Slow movement of a random walk on the range of a random walk in the presence of an external field

In this article, a localisation result is proved for the biased random walk on the range of a simple random walk in high dimensions (d \geq 5). This demonstrates that, unlike in the supercritical percolation setting, a slowdown effect occurs as soon a non-trivial bias is introduced. The proof applies a decomposition of the underlying simple random walk path at its cut-times to relate the associated biased random walk to a one-dimensional random walk in a random environment in Sinai's regime

Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense matrices

Background The behaviour of tumour cells depends on factors such as genetics and the tumour microenvironment. The latter plays a crucial role in normal mammary gland development and also in breast cancer initiation and progression. Breast cancer tissues tend to be highly desmoplastic and dense matrix as a pre-existing condition poses one of the highest risk factors for cancer development. However, matrix influence on tumour cell gene expression and behaviour such as cell migration is not fully elucidated. Results We generated high-density (HD) matrices that mimicked tumour collagen content of 20 mg/cm3 that were ~14-fold stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cell imaging showed breast cancer cells utilizing cytoplasmic streaming and cell body contractility for migration within HD matrix. Cell migration was blocked in the presence of both the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugs individually. This suggests roles for ROCK1 and MMP in cell migration are complicated by compensatory mechanisms. ROCK1 expression and protein activity, were significantly upregulated in HD matrix but these were blocked by treatment with a histone deacetylase (HDAC) inhibitor, MS-275. In HD matrix, the inhibition of ROCK1 by MS-275 was indirect and relied upon protein synthesis and Notch1. Inhibition of Notch1 using pooled siRNA or DAPT abrogated the inhibition of ROCK1 by MS-275. Conclusion Increased matrix density elevates ROCK1 activity, which aids in cell migration via cell contractility. The upregulation of ROCK1 is epigenetically regulated in an indirect manner involving the repression of Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an upregulation of Notch1 levels leading to blockade of ROCK1 expression

“F*ck it! Let’s get to drinking – poison our livers!”: a thematic analysis of alcohol content in contemporary YouTube music videos

Purpose: To describe the portrayal of alcohol content in popular YouTube music videos. Methods: We used inductive thematic analysis to explore the lyrics and visual imagery in 49 UK Top 40 songs and music videos previously found to contain alcohol content, and watched by many British adolescents aged between 11-18 years, and to examine if branded content contravened alcohol industry advertising codes of practice. Results: The analysis generated three themes. First, alcohol content was associated with sexualised imagery or lyrics and the objectification of women. Second, alcohol was associated with image, lifestyle and sociability. Finally, some videos showed alcohol overtly encouraging excessive drinking and drunkenness, including those containing branding, with no negative consequences to the drinker. Conclusion: Our results suggest that YouTube music videos promote positive associations with alcohol use. Further, several alcohol companies adopt marketing strategies in the video medium that are entirely inconsistent with their own or others agreed advertising codes of practice. We conclude that, as a harm reduction measure, policies should change to prevent adolescent exposure to the positive promotion of alcohol and alcohol branding in music videos

Time separation as a hidden variable to the Copenhagen school of quantum mechanics

The Bohr radius is a space-like separation between the proton and electron in the hydrogen atom. According to the Copenhagen school of quantum mechanics, the proton is sitting in the absolute Lorentz frame. If this hydrogen atom is observed from a different Lorentz frame, there is a time-like separation linearly mixed with the Bohr radius. Indeed, the time-separation is one of the essential variables in high-energy hadronic physics where the hadron is a bound state of the quarks, while thoroughly hidden in the present form of quantum mechanics. It will be concluded that this variable is hidden in Feynman's rest of the universe. It is noted first that Feynman's Lorentz-invariant differential equation for the bound-state quarks has a set of solutions which describe all essential features of hadronic physics. These solutions explicitly depend on the time separation between the quarks. This set also forms the mathematical basis for two-mode squeezed states in quantum optics, where both photons are observable, but one of them can be treated a variable hidden in the rest of the universe. The physics of this two-mode state can then be translated into the time-separation variable in the quark model. As in the case of the un-observed photon, the hidden time-separation variable manifests itself as an increase in entropy and uncertainty.Comment: LaTex 10 pages with 5 figure. Invited paper presented at the Conference on Advances in Quantum Theory (Vaxjo, Sweden, June 2010), to be published in one of the AIP Conference Proceedings serie

Quantum Creation of a Universe with Ω≠1\Omega \not = 1: Singular and Non-Singular Instantons

We propose two new classes of instantons which describe the tunneling and/or quantum creation of closed and open universes. The instantons leading to an open universe can be considered as generalizations of the Coleman-De-Luccia solution. They are non-singular, unlike the instantons recently studied by Hawking and Turok, whose prescription has the problem that the singularity is located on the hypersurface connecting to the Lorentzian region, which makes it difficult to remove. We argue that such singularities are harmless if they are located purely in the Euclidean region. We thus obtain new singular instantons leading to a closed universe; unlike the usual regular instantons used for this purpose, they do not require complex initial conditions. The singularity gives a boundary contribution to the action which is small for the instantons leading to sufficient inflation, but changes the sign of the action for small $\phi$ corresponding to short periods of inflation.Comment: 9 pages, revtex, 6 figures, few misprints improve

Concepts and Applications of Aerodynamic Attitude and Orbital Control for Spacecraft in Very Low Earth Orbit

Spacecraft operations below 450km, namely Very Low Earth Orbit (VLEO), can offer significant advantages over traditional low Earth orbits, for example enhanced ground resolution for Earth observation, improved communications latency and link budget, or improved signal-to-noise ratio. Recently, these lower orbits have begun to be exploited as a result of technology development, particularly component miniaturisation and cost-reduction, and concerns over the increasing debris population in commercially exploited orbits. However, the high cost of orbital launch and challenges associated with atmospheric drag, causing orbital decay and eventually re-entry are still a key barrier to their wider use for large commercial and civil spacecraft. Efforts to address the impact of aerodynamic drag are being sought through the development of novel drag-compensation propulsion systems and identification of materials which can reduce aerodynamic drag by specularly reflecting the incident gas. However, the presence of aerodynamic forces can also be utilised to augment or improve spacecraft operations at these very low altitudes by providing the capability to perform coarse pointing control and trim or internal momentum management for example. This paper presents concepts for the advantageous use of spacecraft aerodynamics developed as part of DISCOVERER, a Horizon 2020 funded project with the aim to revolutionise Earth observation satellite operations in VLEO. The combination of novel spacecraft geometries and use of aerodynamic control methods are explored, demonstrating the potential for a new generation of Earth observation satellites operating at lower altitudes

Discoverer - Making commercial satellite operations in very low earth orbit a reality

DISCOVERER is a €5.7M European Commission funded Horizon 2020 project developing technologies to enable commercially-viable sustained-operation of satellites in very low Earth orbits. Why operate closer to the Earth? For communications applications latency is significantly reduced and link budgets improved, and for remote sensing improved link budgets allow higher resolution or smaller instruments, all providing cost benefits. In addition, all applications benefit from increased launch mass to lower altitudes, whilst end-of-life removal is ensured due to the increased atmospheric drag. However, this drag must also be minimised and compensated for. One of the key technologies being developed by DISCOVERER are materials that encourage specular reflection of the residual atmosphere at these altitudes. Combined with appropriate geometric designs these can significantly reduce drag, provide usable lift for aerodynamic attitude and orbit control, and improve the collection efficiency of aerodynamic intakes for atmosphere breathing electric propulsion systems, all of which are being developed as part of DISCOVERER. The paper provides highlights from the developments to date, and the potential for a new class of aerodynamic commercial satellites operating at altitudes below the International Space Station

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure