Search

There is growing concern over climate models that project significant changes in the oceans, with consequences on marine biodiversity and human well-being. However, marine and coastal ecosystems respond differently to climate change-related stressors depending on the ecosystem, species composition and interactions, geomorphologic settings, and spatial distribution, but also on the presence of local stressors interacting cumulatively with climate change-related pressures. Our paper provides a comprehensive review of the current literature about the effects of climate-related pressures on marine and coastal ecosystems and how local stressors affect their resilience. Our work focuses on key marine and coastal ecosystems from three ecoregions: the Caribbean Sea (coral reefs, mangrove forests, seagrass beds), the Mediterranean Sea (the coral Cladocora caespitosa, maërl beds and seagrass beds) and the North-East Atlantic, which include kelp forests, maërl beds, salt marshes and seagrass beds. This review highlights the need for a more comprehensive, multi-species, and multi-stressors approach to predict better changes at the ecosystem and seascape levels of marine and coastal ecosystems. Nevertheless, there is enough evidence to argue that addressing locally key manageable stressors common to multiple ecosystems, such as nutrient enrichment, coastal development, hydrologic disturbances, anchoring or sedimentation, will reduce the identified adverse effects of climate change. This knowledge is critical for practical conservation actions and coastal and marine spatial management at the ecoregion scale and beyond

There is growing concern over climate models that project significant changes in the oceans, with consequences on marine biodiversity and human well-being. However, marine and coastal ecosystems respond differently to climate change-related stressors depending on the ecosystem, species composition and interactions, geomorphologic settings, and spatial distribution, but also on the presence of local stressors interacting cumulatively with climate change-related pressures. Our paper provides a comprehensive review of the current literature about the effects of climate-related pressures on marine and coastal ecosystems and how local stressors affect their resilience. Our work focuses on key marine and coastal ecosystems from three ecoregions: the Caribbean Sea (coral reefs, mangrove forests, seagrass beds), the Mediterranean Sea (the coral Cladocora caespitosa, maërl beds and seagrass beds) and the North-East Atlantic, which include kelp forests, maërl beds, salt marshes and seagrass beds. This review highlights the need for a more comprehensive, multi-species, and multi-stressors approach to predict better changes at the ecosystem and seascape levels of marine and coastal ecosystems. Nevertheless, there is enough evidence to argue that addressing locally key manageable stressors common to multiple ecosystems, such as nutrient enrichment, coastal development, hydrologic disturbances, anchoring or sedimentation, will reduce the identified adverse effects of climate change. This knowledge is critical for practical conservation actions and coastal and marine spatial management at the ecoregion scale and beyond.

Background: In recent years, social media have emerged as important spaces for commercial marketing of health tests, which can be used for the screening and diagnosis of otherwise generally healthy people. However, little is known about how health tests are promoted on social media, whether the information provided is accurate and balanced, and if there is transparency around conflicts of interest. Objective: This study aims to understand and quantify how social media is being used to discuss or promote health tests with the potential for overdiagnosis or overuse to generally healthy people. Methods: Content analysis of social media posts on the anti-Mullerian hormone test, whole-body magnetic resonance imaging scan, multicancer early detection, testosterone test, and gut microbe test from influential international social media accounts on Instagram and TikTok. The 5 tests have been identified as having the following criteria: (1) there are evidence-based concerns about overdiagnosis or overuse, (2) there is evidence or concerns that the results of tests do not lead to improved health outcomes for generally healthy people and may cause harm or waste, and (3) the tests are being promoted on social media to generally healthy people. English language text-only posts, images, infographics, articles, recorded videos including reels, and audio-only posts are included. Posts from accounts with <1000 followers as well as stories, live videos, and non-English posts are excluded. Using keywords related to the test, the top posts were searched and screened until there were 100 eligible posts from each platform for each test (total of 1000 posts). Data from the caption, video, and on-screen text are being summarized and extracted into a Microsoft Excel (Microsoft Corporation) spreadsheet and included in the analysis. The analysis will take a combined inductive approach when generating key themes and a deductive approach using a prespecified fram, BACKGROUND: In recent years, social media have emerged as important spaces for commercial marketing of health tests, which can be used for the screening and diagnosis of otherwise generally healthy people. However, little is known about how health tests are promoted on social media, whether the information provided is accurate and balanced, and if there is transparency around conflicts of interest.OBJECTIVE: This study aims to understand and quantify how social media is being used to discuss or promote health tests with the potential for overdiagnosis or overuse to generally healthy people.METHODS: Content analysis of social media posts on the anti-Mullerian hormone test, whole-body magnetic resonance imaging scan, multicancer early detection, testosterone test, and gut microbe test from influential international social media accounts on Instagram and TikTok. The 5 tests have been identified as having the following criteria: (1) there are evidence-based concerns about overdiagnosis or overuse, (2) there is evidence or concerns that the results of tests do not lead to improved health outcomes for generally healthy people and may cause harm or waste, and (3) the tests are being promoted on social media to generally healthy people. English language text-only posts, images, infographics, articles, recorded videos including reels, and audio-only posts are included. Posts from accounts with <1000 followers as well as stories, live videos, and non-English posts are excluded. Using keywords related to the test, the top posts were searched and screened until there were 100 eligible posts from each platform for each test (total of 1000 posts). Data from the caption, video, and on-screen text are being summarized and extracted into a Microsoft Excel (Microsoft Corporation) spreadsheet and included in the analysis. The analysis will take a combined inductive approach when generating key themes and a deductive approach using a prespecified framework. Quantita

Background: In recent years, social media have emerged as important spaces for commercial marketing of health tests, which can be used for the screening and diagnosis of otherwise generally healthy people. However, little is known about how health tests are promoted on social media, whether the information provided is accurate and balanced, and if there is transparency around conflicts of interest. Objective: This study aims to understand and quantify how social media is being used to discuss or promote health tests with the potential for overdiagnosis or overuse to generally healthy people. Methods: Content analysis of social media posts on the anti-Mullerian hormone test, whole-body magnetic resonance imaging scan, multicancer early detection, testosterone test, and gut microbe test from influential international social media accounts on Instagram and TikTok. The 5 tests have been identified as having the following criteria: (1) there are evidence-based concerns about overdiagnosis or overuse, (2) there is evidence or concerns that the results of tests do not lead to improved health outcomes for generally healthy people and may cause harm or waste, and (3) the tests are being promoted on social media to generally healthy people. English language text-only posts, images, infographics, articles, recorded videos including reels, and audio-only posts are included. Posts from accounts with <1000 followers as well as stories, live videos, and non-English posts are excluded. Using keywords related to the test, the top posts were searched and screened until there were 100 eligible posts from each platform for each test (total of 1000 posts). Data from the caption, video, and on-screen text are being summarized and extracted into a Microsoft Excel (Microsoft Corporation) spreadsheet and included in the analysis. The analysis will take a combined inductive approach when generating key themes and a deductive approach using a prespecified fram, BACKGROUND: In recent years, social media have emerged as important spaces for commercial marketing of health tests, which can be used for the screening and diagnosis of otherwise generally healthy people. However, little is known about how health tests are promoted on social media, whether the information provided is accurate and balanced, and if there is transparency around conflicts of interest.OBJECTIVE: This study aims to understand and quantify how social media is being used to discuss or promote health tests with the potential for overdiagnosis or overuse to generally healthy people.METHODS: Content analysis of social media posts on the anti-Mullerian hormone test, whole-body magnetic resonance imaging scan, multicancer early detection, testosterone test, and gut microbe test from influential international social media accounts on Instagram and TikTok. The 5 tests have been identified as having the following criteria: (1) there are evidence-based concerns about overdiagnosis or overuse, (2) there is evidence or concerns that the results of tests do not lead to improved health outcomes for generally healthy people and may cause harm or waste, and (3) the tests are being promoted on social media to generally healthy people. English language text-only posts, images, infographics, articles, recorded videos including reels, and audio-only posts are included. Posts from accounts with <1000 followers as well as stories, live videos, and non-English posts are excluded. Using keywords related to the test, the top posts were searched and screened until there were 100 eligible posts from each platform for each test (total of 1000 posts). Data from the caption, video, and on-screen text are being summarized and extracted into a Microsoft Excel (Microsoft Corporation) spreadsheet and included in the analysis. The analysis will take a combined inductive approach when generating key themes and a deductive approach using a prespecified framework. Quantita

