Scale-up and scale-down topics facing the industry

Scale-up and scale-down is bringing several challenges along. We present some recent examples where these challenges occur and how extensive hardware characterization by for example computational fluid dynamics has leads to get a better understanding of the processes themselves. The increasing implementation of small scale bioreactor systems like ambr15 and ambr250 as well as the usage of new single use bioreactors (\u3e2-L) in parallel to established glass vessels has led to additional challenges in scale-up and scale-down. The mini-bioreactor systems, originally used for screening approaches, are going to be implemented as small scale testing systems but could also be part of validated scale down models. This means more systems and scales than before have to fit together with respect to process performance and product quality output. To be prepared for this challenge in-depth characterization and comparison of the hardware is needed. We executed an extensive study with several projects to characterize the new small scale systems and to verify their scalability to larger scale and production facility. First the hardware was extensively characterized by computational fluid dynamics. Additionally, we performed for several projects cell culture runs with the different systems in parallel to show scalability and assess the suitability of the systems for actual scale-down model. Apart from the actual cultivation hardware, coming along with the new high performing media generations -chemically defined and well balanced - is the question of media scalability. We are assessing different online probes to characterize media preparation and to define scale-up factors for media preparation scale-up. The evaluation of these probes will be presented. However, not only online signals but also the availability of suitable small scale media preparation models is a topic to be considered. The success of scale-up and scale-down of future processes as well as the process characterization in suitable scale-down models is one of the main challenge biopharmaceutical industry is facing. We hope to show in our case studies how knowledge-driven approaches and extensive characterization may support to be well prepared for these topics

Herschel-PACS photometry of faint stars

Our aims are to determine flux densities and their photometric accuracy for a set of seventeen stars that range in flux from intermediately bright (<2.5 Jy) to faint (>5 mJy) in the far-infrared (FIR). We also aim to derive signal-to-noise dependence with flux and time, and compare the results with predictions from the Herschel exposure-time calculation tool. The PACS faint star sample has allowed a comprehensive sensitivity assessment of the PACS photometer. Accurate photometry allows us to establish a set of five FIR primary standard candidates, namely alpha Ari, epsilon Lep, omega,Cap, HD41047 and 42Dra, which are 2 -- 20 times fainter than the faintest PACS fiducial standard (gamma Dra) with absolute accuracy of <6%. For three of these primary standard candidates, essential stellar parameters are known, meaning that a dedicated flux model code may be run.Comment: 42 pages, 12 figure

Design and experimental performance of local entanglement witness operators

Entanglement is a central concept in quantum information and a key resource for many quantum protocols. In this work we propose and analyze a class of entanglement witnesses that detect the presence of entanglement in subsystems of experimental multi-qubit stabilizer states. The witnesses we propose can be decomposed into sums of Pauli operators and can be efficiently evaluated by either two measurement settings only or at most a number of measurements that only depends on the size of the subsystem of interest. We provide two constructive methods to design the local witness operators, the first one based on the local unitary equivalence between graph and stabilizer states, and the second one based on sufficient and necessary conditions that the respective set of constituent Pauli operators needs to fulfill. We theoretically establish the noise tolerance of the proposed witnesses and benchmark their practical performance by analyzing the local entanglement structure of an experimental seven-qubit quantum error correction code

Utility of Routine Versus Selective Upper Gastrointestinal Series to Detect Anastomotic Leaks After Laparoscopic Gastric Bypass

Background: In up to 4% of laparoscopic Roux-en-Y gastric bypass (LRYGB) procedures, anastomotic leaks occur. Early detection of gastrointestinal leakage is important for successful treatment. Consequently, many centers advocate routine postoperative upper gastrointestinal (UGI) series. The aim of this study was to determine the utility of this practice after LRYGB. Methods: Eight hundred four consecutive patients undergoing LRYGB from June 2000 to April 2010 were analyzed prospectively. The first 382 patients received routine UGI series between the third and fifth postoperative days (group A). Thereafter, the test was only performed when clinical findings (tachycardia, fever, and drainage content) were suspicious for a leak of the gastrointestinal anastomosis (group B; n = 422). Results: Overall, nine of 804 (1.1%) patients suffered from leaks at the gastroenterostomy. In group A, four of 382 (1%) patients had a leak, but only two were detected by the routine UGI series. This corresponds to a sensitivity of 50%. In group B, the sensitivity was higher with 80%. Specificities were comparable with 97% and 91%, respectively. Routine UGI series cost only 1.6% of the overall costs of a non-complicated gastric bypass procedure. With this leak rate and sensitivity, US $86,800 would have to be spent on 200 routine UGI series to find one leak which is not justified. Conclusions: This study shows that routine UGI series have a low sensitivity for the detection of anastomotic leaks after LRYGB. In most cases, the diagnosis is initiated by clinical findings. Therefore, routine upper gastrointestinal series are of limited value for the diagnosis of a lea

Vibrational exciton nanoimaging of phases and domains in porphyrin nanocrystals.

Much of the electronic transport, photophysical, or biological functions of molecular materials emerge from intermolecular interactions and associated nanoscale structure and morphology. However, competing phases, defects, and disorder give rise to confinement and many-body localization of the associated wavefunction, disturbing the performance of the material. Here, we employ vibrational excitons as a sensitive local probe of intermolecular coupling in hyperspectral infrared scattering scanning near-field optical microscopy (IR s-SNOM) with complementary small-angle X-ray scattering to map multiscale structure from molecular coupling to long-range order. In the model organic electronic material octaethyl porphyrin ruthenium(II) carbonyl (RuOEP), we observe the evolution of competing ordered and disordered phases, in nucleation, growth, and ripening of porphyrin nanocrystals. From measurement of vibrational exciton delocalization, we identify coexistence of ordered and disordered phases in RuOEP that extend down to the molecular scale. Even when reaching a high degree of macroscopic crystallinity, identify significant local disorder with correlation lengths of only a few nanometers. This minimally invasive approach of vibrational exciton nanospectroscopy and -imaging is generally applicable to provide the molecular-level insight into photoresponse and energy transport in organic photovoltaics, electronics, or proteins

RanBP2 and SENP3 function in a mitotic SUMO2/3 conjugation-deconjugation cycle on Borealin

The ubiquitin-like SUMO system controls cellular key functions, and several lines of evidence point to a critical role of SUMO for mitotic progression. However, in mammalian cells mitotic substrates of sumoylation and the regulatory components involved are not well defined. Here, we identify Borealin, a component of the chromosomal passenger complex (CPC), as a mitotic target of SUMO. The CPC, which additionally comprises INCENP, Survivin, and Aurora B, regulates key mitotic events, including chromosome congression, the spindle assembly checkpoint, and cytokinesis. We show that Borealin is preferentially modified by SUMO2/3 and demonstrate that the modification is dynamically regulated during mitotic progression, peaking in early mitosis. Intriguingly, the SUMO ligase RanBP2 interacts with the CPC, stimulates SUMO modification of Borealin in vitro, and is required for its modification in vivo. Moreover, the SUMO isopeptidase SENP3 is a specific interaction partner of Borealin and catalyzes the removal of SUMO2/3 from Borealin. These data thus delineate a mitotic SUMO2/3 conjugation-deconjugation cycle of Borealin and further assign a regulatory function of RanBP2 and SENP3 in the mitotic SUMO pathway

Bulk organic aerosol analysis by PTR-MS: an improved methodology for the determination of total organic mass, O:C and H:C ele- mental ratios and the average molecular formula

International audienceWe have recently shown in this journal (Müller et al., Anal. Chem. 2017, 89, 10889-10897) how a proton-transfer-reaction mass spectrometry (PTR-MS) analyzer measured particulate organic matter in urban atmospheres using the "Chemical Analysis of Aerosol Online" (CHARON) inlet. Our initial CHARON studies did not take into account fragmentation of protonated analyte molecules, which introduced a small but significant negative bias in the determination of bulk organic aerosol parameters. Herein, we studied the ionic fragmentation of 26 oxidized organic compounds typically found in atmospheric particles. This allowed us to derive a correction algorithm for the determination of the bulk organic mass concentration, m OA , the bulk-average hydrogen to carbon ratio, (H:C) bulk, the bulk-average oxygen-to-carbon, (O:C) bulk , and the bulk-average molecular formula, MF bulk. The correction algorithm was validated against AMS data using two sets of published data. Finally, we determined MF bulk of particles generated from the reaction of -pinene and ozone and compared and discussed the results in relation to the literature