 30 serum samples revealed unique patterns of protein clustering for each patient, indicating a greater interpatient than intrapatient variability in protein levels of the longitudinally acquired samples. Moreover, the most distinctive proteins in the cluster analysis were identified. Strong clustering patterns within longitudinal intrapatient samples have demonstrated the importance of identifying small changes in protein levels for individuals over time. This underlines the significance of longitudinal serum measurements, that patients can serve as their own controls, and the relevance of the current study set-up for early detection. The TESTBREAST study will continue its pursuit toward establishing a protein panel for early breast cancer detection.     

NEW MACHINING CONCEPT FOR MANUFACTURING MICROSTRUCTURES WITH EXCIMER LASERS

Abstract

The manufacturing of microcomponents with excimer lasers, especially for small series and batch production, is an alternative to other established micromanufacturing methods associated with etch-technology. To avoid long nonproductive times, a general and flexible machining concept is presented, which is based on the mask projection of the excimer laser beam. Beginning the process chain with the workpiece design, a developed preprocessor is able to calculate the overall removal volume from computer-aided design (CAD) data and to break down into elementary volumes that are able to be processed with single laser pulses. Moreover, based on the restrictions of the excimer laser process, a set of NC data is generated to automatically start the production process. The reliability of the system is proven with different geometries such as micro-gear wheels and microlenses.     

Energy-angle distribution measurements for 0.8v020Ne and 209Bi ions penetrating thin carbon foils

Energy-angle distributions have been measured for 0.8v₀, (v₀ = Bohr velocity) Ne and Bi ions penetrating through carbon foils. Comparing the results with a Monte Carlo computer simulation that included an angle dependence only for the elastic collisions, we have observed for Ne projectiles an angle-dependent inelastic loss which, for small angles, is much larger than the elastic contribution in the case of thin foils. In the case of Bi, the energy loss distribution is dominated by elastic collisions. The calculations of Meyer, Klein and Wedell, and Ellmer and Wedell cannot describe the experimental results. The multiple scattering distributions are in agreement with both analytical and Monte Carlo calculations.     

Der fremdgeführte Wechselrichter in Gegentaktschaltung

Ohne Zusammenfassung     

Improved survival and amelioration of nephrotoxic nephritis in intercellular adhesion molecule-1 knockout mice

Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in nephrotoxic nephritis, a model of human rapidly progressive glomerulonephritis. To evaluate the pathogenetic relevance of ICAM-1 in this model, nephrotoxic nephritis was induced in ICAM-1 knockout mice and genetic controls. Mice were preimmunized with rabbit IgG in complete Freund's adjuvant. Seven days later they received rabbit anti-mouse glomerular basement membrane IgG. The early humoral immune responses (levels of circulating mouse anti-rabbit IgG, glomerular deposition of rabbit and mouse IgG and mouse C3c) were not altered in ICAM-1 knockout mice. During 28 d of follow-up, 3 of 19 control nephritic mice and 0 of 16 ICAM-1 knockout mice died. Proteinuria was high in nephritic control mice (means 10 to 12 mg/24 h at all time points investigated) and significantly reduced in nephritic ICAM-1 knockout mice (means <4.4 mg). Mean serum creatinine rose from 29 micromol/L at day -7 to 48 micromol/L (day 28) in nephritic control mice. This increase in serum creatinine was significantly lower in ICAM-1 knockout mice: 27 (day -7) and 36 micromol/L (day 28). Histologic analysis at day 28 revealed that ICAM-1 deficiency in nephrotoxic nephritis mice led to significantly reduced glomerular crescent formation (2+/-3% in ICAM-1 knockout mice versus 13+/-8% in nephritic controls) and tubulointerstitial injury (score 0.4+/-0.4 versus 2.0+/-1.1). By immunohistochemistry, ICAM-1 deficiency in nephritic mice led to significantly reduced (peri-)glomerular and/or interstitial macrophage influx, alpha-smooth muscle actin expression, and type IV collagen accumulation. These data indicate that ICAM-1 is a central mediator of glomerular and tubulointerstitial injury in murine nephrotoxic nephritis.     

Risk of Climate‐Induced Damage in Historic Textiles

Eleven wool and silk historic textiles and two modern artist's canvases were examined to determine their water vapour adsorption, moisture dimensional response and tensile behaviour. All the textiles showed a similar general pattern of moisture response. A rise in ambient relative humidity (RH) from dry conditions produced expansion of a textile until a certain critical RH level after which a contraction occurred to a greater or lesser degree depending on the yarn crimp and the weave geometry. The largest expansion recorded between the dry state and 80% RH was 1.2 and 0.9% for wool and silk textiles, respectively. The largest shrinkage of 0.8% at high RH range was experienced by a modern linen canvas. Two potential damage mechanisms related to the moisture response of the textiles—stress building as a result of shrinkage of the textile restrained in its dimensional response and the fretting fatigue when yarns move with friction one against another—were found insignificant in typical textile display environments unless the textiles are severely degraded or excessively strained in their mounting.     

Experiments on the Dynamic Behavior of the Chemical Looping Combustion Process

The dynamic operation of thermal power plants becomes more and more important due to more diverse and volatile power sources. Load changes of biomass, bituminous coal and methane were conducted during six experimental runs in a chemical looping combustion pilot plant which combines power generation and CO₂ capture. The resulting step responses of the hydrodynamics and gas concentrations were compared to each other to understand the transient behavior of the interconnected fluidized bed system. The influence of the fuel rate and solid circulation on the response time and intensity was assessed.     

Drying of Iron Chloride Solutions: Laser Heating of Levitated Single Particles

Iron chloride solutions are a waste product from the steel industry, which has to be recovered by the so‐called spray roasting process. As this process is a complex sequence of different steps, the drying process of the droplets was separated to get deeper insight into the particle formation process from aqueous iron chloride solutions. Experiments were carried out on single droplets in an acoustic levitator. A CO₂ laser was used as heat source for the drying process. Particles with different shapes were generated by various concentrations of FeCl₂ and laser power. The characteristic time scales and particle size evolution are compared with literature data.     

Heat on – Calibration of IR Spectroscopy at Process Conditions for Continuous Esterification

This work tries to close the gap between continuous synthesis, measurement, calibration, and analysis on R&D scale. By introducing new calibration methods, the full potential of inline ATR-FTIR spectroscopy in continuous reactor setups is unraveled. A fast, fully automated calibration of the reaction mixtures is carried out at process conditions. The use of different compositions underlines the robustness of this calibration method, which was used for the determination of kinetic parameters. The conversion-based calibration significantly increased the precision of the analysis. In difference, the new method only requires the preparation of two calibration mixtures. By that, this method can also be applied to large-scale processes and allows the use of a single measurement setup from R&D to industrial scale.     

Additive manufacturing of PA12 carbon nanotube composites with a novel laser polymer deposition process

The facile manufacture of PA12 MWCNT/silica (50/50 by weight) nanocomposite powders through a high energy mixing process is presented, which are useful to generate 3D objects by a novel Laser Polymer Deposition (LPD) process. The mixing as well as the LPD process led to no discernible changes in the material properties (DSC, SEM, LD) of the core-shell nanocomposites, enabling the recycling of unconverted powder. The built parts yield ultimate tensile stresses and Young's modulus at 10%–20% of the bulk material. Partially unmolten particles and voids were identified as the main mechanical failure mechanism in the built parts. The mechanical properties are better with low additive content (Young's modulus: 89.8 ± 5.4 MPa; UTS: 12.9 ± 5.3 MPa with 0.25 wt% additives). Electronic conductivity up to the region of moderate conductivity could be achieved by multiwalled carbon nanotube (MWCNT) network formation (8 × 10⁻⁴ S cm⁻¹ at 1.25 wt% of additives). A variant of the processing strategy revealed that a higher mechanical strength can be achieved by a laser induced remelting of the traces following their initial construction.