Zk-SNARKs help scale blockchains with Verifiable Off-chain Computations (VOC). zk-SNARK DSL toolkits are key when designing arithmetic circuits but fall short of automating the subsequent proof-generation step in an automated manner. We emphasize the need for portability, interoperability, and manageability in VOC-based solutions and introduce a Proving Service that is designed to provide a scalable and reusable solution for generating zk-SNARK proofs leveraging clouds., Comment: 2 pages, 3 figures

Verifiable decentralized federated learning (FL) systems combining blockchains and zero-knowledge proofs (ZKP) make the computational integrity of local learning and global aggregation verifiable across workers. However, they are not end-to-end: data can still be corrupted prior to the learning. In this paper, we propose a verifiable decentralized FL system for end-to-end integrity and authenticity of data and computation extending verifiability to the data source. Addressing an inherent conflict of confidentiality and transparency, we introduce a two-step proving and verification (2PV) method that we apply to central system procedures: a registration workflow that enables non-disclosing verification of device certificates and a learning workflow that extends existing blockchain and ZKP-based FL systems through non-disclosing data authenticity proofs. Our evaluation on a prototypical implementation demonstrates the technical feasibility with only marginal overheads to state-of-the-art solutions., Comment: 9 pages, 5 figures, This article has been accepted for presentation at the IEEE International Conference on Blockchain and Cryptocurrency (ICBC 2024)

Fluorogenic bioorthogonal reactions enable biomolecule visualization in real time. These reactions comprise reporters that "light up" upon reaction with complementary partners. While the spectrum of fluorogenic chemistries is expanding, few transformations are compatible with live cells due to cross-reactivities or insufficient signal turn-on. To address the need for more suitable chemistries for cellular imaging, we developed a fluorogenic reaction featuring cyclopropenone reporters and phosphines. The transformation involves regioselective activation and cyclization of cyclopropenones to form coumarin products. With optimal probes, the reaction provides >1600-fold signal turn-on, one of the highest fluorescence enhancements reported to date. The bioorthogonal motifs were evaluated in vitro and in cells. The reaction was also found to be compatible with other common fluorogenic transformations, enabling multicomponent, real-time imaging. Collectively, these data suggest that the cyclopropenone-phosphine reaction will bolster efforts to track biomolecule targets in their native settings.

Methylation of cytosines is a prototypic epigenetic modification of the DNA. It has been implicated in various regulatory mechanisms across the animal kingdom and particularly in vertebrates. We mapped DNA methylation in 580 animal species (535 vertebrates, 45 invertebrates), resulting in 2443 genome-scale DNA methylation profiles of multiple organs. Bioinformatic analysis of this large dataset quantified the association of DNA methylation with the underlying genomic DNA sequence throughout vertebrate evolution. We observed a broadly conserved link with two major transitions-once in the first vertebrates and again with the emergence of reptiles. Cross-species comparisons focusing on individual organs supported a deeply conserved association of DNA methylation with tissue type, and cross-mapping analysis of DNA methylation at gene promoters revealed evolutionary changes for orthologous genes. In summary, this study establishes a large resource of vertebrate and invertebrate DNA methylomes, it showcases the power of reference-free epigenome analysis in species for which no reference genomes are available, and it contributes an epigenetic perspective to the study of vertebrate evolution.

Für eine erfolgreiche Integration von Menschen mit Migrationshintergrund in die Gesellschaft ist die Teilhabe am Arbeitsmarkt grundlegend (Scheller, 2015; Klimont et al., 2022). Die Einstellung der österreichischen Bevölkerung gegenüber Migration war dabei 2019 überdurchschnittlich negativ, die Asylpolitik besonders restriktiv (Biffl, 2012). Aus der Arbeitslosen- Statistik geht hervor, dass Menschen aus den sogenannten Fluchtherkunftsländern – die häufigsten Nationalitäten jener Personen, welche einen Asylantrag gestellt haben – die Statistik anführen (Klimont et al., 2022). Folgt dem Antrag ein positiver Bescheid, so geht der Aufenthaltstitel und das Recht auf Asyl oder subsidiären Schutz, welche beide unter dem Begriff internationaler Schutzstatus zusammengefasst werden, mit einher. Zudem führt dieser zu einem freien Arbeitsmarktzugang. Die Disparität am Arbeitsmarkt zwischen allochthoner und autochthoner Bevölkerung kann jedoch nicht vollständig erklärt werden (vgl. Verwiebe et al., 2016; Hofer et al., 2013; Esser, 2006), weshalb Diskriminierung als Begründung offen bleibt (Scherr, 2020). Ziel der Arbeit ist es daher, eventuell bestehende subjektive Diskriminierungserfahrungen, als auch objektive Diskriminierung von Menschen mit internationalem Schutzstatus aufzuzeigen. Zu Beginn der Arbeit wurden dafür die institutionellen Rahmenbedingungen des Arbeitseinstiegs angeführt. Die aktuelle Asylpolitik lässt auf mögliche Unterscheidungen schließen, welche daraufhin anhand des Diskriminierungsverbotes betrachtet wurden. Daran schließt ein theoretischer Teil an, in welchem die Definition und Konstruktion sowie die Arten sozialer Diskriminierung angeführt werden. Weiterhin wird im Unterschied zur objektiven und „faktischen“ Diskriminierung auf subjektive Diskriminierung eingegangen. Die Voraussetzung für letztere ist dabei die subjektive Wahrnehmung der Erfahrung als diskriminierend. Im empirischen Teil sollten bestehende objektive Diskriminierung als auch subjektive Dis, Masterarbeit Universität Innsbruck 2023

