3,757 research outputs found

    THE ROLE OF PROGESTERONE RECEPTOR MEMBRANE COMPONENT 1 IN RECEPTOR TRAFFICKING AND DISEASE

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    The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor (EGFR) in cancer cells, and we reviewed multiple signaling-associated pathways that are important in trafficking wild-type and mutant EGFR. To better understand the potential of PGRMC1 in receptor tyrosine kinase trafficking, we extended our research to the insulin receptor (IR). Changes in insulin signaling have been linked to multiple diseases, because IR plays a key role in glucose metabolism, cellular survival and proliferation. We found PGRMC1 to co-precipitate with IR in cancer cells and in an adipose model system. PGRMC1 increased IR plasma membrane levels in multiple cancer cell lines, and was also found to increase plasma membrane levels of two glucose transporters. Treatment with a PGRMC1 ligand significantly increased IR levels in human adipocytes. Moreover, we demonstrate that both insulin binding and glucose uptake are dependent on PGRMC1

    Implementation of Change to Audits and Inspections Using Action Research

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    The audits and inspections process is a critical component related to a pharmaceutical firm’s compliance in the industry. To be out of compliance has significant ramifications both on the safety and purity of the firm’s products and its viability in the industry. Such firms are routinely audited by boards of health and customers that purchase the firm’s products to ensure they are in compliance with expected standards. The success of hosting the audits and inspection program is the first line of defense in demonstrating compliance. To succeed at these audits and inspections changing with the times is a necessity. The implementation of change in an organization is fraught with challenges. Issues such determining who in the organization are the right people to discover, develop, and diffuse change is a complex process for management. This study will describe how the use of Liberating Structures and coaching were used to change the audits and inspection process for a major pharmaceutical firm. The changes are evaluated through the lens of Adaptive Space and the use of action research to integrate theory and action with the goal of answering the following questions: How might I get the right people on the team to implement a digital auditing process? How might I implement a digital auditing process? In the time involved with the completion of this action research study, COVID-19 hit. This led me to another question: What modifications to the auditing process must be made as a result of COVID-19, how can I modify the auditing approach to incorporate site restrictions The outcome of this effort transformed the auditing process at the firm and was implemented at the firm’s sites worldwide

    Experimental Evidence for Quantum Structure in Cognition

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    We proof a theorem that shows that a collection of experimental data of membership weights of items with respect to a pair of concepts and its conjunction cannot be modeled within a classical measure theoretic weight structure in case the experimental data contain the effect called overextension. Since the effect of overextension, analogue to the well-known guppy effect for concept combinations, is abundant in all experiments testing weights of items with respect to pairs of concepts and their conjunctions, our theorem constitutes a no-go theorem for classical measure structure for common data of membership weights of items with respect to concepts and their combinations. We put forward a simple geometric criterion that reveals the non classicality of the membership weight structure and use experimentally measured membership weights estimated by subjects in experiments to illustrate our geometrical criterion. The violation of the classical weight structure is similar to the violation of the well-known Bell inequalities studied in quantum mechanics, and hence suggests that the quantum formalism and hence the modeling by quantum membership weights can accomplish what classical membership weights cannot do.Comment: 12 pages, 3 figure

    Meaning-focused and Quantum-inspired Information Retrieval

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    In recent years, quantum-based methods have promisingly integrated the traditional procedures in information retrieval (IR) and natural language processing (NLP). Inspired by our research on the identification and application of quantum structures in cognition, more specifically our work on the representation of concepts and their combinations, we put forward a 'quantum meaning based' framework for structured query retrieval in text corpora and standardized testing corpora. This scheme for IR rests on considering as basic notions, (i) 'entities of meaning', e.g., concepts and their combinations and (ii) traces of such entities of meaning, which is how documents are considered in this approach. The meaning content of these 'entities of meaning' is reconstructed by solving an 'inverse problem' in the quantum formalism, consisting of reconstructing the full states of the entities of meaning from their collapsed states identified as traces in relevant documents. The advantages with respect to traditional approaches, such as Latent Semantic Analysis (LSA), are discussed by means of concrete examples.Comment: 11 page

