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The new Directive on Product Liability is hard to overestimate, as it is nothing less than a complete overhaul of the 1985 Product Liability Directive (PLD), which still lies at the heart of EU tort law. One focus of the reform act is the challenge posed by digital transformation. To accommodate the new category of digital devices, the concept of product is widened so as to include software and related services, and the strict ex ante perspective for the finding of product defect is attenuated to account for continued control of the manufacturer post-marketing. Further to broadening the scope of application, the protective perimeter of the Directive is expanded, namely to include data used for private purposes. The second focus of the reform act, of at least equal importance, are changes to the liability regime for products of any kind, regardless of their digital nature or elements. Thus, e-commerce intermediaries such as platforms are ushered into the scope of the Directive as new defendants, alongside manufacturers, importers, and distributors. With a view to quantum, the € 500 retention for property damage had to go, together with the authority of the Member States to impose a cap on liability under the Directive. Unfortunately, there was no time to revisit the foundations of product liability. Thus, the new Directive holds on to the consumer protection gospel of product liability and excludes commercial property from the scope of protection, even though there is no good reason to discriminate against business interests. As before, national law must and will step in to fill in the gaps in Union law, perpetuating the double-track liability systems that the 1985 Directive helped to create. [ABSTRACT FROM AUTHOR]

ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions.

In technology-infused frontline service encounters, human-based service represents a high degree of uncertainty. However, understanding how technology can meet customer demands without undermining the importance of human interaction is crucial for retailers to remain competitive. However, empirical evidence comparing different types of service encounters (technology-facilitated vs. technology-assisted vs. technology-free) is lacking. Building on existing approaches to technology-enabled services, this study aims to extend the understanding of the optimal type of technology infusion and human interaction in the context of customer trust and willingness to pay. Drawing on social interaction theory, emphasizing that technology can influence the nature and quality of interactions between customers and frontline employees, this paper empirically examines different types of service encounters. A quasi-experimental online study (N = 944) was conducted.General results show that technology infusion within the service encounter has a negative impact on customers' trust in the frontline employee, but a positive impact on customers' willingness to pay. Furthermore, a mediating influence of customers' perceptions of the competence of frontline employees can be demonstrated. The results show that customers place more value on a technology-facilitated encounter than on a technology-assisted service. Based on the findings, this paper derives implications for retail managers at various levels. Since the customer's perception of the competence of front-line employees in using a technology is of high relevance to the customer, the retailer should pay more attention to training employees in the use of these technologies in their interactions with customers because of the perception of service competence and other relationship-building criteria such as trust. In addition, the competent use of these technologies and the customer's perception of them can also affect the customer's willingness to pay and thus the success of the business. [ABSTRACT FROM AUTHOR]

BACKGROUND. Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are neoplasms associated with larger nerves that occur sporadically and in the context of schwannomatosis or neurofibromatosis type 2 or 1. Clinical management of N/S HNSTs is challenging, especially for large tumors, and established systemic treatments are lacking. METHODS. We used next-generation sequencing and array-based DNA methylation profiling to determine the clinically actionable genomic and epigenomic landscapes of N/S HNSTs. RESULTS. Whole-exome sequencing within a precision oncology program identified an activating mutation (p.Asp769Tyr) in the catalytic domain of the ERBB2 receptor tyrosine kinase in a patient with schwannomatosis-associated N/S HNST, and targeted treatment with the small-molecule ERBB inhibitor lapatinib led to prolonged clinical benefit and a lasting radiographic and metabolic response. Analysis of a multicenter validation cohort revealed recurrent ERBB2 mutations (p.Leu755Ser, p.Asp769Tyr, p.Val777Leu) in N/S HNSTs occurring in patients who met diagnostic criteria for sporadic schwannomatosis (3 of 7 patients), but not in N/S HNSTs arising in the context of neurofibromatosis (6 patients) or outside a tumor syndrome (1 patient), and showed that ERBB2-mutant N/S HNSTs cluster in a distinct subgroup of peripheral nerve sheath tumors based on genome-wide DNA methylation patterns. CONCLUSION. These findings uncover a key biological feature of N/S HNSTs that may have important diagnostic and therapeutic implications. FUNDING. This work was supported by grant H021 from DKFZ-HIPO, the University Cancer Center Frankfurt, and the Frankfurt Research Funding Clinician Scientist Program., Introduction Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are peripheral nerve sheath tumors that are recognized as a distinct entity by the 2016 update of the World Health Organization (WHO) [...]