BACKGROUND: Bifidobacteria represent an important gut commensal in humans, particularly during initial microbiome assembly in the first year of life. Enrichment of Bifidobacterium is mediated though the utilization of human milk oligosaccharides (HMOs), as several human-adapted species have dedicated genomic loci for transport and metabolism of these glycans. This results in the release of fermentation products into the gut lumen which may offer physiological benefits to the host. Synbiotic pairing of probiotic species with a cognate prebiotic delivers a competitive advantage, as the prebiotic provides a nutrient niche. METHODS: To determine the fitness advantage and metabolic characteristics of an HMO-catabolizing Bifidobacterium strain in the presence or absence of 2-fucosyllactose (2-FL), conventionally colonized mice were gavaged with either Bifidobacterium pseudocatenulatum MP80 (B.p. MP80) (as the probiotic) or saline during the first 3 days of the experiment and received water or water containing 2-FL (as the prebiotic) throughout the study. RESULTS: 16S rRNA gene sequencing revealed that mice provided only B.p. MP80 were observed to have a similar microbiota composition as control mice throughout the experiment with a consistently low proportion of Bifidobacteriaceae present. Using 1H NMR spectroscopy, similar metabolic profiles of gut luminal contents and serum were observed between the control and B.p. MP80 group. Conversely, synbiotic supplemented mice exhibited dramatic shifts in their community structure across time with an overall increased, yet variable, proportion of Bifidobacteriaceae following oral inoculation. Parsing the synbiotic group into high and moderate bifidobacterial persistence based on the median proportion of Bifidobacteriaceae, significant differences in gut microbial diversity and metabolite profiles were observed. Notably, metabolites associated with the fermentation of 2-FL by bifidobacteria were significantly greater in mice

Für eine erfolgreiche Integration von Menschen mit Migrationshintergrund in die Gesellschaft ist die Teilhabe am Arbeitsmarkt grundlegend (Scheller, 2015; Klimont et al., 2022). Die Einstellung der österreichischen Bevölkerung gegenüber Migration war dabei 2019 überdurchschnittlich negativ, die Asylpolitik besonders restriktiv (Biffl, 2012). Aus der Arbeitslosen- Statistik geht hervor, dass Menschen aus den sogenannten Fluchtherkunftsländern – die häufigsten Nationalitäten jener Personen, welche einen Asylantrag gestellt haben – die Statistik anführen (Klimont et al., 2022). Folgt dem Antrag ein positiver Bescheid, so geht der Aufenthaltstitel und das Recht auf Asyl oder subsidiären Schutz, welche beide unter dem Begriff internationaler Schutzstatus zusammengefasst werden, mit einher. Zudem führt dieser zu einem freien Arbeitsmarktzugang. Die Disparität am Arbeitsmarkt zwischen allochthoner und autochthoner Bevölkerung kann jedoch nicht vollständig erklärt werden (vgl. Verwiebe et al., 2016; Hofer et al., 2013; Esser, 2006), weshalb Diskriminierung als Begründung offen bleibt (Scherr, 2020). Ziel der Arbeit ist es daher, eventuell bestehende subjektive Diskriminierungserfahrungen, als auch objektive Diskriminierung von Menschen mit internationalem Schutzstatus aufzuzeigen. Zu Beginn der Arbeit wurden dafür die institutionellen Rahmenbedingungen des Arbeitseinstiegs angeführt. Die aktuelle Asylpolitik lässt auf mögliche Unterscheidungen schließen, welche daraufhin anhand des Diskriminierungsverbotes betrachtet wurden. Daran schließt ein theoretischer Teil an, in welchem die Definition und Konstruktion sowie die Arten sozialer Diskriminierung angeführt werden. Weiterhin wird im Unterschied zur objektiven und „faktischen“ Diskriminierung auf subjektive Diskriminierung eingegangen. Die Voraussetzung für letztere ist dabei die subjektive Wahrnehmung der Erfahrung als diskriminierend. Im empirischen Teil sollten bestehende objektive Diskriminierung als auch subjektive Dis, Nadia Heiss, Masterarbeit Universität Innsbruck 2023

Mantamonads were long considered to represent an “orphan” lineage in the tree of eukaryotes, likely branching near the most frequently assumed position for the root of eukaryotes. Recent phylogenomic analyses have placed them as part of the “CRuMs” supergroup, along with collodictyonids and rigifilids. This supergroup appears to branch at the base of Amorphea, making it of special importance for understanding the deep evolutionary history of eukaryotes. However, the lack of representative species and complete genomic data associated with them has hampered the investigation of their biology and evolution. Here, we isolated and described two new species of mantamonads, Mantamonas vickermani sp. nov. and Mantamonas sphyraenae sp. nov., for each of which we generated transcriptomic sequence data, as well as a high-quality genome for the latter. The estimated size of the M. sphyraenae genome is 25 Mb; our de novo assembly appears to be highly contiguous and complete with 9,416 predicted protein-coding genes. This near-chromosome-scale genome assembly is the first described for the CRuMs supergroup., The authors thank Drs. J.Z. Xiang, D. Xu, and H. Shang at the Weill Cornell’s Genome Resources Core Facility for their assistance with Illumina sequencing. We also thank Dr. S. Goodwin in the NGS sequencing core at Cold Spring Harbor Laboratory for her help with PacBio sequencing, Drs. J.A. Burns and A.A. Pittis for their initial data analysis efforts and K. Lukacs for her help with maintaining the M. sphyraenae cultures. This work was funded by the Simons Foundation Grant awards to EK (SF-382790 & SF-876199). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC Starting Grant No 803151 to L.E., and ERC Advanced Grants No 322669 and 787904 to P.L.-G. and D.M., respectively). L.J.G. was funded by the Horizon 2020 research and innovation programme under the European Marie Skłodowska-Curie Individual Fellowship H2020-MSCA-IF-2020 (grant agreement no. 101022101 - FungEye). GT was supported by the 2019 BP 00208 Beatriu de Pinos-3 Postdoctoral Program (BP3; 801370). Work in the Dacks lab is supported by Discovery Grants from the Natural Sciences and Engineering Research Council of Canada (RES0043758, RES0046091)., Peer Reviewed, "Article signat per 17 autors/es: Jazmin Blaz, Luis Javier Galindo, Aaron A. Heiss, Harpreet Kaur, Guifré Torruella, Ashley Yang, L. Alexa Thompson, Alexander Filbert, Sally Warring, Apurva Narechania, Takashi Shiratori, Ken-ichiro Ishida, Joel B. Dacks, Purificación López-García, David Moreira, Eunsoo Kim & Laura Eme", Postprint (published version)

