Self-organisation in LTE networks : an investigation

Mobile telecommunications networks based on Long Term Evolution (LTE) technology promise faster throughput to their users. LTE networks are however susceptible to a phenomenon known as inter-cell interference which can greatly reduce the throughput of the network causing unacceptable degradation of performance for cell edge users. A number of approaches to mitigating or minimising inter-cell interference have been presented in the literature such as randomisation, cancellation and coordination. The possibility of coordination between network nodes in an LTE network is made possible through the introduction of the X2 network link. This thesis explores approaches to reducing the effect of inter-cell interference on the throughput of LTE networks by using the X2 link to coordinate the scheduling of radio resources. Three approaches to the reduction of inter-cell interference were developed. Localised organisation is a centralised scheme in which a scheduler is optimised by a Genetic Algorithm (GA) to reduce interference. Networked organisation makes use of the X2 communications link to enable the network nodes to exchange scheduling information in a way that lowers the level of interference across the whole network. Finally a more distributed and de-centralised approach is taken in which each of the network nodes optimises its own scheduling in coordination with its neighbours. An LTE network simulator was built to allow for experimental comparison between these techniques and a number of existing approaches and to serve as a test bed for future algorithm development. These approaches were found to significantly improve the throughput of the cell edge users who were most affected by intereference. In particular the networked aspect of these approaches yielded the best initial results showing clear improvement over the existing state of the art. The distributed approach shows significant promise given further development.EPSR

Vpu-induced proteasomal degradation of tetherin involves ERAD.

<p>(A) The ERAD pathway is involved in Vpu-mediated tetherin depletion. 293T cells were transfected in duplicate with 100 nM of either a non-silencing control siRNA, or of a siRNA pool targeting p97. Twenty-four hours later, these cells were transfected with Flag-tagged tetherin in the presence or absence of Vpu (with a molar ratio of 2∶1 in favor of Vpu). Duplicate cell lysates were pooled for western blot analysis (left panel). Actin served as a loading control. Note that both parts of the figure come from the same scan of the same blot. The effect of the different siRNAs on Vpu-mediated tetherin depletion was quantified by densitometry and a plot was generated from the results of two independent experiments performed in duplicate (right panel). The values obtained in the absence of Vpu were given the arbitrary value of 100%. (B) Vpu-mediated tetherin depletion does not require ubiquitination of tetherin cytosolic lysines. 293T cells were co-transfected in duplicate with or without Vpu in the presence of either HA-tagged wild type tetherin or its counterpart having both its cytosolic lysines K18 and K21 replaced with arginines (KcytoR tetherin). Duplicate extracts were pooled and analyzed by western blotting. PCNA served as a loading control. Vpu-mediated tetherin depletion was quantified by densitometry, and a plot was generated from the results of two independent experiments performed in duplicate (right panel). The values obtained in the absence of Vpu were given the arbitrary value of 100%. Sizes of molecular weight markers are shown in kilodaltons.</p

A β-TrCP dominant negative prevents Vpu-mediated tetherin degradation.

<p>293T were transfected with HA-tagged tetherin with or without Vpu, in the presence of either a Flag-tagged dominant negative β-TrCP-ΔF or a Flag-tagged wild type β-TrCP1. The molar ratio of β-TrCP to Vpu to tetherin constructs was 2.5∶2∶1. A GFP plasmid was included to exclude variations in transfection efficiency. The resulting duplicate lysates were pooled for gel loading, and proteins levels were determined by western blotting. Actin served as a loading control. The depicted figure is representative of four independent experiments performed in duplicate. Sizes of molecular weight markers are shown in kilodaltons.</p

Vpu and β-TrCP co-immunoprecipitate with tetherin.

<p>293T cells were transfected with the indicated Vpu and β-TrCP-ΔF constructs, in the presence or absence of HA-tetherin (with a molar ratio of 2∶1 in the favor of Vpu). Equal amounts of lysates were subjected to immunoprecipitation with an anti-HA resin and analyzed by western blotting. PCNA served as a loading control. The first left lane was cut and pasted from another position from the same scan of the same blot. The figure is representative of two independent experiments. Sizes of molecular weight markers are shown in kilodaltons.</p

β-TrCP interaction motif is required for Vpu-induced tetherin level reduction and for its ability to rescue virion release.

<p>(A) β-TrCP interaction motif is required for Vpu-induced tetherin depletion. HIV-1 deleted for the Vpu gene was produced from 293T cells in the presence or absence of Flag-tagged tetherin. Where indicated, Vpu wild type, or mutated in one (Vpu S52A) or both serines (Vpu 2S/A) known to be required for β-TrCP interaction, was added <i>in trans</i>. The effect of these different Vpu constructs on tetherin protein level was monitored by western blotting. The extracts of duplicate samples were pooled for gel loading. Equal loading was controlled by monitoring PCNA, and the viral p55 Gag protein was examined to exclude variations of transfection efficiency. The depicted gel is representative of three independent experiments. Sizes of molecular weight markers are shown in kilodaltons. (B) β-TrCP interaction motif is required for Vpu-induced rescue of virion release. Titer of the viral output obtained during the above experiment was measured on HeLa indicator cells. The titer of the virus produced in the absence of either tetherin or Vpu was given the arbitrary score of 100%. The plot was generated from two independent experiments performed in duplicate.</p

Additional file 6: Figure S6. of Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells

Gating strategy for assessment of engraftment of HSPCs in bone marrow. A representative example for the assessment of engraftment of HSPCs in bone marrow is shown. Percentages of cell populations were determined as follows: Total HSPCs: Í34+ cells (of CD45+ cells), more primitive cells: Í38- or CD90+ cells (of CD45 + CD34+ or CD45+ cells). (TIF 5264 kb

Emergence of resistance in the mice under monotherapy with TMC278-LA.

*<p>S = susceptible (wildtype strain).</p>**<p>#192 showed suppressed HIV RNA under TMC278-LA monotherapy.</p>***<p>#191, 224 showed viral failure under the ART regimen of 3TC, TDF and TMC278-LA. #190 gave a positive signal for HIV RNA but below the limit of detection (<800 copies/ml)</p><p>#221, 245 only baseline analyses have been done, and therefore data from these mice were not integrated in the table.</p><p>¶#n.d. = not done.</p