Relative Size Research Articles

Abstract 6875: Preclinical development of a novel small molecule multitarget inhibitor LCI133 for endometrial adenocarcinoma

Abstract Objective: Endometrial cancer (EC) is the most common gynecologic malignancy with rising mortality and limited targeted therapies. LCI133, an in silico-designed triple inhibitor of CDK4/6-CDK9-AURK, has demonstrated nano-molar potency against PTEN-mutant EC cells lines and favorable in vivo tolerability. Genetically engineered mouse model (GEMM) is the optimal approach to investigate cancer therapeutics in an immunocompetent setting. The objective of this study is to: 1) describe the physiochemical and pharmacokinetic properties of LCI133, 2) establish and characterize the Pgr-Cre; Pten fl/fl GEMM of EC, 3) assess the preliminary effect of LCI133 on GEMM disease burden. Methods: 1) LCI133 was profiled for target inhibition by cell-free screen and KinomeSCAN. In vivo PK/ADME properties were assessed as described by Veena Bala.5 In vitro potency was assessed by IC50 assay, cell cycle assay, qRT-PCR and immunoblotting at the indicated timepoints for target biomarkers. 2) Pgr-Cre;Ptenfl/fl mice with conditional PTEN deletion were generated by crossbreeding PTEN floxed mice (Ptenflox)with mice expressing Cre under the regulation of the progesterone receptor promoter (PgRCre). Alterations of PTEN/PI3K/AKT pathway were validated by qRT-PCR and immunoblotting. Histopathologic features of female reproductive tract (FRT) were characterized by H&E and immunohistochemistry staining. FRT relative size was normalized to mouse body mass. 3) Beginning at 4-5 weeks of age, formulated LCI133-HCl was administered to Pgr-Cre;Ptenfl/fl mice intraperitoneally daily for 21 days. Animal weight was recorded during treatment. Relative FRT size, pathology and target inhibition were assessed at endpoint. Results: 1) LCI133 demonstrates favorable preclinical PK/ADME profile. LCI-HCl salt form is superior to free form. 2) We confirmed loss of PTEN in Pgr-Cre;Ptenfl/fl FRT with concomitant increases in pAKT. Endometrial adenocarcinoma with serosal and lympho-vascular invasion in a background of hyperplasia was identified at 7-8 weeks of age with high penetrance. Conditional loss of PTEN correlates with expression of Pgr, predominantly in the endometrium and myometrium. 3) LCI133 treatment was associated with decreased relative FRT size, reduced angiogenesis and target suppression. Conclusion: In silico-designed LCI133, as a highly selective inhibitor against CDK4/6-CDK9-AURK with nano-molar potency and favorable PK/ADME properties, demonstrated promising in vivo therapeutic index in immunocompetent mouse models. Citation Format: Qi Zhang, Vaidehi Mujumdar, Ritchie Delara, Krishnaiah Maddeboina, Dhananjaya Pal, Bharath Yada, Hailey Dryden, Wendel Naumann, Yovanni Casablanca, Erin Crane, Jubilee Brown, Cody Mchale, Donald Durden. Preclinical development of a novel small molecule multitarget inhibitor LCI133 for endometrial adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6875.

Limit Theorems for the Non-Convex Multispecies Curie–Weiss Model

We study the thermodynamic properties of the generalized non-convex multispecies Curie–Weiss model, where interactions among different types of particles (forming the species) are encoded in a generic matrix. For spins with a generic prior distribution, we compute the thermodynamic limit of the generating functional for the moments of the Boltzmann–Gibbs measure using simple interpolation techniques. For Ising spins, we further analyze the fluctuations of the magnetization in the thermodynamic limit under the Boltzmann–Gibbs measure. It is shown that a central limit theorem (CLT) holds for a rescaled and centered vector of species magnetizations, which converges to either a centered or non-centered multivariate normal distribution, depending on the rate of convergence of the relative sizes of the species.

Explainable machine learning algorithms to identify predictors of intention to use family planning among women of reproductive-age in Ethiopia: Evidence from the Performance Monitoring and Accountability (PMA) 2021 survey data set

IntroductionReducing maternal and infant mortality, preventing unintended pregnancies and improving the health of women and their families are all strongly associated with use of family planning (FP). It is widely...

Smart Wash: Accelerated Membrane Washing Method in Immunoblot.

Immunoblot, also known as western blot, is a well-established procedure in life science. It is commonly used to determine the relative size and abundance of specific proteins, as well as posttranslational modifications of proteins. While this method is widely employed due to its simplicity, it can take hours or even days to complete. Despite considerable efforts to reduce the overall procedure time, particularly for antibody incubation, the steps involving membrane rinsing have remained unchanged since the development of the immunoblot technique. In this context, we introduce an innovative device called the "Smart Wash," designed to significantly reduce the washing intervals by utilizing a motorized salad spinner. The principle of Smart Wash is akin to that of a household washing machine: the container holds the membranes during the rinsing cycle, and the basket moves the membranes along with the washing solution in the container. We have optimized the rinsing conditions, including the volume of the washing solution, rotation speed, number of washing cycles, and direction. This straightforward device empowers researchers to significantly enhance the efficiency and productivity of immunoblotting analysis.

