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Intellectual property reassembly: a novel approach to evaluate R&D collaboration outcomes
No full textResearch and development (R&D) collaboration outcomes have usually been evaluated based on the magnitude of outputs, such as new products, patenting, or productivity growth. However, they have yet to be evaluated based on the various directions of mutual learning between collaborators, which have a long-term impact on the post-partnership technology development of the collaborators. This study proposes a framework that evaluates intellectual property (IP) reassembly, which indicates how a focal firm produces new IP based on its learnings from its R&D partnership, as a novel approach to evaluate R&D collaboration. The proposed approach estimates the degree to which IP reassembly (a focal firm's independent patent applications drawing on co-patents) occurs in the following directions: exploitation of, exploration beyond, or complementary to the pre-partnership capabilities of each collaborator. Within the framework, a focal firm's performance can be compared to that of its partner. The proposed framework is illustrated and validated using the case of partnership between Samsung SDI and BOSCH (2008–2012) in their battery development. We discuss implications for contract design, partnership boundaries, and performance evaluation in the context of R&D collaboration
Mother’s day superstorms: pre- and post-storm evolutionary patterns of ARs 13664/8
No full textIn the week including Mother’s Day 2024, active region (AR) 13664 became superactive when AR 13668 emerged nearby, causing multiple X-class flares and coronal mass ejections, and an increase in activity level similar to that inferred from geomagnetic storms associated with the historic 1859 events. By analyzing both global warped toroids on which the active regions are strung, and active-region-scale magnetic flux and helicity, we find (i) the north and south toroids have nearly identical warped patterns, with mostly longitudinal wave numbers m = 1–3; (ii) in three longitude intervals the north and south toroids were tipped away from each other in latitude, with a longitude phase shift between them, creating locations most prone to AR eruptions; (iii) on an active region scale, vector magnetic fields deviate far from potential fields, and therefore contain large amounts of magnetic “free energy” available for conversion into kinetic energy and high-temperature radiation; (iv) the positive and negative polarities converge toward each other, facilitating reconnection and magnetic energy release; and (v) rapid changes in magnetic helicity, caused by helicity injection from below that creates helicity imbalances. Despite the coarser resolution of GONG magnetograms, the derived global toroids are strikingly similar to those derived from the Solar Dynamics Observatory's Helioseismic and Magnetic Imager. We conclude that the Mother’s Day superstorms were caused by enhanced magnetic complexity occurring due to intricate interactions among multiple active regions emerging at nearly the same locations. This suggests that predicting the locations of magnetically complex active regions, and studying and tracking their eruptive states using different proxy parameters can greatly improve our ability to forecast intense storms, not only hours but potentially weeks in advance
Exogenous activation of the adhesion GPCR ADGRD1/GPR133 protects against bone loss by negatively regulating osteoclastogenesis
No full textAdhesion G protein–coupled receptors (GPCRs) play crucial roles in numerous physiological and pathological conditions. However, the functions of adhesion GPCRs remain poorly understood because of the lack of effective modulators. Here, we used the adhesion GPCR D1 (ADGRD1/GPR133) as a model to unveil a strategy for finding exogenous agonists that target adhesion GPCRs while revealing previously unidentified functions of ADGRD1. We identified the small molecule GL64 as a selective agonist of ADGRD1. GL64 activates ADGRD1 by mimicking the stachel sequence. Using GL64 as a chemical tool, we demonstrated that ADGRD1 negatively regulates bone loss by inhibiting osteoclastogenesis. The cAMP-PKA-NFATC1 pathway was identified as the downstream signaling pathway of ADGRD1 in osteoclasts. Furthermore, administering GL64 prevented bone loss and suppressed osteoclast activity in the osteoporosis mouse model induced by ovariectomy. Our findings provide mechanistic insights into the activation of adhesion GPCRs by exogenous agonists and underscore the therapeutic potential of targeting ADGRD1 in osteoclast-related diseases
Multifaceted regulation of the HOX cluster and its implications in oral cancer
No full textBackground
The hypothesis that aberrant expression of homeobox (HOX) transcription factors contributes to oral cancer progression is gaining prominence. However, the mechanism of regulation involved in the clustered dysregulation of HOX clusters is not clearly known.
Results
Our findings revealed that HOXA and HOXB clusters showed significant locus-specific CpG methylation changes compared with the HOXC and HOXD clusters. The constitutively unmethylated regions identified in the HOXA1, HOXA11, HOXB5, HOXB6, HOXB9, HOXC5, HOXC10 and HOXC11 genes may be associated with open chromatin-mediated gene regulation. The methylation of CpG loci within the intron of HOXB9 may serve as a potential marker for distinguishing patients with premalignant and advanced oral tumors. HOXA5 and HOXC9 showed higher transcription factor-mediated interactions with neighboring HOX genes within and across the clusters. Additionally, HOXB9 and HOXC10 were predicted to directly regulate the G2–M checkpoint and hypoxia pathways. HOXA genes can be post-transcriptionally regulated through an antisense-mediated mechanism involving embedded HOX long noncoding RNAs (lncRNAs). Posterior HOX genes were more highly expressed than anterior HOX genes. The HOXC and HOXD cluster gene expression patterns were similar to those of the embedded lncRNAs. HOXA1, HOXC13 and HOXD10 were significantly correlated with the cancer hallmarks driving oral carcinogenesis.
