On the Interaction between TCP and the Wireless Channel in CDMA2000 Networks

In this work, we conducted extensive active measurements on a large nationwide CDMA2000 1xRTT network in order to characterize the impact of both the Radio Link Protocol and more importantly, the wireless scheduler, on TCP. Our measurements include standard TCP/UDP logs, as well as detailed RF layer statistics that allow observability into RF dynamics. With the help of a robust correlation measure, normalized mutual information, we were able to quantify the impact of these two RF factors on TCP performance metrics such as the round trip time, packet loss rate, instantaneous throughput etc. We show that the variable channel rate has the larger impact on TCP behavior when compared to the Radio Link Protocol. Furthermore, we expose and rank the factors that influence the assigned channel rate itself and in particular, demonstrate the sensitivity of the wireless scheduler to the data sending rate. Thus, TCP is adapting its rate to match the available network capacity, while the rate allocated by the wireless scheduler is influenced by the sender's behavior. Such a system is best described as a closed loop system with two feedback controllers, the TCP controller and the wireless scheduler, each one affecting the other's decisions. In this work, we take the first steps in characterizing such a system in a realistic environment

TCP over CDMA2000 Networks: A Cross-Layer Measurement Study

Modern cellular channels in 3G networks incorporate sophisticated power control and dynamic rate adaptation which can have significant impact on adaptive transport layer protocols, such as TCP. Though there exists studies that have evaluated the performance of TCP over such networks, they are based solely on observations at the transport layer and hence have no visibility into the impact of lower layer dynamics, which are a key characteristic of these networks. In this work, we present a detailed characterization of TCP behavior based on cross-layer measurement of transport layer, as well as RF and MAC layer parameters. In particular, through a series of active TCP/UDP experiments and measurement of the relevant variables at all three layers, we characterize both, the wireless scheduler and the radio link protocol in a commercial CDMA2000 network and assess their impact on TCP dynamics. Somewhat surprisingly, our findings indicate that the wireless scheduler is mostly insensitive to channel quality and sector load over short timescales and is mainly affected by the transport layer data rate. Furthermore, with the help of a robust correlation measure, Normalized Mutual Information, we were able to quantify the impact of the wireless scheduler and the radio link protocol on various TCP parameters such as the round trip time, throughput and packet loss rate

Systems biology platform for efficient development and translation of multitargeted therapeutics

Failure to achieve efficacy is among the top, if not the most common reason for clinical trial failures. While there may be many underlying contributors to these failures, selecting the right mechanistic hypothesis, the right dose, or the right patient population are the main culprits. Systems biology is an inter-disciplinary field at the intersection of biology and mathematics that has the growing potential to increase probability of success in clinical trials, delivering a data-driven matching of the right mechanism to the right patient, at the right dose. Moreover, as part of successful selection of targets for a therapeutic area, systems biology is a prime approach to development of combination therapies to combating complex diseases, where single targets have failed to achieve sufficient efficacy in the clinic. Systems biology approaches have become increasingly powerful with the progress in molecular and computational methods and represent a novel innovative tool to tackle the complex mechanisms of human disease biology, linking it to clinical phenotypes and optimizing multiple steps of drug discovery and development. With increasing ability of probing biology at a cellular and organ level with omics technologies, systems biology is here to stay and is positioned to be one of the key pillars of drug discovery and development, predicting and advancing the best therapies that can be combined together for an optimal pharmacological effect in the clinic. Here we describe a systems biology platform with a stepwise approach that starts with characterization of the key pathways contributing to the Mechanism of Disease (MOD) and is followed by identification, design, optimization, and translation into the clinic of the best therapies that are able to reverse disease-related pathological mechanisms through one or multiple Mechanisms of Action (MOA)

Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study

Background ‘Long COVID’ describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models along with certain clinical conditions, and therefore may reduce fatigue associated with Long COVID. We aimed to assess the efficacy, safety and tolerability of AXA1125 in Long COVID. Methods Patients with fatigue-dominant Long COVID were recruited in this single-centre, double-blind, randomised controlled phase 2a pilot study completed in the UK. Patients were randomly assigned (1:1) using an Interactive Response Technology to receive either AXA1125 or matching placebo in a clinical-based setting. Each dose (33.9 g) of AXA1125 or placebo was administered orally in a liquid suspension twice daily for four weeks with a two-week follow-up period. The primary endpoint was the mean change from baseline to day 28 in the phosphocreatine (PCr) recovery rate following moderate exercise, assessed by 31P-magnetic resonance spectroscopy (MRS). All patients were included in the intention to treat analysis. This trial was registered at ClinicalTrials.gov, NCT05152849. Findings Between December 15th 2021, and May 23th 2022, 60 participants were screened, and 41 participants were randomised and included in the final analysis. Changes in skeletal muscle phosphocreatine recovery time constant (τPCr) and 6-min walk test (6MWT) did not significantly differ between treatment (n = 21) and placebo group (n = 20). However, treatment with AXA1125 was associated with significantly reduced day 28 Chalder Fatigue Questionnaire [CFQ-11] fatigue score when compared with placebo (least squares mean difference [LSMD] −4.30, 95% confidence interval (95% CI) −7.14, −1.47; P = 0.0039). Eleven (52.4%, AXA1125) and four (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious or led to treatment discontinuation. Interpretation Although treatment with AXA1125 did not improve the primary endpoint (τPCr-measure of mitochondrial respiration), when compared to placebo, there were significant improvements in fatigue-based symptoms among patients living with Long COVID following a four-week treatment period. Further multicentre studies are needed to validate our findings in a larger cohort of patients with fatigue-dominant Long COVID. Funding Axcella Therapeutics

Stability of Metabolic Networks via Linear-In-Flux-Expressions

International audienceThe methodology named LIFE (Linear-in-Flux Expressions) was developed with the purpose of simulating and analyzing large metabolic systems. With LIFE, the number of model parameters is reduced by accounting for correlations among the parameters of the system. Perturbation analysis on LIFE systems results in less overall variability of the system, leading to results that more closely resemble empirical data. These systems can be associated to graphs, and characteristics of the graph give insight into the dynamics of the system. This work addresses two main problems: 1. for fixed metabolite levels, find all fluxes for which the metabolite levels are an equilibrium, and 2. for fixed fluxes, find all metabolite levels which are equilibria for the system. We characterize the set of solutions for both problems, and show general results relating stability of systems to the structure of the associated graph. We show that there is a structure of the graph necessary for stable dynamics. Along with these general results, we show how stability analysis from the fields of network flows, compartmental systems, control theory and Markov chains apply to LIFE systems

Origin and evolution of Neoproterozoic metaophiolitic mantle rocks from the eastern Desert of Egypt: Implications for tectonic and metamorphic events in the Arabian-Nubian Shield

The mantle rocks from Kadaboura and Madara areas represent sections of dismembered ophiolitic complexes developed during the Neoproterozoic in the Eastern Desert of Egypt, which is located in the northwestern corner of the Arabian–Nubian Shield. The Kadaboura mantle rocks comprise serpentinites and serpentinized dunites, whereas those of the Madara consist of serpentinites and serpentinized pyroxenites.Despite the serpentinization of the studied mantle rocks, few relicts of primary chromite, olivine and pyroxene are preserved. Chromite is partly altered having unaltered Al-rich chromite cores surrounded by Fe-rich chromite and Cr-rich magnetite rims. The unaltered Al-rich chromite cores show compositions equilibrated at temperatures mostly below ~500-600°C, which is a temperature comparable to that estimated for primary chromite in greenschist up to lower amphibolite facies rocks. The high Cr# [100×Cr/(Cr+Al)= 47-76] of the unaltered chromite cores and the Mg-rich nature of the olivine relicts (Fo91–94) indicate that the studied mantle rocks were produced from a highly depleted mantle that experienced high degrees of melt extraction (mostly ~30-40%). This range of melt extraction resembles that estimated for supra-subduction zone peridotites, but higher than that in abyssal and passive margin peridotites. Furthermore, the clinopyroxene relicts show compositions comparable to those from the Mariana forearc peridotites. Bulk-rock geochemistry also reflects derivation from an extremely depleted and a highly refractory mantle source. Modelling of rare-earth elements suggests that the studied mantle rocks were possibly formed by the interaction of their highly depleted harzburgitic mantle precursors with subduction-related melts/fluids during their evolution in a fore-arc basin of the supra-subduction zone.The proposed geodynamic model suggests that the oceanic lithosphere generated during the seafloor spreading of the Mozambique Ocean was emplaced in the upper plate of the intra-oceanic subduction zone, in which the formely depleted Neoproterozoic mantle of the Arabian-Nubian Shield experienced mature phases of hydrous melting, extreme depletion and enrichment

TCP over CDMA2000 Networks: A Cross-Layer Measurement Study

Abstract. Modern cellular channels in 3G networks incorporate sophisticated power control and dynamic rate adaptation which can have a significant impact on adaptive transport layer protocols, such as TCP. Though there exists studies that have evaluated the performance of TCP over such networks, they are based solely on observations at the transport layer and hence have no visibility into the impact of lower layer dynamics, which are a key characteristic of these networks. In this work, we present a detailed characterization of TCP behavior based on cross-layer measurement of transport, as well as RF and MAC layer parameters. In particular, through a series of active TCP/UDP experiments and measurement of the relevant variables at all three layers, we characterize both, the wireless scheduler in a commercial CDMA2000 network and its impact on TCP dynamics. Somewhat surprisingly, our findings indicate that the wireless scheduler is mostly insensitive to channel quality and sector load over short timescales and is mainly affected by the transport layer data rate. Furthermore, we empirically demonstrate the impact of the wireless scheduler on various TCP parameters such as the round trip time, throughput and packet loss rate.

TCP Over CDMA2000 Networks : A Cross-Layer Measurement Study. Available at http://research.sprintlabs.com, Sprint ATL

Abstract. Modern cellular channels in 3G networks incorporate sophisticated power control and dynamic rate adaptation which can have a significant impact on adaptive transport layer protocols, such as TCP. Though there exists studies that have evaluated the performance of TCP over such networks, they are based solely on observations at the transport layer and hence have no visibility into the impact of lower layer dynamics, which are a key characteristic of these networks. In this work, we present a detailed characterization of TCP behavior based on cross-layer measurement of transport, as well as RF and MAC layer parameters. In particular, through a series of active TCP/UDP experiments and measurement of the relevant variables at all three layers, we characterize both, the wireless scheduler in a commercial CDMA2000 network and its impact on TCP dynamics. Somewhat surprisingly, our findings indicate that the wireless scheduler is mostly insensitive to channel quality and sector load over short timescales and is mainly affected by the transport layer data rate. Furthermore, we empirically demonstrate the impact of the wireless scheduler on various TCP parameters such as the round trip time, throughput and packet loss rate.

On the Interaction between TCP and the Wireless Channel in CDMA2000 Networks

In this work, we conducted extensive active measurements on a large nationwide CDMA2000 1xRTT network in order to characterize the impact of both the Radio Link Protocol and more importantly, the wireless scheduler, on TCP. Our measurements include standard TCP/UDP logs, as well as detailed RF layer statistics that allow observability into RF dynamics. With the help of a robust correlation measure, normalized mutual information, we were able to quantify the impact of these two RF factors on TCP performance metrics such as the round trip time, packet loss rate, instantaneous throughput etc. We show that the variable channel rate has the larger impact on TCP behavior when compared to the Radio Link Protocol. Furthermore, we expose and rank the factors that influence the assigned channel rate itself and in particular, demonstrate the sensitivity of the wireless scheduler to the data sending rate. Thus, TCP is adapting its rate to match the available network capacity, while the rate allocated by the wireless scheduler is influenced by the sender’s behavior. Such a system is best described as a closed loop system with two feedback controllers, the TCP controller and the wireless scheduler, each one affecting the other’s decisions. In this work, we take the first steps in characterizing such a system in a realistic environment. I