Stress- und Schmerzbelastung des Schweines bei Entnahme eines Tracheobronchialabstriches im Vergleich zum Nasentupfer und der Fixierung in der Oberkieferschlinge

Ziel der vorliegenden Untersuchung war es, die Belastung für Schweine bei der Entnahme eines Tracheobronchialabstriches (TBA) mit der Entnahme eines Nasentupfers (NT) und mit dem alleinigen Halten in der Oberkieferschlinge (OK) zu vergleichen. Zur Evaluierung der Stressbelastung dienten Cortisolkonzentrationen aus Serum- und Speichelproben sowie aus dem Blutplasma ermittelte Noradrenalin- und Adrenalinkonzentrationen. Hierfür wurden vier Gruppen, drei Versuchs- und eine Kontrollgruppe (KO), zu je 23 klinisch gesunden Tieren für die Cortisolbestimmungen und zu je 31 klinisch gesunden Tieren für die Katecholaminbestimmungen untersucht. Von in der Oberkieferschlinge fixierten Tieren der TBA und NT Gruppe wurde ein Tracheobronchialabstrich bzw. ein Nasentupfer entnommen. Der Tracheobronchialkatheter wurde ohne vorherige Narkose der Tiere in die Luftröhre eingeführt. Bei den Tieren der OK Gruppe erfolgte eine Fixierung in der Oberkieferschlinge für die Dauer von 60 Sekunden. Im Gegensatz dazu wurden die Tiere der KO Gruppe zum Zeitpunkt des Eingriffes ohne Beunruhigung in der Bucht belassen. Im ersten Teilversuch, welcher der Cortisolbestimmung diente, wurde von jedem Schwein viermal Blut und zum selben Zeitpunkt Speichel gewonnen: 30 min vor dem Eingriff sowie je 30 min, 60 min und 90 min danach. Die Katecholaminkonzentrationen wurden im zweiten Teilversuch aus EDTA-Blutproben, die 15 min vor und unmittelbar nach dem Eingriff entnommen wurden, ermittelt. Die Cortisolkonzentrationen nach Durchführung eines Tracheobronchialabstriches entsprechen denen nach Entnahme eines Nasentupfers. Ein vergleichbarer wenn auch etwas verzögerter Cortisolanstieg wird durch die Fixierung mit der Oberkieferschlinge hervorgerufen. Bezugnehmend auf die Noradrenalin-Ergebnisse der vorliegenden Studie konnte gezeigt werden, dass der kurzfristige Stress durch die Tracheobronchialabstriche vergleichbar mit der Nasentupferentnahme ist und beide eine wesentlich höhere Belastung als die alleinige Fixierung mit der Oberkieferschlinge darstellen. Die insgesamt beobachteten Veränderungen der Adrenalinspiegel sind gering und sprechen gegen starken emotionalen Stress und Angst der Schweine nach den durchgeführten Maßnahmen

Impact of iron on CHO metabolism and recombinant protein production

Iron is an essential transition metal required in cell culture medium (CCM) due to its vital role in many cellular processes such as energy metabolism, deoxyribonucleic acid (DNA) biosynthesis or antioxidant functions. However, due to its redox capabilities, iron can also catalyze Fenton reactions favoring the formation of reactive oxygen species (ROS) that may cause severe cellular damages. This study sought to investigate the impact of iron in CCM on Chinese hamster ovary (CHO) cell line performance, on critical quality attributes (CQAs) of different recombinant proteins, on messenger ribonucleic acid (mRNA) expression levels of genes involved in iron homeostasis, and on intracellular iron or labile iron pool (LIP) levels, whereby for the last two readouts a method development was performed prior to analyzing the project relevant samples. Besides the successful establishment of a ferrozine-based assay for detecting total intracellular iron amount and the promising results obtained upon testing the fluorescent probe RhoNox-1 for detecting changes in LIP concentrations, none of the other two (fluorescent) probes tested during method development, namely calcein and TRX-PURO, were able to determine LIP amounts within CHO cells. Since those probes rely on a rather high LIP concentration present within cells, a low LIP present within CHO cells either due to a limited, saturated or low iron uptake, or due to an immediate distribution or usage of iron within the cells once taken up was thus suggested. Data also revealed that iron raw material impurities are strongly impacting cell performance and CQAs. Whereas manganese was identified as the main impurity improving cell performance and altering protein glycosylation level within Cellvento® 4CHO and 4Feed fed-batch platform with manganese presenting additionally an opposite effect on cell culture compared to iron, copper impurity contributed to an overall increased cell performance of the tested CHOZN® cell line in EX-CELL® Advanced CHO Fed-Batch-Medium platform. Usage of low impurity iron raw materials is therefore crucial to decouple the effects of iron and its trace element impurities by controlling and adjusting each element concentration independently and thereby guarantee the run of consistent and stable cell culture processes. Among the different iron sources tested within CCM during a fed-batch experiment, non-chelated iron sources caused a faster decrease in measured iron concentration within the supernatant and led to a higher detected iron amount present within the cell pellets taken during the course of the fed-batch process compared to the tested chelated iron sources, whereas no cell growth was obtained upon ferric chloride (FeCl3) usage. At a first glance, data suggest an increased uptake efficiency for CHO cells upon usage of non-chelated iron sources, however, differences might have rather come from a faster iron precipitate formation within CCM upon usage of non-chelated iron sources, additionally, since mRNA expression levels of genes involved in iron uptake did not indicate for a difference between chelated and non-chelated iron sources. The removal of possible iron precipitates prior to intracellular iron measurement as well as the investigation of the fate of iron in CCM seems thus to be crucial to understand iron-related uptake mechanisms

