Reinforcement Learning in Computing and Network Convergence Orchestration

As computing power is becoming the core productivity of the digital economy era, the concept of Computing and Network Convergence (CNC), under which network and computing resources can be dynamically scheduled and allocated according to users' needs, has been proposed and attracted wide attention. Based on the tasks' properties, the network orchestration plane needs to flexibly deploy tasks to appropriate computing nodes and arrange paths to the computing nodes. This is a orchestration problem that involves resource scheduling and path arrangement. Since CNC is relatively new, in this paper, we review some researches and applications on CNC. Then, we design a CNC orchestration method using reinforcement learning (RL), which is the first attempt, that can flexibly allocate and schedule computing resources and network resources. Which aims at high profit and low latency. Meanwhile, we use multi-factors to determine the optimization objective so that the orchestration strategy is optimized in terms of total performance from different aspects, such as cost, profit, latency and system overload in our experiment. The experiments shows that the proposed RL-based method can achieve higher profit and lower latency than the greedy method, random selection and balanced-resource method. We demonstrate RL is suitable for CNC orchestration. This paper enlightens the RL application on CNC orchestration

Distribution of HLA-A, -B and -DRB1 Genes and Haplotypes in the Tujia Population Living in the Wufeng Region of Hubei Province, China

BACKGROUND: The distribution of HLA alleles and haplotypes varies widely between different ethnic populations and geographic areas. Before any genetic marker can be used in a disease-associated study it is therefore essential to investigate allelic frequencies and establish a genetic database. METHODOLOGY/PRINCIPAL FINDINGS: This is the first report of HLA typing in the Tujia group using the Luminex HLA-SSO method HLA-A, -B and -DRB1 allelic distributions were determined in 124 unrelated healthy Tujia individuals, and haplotypic frequencies and linkage disequilibrium parameters were estimated using the maximum-likelihood method. In total 10 alleles were detected at the HLA-A locus, 21 alleles at the HLA-B locus and 14 alleles at the HLA-DRB1 locus. The most frequently observed alleles in the HLA-I group were HLA-A*02 (35.48%), A*11 (28.23%), A*24 (15.73%); HLA-B*40 (25.00%), B*46 (16.13%), and B*15 (15.73%). Among HLA-DRB1 alleles, high frequencies of HLA-DRB1*09 (25.81%) were observed, followed by HLA-DRB1*15 (12.9%), and DRB1*12 (10.89%). The two-locus haplotypes at the highest frequency were A*02-B*46A (8.47%), followed by A*11-B*40 (7.66%), A*02-B*40 (8.87%), A*11-B*15 (6.45%), A*02-B*15 (6.05%), B*40-DRB1*09 (9.27%) and B*46-DRB1*09 (6.45%). The most common three-locus haplotypes found in the Tujia population were A*02-B*46-DRB1*09 (4.84%) and A*02-B*40-DRB1*09 (4.03%). Fourteen two-loci haplotypes had significant linkage disequilibrium. Construction of a neighbor-joining phylogenetic tree and principal component analysis using the allelic frequencies at HLA-A was performed to compare the Tujia group and twelve other previously reported populations. The Tujia population in the Wufeng of Hubei Province had the closest genetic relationship with the central Han population, and then to the Shui, the Miao, the southern Han and the northern Han ethnic groups. CONCLUSIONS/SIGNIFICANCE: These results will become a valuable source of data for tracing population migration, planning clinical organ transplantation, carrying out HLA-linked disease-associated studies and forensic identification

A class of phase-type ageing models and their lifetime distributions

Ageing is a universal and ever-present biological phenomenon. Yet, describing the ageing mechanism in formal mathematical terms — in particular, capturing the ageing pattern and quantifying the ageing rate — has remained a challenging actuarial modelling endeavour. In this thesis, we propose a class of Coxian-type Markovian models. This class enables a quantitative description of the well-known characteristics of ageing, which is a genetically determined, progressive, and essentially irreversible process. The unique structure of our model features the transition rate for the ageing process and a functional form for the relationship between ageing and death with a shape parameter that captures the biologically deteriorating effect of ageing. The force of moving from one state to another in the Markovian process indicates the intrinsic biological ageing force. The associated increasing exit rate captures the external force of stress due to mortality risk on a living organism. We define an index, called physiological age, to quantify the heterogeneity between individuals. The physiological age can be used to compare the death rate between individuals in which an individual with a higher physiological age has higher mortality rate. The probability in each state at any time is calculated, and the distribution of the physiological age at any chronological age is obtained. We also prove that the distribution of the physiological age at a given time can be approximated by a normal distribution as the Phase-Type Ageing Model (PTAM) allows for a large number of states. The approximation can be used to quickly compute the probability in each state at any given time. The lifetime distribution for each individual readily follows from their physiological ages whose distribution is helpful in quantifying the variability of individual health status in the population. We develop an efficient method to evaluate the PTAM’s likelihood utilising a lifetime data set. Our likelihood calculation uses vectorisation to find simultaneously the density function at observed lifetimes. Furthermore,our method uses uniformisation strategy to stabilise the numerical calculation with a guaranteed accuracy for any error tolerance. We demonstrate that our numerical method is more accurate and faster than the traditional method using matrix exponential. Lastly, we investigate the estimability of the PTAM when only the lifetime data is observable along with some conditions that could improve the model’s estimability in terms of parameters’ identification

