Impact of heart rate in atrial fibrillation versus sinus rhythm on mortality in octogenarian patients with acute coronary syndrome

Introduction: Association of heart rate (HR) with mortality in patients with acute coronary syndrome (ACS) and aged ≥ 80 years are underrepresented in clinical trials. We therefore aimed to investigate the association of HR in atrial fibrillation (AF) versus sinus rhythm (SR) with all-cause mortality in octogenarian patients with ACS. Methods: A total of 336 patients with ACS patients and aged ≥ 80 years were enrolled into the current study. The end point of interest was death from any cause. Association of HR in AF versus SR with mortality was analyzed by Kaplan- Meier curve following log-rank test and multivariable Cox regression analysis. Results: in total, 63 (87.5%) of patients with AF were dead and 147 (59.8%) of patients with SR were dead during the follow-up period. The best cut-off was 80 bpm, with a sensitivity of 62% and specificity of 66%. HR ≤ 80 bpm in SR but not in AF was associated with better outcome as compared with HR > 80 bpm (Chi-Square = 26.55, Log rank P < 0.001). In SR subgroup, the hazard ratios of HR ≤ 80 bpm were 0.51(95% CI 0.37-0.70, P < 0.001) adjusted for age, 0.46 (95%CI 0.33-0.63, P < 0.001) adjusted for gender, 0.62 (95%CI 0.42- 0.93, P = 0.020) adjusted for multivariables respectively. In AF subgroup, the hazard ratios of HR ≤ 80 bpm were 0.83(95% CI 0.49-1.38, P = 0.464) adjusted for age, 0.96 (95%CI 0.59-1.58, P = 0.882) adjusted for gender, 0.72(95% CI 0.41-1.26, P = 0.249) adjusted for multivariables respectively. Conclusion: The current study demonstrates that heart rate is an independent prognostic predictor for all-cause mortality, and HR ≤ 80 bpm is associated with improved outcome in SR but not in AF in octogenarian patients with ACS

Nurr1 regulates Top IIβ and functions in axon genesis of mesencephalic dopaminergic neurons

<p>Abstract</p> <p>Background</p> <p>NURR1 (also named as NR4A2) is a member of the steroid/thyroid hormone receptor family, which can bind to DNA and modulate expression of target genes. Previous studies have shown that NURR1 is essential for the nigral dopaminergic neuron phenotype and function maintenance, and the defects of the gene are possibly associated with Parkinson's disease (PD).</p> <p>Results</p> <p>In this study, we used new born <it>Nurr1 </it>knock-out mice combined with Affymetrix genechip technology and real time polymerase chain reaction (PCR) to identify <it>Nurr1 </it>regulated genes, which led to the discovery of several transcripts differentially expressed in the nigro-striatal pathway of <it>Nurr1 </it>knock-out mice. We found that an axon genesis gene called <it>Topoisomerase IIβ </it>(<it>Top IIβ</it>) was down-regulated in <it>Nurr1 </it>knock-out mice and we identified two functional NURR1 binding sites in the proximal <it>Top IIβ </it>promoter. While in <it>Top IIβ </it>null mice, we saw a significant loss of dopaminergic neurons in the substantial nigra and lack of neurites along the nigro-striatal pathway. Using specific TOP II antagonist ICRF-193 or <it>Top IIβ </it>siRNA in the primary cultures of ventral mesencephalic (VM) neurons, we documented that suppression of TOP IIβ expression resulted in VM neurites shortening and growth cones collapsing. Furthermore, microinjection of ICRF-193 into the mouse medial forebrain bundle (MFB) led to the loss of nigro-striatal projection.</p> <p>Conclusion</p> <p>Taken together, our findings suggest that <it>Top IIβ </it>might be a down-stream target of <it>Nurr1</it>, which might influence the processes of axon genesis in dopaminergic neurons via the regulation of TOP IIβ expression. The <it>Nurr1-Top IIβ </it>interaction may shed light on the pathologic role of <it>Nurr1 </it>defect in the nigro-striatal pathway deficiency associated with PD.</p

