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1. An Efficient Way to Find Optimal Crossover Designs Using CVX for Precision Medicine: Optimal Crossover Designs via CVX

   https://doi.org/10.52933/jdssv.v4i3.83  

   Li, Yin; Wong, Weng Kee; Zhou, Hua; Chough_Carriere, Keumhee (June 2024, Journal of Data Science, Statistics, and Visualisation)

   Crossover designs play an increasingly important role in precision medicine. We show the search of an optimal crossover design can be formulated as a convex optimization problem and convex optimization tools, such as CVX, can be directly used to search for an optimal crossover design.  We first demonstrate how to transform crossover design problems into convex optimization problems and show CVX can effortlessly find optimal crossover designs that coincide with a few theoretical crossover optimal designs in the literature. The proposed approach is especially useful when it becomes problematic to construct optimal designs analytically for complicated models. We then apply CVX to find crossover designs for models with auto-correlated error structures or when the information matrices may be singular and analytical answers are unavailable. We also construct N-of-1 trials frequently used in precision medicine to estimate treatment effects on the individuals or to estimate average treatment effects, including finding dual-objective optimal crossover designs. 

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2. Patterns of crossover distribution in Drosophila mauritiana necessitate a re-thinking of the centromere effect on crossing over

   https://doi.org/10.1093/genetics/iyaf039  

   Hawley, R Scott; Price, Andrew; Li, Hua; Jagannathan, Madhav; Staber, Cynthia; Hughes, Stacie E; Williams, Stefanie; Perera, Anoja; Egidy, Rhonda R; Lawlor, Amanda; et al (March 2025, GENETICS)

   MacQueen, A (Ed.)

   Abstract We present an SNP-based crossover map for Drosophila mauritiana. Using females derived by crossing 2 different strains of D. mauritiana, we analyzed crossing over on all 5 major chromosome arms. Analysis of 105 male progeny allowed us to identify 327 crossover chromatids bearing single, double, or triple crossover events, representing 398 crossover events. We mapped the crossovers along these 5 chromosome arms using a genome sequence map that includes the euchromatin-heterochromatin boundary. Confirming previous studies, we show that the overall crossover frequency in D. mauritiana is higher than is seen in Drosophila melanogaster. Much of the increase in exchange frequency in D. mauritiana is due to a greatly diminished centromere effect. Using larval neuroblast metaphases from D. mauritiana—D. melanogaster hybrids we show that the lengths of the pericentromeric heterochromatin do not differ substantially between the species, and thus cannot explain the observed differences in crossover distribution. Using a new and robust maximum likelihood estimation tool for obtaining Weinstein tetrad distributions, we observed an increase in bivalents with 2 or more crossovers when compared with D. melanogaster. This increase in crossing over along the arms of D. mauritiana likely reflects an expansion of the crossover-available euchromatin caused by a difference in the strength of the centromere effect. The crossover pattern in D. mauritiana conflicts with the commonly accepted view of centromeres as strong polar suppressors of exchange (whose intensity is buffered by sequence nonspecific heterochromatin) and demonstrates the importance of expanding such studies into other species of Drosophila. 

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3. Seismological expression of the iron spin crossover in ferropericlase in the Earth’s lower mantle

   https://doi.org/10.1038/s41467-021-26115-z  

   Shephard, Grace E.; Houser, Christine; Hernlund, John W.; Valencia-Cardona, Juan J.; Trønnes, Reidar G.; Wentzcovitch, Renata M. (October 2021, Nature Communications)

   Abstract The two most abundant minerals in the Earth’s lower mantle are bridgmanite and ferropericlase. The bulk modulus of ferropericlase (Fp) softens as iron d-electrons transition from a high-spin to low-spin state, affecting the seismic compressional velocity but not the shear velocity. Here, we identify a seismological expression of the iron spin crossover in fast regions associated with cold Fp-rich subducted oceanic lithosphere: the relative abundance of fast velocities in P- and S-wave tomography models diverges in the ~1,400-2,000 km depth range. This is consistent with a reduced temperature sensitivity of P-waves throughout the iron spin crossover. A similar signal is also found in seismically slow regions below ~1,800 km, consistent with broadening and deepening of the crossover at higher temperatures. The corresponding inflection in P-wave velocity is not yet observed in 1-D seismic profiles, suggesting that the lower mantle is composed of non-uniformly distributed thermochemical heterogeneities which dampen the global signature of the Fp spin crossover. 

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4. DNA T-shaped crossover tiles for 2D tessellation and nanoring reconfiguration

   https://doi.org/10.1038/s41467-023-43558-8  

   Yang, Qi; Chang, Xu; Lee, Jung Yeon; Saji, Minu; Zhang, Fei (November 2023, Nature Communications)

   Abstract DNA tiles serve as the fundamental building blocks for DNA self-assembled nanostructures such as DNA arrays, origami, and designer crystals. Introducing additional binding arms to DNA crossover tiles holds the promise of unlocking diverse nano-assemblies and potential applications. Here, we present one-, two-, and three-layer T-shaped crossover tiles, by integrating T junction with antiparallel crossover tiles. These tiles carry over the orthogonal binding directions from T junction and retain the rigidity from antiparallel crossover tiles, enabling the assembly of various 2D tessellations. To demonstrate the versatility of the design rules, we create 2-state reconfigurable nanorings from both single-stranded tiles and single-unit assemblies. Moreover, four sets of 4-state reconfiguration systems are constructed, showing effective transformations between ladders and/or rings with pore sizes spanning ~20 nm to ~168 nm. These DNA tiles enrich the design tools in nucleic acid nanotechnology, offering exciting opportunities for the creation of artificial dynamic DNA nanopores. 

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5. Conformational dynamics modulating electron transfer

   https://doi.org/10.1063/5.0102707  

   Matyushov, Dmitry V. (September 2022, The Journal of Chemical Physics)

   Diffusional dynamics of the donor–acceptor distance are responsible for the appearance of a new time scale of diffusion over the distance of electronic tunneling in electron-transfer reactions. The distance dynamics compete with the medium polarization dynamics in the dynamics-controlled electron-transfer kinetics. The pre-exponential factor of the electron-transfer rate constant switches, at the crossover distance, between a distance-independent, dynamics-controlled plateau and exponential distance decay. The crossover between two regimes is controlled by an effective relaxation time slowed down by a factor exponentially depending on the variance of the donor–acceptor displacement. Flexible donor–acceptor complexes must show a greater tendency for dynamics-controlled electron transfer. Energy chains based on electron transport are best designed by placing the redox cofactors near the crossover distance. 

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