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Cancer progression and treatment can be informed by reconstructing its evolutionary history from tumor cells [Lim et al., 2020]. Although many methods exist to estimate evolutionary trees (called phylogenies) from molecular sequences, traditional approaches assume the input data are error-free and the output tree is fully resolved. These assumptions are challenged in tumor phylogenetics because single-cell sequencing produces sparse, error-ridden data and because tumors evolve clonally [Jahn et al., 2016; Schwartz and Schäffer, 2017]. Here, we study the theoretical utility of methods based on quartets (four-leaf, unrooted phylogenetic trees) and triplets (three-leaf, rooted phylogenetic trees), in light of these barriers. Quartets and triplets have long been used as the building blocks for reconstructing the evolutionary history of species [Wilkinson et al., 2005]. The reason triplet-based methods (e.g., MP-EST [Liu et al., 2010]) and quartet-based methods (e.g., ASTRAL [Mirarab et al., 2014]) have garnered such success in species phylogenetics is their good statistical properties under the Multi-Species Coalescent (MSC) model [Pamilo and Nei, 1988; Rannala and Yang, 2003]; see Allman et al. (2011) and Degnan (2006) for identifiability results under the MSC model for quartets and triplets, respectively. Inspired by these efforts, we study the utility of quartets and triplets for estimating cell lineage trees under a popular tumor phylogenetics model [Jahn et al., 2016; Ross and Markowetz, 2016; Wu, 2019; Kizilkale et al., 2022] with two phases. First, mutations arise on a (highly unresolved) cell lineage tree according to the infinite sites model, and second, errors (false positives and false negatives) and missing values are introduced to the resulting mutation data in an unbiased fashion, mimicking data produced by single-cell sequencing protocols. This infinite sites plus unbiased error and missingness (IS+UEM) model generates mutations (rather than gene genealog

Finding a tree with the minimum total distance to a given set of trees (the median tree) is increasingly needed in phylogenetics. Defining tree distance as the number of induced four-taxon unrooted (i.e., quartet) trees with different topologies, the median of a set of gene trees is a statistically consistent estimator of the species tree under several models of gene tree species tree discordance. Because of this, median trees defined with quartet distance are widely used in practice for species tree inference. Nevertheless, the problem is NP-Hard and the widely-used solutions are heuristics. In this paper, we pave the way for a new type of heuristic solution to this problem. We show that the optimal place to add a subtree of size m onto a tree with n leaves can be found in time that grows quasi-linearly with n and is nearly independent of m. This algorithm can be used to perform subtree prune and regraft (SPR) moves efficiently, which in turn enables the hill-climbing heuristic search for the optimal tree. In exploratory experiments, we show that our algorithm can improve the quartet score of trees obtained using the existing widely-used methods.

Species tree estimation is a basic step in many biological research projects, but is complicated by the fact that gene trees can differ from the species tree due to processes such as incomplete lineage sorting (ILS), gene duplication and loss (GDL), and horizontal gene transfer (HGT), which can cause different regions within the genome to have different evolutionary histories (i.e., "gene tree heterogeneity"). One approach to estimating species trees in the presence of gene tree heterogeneity resulting from ILS operates by computing trees on each genomic region (i.e., computing "gene trees") and then using these gene trees to define a matrix of average internode distances, where the internode distance in a tree T between two species x and y is the number of nodes in T between the leaves corresponding to x and y. Given such a matrix, a tree can then be computed using methods such as neighbor joining. Methods such as ASTRID and NJst (which use this basic approach) are provably statistically consistent, very fast (low degree polynomial time) and have had high accuracy under many conditions that makes them competitive with other popular species tree estimation methods. In this study, inspired by the very recent work of weighted ASTRAL, we present weighted ASTRID, a variant of ASTRID that takes the branch uncertainty on the gene trees into account in the internode distance. Our experimental study evaluating weighted ASTRID shows improvements in accuracy compared to the original (unweighted) ASTRID while remaining fast. Moreover, weighted ASTRID shows competitive accuracy against weighted ASTRAL, the state of the art. Thus, this study provides a new and very fast method for species tree estimation that improves upon ASTRID and has comparable accuracy with the state of the art while remaining much faster. Weighted ASTRID is available at https://github.com/RuneBlaze/internode.

Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)-Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease.

Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)-Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease

Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)-Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease.

En el presente trabajo se estudian los símbolos astrales como las ruedas, esvásticas, trísqueles y crecientes lunares, cuando aparecen en ofrendas votivas a divinidades célticas en el occidente romano. A partir de la presencia de estos símbolos en numerosas estelas funerarias y en contextos arqueológicos relacionados con la muerte en áreas de intensa presencia cultural céltica, se formula la hipótesis según la cual las divinidades celtas que se relacionan con estos símbolos en todo el occidente romano, tendrían un carácter estelar y, además, una vinculación mitológica y ritual con el mundo funerario., In this paper, we study astral symbols such as wheels, swastikas, triskelions and lunar crescents when they appear in votive offerings dedicated to Celtic divinities in the Western regions of the Roman Empire. From the presence of these symbols in numerous funeral steles and in archaeological contexts related to death in areas of intense Celtic cultural presence, we formulate the hypothesis that the Celtic divinities related to these symbols throughout the Roman West have an astral character and, in addition, a mythological and ritual connection with the funerary world.

