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Permafrost-agroecosystems include all cultivation and pastoral activities in areas underlain by permafrost. These systems support local livelihoods and food production and are rarely considered in global agricultural studies but may become more relevant as climate change is increasing opportunities for food production in high latitude and mountainous areas. The exact locations and amount of agricultural production in areas containing permafrost are currently unknown, therefore we provide an overview of countries where both permafrost and agricultural activities are present. We highlight the socioecological diversity and complexities of permafrostagroecosystems through seven case studies: (1) crop cultivation in Alaska, USA; (2) Indigenous food systems and crop cultivation in the Northwest Territories, Canada; (3) horse and cattle husbandry and Indigenous hay production in the Sakha Republic, Russia; (4) mobile pastoralism and husbandry in Mongolia; (5) yak pastoralism in the Central Himalaya, Nepal; (6) berry picking and reindeer herding in northern Fennoscandia; and (7) reindeer herding in northwest Russia. We discuss regional knowledge gaps associated with permafrost and make recommendations to policy makers and land users for adapting to changing permafrost environments. A better understanding of permafrost-agroecosystems is needed to help sustainably manage and develop these systems considering rapidly changing climate, environments, economies, and industries.

Classification of introns, which is crucial to understanding their evolution and splicing, has historically been binary and has resulted in the naming of major and minor introns that are spliced by their namesake spliceosome. However, a broad range of intron consensus sequences exist, leading us to here reclassify introns as minor, minor-like, hybrid, major-like, major and non-canonical introns in 263 species across six eukaryotic supergroups. Through intron orthology analysis, we discovered that minor-like introns are a transitory node for intron conversion across evolution. Despite close resemblance of their consensus sequences to minor introns, these introns possess an AG dinucleotide at the -1 and -2 position of the 5' splice site, a salient feature of major introns. Through combined analysis of CoLa-seq, CLIP-seq for major and minor spliceosome components, and RNAseq from samples in which the minor spliceosome is inhibited we found that minor-like introns are also an intermediate class from a splicing mechanism perspective. Importantly, this analysis has provided insight into the sequence elements that have evolved to make minor-like introns amenable to recognition by both minor and major spliceosome components. We hope that this revised intron classification provides a new framework to study intron evolution and splicing.

Permafrost-agroecosystems encompass northern social-ecological systems which include both cultivation of arable permafrost-affected soils, and animal husbandry practices. These heterogeneous food and cultural systems are being affected by a warming climate. Examples include increasing opportunities for growing crops through longer growing seasons, as well as impacts on animals’ local and long-distance migratory movements and their food sources. Furthermore, climate change driven permafrost thaw and thaw accelerated by land clearance is rapidly changing the biophysical and socioeconomic aspects of these systems. Therefore, an international collaboration encompassing experts from North America, Europe and Asia is working on increasing our understanding of permafrost-agroecosystems and contributing to the adaptation, resilience, and sustainability strategy of these rapidly evolving systems. The International Permafrost Association Permafrost-Agroecosystem Action Group is composed of ~30 members from 7 countries. The objectives of our action group are to share knowledge and build networking capacities through meetings and webinar presentation as well as to collaborate on publications and produce the first geospatial dataset of permafrost-agroecosystems. Our poster presentation provides an overview of the group’s activities including providing case studies from a range of high-latitude and high-altitude areas as part of a group manuscript in preparation and an update on our mapping activities.

Modern research increasingly relies on automated methods to assist researchers. An example of this is Optical Chemical Structure Recognition (OCSR), which aids chemists in retrieving information about chemicals from large amounts of documents. Markush structures are chemical structures that cannot be parsed correctly by OCSR and cause errors. The focus of this research was to propose and test a novel method for classifying Markush structures. Within this method, a comparison was made between fixed-feature extraction and end-to-end learning (CNN). The end-to-end method performed significantly better than the fixed-feature method, achieving 0.928 (0.035 SD) Macro F1 compared to the fixed-feature method's 0.701 (0.052 SD). Because of the nature of the experiment, these figures are a lower bound and can be improved further. These results suggest that Markush structures can be filtered out effectively and accurately using the proposed method. When implemented into OCSR pipelines, this method can improve their performance and use to other researchers., Comment: 15 pages, 9 tables, 16 figures

Un livre à la fois théorique et pratique Cet ouvrage a pour objectif de rendre accessible, progressivement, les spécifications techniques qui constituent le socle de la 5G. Il détaille la Release-15 du standard 3GPP ainsi que les orientations futures (Release-16, Release-17). Il s'ouvre sur les interviews d'acteurs majeurs du monde des télécommunications (constructeurs, opérateurs et utilisateurs), qui partagent leur vision quant à l'introduction de la 5G, ses atouts et complexités. Sont décrits ensuite les principaux cas d'usage de la 5G ainsi que leurs applications possibles. L'eMBB est le principal objectif des premiers déploiements 5G des opérateurs, tandis qu'URLLC ouvre les réseaux mobiles à l'industrie 4.0 (transports autonomes, santé ou robotique). Enfin, mMTC s'appuie sur les modernisations des standards LTE-M et NB-IoT pour répondre aux besoins de l'IoT massif, ces technologies ayant évolué pour s'insérer dans le système 5G avec le niveau de performance attendu. Au-delà de ces applications, cet ouvrage couvre, avec des cas pratiques et de nombreuses illustrations, les aspects techniques suivants : architecture système (5GS), du réseau coeur (5GC) et du réseau d'accès radio de nouvelle génération (NG-RAN) ; principes de la transmission multi-antennes et de la formation de faisceaux NR ; types de mesures radio et signaux de référence correspondants en NR ; couches protocolaires de l'interface radio (5G NR), fonctionnalités et traitements de signaux correspondants ; interopérabilité entre LTE et NR ; signaux et fonctionnalités de l'accès initial NR, LTE-M/NB-IoT ; structure de transmission NR et LTE-M/NB-IoT pour les données et le contrôle. À qui s'adresse cet ouvrage ? Aux ingénieurs et consultants télécoms travaillant à la mise en oeuvre des réseaux 5G. Aux chercheurs et ingénieurs de recherche impliqués dans la conception et le développement de solutions 5G. Aux enseignants-chercheurs ainsi qu'aux étudiants d'écoles d'ingénieurs et de masters universitaire

In this chapter, we trace processes and consequences associated with one man’s ventures into those new worlds, and the shifting motivations and mechanisms that framed his journey. Bob Resa has played a crucial role in brokering relationships between Febi and Kubo people from tributary watersheds of the upper Strickland River (Western Province) and others who, it seems, control access to the possible futures that those people now imagine for themselves.

Open government data (OGD) is believed to enhance democratic outcomes by empowering citizens with the information necessary to participate in meaningful ways. Nonetheless, questions remain about whether OGD is indeed empowering citizens to participate or if the data that governments publish is more reflective of the interests of non-citizen stakeholders. Using the metadata of 2607 publicly available datasets scraped from New York City’s open data portal, this exploratory study employs qualitative content analysis to identify what types of data are published and what the data say about OGD’s potential as a tool for advancing inclusion in democratic processes. The analysis focused particularly on the datasets’ relevance to five particular stakeholder groups: citizens, private sector firms, nonprofits, researchers, and the city’s internal agencies. Findings showed that non-citizen-relevant datasets not only outnumbered citizen-relevant datasets by a large margin but they were also viewed and downloaded at higher rates too. I discuss the implications for inclusion in democratic processes, including power imbalances among OGD user groups, the discretionary power data publishers possess, and, ultimately, whether the types of data cities publish is sufficient for empowering an informed citizenry, as an effective democracy demands.

We report first laboratory rest frequencies for rotational transitions of protonated methylamine, CH3NH3+ , measured in a cryogenic 22-pole ion trap machine and employing an action spectroscopy scheme. For this prolate symmetric top molecule thirteen transitions between 80 and 240 GHz were detected in the ground vibrational state, covering J(K ) = 2(K ) - 1(K ) up to J(K ) = 6(K ) - 5(K ) with K = 0, 1, 2. Some transitions exhibit noticeable structure that is attributed to internal rotation splitting. As the CN radical and several of its hydrogenated and protonated forms up to methylamine, CH3NH2, are well known entities in the laboratory and in space, protonated methylamine, CH3NH3+ , is a promising candidate for future radio astronomical detection.

Context. The giant molecular cloud Sagittarius B2 (hereafter Sgr B2) is the most massive region with ongoing high-mass star formation in the Galaxy. Two ultra-compact HII (UCHIT ) regions were identified in Sgr B2's central hot cores, Sgr B2(M) and Sgr B2(N). Aims. Our aim is to characterize the properties of the HII regions in the entire Sgr B2 cloud. Comparing the Hii regions and the dust cores, we aim to depict the evolutionary stages of different parts of Sgr B2. Methods. We use the Very Large Array in its A, CnB, and D configurations, and in the frequency band C (similar to 6 GHz) to observe the whole Sgr B2 complex. Using ancillary VLA data at 22.4 GHz and ALMA data at 96 GHz, we calculated the physical parameters of the UCHIT regions and their dense gas environment. Results. We identify 54 UCHIT regions in the 6 GHz image, 39 of which are also detected at 22.4 GHz. Eight of the 54 UCHII regions are newly discovered. The UCHIT regions have radii between 0.006 pc and 0.04 pc, and have emission measure between 10(6) pc cm(-6) and 10 9 pc cm(-6). The UCHIT regions are ionized by stars of types from B0.5 to O6. We found a typical gas density of similar to 10(6)-10(9) cm(-3) around the UCHIT regions. The pressure of the UCHIT regions and the dense gas surrounding them are comparable. The expansion timescale of these UCHIT regions is determined to be similar to 10(4)-10(5) yr. The percentage of the dust cores that are associated with HII regions are 33%, 73%, 4%, and 1% for Sgr B2(N), Sgr B2(M), Sgr B2(S), and Sgr B2(DS), respectively. Two-thirds of the dust cores in Sgr B2(DS) are associated with outflows. Conclusions. The electron densities of the UCHIT regions we identified are in agreement with that of typical UCHIT regions, while the radii are smaller than those of the typical UCHIT regions. The dust cores in Sgr B2(M) are more evolved than in Sgr B2(N). The dust cores in Sgr B2(DS) are younger than in Sgr B2(M) or Sgr B2(N).

Public administration (PA) increasingly faces new and emerging challenges. To address such challenges, researchers can work collaboratively with practitioners to identify and tackle the most pressing issues. Yet, intentionally establishing an ongoing dialogue not only between researchers and practitioners but between researchers, practitioners, and the communities that PA scholarship and practice are intended to impact can enhance all stakeholders' understanding of complex social problems and improve solutions. Forms of participatory and context-based research such as this are called many things across disciplines, but PA has yet to embrace such approaches fully. Thus, we introduce a framework entitled CO-DESIGN, intended to illustrate the process of advancing PA research through the co-production of knowledge between researchers, practitioners, and communities. Additionally, it serves as an acronym outlining eight focal areas we argue the co-production of knowledge can help advance. We discuss the CO-DESIGN process and agenda, including its implications for the field.

Identifying, detecting, and localizing extreme weather events is a crucial first step in understanding how they may vary under different climate change scenarios. Pattern recognition tasks such as classification, object detection, and segmentation (i.e., pixel-level classification) have remained challenging problems in the weather and climate sciences. While there exist many empirical heuristics for detecting extreme events, the disparities between the output of these different methods even for a single event are large and often difficult to reconcile. Given the success of deep learning (DL) in tackling similar problems in computer vision, we advocate a DL-based approach. DL, however, works best in the context of supervised learning - when labeled datasets are readily available. Reliable labeled training data for extreme weather and climate events is scarce. We create "ClimateNet" - an open, community-sourced human-expert-labeled curated dataset that captures tropical cyclones (TCs) and atmospheric rivers (ARs) in highresolution climate model output from a simulation of a recent historical period.We use the curated ClimateNet dataset to train a state-of-the-art DL model for pixel-level identification - i.e., segmentation - of TCs and ARs. We then apply the trained DL model to historical and climate change scenarios simulated by the Community Atmospheric Model (CAM5.1) and show that the DL model accurately segments the data into TCs, ARs, or "the background" at a pixel level. Further, we show how the segmentation results can be used to conduct spatially and temporally precise analytics by quantifying distributions of extreme precipitation conditioned on event types (TC or AR) at regional scales. The key contribution of this work is that it paves the way for DL-based automated, high-fidelity, and highly precise analytics of climate data using a curated expert-labeled dataset - ClimateNet. ClimateNet and the DL-based segmentation method provide several unique capabilit

Context. We present a full analysis of a broadband spectral line survey of Sagittarius B2 (Main), one of the most chemically rich regions in the Galaxy located within the giant molecular cloud complex Sgr B2 in the central molecular zone. Aims. Our goal is to derive the molecular abundances and temperatures of the high-mass star-forming region Sgr B2(M) and thus its physical and astrochemical conditions. Methods. Sgr B2(M) was observed using the Heterodyne Instrument for the Far-Infrared (HIFI) on board the Herschel Space Observatory in a spectral line survey from 480 to 1907 GHz at a spectral resolution of 1.1 MHz, which provides one of the largest spectral coverages ever obtained toward this high-mass star-forming region in the submillimeter with high spectral resolution and includes frequencies >1 THz that are unobservable from the ground. We modeled the molecular emission from the submillimeter to the far-infrared using the XCLASS program, which assumes local thermodynamic equilibrium. For each molecule, a quantitative description was determined taking all emission and absorption features of that species across the entire spectral range into account. Because of the wide frequency coverage, our models are constrained by transitions over an unprecedented range in excitation energy. Additionally, we derived velocity resolved ortho/para ratios for those molecules for which ortho and para resolved molecular parameters are available. Finally, the temperature and velocity distributions are analyzed and the derived abundances are compared with those obtained for Sgr B2(N) from a similar HIFI survey. Results. A total of 92 isotopologues were identified, arising from 49 different molecules, ranging from free ions to complex organic compounds and originating from a variety of environments from the cold envelope to hot and dense gas within the cores. Sulfur dioxide, methanol, and water are the dominant contributors. Vibrationally excited HCN (v(2) = 1) and HNC (v(2) = 1) ar

Identifying, detecting, and localizing extreme weather events is a crucial first step in understanding how they may vary under different climate change scenarios. Pattern recognition tasks such as classification, object detection, and segmentation (i.e., pixel-level classification) have remained challenging problems in the weather and climate sciences. While there exist many empirical heuristics for detecting extreme events, the disparities between the output of these different methods even for a single event are large and often difficult to reconcile. Given the success of deep learning (DL) in tackling similar problems in computer vision, we advocate a DL-based approach. DL, however, works best in the context of supervised learning - when labeled datasets are readily available. Reliable labeled training data for extreme weather and climate events is scarce. We create "ClimateNet" - an open, community-sourced human-expert-labeled curated dataset that captures tropical cyclones (TCs) and atmospheric rivers (ARs) in highresolution climate model output from a simulation of a recent historical period.We use the curated ClimateNet dataset to train a state-of-the-art DL model for pixel-level identification - i.e., segmentation - of TCs and ARs. We then apply the trained DL model to historical and climate change scenarios simulated by the Community Atmospheric Model (CAM5.1) and show that the DL model accurately segments the data into TCs, ARs, or "the background" at a pixel level. Further, we show how the segmentation results can be used to conduct spatially and temporally precise analytics by quantifying distributions of extreme precipitation conditioned on event types (TC or AR) at regional scales. The key contribution of this work is that it paves the way for DL-based automated, high-fidelity, and highly precise analytics of climate data using a curated expert-labeled dataset - ClimateNet. ClimateNet and the DL-based segmentation method provide several unique capabilit

Context. We present a full analysis of a broadband spectral line survey of Sagittarius B2 (Main), one of the most chemically rich regions in the Galaxy located within the giant molecular cloud complex Sgr B2 in the central molecular zone. Aims. Our goal is to derive the molecular abundances and temperatures of the high-mass star-forming region Sgr B2(M) and thus its physical and astrochemical conditions. Methods. Sgr B2(M) was observed using the Heterodyne Instrument for the Far-Infrared (HIFI) on board the Herschel Space Observatory in a spectral line survey from 480 to 1907 GHz at a spectral resolution of 1.1 MHz, which provides one of the largest spectral coverages ever obtained toward this high-mass star-forming region in the submillimeter with high spectral resolution and includes frequencies >1 THz that are unobservable from the ground. We modeled the molecular emission from the submillimeter to the far-infrared using the XCLASS program, which assumes local thermodynamic equilibrium. For each molecule, a quantitative description was determined taking all emission and absorption features of that species across the entire spectral range into account. Because of the wide frequency coverage, our models are constrained by transitions over an unprecedented range in excitation energy. Additionally, we derived velocity resolved ortho/para ratios for those molecules for which ortho and para resolved molecular parameters are available. Finally, the temperature and velocity distributions are analyzed and the derived abundances are compared with those obtained for Sgr B2(N) from a similar HIFI survey. Results. A total of 92 isotopologues were identified, arising from 49 different molecules, ranging from free ions to complex organic compounds and originating from a variety of environments from the cold envelope to hot and dense gas within the cores. Sulfur dioxide, methanol, and water are the dominant contributors. Vibrationally excited HCN (v(2) = 1) and HNC (v(2) = 1) ar

Simple graph algorithms such as PageRank have been the target of numerous hardware accelerators. Yet, there also exist much more complex graph mining algorithms for problems such as clustering or maximal clique listing. These algorithms are memory-bound and thus could be accelerated by hardware techniques such as Processing-in-Memory (PIM). However, they also come with nonstraightforward parallelism and complicated memory access patterns. In this work, we address this problem with a simple yet surprisingly powerful observation: operations on sets of vertices, such as intersection or union, form a large part of many complex graph mining algorithms, and can offer rich and simple parallelism at multiple levels. This observation drives our cross-layer design, in which we (1) expose set operations using a novel programming paradigm, (2) express and execute these operations efficiently with carefully designed set-centric ISA extensions called SISA, and (3) use PIM to accelerate SISA instructions. The key design idea is to alleviate the bandwidth needs of SISA instructions by mapping set operations to two types of PIM: in-DRAM bulk bitwise computing for bitvectors representing high-degree vertices, and near-memory logic layers for integer arrays representing low-degree vertices. Set-centric SISA-enhanced algorithms are efficient and outperform hand-tuned baselines, offering more than 10x speedup over the established Bron-Kerbosch algorithm for listing maximal cliques. We deliver more than 10 SISA set-centric algorithm formulations, illustrating SISA's wide applicability., Comment: Proceedings of the 54th IEEE/ACM International Symposium on Microarchitecture (MICRO'21), 2021

Un livre à la fois théorique et pratique Cet ouvrage a pour objectif de rendre accessible, progressivement, les spécifications techniques qui constituent le socle de la 5G. Il détaille la Release-15 du standard 3GPP ainsi que les orientations futures (Release-16, Release-17). Il s'ouvre sur les interviews d'acteurs majeurs du monde des télécommunications (constructeurs, opérateurs et utilisateurs), qui partagent leur vision quant à l'introduction de la 5G, ses atouts et complexités. Sont décrits ensuite les principaux cas d'usage de la 5G ainsi que leurs applications possibles. L'eMBB est le principal objectif des premiers déploiements 5G des opérateurs, tandis qu'URLLC ouvre les réseaux mobiles à l'industrie 4.0 (transports autonomes, santé ou robotique). Enfin, mMTC s'appuie sur les modernisations des standards LTE-M et NB-IoT pour répondre aux besoins de l'IoT massif, ces technologies ayant évolué pour s'insérer dans le système 5G avec le niveau de performance attendu. Au-delà de ces applications, cet ouvrage couvre, avec des cas pratiques et de nombreuses illustrations, les aspects techniques suivants : architecture système (5GS), du réseau coeur (5GC) et du réseau d'accès radio de nouvelle génération (NG-RAN) ; principes de la transmission multi-antennes et de la formation de faisceaux NR ; types de mesures radio et signaux de référence correspondants en NR ; couches protocolaires de l'interface radio (5G NR), fonctionnalités et traitements de signaux correspondants ; interopérabilité entre LTE et NR ; signaux et fonctionnalités de l'accès initial NR, LTE-M/NB-IoT ; structure de transmission NR et LTE-M/NB-IoT pour les données et le contrôle. À qui s'adresse cet ouvrage ? Aux ingénieurs et consultants télécoms travaillant à la mise en oeuvre des réseaux 5G. Aux chercheurs et ingénieurs de recherche impliqués dans la conception et le développement de solutions 5G. Aux enseignants-chercheurs ainsi qu'aux étudiants d'écoles d'ingénieurs et de masters universitaire

Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.

Un livre à la fois théorique et pratique Cet ouvrage a pour objectif de rendre accessible, progressivement, les spécifications techniques qui constituent le socle de la 5G. Il détaille la Release-15 du standard 3GPP ainsi que les orientations futures (Release-16, Release-17). Il s'ouvre sur les interviews d'acteurs majeurs du monde des télécommunications (constructeurs, opérateurs et utilisateurs), qui partagent leur vision quant à l'introduction de la 5G, ses atouts et complexités. Sont décrits ensuite les principaux cas d'usage de la 5G ainsi que leurs applications possibles. L'eMBB est le principal objectif des premiers déploiements 5G des opérateurs, tandis qu'URLLC ouvre les réseaux mobiles à l'industrie 4.0 (transports autonomes, santé ou robotique). Enfin, mMTC s'appuie sur les modernisations des standards LTE-M et NB-IoT pour répondre aux besoins de l'IoT massif, ces technologies ayant évolué pour s'insérer dans le système 5G avec le niveau de performance attendu. Au-delà de ces applications, cet ouvrage couvre, avec des cas pratiques et de nombreuses illustrations, les aspects techniques suivants : architecture système (5GS), du réseau coeur (5GC) et du réseau d'accès radio de nouvelle génération (NG-RAN) ; principes de la transmission multi-antennes et de la formation de faisceaux NR ; types de mesures radio et signaux de référence correspondants en NR ; couches protocolaires de l'interface radio (5G NR), fonctionnalités et traitements de signaux correspondants ; interopérabilité entre LTE et NR ; signaux et fonctionnalités de l'accès initial NR, LTE-M/NB-IoT ; structure de transmission NR et LTE-M/NB-IoT pour les données et le contrôle. À qui s'adresse cet ouvrage ? Aux ingénieurs et consultants télécoms travaillant à la mise en oeuvre des réseaux 5G. Aux chercheurs et ingénieurs de recherche impliqués dans la conception et le développement de solutions 5G. Aux enseignants-chercheurs ainsi qu'aux étudiants d'écoles d'ingénieurs et de masters universitaire

The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14–16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast.

The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14–16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast.

Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.

The ultrafast dynamics of unsubstituted spironaphthopyran (SNP) were investigated using femtosecond transient UV and visible absorption spectroscopy in three different solvents and by semi-classical nuclear dynamics simulations. The primary ring-opening of the pyran unit was found to occur in 300 fs yielding a non-planar intermediate in the first singlet excited state (S-1). Subsequent planarisation and relaxation to the product ground state proceed through barrier crossing on the S-1 potential energy surface (PES) and take place within 1.1 ps after excitation. Simulations show that more than 90% of the trajectories involving C-O bond elongation lead to the planar, open-ring product, while relaxation back to the S-0 of the closed-ring form is accompanied by C-N elongation. All ensuing spectral dynamics are ascribed to vibrational relaxation and thermalisation of the product with a time constant of 13 ps. The latter shows dependency on characteristics of the solvent with solvent relaxation kinetics playing a role., Funding Agencies|Max Planck Society

The ultrafast dynamics of unsubstituted spironaphthopyran (SNP) were investigated using femtosecond transient UV and visible absorption spectroscopy in three different solvents and by semi-classical nuclear dynamics simulations. The primary ring-opening of the pyran unit was found to occur in 300 fs yielding a non-planar intermediate in the first singlet excited state (S-1). Subsequent planarisation and relaxation to the product ground state proceed through barrier crossing on the S-1 potential energy surface (PES) and take place within 1.1 ps after excitation. Simulations show that more than 90% of the trajectories involving C-O bond elongation lead to the planar, open-ring product, while relaxation back to the S-0 of the closed-ring form is accompanied by C-N elongation. All ensuing spectral dynamics are ascribed to vibrational relaxation and thermalisation of the product with a time constant of 13 ps. The latter shows dependency on characteristics of the solvent with solvent relaxation kinetics playing a role., Funding Agencies|Max Planck Society

Contains fulltext : 202645.pdf (publisher's version ) (Open Access), Type 2A protein phosphatases (PP2As) are highly expressed in the brain and regulate neuronal signaling by catalyzing phospho-Ser/Thr dephosphorylations in diverse substrates. PP2A holoenzymes comprise catalytic C-, scaffolding A-, and regulatory B-type subunits, which determine substrate specificity and physiological function. Interestingly, de novo mutations in genes encoding A- and B-type subunits have recently been implicated in intellectual disability (ID) and developmental delay (DD). We now report 16 individuals with mild to profound ID and DD and a de novo mutation in PPP2CA, encoding the catalytic Calpha subunit. Other frequently observed features were severe language delay (71%), hypotonia (69%), epilepsy (63%), and brain abnormalities such as ventriculomegaly and a small corpus callosum (67%). Behavioral problems, including autism spectrum disorders, were reported in 47% of individuals, and three individuals had a congenital heart defect. PPP2CA de novo mutations included a partial gene deletion, a frameshift, three nonsense mutations, a single amino acid duplication, a recurrent mutation, and eight non-recurrent missense mutations. Functional studies showed complete PP2A dysfunction in four individuals with seemingly milder ID, hinting at haploinsufficiency. Ten other individuals showed mutation-specific biochemical distortions, including poor expression, altered binding to the A subunit and specific B-type subunits, and impaired phosphatase activity and C-terminal methylation. Four were suspected to have a dominant-negative mechanism, which correlated with severe ID. Two missense variants affecting the same residue largely behaved as wild-type in our functional assays. Overall, we found that pathogenic PPP2CA variants impair PP2A-B56(delta) functionality, suggesting that PP2A-related neurodevelopmental disorders constitute functionally converging ID syndromes.

Context. The giant molecular cloud Sagittarius B2 (hereafter Sgr B2) is the most massive region with ongoing high-mass star formation in the Galaxy. In the southern region of the 40-pc large envelope of Sgr B2, we encounter the Sgr B2(DS) region, which hosts more than 60 high-mass protostellar cores distributed in an arc shape around an extended HII region. Hints of non-thermal emission have been found in the HII region associated with Sgr B2(DS). Aims. We seek to characterize the spatial structure and the spectral energy distribution of the radio continuum emission in Sgr B2(DS). We aim to disentangle the contribution from the thermal and non-thermal radiation, as well as to study the origin of the non-thermal radiation. Methods. We used the Very Large Array in its CnB and D configurations, and in the frequency bands C (4-8 GHz) and X (8-12 GHz) to observe the whole Sgr B2 complex. Continuum and radio recombination line maps are obtained. Results. We detect radio continuum emission in Sgr B2(DS) in a bubble-shaped structure. From 4 to 12 GHz, we derive a spectral index between -1.2 and -0.4, indicating the presence of non-thermal emission. We decomposed the contribution from thermal and non-thermal emission, and find that the thermal component is clumpy and more concentrated, while the non-thermal component is more extended and diffuse. The radio recombination lines in the region are found to be not in local thermodynamic equilibrium but stimulated by the non-thermal emission. Conclusions. Sgr B2(DS) shows a mixture of thermal and non-thermal emission at radio wavelengths. The thermal free-free emission is likely tracing an Hii region ionized by an O 7 star, while the non-thermal emission can be generated by relativistic electrons created through first-order Fermi acceleration. We have developed a simple model of the Sgr B2(DS) region and found that first-order Fermi acceleration can reproduce the observed flux density and spectral index.

Context. Sagittarius B2 (north) is a chemically rich, high-mass star-forming region located within the giant molecular cloud complex Sgr B2 in the central molecular zone of our Galaxy. Dust continuum emission at 242 GHz, obtained at high angular resolution with the Atacama Large Millimeter Array (ALMA), reveals that it has a filamentary structure on scales of 0.1 pc. Aims. We aim to characterize the filamentary structure of Sgr B2(N) and its kinematic properties using multiple molecular dense gas tracers. Methods. We have used an unbiased, spectral line-survey that covers the frequency range from 211 to 275 GHz and obtained with ALMA (angular resolution of 0 : 00 4, or 3300 au) to study the small-scale structure of the dense gas in Sgr B2(N). In order to derive the kinematic properties of the gas in a chemically line-rich source like Sgr B2(N), we have developed a python-based tool that stacks all the detected line transitions of any molecular species. This allows us to increase the signal-to-noise ratio (S/N) of our observations and average out line blending effects, which are common in line-rich regions. Results. A filamentary network is visible in Sgr B2(N) in the emission maps of the molecular species CH3OCHO, CH3OCH3, CH3OH and H2CS. In total, eight filaments are found that converge to the central hub (with a mass of 2000 M-circle dot, assuming a temperature of 250 K) and extending for about 0.1 pc (up to 0.5 pc). The spatial structure, together with the presence of the massive central region, suggest that these filaments may be associated with accretion processes, transporting material from the outer regions to the central dense hub. We derive velocity gradients along the filaments of about 20-100 km s(-1) pc(-1), which are 10-100 times larger than those typically found on larger scales (similar to 1 pc) in other star-forming regions. The mass accretion rates of individual filaments are (sic)0.05 M-circle dot yr(-1), which result in a total accretion rate of 0

Contains fulltext : 202645.pdf (publisher's version ) (Open Access), Type 2A protein phosphatases (PP2As) are highly expressed in the brain and regulate neuronal signaling by catalyzing phospho-Ser/Thr dephosphorylations in diverse substrates. PP2A holoenzymes comprise catalytic C-, scaffolding A-, and regulatory B-type subunits, which determine substrate specificity and physiological function. Interestingly, de novo mutations in genes encoding A- and B-type subunits have recently been implicated in intellectual disability (ID) and developmental delay (DD). We now report 16 individuals with mild to profound ID and DD and a de novo mutation in PPP2CA, encoding the catalytic Calpha subunit. Other frequently observed features were severe language delay (71%), hypotonia (69%), epilepsy (63%), and brain abnormalities such as ventriculomegaly and a small corpus callosum (67%). Behavioral problems, including autism spectrum disorders, were reported in 47% of individuals, and three individuals had a congenital heart defect. PPP2CA de novo mutations included a partial gene deletion, a frameshift, three nonsense mutations, a single amino acid duplication, a recurrent mutation, and eight non-recurrent missense mutations. Functional studies showed complete PP2A dysfunction in four individuals with seemingly milder ID, hinting at haploinsufficiency. Ten other individuals showed mutation-specific biochemical distortions, including poor expression, altered binding to the A subunit and specific B-type subunits, and impaired phosphatase activity and C-terminal methylation. Four were suspected to have a dominant-negative mechanism, which correlated with severe ID. Two missense variants affecting the same residue largely behaved as wild-type in our functional assays. Overall, we found that pathogenic PPP2CA variants impair PP2A-B56(delta) functionality, suggesting that PP2A-related neurodevelopmental disorders constitute functionally converging ID syndromes.

Ethylmalonic encephalopathy (EE) is a rapidly progressive autosomal recessive mitochondrial disease caused by biallelic pathogenic variants in the ETHE1 gene that encodes the mitochondrial sulfur dioxygenase. It is characterized by neurodevelopmental delay and regression, pyramidal and extrapyramidal signs, recurrent petechiae, chronic diarrhea, and orthostatic acrocyanosis. Laboratory findings include elevated serum levels of lactate and C4-C5 acylcarnitines, and elevated urinary excretion of ethylmalonic acid and C4-C6 acylglycines, notably isobutyrylglycine and 2-methylbutyrylglycine. These findings are attributed to deficiency of the mitochondrial sulfur dioxygenase resulting in toxic accumulation of hydrogen sulfide metabolites in vascular endothelium and mucosal cells of the large intestine. Medical management has thus far been directed toward decreasing the accumulation of hydrogen sulfide metabolites using a combination of metronidazole and N-acetylcysteine. More recently, orthotopic liver transplant (OLT) has been reported as a new therapeutic option for EE. Here, we report two additional cases of EE who achieved psychomotor developmental improvement after 7- and 22-months following OLT. The second case serves as the longest developmental outcome follow-up reported, thus far, following OLT for EE. This report provides additional evidence to validate OLT as a promising therapeutic approach for what was considered to be a fatal disease.

The ultrafast dynamics of unsubstituted spironaphthopyran (SNP) were investigated using femtosecond transient UV and visible absorption spectroscopy in three different solvents and by semi-classical nuclear dynamics simulations. The primary ring-opening of the pyran unit was found to occur in 300 fs yielding a non-planar intermediate in the first singlet excited state (S-1). Subsequent planarisation and relaxation to the product ground state proceed through barrier crossing on the S-1 potential energy surface (PES) and take place within 1.1 ps after excitation. Simulations show that more than 90% of the trajectories involving C-O bond elongation lead to the planar, open-ring product, while relaxation back to the S-0 of the closed-ring form is accompanied by C-N elongation. All ensuing spectral dynamics are ascribed to vibrational relaxation and thermalisation of the product with a time constant of 13 ps. The latter shows dependency on characteristics of the solvent with solvent relaxation kinetics playing a role., Funding Agencies|Max Planck Society

Context. Sagittarius B2 (north) is a chemically rich, high-mass star-forming region located within the giant molecular cloud complex Sgr B2 in the central molecular zone of our Galaxy. Dust continuum emission at 242 GHz, obtained at high angular resolution with the Atacama Large Millimeter Array (ALMA), reveals that it has a filamentary structure on scales of 0.1 pc. Aims. We aim to characterize the filamentary structure of Sgr B2(N) and its kinematic properties using multiple molecular dense gas tracers. Methods. We have used an unbiased, spectral line-survey that covers the frequency range from 211 to 275 GHz and obtained with ALMA (angular resolution of 0 : 00 4, or 3300 au) to study the small-scale structure of the dense gas in Sgr B2(N). In order to derive the kinematic properties of the gas in a chemically line-rich source like Sgr B2(N), we have developed a python-based tool that stacks all the detected line transitions of any molecular species. This allows us to increase the signal-to-noise ratio (S/N) of our observations and average out line blending effects, which are common in line-rich regions. Results. A filamentary network is visible in Sgr B2(N) in the emission maps of the molecular species CH3OCHO, CH3OCH3, CH3OH and H2CS. In total, eight filaments are found that converge to the central hub (with a mass of 2000 M-circle dot, assuming a temperature of 250 K) and extending for about 0.1 pc (up to 0.5 pc). The spatial structure, together with the presence of the massive central region, suggest that these filaments may be associated with accretion processes, transporting material from the outer regions to the central dense hub. We derive velocity gradients along the filaments of about 20-100 km s(-1) pc(-1), which are 10-100 times larger than those typically found on larger scales (similar to 1 pc) in other star-forming regions. The mass accretion rates of individual filaments are (sic)0.05 M-circle dot yr(-1), which result in a total accretion rate of 0

Context. The giant molecular cloud Sagittarius B2 (hereafter Sgr B2) is the most massive region with ongoing high-mass star formation in the Galaxy. In the southern region of the 40-pc large envelope of Sgr B2, we encounter the Sgr B2(DS) region, which hosts more than 60 high-mass protostellar cores distributed in an arc shape around an extended HII region. Hints of non-thermal emission have been found in the HII region associated with Sgr B2(DS). Aims. We seek to characterize the spatial structure and the spectral energy distribution of the radio continuum emission in Sgr B2(DS). We aim to disentangle the contribution from the thermal and non-thermal radiation, as well as to study the origin of the non-thermal radiation. Methods. We used the Very Large Array in its CnB and D configurations, and in the frequency bands C (4-8 GHz) and X (8-12 GHz) to observe the whole Sgr B2 complex. Continuum and radio recombination line maps are obtained. Results. We detect radio continuum emission in Sgr B2(DS) in a bubble-shaped structure. From 4 to 12 GHz, we derive a spectral index between -1.2 and -0.4, indicating the presence of non-thermal emission. We decomposed the contribution from thermal and non-thermal emission, and find that the thermal component is clumpy and more concentrated, while the non-thermal component is more extended and diffuse. The radio recombination lines in the region are found to be not in local thermodynamic equilibrium but stimulated by the non-thermal emission. Conclusions. Sgr B2(DS) shows a mixture of thermal and non-thermal emission at radio wavelengths. The thermal free-free emission is likely tracing an Hii region ionized by an O 7 star, while the non-thermal emission can be generated by relativistic electrons created through first-order Fermi acceleration. We have developed a simple model of the Sgr B2(DS) region and found that first-order Fermi acceleration can reproduce the observed flux density and spectral index.

The ultrafast dynamics of unsubstituted spironaphthopyran (SNP) were investigated using femtosecond transient UV and visible absorption spectroscopy in three different solvents and by semi-classical nuclear dynamics simulations. The primary ring-opening of the pyran unit was found to occur in 300 fs yielding a non-planar intermediate in the first singlet excited state (S-1). Subsequent planarisation and relaxation to the product ground state proceed through barrier crossing on the S-1 potential energy surface (PES) and take place within 1.1 ps after excitation. Simulations show that more than 90% of the trajectories involving C-O bond elongation lead to the planar, open-ring product, while relaxation back to the S-0 of the closed-ring form is accompanied by C-N elongation. All ensuing spectral dynamics are ascribed to vibrational relaxation and thermalisation of the product with a time constant of 13 ps. The latter shows dependency on characteristics of the solvent with solvent relaxation kinetics playing a role., Funding Agencies|Max Planck Society

The ultrafast dynamics of unsubstituted spironaphthopyran (SNP) were investigated using femtosecond transient UV and visible absorption spectroscopy in three different solvents and by semi-classical nuclear dynamics simulations. The primary ring-opening of the pyran unit was found to occur in 300 fs yielding a non-planar intermediate in the first singlet excited state (S-1). Subsequent planarisation and relaxation to the product ground state proceed through barrier crossing on the S-1 potential energy surface (PES) and take place within 1.1 ps after excitation. Simulations show that more than 90% of the trajectories involving C-O bond elongation lead to the planar, open-ring product, while relaxation back to the S-0 of the closed-ring form is accompanied by C-N elongation. All ensuing spectral dynamics are ascribed to vibrational relaxation and thermalisation of the product with a time constant of 13 ps. The latter shows dependency on characteristics of the solvent with solvent relaxation kinetics playing a role., Funding Agencies|Max Planck Society

Nature-based tourism is often advocated as a desirable conservation strategy for smallscale fishing communities as it gives local people motivation to protect wildlife and ecosystems that attract visitors, while benefiting the community. However, valuation of environmental inputs in nature-based tourism, for instance charismatic species or scenic amenities, needs to be done correctly. Often, there are inter-sectoral costs and benefits involved that are not counted, so that determining the value of the environmental inputs to local communities may be more complex than simpler calculations might indicate. We model whales as an input to the production of wildlife viewing trips, but recognize that this occurs within a community dependent on a seasonal fishery. Standard theory suggests that industry will switch from fishing to whale watching every year when whale watching becomes marginally more profitable than fishing. We develop a simple theoretical model that allows us to analyze the interaction between the extractive and the non-extractive activities. As a case study, we use whale watching in the small coastal communities of the Bahía Magdalena lagoon complex in Baja, México.