Sluggish and Chemically-Biased Interstitial Diffusion in Concentrated Solid Solution Alloys: Mechanisms and Methods

Interstitial diffusion is a pivotal process that governs the phase stability and irradiation response of materials in non-equilibrium conditions. In this work, we study sluggish and chemically-biased interstitial diffusion in Fe-Ni concentrated solid solution alloys (CSAs) by combining machine learning (ML) and kinetic Monte Carlo (kMC), where ML is used to accurately and efficiently predict the migration energy barriers on-the-fly. The ML-kMC reproduces the diffusivity that was reported by molecular dynamics results at high temperatures. With this powerful tool, we find that the observed sluggish diffusion and the "Ni-Ni-Ni"-biased diffusion in Fe-Ni alloys are ascribed to a unique "Barrier Lock" mechanism, whereas the "Fe-Fe-Fe"-biased diffusion is influenced by a "Component Dominance" mechanism. Inspired by the mentioned mechanisms, a practical AvgS-kMC method is proposed for conveniently and swiftly determining interstitial-mediated diffusivity by only relying on the mean energy barriers of migration patterns. Combining the AvgS-kMC with the differential evolutionary algorithm, an inverse design strategy for optimizing sluggish diffusion properties is applied to emphasize the crucial role of favorable migration patterns.Comment: 30 pages,9 figure

Topological Susceptibility under Gradient Flow

We study the impact of the Gradient Flow on the topology in various models of lattice field theory. The topological susceptibility $\chi_{\rm t}$ is measured directly, and by the slab method, which is based on the topological content of sub-volumes ("slabs") and estimates $\chi_{\rm t}$ even when the system remains trapped in a fixed topological sector. The results obtained by both methods are essentially consistent, but the impact of the Gradient Flow on the characteristic quantity of the slab method seems to be different in 2-flavour QCD and in the 2d O(3) model. In the latter model, we further address the question whether or not the Gradient Flow leads to a finite continuum limit of the topological susceptibility (rescaled by the correlation length squared, $\xi^{2}$). This ongoing study is based on direct measurements of $\chi_{\rm t}$ in $L \times L$ lattices, at $L/\xi \simeq 6$.Comment: 8 pages, LaTex, 5 figures, talk presented at the 35th International Symposium on Lattice Field Theory, June 18-24, 2017, Granada, Spai

Peripheral arterial occlusive disease: Global gene expression analyses suggest a major role for immune and inflammatory responses

<p>Abstract</p> <p>Background</p> <p>Peripheral arterial disease (PAD), a major manifestation of atherosclerosis, is associated with significant cardiovascular morbidity, limb loss and death. However, mechanisms underlying the genesis and progression of the disease are far from clear. Genome-wide gene expression profiling of clinical samples may represent an effective approach to gain relevant information.</p> <p>Results</p> <p>After histological classification, a total of 30 femoral artery samples, including 11 intermediate lesions, 14 advanced lesions and 5 normal femoral arteries, were profiled using Affymetrix microarray platform. Following real-time RT-PCR validation, different algorithms of gene selection and clustering were applied to identify differentially expressed genes. Under a stringent cutoff, i.e., a false discovery rate (FDR) <0.5%, we found 366 genes were differentially regulated in intermediate lesions and 447 in advanced lesions. Of these, 116 genes were overlapped between intermediate and advanced lesions, including 68 up-regulated genes and 48 down-regulated ones. In these differentially regulated genes, immune/inflammatory genes were significantly up-regulated in different stages of PAD, (85/230 in intermediate lesions, 37/172 in advanced lesions). Through literature mining and pathway analysis using different databases such as Gene Ontology (GO), and the Kyoto Encyclopedia of Gene and Genomics (KEGG), genes involved in immune/inflammatory responses were significantly enriched in up-regulated genes at different stages of PAD(p < 0.05), revealing a significant correlation between immune/inflammatory responses and disease progression. Moreover, immune-related pathways such as Toll-like receptor signaling and natural killer cell mediated cytotoxicity were particularly enriched in intermediate and advanced lesions (P < 0.05), highlighting their pathogenic significance during disease progression.</p> <p>Conclusion</p> <p>Lines of evidence revealed in this study not only support previous hypotheses, primarily based on studies of animal models and other types of arterial disease, that inflammatory responses may influence the development of PAD, but also permit the recognition of a wide spectrum of immune/inflammatory genes that can serve as signatures for disease progression in PAD. Further studies of these signature molecules may eventually allow us to develop more sophisticated protocols for pharmaceutical interventions.</p