In this paper, we study astral symbols such as wheels, swastikas, triskelions and lunar crescents when they appear in votive offerings dedicated to Celtic divinities in the Western regions of the Roman Empire. From the presence of these symbols in numerous funeral steles and in archaeological contexts related to death in areas of intense Celtic cultural presence, we formulate the hypothesis that the Celtic divinities related to these symbols throughout the Roman West have an astral character and, in addition, a mythological and ritual connection with the funerary world., En el presente trabajo se estudian los símbolos astrales como las ruedas, esvásticas, trísqueles y crecientes lunares, cuando aparecen en ofrendas votivas a divinidades célticas en el occidente romano. A partir de la presencia de estos símbolos en numerosas estelas funerarias y en contextos arqueológicos relacionados con la muerte en áreas de intensa presencia cultural céltica, se formula la hipótesis según la cual las divinidades celtas que se relacionan con estos símbolos en todo el occidente romano, tendrían un carácter estelar y, además, una vinculación mitológica y ritual con el mundo funerario.

En el presente trabajo se estudian los símbolos astrales como las ruedas, esvásticas, trísqueles y crecientes lunares, cuando aparecen en ofrendas votivas a divinidades célticas en el occidente romano. A partir de la presencia de estos símbolos en numerosas estelas funerarias y en contextos arqueológicos relacionados con la muerte en áreas de intensa presencia cultural céltica, se formula la hipótesis según la cual las divinidades celtas que se relacionan con estos símbolos en todo el occidente romano, tendrían un carácter estelar y, además, una vinculación mitológica y ritual con el mundo funerario., In this paper, we study astral symbols such as wheels, swastikas, triskelions and lunar crescents when they appear in votive offerings dedicated to Celtic divinities in the Western regions of the Roman Empire. From the presence of these symbols in numerous funeral steles and in archaeological contexts related to death in areas of intense Celtic cultural presence, we formulate the hypothesis that the Celtic divinities related to these symbols throughout the Roman West have an astral character and, in addition, a mythological and ritual connection with the funerary world.

Aim of this work is to assess the informativeness of protein dynamics in the detection of similarities among distant homologous proteins. To this end, an approach to perform large-scale comparisons of protein domain flexibilities is proposed. CONCOORD is confirmed as a reliable method for fast conformational sampling. The root mean square fluctuation of alpha carbon positions in the essential dynamics subspace is employed as a measure of local flexibility and a synthetic index of similarity is presented. The dynamics of a large collection of protein domains from ASTRAL/SCOP40 is analyzed and the possibility to identify relationships, at both the family and the superfamily levels, on the basis of the dynamical features is discussed. The obtained picture is in agreement with the SCOP classification, and furthermore suggests the presence of a distinguishable familiar trend in the flexibility profiles. The results support the complementarity of the dynamical and the structural information, suggesting that information from dynamics analysis can arise from functional similarities, often partially hidden by a static comparison. On the basis of this first test, flexibility annotation can be expected to help in automatically detecting functional similarities otherwise unrecoverable.

[ES] Los detalles iconográficos que caracterizan a las representaciones hispano-romanas del Rapto de Europa, aludiendo a su condición de divinidad astral y diosa del Amor, sugieren la posibilidad de que, al igual que en Oriente, también en la Península Ibérica, Europa asumiera la faceta erótica y de fecundidad de la diosa Astarté, cuyo culto está atestiguado por las fuentes literarias, epigráficas y arqueológicas. Asimismo, la distribución geográfica de los documentos arqueológicos por la mitad sur de la Península Ibérica y Baleares acentúa ese posible sincretismo en aquellas regiones donde existía un fuerte arraigo del culto oriental a Astarté desde la época de las colonizaciones., [EN] The iconographic details with characterize lo time Hispanic—roman representations of Europe s abduction, os astral divinity ant! goddess of fertility. suggest ¡he possibility. same it is in the East, t/mat Europe assumed time erotic and fertility facet of time Goddess Astarté, whose cult is attested b-v literary, epigraphical and archaeological sources. Likewise,

The United States Navy uses a number of different systems to predict underwater acoustic transmission loss for operational forces. Historically, these systems have used different acoustic models and supporting databases, resulting in significantly different predictions. Major efforts to bring all acoustic models and databases under configuration control in the Oceanographic and Atmospheric Master Library (OAML) have reduced, but not eliminated, differences in acoustic predictions. Comparisons of 1600 transmission loss runs from the AntiSubmarine Warfare Tactical Decision Aid (ASWTDA) and the Tactical Environmental Support System (TESS) were made in the Mediterranean and Sea of Japan for the months of January and July. All inputs to the acoustic models were provided by the respective system databases. Significant differences between ASWTDA and TESS in the areas investigated are evident in regions of complex bathymetry, and these differences become more acute with higher freuency., http://archive.org/details/acomparisonofpas1094539894, Commander, United States Navy, Approved for public release; distribution is unlimited.

The development of new decision support systems for Antisubmarine warfare will entail the installation of propagation loss models on ASW aircraft. The decision to put either a range dependent or range independent model in the system will affect the predic, http://archive.org/details/acomparisonofast1094539952, Lieutenant, United States Navy, Approved for public release; distribution is unlimited.