On the current practice of New Business Development in the German chemical industry

The results of a survey on the practice of new business development conducted in 17 chemical industry companies and related business sectors, such as service providers, are presented in this article. The objectives and organizational setup of New Business Development were found to be exceptionally heterogeneous and to cover a broad spectrum. The differentiation between New Business Development and Innovation Management was also not consistent between the companies. All the companies underlined the importance of technical and scientific know-how for new business development staff, but also emphasized the relevance of interdisciplinary competencies at the interface between natural science and business. Small companies follow a rather opportunistic New Business Development approach without dedicated organizational structures. Larger companies, on the other hand, employ a Stage-Gate process and largely derive their ideas from megatrends. Differences between small and larger companies are discussed in the article at hand

Understanding the market dynamics of biosimilars

Biosimilars represent an attractive market opportunity in the pharmaceutical industry. In order to understand the underlying market dynamics and to identify the success factors of the biosimilars market, a PEST (political, economic, social, technological) analysis was conducted based on desk research and expert interviews with market participants and stakeholders. The regulatory environment for biosimilars seems to be well established and both the required manufacturing technology and the necessary analytical capabilities for biosimilar development are available. The potential market is expected to grow due to the overall dynamics in the biologics market and the patent expiration of blockbuster drugs. The perspective of the scientific community towards biosimilars has changed from skeptical to rather positive in the last 10 years, probably reflecting the evolution of regulatory guidelines and technological progress. However, physicians, responsible for the prescription of drugs, are still rather skeptical about biosimilars and need to be better informed in order to increase the currently low market penetration of biosimilars. Taken together, the biosimilars industry is expected to step out of its infancy stage and now enter the growth phase

Etude de complexes protéiques non covalents par spectrométrie de masse FT-ICR.

The outstanding analytical performances of electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR MS) were applied to study non-covalent interactions in protein complexes. In a first part, the application of this technique to the detection of intact protein complexes was developed on the system of Creatine kinase (CK) and its ligands ADP and ATP, leading to the observation of these complexes in the gas phase. Specific and non- specific contributions of these interaction were separated by means of a statictical model, yielding interaction constants (K1,ADP=11.8 ± 1.5 μM, K2,ADP=48 ± 6 μM, K1,ATP=27 ± 7 μM, K2,ATP=114 ± 27 μM) that are in fair agreement with literature values. In a second part, methods to study the surface accessibility of protein complexes by chemical modification in solution, either reversible (H/D exchange) or irreversible (specific modification of His and Lys by DEPC) were developed and implemented. The modification site was identified either by a bottom-up (enzymatic digestion followed by mass measurement of the resulting peptides) or a top-down approach (gas phase fragmentation of the entire protein by electron capture dissociation [ECD]). Within the framework of the current instrumentation, the latter approach yields reasonable results for proteins as large as 17 kDa and should be extendible to 25 kDa. Application of the different analytical strategies yielded insight into the structure and conformational dynamics of prion protein (PrP) oligomers that were obtained by partial thermal denaturation of the monomeric species in vitro. Increase in deuterium incorporation in some regions of the oligomeric species (compared to the monomer) reflects partial unfolding of the protein, as indicated by the unfolding of an α helix.Les qualités analytiques de la spectrométrie de masse à résonance cyclotronique ionique et à transformée de Fourier, combinée à une source d'électronébulisation (ESI-FT-ICR) ont été mises à profit pour l'étude d'interactions non-covalentes dans des assemblages protéiques. Dans une première partie, l'utilisation de cette technique pour la détection de complexes protéiques intacts a été développée sur le système constitué de la créatine kinase (CK) et de ses ligands ADP et ATP, conduisant à l'observation de ces complexes en phase gazeuse. Les parts spécifiques et non spécifiques de ces interactions ont été séparées par un modèle statistique, conduisant à la détermination des constantes de dissociation (K1,ADP=11.8 ± 1,5 μM, K2,ADP=48 ± 6 μM, K1,ATP=27 ± 7 μM, K2,ATP=114 ± 27 μM ) qui sont en accord avec la littérature. Dans une seconde partie, des techniques pour l'étude de l'accessibilité de surface de complexes de protéines par modification chimique en solution, aussi bien réversibles (échanges H/D) qu'irréversibles (modification spécifique d'histidine et de lysine par le DEPC) ont été mises au point et appliquées. Les sites de modification ont été localisés soit par une approche « bottom-up » (digestion enzymatique suivie d'une mesure de masse des peptides résultants) soit par une approche « top-down » (fragmentation en phase gazeuse de la protéine intacte par dissociation par capture d'électrons [ECD]). Dans le cadre de l'instrumentation actuelle, cette dernière approche a conduit à des résultats pour des protéines allant jusqu'à 17 kDa et pourrait être étendue jusqu'à des protéines de 25 kDa. Ces différentes stratégies analytiques ont été appliquées à des oligomères de la protéine du prion (PrP) obtenus par dénaturation thermique partielle in vitro de l'espèce monomérique. L'accroissement de l'incorporation de deutérium dans certaines régions de la forme oligomèrique (par rapport au monomère) reflète un dépliement partiel de la protéine, en particulier au niveau d'une hélice

Comprehensive Virtual Mathematics Training - A Crucial Support to Bridge the Gap for Undergraduate Students

We present an integrated virtual learning based approach to support undergraduate students in developing their mathematical knowledge and skills. The approach consists of three elements. First, a pre-study web-based mathematics training course for pre-assessment and self-study. Secondly, the traditional classroom lecture that is supplemented with specific examples from application fields involving dedicated literature and case examples from other courses (e.g., physical chemistry). Finally, lectures have been recorded using an easy-to-use system to provide the students with after-class self-learning material. The latter proves especially useful for extra-occupational students. The approach has been developed and implemented for chemistry undergraduate courses but can be easily adapted for any kind of engineering study course

A deconvolution method for the separation of specific versus nonspecific interactions in noncovalent protein-ligand complexes analyzed by ESI-FT-ICR mass spectrometry.

A method to separate specific and nonspecific noncovalent interactions observed in ESI mass spectra between a protein and its ligands is presented. Assuming noncooperative binding, the specific ligand binding is modeled as a statistical distribution on identical binding sites. For the nonspecific fraction we assume a statistical distribution on a large number of "nonspecific" interacting sites. The model was successfully applied to the noncovalent interaction between the protein creatine kinase (CK) and its ligands adenosine diphosphate (ADP) and adenosine triphosphate (ATP) that both exhibit nonspecific binding in the mass spectrum. The two sequential dissociation constants obtained by applying our method are K(1,diss) = 11.8 +/- 1.5 microM and K(2,diss) = 48 +/- 6 microM for ADP. For ATP, the constants are K(1,diss) = 27 +/- 7 microM and K(2,diss) = 114 +/- 27 microM. All constants are in good correlation with reported literature values. The model should be valuable for systems with a large dissociation constant that require high ligand concentrations and thus have increased potential of forming nonspecific adducts

Conformational dynamics and oligomerization pathways of prion protein investigated by rational mutagenesis

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Business Chemistry: The successful establishment of an interdisciplinary field

The article presents the development of Business Chemistry at seven German and one Swiss universities. Besides highlighting the course of study in general and it's development, the respective universities present benefits but also specific challenges they had to face when introducing Business Chemistry. Followed by a short introduction of Business Chemistry itself, its development and the status quo, every university presented their individual perspectives on the course of study. Overall, the article should provide our readers with an overview of Business Chemistry and sensitize them for the differences in the study programs, even though the courses of study were developed in ac cordance with all respective universities

Diversity in prion protein oligomerization pathways results from domain expansion as revealed by hydrogen/deuterium exchange and disulfide linkage

The prion protein (PrP) propensity to adopt different structures is a clue to its biological role. PrP oligomers have been previously reported to bear prion infectivity or toxicity and were also found along the pathway of in vitro amyloid formation. In the present report, kinetic and structural analysis of ovine PrP (OvPrP) oligomerization showed that three distinct oligomeric species were formed in parallel, independent kinetic pathways. Only the largest oligomer gave rise to fibrillar structures at high concentration. The refolding of OvPrP into these different oligomers was investigated by analysis of hydrogen/deuterium exchange and introduction of disulfide bonds. These experiments revealed that, before oligomerization, separation of contacts in the globular part (residues 127–234) occurred between the S1–H1–S2 domain (residues 132–167) and the H2–H3 bundle (residues 174–230), implying a conformational change of the S2–H2 loop (residues 168–173). The type of oligomer to be formed depended on the site where the expansion of the OvPrP monomer was initiated. Our data bring a detailed insight into the earlier conformational changes during PrP oligomerization and account for the diversity of oligomeric entities. The kinetic and structural mechanisms proposed here might constitute a physicochemical basis of prion strain genesis