Estimator selection for regression functions in exponential families with application to changepoint detection

E-print/Working paper (2023)

Einleitung : Neue Perspektiven auf den Heimat-Begriff

in Carstensen, Thorsten; Kohns, Oliver (Eds.) Heimat in Literatur und Kultur : neue Perspektiven (2023)

A matter of habit? Stressful life events and cognitive flexibility in 15-month-olds

in Infant Behavior and Development (2023), 71 file://localhost/Users/robert.kumsta/Documents/Papers%20Library/Tisborn-A%20matter%20of%20habit-%20Stressful%20life%20events%20and%20cognitive%20flexibility%20in%2015-month-olds-2023-Infant%20Behavior%20and%20Development.pdf

Exposure to chronic stress is associated with habitual learning in adults. We studied the origins of this association by examining the link between stressful life events and infant cognitive flexibility ... [more ▼]

Exposure to chronic stress is associated with habitual learning in adults. We studied the origins of this association by examining the link between stressful life events and infant cognitive flexibility. The final sample consisted of N = 72 fifteen-month-old infants and their mothers. Mothers completed a survey on pre- and postnatal negative life events. To assess chronic stress physiologically, infant and maternal hair cortisol concentrations were determined for cortisol accumulation during the past 3 months. Each infant participated in two cognitive tasks in the laboratory. An instrumental learning task tested infants’ ability to disengage from a habituated action when this action became ineffective (Seehagen et al., 2015). An age-adequate version of the A-not-B task tested infants’ ability to find a toy at location B after repeatedly finding it at location A. Correlations between cortisol concentrations and postnatal negative life events (number, perceived impact) did not yield significance. Infant and maternal hair cortisol concentrations were not correlated. Infants’ ability to shift to a new action in either task, controlled for acute stress, correlated neither with pre- and postnatal negative life events nor with cortisol concentrations. Taken together, these results indicate that the potential link between long-term stress exposure and cognitive flexibility might not be present in samples with low levels of psychosocial stress. [less ▲]

Probabilistic Deontic Logics for Reasoning about Uncertain Norms

in IfCoLog Journal of Logics and Their Applications (2023)

In this article, we present a proof-theoretical and model-theoretical approach to probabilistic logic for reasoning about uncertainty about normative state- ments. We introduce two logics with languages ... [more ▼]

In this article, we present a proof-theoretical and model-theoretical approach to probabilistic logic for reasoning about uncertainty about normative state- ments. We introduce two logics with languages that extend both the language of monadic deontic logic and the language of probabilistic logic. The first logic allows statements like “the probability that one is obliged to be quiet is at least 0.9”. The second logic allows iteration of probabilities in the language. We axiomatize both logics, provide the corresponding semantics and prove that the axiomatizations are sound and complete. We also prove that both logics are decidable. In addition, we show that the problem of deciding satisfiability for the simpler of our two logics is in PSPACE, no worse than that of deontic logic. [less ▲]

Reactive microglia are the major source of tumor necrosis factor alpha and contribute to astrocyte dysfunction and acute seizures in experimental temporal lobe epilepsy.

in Glia (2023), 71(2), 168-186

Extensive microglia reactivity has been well described in human and experimental temporal lobe epilepsy (TLE). To date, however, it is not clear whether and based on which molecular mechanisms microglia ... [more ▼]

Extensive microglia reactivity has been well described in human and experimental temporal lobe epilepsy (TLE). To date, however, it is not clear whether and based on which molecular mechanisms microglia contribute to the development and progression of focal epilepsy. Astroglial gap junction coupled networks play an important role in regulating neuronal activity and loss of interastrocytic coupling causally contributes to TLE. Here, we show in the unilateral intracortical kainate (KA) mouse model of TLE that reactive microglia are primary producers of tumor necrosis factor (TNF)α and contribute to astrocyte dysfunction and severity of status epilepticus (SE). Immunohistochemical analyses revealed pronounced and persistent microglia reactivity, which already started 4 h after KA-induced SE. Partial depletion of microglia using a colony stimulating factor 1 receptor inhibitor prevented early astrocyte uncoupling and attenuated the severity of SE, but increased the mortality of epileptic mice following surgery. Using microglia-specific inducible TNFα knockout mice we identified microglia as the major source of TNFα during early epileptogenesis. Importantly, microglia-specific TNFα knockout prevented SE-induced gap junction uncoupling in astrocytes. Continuous telemetric EEG recordings revealed that during the first 4 weeks after SE induction, microglial TNFα did not significantly contribute to spontaneous generalized seizure activity. Moreover, the absence of microglial TNFα did not affect the development of hippocampal sclerosis but attenuated gliosis. Taken together, these data implicate reactive microglia in astrocyte dysfunction and network hyperexcitability after an epileptogenic insult. [less ▲]

Eliminating oncogenic RAS: back to the future at the drawing board.

in Biochemical Society transactions (2023)

RAS drug development has made enormous strides in the past ten years, with the first direct KRAS inhibitor being approved in 2021. However, despite the clinical success of covalent KRAS-G12C inhibitors ... [more ▼]

RAS drug development has made enormous strides in the past ten years, with the first direct KRAS inhibitor being approved in 2021. However, despite the clinical success of covalent KRAS-G12C inhibitors, we are immediately confronted with resistances as commonly found with targeted drugs. Previously believed to be undruggable due to its lack of obvious druggable pockets, a couple of new approaches to hit this much feared oncogene have now been carved out. We here concisely review these approaches to directly target four druggable sites of RAS from various angles. Our analysis focuses on the lessons learnt during the development of allele-specific covalent and non-covalent RAS inhibitors, the potential of macromolecular binders to facilitate the discovery and validation of targetable sites on RAS and finally an outlook on a future that may engage more small molecule binders to become drugs. We foresee that the latter could happen mainly in two ways: First, non-covalent small molecule inhibitors may be derived from the development of covalent binders. Second, reversible small molecule binders could be utilized for novel targeting modalities, such as degraders of RAS. Provided that degraders eliminate RAS by recruiting differentially expressed E3-ligases, this approach could enable unprecedented tissue- or developmental stage-specific destruction of RAS with potential advantages for on-target toxicity. We conclude that novel creative ideas continue to be important to exterminate RAS in cancer and other RAS pathway-driven diseases, such as RASopathies. [less ▲]

You Can Dance! Generating Music-Conditioned Dances on Real 3D Scans.

Scientific Conference (2023)

The Limits of Consumer Law in Pursing Sustainability

in Nowag, Julian (Ed.) Research Handbook on Sustainability and Competition Law (2023)

This Chapter critically examines the limits of consumer law in pursuing sustainability. It uses the case of consumer sales of goods contracts, commercial communications and other marketing practices, and ... [more ▼]

This Chapter critically examines the limits of consumer law in pursuing sustainability. It uses the case of consumer sales of goods contracts, commercial communications and other marketing practices, and financial products and services to depict the potential and limitations of the current and proposed measures. The Chapter demonstrates that some consumer law provisions contradict consumer theories and scientific studies and provides targeted and actionable policy recommendations to address these deficiencies. [less ▲]

Water science must be Open Science

in Nature Water (2023), 1(1), 4--6

Since water is a common good, the outcome of water-related research should be accessible to everyone. Since Open Science is more than just open access research articles, journals must work with the ... [more ▼]

Since water is a common good, the outcome of water-related research should be accessible to everyone. Since Open Science is more than just open access research articles, journals must work with the research community to enable fully open and FAIR science [less ▲]

Inside out: A relational perspective on Luxembourg

Report (2023)

The paper adds to the synthesis of the 2922 INURA-Annual Meeting held in Luxembourg and includes a reflection on the practice of comparative analysis and exchange of experience in urban policy and ... [more ▼]

The paper adds to the synthesis of the 2922 INURA-Annual Meeting held in Luxembourg and includes a reflection on the practice of comparative analysis and exchange of experience in urban policy and planning. The informed statements made by INURA-members on related issues in Luxembourg are considered rather different (and very much to the point), compared to the often less informed praise by visitors from outside. This peculiar outcome of 'relationality' from outside may hinder a more effective policy response to be developed within the country. [less ▲]