The method evaluation of culturing df-1 to proliferate canine distemper virus in mink with cephodex microcarrier

As an acute and highly lethal infectious disease, there is no specific therapeutic drug for canine distemper (CD). Although the process of large-scale production of canine distemper virus (CDV) vaccine of mink has been greatly improved, there are still many deficiencies to be perfected. As one of the most promising technologies for large-scale vaccine production, microcarrier suspension culture technology needs to be further improved. In this study, the application effect of the new Cephodex microcarrier in CDV culture was evaluated to establish a set of technical process for DF-1 cell high-density growth and CDV efficient proliferation. To perfect the large-scale CDV production process, Cephodex was used to suspension culture DF-1 cells for proliferating CDV. In a shake flasks culture system, the optimal culture conditions were established by optimizing culture temperature, virus inoculation and harvest time. Therefore, mink CD vaccine high-efficiency production was laid on the preliminarily established technology of CDV microcarrier suspension culture. The cell density could reach over 3×106 cells/mL after 72 h cultured with Cephodex microcarrier at 37°C. Proliferated at 35°C, the CDV titer after 72 h was about 100.5 TCID50/0.1ml higher than that at 33°C and 37°C. These results show that the Cephodex microcarrier could be used for large-scale culture of DF-1 cells and efficient proliferation of CDV

Learning and innovative elements of strategy adoption rules expand cooperative network topologies

Cooperation plays a key role in the evolution of complex systems. However, the level of cooperation extensively varies with the topology of agent networks in the widely used models of repeated games. Here we show that cooperation remains rather stable by applying the reinforcement learning strategy adoption rule, Q-learning on a variety of random, regular, small-word, scale-free and modular network models in repeated, multi-agent Prisoners Dilemma and Hawk-Dove games. Furthermore, we found that using the above model systems other long-term learning strategy adoption rules also promote cooperation, while introducing a low level of noise (as a model of innovation) to the strategy adoption rules makes the level of cooperation less dependent on the actual network topology. Our results demonstrate that long-term learning and random elements in the strategy adoption rules, when acting together, extend the range of network topologies enabling the development of cooperation at a wider range of costs and temptations. These results suggest that a balanced duo of learning and innovation may help to preserve cooperation during the re-organization of real-world networks, and may play a prominent role in the evolution of self-organizing, complex systems.Comment: 14 pages, 3 Figures + a Supplementary Material with 25 pages, 3 Tables, 12 Figures and 116 reference

Flat edge modes of graphene and of Z2 topological insulator

A graphene nano-ribbon in the zigzag edge geometry exhibits a specific type of gapless edge modes with a partly flat band dispersion. We argue that the appearance of such edge modes are naturally understood by regarding graphene as the gapless limit of a Z2 topological insulator. To illustrate this idea, we consider both Kane-Mele (graphene-based) and Bernevig-Hughes-Zhang models: the latter is proposed for HgTe/CdTe 2D quantum well. Much focus is on the role of valley degrees of freedom, especially, on how they are projected onto and determine the 1D edge spectrum in different edge geometries