Building Up Demand-Oriented Charging Infrastructure for Electric Vehicles in Germany

Mobility offerings have never been as abundant and varied as the present. While users welcome new and innovative mobility options, this current paradigm shift presents a challenge for authorities that plan, organize, and operate such services. In particular, integrating new mobility services into existing infrastructure systems can generate problems of acceptance, co-operability, and compatibility. This problem is especially relevant for electric vehicles. Limited range and battery capacity of battery electric vehicles make them dependent on charging infrastructure, which in turn hinders their acceptance. In light of the German government’s goal of one million electric vehicles by 2020, establishing a demand-oriented charging infrastructure is of crucial importance. However, numerous questions remain unanswered regarding the quantity, type, and location of electric vehicle charging stations in Germany. This article presents the findings of the project “LADEN2020: Concept to build up a demand-oriented charging infrastructure in Germany between today and 2020.” The research project develops a systematically comprehensible and consistent strategy for electric vehicle charging infrastructure in Germany. The paper presents the methodological framework to estimate the charging demand for daily and long-distance travel, which is unique and innovative as similar comprehensive and consistent analytical tools do not exist to date

Wissenschaftliche Auswertung über Theorien und Instrumente für ein Inklusives Wachstum in Deutschland

Vor dem Hintergrund von Digitalisierung und Industrie 4.0 ändert sich die Arbeitswelt umfassend. Dabei ist die Entwicklung nicht nur von Fragen der potenziellen Substituierbarkeit des Menschen durch technische Systeme geprägt, sondern auch von den Möglichkeiten einer immer engeren Kooperation zwischen Mensch und Maschine, mit dem Ziel, die herausragenden Fähigkeiten des Menschen mit den besonderen Eigenschaften von Maschinen als "Bestes aus zwei Welten" zu vereinen. Dazu gehört auch, dass der Mensch von den technischen Systemen eine Unterstützung erfährt, die im Idealfall genau seinen Fähigkeiten und Bedürfnissen sowie den Anforderungen des Arbeitskontextes entspricht. Um diesen Anspruch zu erfüllen, werden seit einigen Jahren vermehrt digitale Assistenzsysteme in der betrieblichen Praxis eingesetzt. Der weitaus prominenteste Anwendungsfall sind Systeme zur Werkerführung (pick-by-light und verwandte), die etwa in der variantenreichen Fertigung eingesetzt werden. Darüber hinaus ist zu erwarten, dass aufgrund der fortschreitenden technologischen Entwicklung insbesondere kognitiv unterstützende Funktionen zukünftig nicht mehr an spezielle Geräte gebunden sein werden, sondern sich die Assistenz in Form einer umfassenden Software-Integration und eines gemeinsamen Datenraumes auf nahezu jedem technischen Gerät realisieren wird - ganz gleich, ob es eine Werkzeugmaschine oder ein Smartphone ist. Um den Entwicklungsstand von digitalen Assistenzsystemen zu beschreiben und ihren Beitrag im Hinblick auf Inklusion/Diversity, Gesunderhaltung und Arbeitsqualität abzuschätzen, wurde in der vorliegenden Studie ein Klassifikationsschema gemäß Art der Unterstützung (physisch, sensorisch, kognitiv), Anforderungsniveau (niedrig, mittel, hoch, variabel) und Zielsetzung der Unterstützung (kompensatorisch, erhaltend, erweiternd) entwickelt Aufbauend darauf werden die Potenziale von digitalen Assistenzsystemen anhand von 16 Praxisbeispielen veranschaulicht und in einer Gesamtbetrachtung die Erfolgsfaktoren für eine betriebliche Umsetzung diskutiert. Abschließend werden Gestaltungsoptionen für die Politik aufgezeigt, um bei einer weiteren Verbreitung von digitalen Assistenzsystemen im Betrieb die Potenziale für eine verbesserte Teilhabe, höhere Arbeitsqualität und gesünderes Arbeiten zu heben und zur Etablierung eines Leitmarktes für gute digital assistierte Arbeit in Deutschland beizutragen.Against the background of digitalization and industry 4.0, the world of work changes comprehensively. The development is characterised not only by questions of the potential substitutability of humans by technical