julilili42/papers huggingface dataset:
Hardware-Based Evaluation of Scalable and Resilient Multicast With BIER in P4
2021-01-01

Traditional IP multicast (IPMC) maintains state per IPMC group in core devices to distribute one-to-many traffic along tree-like structures through the network. This limits its scalability because whenever subscribers of IPMC groups change, forwarding state in the core network needs to be updated. Bit Index Explicit Replication (BIER) has been proposed by the IETF for efficient transport of IPMC traffic without the need of IPMC-group-dependent state in core devices. However, legacy devices do not offer the required features to implement BIER. P4 is a programming language which follows the software-defined networking (SDN) paradigm. It provides a programmable data plane by programming the packet processing pipeline of P4 devices. The contribution of this article is threefold. First, we provide a hardware-based prototype of BIER and BIER fast reroute (BIER-FRR) which leverages packet recirculation. Our target is the P4-programmable high-performance switching ASIC Tofino; the source code is publicly available. Second, we perform an experimental evaluation, with regard to failover time and throughput, which shows that up to 100 Gb/s throughput can be obtained and that failures affect BIER forwarding for less than 1 ms. However, throughput can decrease if switch-internal packet loss occurs due to missing recirculation capacity. As a remedy, we add more recirculation capacity by turning physical ports into loopback mode. To quantify the problem, we derive a prediction model for reduced throughput whose results are in good accordance with measured values. Third, we provide a provisioning rule for recirculation ports, that is applicable to general P4 programs, to avoid switch-internal packet loss due to packet recirculation. In a case study we show that BIER requires only a few such ports under realistic mixes of unicast and multicast traffic.
Predisposing and Precipitating Factors for Delirium in the Very Old (≥80 Years): A Prospective Cohort Study of 3,076 Patients
2021-01-01

Background: Predisposing and precipitating factors for delirium for the elderly, over the age of 65 years, are known, but not for the very old, over 80 years. As the society is getting older and evermore patients will reach &gt;80 years, more evidence of the factors and their contribution to delirium is required in this patient group. Methods: In the course of 1 year, 3,076 patients above 80 years were screened prospectively for delirium based on a Delirium Observation Screening (DOS) scale, Intensive Care Delirium Screening Checklist (ICDSC), and a DSM (Diagnostic and Statistical Manual)-5 nursing instrument (ePA-AC) construct. Relevant predisposing and precipitating factors for delirium were assessed with a multiple regression analysis. Results: Of 3,076 patients above 80 years, 1,285 (41.8%) developed a delirium, which led to twice prolonged hospitalization (p &lt; 0.001), requirement for subsequent assisted living (OR 2.2, CI: 1.73–2.8, p &lt; 0.001), and increased mortality (OR 24.88, CI: 13.75–45.03, p &lt; 0.001). Relevant predisposing factors were dementia (OR 15.6, CI: 10.17–23.91, p &lt; 0.001), pressure sores (OR 4.61, CI: 2.74–7.76, p &lt; 0.001), and epilepsy (OR 3.65, CI: 2.12–6.28, p &lt; 0.0001). Relevant precipitating factors were acute renal failure (4.96, CI: 2.38–10.3, p &lt; 0.001), intracranial hemorrhage (OR 8.7, CI: 4.27–17.7, p &lt; 0.001), and pleural effusions (OR 3.25, CI: 1.77–17.8, p &lt; 0.001). Conclusion: Compared to the general delirium rate of approximately 20%, the prevalence of delirium doubled above the age of 80 years (41.8%) due to predisposing factors uncommon in younger patients.
Unnecessary reliance on multilevel modelling to analyse nested data in neuroscience: When a traditional summary-statistics approach suffices
2021-01-01

Nested data structures create statistical dependence that influences the effective sample size and statistical power of a study. Several methods are available for dealing with nested data, including the summary-statistics approach and multilevel modelling (MLM). Recent publications have heralded MLM as the best method for analysing nested data, claiming benefits in power over summary-statistics approaches (e.g., the <i>t</i>-test). However, when cluster size is equal, these approaches are mathematically equivalent. We conducted statistical simulations demonstrating equivalence of MLM and summary-statistics approaches for analysing nested data and provide supportive cases for the utility of the conventional summary-statistics approach in nested experiments. Using statistical simulations, we demonstrate that losses in power in the summary-statistics approach discussed in the previous literature are unsubstantiated. We also show that MLM sometimes suffers from frequent singular fit errors, especially when intraclass correlation is low. There are indeed many situations in which MLM is more appropriate and desirable, but researchers should be aware of the possibility that simpler analysis (i.e., summary-statistics approach) does an equally good or even better job in some situations.
Systematic Review of Osteochondral Allograft Transplant Immunology: How We Can Further Optimize Outcomes
2021-01-01

Abstract Despite the growing success for osteochondral allograft (OCA) transplantation in treating large articular cartilage lesions in multiple joints, associated revision and failure rates are still higher than desired. While immunorejection responses have not been documented, the effects of the host's immune responses on OCA transplantation failures have not been thoroughly characterized. The objective of this study was to systematically review clinically relevant peer-reviewed evidence pertaining to the immunology of OCAs to elucidate theragnostic strategies for improving functional graft survival and outcomes for patients undergoing OCA transplantation. This systematic review of Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, MEDLINE, PubMed, and EMBASE suggests that host immune responses play key roles in incorporation and functional survival of OCA transplants. OCA rejection has not been reported; however, graft integration through creeping substitution is reliant on host immune responses. Prolonged inflammation, diminished osteogenic potential for healing and incorporation, and relative bioburden are mechanisms that may be influenced by the immune system and contribute to undesirable outcomes after OCA transplantation. Based on the safety and efficacy of OCA transplantation and its associated benefits to a large and growing patient population, basic, preclinical, and clinical osteoimmunological studies on OCA transplantation that comprehensively assess and correlate cellular, molecular, histologic, biomechanical, biomarkers, diagnostic imaging, arthroscopic, functional, and patient-reported outcome measures are of high interest and importance.
Landscape of T‐cell repertoires with public COVID‐19‐associated T‐cell receptors in pre‐pandemic risk cohorts
2021-01-01

Abstract Objectives T cells have an essential role in the antiviral defence. Public T‐cell receptor (TCR) clonotypes are expanded in a substantial proportion of COVID‐19 patients. We set out to exploit their potential use as read‐out for COVID‐19 T‐cell immune responses. Methods We searched for COVID‐19‐associated T‐cell clones with public TCRs, as defined by identical complementarity‐determining region 3 (CDR3) beta chain amino acid sequence that can be reproducibly detected in the blood of COVID‐19 patients. Of the different clonotype identification algorithms used in this study, deep sequencing of brain tissue of five patients with fatal COVID‐19 delivered 68 TCR clonotypes with superior representation across 140 immune repertoires of unrelated COVID‐19 patients. Results Mining of immune repertoires from subjects not previously exposed to the virus showed that these clonotypes can be found in almost 20% of pre‐pandemic immune repertoires of healthy subjects, with lower representation in repertoires from risk groups like individuals above the age of 60 years or patients with cancer. Conclusion Together, our data show that at least a proportion of the SARS‐CoV‐2 T‐cell response is mediated by public TCRs that are present in repertoires of unexposed individuals. The lower representation of these clones in repertoires of risk groups or failure to expand such clones may contribute to more unfavorable clinical COVID‐19 courses.
Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease
2021-01-01

Abstract Introduction Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD‐MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD‐MC and could help predict risk for dementia during trial enrollment. Methods We created a dementia risk score by entering standardized gray‐matter volumes from 231 DIAD‐MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD‐MC followed longitudinally. Results Our risk score separated asymptomatic versus demented DIAD‐MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%–98.2%]) and improved prediction beyond established methods based on familial age of onset. Discussion Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD‐MC participants for prevention trials.
Therapy of lymphoma by immune checkpoint inhibitors: the role of T cells, NK cells and cytokine-induced tumor senescence
2021-01-01

Background Although antibodies blocking immune checkpoints have already been approved for clinical cancer treatment, the mechanisms involved are not yet completely elucidated. Here we used a λ-MYC transgenic model of endogenously growing B-cell lymphoma to analyze the requirements for effective therapy with immune checkpoint inhibitors. Methods Growth of spontaneous lymphoma was monitored in mice that received antibodies targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein-4, and the role of different immune cell compartments and cytokines was studied by in vivo depletion experiments. Activation of T and natural killer cells and the induction of tumor senescence were analyzed by flow cytometry. Results On immune checkpoint blockade, visible lymphomas developed at later time points than in untreated controls, indicating an enhanced tumor control. Importantly, 20% to 30% of mice were even long-term protected and did never develop clinical signs of tumor growth. The therapeutic effect was dependent on cytokine-induced senescence in malignant B cells. The proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor (TNF) were necessary for the survival benefit as well as for senescence induction in the λ-MYC model. Antibody therapy improved T-cell functions such as cytokine production, and long-time survivors were only observed in the presence of T cells. Yet, NK cells also had a pronounced effect on therapy-induced delay of tumor growth. Antibody treatment enhanced numbers, proliferation and IFN-γ expression of NK cells in developing tumors. The therapeutic effect was fully abrogated only after depletion of both, T cells and NK cells, or after ablation of either IFN-γ or TNF. Conclusions Tumor cell senescence may explain why patients responding to immune checkpoint blockade frequently show stable growth arrest of tumors rather than complete tumor regression. In the lymphoma model studied, successful therapy required both, tumor-directed T-cell responses and NK cells, which control, at least partly, tumor development through cytokine-induced tumor senescence.
Poly- and Monoamine Metabolism in <b><i>Streptomyces coelicolor</i></b>: The New Role of Glutamine Synthetase-Like Enzymes in the Survival under Environmental Stress
2021-01-01

Soil bacteria from the genus &lt;i&gt;Streptomyces&lt;/i&gt;, phylum Actinobacteria, feature a complex metabolism and diverse adaptations to environmental stress. These characteristics are consequences of variable nutrition availability in the soil and allow survival under changing nitrogen conditions. &lt;i&gt;Streptomyces coelicolor&lt;/i&gt; is a model organism for Actinobacteria and is able to use nitrogen from a variety of sources including unusual compounds originating from the decomposition of dead plant and animal material, such as polyamines or monoamines (like ethanolamine). Assimilation of nitrogen from these sources in &lt;i&gt;S. coelicolor&lt;/i&gt; remains largely unstudied. Using microbiological, biochemical and in silico approaches, it was recently possible to postulate polyamine and monoamine (ethanolamine) utilization pathways in &lt;i&gt;S. coelicolor.&lt;/i&gt; Glutamine synthetase-like enzymes (GS-like) play a central role in these pathways. Extensive studies have revealed that these enzymes are able to detoxify polyamines or monoamines and allow the survival of &lt;i&gt;S. coelicolor&lt;/i&gt; in soil containing an excess of these compounds. On the other hand, at low concentrations, polyamines and monoamines can be utilized as nitrogen and carbon sources. It has been demonstrated that the first step in poly-/monoamine assimilation is catalyzed by GlnA3 (a γ-glutamylpolyamine synthetase) and GlnA4 (a γ-glutamylethanolamide synthetase), respectively. First insights into the regulation of polyamine and ethanolamine metabolism have revealed that the expression of the &lt;i&gt;glnA3&lt;/i&gt; and the &lt;i&gt;glnA4&lt;/i&gt; gene are controlled on the transcriptional level.
A new species of Cricosaurus (Thalattosuchia, Metriorhynchidae) based upon a remarkably well-preserved skeleton from the Upper Jurassic of Germany
2021-01-01

Herein we describe a new and exceptionally well-preserved skeleton of the metriorhynchid thalattosuchian Cricosaurus from the upper Kimmeridgian Torleite Formation of Painten in Bavaria (Southern Germany).The specimen is articulated, shows soft-tissue preservation, and represents one of the most complete metriorhynchid skeletons known.The exceptional preservation allows us to explore the morphological variation of the tail region in the Metriorhynchidae, a part of the skeleton that has long been neglected.Based on our description and phylogenetic analyses, we name this specimen Cricosaurus albersdoerferi sp.nov.Our phylogenetic analyses recover a Cricosaurus subclade composed of four species from Southern Germany and one from Argentina.We provide revised diagnoses for the Southern German members of this subclade, revealing the presence of at least four closely-related Cricosaurus species in the upper Kimmeridgian-early Tithonian of Southern Germany.Interestingly, within this subclade there is evidence of rapid change in tail construction and feeding ecology.However, there is no evidence of sympatry between these taxa, and the two species known from the same ammonite subzone are exclusively found in different northern-Tethys lagoons.Most interesting, however, is the variation in the skulls, dorsal neural spines, the tail displacement units, and flukes between these different species.This previously unexplored variation within Metriorhynchidae hints to differences in locomotory abilities between different species.
Time domain astronomy with the THESEUS satellite
2021-01-01

THESEUS is a medium size space mission of the European Space Agency, currently under evaluation for a possible launch in 2032. Its main objectives are to investigate the early Universe through the observation of gamma-ray bursts and to study the gravitational waves electromagnetic counterparts and neutrino events. On the other hand, its instruments, which include a wide field of view X-ray (0.3-5 keV) telescope based on lobster-eye focussing optics and a gamma-ray spectrometer with imaging capabilities in the 2-150 keV range, are also ideal for carrying out unprecedented studies in time domain astrophysics. In addition, the presence onboard of a 70 cm near infrared telescope will allow simultaneous multiwavelegth studies. Here we present the THESEUS capabilities for studying the time variability of different classes of sources in parallel to, and without affecting, the gamma-ray bursts hunt.
Peptidoglycan Salvage Enables the Periodontal Pathogen <b><i>Tannerella forsythia</i></b> to Survive within the Oral Microbial Community
2021-01-01

&lt;i&gt;Tannerella forsythia&lt;/i&gt; is an anaerobic, fusiform Gram-negative oral pathogen strongly associated with periodontitis, a multibacterial inflammatory disease that leads to the destruction of the teeth-supporting tissue, ultimately causing tooth loss. To survive in the oral habitat, &lt;i&gt;T. forsythia&lt;/i&gt; depends on cohabiting bacteria for the provision of nutrients. For axenic growth under laboratory conditions, it specifically relies on the external supply of &lt;i&gt;N&lt;/i&gt;-acetylmuramic acid (MurNAc), which is an essential constituent of the peptidoglycan (PGN) of bacterial cell walls. &lt;i&gt;T. forsythia&lt;/i&gt; comprises a typical Gram-negative PGN; however, as evidenced by genome sequence analysis, the organism lacks common enzymes required for the &lt;i&gt;de novo&lt;/i&gt; synthesis of precursors of PGN, which rationalizes its MurNAc auxotrophy. Only recently insights were obtained into how &lt;i&gt;T. forsythia&lt;/i&gt; gains access to MurNAc in its oral habitat, enabling synthesis of the own PGN cell wall. This report summarizes &lt;i&gt;T. forsythia&lt;/i&gt;’s strategies to survive in the oral habitat by means of PGN salvage pathways, including recovery of exogenous MurNAc and PGN-derived fragments but also polymeric PGN, which are all derived from cohabiting bacteria either via cell wall turnover or decay of cells. Salvage of polymeric PGN presumably requires the removal of peptides from PGN by an unknown amidase, concomitantly with the translocation of the polymer across the outer membrane. Two recently identified exo-lytic &lt;i&gt;N&lt;/i&gt;-acetylmuramidases (Tf_NamZ1 and Tf_NamZ2) specifically cleave the peptide-free, exogenous (nutrition source) PGN in the periplasm and release the MurNAc and disaccharide substrates for the transporters Tf_MurT and Tf_AmpG, respectively, whereas the peptide-containing, endogenous (the self-cell wall) PGN stays unattached. This review also outlines how &lt;i&gt;T. forsythia&lt;/i&gt; synthesises the PGN precursors UDP-MurNAc and UDP-&lt;i&gt;N&lt;/i&gt;-acetylglucosamine (UDP-GlcNAc), involving homologs of the &lt;i&gt;Pseudomonas&lt;/i&gt; sp. recycling enzymes AmgK/MurU and a monofunctional uridylyl transferase (named Tf_GlmU*), respectively.
An integrated workflow for enhanced taxonomic and functional coverage of the mouse fecal metaproteome
2021-01-01

Intestinal microbiota plays a key role in shaping host homeostasis by regulating metabolism, immune responses and behavior. Its dysregulation has been associated with metabolic, immune and neuropsychiatric disorders and is accompanied by changes in bacterial metabolic regulation. Although proteomics is well suited for analysis of individual microbes, metaproteomics of fecal samples is challenging due to the physical structure of the sample, presence of contaminating host proteins and coexistence of hundreds of taxa. Furthermore, there is a lack of consensus regarding preparation of fecal samples, as well as downstream bioinformatic analyses following metaproteomics data acquisition. Here we assess sample preparation and data analysis strategies applied to mouse feces in a typical mass spectrometry-based metaproteomic experiment. We show that subtle changes in sample preparation protocols may influence interpretation of biological findings. Two-step database search strategies led to significant underestimation of false positive protein identifications. Unipept software provided the highest sensitivity and specificity in taxonomic annotation of the identified peptides of unknown origin. Comparison of matching metaproteome and metagenome data revealed a positive correlation between protein and gene abundances. Notably, nearly all functional categories of detected protein groups were differentially abundant in the metaproteome compared to what would be expected from the metagenome, highlighting the need to perform metaproteomics when studying complex microbiome samples.
TheTwo, theOne, theMany, theNone:Rethinking the Republics of Spaniards and Indians in the Sixteenth-Century Spanish Indies
2021-01-01

Abstract For a half-century, the historiography on Spanish Habsburg rule suggested that the crown envisioned Indies society as best divided into two segregated sociolegal groups: the republic of the Spaniards and the republic of the Indians. This model was popularized by the eminent mid twentieth century Swedish historian Magnus Mörner and has since become a foundational concept in the field. However, using extensive archival evidence, this article suggests that the Mörner Thesis of the Two Republics is flawed. Historicizing sixteenth-century uses of the concept of the republic, it finds that contemporaries conceived of a complex social order in which many political communities such as municipalities and groups of petitioners could overlap within larger meta-republics, such as the Indies republic and the Christian faith-republic. It then turns to subjects’ uses of the two republics, noting that this conceptual duality appeared rarely in the petitions of Spanish officials, commoners, Indians, Afro-descendants, and mestizos, and was also rare in royal and viceregal legislation. Moreover, this binary most often served to suggest Spaniards’ and Indians’ common ground. The article then reflects on other approaches to understanding the Indies’ Spanish-Indian binary, the place of non-Spanish, non-Indian vassals within republic-thinking, and the staggering complexity of Indies laws, categories, and social interactions.