xIV-LDDMM Toolkit: A Suite of Image-Varifold Based Technologies for Representing and Mapping 3D Imaging and Spatial-omics Data Simultaneously Across Scales.

Advancements in imaging and molecular techniques enable the collection of subcellular-scale data. Diversity in measured features, resolution, and physical scope of capture across technologies and experimental protocols pose numerous challenges to integrating data with reference coordinate systems and across scales. This resource paper describes a collection of technologies that we have developed for cross-modality 3D mapping for the alignment of transcriptomics at the micron scales of genes and cells to the anatomical tissue scales.

Simulated fire video collection for advancing understanding of human behavior in building fires.

Introduction: The goal of the present research was to develop a video collection of simulated fires to investigate how people perceive growing building fires. In fire safety science, a critical factor to occupant responses to building fires is the pre-movement period, determined by how long it takes an individual to initiate taking protective action with an incipient fire. Key to studying the psychological processes that contribute to the duration of the pre-movement period is presenting human subjects with building fires.

Coupled changes between ruminating thoughts and resting-state brain networks during the transition into adulthood.

Perseverative negative thoughts, known as rumination, might arise from emotional challenges and preclude mental health when transitioning into adulthood. Due to its multifaceted nature, rumination can take several ruminative response styles, that diverge in manifestations, severity, and mental health outcomes. Still, prospective ruminative phenotypes remain elusive insofar.

Joint response from Latin American, European Obstetric Violence Observatories and others organizations all over Europe to the Joint Position Statement on Substandard and Disrespectful Care in Labour - Because Words Matter.

The issue of obstetric violence is internationally acknowledged as a serious violation of human rights. First identified by the Committee of Experts of the Inter-American Belém do Pará Convention in 2012, it is recognized as a form of gender-based violence that infringes upon women's rights during childbirth. Nations such as Argentina, Mexico, Venezuela, and certain regions in Spain have implemented laws against it, highlighting its severity and the need for protective legislation.

Cross-modality mapping using image varifolds to align tissue-scale atlases to molecular-scale measures with application to 2D brain sections.

This paper explicates a solution to building correspondences between molecular-scale transcriptomics and tissue-scale atlases. This problem arises in atlas construction and cross-specimen/technology alignment where specimens per emerging technology remain sparse and conventional image representations cannot efficiently model the high dimensions from subcellular detection of thousands of genes. We address these challenges by representing spatial transcriptomics data as generalized functions encoding position and high-dimensional feature (gene, cell type) identity.

Groundwater irrigation reduces overall poverty but increases socioeconomic vulnerability in a semiarid region of southern India.

The development of irrigation is generally considered an efficient way to reduce poverty in rural areas, although its impact on the inequality between farmers is more debated. In fact, assessing the impact of water management on different categories of farmers requires resituating it within the different dimensions of the local socio-technical context. We tested this hypothesis in a semi-arid area in Karnataka, South India, where groundwater irrigation was introduced five decades ago.

Human Vitamin K Epoxide Reductase as a Target of Its Redox Protein.

Human vitamin K epoxide reductase (hVKORC1) enzymatic activity requires an initial activation by a specific redox protein, a less studied step in the hVKORC1 vital cycle. Significant steric conditions must be met by enzymes, being that to adapt their configurations is mandatory for hVKORC1 activation. We studied, by molecular dynamics (MD) simulations, the folding and conformational plasticity of hVKORC1 in its inactive (fully oxidised) state using available structures, crystallographic and from de novo modelling.

The Inherent Coupling of Intrinsically Disordered Regions in the Multidomain Receptor Tyrosine Kinase KIT.

RTK KIT regulates a variety of crucial cellular processes via its cytoplasmic domain (CD), which is composed of the tyrosine kinase domain, crowned by the highly flexible domains-the juxtamembrane region, kinase insertion domain, and C-tail, which are key recruitment regions for downstream signalling proteins. To prepare a structural basis for the characterization of the interactions of KIT with its signalling proteins (KIT INTERACTOME), we generated the 3D model of the full-length CD attached to the transmembrane helix. This generic model of KIT in inactive state was studied by molecular dynamics simulation under conditions mimicking the natural environment of KIT.

Molecular Computational Anatomy: Unifying the Particle to Tissue Continuum via Measure Representations of the Brain.

Objective: The objective of this research is to unify the molecular representations of spatial transcriptomics and cellular scale histology with the tissue scales of computational anatomy for brain mapping.

Impact Statement: We present a unified representation theory for brain mapping based on geometric varifold measures of the microscale deterministic structure and function with the statistical ensembles of the spatially aggregated tissue scales.

Introduction: Mapping across coordinate systems in computational anatomy allows us to understand structural and functional properties of the brain at the millimeter scale.

A Langevin-Based Model With Moving Posturographic Target to Quantify Postural Control.

Falls are a major concern of public health, particularly for older adults, as the consequences of falls include serious injuries and death. Therefore, the understanding and evaluation of postural control is considered key, as its deterioration is an important risk factor predisposing to falls. In this work we introduce a new Langevin-based model, local recall, that integrates the information from both the center of pressure (CoP) and the center of mass (CoM) trajectories, and compare its accuracy to a previously proposed model that only uses the CoP.

Identification of the Primary Factors Determining theSpecificity of Human VKORC1 Recognition by Thioredoxin-Fold Proteins.