Conclusion
The functional consequence of HOX genes dysregulation was driven by diverse DNA and RNA epigenetic mechanisms affecting the transcriptional and post-transcriptional regulation contributing to the oral cancer progression
The First General Assembly of Virginia:Deerskin, Ruffs and the View from Tsenacommacah
No full textOn a November evening in 1618, the newly appointed governor of Virginia, George Yeardley, dined with James I at the royal hunting lodge in Newmarket, speaking to the king about his plans to turn Virginia into the English civil society investors had long promised it might become. One of Yeardley’s primary tasks was to inaugurate what has become known as the First General Assembly, held in Jamestown in 1619 in the heart of a region that its Powhatan inhabitants called Tsenacommacah. This article examines the assembly within the context of the Powhatan Chesapeake, examining how English attempts at establishing this meeting, ‘in the nature of a Parliament’, operated within a broader Indigenous political landscape. It considers some of the methodological challenges that historians face when writing about political assemblies in colonised spaces, arguing for the value of approaches that place a greater emphasis on Indigenous sources, knowledge and perspectives. A focus on material culture and archaeological remains, from embroidered deerskins to goffering irons, demonstrates how different claims to authority were tangibly imparted and contested, offering a more expansive archive of seventeenth-century transatlantic political culture
Investigating driver responses to automated vehicles in a bottleneck scenario: The impact of lateral offset and eHMI
No full textThis driving simulator study investigated drivers’ responses to an approaching automated or manual vehicle in a bottleneck scenario. Participants were asked to decide whether to pass through the bottleneck, or yield for the approaching vehicle, across numerous trials. Prior to each trial, they were informed whether the approaching vehicle was an automated vehicle (AV) or a manually driven vehicle (MV). Although participants were told that the MV was controlled by the experimenter using a distributed simulator, both vehicles were actually controlled by the system, and behaved in the same way. The kinematics of the approaching vehicle, such as its yielding behaviour (with or without lateral offset), and the presence of external Human Machine Interfaces (eHMIs, AV only) were manipulated. 40 participants took part in this study. Results indicated that participants’ subjective responses and behaviours did not differ between the AVs and MVs. The approaching vehicle’s lateral offset was seen to be the most influential source of information for participants, followed by information from the eHMI. Participants were more likely to pass through the bottleneck first, and had a shorter decision time, when encountering yielding vehicles with “away offsets”, which involved the vehicle moving away from the road centre line. This condition also led to higher perceived safety, comprehension, and trust ratings. Conversely, drivers were more likely to yield and had a shorter decision time when encountering non-yielding vehicles without any lateral offset. The lateral offset of non-yielding vehicles did not have an impact on drivers’ perceived safety and trust. However, non-yielding with “towards offsets” (towards the centre line) led to a higher comprehension score. Participants also passed through the bottleneck significantly more often and provided higher ratings for perceived safety and trust when the yielding vehicles presented an eHMI. This was regardless of lateral deviation. However, the eHMI only led to a higher rating of comprehension when the AV yielded without an offset. This study shows the value of using lateral offsets to communicate vehicles’ intentions in bottleneck scenarios. While the eHMI could enhance the driver’s understanding of the yielding AV, some participants also noted that it introduced uncertainty. Therefore, the need for eHMI should be further discussed
When the Woman Writes: Screenwriting, Censorship and Style in Sorry, Wrong Number (1948)
No full text‘The Way Enthusiasm Builds’:Frame Amplification and Emotional Reinforcement in Participatory Policymaking
No full textTo create policies about complex environmental challenges, it is vital to involve multiple stakeholders. Whilst research hasshown how emotions may influence multi-stakeholder collaborations, the role of emotions in participatory policymakingis not sufficiently understood. This study focuses on the role of emotions during a series of citizen workshops that feed intourban tree management policies. Specifically, we explore how emotions are related to the deliberation of citizens’ frames(i.e. sensemaking schemata). Our findings demonstrate inherent interconnections between participants’ frames and emo-tions. We identify a chain of mechanisms by which the expression of frames and associated emotions during interactionsled to an intertwined amplification of citizens’ frames and reinforcement of their emotions. We also explain the cases of‘separation’ where this did not occur. Our model extends prior insights into the relationship between frames and emotionsand demonstrates how citizen workshops serve not only to gain citizens’ input into public policies, but also to cultivate theirframes through emotional reinforcement