Location Of Substructures Research Articles

Abstract LB076: A novel spatial trajectory inference method for detecting regional breast cancer progression from spatial transcriptomics data

Abstract Spatial transcriptomics is a rapidly emerging field that allows for the study of gene expression within a tissue sample. This technology has the potential to provide valuable insights into the molecular mechanisms underlying cancer progression and could be particularly useful in identifying specific regional cancer progression. By studying the regional spatial trajectory of cancer progression, we can develop more targeted therapies and better predict the likelihood of metastasis. Additionally, analyzing gene expression patterns in specific regions of the tissue can reveal the molecular mechanisms driving cancer growth in those areas, potentially uncovering new therapeutic targets. In this study, we created a spatial trajectory analysis method, named as stLearn - PSeudo-Time-Space (PSTS) algorithm, to investigate specific regional cancer progression. Spatial trajectory analysis is a statistical method that allows for the identification of patterns of transitional gene expression over time and space within a tissue sample. In detail, this method incorporates spatial features, such as tissue sub-structure locations and gene expression changes, to model the trajectory from a single snapshot of transcriptomics data. Also, we evaluated the effectiveness of PSTS by utilizing the cancer progression model in human breast cancer samples. Using this approach, we were able to identify specific regions within the breast tissue that displayed distinct progression branching trajectories patterns of transitional gene expression associated with ductal carcinoma in situ and invasive ductal carcinoma. These regions were found to be characterized by a high level of cellular diversity and were associated with aggressive forms of breast cancer. The results of this study suggest that spatial transcriptomics and spatial trajectory analysis could be a powerful tool for identifying specific regional cancer progression and may help to inform the biomarkers for the development of targeted therapies for breast cancer. Overall, this study highlights the potential of spatial transcriptomics and spatial trajectory analysis to provide valuable insights into the molecular mechanisms underlying cancer progression and could have significant implications for the diagnosis and treatment of cancer. Citation Format: Duy Pham, Quan Nguyen. A novel spatial trajectory inference method for detecting regional breast cancer progression from spatial transcriptomics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB076.

Experimental Study of Transmission Tower Damage Detection Using Time Series Model

In order to solve damage detection problem of transmission tower, a damage index based on inter-storey stiffness and cepstral distance is presented. First, transmission tower model is established and the tower is divided into six sub-structures. Thus, we only need to identify the sub-structure location where the damaged rods are included. Then, autoregressive model is introduced, the cepstral distance between autoregressive models under damaged and undamaged states is given, and a damage index based on inter-storey stiffness and cepstral distance is proposed. Finally, the experiment of transmission tower model is conducted to evaluate the effectiveness of detecting the damaged layer of transmission tower. The analysis results of the experimental signals show that the damage index based on inter-storey stiffness and cepstral distance is an available method for damage detection of transmission tower, and the damage feature can be well extracted with the damage index.

Toxicity of Radiosurgery for Brainstem Metastases

Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a review of all available studies reporting SRS treatment for BSM was performed. Twenty-nine retrospective studies investigating SRS for BSM were reviewed. The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events, varied from 0 to 9.5% (mean 3.4 ± 2.9%). Overall, the median time to toxicity after SRS was 3 months, with 90% of toxicities occurring before 9 months. A total of 1243 cases had toxicity and location data available. Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811). Current data suggest that brainstem substructure location does not predict for toxicity and lesion volume within this cohort with median tumor volumes 0.04-2.8 cc does not predict for toxicity.

Influence of Ageing on Tendon Homeostasis.

Tendon functional competence and structural integrity rely on homeostasis of tendon cell metabolism and extracellular matrix macromolecules. The clear link between tendinopathies and increasing age suggests a slow change to tendon homeostasis, which increases susceptibility to damage. Despite this well evidenced association between increasing age and tendon damage, changes to tendon mechanical properties with ageing are not clear with different studies reporting conflicting results. More recent research suggests that age-related changes occur at specific sub-structure locations and may be overlooked by measuring properties of the whole tendon. In this chapter we review changes to tendon mechanical properties, structure and composition. Mechanisms speculated to contribute to tendon change with age such as cellular senescence, ageing stem cell population, reactive oxygen species and formation of advanced glycation end-product crosslinks are discussed. Understanding age-related changes to tendon homeostasis are key to understanding increased incidence of tendon injuries in the ageing population.

Comparative morphology and phylogenetic significance of Gregory’s diverticulum in sand dollars (Echinoidea: Clypeasteroida)

Several derived sand dollar (Echinoidea: Clypeasteroida) families are characterized by the presence of Gregory’s diverticulum, an accessory organ of the digestive tract. This soft tissue structure is composed of a central tubular cecum that gives off multiple lobes into the periphery of the test. Most notable are the organ’s capacity to selectively store sand grains that the animal has taken up from the surrounding sediment as well as the gradual reduction of Gregory’s diverticulum during ontogeny. Several aspects of the biology of this structure have remained unexplored, including the organ’s precise morphology and structural diversity. In order to provide a concise basis for future histological, physiological, and functional analyses, a comprehensive comparative morphological and phylogenetic study across numerous taxa was undertaken. Taxon sampling comprised over 100 clypeasteroid species, including various fossil taxa. This extensive dataset permits establishing a concise terminology that incorporates all of the organ’s substructures. In addition, three-dimensional models of Gregory’s diverticulum are presented that provide an improved spatial understanding of the organ’s morphology in situ. The combined data from dissection, X-ray imaging, microcomputed tomography, and magnetic resonance imaging reveal a previously unknown variability of the structure, which also yields several phylogenetically informative morphological characters. Among those sand dollar families that possess Gregory’s diverticulum, the organ is present in two distinct shapes, which can be distinguished by the number, shape, and location of substructures. In addition, the data provide unequivocal evidence that Gregory’s diverticulum is absent in the extant taxa Rotulidae and Astriclypeidae, but also in the enigmatic Marginoproctus.

Subhaloes going Notts: the subhalo-finder comparison project

We present a detailed comparison of the substructure properties of a single Milky Way sized dark matter halo from the Aquarius suite at five different resolutions, as identified by a variety of different (sub-)halo finders for simulations of cosmic structure formation. These finders span a wide range of techniques and methodologies to extract and quantify substructures within a larger non-homogeneous background density (e.g. a host halo). This includes real-space, phase-space, velocity-space and time- space based finders, as well as finders employing a Voronoi tessellation, friends-of-friends techniques, or refined meshes as the starting point for locating substructure.A common post-processing pipeline was used to uniformly analyse the particle lists provided by each finder. We extract quantitative and comparable measures for the subhaloes, primarily focusing on mass and the peak of the rotation curve for this particular study. We find that all of the finders agree extremely well on the presence and location of substructure and even for properties relating to the inner part part of the subhalo (e.g. the maximum value of the rotation curve). For properties that rely on particles near the outer edge of the subhalo the agreement is at around the 20 per cent level. We find that basic properties (mass, maximum circular velocity) of a subhalo can be reliably recovered if the subhalo contains more than 100 particles although its presence can be reliably inferred for a lower particle number limit of 20. We finally note that the logarithmic slope of the subhalo cumulative number count is remarkably consistent and <1 for all the finders that reached high resolution. If correct, this would indicate that the larger and more massive, respectively, substructures are the most dynamically interesting and that higher levels of the (sub-)subhalo hierarchy become progressively less important.

The interdependence of wavelength, redundancy and dose in sulfur SAD experiments

In the last decade, the popularity of sulfur SAD anomalous dispersion experiments has spread rapidly among synchrotron users as a quick and streamlined way of solving the phase problem in macromolecular crystallography. On beamline 10 at SRS (Daresbury Laboratory, UK), a versatile design has allowed test data sets to be collected at six wavelengths between 0.979 and 2.290 A in order to evaluate the importance and the interdependence of experimental variables such as the Bijvoet ratio, wavelength, resolution limit, data redundancy and absorbed X-ray dose in the sample per data set. All the samples used in the experiments were high-quality hen egg-white lysozyme crystals. X-radiation damage was found to affect disulfide bridges after the crystals had been given a total dose of 0.20 x 10(7) Gy. However, with such a total dose, it was still possible in all cases to find a strategy to collect data sets to determine the sulfur substructure and produce good-quality phases by choosing an optimum combination of wavelength, exposure time and redundancy. A |Delta(ano)|/sigma(Delta(ano)) greater than 1.5 for all resolution shells was a necessary requirement for successful sulfur SAD substructure location. Provided this is achieved, it seems possible to find an optimum compromise between wavelength, redundancy and dose to provide phasing information. The choice of the wavelength should then follow the sample composition and the diffracting properties of the crystal. For strongly diffracting crystals, wavelengths equal or shorter than 1.540 A can be selected to capture the available data (provided the Bijvoet ratio is reasonable), while a longer wavelength, to gain as high a Bijvoet ratio as possible, must be used for more weakly diffracting crystals. These results suggest that an approach to a sulfur SAD experiment based on a complete description of the crystal system and the instrument for data collection is useful.

