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N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully functional platforms are not yet available.
Here, we present the open source StudyU platform, which includes the StudyU Designer and StudyU app.
With the StudyU Designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials.
The StudyU app is a smartphone app with innovative user-centric elements for participants to partake in trials published through the StudyU Designer to assess the effects of different interventions on their health.
Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner.
We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice.
Physically interacting proteins form macromolecule complexes that drive diverse cellular processes. Advances in experimental techniques that capture interactions between proteins provide us with protein-protein interaction (PPI) networks from several model organisms. These datasets have enabled the prediction and other computational analyses of protein complexes. Here we provide a systematic review of the state-of-the-art algorithms for protein complex prediction from PPI networks proposed in the past two decades. The existing approaches that solve this problem are categorized into three groups, including: cluster-quality-based, node affinity-based, and network embedding-based approaches, and we compare and contrast the advantages and disadvantages. We further include a comparative analysis by computing the performance of eighteen methods based on twelve well-established performance measures on four widely used benchmark protein-protein interaction networks. Finally, the limitations and drawbacks of both, current data and approaches, along with the potential solutions in this field are discussed, with emphasis on the points that pave the way for future research efforts in this field. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
Starch is a complex carbohydrate polymer produced by plants and especially by crops in huge amounts. It consists of amylose and amylopectin, which have alpha-1,4-and alpha-1,6-linked glucose units. Despite this simple chemistry, the entire starch metabolism is complex, containing various (iso)enzymes/proteins. However, whose interplay is still not yet fully understood. Starch is essential for humans and animals as a source of nutrition and energy. Nowadays, starch is also commonly used in non-food industrial sectors for a variety of purposes. However, native starches do not always satisfy the needs of a wide range of (industrial) applications. This review summarizes the structural properties of starch, analytical methods for starch characterization, and in planta starch modifications.
Review of Ross Clare: Ancient Greece and Rome in Videogames. Representation, Play, Transmedia
(2023)
Aging has been viewed both as a random process due to accumulation of molecular and cellular damage over time and as a programmed process linked to cellular pathway important for growth and maturation. These views converge on mitochondria as both the major producer of damaging reactive oxidant species (ROS) and as signaling organelles. A finite proton leak across the inner mitochondrial membrane leading to a slight uncoupling of oxidative phosphorylation and respiration is an intrinsic property of all mitochondria and according to the "uncoupling to survive" hypothesis it has evolved to protect against ROS production to minimize oxidative damage. This hypothesis is supported by evidence linking an increased endogenous, uncoupling protein (UCP1) mediated, as well as experimentally induced mitochondrial uncoupling to an increased lifespan in rodents. This is possibly due to the synergistic activation of molecular pathways linked to life extending effects of caloric restriction as well as a mitohormetic response. Mitohormesis is an adaptive stress response through mitonuclear signaling which increases stress resistance resulting in health promoting effects. Part of this response is the induction of fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), two stress-induced mitokines which elicit beneficial systemic metabolic effects via endocrine action.
Purpose Modern food technology allows designing products aiming to simulate and replace traditional food. In affluent societies there is a rising tendency to consume foods derived from plants including milk imitations or plant drinks based on cereals, nuts, legumes, oil seeds or other plant families. Herein we review production and composition of such drinks, summarize consumers' motivations to change from milk to plant drinks and highlight nutritional and health implications of consuming plant drinks instead of milk, in particular if non-fortified and if consumed by infants, children, adolescents and the elderly. Results Whereas the macronutrient concentrations of some plant drinks (soy) may approach in some cases (protein) that of cow's milk, the nutritional quality of most plant drinks, e.g., the biological value of protein and the presence and amount of vitamins and essential minerals with high bioavailability does not. If cow's milk is exchanged for non-fortified and non-supplemented plant drinks consumers may risk deficiencies of calcium, zinc, iodine, vitamins B2, B12, D, A, and indispensable amino acids, particularly in infants and toddlers who traditionally consume significant portions of milk. The vegetable nature, appearance and taste of such plant drinks may be appealing to adult consumers and be chosen for adding variety to the menu. However, in young children fed exclusively such plant drinks severe metabolic disturbances may occur. Conclusion Parents, dietitians, physicians and consumers should be aware of such potential risks, if non-fortified plant drinks are consumed instead of milk.
In this chapter we review the basic principles of photocurrent generation in bulk heterojunction organic solar cells, discuss the loss channels limiting their efficiency, and present case studies of several polymer-fullerene blends. Using steady-state and transient, optical, and electrooptical techniques, we create a precise picture of the fundamental processes that ultimately govern solar cell efficiency.
In this paper, I discuss Karen Ng's reconstruction of Hegel's concept of life. On Ng's account, Hegel's conception of life has a remarkable double role to play: Life is both the proper object of judgment as well as a fundamental characterization of the activity of the judging subject. In a first step, I highlight the insight that Ng's account sheds on the internal connection of life and self-consciousness and the peculiar normativity of life. In a second step, I raise three concerns about Ng's strong focus on the logical notion of life which she characterizes as non-empirical and a priori. I argue that in order to uncover the full significance of the notion of life for Hegel we have to turn to his Philosophy of Nature and Spirit.
Tacitus and cinema
(2021)
Brownian motion and viscoelastic anomalous diffusion in homogeneous environments are intrinsically Gaussian processes. In a growing number of systems, however, non-Gaussian displacement distributions of these processes are being reported. The physical cause of the non-Gaussianity is typically seen in different forms of disorder. These include, for instance, imperfect "ensembles" of tracer particles, the presence of local variations of the tracer mobility in heteroegenous environments, or cases in which the speed or persistence of moving nematodes or cells are distributed. From a theoretical point of view stochastic descriptions based on distributed ("superstatistical") transport coefficients as well as time-dependent generalisations based on stochastic transport parameters with built-in finite correlation time are invoked. After a brief review of the history of Brownian motion and the famed Gaussian displacement distribution, we here provide a brief introduction to the phenomenon of non-Gaussianity and the stochastic modelling in terms of superstatistical and diffusing-diffusivity approaches.
Electrochemical methods offer the simple characterization of the synthesis of molecularly imprinted polymers (MIPs) and the readouts of target binding. The binding of electroinactive analytes can be detected indirectly by their modulating effect on the diffusional permeability of a redox marker through thin MIP films. However, this process generates an overall signal, which may include nonspecific interactions with the nonimprinted surface and adsorption at the electrode surface in addition to (specific) binding to the cavities. Redox-active low-molecular-weight targets and metalloproteins enable a more specific direct quantification of their binding to MIPs by measuring the faradaic current. The in situ characterization of enzymes, MIP-based mimics of redox enzymes or enzyme-labeled targets, is based on the indication of an electroactive product. This approach allows the determination of both the activity of the bio(mimetic) catalyst and of the substrate concentration.
The biosynthesis of the molybdenum cofactor (Moco) is highly conserved among all kingdoms of life. In all molybdoenzymes containing Moco, the molybdenum atom is coordinated to a dithiolene group present in the pterin-based 6-alkyl side chain of molybdopterin (MPT). In general, the biosynthesis of Moco can be divided into four steps in in bacteria: (i) the starting point is the formation of the cyclic pyranopterin monophosphate (cPMP) from 5 '-GTP, (ii) in the second step the two sulfur atoms are inserted into cPMP leading to the formation of MPT, (iii) in the third step the molybdenum atom is inserted into MPT to form Moco and (iv) in the fourth step bis-Mo-MPT is formed and an additional modification of Moco is possible with the attachment of a nucleotide (CMP or GMP) to the phosphate group of MPT, forming the dinucleotide variants of Moco. This review presents an update on the well-characterized Moco biosynthesis in the model organism Escherichia coli including novel discoveries from the recent years.
Plans are currently being drafted for the next decade of action on biodiversity-both the post-2020 Global Biodiversity Framework of the Convention on Biological Diversity (CBD) and Biodiversity Strategy of the European Union (EU). Freshwater biodiversity is disproportionately threatened and underprioritized relative to the marine and terrestrial biota, despite supporting a richness of species and ecosystems with their own intrinsic value and providing multiple essential ecosystem services. Future policies and strategies must have a greater focus on the unique ecology of freshwater life and its multiple threats, and now is a critical time to reflect on how this may be achieved. We identify priority topics including environmental flows, water quality, invasive species, integrated water resources management, strategic conservation planning, and emerging technologies for freshwater ecosystem monitoring. We synthesize these topics with decades of first-hand experience and recent literature into 14 special recommendations for global freshwater biodiversity conservation based on the successes and setbacks of European policy, management, and research. Applying and following these recommendations will inform and enhance the ability of global and European post-2020 biodiversity agreements to halt and reverse the rapid global decline of freshwater biodiversity.
The origins and development of the arid and highly seasonal steppe-desert biome in Central Asia, the largest of its kind in the world, remain largely unconstrained by existing records. It is unclear how Cenozoic climatic, geological, and biological forces, acting at diverse spatial and temporal scales, shaped Central Asian ecosystems through time. Our synthesis shows that the Central Asian steppe-desert has existed since at least Eocene times but experienced no less than two regime shifts, one at the Eocene-Oligocene Transition and one in the mid-Miocene. These shifts separated three successive "stable states," each characterized by unique floral and faunal structures. Past responses to disturbance in the Asian steppe-desert imply that modern ecosystems are unlikely to recover their present structures and diversity if forced into a new regime. This is of concern for Asian steppes today, which are being modified for human use and lost to desertification at unprecedented rates.
Starch is one of the most popular nutritional sources for both human and animals. Due to the variation of its nutritional traits and biochemical specificities, starch has been classified into rapidly digestible, slowly digestible and resistant starch. Resistant starch has its own unique chemical structure, and various forms of resistant starch are commercially available. It has been found being a multiple-functional regulator for treating metabolic dysfunction. Different functions of resistant starch such as modulation of the gut microbiota, gut peptides, circulating growth factors, circulating inflammatory mediators have been characterized by animal studies and clinical trials. In this mini-review, recent remarkable progress in resistant starch on gut microbiota, particularly the effect of structure, biochemistry and cell signaling on nutrition has been summarized, with highlights on its regulatory effect on gut microbiota.
Fragmentation of landscapes creates a transition zone in between natural habitats or different kinds of land use. In forested and agricultural landscapes with transition zones, microclimate and matter cycling are markedly altered. This probably accelerates and is intensified by global warming. However, there is no consensus on defining transition zones and quantifying relevant variables for microclimate and matter cycling across disciplines. This article is an attempt to a) revise definitions and offer a framework for quantitative ecologists, b) review the literature on microclimate and matter cycling in transition zones and c) summarise this information using meta-analysis to better understand bio-geochemical and bio-geophysical processes and their spatial extent in transition zones. We expect altered conditions in soils of transition zones to be 10-20 m with a maximum of 50 m, and 25-50 m for above-ground space with a maximum of 125 m.
We study differential cohomology on categories of globally hyperbolic Lorentzian manifolds. The Lorentzian metric allows us to define a natural transformation whose kernel generalizes Maxwell's equations and fits into a restriction of the fundamental exact sequences of differential cohomology. We consider smooth Pontryagin duals of differential cohomology groups, which are subgroups of the character groups. We prove that these groups fit into smooth duals of the fundamental exact sequences of differential cohomology and equip them with a natural presymplectic structure derived from a generalized Maxwell Lagrangian. The resulting presymplectic Abelian groups are quantized using the CCR-functor, which yields a covariant functor from our categories of globally hyperbolic Lorentzian manifolds to the category of C∗-algebras. We prove that this functor satisfies the causality and time-slice axioms of locally covariant quantum field theory, but that it violates the locality axiom. We show that this violation is precisely due to the fact that our functor has topological subfunctors describing the Pontryagin duals of certain singular cohomology groups. As a byproduct, we develop a Fréchet–Lie group structure on differential cohomology groups.
Macroecology and biogeography are concerned with understanding biodiversity patterns across space and time. In the past, the two disciplines have addressed this question mainly with correlative approaches, despite frequent calls for more mechanistic explanations. Recent advances in computational power, theoretical understanding, and statistical tools are, however, currently facilitating the development of more system-oriented, mechanistic models. We review these models, identify different model types and theoretical frameworks, compare their processes and properties, and summarize emergent findings. We show that ecological (physiology, demographics, dispersal, biotic interactions) and evolutionary processes, as well as environmental and human-induced drivers, are increasingly modelled mechanistically; and that new insights into biodiversity dynamics emerge from these models. Yet, substantial challenges still lie ahead for this young research field. Among these, we identify scaling, calibration, validation, and balancing complexity as pressing issues. Moreover, particular process combinations are still understudied, and so far models tend to be developed for specific applications. Future work should aim at developing more flexible and modular models that not only allow different ecological theories to be expressed and contrasted, but which are also built for tight integration with all macroecological data sources. Moving the field towards such a ‘systems macroecology’ will test and improve our understanding of the causal pathways through which eco-evolutionary processes create diversity patterns across spatial and temporal scales.
Cities and Mental Health
(2017)
Background: More than half of the global population currently lives in cities, with an increasing trend for further urbanization. Living in cities is associated with increased population density, traffic noise and pollution, but also with better access to health care and other commodities. Methods: This review is based on a selective literature search, providing an overview of the risk factors for mental illness in urban centers. Results: Studies have shown that the risk for serious mental illness is generally higher in cities compared to rural areas. Epidemiological studies have associated growing up and living in cities with a considerably higher risk for schizophrenia. However, correlation is not causation and living in poverty can both contribute to and result from impairments associated with poor mental health. Social isolation and discrimination as well as poverty in the neighborhood contribute to the mental health burden while little is known about specific inter actions between such factors and the built environment. Conclusion: Further insights on the interaction between spatial heterogeneity of neighborhood resources and socio-ecological factors is warranted and requires interdisciplinary research.