To Plan or Not to Plan? Exploring Entrepreneurial Logics in Digital Servitization

Digital servitization is of increasing concern for manufacturers to exploit the potentials of digitaliza-tion with new service offerings. In this context, substantial changes within a firm´s capabilities, processes and mindset of employees need to be considered. To better understand such changes, we carve out behavioral logics of manufacturers undergoing digital servitization. An alternate template research design is used to discover the entrepreneurial logics of effectuation, causation, and bricolage. For this purpose, we conducted 13 semi-structured interviews with experts from the German manufacturing industry. Our results show that firms approaching digital servitization via hybrid decision logics. Causation can be found within all organizations. Effectuation is integrated to various degrees. Against it, the bricolage-logic is barely present. In total, the results provide new insights for digital servitization and for organizational ambidexterity

A robust and efficient mechanism for constructing multicast acknowledgment trees

A great variety of todays networked applications require a reliable multicast service. A number of the proposed reliable multicast protocols use a positive acknowledgment scheme, which returns ACKs to the sender to confirm correct delivery. To avoid the well-known implosion problem in the case of large receiver groups, often a tree-based approach is used, i.e., receivers are organized in a tree and ACK messages are passed along the edges of this so-called ACK tree. For building up this tree variations of the Expanding Ring Search (ERS) scheme have been proposed. However, our simulations show that ERS scales poorly. In this paper, we propose an alternative scheme for building up ACK trees. This scheme is based on a so-called token repository service, wherena token represents the right to connect to a certain node in the corresponding ACK tree. Nodes that want to join a group just request a token for this group from the (distributed) token repository service. Our simulations show that our scheme causes a much lower message overhead than ERS. Moreover, the quality of the resulting ACK trees in terms of delay and reliability is in many cases higher if generated with our scheme

A delay analysis of tree-based reliable multicast protocols

We present a comparative delay analysis of tree-based reliable multicast protocols and show the influence of varying sending rates, group sizes, packet loss probabilities and branching factors of the control tree. Besides the average delivery delay we consider the delay to reliably deliver all packets and the round trip delay. The former two examines the delay between generation of a packet at the sender and correct reception at a randomly chosen receiver or all receivers, respectively. The latter is the delay between generation of a packet at the sender and reception of all acknowledgment packets at the sender. Our numerical results show that all tree-based protocols provide low delays and good scalability. From the four considered protocol classes, NAK-based protocols achieve the best scalability but ACK-based protocols achieve the lowest delays. An important aspect of our work is to be of practical relevance rather than being of only theoretical nature. Therefore, we have compared the analytical results with a RMTP and TMTP simulation. Both show similar results which confirms that our analysis can help to choose a suitable protocol and to tune them for improved performance

rAAV-vermittelte, hydrogel-gebundene Überexpression des humanen insulinartigen Wachstumsfaktors I (hIGF-I) verbessert die Reparatur von fokalen Knorpelschäden und reduziert die perifokale Arthrose - eine Langzeitstudie in einem Großtiermodell der Mikrofrakturierung

Zusammenfassung Chondrale Defekte regenerieren nicht, stattdessen bildet sich ein qualitativ minder-wertiges Regenerationsgewebe. Trotz etablierter klinischer Ansätze, wie mark¬raum-stimulierende Verfahren, können diese Defekte ein Ausgangspunkt für Arthrose sein. Ein erfolgs¬versprechender experimenteller Ansatz zur Ver¬besserung der Knorpelheilung ist die lokale Überexpression von therapeutischen Sequenzen durch Gentransfer¬vektoren, die an Biomaterialien gekoppelt sind. Wachstumsfaktoren können so kontrolliert, kontinuierlich, lokal und präzise abgegeben werden, ohne einen wesentlichen Einfluss auf die Gelenkhomöostase auszuüben. Die vorliegende Arbeit untersuchte die Langzeiteffekte einer rekombinanten adeno-assoziierten Virus (rAAV)-Vektor vermittelten hydrogel-gebundenen (Alginat, AlgPH155) Überexpression des humanen insulinartigen Wachstumsfaktors I (hIGF-I) (IGF I/AlgPH155) in einem Minischweinmodell der Therapie vollschichtiger Knorpel-defekte durch Mikrofrakturierung. Ein Jahr postoperativ fand sich in vivo eine signifikant verstärkte IGF-I-Immunreaktivität in der tiefen Zone des Reparaturgewebes als Zeichen einer persistierenden Trans¬gen-expression im Vergleich zur Überexpression des Kontrollvektors lacZ (lacZ/AlgPH155). Zudem führte die Behandlung mit IGF-I/AlgPH155 zu signifikant verbesserten Strukturparametern wie „Defekt¬füllung“, „Oberflächenbeschaffenheit“, „Zellmorphologie“ sowie insbesondere zu einer signifikanten Verbesserung der Gesamt¬punktzahl des histo¬logischen Bewertungssystems. Flankierend hierzu führte die Therapie mit IGF I/AlgPH155 zu einer signifikant vermehrten Typ-II-Kollagenbildung in der oberen Zone des Reparaturgewebes. Die Analyse der Mikrostruktur des subchondralen Knochens zeigte keine signifikanten Unterschiede zwischen den Behandlungsgruppen. Der histologische Schweregrad der defektassoziierten perifokalen Arthrose war ein Jahr postoperativ durch Therapie mit IGF-I/AlgPH155 signifikant vermindert. Die Ergebnisse der vorliegenden Arbeit zeigen, dass eine rAAV-vermittelte, hydrogel-gebundene lokale Überexpression von hIGF-I positive Langzeiteffekte auf die Heilung von Knorpeldefekten hat und sich zudem protektiv auf den umgebenden Knorpel auswirkt.Abstract Articular cartilage defects do not regenerate, instead they are filled with a cartilaginous repair tissue of lesser quality. Despite established clinical approaches such as marrow stimulating techniques, these defects can represent a starting point of secondary osteoarthritis (OA). A promising experimental approach to enhance articular cartilage repair is the local biomaterial-guided overexpression of therapeutic sequences delivered by gene transfer vectors. Growth factors can be released in a controlled, continuous, local and precise manner without having a significant influence on joint homeostasis. The present study investigated the long-term effects of recombinant adeno-associated viral (rAAV)-vector and hydrogel (alginate, AlgPH155) guided overexpression of the human insulin-like growth-factor-I (hIGF-I) (IGF-I/AlgPH155) in a minipig model of full thickness chondral defects treated with microfracture. One year postoperatively, IGF-I immunoreactivity was significantly increased in the deep zone of the repair tissue as sign of persistent transgene overexpression compared to the overexpression of the control vector lacZ (lacZ/AlgPH155) in vivo. In addition, treatment with IGF-I/AlgPH155 led to significantly improved structural parameters “defect filling”, “surface quality”, “cell morphology” as well as a significant improvement in the overall score of the histological evaluation system. Furthermore type-II collagen expression was significantly enhanced in the upper zone of the cartilaginous repair tissue upon treatment with IGF-I/AlgPH155. Analysis of the microstructure of the subchondral bone showed no significant differences between the treatment groups. Of note, the histological severity of the defect-associated perifocal OA was significantly reduced following therapy with IGF I/AlgPH155 at 1 year postoperatively. The results of the present work show that rAAV-mediated, hydrogel-guided over-expression of hIGF-I has positive long-term effects on the healing of cartilage defects and protects the surrounding articular cartilage

Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis

<p>Abstract</p> <p>Background</p> <p>Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC).</p> <p>Methods</p> <p>To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed.</p> <p>Results</p> <p>Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations.</p> <p>Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01).</p> <p>Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells.</p> <p>Conclusion</p> <p>Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia.</p

Hydrogel-Guided, rAAV-Mediated IGF-I Overexpression Enables Long-Term Cartilage Repair and Protection against Perifocal Osteoarthritis in a Large-Animal Full-Thickness Chondral Defect Model at One Year In Vivo

The regeneration of focal articular cartilage defects is complicated by the reduced quality of the repair tissue and the potential development of perifocal osteoarthritis (OA). Biomaterial-guided gene therapy may enhance cartilage repair by controlling the release of therapeutic sequences in a spatiotemporal manner. Here, the benefits of delivering a recombinant adeno-associated virus (rAAV) vector coding for the human insulin-like growth factor I (IGF-I) via an alginate hydrogel (IGF-I/AlgPH155) to enhance repair of full-thickness chondral defects following microfracture surgery after one year in minipigs versus control (lacZ/AlgPH155) treatment are reported. Sustained IGF-I overexpression is significantly achieved in the repair tissue of defects treated with IGF-I/AlgPH155 versus those receiving lacZ/AlgPH155 for one year and in the cartilage surrounding the defects. Administration of IGF-I/AlgPH155 significantly improves parameters of cartilage repair at one year relative to lacZ/AlgPH155 (semiquantitative total histological score, cell densities, matrix deposition) without deleterious or immune reactions. Remarkably, delivery of IGF-I/AlgPH155 also significantly reduces perifocal OA and inflammation after one year versus lacZ/AlgPH155 treatment. Biomaterial-guided rAAV gene transfer represents a valuable clinical approach to promote cartilage repair and to protect against OA

Vergleich des Rechtsschutzes im Vergabeverfahren ober- und unterhalb der Schwellenwerte

Das Vergaberecht unterliegt einer Zweiteilung in die Bereiche ober- und unterhalb der Schwellenwerte der EU-Vergaberichtlinien. Diese Zweiteilung zieht abweichende Regelungen in Bezug auf den Rechtsschutz nach sich, was für öffentliche Auftraggeber in der Praxis eine besondere Herausforderung darstellt. Diese Arbeit vergleicht daher die Rechtsschutzmöglichkeiten für Bieter ober- und unterhalb der Schwellenwerte. Dabei werden die Voraussetzungen des Rechtsschutzanspruchs, der Rechtsweg und einzelne bieterschützende Vorschriften analysiert. Im Zuge des Vergleichs der Rechtsschutzmöglichkeiten wird auch erörtert, ob ein Ausbau der Effektivität des Primärrechtsschutzes im Unterschwellenbereich sinnvoll ist. Die Arbeit zeigt außerdem Risiken für öffentliche Auftraggeber und mögliche Lösungsansätze zur Risikominimierung auf