Reconstructing the Triaxial Shapes of Dark Matter Halos from the Anisotropic Spatial Distributions of their Substructures in the Concordance Cosmology

We develop an algorithm to reconstruct the triaxial shapes of dark matter halos from the anisotropic spatial distributions of their substructures for the concordance background cosmology. First, we construct an analytic model for the anisotropic spatial distribution of dark halo substructures under the assumption that the tidal field with nonzero trace in the triaxial mass distribution of the host halos generates the substructure bulk motions toward the major principal axes of the hosts. Our analytic model implies that the degree of anisotropy depends sensitively on the triaxiality of the host halos as well as the correlation between the substructure locations and the tidal shear field. Second, we set the axis ratios of the triaxial host halos as free parameters in the analytic model, fit the model to the numerical results from high-resolution N-body simulation of the concordance cosmology, and reconstruct the two axis ratios of the host halos from the best-fit values of the free parameters. The comparison of the reconstructed axis ratios with the numerical results reveals good agreement. Finally, we conclude that our analytic model may provide a physical understanding of the anisotropic spatial distribution of dark halo substructures and a new way to reconstruct in principle the triaxial shapes of dark matter halos from the observables.

Locating the anomalous scatterer substructures in halide and sulfur phasing.

Improved data quality now makes it feasible to exploit the weak anomalous signal derived only from the sulfurs inherent to the protein or in particular from halide ions incorporated by soaking. The latter technique requires the location of a high number of partially occupied halide sites. This number appears to be roughly proportional to the exposed protein surface. This paper explores the application of dual-space ab initio methods as implemented in the program SHELXD to the location of substructures of sulfur in SAD experiments, bromide in SAD and MAD experiments and iodide using SAD and SIRAS to determine the anomalous-atom substructure. Sets of atoms consistent with the Patterson function were generated as a starting point for the dual-space recycling procedure in SHELXD. The substructure is then expanded to the full structure by maximum-likelihood phasing with SHARP and density modification with the program DM. Success in the location of the substructures and subsequent phasing depends critically on the quality of the data and on the extent of the anomalous signal. This varies with each crystal and soak, but for the same crystal the significance of the anomalous signal was found to be highly sensitive to the redundancy of the intensity measurements, which in some cases made all the difference. This is illustrated by the determination of the previously unknown structure of repeat 11 of the human mannose-6-phosphate/insulin-like growth factor II receptor (Man6P/IGFII-receptor), with 310 amino acids in the asymmetric unit, which was phased by soaking the crystals in a cryoprotectant solution containing halide anions.

Seismic Design of Lifeline Bridge using Hybrid Seismic Isolation

This paper presents the merits of a hybrid seismic isolation system used for the seismic design of a major bridge. The bridge is analyzed for two different arrangements of seismic isolation systems. The first arrangement consists of friction pendulum bearings at all substructure locations; the other incorporates a hybrid system where laminated elastomeric bearings are used at the abutments and friction pendulum bearings at the piers. Analysis results have demonstrated that the hybrid seismic isolation system provided a structure with a fundamental period long enough to attract smaller seismic forces, while controlling the magnitude of isolation bearings displacements. It also provided a more uniform distribution of seismic forces among substructure elements. As a result, higher seismic forces on the piers were reduced, allowing for a more economical design of substructures. The hybrid seismic isolation system helped to control the wind-induced vibrations and reduced the sizes of the isolation bearings.