Spartacus - Männermuskeln, Heldenbilder oder: die Befreiung der Moral

"Spartacus", das ist der Mann mit dem entschlossenen Blick aus stahlblauen Augen, ein Gesicht mit klassisch-gerader Nase und darunter ein eckiges Kinn mit unübersehbarem Grübchen, ein Körper mit muskolösen nackten Armen und Schenkeln - "Spartacus" ist für viele der Filmschauspieler Kirk Douglas in einer seiner bekanntesten Rollen, in Spartacus von Stanley Kubrick (USA, 1960)

Near-equilibrium measurement of quantum size effects using Kelvin probe force microscopy

In nano-structures such as thin films electron confinement results in the quantization of energy levels in the direction perpendicular to the film. The discretization of the energy levels leads to the oscillatory dependence of many properties on the film thickness due to quantum size effects. Pb on Si(111) is a specially interesting system because a particular relationship between the Pb atomic layer thickness and its Fermi wavelength leads to a periodicity of the oscillation of two atomic layers. Here, we demonstrate how the combination of scanning force microscopy (SFM) and Kelvin probe force microscopy (KPFM) provides a reliable method to monitor the quantum oscillations in the work function of Pb ultra-thin film nano-structures on Si(111). Unlike other techniques, with SFM/KPFM we directly address single Pb islands, determine their height while suppressing the influence of electrostatic forces, and, in addition, simultaneously evaluate their local work function by measurements close to equilibrium, without current-dependent and non-equilibrium effects. Our results evidence even-odd oscillations in the work function as a function of the film thickness that decay linearly with the film thickness, proving that this method provides direct and precise information on the quantum states.Comment: This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Nanoscale, copyright Royal Society of Chemistry after peer review. To access the final edited and published work see doi belo

Dynamic process control of twin-column periodic countercurrent chromatography processes

Twin-column periodic countercurrent chromatography has become a promising solution for continuous downstream processes as chromatography equipment for both process development and GMP manufacturing has become available. Twin-column periodic countercurrent processes have been utilized successfully in many applications including purification of biologics, such as monoclonal antibodies (mAbs), bispecific antibodies and fusion proteins, the purification of peptides and also small molecules such as antibiotics and fatty acid ethyl esters. This presentation deals with the online UV-based control of two twin-column periodic countercurrent processes, 2C-PCC and MCSGP, covering applications in chromatographic capture and polishing. 2C-PCC is a capture process significantly improving the process performance (productivity, resin utilization, buffer consumption, product concentration) of affinity capture, e.g. the capture of mAbs, in comparison to traditional single column chromatography. MCSGP is a polishing process to solve difficult ternary separation challenges, allowing purification with high product yield and purity in situations where traditional single column chromatography faces a yield-purity trade-off. For robust operation in view of commercial manufacturing using these two cyclic processes, UV-based dynamic control strategies have been developed and tested. In this presentation a UV-based control strategy for 2C-PCC based on online-determination of breakthrough curve signals is introduced and case studies for its application in protein A chromatography are shown. The control strategy accounts for changes in resin capacity and, in case of continuous upstream, for changes in titer occurring over time, and adjusts the operating parameters such that capacity utilization and yield are kept constant. A second control strategy for MCSGP based on the online evaluation of the elution peak signal is presented based on a case study. The method accounts for shifts of the product peak e.g. due to changes in temperature and buffer preparation (e.g. during buffer refill). An application of the control strategy in protein purification is presented. The presented methods represent important tools for robust manufacturing using twin column processe

Increased prevalence of colorectal adenomas in women with breast cancer

Background: The frequency of colorectal adenomas and carcinomas was investigated in a large cohort of women with breast cancer in comparison with matched controls, since data on the occurrence of second tumors in women with breast cancer is controversial. Design: In a cohort study, 188 consecutive women (median age 57 years) with primary breast cancer and 376 age-matched women who served as controls were examined by total colonoscopy. Breast cancer patients and controls were compared for the frequency of colorectal adenomas and carcinomas. Results: Women with breast cancer showed a higher risk of colorectal adenomas than controls (14.9 vs. 9.3%, p = 0.047, OR 1.7, 95% Cl 1.0-2.9). This increased prevalence resulted primarily from an increased prevalence in the age group 65-85 (31 vs. 10%, p = 0.004, OR 3.8, 95% Cl 1.6-9.3). Colorectal carcinomas were found infrequently in both groups (2 in each group). Women with breast cancer receiving anti-estrogen therapy showed a trend towards a lower risk of adenomas compared to women without anti-estrogen therapy (3.7 vs. 17.2%, p = 0.053, OR 0.16, 95% Cl 0.0-1.1). Conclusions: Women with breast cancer above the age of 65 years have an increased risk of colorectal adenomas compared to women without breast cancer. Women with a diagnosis of breast cancer should especially be encouraged to participate in colorectal cancer-screening programs which, in most countries, call for screening of all average-risk individuals over the age of 50 years

Aggregation Stability of a Monoclonal Antibody During Downstream Processing

ABSTRACT: Purpose: To study the effect of several operative parameters, particularly pH and salt concentration, on the stability and aggregation kinetics of IgG solutions under the conditions typically encountered in downstream processing. Methods: The time evolution of the aggregates is analyzed by a combination of dynamic light scattering, size exclusion chromatography (SEC) and field flow fractionation (FFF). Secondary structure changes are monitored by circular dichroism. Results: For the given antibody, it is found that at pH lower than 4.0 addition of salt induces a reversible aggregation to oligomers accompanied by an increase in the content of the β-sheet structure. The aggregation rate increases monotonically with the salt concentration. Both the SEC and FFF techniques are successfully applied to obtain the oligomer distributions, and their results are consistent. The modified Lumry-Eyring kinetic model can well describe the time evolutions of the oligomers. Conclusions: For the given antibody, low pH and presence of salt induce conformational changes that are responsible for the reversible aggregation, but in the investigated conditions only small soluble oligomers are formed and oligomer sizes larger than trimer are negligible. For this reason, no accompanied macroscopic changes can be observe

Dynamic process control of continuous twin-column chromatography

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Design of a twin-column countercurrent purification (MCSGP) unit for the polishing of an oligonucleotide sequence

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Hereditary angioedema (HAE) in children and adolescents : a consensus on therapeutic strategies

Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis