Effective cell culture operations by implementing accurate, non-invasive determination of the critical process parameter pH in Roche`s Drug Substance Network

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The ammonite genus Diaziceras Spath, 1921, from the Campanian of KwaZulu-Natal, South Africa, and Madagascar

The ammonite genus Diaziceras Spath, 1921, and the type species, D. tissotiaeforme are revised and referred to the subfamily Lenticeratinae Hyatt, 1900, of the family Sphenodiscidae Hyatt, 1900. Skoumalia Summesberger, 1979, is interpreted as a junior synonym of Diaziceras. Diaziceras guillantoni Hourcq, 1949, and D. spathi Hourcq, 1949, are regarded as synonyms of D. tissotiaeforme, and all are referred to the Lower Campanian on the basis of records from Madagascar

Additive, Dynamic and Multiplicative Regression

We survey and compare model-based approaches to regression for cross-sectional and longitudinal data which extend the classical parametric linear model for Gaussian responses in several aspects and for a variety of settings. Additive models replace the sum of linear functions of regressors by a sum of smooth functions. In dynamic or state space models, still linear in the regressors, coefficients are allowed to vary smoothly with time according to a Bayesian smoothness prior. We show that this is equivalent to imposing a roughness penalty on time-varying coefficients. Admitting the coefficients to vary with the values of other covariates, one obtains a class of varying-coefficient models (Hastie and Tibshirani, 1993), or in another interpretation, multiplicative models. The roughness penalty approach to non- and semiparametric modelling, together with Bayesian justifications, is used as a unifying and general framework for estimation. The methodological discussion is illustrated by some real data applications

Cretaceous faunas from Zululand and Natal, South Africa. The ammonite genus Codazziceras Etayo-Serna, 1979

A new species of the Coniacian ammonite genus Codazziceras Etayo-Serna, 1979, previously known with certainty only from Colombia, is described from the St Lucia Formation of northern KwaZulu-Natal

Ammonites from offshore deposits near Bogenfels, Namibia

Pyritized ammonite nuclei and fragments were recovered by vibracore sampling from offshore deposits near Bogenfels, Namibia. Although these could only be identified at genus level, the association of Baculites and Scaphites suggest a Coniacian age for these deposits which conforms with the age of the associated foraminifera

Cretaceous faunas from Zululand and Natal, South Africa. A new species of the ammonite genus Salaziceras Breistroffer, 1936, from the Lower Cenomanian Mzinene Formation

A diminutive ammonite collected by E.C.N. Van Hoepen from the Cenomanian part of the Mzinene Formation of the Skoenberg in northern KwaZulu-Natal, is described as Salaziceras simplex sp. nov., and interpreted as one of the last survivors of the genus

A dynamic Bayes Network for visual pedestrian tracking

Many tracking systems rely on independent single frame detections that are handled as observations in a recursive estimation framework. If these observations are imprecise the generated trajectory is prone to be updated towards a wrong position. In contrary to existing methods our novel approach suggests a Dynamic Bayes Network in which the state vector of a recursive Bayes filter, as well as the location of the tracked object in the image are modelled as unknowns. These unknowns are estimated in a probabilistic framework taking into account a dynamic model, prior scene information, and a state-of-the-art pedestrian detector and classifier. The classifier is based on the Random Forests-algorithm and is capable of being trained incrementally so that new training samples can be incorporated at runtime. This allows the classifier to adapt to the changing appearance of a target and to unlearn outdated features. The approach is evaluated on a publicly available dataset captured in a challenging outdoor scenario. Using the adaptive classifier, our system is able to keep track of pedestrians over long distances while at the same time supporting the localisation of the people. The results show that the derived trajectories achieve a geometric accuracy superior to the one achieved by modelling the image positions as observations

Carbon dioxide driven pH reference method for transfer and scaling of fermentation processes

