66 research outputs found

    Power Play in the German Wine Business: Are German Wine Co-operatives able to Use their Power to manage their Business Relationships?

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    Due to the pyramidal-hierarchical structure of supply chain networks power is an essential part of them and the fact that it is very often unequally distributed among the participants is quite obvious, which might represent great difficulties for member-owned enterprise coops. By clarifying the concept of power and identifying its five different sources, we were able to build hypotheses of how power affects cooperation and coordination – the two main elements of chain management in wine business. The first aim of our research is to elaborate on the question of power. Furthermore, we will construct some hypotheses regarding the use of power as a chain management instrument. Our second aim is to apply our general findings to the wine production chain, analysing the power play between cooperatives and retailers, and between cooperatives and their members. Due to the explorative nature of our study, we based the elaboration of our second aim on oral interviews, which were conducted in 2009, as well as in 2010, at five major international food and beverage fairs (twice ProWein, Anuga, and twice Fruit Logistica) in Germany. In addition, we conducted a comprehensive review of the Lebensmittelzeitung – the leading German food and beverage newspaper – for the last five years. Discussing our hypotheses in the context of the German wine sector, in which cooperatives are still of high importance, we were able to show that power is a very useful tool for managing strictlycoordinated chains. However, depending on which source the power originates from, its effect may be completely different

    Membrane protein production in Escherichia coli cell-free lysates

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    AbstractCell-free protein production has become a core technology in the rapidly spreading field of synthetic biology. In particular the synthesis of membrane proteins, highly problematic proteins in conventional cellular production systems, is an ideal application for cell-free expression. A large variety of artificial as well as natural environments for the optimal co-translational folding and stabilization of membrane proteins can rationally be designed. The high success rate of cell-free membrane protein production allows to focus on individually selected targets and to modulate their functional and structural properties with appropriate supplements. The efficiency and robustness of lysates from Escherichia coli strains allow a wide diversity of applications and we summarize current strategies for the successful production of high quality membrane protein samples

    How singers adapt to room acoustical conditions

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    Previous studies on adaptation of performers to room acoustic conditions mostly focused on musicians. The present study deals with the strategies used by singers, whose musical instrument is inherently part of themselves, inducing a specific perception of the sound they produce. To overcome the variations of the acoustical characteristics of the rooms where they perform, singers tend to vary their sound production (e.g. sound intensity, spectral balance, tempo, articulation). To which extend do singers change their sound production when singing in different rooms? The methodology involves 7 rooms with different acoustical characteristics in which 4 singers performed 3 excerpts a capella of musical pieces. In each place, they were recorded by means of nearfield microphone capturing only the singing voice, i.e. without reverberation from the room. Omnidirectional and binaural room acoustic measurements were also performed on stage. Room acoustical parameters are derived from the measured impulse responses and musical descriptors are extracted from each note of the singing recordings, allowing to quantify the musical performances. The degree of correlation between singing and room acoustics is further considered, revealing both common and specific strategies used by the singers

    Crystal Structure of a PCP/Sfp Complex Reveals the Structural Basis for Carrier Protein Posttranslational Modification

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    SummaryPhosphopantetheine transferases represent a class of enzymes found throughout all forms of life. From a structural point of view, they are subdivided into three groups, with transferases from group II being the most widespread. They are required for the posttranslational modification of carrier proteins involved in diverse metabolic pathways. We determined the crystal structure of the group II phosphopantetheine transferase Sfp from Bacillus in complex with a substrate carrier protein in the presence of coenzyme A and magnesium, and observed two protein-protein interaction sites. Mutational analysis showed that only the hydrophobic contacts between the carrier protein’s second helix and the C-terminal domain of Sfp are essential for their productive interaction. Comparison with a similar structure of a complex of human proteins suggests that the mode of interaction is highly conserved in all domains of life

    A Qualitative Study of Serious Illness Conversations in Patients with Advanced Cancer

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    BACKGROUND: Conversations with seriously ill patients about their values and goals have been associated with reduced distress, a better quality of life, and goal-concordant care near the end of life. Yet, little is known about how such conversations are conducted. OBJECTIVE: To characterize the content of serious illness conversations and identify opportunities for improvement. DESIGN: Qualitative analysis of audio-recorded, serious illness conversations using an evidence-based guide and obtained through a cluster randomized controlled trial in an outpatient oncology setting. Setting/Measurements: Clinicians assigned to the intervention arm received training to use the "Serious Illness Conversation Guide" to have a serious illness conversation about values and goals with advanced cancer patients. Conversations were de-identified, transcribed verbatim, and independently coded by two researchers. Key themes were analyzed. RESULTS: A total of 25 conversations conducted by 16 clinicians were evaluated. The median conversation duration was 14 minutes (range 4-37), with clinicians speaking half of the time. Thematic analyses demonstrated five key themes: (1) supportive dialogue between patients and clinicians; (2) patients' openness to discuss emotionally challenging topics; (3) patients' willingness to articulate preferences regarding life-sustaining treatments; (4) clinicians' difficulty in responding to emotional or ambiguous patient statements; and (5) challenges in discussing prognosis. CONCLUSIONS: Data from this exploratory study suggest that seriously ill patients are open to discussing values and goals with their clinician. Yet, clinicians may struggle when disclosing a time-based prognosis and in responding to patients' emotions. Such skills should be a focus for additional training for clinicians caring for seriously ill patients