systems, but also by the possibilities of an ever closer cooperation between man and machine, with the aim of combining the outstanding abilities of man with the special characteristics of machines as "best from two worlds". This also means that the human being is supported by technical systems, which, in an ideal situation, exactly match his abilities and needs, as well as the requirements of the working context. In order to meet this demand, digital assistance systems have been increasingly used in the last years. The most prominent applications are systems for worker guidance (pick-by-light and related), which are used, for example, in multi-variant assembly. Moreover, it is to be expected that, due to the ongoing technological development, especially cognitive support functions will no longer be bound to specific devices in the future, but that the assistance will be realised by means of comprehensive software integration and a common data space on almost every technical device, independent of whether it is a machine tool or a smartphone. To describe the stage of development for digital assistance systems and assess their contribution to inclusion/diversity, health and work quality, a classification scheme was developed in the present study according to type of support (physical, sensory, cognitive), degree of support (low, medium, high, variable) and objective of support (compensatory, sustaining, expanding) and Building on this, the potentials of digital assistance systems are illustrated by 16 practical examples and success factors for the operational implementation are discussed. Finally, policy measure to unlock potentials for more participation, higher quality of work and healthier work in the course of a further diffusion of digital assistance systems in businesses and to support the establishment of a lead market in Germany for good digitally assisted work are presented

Local anesthesia in piglets undergoing castration-A comparative study to investigate the analgesic effects of four local anesthetics on the basis of acute physiological responses and limb movements

Surgical castration of male piglets without analgesia is a painful procedure. This prospective, randomized and double-blinded study aimed to evaluate the analgesic effects of four different local anesthetics for piglet castration during the first week of life. In total, 54 piglets aged 3 to 7 days were distributed into 6 treatment groups: handling (H);castration without pain relief (sodium chloride, NaCl);and castration with a local anesthetic: 4% procaine (P), 2% lidocaine (L), 0.5% bupivacaine (B) or 20 mg/ml mepivacaine (M). By excluding stress and fear as disruptive factors via a minimum anesthesia model, all piglets received individual minimum alveolar concentration (MAC) isoflurane anesthesia. Twenty minutes before castration, all treatment groups except group H received one injection per testis. Then, 0.5 ml of a local anesthetic or NaCl was injected intratesticularly (i.t.), and 0.5 ml was administered subscrotally. Acute physiological responses to noxious stimuli at injection and castration were evaluated by measuring blood pressure (BP), heart rate (HR), cortisol, epinephrine, norepinephrine and chromogranin A (CgA);limb movements were quantified. The results confirm that castration without analgesia is highly painful. Surgical castration without pain relief revealed significant changes in mean arterial blood pressure (MAP) and HR. Local anesthetic administration significantly reduced changes in BP and HR associated with castration. Piglets receiving a preoperative local anesthetic exhibited the fewest limb movements during castration, while the NaCl group exhibited the most. Injection itself was not associated with significant changes in MAP or HR. However, many piglets exhibited limb movements during injection, indicating that the injection itself causes nociceptive pain. No significant differences were found between groups regarding parameters of plasma cortisol, catecholamines and CgA. In conclusion, all four local anesthetics administered are highly effective at reducing signs of nociception during castration under light isoflurane anesthesia. However, injection of a local anesthetic seems to be painful