Austrian Science Fund Research Articles

Fast Convex Optimization via Time Scale and Averaging of the Steepest Descent

In a Hilbert setting, we develop a gradient-based dynamic approach for fast solving convex optimization problems. By applying time scaling, averaging, and perturbation techniques to the continuous steepest descent (SD), we obtain high-resolution ordinary differential equations of the Nesterov and Ravine methods. These dynamics involve asymptotically vanishing viscous damping and Hessian-driven damping (either in explicit or implicit form). Mathematical analysis does not require developing a Lyapunov analysis for inertial systems. We simply exploit classical convergence results for SD and its external perturbation version, then use tools of differential and integral calculus, including Jensen’s inequality. The method is flexible, and by way of illustration, we show how it applies starting from other important dynamics in optimization. We consider the case in which the initial dynamic is the regularized Newton method, then the case in which the starting dynamic is the differential inclusion associated with a convex lower semicontinuous potential, and finally we show that the technique can be naturally extended to the case of a monotone cocoercive operator. Our approach leads to parallel algorithmic results, which we study in the case of fast gradient and proximal algorithms. Our averaging technique shows new links between the Nesterov and Ravine methods. Funding: The research of R.I. Boţ and D.-K. Nguyen was supported by the Austrian Science Fund (FWF), projects W 1260 and P 34922-N.

Value-Positivity for Matrix Games

Matrix games are the most basic model in game theory, and yet robustness with respect to small perturbations of the matrix entries is not fully understood. In this paper, we introduce value positivity and uniform value positivity, two properties that refine the notion of optimality in the context of polynomially perturbed matrix games. The first concept captures how the value depends on the perturbation parameter, and the second consists of the existence of a fixed strategy that guarantees the value of the unperturbed matrix game for every sufficiently small positive parameter. We provide polynomial-time algorithms to check whether a polynomially perturbed matrix game satisfies these properties. We further provide the functional form for a parameterized optimal strategy and the value function. Finally, we translate our results to linear programming and stochastic games, where value positivity is related to the existence of robust solutions. Funding: This research was supported by Fondation CFM pour la Recherche, the H2020 European Research Council [Grant ERC-CoG-863818 (ForM-SMArt)], the Austrian Science Fund [Grant 10.55776/COE12], ANID Chile [Grant ACT210005], and Agence Nationale de la Recherche [Grant ANR-21-CE40-0020].

Association of inflammatory markers and ultrasonographic indicators of endothelial (dys)function in humans

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Austrian Science Fund (FWF) Introduction It has been widely known that chronic inflammation is a crucial factor in the process of atherogenesis and atherosclerosis. Also, endothelial dysfunction presents the first and still reversible step of that process.(1) It is a challenge to find a laboratory marker whose levels would be informative about the extent of endothelial dysfunction and atherogenesis in humans. Purpose The aim of the present study was to determine associations between markers of chronic, low-grade inflammation and ultrasonographic indicators of endothelial (dys)function in healthy volunteers (H) and in patients with metabolic syndrome (MS). Methods Any kind of clinically manifest acute inflammatory or infectious disease, as well as chronic inflammatory, autoimmune or malignant disease was an exclusion criterion for participation. Serum levels of C-reactive protein (CRP) were measured using standard clinical chemistry analyser, and serum levels of interleukin-6 (IL-6) using electro-chemiluminescence immunoassay. Blood vessel wall function was quantified as flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD), which were measured automatically and continuously using the ultrasound device with linear probe (10 MHz) and the software for ultrasound blood vessel diameter analysis,(2) following currently valid guidelines.(3,4,5) Results A total of 130 individuals were enrolled in the study (65 H and 65 MS), with a median age of 56 (IQR 50.0, 60.0) years and 47.7% women in each group. CRP and IL-6 levels, although being very low and within the intervals that are considered normal in everyday clinical practice for both groups [CRP - H: 1.2 (0.6, 2.3), MS: 2.4 (1.2, 5.5) μg/mL; IL-6 - H: 2.3 (1.7, 3.0), MS: 4.1 (2.7, 6.8) pg/mL], were significantly higher in the MS compared to H (both p<0.001). The MS group also had significantly lower FMD (p=0.013) and NMD (p=0.033) compared to H. In H, IL-6 levels were significantly negatively correlated with FMD (r=-0.46, p<0.001), but not with NMD; whereas no significant associations of IL-6 levels with FMD or NMD were observed in the MS group. CRP levels were not significantly associated with FMD or NMD in neither the H nor MS group. Conclusion Higher IL-6 serum levels in the absence of acute inflammatory or infectious disease are significantly associated with lower FMD values among individuals with low risk for cardiovascular diseases, who are still considered healthy. Direct correlation is attenuated and lost among individuals with developed clinical signs of metabolic syndrome, probably due to its complex pathophysiology, as well as redundant and interdependent mechanisms contributing to the occurrence of endothelial dysfunction in such an environment. Further investigation on larger cohorts is needed to determine whether IL-6 serum levels could serve as a marker of endothelial dysfunction in individuals without clinically developed traditional risk factors and symptoms of cardiovascular disease.

High-throughput proteomic analysis unveils metabolic and mitochondrial signaling rewiring by chronic ivabradine treatment in duchenne muscular dystrophy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Austrian Science Fund (FWF) Objective Ivabradine (IVA) is indicated in symptomatic treatment of chronic stable angina, heart failure, and also in those who are unable to tolerate or have contraindications to the use of beta-blockers. It has been showed IVA may have cardiovascular benefits in Duchenne muscular dystrophy (DMD) patients. This study was aimed to investigate the sustained impact of chronic ivabradine (IVA) administration on cardiac function and potential underlying mechanism using high throutput proteomic analysis. Methods DMDmdx male and Sprague–Dawley wt (Sprague–Dawley) male rats were randomly allocated to vehicle (n = 6) or IVA (n=6; 10 mg/kg/day via drinking water for four months). Transthoracic echocardiography and unbiased proteomic analysis were performed to assess cardiac function and left ventricular (LV) tissue, respectively. Protein-protein interactions were graphically represented, and cluster analysis with subsequent enrichment analyses was conducted. Results Chronic IVA treatment significantly enhanced the LV ejection fraction (p<0.05 compared to vehicle-treated DMDmdx rats). Proteomic data identified possible transcription factors (SPI1, IRF1, PPARA), consistent with previous studies. The reduction in copper metabolic changes associated with DMD can be attributed to the upregulation of Atox1 following IVA treatment. Mitochondrial dysfunction was effectively mitigated by IVA, as indicated by the different abundance of mitochondrial proteins. In addition, intercellular adhesion molecule 1 showed a reduction in the number of animals treated with ivabradine, indicating a further positive effect of the treatment. Conclusion In summary, this study demonstrated the beneficial effects of IVA in DMDmdx rat hearts. Cluster analysis of proteomic data revealed notable changes in cardiac metabolism, inflammation, and mitochondrial function. Ivabradine has emerged as a potential therapeutic approach to address these shifts, while proteomic pathway analysis may uncover new drugable targets to alleviate cardiomyopathy progression in DMD.Interaction of IvabradinProtein-protein interaction network

Uncovering Sophisticated Discrimination with the Help of Credence Goods Markups: Evidence from a Natural Field Experiment

Credence goods, such as repair and healthcare services, are characterized by profound information asymmetries between less-informed customers and better-informed expert sellers. These information asymmetries open the door for fraudulent behavior on the seller side. In a preregistered natural field experiment, we vary in one dimension the seller’s perception of whether the service is an ordinary or a credence good service and in the second dimension whether the customer is a member of a minority or a member of the majority. This allows us to measure the size of the induced credence goods markup and to address the question whether it interacts systematically with discrimination. We document the existence of a large credence goods markup, on average. Moreover, we find that members of the minority pay a sizeable discriminatory markup if the good is perceived as a credence good but not if it is perceived as an ordinary good. Our results show that sellers engage in sophisticated discrimination where informational asymmetries are used to hide discriminatory (fraudulent) behavior. With the help of an ex post survey, we derive a possible explanation for our results. This paper was accepted by Maria Claire Villeval, behavioral economics and decision analysis. Funding: Financial support was provided by the Austrian Science Fund [Special Research Area Grant SFB F63 and Grants P26901 and P27912]. Supplemental Material: The online appendices and data files are available at https://doi.org/10.1287/mnsc.2022.02666 .

