Unravelling the signaling power of pollutants

Exposure to environmental pollutants contributes to diverse pathologies, including pulmonary disease, lower respiratory infections, cancer, and stroke. Pollutants' entry can occur through inhalation, traversing endothelial and epithelial barriers, and crossing the blood-brain barrier, leading to a wide distribution throughout the human body via systemic circulation. Pollutants cause cellular damage by multiple mechanisms encompassing oxidative stress, mitochondrial dysfunction, (neuro)inflammation, and protein instability/proteotoxicity. Sensing pollutants has added a new dimension to disease progression and drug failure. Understanding the molecular pathways and potential receptor binding/signaling that underpin 'sensing' could contribute to ways to combat the detrimental effects of pollutants. We highlight key points of pollutant signaling, crosstalk with receptors acting as drug targets for chronic diseases, and discuss the potential for future therapeutics.</p

Potkleibossen in Noord- en Oost-Drenthe:Ondergrond, cultuurgeschiedenis en vegetatie

Two specific regions in the north and east of the province of Drenthe (northern Netherlands) contain shallow heavy clay soils that date from the Elsterien Ice Age (475,000—410,000 years BP). As these soils are unsuittable for human settlement or arable farming these regions include a relatively high numberof ancient woodlands. The paper describes the geological, cultural-historical and ecological characteristics of three of these woodlands. Glacial clay soils dating from this second—tolast ice age occur exclusively in places where all younger sediments have been eroded. This is only the case at the edge of the DrentsPlateau. The blackish grey clay layers are extremely stagnant, making them suitable for nothing but grassland. But in the Middle Ages the clay was found to be very well suited for the production of bricks and tiles.This is why the largest monastery in the Netherlands — the Cistercian Abbey of Aduard — founded several brick and tile factories in these glacial clay areas in the 13th and 14th centuries. In the 16th and 17th centuries local noblemen and industrial entrepreneurs took over this brick industry, which remained active until the mid-20th century. The best preserved brick-production landscape is in the ancient woodland of De Kleibosch (Foxwolde), where numerous clay pits, field oven relics and heaps of misfired bricks are the silent witnesses of this historical brick industry. Most ancient woodlands on glacial clay soilshave been used as commons by local farmers since medieval times. Written sources like village by-laws tell us that these woodlands produced vast amounts of oak timber, coppice wood and faggots, and were also extensively used for herding cattle and pigs. Because of their rich clay soil and long history of humanexploitation, the last five remnants of this particular type of ancient woodlands contain a unique flora including more than 25 native tree and shrub species and many rare ancient woodland plants. Even though the original woodland was reclaimed in the 19th and 20th centuries, the hedges and woodbanks appearto contain many relics of this ancient woodland vegetation. They therefore deserve speccial attention from researchers, nature managers and politicians to guarantee a sustainable future for these very rare historical-ecological landscapes

Evaluating proposals in innovation contests:Exploring negative scoring spillovers in the absence of a strict evaluation sequence

Prior research demonstrated that, when a strict evaluation sequence is present in innovation contests, the score of the previously evaluated proposal negatively influences the scoring of a subsequent proposal. In this paper, we expand our understanding of such negative scoring spillovers by analysing a setting where not only the previously evaluated proposal, but all other proposals within the same meeting can potentially contribute to negative scoring spillovers. We rely on a sample of 561 proposals in 53 publicly funded innovation contests, launched within the scope of four regional innovation programs in the Netherlands. We also introduce an alternative methodological approach with peer effects to adequately model and test the existence of negative scoring spillovers in contests where a strict evaluation sequence is absent. We provide evidence that, in such contests, proposals can mutually influence each other and that the magnitude of these spillovers depends on the design of the innovation contest. We also discuss the implications of these findings for the specific literature on innovation contests and the broader literature on evaluation spillovers in decision-making processes

An iterative sample scenario approach for the dynamic dispatch waves problem

A challenge in same-day delivery operations is that delivery requests are typically not known beforehand, but are instead revealed dynamically during the day. This uncertainty introduces a trade-off between dispatching vehicles to serve requests as soon as they are revealed to ensure timely delivery, and delaying the dispatching decision to consolidate routing decisions with future, currently unknown requests. In this paper, we study the dynamic dispatch waves problem, a same-day delivery problem in which vehicles are dispatched at fixed decision moments. At each decision moment, the system operator must decide which of the known requests to dispatch, and how to route these dispatched requests. The operator's goal is to minimize the total routing cost while ensuring that all requests are served on time. We propose iterative conditional dispatch (ICD), an iterative solution construction procedure based on a sample scenario approach. ICD iteratively solves sample scenarios to classify requests to be dispatched, postponed, or undecided. The set of undecided requests shrinks in each iteration until a final dispatching decision is made in the last iteration. We develop two variants of ICD: one variant based on thresholds, and another variant based on similarity. A significant strength of ICD is that it is conceptually simple and easy to implement. This simplicity does not harm performance: through rigorous numerical experiments, we show that both variants efficiently navigate the large state and action spaces of the dynamic dispatch waves problem and quickly converge to a high-quality solution. Finally, we demonstrate that the threshold-based ICD variant achieves excellent results on instances from the EURO meets NeurIPS 2022 vehicle routing competition, nearly matching the performance of the winning machine learning-based strategy

eHealth tools to assess the neurological function for research, in absence of the neurologist:a systematic review, part I (software)