For the last decades, engineering aspects were in the focus for scale up, scale down as well as transfers of fermentation processes. For cell culture processes however, comparability of process parameters like pCO2, lactate concentration, growth rates, base addition and ultimately product concentration and quality attributes between large and small scale was not sufficiently addressed by those parameters alone. On the other hand, parameters exist like pH and dissolved oxygen, that are both equipment and location independent and that are usually maintained by respective control loops. Especially pH has been proven to be of particular significance for process performance, and therefore for scaling purposes as well. The current standard approach to monitor and adjust bioreactor probes however relies on sample based pH offline reading. pH in a sample depends on a variety of parameters like CO2 degassing, temperature, overall respiration of suspended cells and the like, and might differ from the actual bioreactor pH after sampling. Adding to that, offline measurement methods might deliver different results depending on device type, probe age, media properties, daily adjustment procedures, response times, operator effects and so on. Clearly, the sum of those offsets cannot be detected or quantified using the very same sample based pH offline measurement that introduces those offsets in the first place. Direct cross-site comparison of pH values that are desperately needed for efficient process transfer is impossible in required accuracy, relying on sample based pH offline measurement. To decrease the risk of process variability and potential quality issues, increase efficiency of troubleshooting, scaling and process transfers a method that allows detecting otherwise undetectable pH offsets is essential. In this work, we present a carbon dioxide based alternative method that allows challenging the standard approach, and is able to establish comparable pH values globally by decreasing dependency onto sample based pH offline measurement. In cell free culture media, a bioreactor state where carbon dioxide addition equals carbon dioxide removal leads to stable pH and a net carbon dioxide mass transfer between the gas phase and the liquid phase of zero. In this case, carbon dioxide concentration in the gas phase is not any more a function of parameters that influence mass transfer kinetics, and can therefore be considered scale independent. We have shown that pH values that are derived from this chemical relation are superior to standard sample based pH offline reading, and are able to decrease process variability and increase comparability of process performance between runs, scales and sites. Furthermore, troubleshooting efforts as well as process development are a lot more effective, if pH as one key parameter that adds to process variability can be knocked out or at least quantified. Major automation opportunities in scale down model development like fully automated carbon dioxide removal control strategies that massively depend on comparable pH controller behavior were developed. Phase III development of a late stage project delivering bispecific antibodies already was performed exclusively relying on this carbon dioxide based pH reference method. Another project did switch to this method during phase III development to enable more efficient process development. Scale up has been performed successfully up to 400L scale, feasibility studies were performed in 12K scale in three different projects. Results out of this data will be presented, including important considerations for this kind of approac

Effekte von Diabetes mellitus auf den Bandscheibenstatus - Analyse im Rahmen der populationsbasierten KORA-Studie

Ziel: Ziel der Arbeit war die Untersuchung des degenerativen Einflusses von Prädiabetes und Diabetes mellitus auf die thorakalen und lumbalen Bandscheiben in einer deutschen populationsbasierten Kohorte mittels MRT-Bildgebung. Material und Methoden: Aus der KORA FF4 Kohorte wurden 400 Probanden mit zuvor erhobenem Diabetesstatus mittels 3 Tesla Ganzkörper MRT untersucht. Die Erfassung des Bandscheibenstatus erfolgte mit Hilfe des Pfirrmann Scores in T1-gewichteten Dixon-Sequenzen und T2-gewichteten HASTE-Sequenzen. Die gesammelten Werte wurden mit den Gesundheitsdaten der Probanden korreliert. Neben dem Diabetesstatus wurden folgende den Bandscheibenstatus beeinflussende Faktoren untersucht: Alter, Geschlecht, BMI, HbA1c, arterielle Hypertonie, HDL, LDL, Nikotin- und Alkoholkonsum. Ergebnisse: Insgesamt wurden 385 Probanden in die Studie eingeschlossen. Diabetiker wiesen im Vergleich zur Kontrollgruppe und den Prädiabetikern signifikant mehr degenerative Veränderungen im Bereich der Bandscheiben Th7/8 und L3/4 auf (p0,05; Prolaps p>0,05), jedoch ergab sich eine signifikante Korrelation zwischen dem HbA1c und Bandscheibenprolapsen (p=0,044). Fazit: DM hat in dieser Studie einen signifikanten Einfluss auf die Bandscheibendegeneration der Bandscheiben Th7/8 und L3/4. In der Gesamtbetrachtung der Bandscheiben der Brust- und Lendenwirbelsäule konnte dies nicht bestätigt werden. Als unabhängiger Einflussfaktor auf Protrusion, Prolaps und Degenerationen zeigte sich das Alter. Ein erhöhter BMI und arterielle Hypertonie hatten zudem Einfluss auf die Bandscheibendegeneration

Cretaceous faunas from Zululand and Natal, South Africa. Systematic palaeontolgy and stratigraphical potential of the Upper Campanian-Maastrichtian Inoceramidae (Bivalvia)

Thirty three species of Inoceramidae, of which two are new, are described from KwaZulu. They fall into four zonal assemblages that can be correlated with sequences recognized elsewhere: the Cataceramus flexus Zone and the 'Inoceramus' tenuilineatus Zone are referred to the lower Upper Campanian. The Trochoceramus radiosus Zone is referred to the upper Lower Maastrichtian. The 'Inoceramus' ianjonaensis Zone is referred to the lower Upper Maastrichtian, and represents the youngest known assemblage of true inoceramids. There is no evidence for upper Upper Campanian or lower Lower Maastrichtian inoceramids, and this, together with the geological context of the faunas, indicates the presence of a regional unconformity at this level. This is confirmed by the associated ammonite assemblages. The inoceramid faunas include many taxa that have a wide distribution in the northern hemisphere, and provide a basis for correlation with the ammonite and inoceramid zonations recognized in the U.S. Western Interior, and the European ammonite and belemnite succession