Engineered Knottin Peptide Enables Noninvasive Optical Imaging of Intracranial Medulloblastoma

Central nervous system tumors carry grave clinical prognoses due to limited effectiveness of surgical resection, radiation, and chemotherapy. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. We demonstrate that mouse cerebellar medulloblastoma (MB) can be targeted and illuminated with a fluorescent, engineered cystine knot (knottin) peptide that binds with high affinity to α β , α β , and α β integrin receptors. This integrin-binding knottin peptide, denoted EETI 2.5F, was evaluated as a molecular imaging probe in both orthotopic and genetic models of MB. Following tail vein injection, fluorescence arising from dye-conjugated EETI 2.5F was localized to the tumor compared with the normal surrounding brain tissue, as measured by optical imaging. The imaging signal intensity correlated with tumor volume. Due to its unique ability to bind to α β integrin, EETI 2.5F showed superior in vivo and ex vivo brain tumor imaging contrast compared with other engineered integrin-binding knottin peptides and with c(RGDfK), a well-studied integrin-binding peptidomimetic. Next, EETI 2.5F was fused to an antibody fragment crystallizable (Fc) domain (EETI 2.5F-Fc) to determine if a larger integrin-binding protein could also target intracranial brain tumors. EETI 2.5F-Fc, conjugated to a fluorescent dye, illuminated MB following i.v. injection and was able to distribute throughout the tumor parenchyma. In contrast, brain tumor imaging signals were not detected in mice injected with EETI 2.5F proteins containing a scrambled integrin-binding sequence, demonstrating the importance of target specificity. These results highlight the potential of using EETI 2.5F and EETI 2.5-Fc as targeted molecular probes for brain tumor imaging

Identifying Opportunities for Aligning Production and Consumption in the U.S. Fisheries by Considering Seasonality

Seasonality is a natural feature of wild caught fisheries that introduces variation in food supply, and which often is amplified by fisheries management systems. Seasonal timing of landings patterns and linkages to consumption patterns can have a potentially strong impact on income for coastal communities as well as import patterns. This study characterizes the relationship between seasonality in seafood production and consumption in the United States by analyzing monthly domestic fisheries landings and imports and retail sales of farmed and wild seafood from 2017 to 2019. Analyses were conducted for total seafood sales, by product form, by species group, and by region of the United States. The data reveal strong seasonal increases in consumption around December and March. Seasonal increases in consumption in Spring and Summer occurred in parallel with domestic fishing production. Domestic landings vary by region, but most regions have peak fishing seasons between May and October. Alaska has the largest commercial fishery in the United States and seasonal peaks in Alaska (July/August, February/March) strongly influence seasonality in national landings. Misalignment between domestic production and consumption in some seasons and species groups creates opportunities for imports to supplement demand and lost opportunities for domestic producers.publishedVersio

Integrating Life Cycle and Impact Assessments to Map Food's Cumulative Environmental Footprint

Producing food exerts pressures on the environment. Understanding the location and magnitude of food production is key to reducing the impacts of these pressures on nature and people. In this Perspective, Kuempel et al. outline an approach for integrating life cycle assessment and cumulative impact mapping data and methodologies to map the cumulative environmental pressure of food systems. The approach enables quantification of current and potential future environmental pressures, which are needed to reduce the net impact of feeding humanity. © 2020 The AuthorsFeeding a growing, increasingly affluent population while limiting environmental pressures of food production is a central challenge for society. Understanding the location and magnitude of food production is key to addressing this challenge because pressures vary substantially across food production types. Applying data and models from life cycle assessment with the methodologies for mapping cumulative environmental impacts of human activities (hereafter cumulative impact mapping) provides a powerful approach to spatially map the cumulative environmental pressure of food production in a way that is consistent and comprehensive across food types. However, these methodologies have yet to be combined. By synthesizing life cycle assessment and cumulative impact mapping methodologies, we provide guidance for comprehensively and cumulatively mapping the environmental pressures (e.g., greenhouse gas emissions, spatial occupancy, and freshwater use) associated with food production systems. This spatial approach enables quantification of current and potential future environmental pressures, which is needed for decision makers to create more sustainable food policies and practices. © 2020 The Author

Human Resources and the Resource Based View of the Firm

The resource-based view (RBV) of the firm has influenced the field of strategic human resource management (SHRM) in a number of ways. This paper explores the impact of the RBV on the theoretical and empirical development of SHRM. It explores how the fields of strategy and SHRM are beginning to converge around a number of issues, and proposes a number of implications of this convergence

Dynamin impacts homology-directed repair and breast cancer response to chemotherapy

