Advancing Customer Feedback Systems with Blockchain

Organizations have to adjust to changes in the ecosystem, and customer feedback systems (CFS) provide important information to adapt products and services to changing customer preferences. However, current systems are limited to single-dimensional rating scales and are subject to self-selection biases. The work contributes design principles for CFS and implements a CFS that advances current systems by means of contextualized feedback according to specific organizational objectives. The authors apply Design Science Research (DSR) methodology and report on a longitudinal DSR journey considering multiple stakeholder values by utilizing value-sensitive design methods. They conducted expert interviews, design workshops, demonstrations, and a four-day experiment in an organizational setup, involving 132 customers of a major Swiss library. In the process, the identified design principles and the implemented software artifact were validated qualitatively and quantitatively, leading to conclusions for their efficient instantiation. The authors found that i) blockchain technology can afford four design principles of effective CFS. Also, ii) combining DSR with value-sensitive design methods explicitly provides rationale for design principles in the form of identified important values. Moreover, iii) combining DSR with value-sensitive design methods makes the construction of software artifacts more efficient it terms of design time by restricting the design space of a software artifact to those options that align with stakeholder values. The findings of this work thus extend the knowledge about the design of CFS and offer both researchers a theoretical contribution to reasoning about design principles and managers and decision makers a guide for the efficient design of software artifacts

Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL

Here, we provide evidence for a detrimental role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in neural death in T cell-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Clinical severity and neuronal apoptosis in brainstem motor areas were substantially reduced upon brain-specific blockade of TRAIL after induction of EAE through adoptive transfer of encephalitogenic T cells. Furthermore, TRAIL-deficient myelin-specific lymphocytes showed reduced encephalitogenicity when transferred to wild-type mice. Conversely, intracerebral delivery of TRAIL to animals with EAE increased clinical deficits, while naive mice were not susceptible to TRAIL. Using organotypic slice cultures as a model for living brain tissue, we found that neurons were susceptible to TRAIL-mediated injury induced by encephalitogenic T cells. Thus, in addition to its known immunoregulatory effects, the death ligand TRAIL contributes to neural damage in the inflamed brain

Risk response strategies for collaborative university-industry R&D funded programs

Universities are centers of knowledge in our societies and their role when it comes to innovation has become more important over the years. Companies have several reasons to engage in research collaborations with universities, namely to gain access to innovative technologies. University-Industry R&D collaborations are expected to play an important role in regional economies, and to fulfill the industry’s demand for innovative products, technologies and processes. However, the knowledge on what are the potential risks resulting from these collaborations and the risk response strategies to reduce the negative risk impacts and to enhance positive risk impacts is still limited. Thus, this paper aims to fill the gap in literature when it comes to risk identification and risk responses’ planning, by identifying, based on a case study analysis, 19 potential risks and 53 potential risk response strategies.INCT-EN - Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção(SFRH/BPD/111033/2015

Designing a Process Mining-Enabled Decision Support System for Business Process Standardization in ERP Implementation Projects

Process standardization allows to optimize ERP systems and is a nec-essary step prior to ERP implementation projects. Traditional approaches to standardizing business processes are based on manually created "de-jure" process models, which are distorted, error-prone, simplistic, and often deviating from process reality. Theoretically embedded in the organizational contingency theory as kernel theory, this paper employs a design science approach to design a process mining-enabled decision support system (DSS) which combines bottom-up process mining models with manually added top-down standardization infor-mation to recommend a suitable standard process specification from a repository. Extended process models of the as-is process are matched against a repository of best-practice standard process model using an attributebased process similarity matching algorithm. Thus, the DSS aims to reduce the overall costs of process standardization, to optimize the degree of fit between the organization and the implemented processes, and to minimize the degree of organizational change re-quired in standardization and ERP implementation projects. This paper imple-ments a working prototype instantiation in the open-source process analytics platform Apromore based on a real-life event log and standardization attributes for the Purchase-to-Pay and Order-to-Cash processes from three SAP R/3 ERP systems at the industry partner

Personality and Augmenting/Reducing (A/R) in auditory event-related potentials (ERPs) during emotional visual stimulation

An auditory augmenting/reducing ERP paradigm recorded for 5 intensity tones with emotional visual stimulation was used, for the first time, to test predictions derived from the revised Reinforcement Sensitivity Theory (rRST) of personality with respect to two major factors: behavioral inhibition system (BIS), fight/flight/freeze system (FFFS). Higher BIS and FFFS scores were negatively correlated with N1/P2 slopes at central sites (C3, Cz, C4). Conditional process analysis revealed that the BIS was a mediator of the association between the N1/P2 slope and the FFFS scores. An analysis of covariance showed that lower BIS scorers exhibited larger N1/P2 amplitudes across all tone intensities while watching negative, positive and neutral pictures. Additionally, lower FFFS scorers compared to higher FFFS scorers disclosed larger N1/P2 amplitudes to the highest tone intensities and these differences were even more pronounced while watching positive emotional pictures. Findings were explained assuming the operation of two different, but related processes: transmarginal inhibition for the BIS; the attention/emotional gating mechanism regulating cortical sensory input for the FFFS trait. These findings appear consistent with predictions derived from the rRST, which traced fear and anxiety to separate but interacting neurobehavioural systems

Low-dose oral immunization with lyophilized tissue of herbicide-resistant lettuce expressing hepatitis B surface antigen for prototype plant-derived vaccine tablet formulation

Efficient immunization against hepatitis B virus (HBV) and other pathogens with plant-based oral vaccines requires appropriate plant expressors and the optimization of vaccine compositions and administration protocols. Previous immunization studies were mainly based on a combination of the injection of a small surface antigen of HBV (S-HBsAg) and the feeding with raw tissue containing the antigen, supplemented with an adjuvant, and coming from plants conferring resistance to kanamycin. The objective of this study was to develop a prototype oral vaccine formula suitable for human immunization. Herbicide-resistant lettuce was engineered, stably expressing through progeny generation micrograms of S-HBsAg per g of fresh weight and formed into virus-like particles (VLPs). Lyophilized tissue containing a relatively low, 100-ng VLP-assembled antigen dose, administered only orally to mice with a long, 60-day interval between prime and boost immunizations and without exogenous adjuvant, elicited mucosal and systemic humoral anti-HBs responses at the nominally protective level. Lyophilized tissue was converted into tablets, which preserved S-HBsAg content for at least one year of room temperature storage. The results of the study provide indications on immunization methodology using a durable, efficacious, and convenient plant-derived prototype oral vaccine against hepatitis B

Plant expression, lyophilisation and storage of HBV medium and large surface antigens for a prototype oral vaccine formulation

Current immunisation programmes against hepatitis B virus (HBV) increasingly often involve novel tri-component vaccines containing—together with the small (S-HBsAg)—also medium and large surface antigens of HBV (M- and L-HBsAg). Plants producing all HBsAg proteins can be a source of components for a potential oral ‘triple’ anti-HBV vaccine. The objective of the presented research was to study the potential of M/L-HBsAg expression in leaf tissue and conditions of its processing for a prototype oral vaccine. Tobacco and lettuce carrying M- or L-HBsAg genes and resistant to the herbicide glufosinate were engineered and integration of the transgenes was verified by PCR and Southern hybridizations. M- and L-HBsAg expression was confirmed by Western blot and assayed by ELISA at the level of micrograms per g of fresh weight. The antigens displayed a common S domain and characteristic domains preS2 and preS1 and were assembled into virus-like particles (VLPs). Leaf tissues containing M- and L-HBsAg were lyophilised to produce a starting material of an orally administered vaccine formula. The antigens were distinctly sensitive to freeze-drying conditions and storage temperature, in the aspect of stability of S and preS domains and formation of multimeric particles. Efficiency of lyophilisation and storage depended also on the initial antigen content in plant tissue, yet M-HBsAg appeared to be approximately 1.5–2 times more stable than L-HBsAg. The results of the study provide indications concerning the preparation of two other constituents, next to S-HBsAg, for a plant-derived prototype oral tri-component vaccine against hepatitis B

PDE8 Regulates Rapid Teff Cell Adhesion and Proliferation Independent of ICER

BACKGROUND: Abolishing the inhibitory signal of intracellular cAMP by phosphodiesterases (PDEs) is a prerequisite for effector T (Teff) cell function. While PDE4 plays a prominent role, its control of cAMP levels in Teff cells is not exclusive. T cell activation has been shown to induce PDE8, a PDE isoform with 40- to 100-fold greater affinity for cAMP than PDE4. Thus, we postulated that PDE8 is an important regulator of Teff cell functions. METHODOLOGY/PRINCIPAL FINDINGS: We found that Teff cells express PDE8 in vivo. Inhibition of PDE8 by the PDE inhibitor dipyridamole (DP) activates cAMP signaling and suppresses two major integrins involved in Teff cell adhesion. Accordingly, DP as well as the novel PDE8-selective inhibitor PF-4957325-00 suppress firm attachment of Teff cells to endothelial cells. Analysis of downstream signaling shows that DP suppresses proliferation and cytokine expression of Teff cells from Crem-/- mice lacking the inducible cAMP early repressor (ICER). Importantly, endothelial cells also express PDE8. DP treatment decreases vascular adhesion molecule and chemokine expression, while upregulating the tight junction molecule claudin-5. In vivo, DP reduces CXCL12 gene expression as determined by in situ probing of the mouse microvasculature by cell-selective laser-capture microdissection. CONCLUSION/SIGNIFICANCE: Collectively, our data identify PDE8 as a novel target for suppression of Teff cell functions, including adhesion to endothelial cells

Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease

Bacterial and viral infections have long been implicated in pathogenesis and progression of multiple sclerosis (MS). Incidence and severity of its animal model experimental autoimmune encephalomyelitis (EAE) can be enhanced by concomitant administration of pertussis toxin (PTx), the major virulence factor of Bordetella pertussis. Its adjuvant effect at the time of immunization with myelin antigen is attributed to an unspecific activation and facilitated migration of immune cells across the blood brain barrier into the central nervous system (CNS). In order to evaluate whether recurring exposure to bacterial antigen may have a differential effect on development of CNS autoimmunity, we repetitively administered PTx prior to immunization. Mice weekly injected with PTx were largely protected from subsequent EAE induction which was reflected by a decreased proliferation and pro-inflammatory differentiation of myelin-reactive T cells. Splenocytes isolated from EAE-resistant mice predominantly produced IL-10 upon re-stimulation with PTx, while non-specific immune responses were unchanged. Longitudinal analyses revealed that repetitive exposure of mice to PTx gradually elevated serum levels for TGF-β and IL-10 which was associated with an expansion of peripheral CD4+CD25+FoxP3+ regulatory T cells (Treg). Increased frequency of Treg persisted upon immunization and thereafter. Collectively, these data suggest a scenario in which repetitive PTx treatment protects mice from development of CNS autoimmune disease through upregulation of regulatory cytokines and expansion of CD4+CD25+FoxP3+ Treg. Besides its therapeutic implication, this finding suggests that encounter of the immune system with microbial products may not only be part of CNS autoimmune disease pathogenesis but also of its regulation