An Improved Link Model for Window Flow Control and Its Application to FAST TCP

This paper presents a link model which captures the queue dynamics in response to a change in a transmission control protocol (TCP) source's congestion window. By considering both self-clocking and the link integrator effect, the model generalizes existing models and is shown to be more accurate by both open loop and closed loop packet level simulations. It reduces to the known static link model when flows' round trip delays are identical, and approximates the standard integrator link model when there is significant cross traffic. We apply this model to the stability analysis of fast active queue management scalable TCP (FAST TCP) including its filter dynamics. Under this model, the FAST control law is linearly stable for a single bottleneck link with an arbitrary distribution of round trip delays. This result resolves the notable discrepancy between empirical observations and previous theoretical predictions. The analysis highlights the critical role of self-clocking in TCP stability, and the proof technique is new and less conservative than existing ones

Implementation of Provably Stable MaxNet

MaxNet TCP is a congestion control protocol that uses explicit multi-bit signalling from routers to achieve desirable properties such as high throughput and low latency. In this paper we present an implementation of an extended version of MaxNet. Our contributions are threefold. First, we extend the original algorithm to give both provable stability and rate fairness. Second, we introduce the MaxStart algorithm which allows new MaxNet connections to reach their fair rates quickly. Third, we provide a Linux kernel implementation of the protocol. With no overhead but 24-bit price signals, our implementation scales from 32 bit/s to 1 peta-bit/s with a 0.001% rate accuracy. We confirm the theoretically predicted properties by performing a range of experiments at speeds up to 1 Gbit/sec and delays up to 180 ms on the WAN-in-Lab facility

Queue Dynamics With Window Flow Control

This paper develops a new model that describes the queueing process of a communication network when data sources use window flow control. The model takes into account the burstiness in sub-round-trip time (RTT) timescales and the instantaneous rate differences of a flow at different links. It is generic and independent of actual source flow control algorithms. Basic properties of the model and its relation to existing work are discussed. In particular, for a general network with multiple links, it is demonstrated that spatial interaction of oscillations allows queue instability to occur even when all flows have the same RTTs and maintain constant windows. The model is used to study the dynamics of delay-based congestion control algorithms. It is found that the ratios of RTTs are critical to the stability of such systems, and previously unknown modes of instability are identified. Packet-level simulations and testbed measurements are provided to verify the model and its predictions

Negative predictive value and potential cost savings of acute nuclear myocardial perfusion imaging in low risk patients with suspected acute coronary syndrome: A prospective single blinded study

<p>Abstract</p> <p>Background</p> <p>Previous studies from the USA have shown that acute nuclear myocardial perfusion imaging (MPI) in low risk emergency department (ED) patients with suspected acute coronary syndrome (ACS) can be of clinical value. The aim of this study was to evaluate the utility and hospital economics of acute MPI in Swedish ED patients with suspected ACS.</p> <p>Methods</p> <p>We included 40 patients (mean age 55 ± 2 years, 50% women) who were admitted from the ED at Lund University Hospital for chest pain suspicious of ACS, and who had a normal or non-ischemic ECG and no previous myocardial infarction. All patients underwent MPI from the ED, and the results were analyzed only after patient discharge. The current diagnostic practice of admitting the included patients for observation and further evaluation was compared to a theoretical "MPI strategy", where patients with a normal MPI test would have been discharged home from the ED.</p> <p>Results</p> <p>Twenty-seven patients had normal MPI results, and none of them had ACS. MPI thus had a negative predictive value for ACS of 100%. With the MPI strategy, 2/3 of the patients would thus have been discharged from the ED, resulting in a reduction of total hospital cost by some 270 EUR and of bed occupancy by 0.8 days per investigated patient.</p> <p>Conclusion</p> <p>Our findings in a Swedish ED support the results of larger American trials that acute MPI has the potential to safely reduce the number of admissions and decrease overall costs for low-risk ED patients with suspected ACS.</p

