| 1. |
- Agndal, Henrik, 1972, et al.
(författare)
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Trust, distrust, and open-book accounting in three client-vendor relationships
- 2024
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Ingår i: Contemporary Accounting Research. - 0823-9150 .- 1911-3846. ; 41:1, s. 292-323
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Tidskriftsartikel (refereegranskat)abstract
- Extant management accounting research has conceptualized the interplay between trust, distrust, and open-book accounting (OBA) as a relationship-level phenomenon, largely ignoring that inter-organizational relationships are often complex entities that comprise multiple arenas of exchange where (dis)trust and OBA can interact in different—and potentially contradictory—ways. To address this theoretical oversight, we draw on relational exchange theory to propose that (dis)trust largely forms within OBA domains where different forms of data are exchanged for different purposes. Trust and distrust may thereby coexist within a relationship. We also propose that (dis)trust spills over to influence the conditions for OBA in other domains. Consequently, trust and distrust not only take shape in cumulative processes within OBA domains but also diffuse between domains in a relationship. Empirical observations from a longitudinal case study of a retail buyer's attempts to introduce OBA in three vendor relationships lead us to suggest that competence-trust spillover is determined largely by domain similarity, while goodwill-trust spillover relies to a greater extent on staff mobility between OBA domains. Overall, the negative effects of distrust spillover on the implementation of OBA appear greater than the positive effects of trust spillover. Our study shows that, by analyzing the domain-specific nature of trust and distrust, future research can increase our understanding of the relationship between data characteristics and (dis)trust, as well as explain how trust and distrust interact to determine conditions for data exchange between organizations.
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| 2. |
- Arévalo-Martinez, Marycarmen, et al.
(författare)
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Myocardin related transcription factor and galectin-3 drives lipid accumulation in human blood vessels
- 2024
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Ingår i: Vascular Pharmacology. - 1537-1891. ; 156
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Diabetes and hypertension are important risk factors for vascular disease, including atherosclerosis. A driving factor in this process is lipid accumulation in smooth muscle cells of the vascular wall. The glucose- and mechano-sensitive transcriptional coactivator, myocardin-related transcription factor A (MRTF-A/MKL1) can promote lipid accumulation in cultured human smooth muscle cells and contribute to the formation of smooth muscle-derived foam cells. The purpose of this study was to determine if intact human blood vessels ex vivo can be used to evaluate lipid accumulation in the vascular wall, and if this process is dependent on MRTF and/or galectin-3/LGALS3. Galectin-3 is an early marker of smooth muscle transdifferentiation and a potential mediator for foam cell formation and atherosclerosis.APPROACH AND RESULTS: Human mammary arteries and saphenous veins were exposed to altered cholesterol and glucose levels in an organ culture model. Accumulation of lipids, quantified by Oil Red O, was increased by cholesterol loading and elevated glucose concentrations. Pharmacological inhibition of MRTF with CCG-203971 decreased lipid accumulation, whereas adenoviral-mediated overexpression of MRTF-A had the opposite effect. Cholesterol-induced expression of galectin-3 was decreased after inhibition of MRTF. Importantly, pharmacological inhibition of galectin-3 with GB1107 reduced lipid accumulation in the vascular wall after cholesterol loading.CONCLUSION: Ex vivo organ culture of human arteries and veins can be used to evaluate lipid accumulation in the intact vascular wall, as well as adenoviral transduction and pharmacological inhibition. Although MRTF and galectin-3 may have beneficial, anti-inflammatory effects under certain circumstances, our results, which demonstrate a significant decrease in lipid accumulation, support further evaluation of MRTF- and galectin-3-inhibitors for therapeutic intervention against atherosclerotic vascular disease.
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| 3. |
- Backman, Helena, et al.
(författare)
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All-cause and cause-specific mortality by spirometric pattern and sex - a population-based cohort study
- 2024
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Ingår i: THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE. - : Sage Publications. - 1753-4658 .- 1753-4666. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic airway obstruction (CAO) and restrictive spirometry pattern (RSP) are associated with mortality, but sex-specific patterns of all-cause and specific causes of death have hardly been evaluated. Objectives: To study the possible sex-dependent differences of all-cause mortality and patterns of cause-specific mortality among men and women with CAO and RSP, respectively, to that of normal lung function (NLF). Design: Population-based prospective cohort study. Methods: Individuals with CAO [FEV1/vital capacity (VC) < 0.70], RSP [FEV1/VC >= 0.70 and forced vital capacity (FVC) < 80% predicted] and NLF (FEV1/VC >= 0.70 and FVC >= 80% predicted) were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-2004. Mortality data were collected through April 2016, totally covering 19,000 patient-years. Cox regression and Fine-Gray regression accounting for competing risks were utilized to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, body mass index, sex, smoking habits and pack-years. Results: The adjusted hazard for all-cause mortality was higher in CAO and RSP than in NLF (HR, 95% CI; 1.69, 1.31-2.02 and 1.24, 1.06-1.71), and the higher hazards were driven by males. CAO had a higher hazard of respiratory and cardiovascular death than NLF (2.68, 1.05-6.82 and 1.40, 1.04-1.90). The hazard of respiratory death was significant in women (3.41, 1.05-11.07) while the hazard of cardiovascular death was significant in men (1.49, 1.01-2.22). In RSP, the higher hazard for respiratory death remained after adjustment (2.68, 1.05-6.82) but not for cardiovascular death (1.11, 0.74-1.66), with a similar pattern in both sexes. Conclusion: The higher hazard for all-cause mortality in CAO and RSP than in NLF was male driven. CAO was associated with respiratory death in women and cardiovascular death in men, while RSP is associated with respiratory death, similarly in both sexes.
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| 4. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 5. |
- Torén, Kjell, et al.
(författare)
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Restrictive Spirometric Pattern and Preserved Ratio Impaired Spirometry in a Population 50-64 Years.
- 2024
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Ingår i: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621.
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Knowledge regarding prevalence and shared and unique characteristics of Restrictive spirometric pattern (RSP) and Preserved ratio impaired spirometry (PRISm) is lacking for a general population investigated with post-bronchodilator spirometry and computed tomography of the lungs.OBJECTIVES: To investigate shared and unique features for RSP and PRISm.METHODS: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population sample of 28,555 people aged 50 - 64 years (including 14,558 never-smokers) was assessed. The participants answered a questionnaire and underwent computed tomography of the lungs, post-bronchodilator spirometry, and coronary artery calcification score (CACS). Odds ratios (OR) with 95% confidence intervals (CI) were calculated using adjusted logistic regression. RSP was defined as FEV1/FVC≥0.70 and FVC<80%. PRISm was defined as FEV1/FVC≥0.70 and FEV1<80%. A local reference equation was applied.MEASUREMENTS AND RESULTS: The prevalence of RSP and PRISm were 5.1% (95% CI 4.9 - 5.4) and 5.1% (95% CI 4.8 - 5.3), respectively, with similar values seen in never-smokers. For RSP and PRISm, shared features were current smoking, dyspnea, chronic bronchitis, rheumatic disease, diabetes, ischemic heart disease (IHD), bronchial wall thickening, interstitial lung abnormalities (ILA), and bronchiectasis. Emphysema was uniquely linked to PRISm (OR 1.69, 1.36-2.10) vs 1.10 (0.84-1.43) for RSP. CACS≥300 was related to PRISm, but not among among never-smokers.CONCLUSIONS: PRISm and RSP have respiratory, cardiovascular, and metabolic conditions as shared features. Emphysema is only associated with PRISm. Coronary atherosclerosis may be associated with PRISm. Our results indicate that RSP and PRISm may share more features than not. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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| 6. |
- van Klaveren, Sjors, et al.
(författare)
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Galectin-8N-Selective 4-Halophenylphthalazinone-Galactals Double π-Stack in a Unique Pocket
- 2024
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Ingår i: ACS Medicinal Chemistry Letters. - 1948-5875. ; 15:8, s. 1319-1324
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-8 contains two different carbohydrate recognition domains (CRDs). Selective inhibitors for at least one CRD are desirable for galectin-8 biology studies and potentially for pharmacological purposes. Structure-guided design led to the discovery of potent and selective glycomimetic-heterocycle hybrid ligands, with a 4-(p-bromophenyl)phthalazinone derivative displaying a 34 μM Kd for galectin-8N (N-terminal CRD), no binding to galectin-8C (C-terminal CRD), -1, -3, -4N, -7, -9C, or -9N, and >40-fold selectivity over galectin-4C. Selectivity was achieved with the halogenated 4-phenylphthalazinone moiety occupying a galectin-8N-specific sub-pocket. A 1.30 Å resolution X-ray structure revealed the phthalazinone moiety stacking with Arg45 and the 4-bromophenyl moiety stacking both Arg59 and Tyr141 of galectin-8N. Physicochemical and in vitro ADME studies revealed a desirable LogD, which also translated to good passive permeability. The chemical, microsome, and plasma stability support these compounds as promising tool compounds and candidates for hit-to-lead optimization.
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| 7. |
- Verteramo, Maria Luisa, et al.
