HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis

The tumor suppressor BRCA2 is essential for homologous recombination (HR), replication fork stability, and DNA interstrand crosslink repair in vertebrates. We identify HSF2BP, a protein previously described as testis specific and not characterized functionally, as an interactor of BRCA2 in mouse embryonic stem cells, where the 2 proteins form a constitutive complex. HSF2BP is transcribed in all cultured human cancer cell lines tested and elevated in some tumor samples. Inactivation of the mouse Hsf2bp gene results in male infertility due to a severe HR defect during spermatogenesis. The BRCA2-HSF2BP interaction is highly evolutionarily conserved and maps to armadillo repeats in HSF2BP and a 68-amino acid region between the BRC repeats and the DNA binding domain of human BRCA2 (Gly2270-Thr2337) encoded by exons 12 and 13. This region of BRCA2 does not harbor known cancer-associated missense mutations and may be involved in the reproductive rather than the tumor-suppressing function of BRCA2. BRCA2 is a key homologous recombination mediator in vertebrates. Brandsma et al. show that it directly interacts with a testis-expressed protein, HSF2BP, and that male mice deficient for HSF2BP are infertile due to a meiotic recombination defect. They also find that HSF2BP contributes to DNA repair in mouse embryonic stem cells

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

Estimating bounds on expected plateau size in MAXSAT problems

Also published as book chapter: Engineering Stochastic Local Search Algorithms. Designing, Implementing and Analyzing Effective Heuristics, 2009 / Thomas Stützle, Mauro Birattari, Holger H. Hoos (eds.), pp.31-45Stochastic local search algorithms can now successfully solve MAXSAT problems with thousands of variables or more. A key to this success is how effectively the search can navigate and escape plateau regions. Furthermore, the solubility of a problem depends on the size and exit density of plateaus, especially those closest to the optimal solution. In this paper we model the plateau phenomenon as a percolation process on hypercube graphs. We develop two models for estimating bounds on the size of plateaus and prove that one is a lower bound and the other an upper bound on the expected size of plateaus at a given level. The models’ accuracy is demonstrated on controlled random hypercube landscapes. We apply the models to MAXSAT through analogy to hypercube graphs and by introducing an approach to estimating, through sampling, a key parameter of the models. Using this approach, we assess the accuracy of our bound estimations on uniform random and structured benchmarks. Surprisingly, we find similar trends in accuracy across random and structured problem instances. Less surprisingly, we find a high accuracy on smaller plateaus with systematic divergence as plateaus increase in size.Andrew M. Sutton, Adele E. Howe, and L. Darrell Whitle