Ancyromonads are small biflagellated protists with a bean-shaped morphology. They are cosmopolitan in marine, freshwater, and soil environments, where they attach to surfaces while feeding on bacteria. These poorly known grazers stand out by their uncertain phylogenetic position in the tree of eukaryotes, forming a deep-branching “orphan” lineage that is considered key to a better understanding of the early evolution of eukaryotes. Despite their ecological and evolutionary interest, only limited knowledge exists about their true diversity. Here, we aimed to characterize ancyromonads better by integrating environmental surveys with behavioral observation and description of cell morphology, for which sample isolation and culturing are indispensable. We studied 18 ancyromonad strains, including 14 new isolates and seven new species. We described three new and genetically divergent genera: Caraotamonas, Nyramonas, and Olneymonas, together encompassing four species. The remaining three new species belong to the already-known genera Fabomonas and Ancyromonas. We also raised Striomonas, formerly a subgenus of Nutomonas, to full genus status, on morphological and phylogenetic grounds. We studied the morphology of diverse ancyromonads under light and electron microscopy and carried out molecular phylogenetic analyses, also including 18S rRNA gene sequences from several environmental surveys. Based on these analyses, we have updated the taxonomy of Ancyromonadida., This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC Starting Grant No 803151 to L.E. and ERC Advanced Grants No 322669 and 787904 to P.L.-G. and D.M., respectively). GT was supported by the 2019 BP 00208 Beatriu de Pinos-3 Postdoctoral Program (BP3; 801370). LG was funded by the Horizon 2020 research and innovation programme under the European Marie Skłodowska-Curie Individual Fellowship H2020-MSCA-IF-2020 (grant agreement no. 101022101 —FungEye). We are thankful for access to the Imagerie-Gif core facility at the Institute for Integrative Biology of the Cell (Gif-sur-Yvette, France) and the Electron Microscopy Facility (EMF) of the Institut de Biologie Paris-Seine (Paris, France). We thank members of the UNICELL single-cell genomics platform (https://www.deemteam.fr/en/unicell) for help in cell isolation and rRNA gene sequencing. We also thank Kaleigh Lukacs for assistance with culture maintenance., Peer Reviewed, "Article signat per 12 autors/es: Naoji Yubuki, Guifré Torruella, Luis Javier Galindo, Aaron A. Heiss, Maria Cristina Ciobanu, Takashi Shiratori, Ken-ichiro Ishida, Jazmin Blaz, Eunsoo Kim, David Moreira, Purificación López-García, Laura Eme", Postprint (published version)

Increased labor scarcity and input costs, as well as the demand for ecologically more sound control of growing conditions while maintaining yield and quality in both viticulture as well as horticulture have proliferated the requirements for the current technologies such as implements and autonomous vehicles used in these domains. The increasing employment of such technology, however, brings up the issue of compatibility, in terms of data exchange, connectivity, and communication between the implements and autonomous vehicles used. Besides that, conducting the connection and communication in a standardized means adds more complexity to the issue. To properly address the above-mentioned issue, this work focused on developing a middleware that introduced the ISO 11783 standard-based communication to the setup for both, a weeder robot and a combination of a sprayer and a retrofitted tractor. The developed middleware also considered the information exchange with external systems such as real-time decision-making sensor systems and a farming controller to accurately carry out the field applications of weeding and spraying. The correctness of the weeding quality computation and the spraying coverage indicating the performance of the developed setups were verified before conducting in-field applications. The subsequent in-field weeding application indicated an adequate evaluation of the weeding quality with a variation from 94 to 100 % and zeros in the regions of the weeding path where the weeding was not necessary. The assessment of the spraying applications based on the comparison between the prescribed and the as-applied information showed a mean value of 1.08×104 mm3 m-2 for the absolute deviation from the maximum prescribed rate. Further analyses indicated that the as-applied rate varied with a deviation of 10 % during the field application, which was below the defined threshold.

Background Epigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. Methods We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000–2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. Results We included 669 men with 1,178 visits between 2000–2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. Conclusions Our findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sources. Peer, Background: Epigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. Methods: We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000–2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. Results: We included 669 men with 1,178 visits between 2000–2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. Conclusions: Our findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sou

We combine concepts from multilevel solvers for partial differential equations (PDEs) with neural network based deep learning and propose a new methodology for the efficient numerical solution of high-dimensional parametric PDEs. An in-depth theoretical analysis shows that the proposed architecture is able to approximate multigrid V-cycles to arbitrary precision with the number of weights only depending logarithmically on the resolution of the finest mesh. As a consequence, approximation bounds for the solution of parametric PDEs by neural networks that are independent on the (stochastic) parameter dimension can be derived. The performance of the proposed method is illustrated on high-dimensional parametric linear elliptic PDEs that are common benchmark problems in uncertainty quantification. We find substantial improvements over state-of-the-art deep learning-based solvers. As particularly challenging examples, random conductivity with high-dimensional non-affine Gaussian fields in 100 parameter dimensions and a random cookie problem are examined. Due to the multilevel structure of our method, the amount of training samples can be reduced on finer levels, hence significantly lowering the generation time for training data and the training time of our method., Comment: 42 pages, 5 figures, 5 tables

Randomized neural networks (randomized NNs), where only the terminal layer's weights are optimized constitute a powerful model class to reduce computational time in training the neural network model. At the same time, these models generalize surprisingly well in various regression and classification tasks. In this paper, we give an exact macroscopic characterization (i.e., a characterization in function space) of the generalization behavior of randomized, shallow NNs with ReLU activation (RSNs). We show that RSNs correspond to a generalized additive model (GAM)-typed regression in which infinitely many directions are considered: the infinite generalized additive model (IGAM). The IGAM is formalized as solution to an optimization problem in function space for a specific regularization functional and a fairly general loss. This work is an extension to multivariate NNs of prior work, where we showed how wide RSNs with ReLU activation behave like spline regression under certain conditions and if the input is one-dimensional., Comment: 16 pages + appendix

The authors regret that Loukas Athanasakos (f Department of Natural Resources Management and Agricultural Engineering, Agricultural University of Athens, 11855 Athens, Greece) was not included in the initial submission of the manuscript. The authors would like to apologise for any inconvenience caused.

We study the combinatorial assignment domain, which includes combinatorial auctions and course allocation. The main challenge in this domain is that the bundle space grows exponentially in the number of items. To address this, several papers have recently proposed machine learning-based preference elicitation algorithms that aim to elicit only the most important information from agents. However, the main shortcoming of this prior work is that it does not model a mechanism's uncertainty over values for not yet elicited bundles. In this paper, we address this shortcoming by presenting a Bayesian optimization-based combinatorial assignment (BOCA) mechanism. Our key technical contribution is to integrate a method for capturing model uncertainty into an iterative combinatorial auction mechanism. Concretely, we design a new method for estimating an upper uncertainty bound that can be used to define an acquisition function to determine the next query to the agents. This enables the mechanism to properly explore (and not just exploit) the bundle space during its preference elicitation phase. We run computational experiments in several spectrum auction domains to evaluate BOCA's performance. Our results show that BOCA achieves higher allocative efficiency than state-of-the-art approaches.