Redox (reduction-oxidation) reactions control many important biological processes in all organisms, both prokaryotes and eukaryotes. This reaction is usually accomplished by canonical disulphide-based pathways involving a donor enzyme that reduces the oxidised cysteine residues of a target protein, resulting in the cleavage of its disulphide bonds. Focusing on human vitamin K epoxide reductase (hVKORC1) as a target and on four redoxins (protein disulphide isomerase (PDI), endoplasmic reticulum oxidoreductase (ERp18), thioredoxin-related transmembrane protein 1 (Tmx1) and thioredoxin-related transmembrane protein 4 (Tmx4)) as the most probable reducers of VKORC1, a comparative in-silico analysis that concentrates on the similarity and divergence of redoxins in their sequence, secondary and tertiary structure, dynamics, intraprotein interactions and composition of the surface exposed to the target is provided.

Proceedings of the First Workshop Organized by the IAFSS Working Group on Measurement and Computation of Fire Phenomena (MaCFP).

This paper provides a report of the discussions held at the first workshop on Measurement and Computation of Fire Phenomena (MaCFP) on June 10-11 2017. The first MaCFP work-shop was both a technical meeting for the gas phase subgroup and a planning meeting for the condensed phase subgroup. The gas phase subgroup reported on a first suite of experimental- computational comparisons corresponding to an initial list of target experiments.

Modeling flame extinction and reignition in large eddy simulations with fast chemistry.

This work seeks to support the validation of large eddy simulation models used to simulate fire suppression. The emphasis in the present study is on the prediction of flame extinction and the prevention of spurious reignition using a fast chemistry, mixing-controlled combustion model applicable to realistic fire scenarios of engineering interest. The configuration provides a buoyant, turbulent methane diffusion flame within a controlled co-flowing oxidizer.

Age and Glaucoma-Related Characteristics in Retinal Nerve Fiber Layer and Choroid: Localized Morphometrics and Visualization Using Functional Shapes Registration.

Optical coherence tomography provides high-resolution 3D imaging of the posterior segment of the eye. However, quantitative morphological analysis, particularly relevant in retinal degenerative diseases such as glaucoma, has been confined to simple sectorization and averaging with limited spatial sensitivity for detection of clinical markers. In this paper, we present point-wise analysis and visualization of the retinal nerve fiber layer and choroid from cross-sectional data using functional shapes (fshape) registration.

Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth.

Although in flies the atypical cadherin Fat is an upstream regulator of Hippo signalling, the closest mammalian homologue, Fat4, has been shown to regulate tissue polarity rather than growth. Here we show in the mouse heart that Fat4 modulates Hippo signalling to restrict growth. Fat4 mutant myocardium is thicker, with increased cardiomyocyte size and proliferation, and this is mediated by an upregulation of the transcriptional activity of Yap1, an effector of the Hippo pathway.

Impact of cerium oxide nanoparticles shape on their in vitro cellular toxicity.

Cerium oxides (CeO) nanoparticles, also referred to as nanoceria, are extensively used with a wide range of applications. However, their impact on human health and on the environment is not fully elucidated. The aim of this study was to investigate the influence of the CeO nanoparticles morphology on their in vitro toxicity.

Atlas-based shape analysis and classification of retinal optical coherence tomography images using the functional shape (fshape) framework.

We propose a novel approach for quantitative shape variability analysis in retinal optical coherence tomography images using the functional shape (fshape) framework. The fshape framework uses surface geometry together with functional measures, such as retinal layer thickness defined on the layer surface, for registration across anatomical shapes. This is used to generate a population mean template of the geometry-function measures from each individual.

Parametric Surface Diffeomorphometry for Low Dimensional Embeddings of Dense Segmentations and Imagery.

In the field of Computational Anatomy, biological form (including our focus, neuroanatomy) is studied quantitatively through the action of the diffeomorphism group on example anatomies - a technique called diffeomorphometry. Here we design an algorithm within this framework to pass from dense objects common in neuromaging studies (binary segmentations, structural images) to a sparse representation defined on the surface boundaries of anatomical structures, and embedded into the low dimensional coordinates of a parametric model. Our main new contribution is to introduce an expanded group action to simultaneously deform surfaces through direct mapping of points, as well as images through functional composition with the inverse.

How Intrinsic Molecular Dynamics Control Intramolecular Communication in Signal Transducers and Activators of Transcription Factor STAT5.

Signal Transducer and Activator of Transcription STAT5 is a key mediator of cell proliferation, differentiation and survival. While STAT5 activity is tightly regulated in normal cells, its constitutive activation directly contributes to oncogenesis and is associated with a broad range of hematological and solid tumor cancers. Therefore the development of compounds able to modulate pathogenic activation of this protein is a very challenging endeavor.

Hamiltonian Systems and Optimal Control in Computational Anatomy: 100 Years Since D'Arcy Thompson.

The Computational Anatomy project is the morphome-scale study of shape and form, which we model as an orbit under diffeomorphic group action. Metric comparison calculates the geodesic length of the diffeomorphic flow connecting one form to another. Geodesic connection provides a positioning system for coordinatizing the forms and positioning their associated functional information.

Hotspot mutations in KIT receptor differentially modulate its allosterically coupled conformational dynamics: impact on activation and drug sensitivity.

Receptor tyrosine kinase KIT controls many signal transduction pathways and represents a typical allosterically regulated protein. The mutation-induced deregulation of KIT activity impairs cellular physiological functions and causes serious human diseases. The impact of hotspots mutations (D816H/Y/N/V and V560G/D) localized in crucial regulatory segments, the juxtamembrane region (JMR) and the activation (A-) loop, on KIT internal dynamics was systematically studied by molecular dynamics simulations.

Morphometry of anatomical shape complexes with dense deformations and sparse parameters.

We propose a generic method for the statistical analysis of collections of anatomical shape complexes, namely sets of surfaces that were previously segmented and labeled in a group of subjects. The method estimates an anatomical model, the template complex, that is representative of the population under study. Its shape reflects anatomical invariants within the dataset.