A novel recombinant antibody specific to full-length stromal derived factor-1 for potential application in biomarker studies

Background: Stromal derived factor-1α (SDF-1α/CXCL12) is a chemokine that is up-regulated in diseases characterised by tissue hypoxia, including myocardial infarction, ischaemic cardiomyopathy and remote ischaemic conditioning (RIC), a technique of cyclical, non-injurious ischaemia applied remote from the heart that protects the heat from lethal ischaemia-reperfusion injury. Accordingly, there is considerable interest in SDF-1α as a potential biomarker of such conditions. However, SDF-1α is rapidly degraded and inactivated by dipeptidyl peptidase 4 and other peptidases, and the kinetics of intact SDF-1α remain unknown. Methods & results: To facilitate investigation of full-length SDF-1α we established an ELISA using a novel recombinant human antibody we developed called HCI.SDF1. HCI.SDF1 is specific to the N-terminal sequence of all isoforms of SDF-1 and has a comparable KD to commercially available antibodies. Together with a detection antibody specific to the α-isoform, HCI.SDF1 was used to specifically quantify full-length SDF-1α in blood for the first time. Using RIC applied to the hind limb of Sprague-Dawley rats or the arms of healthy human volunteers, we demonstrate an increase in SDF-1α using a commercially available antibody, as previously reported, but an unexpected decrease in full-length SDF-1α after RIC in both species. Conclusions: We report for the first time the development of a novel recombinant antibody specific to fulllength SDF-1. Applied to RIC, we demonstrate a significant decrease in SDF-1α that is at odds with the literature and suggests a need to investigate the kinetics of full-length SDF-1α in conditions characterised by tissue hypoxia

The Role of the Equine Herpesvirus Type 1 (EHV-1) US3-Encoded Protein Kinase in Actin Reorganization and Nuclear Egress

The serine-threonine protein kinase encoded by US3 gene (pUS3) of alphaherpesviruses was shown to modulate actin reorganization, cell-to-cell spread, and virus egress in a number of virus species. However, the role of the US3 orthologues of equine herpesvirus type 1 and 4 (EHV-1 and EHV-4) has not yet been studied. Here, we show that US3 is not essential for virus replication in vitro. However, growth rates and plaque diameters of a US3-deleted EHV-1 and a mutant in which the catalytic active site was destroyed were significantly reduced when compared with parental and revertant viruses or a virus in which EHV-1 US3 was replaced with the corresponding EHV-4 gene. The reduced plaque sizes were consistent with accumulation of primarily enveloped virions in the perinuclear space of the US3-negative EHV-1, a phenotype that was also rescued by the EHV-4 orthologue. Furthermore, actin stress fiber disassembly was significantly more pronounced in cells infected with parental EHV-1, revertant, or the recombinant EHV-1 expressing EHV-4 US3. Finally, we observed that deletion of US3 in EHV-1 did not affect the expression of adhesion molecules on the surface of infected cells

A NEXT GENERATION OF INNOVATION MODELS? AN INTEGRATION OF THE INNOVATION PROCESS MODEL BIG PICTURE © TOWARDS THE DIFFERENT GENERATIONS OF MODELS

The competition on every market grows harder and harder every year. Innovation is seen by most companies as the only way to survive. For finding good innovations, innovation processes are needed to implement within the firm. This paper deals with the generations of those models. The first part of the paper lists the different generations described in the literature. In the second part the BIG Picture © model created by Dipl.-Ing. Dr. Lercher is introduced and compared to the criteria found in the described models. Therefor the aim of this paper is to give the reader an overview of the existing models and an understanding of the classified model. The estimated results were a classification in the current generation. However, the model shows additional criteria which have not been set by any of the review authors. The point, if this model is still a sixth generation model or already a seventh generation model, was let open for discussion in this paper. Methodology includes an analyses of the described generations of the most frequent cited authors and an evaluation of the new model

An investigation into the role of the CXCR7 Chemokine receptor in acute myocardial infarction and angiogenesis

Introduction: SDF-1α is a chemoattractant cytokine that can deliver both acute and chronic cardioprotective benefits to the heart. Although CXCR4 has been viewed as a main receptor for SDF-1α, a secondary receptor, CXCR7, has emerged as an important mediator of SDF-1α signalling. Interestingly, endothelial CXCR7 has been found to promote regeneration and ameliorate fibrosis in various tissues and organs; however, its exact role in ischaemic disease has yet to be determined. Therefore, we sought to examine the expression and function of CXCR7 in cardiovascular tissues, focusing on its potential as a novel cardioprotective strategy. Methods: RNAscope in situ hybridization, western blotting and flow cytometry were used to investigate expression and function of CXCR7 on endothelial cell lines, isolated mouse endothelial cells, and in the whole mouse heart. We examined CXCR7 downstream signalling pathways in presence and absence of CXCR7 agonists TC14012 and VUF11207 fumarate, as well as the effects of the CXCR7 agonists on endothelial cell migration and acute ischaemia-reperfusion injury. Results: CXCR7 is expressed in the adult mouse heart and in the endothelial cell lines MCEC and HUVEC. Most CXCR7 protein in the endothelial cells was observed to be intracellular under basal conditions. In line with this expression profile, exposure to CXCR7 agonists failed to activate cardioprotective protein kinases ERK1/2 and PI3K/Akt. Moreover, VUF11207 did not ameliorate acute ischaemia-reperfusion injury, whereas the role of both CXCR7 agonists in migration and angiogenesis is less clear. Conclusions: CXCR7 is expressed in the mouse vascular endothelium, but its role in activating cardioprotective signalling pathways, as well as its overall contribution to cardioprotection is unclear. Activation of the CXCR7 receptor does not appear to be a viable acute cardioprotective strategy in mice

