Long Term Potentiation (LTP) and Long Term Depression (LTD) Cause Differential Spatial Redistribution of the Synaptic Vesicle Protein Synaptophysin in the Middle Molecular Layer of the Dentate Gyrus in Rat Hippocampus

The presynaptic modifications that accompany long-term changes in synaptic plasticity are still not fully understood. Synaptophysin is a major synaptic vesicle protein involved in neurotransmitter release. We have used quantitative electron microscopy to study synaptophysin (Syn) immunolabelling in the hippocampus of adult rats 24h after induction in vivo of long term potentiation (LTP), and long term depression (LTD). Electrodes were implanted chronically in hippocampus with stimulation at either the medial (MPP) or lateral perforant path (LPP). 24h following induction of LTP or LTD rats were rapidly perfusion fixed and hippocampal tissue processed to electron microscopy via freeze substitution method. Anti-synaptophysin post-embedding immunolabelling was performed and tissue was imaged in the middle molecular layer (MML) of the dentate gyrus. There was a significant decrease in number of Syn labelled vesicles per unit area of bouton after LTP, but not LTD. An analysis of the spatial distribution of Syn labelled synaptic vesicles showed an increase in nearest neighbour distances, more so in the LTP than the LTD group, which is consistent with the overall decrease of Syn after LTP. These data are in agreement with the suggestion that Syn is involved in clathrin-dependent and “kiss and run” endocytosis which occurs perisynaptically. Thus, an increase in release of neurotransmitter and in consequence endocytosis would be consistent with an increased active zone distance for vesicles containing Syn

The interplay of product modularity, service types, and servitization depth on firm performance:a moderated mediation model

The servitization literature has explored the role that product modularity plays in supporting service design and delivery. Importantly, product modularity has the potential to aid manufacturers in providing customized solutions on a larger scale, thereby strengthening firm performance. However, despite the prospective benefits of product modularity, manufacturers also need considerable servitization depth, which comprises service orientation, resources, and delivery systems, to provide services in a cost-effective manner. Taking this into account, the study both theoretically articulates and empirically tests relationships among product modularity, servitization depth, service types, and firm performance, employing a moderated mediation model. Using survey data collected from 204 manufacturers in the UK and German, the findings indicate that product modularity exerts a positive influence on firm performance, with servitization depth acting as a mediating factor. The mediation effect of servitization depth on the correlation between product modularity and firm performance was found to fluctuate based on the service types offered by the manufacturer. This study adds to the existing literature on servitization and the role of product modularity and servitization depth in achieving superior firm performance

Cost-effectiveness of extended-release niacin/laropiprant added to a stable simvastatin dose in secondary prevention patients not at cholesterol goal in Germany

Coronary heart disease (CHD) remains the leading cause of death in Germany despite statin use to reduce low-density lipoprotein cholesterol (LDL-C) levels; improving lipids beyond LDL-C may further reduce cardiovascular risk. A fixed-dose combination of extended-release niacin (ERN) with laropiprant (LRPT) provides comprehensive lipid management. We adapted a decision-analytic model to evaluate the economic value (incremental cost-effectiveness ratio [ICER] in terms of costs per life-years gained [LYG]) of ERN/LRPT 2 g over a lifetime in secondary prevention patients in a German setting. Two scenarios were modelled: (1) ERN/LRPT 2 g added to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 40 mg; (2) adding ERN/LRPT 2 g compared with titration to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 20 mg. In both scenarios, adding ERN/LRPT was cost-effective relative to simvastatin monotherapy at a commonly accepted threshold of €30,000 per LYG; ICERs for ERN/LRPT were €13,331 per LYG in scenario 1 and €17,684 per LYG in scenario 2. Subgroup analyses showed that ERN/LRPT was cost-effective in patients with or without diabetes, patients aged ≤65 or >65 years and patients with low baseline high-density lipoprotein cholesterol levels; ICERs ranged from €10,342 to €15,579 in scenario 1, and from €14,081 to €20,462 in scenario 2. In conclusion, comprehensive lipid management with ERN/LRPT 2 g is cost-effective in secondary prevention patients in Germany who have not achieved LDL-C goal with simvastatin monotherapy

The Peculiar Motions of Early-Type Galaxies in Two Distant Regions. I. Cluster and Galaxy Selection

The EFAR project is a study of 736 candidate elliptical galaxies in 84 clusters lying in two regions, toward Hercules-Corona Borealis and Perseus-Pisces-Cetus, at distances cz ~ 6000-15,000 km s^-1^. In this paper (the first of a series), we present an introduction to the EFAR project and describe in detail the selection of the clusters and galaxies in our sample. Fundamental data for the galaxies and clusters are given, including accurate new positions for each galaxy and redshifts for each cluster. The galaxy selection functions are determined by using diameters measured from Schmidt sky survey images for 2185 galaxies in the cluster fields. Future papers in this series will present the spectroscopic and photometric observations of this sample, investigate the properties of the fundamental plane for elliptical galaxies, and determine the large- scale peculiar velocity fields in these two regions of the universe

Testing service infusion in manufacturing through machine learning techniques:Looking back and forward

PurposeResponding to calls for deeper analysis of the conceptual foundations of service infusion in manufacturing, this paper examines the underlying assumptions that: (i) manufacturing firms incorporating services follow a pathway, moving from pure-product to pure-service offerings, and (ii) profits increase linearly with this process. We propose that these assumptions are inconsistent with the premises of behavioural and learning theories.Design/methodology/approachMachine learning algorithms are applied to test whether a successive process, from a basic to a more advanced offering, creates optimal performance. The data were gathered through two surveys administered to USA manufacturing firms in 2021 and 2023. The first included a training sample comprising 225 firms, whilst the second encompassed a testing sample of 105 firms.FindingsAnalysis shows that following the base-intermediate-advanced services pathway is not the best predictor of optimal performance. Developing advanced services and then later adding less complex offerings supports better performance.Practical implicationsManufacturing firms follow heterogeneous pathways in their service development journey. Non-servitised firms need to carefully consider their contextual conditions when selecting their initial service offering. Starting with a single service offering appears to be a superior strategy over providing multiple services.Originality/valueThe machine learning approach is novel to the field and captures the key conditions for manufacturers to successfully servitise. Insight is derived from the adoption and implementation year datasets for 17 types of services described in previous qualitative studies. The methods proposed can be extended to assess other process-based models in related management fields (e.g., sand cone)

Unpacking the relationship between digital capabilities, services capabilities, and firm financial performance: A moderated mediation model

Extant research exploring the relationship between servitization, digitalization, and firm financial and market performance provides valuable insights, but yields inconsistent and inconclusive results. This study argues that these inconsistencies arise from the ambiguous nature of servitization. Prior research have operationalized servitization as a business model (service type) or a set of service capabilities, treating these distinct constructs interchangeably. This study, therefore, advanced the proposition that both service capabilities and service type need to be incorporated into an integrated framework. To test this, the research develops and empirically validates a moderated-mediation model for the relationship between digitalization, service type (moderator), service capabilities (mediator) and firm financial and market performance using data from 204 manufacturing firms. The results indicate that service capabilities positively mediate the relationship between digitalization and firm financial and market performance. The moderating effect of the service type on service capabilities and firm financial and market performance are more pronounced for services supporting customers than services supporting products. The findings underline the imperative for manufacturers to develop their digital capabilities to enhance their service capabilities, irrespective of the type of services they offered. The findings contribute by enriching our understanding of the relationship between servitization, digitalization and firm performance.Engineering and Physical Science Research Council through the Digitally Enhanced Advanced Services NetworkPlus funded by grant ref. EP/R044937/

Genotypic Variation in a Foundation Tree (\u3ci\u3ePopulus tremula\u3c/i\u3e L.) Explains Community Structure of Associated Epiphytes

Community genetics hypothesizes that within a foundation species, the genotype of an individual significantly influences the assemblage of dependent organisms. To assess whether these intra-specific genetic effects are ecologically important, it is required to compare their impact on dependent organisms with that attributable to environmental variation experienced over relevant spatial scales. We assessed bark epiphytes on 27 aspen (Populus tremula L.) genotypes grown in a randomized experimental array at two contrasting sites spanning the environmental conditions from which the aspen genotypes were collected. We found that variation in aspen genotype significantly influenced bark epiphyte community composition, and to the same degree as environmental variation between the test sites. We conclude that maintaining genotypic diversity of foundation species may be crucial for conservation of associated biodiversity