(författare)
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Interplay of halogen bonding and solvation in protein-ligand binding
- 2024
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Ingår i: iScience. - 2589-0042. ; 27:4
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Tidskriftsartikel (refereegranskat)abstract
- Halogen bonding is increasingly utilized in efforts to achieve high affinity and selectivity of molecules designed to bind proteins, making it paramount to understand the relationship between structure, dynamics, and thermodynamic driving forces. We present a detailed analysis addressing this problem using a series of protein-ligand complexes involving single halogen substitutions - F, Cl, Br, and I - and nearly identical structures. Isothermal titration calorimetry reveals an increasingly favorable binding enthalpy from F to I that correlates with the halogen size and σ-hole electropositive character, but is partially counteracted by unfavorable entropy, which is constant from F to Cl and Br, but worse for I. Consequently, the binding free energy is roughly equal for Cl, Br, and I. QM and solvation-free-energy calculations reflect an intricate balance between halogen bonding, hydrogen bonds, and solvation. These advances have the potential to aid future drug design initiatives involving halogenated compounds.
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| 8. |
- Wang, Yiran, et al.
(författare)
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Using Run-Time Information to Enhance Static Analysis of Machine Learning Code in Notebooks
- 2024
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Ingår i: COMPANION PROCEEDINGS OF THE 32ND ACM INTERNATIONAL CONFERENCE ON THE FOUNDATIONS OF SOFTWARE ENGINEERING, FSE COMPANION 2024. - : ASSOC COMPUTING MACHINERY. - 9798400706585 ; , s. 497-501
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Konferensbidrag (refereegranskat)abstract
- A prevalent method for developing machine learning (ML) prototypes involves the use of notebooks. Notebooks are sequences of cells containing both code and natural language documentation. When executed during development, these code cells provide valuable run-time information. Nevertheless, current static analyzers for notebooks do not leverage this run-time information to detect ML bugs. Consequently, our primary proposition in this paper is that harvesting this run-time information in notebooks can significantly improve the effectiveness of static analysis in detecting ML bugs. To substantiate our claim, we focus on bugs related to tensor shapes and conduct experiments using two static analyzers: 1) PYTHIA, a traditional rule-based static analyzer, and 2) GPT-4, a large language model that can also be used as a static analyzer. The results demonstrate that using run-time information in static analyzers enhances their bug detection performance and it also helped reveal a hidden bug in a public dataset.
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| 9. |
- Yoshida, Akari, et al.
(författare)
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Development of a novel AAK1 inhibitor via Kinobeads-based screening
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14, s. 6723-6723
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Tidskriftsartikel (refereegranskat)abstract
- A chemical proteomics approach using Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor–immobilized sepharose (TIM-063-Kinobeads) identified main targets such as CaMKKα/1 and β/2, and potential off-target kinases, including AP2-associated protein kinase 1 (AAK1), as TIM-063 interactants. Because TIM-063 interacted with the AAK1 catalytic domain and inhibited its enzymatic activity moderately (IC50 = 8.51 µM), we attempted to identify potential AAK1 inhibitors from TIM-063-derivatives and found a novel AAK1 inhibitor, TIM-098a (11-amino-2-hydroxy-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) which is more potent (IC50 = 0.24 µM) than TIM-063 without any inhibitory activity against CaMKK isoforms and a relative AAK1-selectivity among the Numb-associated kinases family. TIM-098a could inhibit AAK1 activity in transfected cultured cells (IC50 = 0.87 µM), indicating cell-membrane permeability of the compound. Overexpression of AAK1 in HeLa cells significantly reduced the number of early endosomes, which was blocked by treatment with 10 µM TIM-098a. These results indicate TIM-063-Kinobeads-based chemical proteomics is efficient for identifying off-target kinases and re-evaluating the kinase inhibitor (TIM-063), leading to the successful development of a novel inhibitory compound (TIM-098a) for AAK1, which could be a molecular probe for AAK1. TIM-098a may be a promising lead compound for a more potent, selective and therapeutically useful AAK1 inhibitor.
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| 10. |
- Agndal, Henrik, 1972, et al.
(författare)
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Managing appropriation concerns and coordination costs in complex vendor relationships: Integration and isolation as governance strategies
- 2023
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Ingår i: Industrial Marketing Management. - 0019-8501. ; 113, s. 116-127
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Tidskriftsartikel (refereegranskat)abstract
- Many studies have shown that the inter-organizational governance mechanisms required to manage appropriation concerns come into conflict with the mechanisms needed to manage coordination costs. Research has, however, largely left unanswered the question of how client organizations govern complex vendor relationships that involve multiple categories, transactions, and activities where appropriation concerns and coordination costs must be managed simultaneously. We propose that this may be achieved by utilizing two strategies; while integrating some activities, transactions and categories, others can be isolated. Drawing on 23 interviews as well asprocedural documents associated with vendor management, this study examines how a leading automotive manufacturer governs relationships with three vendors. The analysis reveals how corporate and operational-level staff combine formal and informal governance mechanisms as they pursue integration and isolation strategies, enabling the client organization to maintain and develop longterm complex relationships. Our findings lead us to question a tendency in the literature to regard isolation as negative and integration as an ideal strategy for managing long-term relationships. Only when utilized in tandem will isolation and integration strategies enable organizations to align the conflicting governance mechanisms required to manage appropriation concerns and coordination costs.
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