Aperiodic crystals in biology

Biological systems display a broad palette of hierarchically ordered designs spanning over many orders of magnitude in size. Remarkably enough, periodic order, which profusely shows up in nonliving ordered compounds, plays a quite subsidiary role in most biological structures, which can be appropriately described in terms of the more general aperiodic crystal notion instead. In this Topical Review I shall illustrate this issue by considering several representative examples, including botanical phyllotaxis, the geometry of cell patterns in tissues, the morphology of sea urchins, or the symmetry principles underlying virus architectures. In doing so, we will realize that albeit the currently adopted quasicrystal notion is not general enough to properly account for the rich structural features one usually finds in biological arrangements of matter, several mathematical tools and fundamental notions belonging to the aperiodic crystals science toolkit can provide a useful modeling framework to this end.

Enhancing Handover for 5G Mobile Networks using Jump Markov Linear System and Deep Reinforcement Learning

The fifth Generation (5G) mobile networks use millimeter Waves (mmWaves) to offer giga bit data rates. However, unlike microwaves, mmWave links are prone to user and topographic dynamics. They easily get blocked and end up forming irregular cell patterns for 5G. This in turn cause too early, too late, or wrong handoffs (HOs). To mitigate HO challenges, sustain connectivity and avert unnecessary HO, we propose a HO scheme based on Jump Markov Linear System (JMLS) and Deep Reinforcement Learning (DRL). JMLS is widely known to account for abrupt changes in system dynamics. DRL likewise emerges as an artificial intelligence technique for learning highly dimensional and time-varying behaviors. We combine the two techniques to account for time-varying, abrupt, and irregular changes in mmWave link behaviour by predicting likely deterioration patterns of target links. The prediction is optimized by meta training techniques that also reduces training sample size. Thus, the JMLS-DRL platform formulates intelligent and versatile HO policies for 5G. Results show our proposed prediction scheme about target link behavior post HO to be highly reliable. The scheme also averts unnecessary HOs thus ably supports longer dew time.

Radiative-dynamical Simulation of Jupiter’s Stratosphere and Upper Troposphere

We present a two-dimensional radiative-dynamical model of the combined stratosphere and upper troposphere of Jupiter to understand its temperature distribution and meridional circulation pattern. Our study highlights the importance of radiative and mechanical forcing for driving the middle atmospheric circulation on Jupiter. Our model adopts a state-of-the-art radiative transfer scheme with recent observations of Jovian gas abundances and haze distribution. Assuming local radiative equilibrium, latitudinal variation of hydrocarbon abundances is not able to explain the observed latitudinal temperature variations in the mid-latitudes. With mechanical forcing parameterized as a frictional drag on zonal wind, our model produces ∼2 K latitudinal temperature variations observed in low to mid-latitudes in the troposphere and lower stratosphere, but cannot reproduce the observed 5 K temperature variations in the middle stratosphere. In the high latitudes, temperature and meridional circulation depend strongly on polar haze radiation. The simulated residual mean circulation shows either two broad equator-to-pole cells or multi-cell patterns, depending on the frictional drag timescale and polar haze properties. A more realistic wave parameterization and a better observational characterization of haze distribution and optical properties are needed to better understand latitudinal temperature distributions and circulation patterns in the middle atmosphere of Jupiter.

Material Behavior of 2D Steel Lattices with Different Unit-Cell Patterns

Over the past years, two-dimensional lattices have attracted the attention of several researchers because they are lightweight compared with their full-solid counterparts, which can be used in various engineering applications. Nevertheless, since lattices are manufactured by reducing the base material, their stiffnesses then become lower. This study presents the weight efficiency of the lattices defined by relations between the elastic modulus and the weight density of the lattices. In this study, the mechanical behavior of 2D lattices is described by the in-plane elastic modulus. Experimental studies on the elastic modulus of the 2D lattices made of steel are performed. Three lattices having different unit cells, including square, body-centered, and triangular unit cells, are considered. The elastic modulus of each lattice is investigated by tensile testing. All specimens of the lattices are made of steel and manufactured by waterjet cutting. The experimental results of the elastic modulus of the lattices with the considered unit-cell patterns are validated with those obtained from finite element simulations. The results obtained in this study are also compared with the closed-form solutions founded in the literature. Moreover, the unit-cell pattern yielding the best elastic modulus for the lattice is discussed through weight efficiency.

Digitally Driven Aerosol Jet Printing to Enable Customisable Neuronal Guidance

Digitally driven manufacturing technologies such as aerosol jet printing (AJP) can make a significant contribution to enabling new capabilities in the field of tissue engineering disease modeling and drug screening. AJP is an emerging non-contact and mask-less printing process which has distinct advantages over other patterning technologies as it offers versatile, high-resolution, direct-write deposition of a variety of materials on planar and non-planar surfaces. This research demonstrates the ability of AJP to print digitally controlled patterns that influence neuronal guidance. These consist of patterned poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) tracks on both glass and poly(potassium 3-sulfopropyl methacrylate) (PKSPMA) coated glass surfaces, promoting selective adhesion of SH-SY5Y neuroblastoma cells. The cell attractive patterns had a maximum height ≥0.2 μm, width and half height ≥15 μm, Ra = 3.5 nm, and RMS = 4.1. The developed biocompatible PEDOT:PSS ink was shown to promote adhesion, growth and differentiation of SH-SY5Y neuronal cells. SH-SY5Y cells cultured directly onto these features exhibited increased nuclei and neuronal alignment on both substrates. In addition, the cell adhesion to the substrate was selective when cultured onto the PKSPMA surfaces resulting in a highly organized neural pattern. This demonstrated the ability to rapidly and flexibly realize intricate and accurate cell patterns by a computer controlled process.

Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma

Background: Lung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy. Methods: In order to study the relationship between genomic, epigenomic and T cell repertoire heterogeneity in a rare autopsy case from a young female never-smoker with late-stage lung adenocarcinoma (LUAD), we did whole-exome sequencing (WES), DNA methylation and T-cell receptor (TCR) sequencing to characterize the immunogenomic landscape of one primary and 19 synchronous metastatic tumors. Results: We observed heterogeneous mutation, methylation, and T cell patterns across distinct metastases including a set of prevalent T cell clonotypes which were completely excluded from left-side thoracic tumors. Though a limited number of predicted neoantigens were shared, these were associated with homology of the T cell repertoire across metastases. Lastly, ratio of methylated neoantigen coding mutations was negatively associated with T-cell density, richness and clonality, suggesting neoantigen methylation may partially drive immunosuppression. Conclusions: Our study demonstrates heterogeneous genomic and T cell profiles across synchronous metastases and how restriction of unique T cell clonotypes within an individual may differentially shape the genomic and epigenomic landscapes of synchronous lung metastases.

International Consensus on Antinuclear Antibody em Portugal

Introduction: Screening for autoantibodies in HEp-2 cells by indirect immunofluorescence is currently accepted as the gold-standard test for the diagnosis of systemic autoimmune diseases. The main objective of the International Consensus on ANA Patterns is to achieve a consensus on the nomenclature and description of antinuclear antibody morphological patterns. This work aims to build on the International Consensus on ANA Patterns project to establish a nomenclature consensus in Portugal, thus contributing to harmonization in autoimmune diagnosis and promoting diagnostic quality in autoimmune systemic rheumatic diseases.Material and Methods: Participating laboratories identified all the nuclear and cytoplasmic pattern designations in the International Consensus on ANA Patterns (including the anti-cell pattern code), and matched them with the corresponding Portuguese nomenclature in use. The results were aggregated and used as a foundation for nomenclature harmonization work. Consensus meetings followed an iterative process, until a final consensual proposal was drafted.Results: Prior agreement between laboratories was over 75% for 23 of the total 29 anti-cell patterns. The degree to which each laboratory is aligned with the International Consensus on ANA Patterns international reference ranges from 22.1% to 100%. It was possible to write a consensual version of the International Consensus on ANA Patterns nomenclature for Portugal.Discussion: There was a good consensus basis for the nomenclature in the International Consensus on ANA Patterns, despite relevant differences with some translations. The study highlights the need for collaboration among laboratories towards an unambiguous description of laboratory results.Conclusion: This study shows that there is good potential for collaboration between laboratories in order to produce the consensus needed to improve diagnosis and patient follow-up.

OP11 Longitudinal profiling of mucosal immune cell composition using multiplex immunohistochemistry identifies drug- and response-specific patterns in Ulcerative Colitis

Background Interventions targeting key inflammatory mechanisms have expanded the therapeutic repertoire for ulcerative colitis (UC). However, exact molecular mechanisms associated with clinical response remain elusive. We conducted a multiplex-immunohistochemistry (IHC) study to monitor immune cell composition in biopsies from UC patients under 2 approved therapies targeting TNF (infliximab) and integrin (vedolizumab), and a phase IIa clinical trial with the selective IL-6 transsignalling inhibitor olamkicept, to identify spatiotemporal changes of mucosal immune cell compartments in relation to each mechanism of action. Methods Sigmoid biopsies from UC patients exposed to infliximab, vedolizumab or olamkicept (26 patients in total) at baseline and week 2, 6 and 14 after therapy induction were subjected to multiplex IHC for CD3, CD15, CD20, CD68, pSTAT3, and pan-cytokeratin (OPAL/Vectra Polaris, Akoya). Quantitative and spatial immune cell patterns captured by advanced image analysis (inForm, Akoya; R package PhenoptrReports) were analysed for differences between baseline and subsequent time points using Dunnett’s multiple comparisons test (GraphPad Prism 8.4.3). Accepted significance levels: *p<0.05,**p<0.01, ***p<0.001. Results Targeted therapies resulted in overall decrease of immune cell infiltrates (range 1.15–1.22 fold; p=0.017-0.007), irrespective of drug or specified endpoint (remission at week 14) (Fig. 1). Significant drug-specific changes of spatial immune cell distributions were discernible (Fig. 2). Anti-TNF treatment was mainly associated with decrease in CD3+ T cells (p=0.005) localized in the submucosa close to epithelium or in tertiary lymphoid organs. In contrast, integrin targeting resulted in fewer CD15+ neutrophils, mainly in the submucosal compartment (p=0.046). Olamkicept treatment resulted in unique depletion of pSTAT3+ cells in patients achieving remission at week 14 (not observed in remission after infliximab or vedolizumab). To decipher drug-independent features of clinical remission we assessed distance metrics between immune and intestinal epithelial cells in remission and non-remission patients and observed increase (endpoint compared to baseline) of the average distance to the nearest CD20 or CD15 cell in the remission (p=0.0054, p=0.0004) but not in the non-remission group (n.s.). Conclusion Our study strongly suggests that multiplexed spatiotemporally resolved immune cell phenotyping may provide novel insights into the dynamic shifts of immune cell compartments in UC patients undergoing targeted therapy. We propose that such highly resolved digital maps of immune cells could lead to novel tools for therapeutic stratification of IBD patients.