Background Epigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. Methods We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000–2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. Results We included 669 men with 1,178 visits between 2000–2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. Conclusions Our findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sources. Peer, Background: Epigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. Methods: We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000–2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. Results: We included 669 men with 1,178 visits between 2000–2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. Conclusions: Our findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sou

The article outlines the methodology of structural and parametric synthesis of neural network controllers for controlling objects with limiters under incomplete information about the controlled object. Artificial neural networks are used to create controllers that are sequentially integrated into a control system with control objects. Reinforcement learning and pre-building a neural network imitator of the control object are used to synthesize the neural network controller. This approach is particularly effective when classical control system synthesis methods are not applicable due to significant nonlinearity and the difficulty in forming a mathematical model of the control object with the required accuracy. The proposed methods expand the class of technical systems for which direct synthesis of near-optimal control laws is possible. The robustness, adaptability and technical feasibility of neural network controllers make them interesting for practical applications. The main attention in the article is paid to the choice of neural network structure in the imitator and controller, formation of training samples taking into account the limitations of the control object., Comment: 7 pages with 11 figures

Variable rate nitrogen (N) application is subject to spatio-temporal dynamics of multiple parameters and a high dependency on specific local conditions. Furthermore, existing algorithms are barely capable of considering agronomic expert knowledge and common application technology limits the precise in-field realization. This work approached the complexity of site-specific N management in terms of the decision making, as well as the technical and organizational realization in a systemic manner. A commercial real-time N-sensor system’s behavior was transferred into a fuzzy expert system and extended with soil information. The incorporation into a real-time control included also the spatial synchronization of dose rate determination and realization. A digital process chain to facilitate decision making, data management and execution in the field was conceptualized and evaluated with a prototypical implementation. The N-sensor’s algorithms were precisely imitated with a maximum percentage root mean square error of 0.14%, while the multi-parametric system has implied more robust decisions. In field tests, the real-time control has shown acceptable synchronization errors largely below 1 m and with medians in the range of 0.25 m under realistic conditions. The integrated system architecture has shown a high consistency in terms of straightforward and situative expert knowledge acquisition, as well as the suitability for different sensor and application technologies. The work represents a systemic approach for a derivation and employment of machine-readable algorithms from agronomic expert knowledge defining the cause-effect relationships for a site-specific N application. Its generic properties allow a supplementation by other models and can in turn strengthen them further., Die variable Ausbringung von Stickstoff (N) unterliegt zeitlich-räumlichen Dynamiken multipler Parameter sowie einer hohen Abhängigkeit von spezifischen lokalen Begebenheiten. Vorhandene Algorithmen sind kaum in der Lage, agronomisches Expertenwissen zu nutzen und gängige Applikationstechnologie limitiert die präzise Umsetzung im Feld. Diese Arbeit näherte sich der Komplexität von teilflächenspezifischem N-Management bezüglich der Entscheidungsfindung sowie der technischen und organisatorischen Umsetzung auf systemische Weise. Das Verhalten eines kommerziellen, in Echtzeit arbeitenden N-Sensorsystems wurde in ein Fuzzy-Expertensystem transferiert und mit kartierter Bodeninformation kombiniert. Die Umsetzung in einer Echtzeit-Steuerung beinhaltete auch die räumliche Synchronisation von Erfassung und Applikation der Düngermenge. Eine digitale Prozesskette zur Vereinfachung von Entscheidungsfindung, Datenmanagement und Ausführung im Feld wurde konzipiert und mithilfe einer prototypischen Implementierung evaluiert. Die Algorithmen des N-Sensors wurden präzise imitiert, wobei der prozentual ausgedrückte, mittlere quadratische Fehler bei maximal 0,14% lag, während das multi-parametrische System robustere Entscheidungen implizierte. Bei Tests im Feld zeigte die Echtzeit-Steuerung akzeptable Abweichungen in der räumlichen Synchronisation, wobei diese größtenteils unter 1 m lagen und unter realistischen Bedingungen Mediane im Bereich von 0,25 m aufwiesen. Die integrierte Systemarchitektur zeigte eine hohe Konsistenz in Bezug auf den einfachen und situativen Erwerb von Expertenwissen sowie die Eignung für unterschiedliche Sensor- und Applikationstechnologie. Die Arbeit stellt einen systemischen Ansatz für die Ableitung und Nutzung maschinenlesbarer Algorithmen aus agronomischem Expertenwissen dar, welches die Beziehung von Ursache und Wirkung für eine teilflächenspezifische N-Applikation beschreibt. Seine generischen Eigenschaften erlauben eine Ergänzung mit anderen relevante

Due to its decentralised, distributed and scalable nature, swarm robotics has great potential for applications ranging from agriculture to environmental monitoring and logistics. Various swarm control methods and algorithms are currently known, such as virtual leader, vector and potential field, and others. Such methods often show good results in specific conditions and tasks. The variety of tasks solved by the swarm requires the development of a universal control algorithm. In this paper, we propose an evolution of a thermal motion equivalent method (TMEM) inspired by the behavioural similarity of thermodynamic interactions between molecules. Previous research has shown the high efficiency of such a method for terrain monitoring tasks. This work addresses the problem of swarm formation of geometric structures, as required for logistics and formation movement tasks. It is shown that the formation of swarm geometric structures using the TMEM is possible with a special nonlinear interaction function of the agents. A piecewise linear interaction function is proposed that allows the formation of a stable group of agents. The results of the paper are validated by numerical modelling of the swarm dynamics. A linear quadrocopter model is considered as an agent. The fairness of the choice of the interaction function is shown., Comment: 7 pages with 9 figures

Variable rate nitrogen (N) application is subject to spatio-temporal dynamics of multiple parameters and a high dependency on specific local conditions. Furthermore, existing algorithms are barely capable of considering agronomic expert knowledge and common application technology limits the precise in-field realization. This work approached the complexity of site-specific N management in terms of the decision making, as well as the technical and organizational realization in a systemic manner. A commercial real-time N-sensor system’s behavior was transferred into a fuzzy expert system and extended with soil information. The incorporation into a real-time control included also the spatial synchronization of dose rate determination and realization. A digital process chain to facilitate decision making, data management and execution in the field was conceptualized and evaluated with a prototypical implementation. The N-sensor’s algorithms were precisely imitated with a maximum percentage root mean square error of 0.14%, while the multi-parametric system has implied more robust decisions. In field tests, the real-time control has shown acceptable synchronization errors largely below 1 m and with medians in the range of 0.25 m under realistic conditions. The integrated system architecture has shown a high consistency in terms of straightforward and situative expert knowledge acquisition, as well as the suitability for different sensor and application technologies. The work represents a systemic approach for a derivation and employment of machine-readable algorithms from agronomic expert knowledge defining the cause-effect relationships for a site-specific N application. Its generic properties allow a supplementation by other models and can in turn strengthen them further., Die variable Ausbringung von Stickstoff (N) unterliegt zeitlich-räumlichen Dynamiken multipler Parameter sowie einer hohen Abhängigkeit von spezifischen lokalen Begebenheiten. Vorhandene Algorithmen sind kaum in der Lage, agronomisches Expertenwissen zu nutzen und gängige Applikationstechnologie limitiert die präzise Umsetzung im Feld. Diese Arbeit näherte sich der Komplexität von teilflächenspezifischem N-Management bezüglich der Entscheidungsfindung sowie der technischen und organisatorischen Umsetzung auf systemische Weise. Das Verhalten eines kommerziellen, in Echtzeit arbeitenden N-Sensorsystems wurde in ein Fuzzy-Expertensystem transferiert und mit kartierter Bodeninformation kombiniert. Die Umsetzung in einer Echtzeit-Steuerung beinhaltete auch die räumliche Synchronisation von Erfassung und Applikation der Düngermenge. Eine digitale Prozesskette zur Vereinfachung von Entscheidungsfindung, Datenmanagement und Ausführung im Feld wurde konzipiert und mithilfe einer prototypischen Implementierung evaluiert. Die Algorithmen des N-Sensors wurden präzise imitiert, wobei der prozentual ausgedrückte, mittlere quadratische Fehler bei maximal 0,14% lag, während das multi-parametrische System robustere Entscheidungen implizierte. Bei Tests im Feld zeigte die Echtzeit-Steuerung akzeptable Abweichungen in der räumlichen Synchronisation, wobei diese größtenteils unter 1 m lagen und unter realistischen Bedingungen Mediane im Bereich von 0,25 m aufwiesen. Die integrierte Systemarchitektur zeigte eine hohe Konsistenz in Bezug auf den einfachen und situativen Erwerb von Expertenwissen sowie die Eignung für unterschiedliche Sensor- und Applikationstechnologie. Die Arbeit stellt einen systemischen Ansatz für die Ableitung und Nutzung maschinenlesbarer Algorithmen aus agronomischem Expertenwissen dar, welches die Beziehung von Ursache und Wirkung für eine teilflächenspezifische N-Applikation beschreibt. Seine generischen Eigenschaften erlauben eine Ergänzung mit anderen relevante

We study the design of iterative combinatorial auctions (ICAs). The main challenge in this domain is that the bundle space grows exponentially in the number of items. To address this, several papers have recently proposed machine learning (ML)-based preference elicitation algorithms that aim to elicit only the most important information from bidders. However, from a practical point of view, the main shortcoming of this prior work is that those designs elicit bidders' preferences via value queries (i.e., ``What is your value for the bundle $\{A,B\}$?''). In most real-world ICA domains, value queries are considered impractical, since they impose an unrealistically high cognitive burden on bidders, which is why they are not used in practice. In this paper, we address this shortcoming by designing an ML-powered combinatorial clock auction that elicits information from the bidders only via demand queries (i.e., ``At prices $p$, what is your most preferred bundle of items?''). We make two key technical contributions: First, we present a novel method for training an ML model on demand queries. Second, based on those trained ML models, we introduce an efficient method for determining the demand query with the highest clearing potential, for which we also provide a theoretical foundation. We experimentally evaluate our ML-based demand query mechanism in several spectrum auction domains and compare it against the most established real-world ICA: the combinatorial clock auction (CCA). Our mechanism significantly outperforms the CCA in terms of efficiency in all domains, it achieves higher efficiency in a significantly reduced number of rounds, and, using linear prices, it exhibits vastly higher clearing potential. Thus, with this paper we bridge the gap between research and practice and propose the first practical ML-powered ICA., Comment: AAAI 2024 (8 pages + appendix)

The Path-Dependent Neural Jump Ordinary Differential Equation (PD-NJ-ODE) is a model for predicting continuous-time stochastic processes with irregular and incomplete observations. In particular, the method learns optimal forecasts given irregularly sampled time series of incomplete past observations. So far the process itself and the coordinate-wise observation times were assumed to be independent and observations were assumed to be noiseless. In this work we discuss two extensions to lift these restrictions and provide theoretical guarantees as well as empirical examples for them. In particular, we can lift the assumption of independence by extending the theory to much more realistic settings of conditional independence without any need to change the algorithm. Moreover, we introduce a new loss function, which allows us to deal with noisy observations and explain why the previously used loss function did not lead to a consistent estimator.

[Abstract] Objective: Osteoarthritis (OA) is a highly prevalent chronic condition. The subchondral bone plays an important role in onset and progression of OA making it a potential treatment target for disease-modifying therapeutic approaches. However, little is known about changes of periarticular bone mineral density (BMD) in OA and its relation to meniscal coverage and meniscal extrusion at the knee. Thus, the aim of this study was to describe periarticular BMD in the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort at the knee and to analyze the association with structural disease severity, meniscal coverage and meniscal extrusion. Design: Quantitative CT (QCT), MRI and radiographic examinations were acquired in 275 patients with knee osteoarthritis (OA). QCT was used to assess BMD at the femur and tibia, at the cortical bone plate (Cort) and at the epiphysis at three locations: subchondral (Sub), mid-epiphysis (Mid) and adjacent to the physis (Juxta). BMD was evaluated for the medial and lateral compartment separately and for subregions covered and not covered by the meniscus. Radiographs were used to determine the femorotibial angle and were evaluated according to the Kellgren and Lawrence (KL) system. Meniscal extrusion was assessed from 0 to 3. Results: Mean BMD differed significantly between each anatomic location at both the femur and tibia (p < 0.001) in patients with KL0. Tibial regions assumed to be covered with meniscus in patients with KL0 showed lower BMD at Sub (p < 0.001), equivalent BMD at Mid (p = 0.07) and higher BMD at Juxta (p < 0.001) subregions compared to regions not covered with meniscus. Knees with KL2-4 showed lower Sub (p = 0.03), Mid (p = 0.01) and Juxta (p < 0.05) BMD at the medial femur compared to KL0/1. Meniscal extrusion grade 2 and 3 was associated with greater BMD at the tibial Cort (p < 0.001, p = 0.007). Varus malalignment is associated with significant greater BMD at the medial femur

Understanding how exogenous microbes stably colonize the animal gut is essential to reveal mechanisms of action and tailor effective probiotic treatments. Bifidobacterium species are naturally enriched in the gastrointestinal tract of breast-fed infants. Human milk oligosaccharides (HMOs) are associated with this enrichment. However, direct mechanistic proof of the importance of HMOs in this colonization is lacking given milk contains additional factors that impact the gut microbiota. This study examined mice supplemented with the HMO 2'fucosyllactose (2'FL) together with a 2'FL-consuming strain, Bifidobacterium pseudocatenulatum MP80. 2'FL supplementation creates a niche for high levels of B.p. MP80 persistence, similar to Bifidobacterium levels seen in breast-fed infants. This synergism impacted gut microbiota composition, activated anti-inflammatory pathways and protected against chemically-induced colitis. These results demonstrate that bacterial-milk glycan interactions alone drive enrichment of beneficial Bifidobacterium and provide a model for tunable colonization thus facilitating insight into mechanisms of health promotion by bifidobacteriain neonates.

