Integrating Problem Solvers from Analogous Markets in New Product Ideation

Who provides better inputs to new product ideation tasks: problem solvers with expertise in the area for which new products are to be developed, or problem solvers from "analogous" markets that are distant but share an analogous problem or need? Conventional wisdom appears to suggest that target market expertise is indispensable, which is why most managers searching for new ideas tend to stay within their own market context even when they do search outside their firms' boundaries. However, in a unique symmetric experiment that isolates the effect of market origin, we find evidence for the opposite: Although solutions provided by problem solvers from analogous markets show lower potential for immediate use, they demonstrate substantially higher levels of novelty. Also compared to established novelty drivers, this effect appears highly relevant from a managerial perspective: we find that including problem solvers from analogous markets vs. the target market accounts for almost two thirds of the well-known effect of involving lead users instead of average problem solvers. This effect is further amplified when the analogous distance between the markets increases, i.e., when searching in far vs. near analogous markets. Finally, results indicate that the analogous market effect is particularly strong in the upper tail of the novelty distribution, which again underscores the effect's practical importance. All this suggests that it might pay to systematically search across firm-external sources of innovation that were formerly out of scope for most managers. (authors' abstract

The value of scientific knowledge dissemination for scientists:A value capture perspective

Scientific knowledge dissemination is necessary to collaboratively develop solutions to today’s challenges among scientific, public, and commercial actors. Building on this, recent concepts (e.g., Third Mission) discuss the role and value of different dissemination mechanisms for increasing societal impact. However, the value individual scientists receive in exchange for disseminating knowledge differs across these mechanisms, which, consequently, affects their selection. So far, value capture mechanisms have mainly been described as appropriating monetary rewards in exchange for scientists’ knowledge (e.g., patenting). However, most knowledge dissemination activities in science do not directly result in capturing monetary value (e.g., social engagement). By taking a value capture perspective, this article conceptualizes and explores how individual scientists capture value from disseminating their knowledge. Results from our qualitative study indicate that scientists’ value capture consists of a measureable objective part (e.g., career promotion) and a still unconsidered subjective part (e.g., social recognition), which is perceived as valuable due to scientists’ needs. By advancing our understanding of value capture in science, scientists’ selection of dissemination mechanisms can be incentivized to increase both the value captured by themselves and society. Hence, policy makers and university managers can contribute to overcoming institutional and ecosystem barriers and foster scientists’ engagement with society

Multi-disciplinary perspectives on citizen science – synthesizing five “paradigms” of citizen involvement

Research on Open Innovation in Science (OIS) investigates how open and collaborative practices influence the scientific and societal impact of research. Since 2019, the OIS Research Conference has brought together scholars and practitioners from diverse backgrounds to discuss OIS research and case examples. In this meeting report, we describe four session formats that have allowed our multi-disciplinary community to have productive discussions around opportunities and challenges related to citizen involvement in research. However, these sessions also highlighted the need for a better understanding of the underlying rationales of citizen involvement in an increasingly diverse project landscape. Building on the discussions at the 2023 and prior editions of the conference, we outline a conceptual framework of five crowd paradigms and present an associated tool that help understand how citizen involvement in particular projects can help advance science. We illustrate this tool using cases presented at the 2023 conference and discuss how it can facilitate discussions at future conferences as well as guide future research and practice in citizen science

Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver

Activation of the constitutive androstane receptor (CAR) may induce adaptive but also adverse effects in rodent liver, including the induction of drug-metabolizing enzymes, transient hepatocellular proliferation, and promotion of liver tumor growth. Human relevance of CAR-related adverse hepatic effects is controversially debated. Here, we used the chimeric FRG-KO mouse model with livers largely repopulated by human hepatocytes, in order to study human hepatocytes and their response to treatment with the model CAR activator phenobarbital (PB) in vivo. Mice received an intraperitoneal injection with 50 mg/kg body weight PB or saline, and were sacrificed after 72–144 h. Non-repopulated FRG-KO mice were used as additional control. Comprehensive proteomics datasets were generated by merging data obtained by targeted as well as non-targeted proteomics approaches. For the first time, a novel proteomics workflow was established to comparatively analyze the effects of PB on human and murine proteins within one sample. Analysis of merged proteome data sets and bioinformatics data mining revealed comparable responses in murine and human hepatocytes with respect to nuclear receptor activation and induction of xenobiotic metabolism. By contrast, activation of MYC, a key regulator of proliferation, was predicted only for mouse but not human hepatocytes. Analyses of 5-bromo-2′-deoxyuridine incorporation confirmed this finding. In summary, this study for the first time presents a comprehensive proteomic analysis of CAR-dependent effects in human and mouse hepatocytes from humanized FRG-KO mice. The data support the hypothesis that PB does induce adaptive metabolic responses, but not hepatocellular proliferation in human hepatocytes in vivo.publishedVersio

µFBI: A Microfluidic Bead-Based Immunoassay for Multiplexed Detection of Proteins from a µL Sample Volume

BACKGROUND: Over the last ten years, miniaturized multiplexed immunoassays have become robust, reliable research tools that enable researchers to simultaneously determine a multitude of parameters. Among the numerous analytical protein arrays available, bead-based assay systems have evolved into a key technology that enables the quantitative protein profiling of biological samples whilst requiring only a minimal amount of sample material. METHODOLOGY/PRINCIPAL FINDINGS: A microfluidic bead-based immunoassay, µFBI, was developed to perform bead-based multiplexed sandwich immunoassays in a capillary. This setup allows the simultaneous detection of several parameters and only requires 200 ng of tissue lysate in a 1 µL assay volume. In addition, only 1 µL of detection antibodies and 1 µL of the reporter molecule Streptavidin-Phycoerythrin were required. The µFBI was used to compare the expression of seven receptor tyrosine kinases and their degree of tyrosine phosphorylation in breast cancer tissue and in normal tissue lysates. The total amount of HER-2, as well the degree of tyrosine phosphorylation was much higher in breast cancer tissue than in normal tissue. µFBI and a standard bead-based assay led to identical protein expression data. Moreover, it was possible to reduce the quantity of sample material required by a factor of 100 and the quantity of reagents by a factor of 30. CONCLUSIONS/SIGNIFICANCE: The µFBI, microfluidic bead-based immunoassay, allows the analysis of multiple parameters from a very small amount of sample material, such as tumor biopsies or tissue sections

Optimal selection of epitopes for TXP-immunoaffinity mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry (MS) based protein profiling has become one of the key technologies in biomedical research and biomarker discovery. One bottleneck in MS-based protein analysis is sample preparation and an efficient fractionation step to reduce the complexity of the biological samples, which are too complex to be analyzed directly with MS. Sample preparation strategies that reduce the complexity of tryptic digests by using immunoaffinity based methods have shown to lead to a substantial increase in throughput and sensitivity in the proteomic mass spectrometry approach. The limitation of using such immunoaffinity-based approaches is the availability of the appropriate peptide specific capture antibodies. Recent developments in these approaches, where subsets of peptides with short identical terminal sequences can be enriched using antibodies directed against short terminal epitopes, promise a significant gain in efficiency.</p> <p>Results</p> <p>We show that the minimal set of terminal epitopes for the coverage of a target protein list can be found by the formulation as a set cover problem, preceded by a filtering pipeline for the exclusion of peptides and target epitopes with undesirable properties.</p> <p>Conclusions</p> <p>For small datasets (a few hundred proteins) it is possible to solve the problem to optimality with moderate computational effort using commercial or free solvers. Larger datasets, like full proteomes require the use of heuristics.</p

Control of immediate early gene expression by CPEB4-repressor complex-mediated mRNA degradation

BACKGROUND: Cytoplasmic polyadenylation element-binding protein 4 (CPEB4) is known to associate with cytoplasmic polyadenylation elements (CPEs) located in the 3' untranslated region (UTR) of specific mRNAs and assemble an activator complex promoting the translation of target mRNAs through cytoplasmic polyadenylation. RESULTS: Here, we find that CPEB4 is part of an alternative repressor complex that mediates mRNA degradation by associating with the evolutionarily conserved CCR4-NOT deadenylase complex. We identify human CPEB4 as an RNA-binding protein (RBP) with enhanced association to poly(A) RNA upon inhibition of class I histone deacetylases (HDACs), a condition known to cause widespread degradation of poly(A)-containing mRNA. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis using endogenously tagged CPEB4 in HeLa cells reveals that CPEB4 preferentially binds to the 3'UTR of immediate early gene mRNAs, at G-containing variants of the canonical U- and A-rich CPE located in close proximity to poly(A) sites. By transcriptome-wide mRNA decay measurements, we find that the strength of CPEB4 binding correlates with short mRNA half-lives and that loss of CPEB4 expression leads to the stabilization of immediate early gene mRNAs. Akin to CPEB4, we demonstrate that CPEB1 and CPEB2 also confer mRNA instability by recruitment of the CCR4-NOT complex. CONCLUSIONS: While CPEB4 was previously known for its ability to stimulate cytoplasmic polyadenylation, our findings establish an additional function for CPEB4 as the RNA adaptor of a repressor complex that enhances the degradation of short-lived immediate early gene mRNAs