Background: Neurological disorders remain a worldwide concern due to their increasing prevalence and mortality, combined with the lack of available treatment, in most cases. Exploring protective and risk factors associated with the development of neurological disorders will allow for improving prevention strategies. However, ascertaining neurological outcomes in population-based studies can be both complex and costly. The application of eHealth tools in research may contribute to lowering the costs and increase accessibility. The aim of this systematic review is to map existing eHealth tools assessing neurological signs and/or symptoms for epidemiological research. Methods: Four search engines (PubMed, Web of Science, Scopus &amp; EBSCOHost) were used to retrieve articles on the development, validation, or implementation of eHealth tools to assess neurological signs and/or symptoms. The clinical and technical properties of the software tools were summarised. Due to high numbers, only software tools are presented here. Findings: A total of 42 tools were retrieved. These captured signs and/or symptoms belonging to four neurological domains: cognitive function, motor function, cranial nerves, and gait and coordination. An additional fifth category of composite tools was added. Most of the tools were available in English and were developed for smartphone device, with the remaining tools being available as web-based platforms. Less than half of the captured tools were fully validated, and only approximately half were still active at the time of data collection. Interpretation: The identified tools often presented limitations either due to language barriers or lack of proper validation. Maintenance and durability of most tools were low. The present mapping exercise offers a detailed guide for epidemiologists to identify the most appropriate eHealth tool for their research. Funding: The current study was funded by a PhD position at the University of Groningen. No additional funding was acquired.</p

Between Liberation and Control:Mixing Methods to Investigate How Users Experience Menstrual Cycle Tracking Applications

Menstrual Cycle Tracking Applications (MCTAs), like other FemTech applications, are marketed as tools of empowerment. They claim to help menstruators to better understand their cycle and (re)gain control over their bodies by datafication of physical processes and mental states. However, despite technological solutionist promises, the development of such applications is shaped by discourses and knowledge situated in traditional and interlinked biomedical, neoliberal, and patriarchal power systems and archaic taboos. This study answers the research question through both quantitative and qualitative research. For the quantitative part of the research, an automated content analysis of 139 posts and 1988 comments from three different subreddits—r/Periods, r/TwoXChromosomes, and r/birthcontrol—was conducted using R and its RedditExtractoR package. The qualitative part of the study includes the execution of two focus groups with six and seven women, living in the Netherlands, between the ages of 22 and 26 in December 2021, during the COVID-19 pandemic.The research pointed out that both focus group participants and Reddit users use MCTAs to track both their menstruation and associated bodily and mental states and paradoxically experience them as both liberating and controlling. Participants primarily view menstrual cycle tracking applications (MCTAs) as liberating and empowering, as users believe these apps help them to (1) increase their menstrual literacy, (2) be more considerate of themselves during different phases of the menstrual cycle, and (3) generally regain control over their natural cycle. Participants felt controlled in two ways: (1) through the menstrual taboo that is still present in their everyday lives, and (2) through patriarchal notions of femininity and sexuality that are embedded into the design apps. Even though participants are less attentive to neoliberal and biomedical power systems, subtle nudges given by MCTAs make them incorporate these power systems into their data sense

Lifestyle and dry eye disease:an epidemiological perspective

Dry eye disease is a common condition affecting around 10% of the Dutch population. Dry eye disease is a disorder caused by the interplay between several different factors, including internal vulnerabilities and external exposures. In this thesis, the link between several lifestyle factors, including sleep quality, diet, and sedentary behavior, and higher or lower risk of having dry eye disease was explored. The main takeaways for this research is that poor sleep quality is tied to a greater prevalence of dry eye disease. And that a more sedentary lifestyle, especially in conjunction with greater screen-use, is associated with a higher risk of having dry eye. In general, dietary factors, including water intake, caffeine consumption, alcohol consumption, and a Mediterranean diet were not strongly connected to dry eye disease, despite a connection between a Mediterranean diet and lower markers of inflammation in the blood. In summary, dry eye disease is a complex disorder where a holistic approach is necessary, and clinicians should be aware of the high burden of disease that many patients experience. Future research should assess the impact of targeted lifestyle interventions in this patient population on both measures of dry eye disease and broader quality of life metrics

Sulphoxidation reactions catalysed by the Baeyer-Villiger monooxygenase OTEMO from Pseudomonas putida ATCC 17453

The Baeyer-Villiger monooxygenase OTEMO from Pseudomonas putida ATCC 17453 has been employed as biocatalyst in the asymmetric synthesis of a set of optically active sulphoxides. Several alkyl aryl sulphides are oxidized by this biocatalyst leading to the (S)-sulphoxides. Especially for those substrates containing electron-donating groups in the aromatic ring or in the alkyl moiety, good to high enantiopurities can be obtained. OTEMO is also able to perform the kinetic resolution of racemic sulphoxides, but with low enantioselectivities. Finally, parameters that can affect its biocatalytic properties, such as pH, temperature, organic cosolvents and substrate concentration, have been tested to get a better insight into the biocatalytic potential of this hitherto poorly explored oxidative biocatalyst.</p