Bioorthogonal chemistries are powerful tools to investigate biomolecules in their native environments and provide a holistic understanding of cellular functions. These transformations can be performed in complex physiological settings without disturbing endogenous activity (i.e., they are “bioorthogonal”). While the spectrum of bioorthogonal reactions has grown over the last two decades, few reactions can be deployed in cells. Additionally, the majority of cell-compatible chemistries cannot be used together due to cross reactivity issues, largely prohibiting multi-component studies. Most applications have thus been restricted to detecting a single biological target, which is informative but cannot provide a complete picture of cellular function. A more holistic understanding may be possible via the development of compatible reactions to monitor multiple biomolecules simultaneously. Additionally, new methods to visualize biomolecule dynamics and identify biomolecule interaction networks would enable new biological pursuits. To address these limitations, I developed new chemical strategies to probe biomolecule targets in live cells using bioorthogonal cyclopropenone and phosphine reagents.Overall, this thesis focuses on the development of new chemical reactions for applications in cellular systems. In Chapter 1, I introduce the utilities and characteristics of a popular reagent for bioorthogonal applications, phosphines. I summarize the broad types of bioorthogonal chemistries of phosphine probes and their applications. In Chapter 2, I describe a new class of biocompatible reagents: cyclopropeniminium compounds. These probes are stable in aqueous solution and react with phosphines via a distinct mechanism. Due to reactivity differences, these probes were compatible with other existing transformations for multicomponent applications. In Chapter 3, I describe a fluorescence “turn-on” (i.e. fluorogenic) reaction of cyclopropenones and phosphines for deployment in live ce

Bifidobacterium taxa are associated with the breastfed infant gut, namely, due to the bifidogenic nature of human milk’s oligosaccharide fraction. This association provides a model of resource-driven microbial assemblies as human milk oligosaccharides (HMO) are accessible to microbes found in the infant gut but the infant cannot use HMO as a nutrient resource. The catabolism strategy (intracellular versus extracellular) and breadth of HMO structures utilized by a Bifidobacterium microbe impacts fitness and competitive nature in a microbial community. Previous work focused on profiling Bifidobacterium genetic diversity and in vitro metabolism of human milk oligosaccharides (HMO). Chapter 1, a mini-review, attempts to synthesize research, focusing on how functional capabilities provide a fitness advantage to certain Bifidobacterium species when applied to an infant gut. The addendum contains primary research on how Bifidobacterium pseudocatenulatum strains forage for fucosylated HMO.The principal goal of this dissertation was to understand if a Bifidobacterium population could be enriched in a complex microbial community and if persistence could be achieved through introduction of an HMO nutrient resource, 2’-fucosyllactose (2’FL). Chapter 2 introduces how supplementation of 2’FL provides a fitness advantage to a Bifidobacterium pseudocatenulatum strain possessing a fucosylated HMO gene cluster in a mouse model. Even when high colonization resistance was present, 2’FL, a privileged nutrient resource, facilitated persistence and ameliorated a DSS-induced colitis model. Chapter 3 further characterizes the Bifidobacterium pseudocatenulatum persistence mouse model. Bifidobacterial metabolite products from 2’FL catabolism were found locally and systemically, although enrichment of those metabolites was dependent on high levels of B. pseudocatenulatum persisting in the mouse gut. This study also introduces the concept of mice categorized as responders and non-responders in

Bioorthogonal chemistries are powerful tools to investigate biomolecules in their native environments and provide a holistic understanding of cellular functions. These transformations can be performed in complex physiological settings without disturbing endogenous activity (i.e., they are “bioorthogonal”). While the spectrum of bioorthogonal reactions has grown over the last two decades, few reactions can be deployed in cells. Additionally, the majority of cell-compatible chemistries cannot be used together due to cross reactivity issues, largely prohibiting multi-component studies. Most applications have thus been restricted to detecting a single biological target, which is informative but cannot provide a complete picture of cellular function. A more holistic understanding may be possible via the development of compatible reactions to monitor multiple biomolecules simultaneously. Additionally, new methods to visualize biomolecule dynamics and identify biomolecule interaction networks would enable new biological pursuits. To address these limitations, I developed new chemical strategies to probe biomolecule targets in live cells using bioorthogonal cyclopropenone and phosphine reagents.Overall, this thesis focuses on the development of new chemical reactions for applications in cellular systems. In Chapter 1, I introduce the utilities and characteristics of a popular reagent for bioorthogonal applications, phosphines. I summarize the broad types of bioorthogonal chemistries of phosphine probes and their applications. In Chapter 2, I describe a new class of biocompatible reagents: cyclopropeniminium compounds. These probes are stable in aqueous solution and react with phosphines via a distinct mechanism. Due to reactivity differences, these probes were compatible with other existing transformations for multicomponent applications. In Chapter 3, I describe a fluorescence “turn-on” (i.e. fluorogenic) reaction of cyclopropenones and phosphines for deployment in live ce

Bifidobacterium taxa are associated with the breastfed infant gut, namely, due to the bifidogenic nature of human milk’s oligosaccharide fraction. This association provides a model of resource-driven microbial assemblies as human milk oligosaccharides (HMO) are accessible to microbes found in the infant gut but the infant cannot use HMO as a nutrient resource. The catabolism strategy (intracellular versus extracellular) and breadth of HMO structures utilized by a Bifidobacterium microbe impacts fitness and competitive nature in a microbial community. Previous work focused on profiling Bifidobacterium genetic diversity and in vitro metabolism of human milk oligosaccharides (HMO). Chapter 1, a mini-review, attempts to synthesize research, focusing on how functional capabilities provide a fitness advantage to certain Bifidobacterium species when applied to an infant gut. The addendum contains primary research on how Bifidobacterium pseudocatenulatum strains forage for fucosylated HMO.The principal goal of this dissertation was to understand if a Bifidobacterium population could be enriched in a complex microbial community and if persistence could be achieved through introduction of an HMO nutrient resource, 2’-fucosyllactose (2’FL). Chapter 2 introduces how supplementation of 2’FL provides a fitness advantage to a Bifidobacterium pseudocatenulatum strain possessing a fucosylated HMO gene cluster in a mouse model. Even when high colonization resistance was present, 2’FL, a privileged nutrient resource, facilitated persistence and ameliorated a DSS-induced colitis model. Chapter 3 further characterizes the Bifidobacterium pseudocatenulatum persistence mouse model. Bifidobacterial metabolite products from 2’FL catabolism were found locally and systemically, although enrichment of those metabolites was dependent on high levels of B. pseudocatenulatum persisting in the mouse gut. This study also introduces the concept of mice categorized as responders and non-responders in

Understanding how exogenous microbes stably colonize the animal gut is essential to reveal mechanisms of action and tailor effective probiotic treatments. Bifidobacterium species are naturally enriched in the gastrointestinal tract of breast-fed infants. Human milk oligosaccharides (HMOs) are associated with this enrichment. However, direct mechanistic proof of the importance of HMOs in this colonization is lacking given milk contains additional factors that impact the gut microbiota. This study examined mice supplemented with the HMO 2'fucosyllactose (2'FL) together with a 2'FL-consuming strain, Bifidobacterium pseudocatenulatum MP80. 2'FL supplementation creates a niche for high levels of B.p. MP80 persistence, similar to Bifidobacterium levels seen in breast-fed infants. This synergism impacted gut microbiota composition, activated anti-inflammatory pathways and protected against chemically-induced colitis. These results demonstrate that bacterial-milk glycan interactions alone drive enrichment of beneficial Bifidobacterium and provide a model for tunable colonization thus facilitating insight into mechanisms of health promotion by bifidobacteriain neonates.

