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Breast cancer is the most common cancer in women and is largely treatable within the early stages of the disease. However, patient mortality drastically declines as the tumor begins to invade other tissues and metastasize, making aggressive phenotypes especially problematic to treat. Such treatment typically requires an aggressive and decisive multidisciplinary approach. The recent expansion of immunotherapy as a viable treatment option has greatly improved treatment outcomes, especially with aggressive breast cancer phenotypes. Thymidine kinase 1 (TK1) is a DNA salvage pathway enzyme that is highly expressed during S phase and involved in cell cycle repair. Past studies indicated that TK1 is secreted into the serum of cancer patients and that its upregulation is an early event in tumorigenesis, thus suggesting that TK1 upregulation may have potential importance in tumor progression. This study’s objective was to further elucidate TK1’s role in tumor progression and metastasis of breast cancer specifically. We hypothesized that TK1 overexpression in breast cancer may affect invasion. To investigate this, TK1 mRNA transcript levels were analyzed between normal and BRCA patient tissue samples. The wild-type breast cancer cell line HCC 1806 was used, as well as a TK1 knockdown (L133) which was produced using CRISPR-Cas9. Successful TK1 knockdown was verified through western blot and qPCR. Bioinformatics was also performed to analyze the relationship between our breast cancer cell lines and various cell adhesion factors. The cell lines HCC 1806 and L133 were then tested with an invasive scratch assay. Additional western blots were run to further investigate the potential relationship TK1 may have with other cell cycle checkpoint proteins. Results showed that TK1 mRNA transcript levels are higher in BRCA tissues compared to normal controls. Western blot and qPCR indicated that TK1 was successfully knocked down in L133 cells. Bioinformatic differential gene analysis revealed several correlations with cell adhesion factors, with contrasting correlations when compared between the HCC 1806 and L133 cell lines. The invasive scratch assay results indicated that the TK1 knockdown L133 cells were less invasive than HCC 1806 cells. In conclusion, results verified that TK1 is highly expressed in breast cancer and that it may help tumor invasion by influencing cell adhesion factors. Further investigation to understand TK1’s potential interactions with important cell adhesion factors, such as FHL1 or GAS6, may help elucidate other therapeutic targets for preventing disease progression. Citation Format: Eliza E. Bitter, Rachel M. Morris, Toni Mortimer, Kai Barlow, Abigail Schekall, Michelle H. Townsend, Jonathan Skidmore, Brett E. Pickett, Kim L. O'Neill. The potential effects of thymidine kinase 1 on breast cancer invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1322.

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition, etc.; and (c) developing technologies that will be required in the future for a fusion reactor. A brief overview of these activities, presented here, along with new calculations relates the concept of auxiliary heating of inertial fusion targets, and provides possible future directions of research and development for the updated European Roadmap that is due at the end of 2020. This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.

Fast ignition inertial confinement fusion requires the production of a low-density channel in plasma with density scale-lengths of several hundred microns. The channel assists in the propagation of an ultra-intense laser pulse used to generate fast electrons which form a hot spot on the side of pre-compressed fusion fuel. We present a systematic characterization of an expanding laser-produced plasma using optical interferometry, benchmarked against three-dimensional hydrodynamic simulations. Magnetic fields associated with channel formation are probed using proton radiography, and compared to magnetic field structures generated in full-scale particle-in-cell simulations. We present observations of long-lived, straight channels produced by the Habara–Kodama–Tanaka whole-beam self-focusing mechanism, overcoming a critical barrier on the path to realizing fast ignition. This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.

The role of radiative cooling during the evolution of a bow shock was studied in laboratory-astrophysics experiments that are scalable to bow shocks present in jets from young stellar objects. The laboratory bow shock is formed during the collision of two counter-streaming, supersonic plasma jets produced by an opposing pair of radial foil Z-pinches driven by the current pulse from the MAGPIE pulsed-power generator. The jets have different flow velocities in the laboratory frame and the experiments are driven over many times the characteristic cooling time-scale. The initially smooth bow shock rapidly develops small-scale non-uniformities over temporal and spatial scales that are consistent with a thermal instability triggered by strong radiative cooling in the shock. The growth of these perturbations eventually results in a global fragmentation of the bow shock front. The formation of a thermal instability is supported by analysis of the plasma cooling function calculated for the experimental conditions with the radiative packages ABAKO/RAPCAL., 9 pages, 5 figures, Accepted for publication in The Astrophysical Journal on 5th November 2015

A streaked pyrometer has been designed to measure the temperature of ≈100 μm diameter heated targets in the warm dense matter region. The diagnostic has picosecond time resolution. Spatial resolution is limited by the streak camera to 4 μm in one dimension; the imaging system has superior resolution of 1 μm. High light collection efficiency means that the diagnostic can transmit a measurable quantity of thermal emission at temperatures as low as 1 eV to the detector. This is achieved through the use of an f/1.4 objective, and a minimum number of reflecting and refracting surfaces to relay the image over 8 m with no vignetting over a 0.4 mm field of view with 12.5× magnification. All the system optics are highly corrected, to allow imaging with minimal aberrations over a broad spectral range. The detector is a highly sensitive Axis Photonique streak camera with a P820PSU streak tube. For the first time, two of these cameras have been absolutely calibrated at 1 ns and 2 ns sweep speeds under full operational conditions and over 8 spectral bands between 425 nm and 650 nm using a high-stability picosecond white light source. Over this range the cameras had a response which varied between 47 ± 8 and 14 ± 4 photons/count. The calibration of the optical imaging system makes absolute temperature measurements possible. Color temperature measurements are also possible due to the wide spectral range over which the system is calibrated; two different spectral bands can be imaged onto different parts of the photocathode of the same streak camera.