It’s About What Happens in the Meantime: The Temporal Interplay of Individual and Collective Creativity

In creativity research, time is rarely conceptualized as a multidimensional phenomenon. Instead, it is conceived either as an external variable, for coordinating successive phases of an idea journey, interaction patterns, and moments of insight—or as an individual experience, encompassing aspects like stress or timelessness. Based on an ethnography of a music studio, I show how these temporalities coexist and how time is organized as a linear coordination process as well as an experience to enable and align individual and collective creativity. Time is thereby available in three dimensions, as planned time for linear sequencing of collective work steps, as assigned meantime for the spontaneous and parallel allocation of tasks to free time slots, and as idle meantime for indeterminate waiting periods afforded by the material temporality of artifacts and bodies. My findings elucidate that organizing the interplay of all three temporal dimensions favors both individual ideation in indeterminate situations of idleness and collective creative work on predefined tasks in planned phases and ad hoc structured situations. Importantly, I found how the time afforded by artifacts and bodies in creative work is key to enabling and aligning individual creative processes by providing opportunities for relaxation, defocusing, and humor during collective creative processes, based on coordinated interaction. My findings contribute to a social process perspective on creativity by reconsidering the role of individual experiences in creative collaboration from a temporal perspective. Funding: This research was supported by the Austrian Science Fund (FWF) [Grant 10.55776/I4884].

Strategic Responses to Algorithmic Recommendations: Evidence from Hotel Pricing

We study the interaction between algorithmic advice and human decisions using high-resolution hotel-room pricing data. We document that price setting frictions, arising from adjustment costs of human decision makers, induce a conflict of interest with the algorithmic advisor. A model of advice with costly price adjustments shows that, in equilibrium, algorithmic price recommendations are strategically biased and lead to suboptimal pricing by human decision makers. We quantify the losses from the strategic bias in recommendations using as structural model and estimate the potential benefits that would result from a shift to fully automated algorithmic pricing. This paper was accepted by Axel Ockenfels, special issue on the human-algorithm connection. Funding: D. Garcia gratefully acknowledges that this research was funded in part by the Austrian Science Fund [Grant FWF-FG6]. A. K. Wagner gratefully acknowledges financial support from the Anniversary Fund of the Oesterreichische Nationalbank [Project 18878]. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.03740 .

Abstract 196: In vitro modeling of pediatric solid tumor lung metastases

Abstract Metastasis remains the main cause of death in pediatric cancer patients with the lung being one of the most common affected organs. Our inability to cure these patients is largely due to insufficient knowledge about tumor and metastatic niche plasticity, while existing models are not fully effective in mirroring the response seen in clinical setting. Our goal is to overcome these limitations by establishing in vitro lung metastasis models using tumor/lung organoid co-cultures to study lung infiltration of pediatric solid tumors. We successfully established patient-derived lung organoids from pediatric lung tissue and characterized them according to the presence and the localization of the respective lung epithelial cell types. Co-culture conditions of lung organoids with PDX-derived Ewing sarcoma and osteosarcoma cells were optimized and models established, while the establishment of models for other pediatric solid tumor entities is ongoing. We have observed infiltration of the lung organoids by tumor cells, and our preliminary findings suggest distinct patterns of infiltration among different tumor entities. Furthermore, we have performed single-cell RNA sequencing analysis on these co-cultures in comparison to the parental lung organoids and tumor cells, aiming to uncover the specific signaling pathways activated in the lung metastatic niche in response to tumor cell invasion. Additionally, experiments using conditioned medium suggest that the lung organoid secretome is sufficient to induce homing of osteosarcoma and Ewing sarcoma cells to the organoids, with the CXCL12/CXCR4 signaling axis as a prime candidate driver. To ascertain the extent to which our in vitro model recapitulates the in vivo lung metastatic niche, we performed spatial transcriptomics (using VISIUM/10X Genomics) on formalin-fixed paraffin-embedded (FFPE) tissue blocks of paired primary tumors and lung metastasis samples for Ewing sarcoma and osteosarcoma. Comprehensive data analysis is currently ongoing, which will instruct a stepwise incorporation of additional factors into our modular organoid co-culture model, resulting in a better representation of the lung metastatic niche. Further, the analysis of patient-derived material will elucidate the spatial organization of solid tumor lung metastases and contribute to the identification of signaling pathways implicated in lung infiltration. In conclusion, our study not only unravels the complexities of pediatric solid tumor metastasis, but also lays the foundation for exploring the anti-metastatic potential of pathway-specific compounds targeting tumor/lung interactions using the established in vitro lung metastasis models. This study is supported by grant 35353-B of the Austrian Science Fund. Citation Format: Martha Zylka, Christoph Hafemeister, Lukas Watzke, Ulrike Mann, Didier Surdez, E. Alejandro Sweet-Cordero, Bernadette Liegl-Atzwanger, Matthias Dettmer, Matthias Farlik, Florian Halbritter, Martin Metzelder, Heinrich Kovar, Branka Radic-Sarikas. In vitro modeling of pediatric solid tumor lung metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 196.

Finding Creativity in Predictability: Seizing Kairos in Chronos Through Temporal Work in Complex Innovation Processes

Managing temporal complexity is a fundamental challenge in complex innovation processes, yet the temporal work whereby actors seize opportune moments (kairos) in an environment dominated by clock-time structures (chronos) remains elusive. Temporal tensions can partly be resolved through entrainment, that is, by aligning activities with dominant temporal structures. However, although entrainment ensures the exploitation of a predefined path, it is unable to harness unexpected developments as opportunities for exploration. Thus, navigating the competing temporal demands of chronos and kairos requires not just ambidextrous but also ambitemporal organizing. Collecting and analyzing in-depth interview and observational data from pharmaceutical drug discovery and development, we find that actors sometimes resolve temporal tensions through entrainment to ensure coordination and predictability. In other instances, however, actors abductively transform temporal tensions into novel interpretations and new courses of action. As such, temporal tensions become more than a bothersome deviation from the planned schedule, but an opportunity for creative agency. This understanding of kairos—as a process unfolding through temporal work—relies not only on detraining from chronos (i.e., momentarily detaching from the dominant temporal structure to question underlying assumptions), but also on its reframing and reconfiguration. We contribute to the literature on complex innovation and temporality by theorizing a transformative perspective on ambitemporal organizing, which relies less on paradoxical notions and instead emphasizes how kairos is enacted and seized within and from chronos. Funding: This work was supported by German Research Foundation (DFG) funding for the Research Unit “Organized Creativity” [Grant FOR 2161] as well as by the Austrian Science Fund (FWF) [10.55776/I4884].

Report on “Axiomatizing Conditional Normative Reasoning”

This is a report on the project “Axiomatizing Conditional Normative Reasoning” (ANCoR, M 3240-N) funded by the Austrian Science Fund (FWF). The project aims to deepen our understanding of conditional normative reasoning by providing an axiomatic study of it at the propositional but also first-order level. The focus is on a particular framework, the so-called preference-based logic for conditional obligation, whose main strength has to do with the treatment of contrary-to-duty reasoning and reasoning about exceptions. The project considers not only the meta-theory of this family of logics but also its mechanization.

Experimental assessment of playability limits during bowed string attacks

The playability limits in the bow force and bow acceleration parameter space (usually visualized as a Guettler diagram) define the conditions for establishing Helmholtz motion during bowed attacks in bowed-string instruments. Despite few theoretical and numerical studies, there is little empirical validation of these limits. The experimental scanning of a Guettler diagram is a tedious process, as it requires the use of a bowing machine to control the bowing parameters. This study proposes a method for collecting and analyzing data to produce measured Guettler diagrams. Experiments were conducted using a cello string in a monochord arrangement with fixed terminations. The string was excited using a robotic arm that allows control of the playing conditions by changing the bow force and bow acceleration. Each set of measurements contains more than 900 data points to obtain high-resolution Guettler diagrams. In addition, the measurements are repeated in reverse order and after dismounting and remounting the string. The results are compared with existing literature, with particular attention to theoretical limits. The experimental results suggest that the static and dynamic friction coefficients vary with bow force and acceleration, modifying the playability limits. [Work supported by the Austrian Science Fund (FWF) (P34852-N).]

Towards reproducing bowed-string instrument transients using physical modeling

Physical models of bowed-string instruments can forecast various aspects of bow-string interaction. However, accurately replicating transient waveforms of string oscillations remains a challenge. In this work, measured transient behavior of the bowed string is compared with predictions from a simulation model. Fixed boundary conditions are assumed and a finite-width bow, bow-hair compliance, torsional string motion, and an elasto-plastic friction model are incorporated. The latter links relative velocity and friction force through a differential equation, and therefore, exhibits hysteresis behavior. Simulated Guettler diagrams are then compared to measured ones obtained from a robot bowing a monochord. The general shape of the playability region is successfully predicted, but some details in the measured time-domain waveforms are not reproduced by the model. Employing inverse modeling, parameter values for the elasto-plastic friction model are derived, demonstrating the ability to generate reliable reconstructions of the measured transient signals. These results emphasize the need to account for variable friction coefficients in order to reproduce measured signals. This observation aligns with prior findings indicating that static and dynamic friction coefficients vary with bow force and bow acceleration. [Work funded in whole or in part by the Austrian Science Fund (FWF) (P34852-N).]

Efficacy and safety of mTOR inhibition in cutaneous sarcoidosis: a single-centre trial

Sarcoidosis is an inflammatory condition that can affect various organs and tissues, causing the formation of granulomas and subsequent functional impairment. The origin of sarcoidosis remains unknown and there are few treatment options. Mechanistic target of rapamycin (mTOR) activation is commonly seen in granulomas of patients across different tissues and has been shown to induce sarcoidosis-like granulomas in a mouse model. This study aimed to examine the efficacy and safety of the mTOR inhibitor sirolimus as a treatment for cutaneous sarcoidosis. We did a single-centre, randomised study treating patients with persistent and glucocorticoid-refractory cutaneous sarcoidosis with sirolimus at the Vienna General Hospital, Medical University of Vienna (Vienna, Austria). We recruited participants who had persistent, active, and histologically proven cutaneous sarcoidosis. We used an n-of-1 crossover design in a placebo-controlled, double-blind topical treatment period and a subsequent single-arm systemic treatment phase for 4 months in the same participants. Participants initially received either 0·1% topical sirolimus in Vaseline or placebo (Vaseline alone), twice daily. After a washout period, all participants were subsequently administered a 6 mg loading dose followed by 2 mg sirolimus solution orally once daily, aiming to achieve serum concentrations of 6 ng/mL. The primary endpoint was change in the Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) after topical or systemic treatment. All participants were included in the safety analyses, and patients having completed the respective treatment period (topical treatment or systemic treatment) were included in the primary analyses. Adverse events were assessed at each study visit by clinicians and were categorised according to their correlation with the study drug, severity, seriousness, and expectedness. This study is registered with EudraCT (2017-004930-27) and is now closed. 16 participants with persistent cutaneous sarcoidosis were enrolled in the study between Sept 3, 2019, and June 15, 2021. Six (37%) of 16 participants were men, ten (63%) were women, and 15 (94%) were White. The median age of participants was 54 years (IQR 48-58). 14 participants were randomly assigned in the topical phase and 2 entered the systemic treatment phase directly. Daily topical treatment did not improve cutaneous lesions (effect estimate -1·213 [95% CI -2·505 to 0·079], p=0·066). Systemic treatment targeting trough serum concentrations of 6 ng/mL resulted in clinical and histological improvement of skin lesions in seven (70%) of ten participants (median -7·0 [95% CI -16·5 to -3·0], p=0·018). Various morphologies of cutaneous sarcoidosis, including papular, nodular, plaque, scar, and tattoo-associated sarcoidosis, responded to systemic sirolimus therapy with a long-lasting effect for more than 1 year after treatment had been stopped. There were no serious adverse events and no deaths. Short-term treatment with systemic sirolimus might be an effective and safe treatment option for patients with persistent glucocorticoid-refractory sarcoidosis with a long-lasting disease-modulating effect. The effect of sirolimus in granulomatous inflammation should be investigated further in large, multi-centre, randomised clinical trials. Vienna Science and Technology Fund, Austrian Science Fund.