After the initial responsiveness of triple-negative breast cancers (TNBCs) to chemotherapy, they often recur as chemotherapy-resistant tumors, and this has been associated with upregulated homology-directed repair (HDR). Thus, inhibitors of HDR could be a useful adjunct to chemotherapy treatment of these cancers. We performed a high-throughput chemical screen for inhibitors of HDR from which we obtained a number of hits that disrupted microtubule dynamics. We postulated that high levels of the target molecules of our screen in tumors would correlate with poor chemotherapy response. We found that inhibition or knockdown of dynamin 2 (DNM2), known for its role in endocytic cell trafficking and microtubule dynamics, impaired HDR and improved response to chemotherapy of cells and of tumors in mice. In a retrospective analysis, levels of DNM2 at the time of treatment strongly predicted chemotherapy outcome for estrogen receptor-negative and especially for TNBC patients. We propose that DNM2-associated DNA repair enzyme trafficking is important for HDR efficiency and is a powerful predictor of sensitivity to breast cancer chemotherapy and an important target for therapy

Accounting, Soci(et)al Risks, and Public Reason: Governmental Risk Discourses About the ILVA Steel Plant in Taranto (Italy)

The case of the ILVA steel plant in Taranto represents an example of con- trasting, incommensurable sustainability issues, explored in terms of “social” and “societal” risks (Asenova et al. in Managing the risks of public spending cuts in Scotland, 2013; Redistribution of social and societal risk: the impact on individuals, their networks and communities, 2015) [Asenova et al. (2015) refer to social risks as the risks of unemployment, and to societal risks as environmental and health risks.]. The case of ILVA has received significant attention for the great amount of dangerous pollutants spread in the environment, as well as the evidence of higher illness and mortality rates in the districts nearest to the plant. In July 2012, the Italian Judiciary halted activity in the steel plant. Four months after, the Italian Government declared the steel plant site as a “Strategic National Interest Site”, and allowed the company to restart its activity. Drawing on governmentality (Foucault in Questions of method, 1991), the paper aims to explore the role of accounting—here broadly intended as calculative practices (Miller in Soc Res 68:379–396, 2001)—in moulding ministerial discourse to support decisions when the governance of contrasting risks is needed to safeguard public interest. Supported by discourse analysis of governmental speech, the research shows that the Italian Government based its decision on various experts’ risk appraisals: accounting shaped governmental discourse by giving more visibility and relevance to “social” risks (i.e. unemployment, economic development, produc- tivity and competitiveness risks), while silencing “societal” ones (i.e. environmental and health risks). Focusing on a case of incommensurable contrasting issues, the findings contribute to show that accounting concurrently plays a significant role in government decisions legitimizing the business continuity through the creation of a specific risk discourse

How is a sense of well-being and belonging constructed in the accounts of autistic adults?

This small-scale exploratory study sought to develop an understanding of the meaning of well-being and social belonging as represented within the narratives of adults on the autism spectrum. Employing an interpretivist approach facilitated the investigation of potential contributory factors to these lived experiences in order to inform further research regarding both this topic, and service provision for adults on the autism spectrum. The project involved a thematic analysis of issues of the magazine Asperger United (AU). Four broad main themes were identified: meeting personal needs, living with the consequences of an ‘othered’ identity, connection and recognition, and relationships and advocacy. Autistic adults reported many barriers to feeling that they belonged in a number of social spaces and the detrimental effect this had on their wellbeing. Fundamental to positive narratives of wellbeing, were feelings of connection and recognition from others and positive accepting relationships, with autistic-led spaces, particularly the Autscape conference, being frequently cited as of central significance in increasing feelings of wellbeing and belonging. This study has demonstrated a need for less focus on remediation and more on limiting the social isolation of autistic people

Fitting as a temporal sensemaking process: shifting trajectories and stable themes

This study identifies several mechanisms and the overall process by which individuals understand their evolving fit with their work environment. Prior person-environment research has emphasized one-time quantitative assessments of fit, primarily as new entrants enter their work environment. In this study, we employed a qualitative approach to investigate the following question: how do long-tenured professionals make sense of fit over time? Three key findings emerged from the fit-related histories we collected. First, we discovered four prototypical fit trajectories, which were constructed from temporal comparisons with past, present, and future fit, and employed to make momentary sense of events occurring in the work environment. Second, we identified two fit processes that played out over time: a slow accumulation journey and a sudden identity-threat journey. Third, we found that individuals’ set of fit experiences was explained by one of four enduring fit themes, explaining their pattern of fit experiences over time and their reaction to misfit. Most surprising was the significant turnover among our long-tenured participants in the year or so following our interviews. Our findings break from traditional thinking about fit as predicting outcomes in the moment, to fitting as both a journey and a retrospective and prospective process of sensemaking. Keywords: person-environment fit, misfit, temporal, time, process, sensemaking, qualitative, identit

Behavior in behavioral strategy : capturing, measuring, analyzing

Measuring behavior requires research methods that can capture observed outcomes and expose underlying processes and mechanisms. In this chapter, we present a toolbox of instruments and techniques we designed experimental tasks to simulate decision environments and capture behavior. We deployed protocol analysis and text analysis to examine the underlying cognitive processes. In combination, these can simultaneously grasp antecedents, outcomes, processes, and mechanisms. We applied them to collect rich behavioral data on two key topics in strategic management: the exploration–exploitation trade-off and strategic risk-taking. This mix of methods is particularly useful in describing actual behavior as it is, not as it should be, replacing assumptions with data and offering a finer-grained perspective of strategic decision-making