Strategic Foresight Capability and its Impact on Firm Performance: A systematic, AI-based Literature Review

Strategic foresight is a growing field that attracts scholars aiming to reduce the uncertainty of volatile business environments. However, the field must address crucial challenges to advance theory and practice. To achieve this, the thesis presents a systematic, AI-based literature review that structures the foresight field, displays the status quo, and offers research trajectories. A sample of 243 journal-published articles is analyzed to create an organizing framework as well as provide narrative syntheses on foresight capability and its impact on firm performance. This analysis points out that foresight research often lacks theoretical foundations, mixes epistemological dimensions, and does not work toward a shared objective. Still, six research themes and their connections were identified for an organizing framework. Further, the review points out capabilities for successful foresight: Distinct processual and contextual capabilities developed in accordance with a firm’s environment can ensure success. Lastly, the paper emphasizes that “successful foresight” manifests in practice through a positive impact on strategic, organizational, and performance outcomes. Those findings support the efforts of establishing foresight in management studies and improving academic progress. Keywords: Strategic foresight; Firm performance; Foresight capabilities; Literature review; Organizing framework.Strategic foresight is a growing field that attracts scholars aiming to reduce the uncertainty of volatile business environments. However, the field must address crucial challenges to advance theory and practice. To achieve this, the thesis presents a systematic, AI-based literature review that structures the foresight field, displays the status quo, and offers research trajectories. A sample of 243 journal-published articles is analyzed to create an organizing framework as well as provide narrative syntheses on foresight capability and its impact on firm performance. This analysis points out that foresight research often lacks theoretical foundations, mixes epistemological dimensions, and does not work toward a shared objective. Still, six research themes and their connections were identified for an organizing framework. Further, the review points out capabilities for successful foresight: Distinct processual and contextual capabilities developed in accordance with a firm’s environment can ensure success. Lastly, the paper emphasizes that “successful foresight” manifests in practice through a positive impact on strategic, organizational, and performance outcomes. Those findings support the efforts of establishing foresight in management studies and improving academic progress. Keywords: Strategic foresight; Firm performance; Foresight capabilities; Literature review; Organizing framework

Crosslinguistic Image Schema Differential Hypothesis Clarifies Non-Prototypical and Polysemous Spatial Preposition ‘on’ for L2 Learners

A key question for linguistics involves how to determine and account for expressions of non-prototypical spatial relationships between languages. To address this issue, Crosslinguistic Image Schema Differential (CISD) hypothesis is introduced to examine various uses of the English preposition on produced by L2 (second language) learners. Data collection consisted of a grammar test designed to elicit and measure participants’ knowledge of the English preposition on by completing cloze sentences in English, translating these sentences into the L1 (first language), and then drawing visual images of the sentences presented as redescriptions of perceptual events, i.e., image schemas. The most remarkable findings were that two space-relational types (‘encirclement with contact’ and ‘at an edge’) and one image schema (‘concave surface’) were almost completely lacking in the Japanese learners of English (JLEs) who participated in this study. This investigation indicates that simple explicit explanations are possible utilizing the CISD hypothesis.アクセプト後にアブストラクトの変更あり

Pleiotropic and epistatic interactions between stillbirth and calving ease in cattle

Pleiotropic and epistatic interactions were analyzed for stillbirth and calving ease in Fleckvieh cattle, with deregressed breeding values from 7384 bulls used as phenotypes. The genotype data consisted of 41,884 SNPs after quality control. A multivariate linear regression approach was used to obtain pleiotropic and epistatic effects using the CAPE package in R. Total of five regions on chromosomes 6, 14, 17 and 21 showed evidence of pleiotropic interaction. The genes in these significant regions were also relevant to the two phenotypes of interest, such as PLAG1 affecting growth and height, XKR4 affecting rump thickness and insulin levels, ELMOD2 connected to immune response, UCP1 connected to thermoregulation and UBE3A connected to the Prader-Willi syndrome. The results for epistatic effects were less convincing, although they identified connections to possible regulatory genes within chromosome 21

L2 Learners’ Acquisition of the Preposition to : Prototypical and Polysemous Features

This study examined the effects of instruction on the development of the English preposition to in a quasi-experimental setting with intermediate-level Japanese learners of English. Grammar tests were utilized to measure prepositional accuracies to understand the general effects of the treatment sessions that focused on developing knowledge of the preposition to. These tests were also used to verify if the prototypical feature of to (i.e., indicating an endpoint) and polysemous functions (i.e., spatial, temporal, and abstract) were correlated with changes in accuracies before and after the treatment sessions. Results of this investigation revealed that at the initial stage of this experiment there was little evidence that the notion of the prototypical meaning of to in the targeted items was understood, nor were these learners cognizant of the polysemy of the preposition to across spatial, temporal, or abstract contexts. Allowing for lexical substitution for the preposition to with before or until in the grammar tests, more temporal items could be correctly answered indicating a distinction between cognitive factors that may influence processing of the context, and the shared semantic properties of to, before, and until. After the treatment sessions, all targeted items reached very high accuracies in the post-tests for spatial and temporal scenes showing that learning effects could be maintained beyond the period of treatment. Abstract usages, on the other hand, had a lower level of achievement with a higher rate of attrition after the treatment. The general pedagogical implications of these findings suggest that the prototypical features of prepositions should be taught taking into account polysemy and various other factors such as semantic choice, cognitive features, developmental stages and systematicity, as they may affect explicit learning, retention, and implicit usage of prepositions