Experimental Study on Bond Behavior between Plain Reinforcing Bars and Concrete

To evaluate the bond behavior between the reinforcing bar and surrounding concrete, a total of six-group pullout specimens with plain steel bars and two-group specimens with deformed steel bars, serving as a reference, are experimentally investigated and presented in this study. The main test parameters of this investigation include embedment length, surface type of reinforcing bars, and bar diameter. In particular, the bond mechanism of plain steel reinforcing bars against the surrounding concrete was analyzed by comparing with six-group pullout specimens with aluminium alloy bars. The results indicated that the bond stress experienced by plain bars is quite lower than that of the deformed bars given equal structural characteristics and details. Averagely, plain bars appeared to develop only 18.3% of the bond stress of deformed bars. Differing from the bond strength of plain steel bars, which is based primarily on chemical adhesion and friction force, the bond stress of aluminium alloy bars is mainly experienced by chemical adhesion and about 0.21~0.56 MPa, which is just one-tenth of that of plain steel bars. Based on the test results, a bond-slip model at the interface between concrete and plain bars is put forward

Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/Kb Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome

Hantaan virus (HTNV) infections can cause severe hemorrhagic fever with renal syndrome (HFRS) in humans, which is associated with high fatality rates. Cytotoxic T cell (CTL) responses contribute to virus elimination; however, to date, HLA class I allele-restricted HTNV glycoprotein (GP) epitopes recognized by CTLs have not been reported, limiting our understanding of CTL responses against HTNV infection in humans. In this study, 34 HTNV GP nine-mer epitopes that may bind to HLA-A*0201 molecules were predicted using the BIMAS and SYFPEITHI database. Seven of the epitopes were demonstrated to bind to HLA-A*0201 molecules with high affinity via the T2 cell binding assay and were successfully used to synthesize peptide/HLA-A*0201 tetramers. The results of tetramer staining showed that the frequencies of each epitope-specific CTL were higher in patients with milder HFRS, which indicated that the epitopes may induce protective CTL responses after HTNV infection. IFN-γ-enzyme-linked immunospot analysis further confirmed the immunoreactivity of epitopes by eliciting epitope-specific IFN-γ-producing CTL responses. In an HTNV challenge trial, significant inhibition of HTNV replication characterized by lower levels of antigens and RNA loads was observed in major target organs (liver, spleen, and kidneys) of HLA-A2.1/Kb transgenic mice pre-vaccinated with nonapeptides VV9 (aa8–aa16, VMASLVWPV), SL9 (aa996–aa1004, SLTECPTFL) and LL9 (aa358–aa366, LIWTGMIDL). Importantly, LL9 exhibited the best ability to induce protective CTL responses and showed a prominent effect on the kidneys, potentially preventing kidney injury after HTNV infection. Taken together, our results highlight that HTNV GP-derived HLA-A*0201-restricted epitopes could elicit protective CTL responses against the virus, and that epitope LL9 functions as an immunodominant protective epitope that may advance the design of safe and effective CTL-based HTNV peptide vaccines for humans

The assessment of Hantaan virus-specific antibody responses after the immunization program for hemorrhagic fever with renal syndrome in northwest China

Xianyang city is one of the main hemorrhagic fever with renal syndrome (HFRS) epidemic areas in northwest China. Although the HFRS immunity program has been provided in this city, HFRS is still occurred every year. In order to implement the vaccination program effectively and to control HFRS, the analysis of antibody responses specific to Hantaan virus (HTNV) in individuals after vaccination is essential. In this study, a total of 100 subjects were divided into 5 groups: unvaccinated, 1, 3, 29 and 33 months after boost vaccination. The levels and the positive rates of HTNV-NP-specific IgM and IgG antibodies as well as HTNV neutralizing antibodies were significantly increased in the serum of the vaccinated individuals. The positive rates and levels of HTNV-NP-specific IgG and HTNV neutralizing antibody reached their highest values at 3 months respectively and could be sustained up to 33 months after vaccination. Moreover, the titres of HTNV-NP-specific IgM or IgG antibody and the titres of HTNV neutralizing antibody at 1 month after vaccination have a positive correlation. The level of HTNV-NP-specific IgG antibody was much higher than that of HTNV-NP-specific IgM antibody or HTNV neutralizing antibody. In addition, the strongest responses of antibody-secreting cells were observed at 3 months after vaccination, which was consistent with the serum results. Therefore, the HFRS immunization program is effective to induce humoral immunity in the population of northwest China

Structure and Function of HLA-A*02-Restricted Hantaan Virus Cytotoxic T Cell Epitope that Mediates Effective Protective Responses in HLA-A2.1/Kb Transgenic Mice

Hantavirus infections cause severe emerging diseases in humans and are associated with high mortality rates; therefore, they have become a global public health concern. Our previous study showed that the CD8+ T-cell epitope aa129-aa137 (FVVPILLKA, FA9) of the Hantaan virus (HTNV) nucleoprotein (NP), restricted by human leukocyte antigen (HLA)-A*02, induced specific CD8+ T-cell responses that controlled HTNV infection in humans. However, the in vivo immunogenicity of peptide FA9 and the effect of FA9-specific CD8+ T-cell immunity remain unclear. Here, based on a detailed structural analysis of the peptide FA9/HLA-A*0201 complex and functional investigations using HLA-A2.1/Kb transgenic mice, we found that the overall structure of the peptide FA9/HLA-A*0201 complex displayed a typical MHC class I fold with Val2 and Ala9 as primary anchor residues and Val3 and Leu7 as secondary anchor residues that allow peptide FA9 to bind tightly with an HLA-A*0201 molecule. Residues in the middle portion of peptide FA9 extruding out of the binding groove may be the sites that allow for recognition by T cell receptors. Immunization with peptide FA9 in HLA-A2.1/Kb transgenic mice induced FA9-specific cytotoxic T cell responses characterized by the induction of high expression levels of IFN-γ, TNF-α, granzyme B, and CD107a. In an HTNV challenge trial, significant reductions in the levels of both the antigens and the HTNV RNA loads were observed in the liver, spleen and kidneys of transgenic mice pre-vaccinated with peptide FA9. Thus, our findings highlight the ability of HTNV epitope-specific CD8+ T-cell immunity to control HTNV and support the possibility that the HTNV-NP FA9 peptide, naturally processed in vivo in an HLA-A*02-restriction manner, may be a good candidate for the development HTNV peptide vaccines

Down-regulation of WWP2 aggravates Type 2 diabetes mellitus-induced vascular endothelial injury through modulating ubiquitination and degradation of DDX3X

Abstract Background Endothelial injury caused by Type 2 diabetes mellitus (T2DM) is considered as a mainstay in the pathophysiology of diabetic vascular complications (DVCs). However, the molecular mechanism of T2DM-induced endothelial injury remains largely unknown. Here, we found that endothelial WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) act as a novel regulator for T2DM-induced vascular endothelial injury through modulating ubiquitination and degradation of DEAD-box helicase 3 X-linked (DDX3X). Methods Single-cell transcriptome analysis was used to evaluate WWP2 expression in vascular endothelial cells of T2DM patients and healthy controls. Endothelial-specific Wwp2 knockout mice were used to investigate the effect of WWP2 on T2DM-induced vascular endothelial injury. In vitro loss- and gain-of-function studies were performed to assess the function of WWP2 on cell proliferation and apoptosis of human umbilical vein endothelial cells. The substrate protein of WWP2 was verified using mass spectrometry, coimmunoprecipitation assays and immunofluorescence assays. The mechanism of WWP2 regulation on substrate protein was investigated by pulse-chase assay and ubiquitination assay. Results The expression of WWP2 was significantly down-regulated in vascular endothelial cells during T2DM. Endothelial-specific Wwp2 knockout in mice significantly aggravated T2DM-induced vascular endothelial injury and vascular remodeling after endothelial injury. Our in vitro experiments showed that WWP2 protected against endothelial injury by promoting cell proliferation and inhibiting apoptosis in ECs. Mechanically, we found that WWP2 is down-regulated in high glucose and palmitic acid (HG/PA)-induced ECs due to c-Jun N-terminal kinase (JNK) activation, and uncovered that WWP2 suppresses HG/PA-induced endothelial injury by catalyzing K63-linked polyubiquitination of DDX3X and targeting it for proteasomal degradation. Conclusion Our studies revealed the key role of endothelial WWP2 and the fundamental importance of the JNK-WWP2-DDX3X regulatory axis in T2DM-induced vascular endothelial injury, suggesting that WWP2 may serve as a new therapeutic target for DVCs