The Struggle for Technology: Towards a Realistic Political Theory of Technology

Pieter Lemmens’ neo-Marxist approach to technology urges us to rethink how to do political philosophy of technology. First, Lemmens’ high level of abstraction raises the question of how empirically informed a political theory of technology needs to be. Second, his dialectical focus on a “struggle” between humans and technologies reveals the limits of neo-Marxism. Political philosophy of technology needs to return “to the things themselves”. The political significance of technologies cannot be reduced to its origins in systems of production or social organization, but requires study at the micro-level, where technologies help to shape engagement, interaction, power, and social awareness.     

Supply chain performance for deteriorating items with cooperative advertising

To study the effect of cooperative advertising on the supply chain of deteriorating items, this paper establishes a Stackelberg game model for a two-echelon deteriorating items supply chain composed of one manufacturer and one retailer under a given support program with an exogenous participation rate. The manufacturer as the leader determines the wholesale price and production rate, and the retailer as the follower determines the retail price and advertising strategies. The strategies of the players under the decentralized scenario and the centralized scenario are respectively characterized. Numerical simulations and sensitivity analysis are conducted to gain some managerial insights. It is shown that the pricing, advertising and production strategies are negatively correlated to deteriorating coefficient, and both the profit and the channel efficiency decrease with deteriorating coefficient; The interaction between price, advertising investment and production rate results in a higher retail price of the centralized channel compared to that of the decentralized channel; Implementing the cooperative advertising program does improve the performance of the supply chain in some cases and the participation rate roughly at 0.5 is most preferable, but it is also possible to distort incentive and damage the channel performance when the participation rate reaches a relatively high level.     

Dual hesitant fuzzy information aggregation with Einstein t-conorm and t-norm

Dual hesitant fuzzy set (DHFS) is a new generalization of fuzzy set (FS) consisting of two parts (i.e., the membership hesitancy function and the non-membership hesitancy function), which confronts several different possible values indicating the epistemic degrees whether certainty or uncertainty. It encompasses fuzzy set (FS), intuitionistic fuzzy set (IFS), and hesitant fuzzy set (HFS) so that it can handle uncertain information more flexibly in the process of decision making. In this paper, we propose some new operations on dual hesitant fuzzy sets based on Einstein t-conorm and t-norm, study their properties and relationships and then give some dual hesitant fuzzy aggregation operators, which can be considered as the generalizations of some existing ones under fuzzy, intuitionistic fuzzy and hesitant fuzzy environments. Finally, a decision making algorithm under dual hesitant fuzzy environment is given based on the proposed aggregation operators and a numerical example is used to demonstrate the effectiveness of the method.     

Feature network-driven quadrant mapping for summarizing customer reviews

With the rapid growth of e-commerce, customers increasingly write online reviews of the product they purchase. These customer reviews are one of the most valuable sources of information affecting selection of products or services. Summarizing these customer reviews is becoming an interesting area of research, inspiring researchers to develop a more condensed, concise summarization for users. However, most of the current efforts at summarization are based on general product features without feature’s relationship. As a result, these summaries either ignore feedback from customers or do a poor job of reflecting the opinions expressed in customer reviews. To remedy this summarization shortcoming, we propose a feature network-driven quadrant mapping that captures and incorporates opinions from customer reviews. Our focus is on construction of a feature network, which is based on co-occurrence and sematic similarities, and a quadrant display showing the opinions polarity of feature groups. Moreover, the proposed approach involves clustering similar product features, and thus, it is different from standard text summarization based on abstraction and extraction. The summarized results can help customers better understand the overall opinions about a product.     

Exosomes: mobile platforms for targeted and synergistic signaling across cell boundaries

Intercellular communications play a vital role during tissue patterning, tissue repair, and immune reactions, in homeostasis as well as in disease. Exosomes are cell-derived secreted vesicles, extensively studied for their role in intercellular communication. Exosomes have the intrinsic ability to package multiple classes of proteins and nucleic acids within their lumens and on their membranes. Here, we explore the hypothesis that exosomal targeting may represent a cellular strategy that has evolved to deliver specific combinations of signals to specific target cells and influence normal or pathological processes. This review aims to evaluate the available evidence for this hypothesis and to identify open questions whose answers will illuminate our understanding and applications of exosome biology.     

Metabolic changes during B cell differentiation for the production of intestinal IgA antibody

To sustain the bio-energetic demands of growth, proliferation, and effector functions, the metabolism of immune cells changes dramatically in response to immunologic stimuli. In this review, I focus on B cell metabolism, especially regarding the production of intestinal IgA antibody. Accumulating evidence has implicated not only host-derived factors (e.g., cytokines) but also gut environmental factors, including the possible involvement of commensal bacteria and diet, in the control of B cell metabolism during intestinal IgA antibody production. These findings yield new insights into the regulation of immunosurveillance and homeostasis in the gut.     

Old drugs with new skills: fenoprofen as an allosteric enhancer at melanocortin receptor 3

The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC₃, MC₄, and MC₅ receptors. In a model of inflammatory arthritis, fenoprofen afforded potent inhibition while ibuprofen was nearly inactive. Fenoprofen presented anti-arthritic actions on cartilage integrity and synovitis, effects markedly attenuated in Mc3r?/? mice. Fenoprofen displayed pro-resolving properties promoting macrophage phagocytosis and efferocytosis, independently of cyclooxygenase inhibition. In conclusion, combining repositioning with advances in G-protein coupled receptor biology (allosterism) may lead to potential new therapeutics. In addition, MC₃ PAMs emerged as a viable approach to the development of innovative therapeutics for joint diseases.     

Proliferation status defines functional properties of endothelial cells

Homeostasis of solid tissue is characterized by a low proliferative activity of differentiated cells while special conditions like tissue damage induce regeneration and proliferation. For some cell types it has been shown that various tissue-specific functions are missing in the proliferating state, raising the possibility that their proliferation is not compatible with a fully differentiated state. While endothelial cells are important players in regenerating tissue as well as in the vascularization of tumors, the impact of proliferation on their features remains elusive. To examine cell features in dependence of proliferation, we established human endothelial cell lines in which proliferation is tightly controlled by a doxycycline-dependent, synthetic regulatory unit. We observed that uptake of macromolecules and establishment of cell–cell contacts was more pronounced in the growth-arrested state. Tube-like structures were formed in vitro in both proliferating and non-proliferating conditions. However, functional vessel formation upon transplantation into immune-compromised mice was restricted to the proliferative state. Kaposi’s sarcoma-associated herpes virus (KSHV) infection resulted in reduced expression of endothelial markers. Upon transplantation of infected cells, drastic differences were observed: proliferation arrested cells acquired a high migratory activity while the proliferating counterparts established a tumor-like phenotype, similar to Kaposi Sarcoma lesions. The study gives evidence that proliferation governs endothelial functions. This suggests that several endothelial functions are differentially expressed during angiogenesis. Moreover, since proliferation defines the functional properties of cells upon infection with KSHV, this process crucially affects the fate of virus-infected cells.     

Assembly and regulation of ASC specks

The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function. In several inflammatory diseases, ASC specks can be found in the extracellular space and its presence correlates with poor prognosis. Here, we review the role of ASC in inflammation, and focus on the structural mechanisms that lead to ASC speck formation, the regulation of ASC function during inflammasome assembly, and the importance of ASC specks in disease.     

Assessing heterogeneity in oligomeric AAA+ machines

ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.