    Media ethnography

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    Contents Editorial Thematic Focus: Media Ethnography Media Ethnography and Participation in Online Practices / David Waldecker, Kathrin Englert, Wolfgang Ludwig-Mayerhofer, Oliver Schmidtke The Story is Everywhere. Dispersed Situations in a Literary Role Play Game / Wolfgang Reißmann Co-operation and/as Participant Observation: Reflections on Ethnographic Fieldwork in Morocco / Simon Holdermann Ethnomethodological Media Ethnography: Exploring Everyday Digital Practices in Families with Young Children / Clemens Eisenmann, Jan Peter, Erik Wittbusch Cooperation and Difference. Camera Ethnography in the Research Project ‘Early Childhood and Smartphone’ / Bina E. Mohn, Pip Hare, Astrid Vogelpohl, Jutta Wiesemann Reports Coordinations, or Computing is Work / Sebastian Gießman

    Limbic Justice—Amygdala Involvement in Immediate Rejection in the Ultimatum Game

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    Imaging studies have revealed a putative neural account of emotional bias in decision making. However, it has been difficult in previous studies to identify the causal role of the different sub-regions involved in decision making. The Ultimatum Game (UG) is a game to study the punishment of norm-violating behavior. In a previous influential paper on UG it was suggested that frontal insular cortex has a pivotal role in the rejection response. This view has not been reconciled with a vast literature that attributes a crucial role in emotional decision making to a subcortical structure (i.e., amygdala). In this study we propose an anatomy-informed model that may join these views. We also present a design that detects the functional anatomical response to unfair proposals in a subcortical network that mediates rapid reactive responses. We used a functional MRI paradigm to study the early components of decision making and challenged our paradigm with the introduction of a pharmacological intervention to perturb the elicited behavioral and neural response. Benzodiazepine treatment decreased the rejection rate (from 37.6% to 19.0%) concomitantly with a diminished amygdala response to unfair proposals, and this in spite of an unchanged feeling of unfairness and unchanged insular response. In the control group, rejection was directly linked to an increase in amygdala activity. These results allow a functional anatomical detection of the early neural components of rejection associated with the initial reactive emotional response. Thus, the act of immediate rejection seems to be mediated by the limbic system and is not solely driven by cortical processes, as previously suggested. Our results also prompt an ethical discussion as we demonstrated that a commonly used drug influences core functions in the human brain that underlie individual autonomy and economic decision making

    The role of multixenobiotic transporters in predatory marine molluscs as counter-defense mechanisms against dietary allelochemicals

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    Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 152 (2010): 288-300, doi:10.1016/j.cbpc.2010.05.003.Multixenobiotic transporters have been extensively studied for their ability to modulate the disposition and toxicity of pharmacological agents, yet their influence in regulating the levels of dietary toxins within marine consumers has only recently been explored. This study presents functional and molecular evidence for multixenobiotic transporter-mediated efflux activity and expression in the generalist gastropod Cyphoma gibbosum, and the specialist nudibranch Tritonia hamnerorum, obligate predators of chemically defended gorgonian corals. Immunochemical analysis revealed that proteins with homology to permeability glycoprotein (P-gp) were highly expressed in T. hamnerorum whole animal homogenates and localized to the apical tips of the gut epithelium, a location consistent with a role in protection against ingested prey toxins. In vivo dye assays with specific inhibitors of efflux transporters demonstrated the activity of P-gp and multidrug resistance-associated protein (MRP) families of ABC transporters in T. hamnerorum. In addition, we identified eight partial cDNA sequences encoding two ABCB and two ABCC proteins from each molluscan species. Digestive gland transcripts of C. gibbosum MRP-1, which have homology to vertebrate glutathione-conjugate transporters, were constitutively expressed regardless of gorgonian diet. This constitutive expression may reflect the ubiquitous presence of high affinity substrates for C. gibbosum glutathione transferases in gorgonian tissues likely necessitating export by MRPs. Our results suggest that differences in multixenobiotic transporter expression patterns and activity in molluscan predators may stem from the divergent foraging strategies of each consumer.Financial support was provided by the Ocean Life Institute Tropical Research Initiative Grant (WHOI) to KEW and MEH; the Robert H. Cole Endowed Ocean Ventures Fund (WHOI) to KEW; the National Undersea Research Center – Program Development Proposal (CMRC-03PRMN0103A) to KEW; and the National Science Foundation (Graduate Research Fellowship to KEW and DEB-0919064 to EES)

    Dictator Games: A Meta Study

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    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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