The Ras superfamily at a glance

The Ras superfamily of small guanosine triphosphatases (GTPases) comprise over 150 human members (Table S1 in [supplementary material][1]), with evolutionarily conserved orthologs found in Drosophila, C. elegans, S. cerevisiae, S. pombe, Dictyostelium and plants ([Colicelli, 2004][2]). The Ra

No evidence of autoimmunity to human OX1 or OX2 orexin receptors in Pandemrix-vaccinated narcoleptic children

Narcolepsy type 1, likely an immune-mediated disease, is characterized by excessive daytime sleepiness and cataplexy. The disease is strongly associated with human leukocyte antigen (HLA) DQB1∗06:02. A significant increase in the incidence of childhood and adolescent narcolepsy was observed after a vaccination campaign with AS03-adjuvanted Pandemrix influenza vaccine in Nordic and several other countries in 2010 and 2011. Previously, it has been suggested that a surface-exposed region of influenza A nucleoprotein, a structural component of the Pandemrix vaccine, shares amino acid residues with the first extracellular domain of the human OX2 orexin/hypocretin receptor eliciting the development of autoantibodies. Here, we analyzed, whether H1N1pdm09 infection or Pandemrix vaccination contributed to the development of autoantibodies to the orexin precursor protein or the OX1 or OX2 receptors. The analysis was based on the presence or absence of autoantibody responses against analyzed proteins. Entire OX1 and OX2 receptors or just their extracellular N-termini were transiently expressed in HuH7 cells to determine specific antibody responses in human sera. Based on our immunofluorescence analysis, none of the 56 Pandemrix-vaccinated narcoleptic patients, 28 patients who suffered from a laboratory-confirmed H1N1pdm09 infection or 19 Pandemrix-vaccinated controls showed specific autoantibody responses to prepro-orexin, orexin receptors or the isolated extracellular N-termini of orexin receptors. We also did not find any evidence for cell-mediated immunity against the N-terminal epitopes of OX2. Our findings do not support the hypothesis that the surface-exposed region of the influenza nucleoprotein A would elicit the development of an immune response against orexin receptors. © 2020 The AuthorsPeer reviewe

An Accurate Link Model and Its Application to Stability Analysis of FAST TCP

This paper presents a link model which captures the queue dynamics when congestion windows of TCP sources change. By considering both the self-clocking and the link integrator effects, the model is a generalization of existing models and is shown to be more accurate by both open loop and closed loop packet level simulations. It reduces to the known static link model when flows' round trip delays are similar, and approximates the standard integrator link model when the heterogeneity of round trip delays is significant. We then apply this model to the stability analysis of FAST TCP. It is shown that FAST TCP flows over a single link are always linearly stable regardless of delay distribution. This result resolves the notable discrepancy between empirical observations and previous theoretical predictions. The analysis highlights the critical role of self-clocking in TCP stability and the scalability of FAST TCP with respect to delay. The proof technique is new and less conservative than the existing ones

Comprehensive and unbiased multiparameter high-throughput screening by compaRe finds effective and subtle drug responses in AML models

Large-scale multiparameter screening has become increasingly feasible and straightforward to perform thanks to developments in technologies such as high-content microscopy and high-throughput flow cytometry. The automated toolkits for analyzing similarities and differences between large numbers of tested conditions have not kept pace with these technological developments. Thus, effective analysis of multiparameter screening datasets becomes a bottleneck and a limiting factor in unbiased interpretation of results. Here we introduce compaRe, a toolkit for large-scale multiparameter data analysis, which integrates quality control, data bias correction, and data visualization methods with a mass-aware gridding algorithm-based similarity analysis providing a much faster and more robust analyses than existing methods. Using mass and flow cytometry data from acute myeloid leukemia and myelodysplastic syndrome patients, we show that compaRe can reveal interpatient heterogeneity and recognizable phenotypic profiles. By applying compaRe to high-throughput flow cytometry drug response data in AML models, we robustly identified multiple types of both deep and subtle phenotypic response patterns, highlighting how this analysis could be used for therapeutic discoveries. In conclusion, compaRe is a toolkit that uniquely allows for automated, rapid, and precise comparisons of large-scale multiparameter datasets, including high-throughput screens.Peer reviewe

HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner