Linking and link complexity of geometrically constrained pairs of rings

We investigate and compare the effects of two different constraints on the geometrical properties and linking of pairs of polygons on the simple cubic lattice, using Monte Carlo methods. One constraint is to insist that the centres of mass of the two polygons are less than distance $d$ apart, and the other is to insist that the radius of gyration of the \emph{pair} of polygons is less than $R$. The second constraint results in links that are quite spherically symmetric, especially at small values of $R$, while the first constraint gives much less spherically symmetric pairs, prolate at large $d$ and becoming more oblate at smaller $d$. These effects have an influence on the observed values of the linking probability and link spectrum.

An Evaluation of First-Come, First-Served Scheduling in a Geometrically-Constrained Wet Bulk Terminal

In 2022, a new sea lock at IJmuiden is expected to open, permitting an increase in marine traffic of larger ships from the sea to the port. In the interest of facilitating operations, we evaluate the impact of the current first-come, first-served (FCFS) admittance policy in the context of berth allocation for a wet bulk terminal in the port. Four model types are constructed: optimal FCFS; no FCFS with fixed arrival times; 48-h arrival time relaxation; and complete arrival time relaxation. Comparison of the model types is done by means of a rolling time window: of each day within the time frame, a schedule was created for the following 2 weeks, after which the objective value was calculated. When comparing the average of all objective values, it was found that the optimal FCFS model already shows an improvement compared to the historical situation. Between the FCFS and the no FCFS model, there are no considerable differences, because the vessels are constrained to be scheduled on/after their arrival time at the port. When relaxation is allowed, a considerable efficiency gain is possible, especially if larger ships arrive at the port.

A tumor-specific mechanism of Treg enrichment mediated by the integrin αvβ8

Regulatory T cells (Tregs) that promote tumor immune evasion are enriched in certain tumors and correlate with poor prognosis. However, mechanisms for Treg enrichment remain incompletely understood. We described a mechanism for Treg enrichment in mouse and human tumors mediated by the αvβ8 integrin. Tumor cell αvβ8 bound to latent transforming growth factor–β (L–TGF-β) presented on the surface of T cells, resulting in TGF-β activation and immunosuppressive Treg differentiation in vitro. In vivo, tumor cell αvβ8 expression correlated with Treg enrichment, immunosuppressive Treg gene expression, and increased tumor growth, which was reduced in mice by αvβ8 inhibition or Treg depletion. Structural modeling and cell-based studies suggested a highly geometrically constrained complex forming between αvβ8-expressing tumor cells and L–TGF-β–expressing T cells, facilitating TGF-β activation, independent of release and diffusion, and providing limited access to TGF-β inhibitors. These findings suggest a highly localized tumor-specific mechanism for Treg enrichment.

Synthesis of Chromeno[3,4-b]piperazines by an Enol-Ugi/Reduction/Cyclization Sequence

Keto piperazines and aminocoumarins are privileged building blocks for the construction of geometrically constrained peptides and therefore valuable structures in drug discovery. Combining these two heterocycles provides unique rigid polycyclic peptidomimetics with drug-like properties including many points of diversity that could be modulated to interact with different biological receptors. This work describes an efficient multicomponent approach to condensed chromenopiperazines based on the novel enol-Ugi reaction. Importantly, this strategy involves the first reported post-condensation transformation of an enol-Ugi adduct.

Those who can don’t want to, and those who want to can’t: eco-evolutionary constraints to decomposition explain soil carbon persistence

Reliable manipulation of soil organic matter (SOM) – a necessity for optimal land management – is constrained by our limited mechanistic understanding of SOM formation. Here we add to existing frameworks a novel mechanistic element that may underpin SOM dynamics, based on evolutionary-ecological rather than chemical or physical limitations to decomposition. We argue that decomposition of some substrates may be ecologically constrained in mycelial fungi, evolutionarily constrained in co-operating bacteria, and geometrically constrained in unicellular microbes. We describe and test a mathematical model based on our framework, providing a proof-of-concept that substrate can plausibly be spared decomposition and accumulate even when it is physically and chemically accessible. Our framework can explain a variety of SOM dynamics, including priming and the suppression of decomposition by nitrogen addition, as well as the typical composition of SOM. An augmented mechanistic framework for understanding SOM dynamics can help guide targeted empirical study, which in turn can contribute to more optimised land management.