    Greened out: mitigating the impacts of eco-gentrification through community dialogue

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    Cities are increasingly employing green infrastructure, defined as a network of multi-functional open spaces within cities and between cities – including green corridors, green streets, formal parks and street trees – to promote resilience and provide clean air, flood protection and erosion control. Yet there is a growing link between these efforts and rising property values and – in some cities, including Washington, DC – displacement. This history of greening and subsequent displacement can hinder successful green-infrastructure implementation. The geographical areas with the greatest need for these amenities and other resilience strategies are often those with high concentrations of low-income, racial minorities who have traditionally been disenfranchised from local planning and development processes due to a lack of knowledge and limited access, as well as institutional racism. In these areas, the perception of green infrastructure is that of something planned by others, for others, with little direct benefit to the community. This exploratory research, which examines lived experiences, builds upon the quantitative documentation of gentrification and demographic shifts in Washington, DC. Through a series of listening sessions, the study explores residents’ experiences of green infrastructure, gentrification and civic engagement in their community. The study uncovers ways in which policymakers and planners can increase support for and the success of green-infrastructure implementation by amplifying the voices of stakeholders, including communities with vulnerable populations, in the planning process

    Deformation and Flexibility Equations for Idealized ARIS Umbilicals, Under Planar End-Loading Conditions

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    The International Space Station (ISS) relies on the Active Rack Isolation System (ARIS) as the central component of an integrated, station-wide strategy to isolate microgravity space-science experiments. ARIS uses electromechanical actuators to isolate an International Standard Payload Rack (ISPR) from disturbances due to the motion of the ISS. Disturbances to microgravity experiments on ARIS-isolated racks are primarily transmitted via the ARIS power and vacuum umbilicals. Recent experimental tests indicate that these umbilicals resonate at frequencies outside the ARIS controller's bandwidth. at levels of potential concern for certain microgravity experiments. Reduction in the umbilical resonant frequencies could help to address this issue. This paper develops equations for the in-plane deflections and flexibilities of an idealized umbilical (thin, flexible, cantilever beam) under end-point, in-plane loading (inclined-force and moment). The effect of gravity is neglected due to the on:orbit application. The analysis assumes an initially straight. cantilevered umbilical with uniform cross-section. which undergoes large deflections with no plastic deformation, such that the umbilical terminus remains in a single quadrant and the umbilical slope changes monotonically. The analysis is applicable to the ARIS power and vacuum umbilicals. under the indicated assumptions

    Embracing Deference

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    A fundamental conceptual problem has long dogged discussions about scientific and other expert evidence in the courtroom. In American law, the problem was most famously posed by Judge Learned Hand, who asked: [H]ow can the jury judge between two statements each founded upon an experience confessedly foreign in kind to their own? It is just because they are incompetent for such a task that the expert is necessary at all. This puzzle, sometimes known as the expert paradox, is quite general. It applies not only to the jury as factfinder, but also to the judge as gate- keeper under the Daubert v. Merrell Dow Pharmaceuticals, Inc. regime and Federal Rule of Evidence 702. It also applies when there is no jury at all, whether in a bench trial, administrative proceeding, or civil law jurisdiction. When it comes to scientific and other specialized knowledge, legal actors are inevitably non-experts. And if legal actors are faced with the so- called battle of the experts, how are they to decide between the warring experts? After all, to quote Judge Hand again, [i]t is just because they are incompetent for such a task that the expert is necessary at all. As one of us has previously argued, because of this epistemic competency problem, the Daubert approach to expert evidence is a mistake. The solution to the problem of expert evidence is not judicial gatekeeping, but rather to change the substantive question asked of legal actors
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