Interfacial Degradation Processes in Solid-State Batteries during High Temperature Processing and the Mitigation Strategies

Garnet-type solid electrolytes have been extensively investigated in recent times as potential candidates for solid-state batteries. Among them, garnets with nominal composition Li7La3Zr2O12(LLZO) have received particular attention due to their high Li-ion conductivity (10-3 Scm-1) at room temperature and chemical stability against metallic lithium besides possessing a large electrochemical window >5V.[1] Despite of striking properties, LLZO suffers from several challenges such as interfacial instability with cathodes, e.g., LCO, during high temperature processing, resulting in a huge interface resistance, which is one of the fundamental reasons for the failure of solid-state batteries based on LLZO.[2-4] So far, the high interfacial impedance has been related to LLZO|LCO interface decomposition occurring due to diffusion of Co across the cathode-electrolyte interface. Herein, we investigated the hypothesis that interfacial degradation originate from the incorporation of Co into the LLZO lattice. The solubility limit of Co is determined to be 0.16 per formula unit, whilst the concentrations beyond promote phase transition (cubic LLZO-to-tetragonal LLZO). We investigated in detail the temperature-dependent Co diffusion into LLZO and concluded that detrimental cross diffusion could take place at any relevant process condition. Besides, the optimal protective Al2O3 coating thickness for relevant temperatures was studied, which allowed to create a process diagram to provide mitigation strategies towards enabling stable LCO|LLZO interface in all-solid-state batteries. Keywords: Solid-state batteries, Interfaces, cross diffusion, interfacial degradation AcknowledgementsD.R. acknowledges financial support by the Austrian Federal Ministry for Digital and Economic Affairs, the National Foundation for Research, Technology and Development and the Christian Doppler Research Association (Christian Doppler Laboratory for Solid-State Batteries). D.R. and J. F. acknowledges financial support by the Austrian Science Fund (FWF) in the frame of the project InterBatt (P 31437). D.K. acknowledges funding by the European Union’s Horizon 2020 Research and Innovation Programme (Grant No. 823717, project “ESTEEM3”) and by the Zukunftsfond Steiermark.Reference[1] Murugan, R., Thangadurai, V. and Weppner, W., 2007. Fast Lithium Ion Conduction in Garnet‐type Li7La3Zr2O12. Angew. Chemie. Int. Edt., 46(41), 7778-7781.[2] Chen, X., Xie, J., Zhao, X., & Zhu, T., 2021. Electrochemical Compatibility of Solid‐State Electrolytes with Cathodes and Anodes for All‐Solid‐State Lithium Batteries: A Review. Adv. Energy Sustain. Res., 2(5), 2000101.[3] Sakuda, A., Hayashi, A., Tatsumisago, M., 2010. Interfacial Observation Between LiCoO2 Electrode and Li2S-P2S5 Solid Electrolytes of All-Solid-State Lithium Secondary Batteries Using Transmission Electron Microscopy. Chem. Mater., 22(3), 949–956.[4] Ihrig, M., Kuo, L.Y., Lobe, S., Laptev, A.M., Lin, C.A., Tu, C.H., Ye, R., Kaghazchi, P., Cressa, L., Eswara, S. and Lin, S.K., 2023. Thermal Recovery of the Electrochemically Degraded LiCoO2/Li7La3Zr2O12: Al, Ta Interface in an All-Solid-State Lithium Battery. ACS Appl. Mater. Interfaces.

All employees benefit: arguments that help increase support for affirmative action in academic careers

The goal of affirmative action programs is to establish equal opportunities for women and men. Past research has focused on one type of affirmative action, namely quotas, and found that the implementation of quotas is often met by a backlash from employees. The current study adds to the literature by investigating fairness and importance perceptions of career development programs offered only to women at Austrian universities or the Austrian Science Fund. Using the model of attitudes toward affirmative action programs the current experimental study tested whether providing participants with information about the benefits (gain-message condition) or costs (loss-message condition) of the implementation of affirmative action programs influenced participants’ perceptions of affirmative action programs. In the current online study, the 510 participants (52.5% cisgender women and 47.5% cisgender men; Mage = 29.5, SD = 9.5) from German-speaking countries in Europe gave on average higher fairness and importance ratings to career development programs offered to all employees than to such programs offered specifically to women. Men in the gain-message condition and loss-message condition gave higher fairness ratings to affirmative action programs than did men in the control condition (i.e., men who read a text that gave no justification for the implementation of affirmative action programs). Men in the gain-message condition also gave higher importance ratings to affirmative action programs than did men in the control condition. Women were not influenced in their ratings by the justification of the implementation of affirmative action programs. Nevertheless, women’s perceptions of affirmative action programs were more favorable than men’s. When implementing affirmative action programs in organizations, providing information that explains why affirmative action is needed and how all employees benefit therefrom can increase support from men who, as seen from past research, are known to be most opposed to affirmative action.

Running Freight on the River. A Clean Cargo Prefiguration

We are interested in exploring the types of futures that are preferable for us all. Discussions of preferable futures can be made difficult by a lack of understanding of the lived experience of that possible future. We like to think that some wise person once said: “I hear futures and I forget. I see futures and I remember. I do futures and I understand.” In order to explore scenarios of possible futures, we thus look into experiential modalities. This exposition examines our Danube Clean Cargo project. The prefigurative process imagined what small scale localised transport could be like and attempted to run a pilot scheme. Reporting on that, merging the quantitative, qualitative and experiential aspects of the project, we present some resulting insights and imaginations. The project leaves us with speculations and visions drawn out by the process of prefiguration. It also leaves us with questions around heterotopic instantiations, queered economics and the everyday to be pondered as artistic research. This helps us reflect on the process of imagination and speculation, on dreams of various freedoms and the harsh realities of logistics chains. The exposition develops ideas in both internal and external reflective modes. The exposition is oriented along a chart of the Danube river for the region of interest. Along the south bank of the Danube the project and its internal reflections are arrayed as episodic text fragments, leading up to a short vision that echoes older stories of sailing cargo barges. Along the north bank a more external reflection is positioned, bringing the project and its understandings into context with a collection of previous developments and external references. The entire exposition is arranged as a single page paper nautical chart, which in contrast to a digital chart plotter, always displays all of the information and does not hide features. This exposition is part of Curiouser and Curiouser, cried Alice: Rebuilding Janus from Cassandra and Pollyanna (CCA), an art-based research project from Design Investigations (ID2) at the University of Applied Arts Vienna and Time's Up. It is supported by the Programme for Arts-based Research (PEEK) from the Austrian Science Fund (FWF): AR561.

Enhancing Branch-and-Bound for Multiobjective 0-1 Programming

In the biobjective branch-and-bound literature, a key ingredient is objective branching, that is, to create smaller and disjoint subproblems in the objective space, obtained from the partial dominance of the lower bound set by the upper bound set. When considering three or more objective functions, however, applying objective branching becomes more complex, and its benefit has so far been unclear. In this paper, we investigate several ingredients that allow us to better exploit objective branching in a multiobjective setting. We extend the idea of probing to multiple objectives for the 0-1 case, enhance it in several ways, and show that, when coupled with objective branching, it results in significant speedups in terms of CPU times. We also show how to adapt it to the general integer case. Furthermore, we investigate cut generation based on the objective branching constraints. Besides, we generalize the best bound idea for node selection to multiple objectives, and we show that the proposed rules outperform, in the multiobjective literature, the commonly employed depth-first and breadth-first strategies. We also analyze problem-specific branching rules. We test the proposed ideas on available benchmark instances for three problem classes with three and four objectives, namely, the capacitated facility location problem, the uncapacitated facility location problem, and the knapsack problem. Our enhanced multiobjective branch-and-bound algorithm outperforms the best existing branch-and-bound–based approach and is the first to obtain competitive and even slightly better results than a state-of-the-art objective space search method on a subset of the problem classes. History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms – Discrete. Funding: This work was supported in whole, or in part, by the Austrian Science Fund [Grant P 31366]. Supplemental Material: The online supplement is available at https://doi.org/10.1287/ijoc.2022.0299 .

Biomarker-based risk prediction for the onset of neuroinflammation in X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is highly variable, ranging from slowly progressive adrenomyeloneuropathy to severe brain demyelination and inflammation (cerebral ALD, CALD) affecting males with childhood peak onset. Risk models integrating blood-based biomarkers to indicate CALD onset, enabling timely interventions, are lacking. Therefore, we evaluated the prognostic value of blood biomarkers in addition to current neuroimaging predictors for early detection of CALD. We measured blood biomarkers in a retrospective, male CALD risk-assessment cohort consisting of 134 X-ALD patients and 66 controls and in a phenotype-blinded validation set (25 X-ALD boys, 4-13 years) using Simoa®and Luminex® technologies. Among 25 biomarkers indicating axonal damage, astrocye/microglia activation, or immune-cell recruitment, neurofilament light chain (NfL) had the highest prognostic value for early indication of childhood/adolescent CALD. A plasma NfL cut-off level of 8.33pg/mL, determined in the assessment cohort, correctly discriminated CALD with an accuracy of 96% [95% CI: 80-100] in the validation group. Multivariable logistic regression models revealed that combining NfL with GFAP or cytokines/chemokines (IL-15, IL-12p40, CXCL8, CCL11, CCL22, and IL-4) that were significantly elevated in CALD vs healthy controls had no additional benefit for detecting neuroinflammation. Some cytokines/chemokines were elevated only in childhood/adolescent CALD and already upregulated in asymptomatic X-ALD children (IL-15, IL-12p40, and CCL7). In adults, NfL levels distinguished CALD but were lower than in childhood/adolescent CALD patients with similar (MRI) lesion severity. Blood GFAP did not differentiate CALD from non-inflammatory X-ALD. Biomarker-based risk prediction with a plasma NfL cut-off value of 8.33pg/mL, determined by ROC analysis, indicates CALD onset with high sensitivity and specificity in childhood X-ALD patients. A specific pro-inflammatory cytokine/chemokine profile in asymptomatic X-ALD boys may indicate a primed, immanent inflammatory state aligning with peak onset of CALD. Age-related differences in biomarker levels in adult vs childhood CALD patients warrants caution in predicting onset and progression of CALD in adults. Further evaluations are needed to assess clinical utility of the NfL cut-off for risk prognosis of CALD onset. Austrian Science Fund, European Leukodystrophy Association.

Oriented Calmness and Sweeping Process Dynamics

Daniilidis and Drusviatskiy, in 2017, extended the celebrated Kurdyka–Łojasiewicz inequality from definable functions to definable multivalued maps by establishing that the coderivative mapping admits a desingularization around every critical value. As was the case in the gradient dynamics, this desingularization yields a uniform control of the lengths of all bounded orbits of the corresponding sweeping process. In this paper, working outside the framework of o-minimal geometry, we characterize the existence of a desingularization for the coderivative in terms of the behavior of the sweeping process orbits and the integrability of the talweg function. These results are close in spirit with the ones in Bolte et al., 2010, in which characterizations for the desingularization of the (sub)gradient of functions is obtained. Funding: A. Daniilidis was supported by the Austrian Science Fund [Grant FWF P-36344N], Fondo Nacional de Desarrollo Científico y Tecnológico [Grant 1211217], and Centro de Modelamiento Matemático [Grant FB210005]. S. Tapia was supported by Agencia Nacional de Investigación y Desarrollo (Chile)-Programa de Fortalecimiento de Capital Humano Académico Doctorado Nacional [Grant 2018-21181905].

The Role of EAAT4 in Epidermal Differentiation and Calcium Homeostasis During Aging

The Role of EAAT4 in Epidermal Differentiation and Calcium Homeostasis During Aging