Bioorthogonal phosphines were introduced in the context of the Staudinger ligation over 20 years ago. Since that time, phosphine probes have been used in myriad applications to tag azide-functionalized biomolecules. The Staudinger ligation also paved the way for the development of other phosphorus-based chemistries, many of which are widely employed in biological experiments. Several reviews have highlighted early achievements in the design and application of bioorthogonal phosphines. This review summarizes more recent advances in the field. We discuss innovations in classic Staudinger-like transformations that have enabled new biological pursuits. We also highlight relative newcomers to the bioorthogonal stage, including the cyclopropenone-phosphine ligation and the phospha-Michael reaction. The review concludes with chemoselective reactions involving phosphite and phosphonite ligations. For each transformation, we describe the overall mechanism and scope. We also showcase efforts to fine-tune the reagents for specific functions. We further describe recent applications of the chemistries in biological settings. Collectively, these examples underscore the versatility and breadth of bioorthogonal phosphine reagents.

Modeling a crystal as a periodic point set, we present a fingerprint consisting of density functions that facilitates the efficient search for new materials and material properties. We prove invariance under isometries, continuity, and completeness in the generic case, which are necessary features for the reliable comparison of crystals. The proof of continuity integrates methods from discrete geometry and lattice theory, while the proof of generic completeness combines techniques from geometry with analysis. The fingerprint has a fast algorithm based on Brillouin zones and related inclusion-exclusion formulae. We have implemented the algorithm and describe its application to crystal structure prediction.

Das Kartellrecht bezweckt gem. Art. 1 KG den Schutz der marktwirtschaftlichen Ordnung vor Kartellen und anderen Wettbewerbsbeschränkungen. Um diesen Schutz zu gewährleisten, hat der Gesetzgeber einerseits ein verwaltungsrechtliches Instrumentarium geschaffen (Art. 18 ff. KG), andererseits aber auch zivilrechtliche Ansprüche von Personen vorgesehen, die durch Wettbewerbsverstösse beeinträchtigt wurden (Art. 12 ff. KG). Die erstgenannte Schiene der Kartellrechtsdurchsetzung wird durch-aus intensiv genutzt, wenngleich die begrenzten Behördenressourcen Priorisierungen unvermeidlich machen. Ganz anders als in der EU, ruht hingegen die private Kartellrechtsdurchsetzung mittels zivilrechtlicher Ansprüche in der Schweiz bekanntlich in einem nur selten gestörten Dornröschenschlaf. Vor allem für den deliktischen Anspruch aus Art. 12 Abs. 1 lit. b i.V.m. Art. 41 OR wurden die Gründe hierfür bereits herausgearbeitet. Es sind dies namentlich Schwächen in der Anspruchsausgestaltung, wie beispielsweise kurze Verjährung und fehlende Anspruchsberechtigung von Konsumenten, aber wohl auch eine noch fehlende Rechtstradition der privaten Kartellrechtsdurchsetzung, die Anspruchsinhaber vor dem, infolge mangelnder Kasuistik schlecht kalkulier-baren Verfahrensrisiko zurückschrecken lässt. Ansprüche aus Vertrag haben demgegenüber in Literatur und Praxis weitaus weniger Aufmerksamkeit erfahren, obgleich sie potentiell eine wichtige Funktion im Gefüge des «private enforcement» einnehmen. Während nämlich der deliktische Anspruch aus Art. 12 Abs. 1 lit. b KG i.V.m. Art. 41 OR seinem dogmatischen Kern nach die wettbewerblichen Verhaltenspflichten gegenüber «jedermann», im hiesigen Kontext also gegenüber allen anderen unternehmerischen Marktteilnehmern adressiert, können mittels vertraglicher Ansprüche die spezifischen Umstände einer Sonderverbindung berücksichtigt werden, welche die Parteien in eine grössere Nähe zueinander bringt und ihnen damit andere, tendenziell anforderungsreichere Verhalte

BackgroundSeveral epigenome-wide association studies (EWAS) of ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) have been reported. However, EWAS of PM2.5 elements (PEs), reflecting different emission sources, are very limited.ObjectivesWe performed EWAS of short- and intermediate-term exposure to PM2.5 and 13 PEs. We hypothesized that significant changes in DNAm may vary by PM2.5 mass and its elements.MethodsWe repeatedly collected blood samples in the Normative Aging Study and measured leukocyte DNA methylation (DNAm) with the Illumina HumanMethylation450K BeadChip. We collected daily PM2.5 and 13 PEs at a fixed central site. To estimate the associations between each PE and DNAm at individual cytosine-phosphate-guanine (CpG) sites, we incorporated a distributed-lag (0-27 d) term in the setting of median regression with subject-specific intercept and examined cumulative lag associations. We also accounted for selection bias due to loss to follow-up and mortality prior to enrollment. Significantly differentially methylated probes (DMPs) were identified using Bonferroni correction for multiple testing. We further conducted regional and pathway analyses to identify significantly differentially methylated regions (DMRs) and pathways.ResultsWe included 695 men with 1,266 visits between 1999 and 2013. The subjects had a mean age of 75 years. The significant DMPs, DMRs, and pathways varied by to PM2.5 total mass and PEs. For example, PM2.5 total mass was associated with 2,717 DMPs and 10,470 DMRs whereas Pb was associated with 3,173 DMPs and 637 DMRs. The identified pathways by PM2.5 mass were mostly involved in mood disorders, neuroplasticity, immunity, and inflammation, whereas the pathways associated with motor vehicles (BC, Cu, Pb, and Zn) were related with cardiovascular disease and cancer (e.g., "PPARs signaling").ConclusionsPM2.5 and PE were associated with methylation changes at multiple probes and along multiple pathways

Background & objective: Contralesional 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis combined with speech-language therapy (SLT) has shown positive results on the recovery of naming in subacute (5–45 days) post-stroke aphasia. NORTHSTAR-CA is an extension of the previously reported NORTHSTAR trial to chronic aphasia (>6 months post-stroke) designed to compare the effectiveness of the same rTMS protocol in both phases. Methods: Sixty-seven patients with left middle cerebral artery infarcts (28 chronic, 39 subacute) were recruited (01-2014 to 07-2019) and randomized to receive rTMS (N = 34) or sham stimulation (N = 33) with SLT for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment. Chronic and subacute results were compared. Results: Adverse events were rare, mild, and did not differ between groups. Language outcomes improved significantly in all groups irrespective of treatment and recovery phase. At 30-day follow-up, there was a significant interaction of stimulation and recovery phase on naming recovery (P <.001). Naming recovery with rTMS was larger in subacute (Mdn = 1.91/IQR =.77) than chronic patients (Mdn =.15/IQR = 1.68/P =.015). There was no significant rTMS effect in the chronic aphasia group. Conclusions: The addition of rTMS to SLT led to significant supplemental gains in naming recovery in the subacute phase only. While this needs confirmation in larger studies, our results clarify neuromodulatory vs training-induced effects and indicate a possible window of opportunity for contralesional inhibitory stimulation interventions in post-stroke aphasia. NORTHSTAR trial registration: https://clinicaltrials.gov/ct2/show/NCT02020421.

Successful transformation requires organizations to structure and operate in new ways, which requires creating many new patterns for designing teams and their collaborations with other groups. Anna Wiedemann et al. introduce an example of an organizational structure tactic for enabling successful evolutionary change with a small group of development teams supported by a vendor-managed operations environment.