Integrative taxonomy reveals cryptic diversity within the Euphorbia nicaeensis alliance (Euphorbiaceae) in the central Balkan Peninsula

The Eurasian steppes are the second-largest continuous biome on Earth. Euphorbia glareosa, a member of the Euphorbia nicaeensis alliance, is a widespread species in the macroclimatically defined zonal Pontic steppes and westerly and southerly adjacent extrazonal steppe outposts determined by local climatic, topographic, and edaphic conditions. In the extrazonal steppes, in particular within the Anatolian, Danubian, Thracian, and Pannonian grasslands, it is more or less continuously distributed, but with several disjunct occurrences in the central Balkan Peninsula, which is renowned for its high biodiversity. Several (infra)specific taxa have been recognised within E. glareosa s.l., but relationships among them remain elusive. We applied an integrative approach ranging from cytogenetics (relative genome size and ploidy estimation, chromosome counting) and morphometrics to phylogenetics (internal ribosomal transcribed spacer sequencing and amplified length polymorphism fingerprinting), with geographic focus on the central and eastern Balkan Peninsula. We inferred multiple polyploidisations within the group and complex phylogenetic patterns. We uncovered cryptic lineages in the central Balkan Peninsula, where the description of two new species, diploid E. balcanica, and tetraploid E. skopjensis was necessary. In addition, we revealed high diversity, partly related to polyploidisations, among the populations from the eastern Balkan and Pontic steppes, likely pertaining to different species. Finally, the main phylogeographic split within E. glareosa is between (1) Pannonian, central and eastern Balkan populations, and (2) the easternmost Balkan, Pontic, and Anatolian populations. Our results thus highlight the outstanding conservation value of the extrazonal European steppes that are not just an outpost of zonal Eurasian steppes. We also point to the remarkable biodiversity of the central and eastern Balkan Peninsula and the need for further in-depth studies of this biodiversity hotspot.

Introducing the AIDA-TNG project: Galaxy formation in alternative dark matter models

We introduce the AIDA-TNG project, a suite of cosmological magnetohydrodynamic simulations that simultaneously model galaxy formation and different variations in the underlying dark matter model. We consider the standard cold dark matter model and five variations, including three warm dark matter scenarios and two self-interacting models with a constant or velocity-dependent cross-section. In each model, we simulated two cosmological boxes of 51.7 and 110.7 Mpc on a side with the same initial conditions as TNG50 and TNG100, and we combined the variations in the physics of dark matter with the fiducial IllustrisTNG galaxy formation model. The AIDA-TNG runs are thus ideal for studying the simultaneous effects of baryons and alternative dark matter models on observable properties of galaxies and large-scale structures. We resolved haloes in the range between 10^8 and $4 $M_⊙ and scales down to the nominal resolution of 570 pc in the highest-resolution runs. This work presents the first results on statistical quantities such as the halo mass function and the matter power spectrum. We quantified the modification in the number of haloes and the power on scales smaller than 1 Mpc due to the combination of baryonic and dark matter physics. Despite being calibrated on cold dark matter, we find that the TNG galaxy formation model can produce a realistic galaxy population in all scenarios. The stellar and gas mass fraction, stellar mass function, black hole mass as a function of stellar mass, and star formation rate density are very similar in all dark matter models, with some deviations only in the most extreme warm dark matter model. Finally, we also quantify changes in halo structure due to warm and self-interacting dark matter, which appear in the density profiles, concentration-mass relation, and galaxy sizes.

Relationship of Anthropometric Values and Splenic Size

ABSTRACTIntroductionThe splenic size is influenced by anthropometric parameters. This present study assessed the correlations between various sonographic splenic measurements with height, weight, and body mass index (BMI).MethodsFollowing the ethical approval, the scanning procedure was explained to the 391 patients and consent was obtained. Using a purposive sampling technique, the spleen was measured using a Zianfeng XF30A(XF50) ultrasound system. The intra‐observer error was found to be < 5%. The heights and weights of the study subjects were measured using the FM‐S120 weight and height scale.ResultsThe mean age of the study subjects was 35.15 ± 15.67 years with male and female consisting of 203 (51.92%) and 188 (48.08%), respectively. The mean cranio‐caudal length (CCL), width, depth, and volume were 9.97 ± 1.3, 4.41 ± 0.59, 7.60 ± 1.2 cm, and 180.34 ± 57.94 cm3, respectively. Student t‐test revealed that there was no statistically significant difference in splenic size measurements between sexes. The mean height, weight, and BMI were 1.59 ± 0.15 m, 64.12 ± 15.71 kg, and 24.49 ± 4.35 kg/m2, respectively. Moderate to strong significant positive correlations (r = 0.4–0.79, ρ < 0.05) were recorded for height and weight with CCL, splenic width, and splenic depth, while a significantly strong positive correlation (r = 0.60–0.79, ρ < 0.05) was recorded for splenic volume with subject height and weight.ConclusionThis study emphasizes the importance of anthropometric parameters (height and weight) in the assessment of splenic size.

The Limit to Concentric Electrohydrodynamic Analysis of a Sedimenting Compound Drop

Abstract Researchers have extensively investigated the phenomenon of electrohydrodynamic sedimentation of single drops. But until now, very few have addressed the electrohydrodynamic settling of a compound drop when it is under dual effect of charge convection and interface deformation. The choice between analysis for concentric or eccentric regime is a crucial decision that must be made before beginning any compound drop analysis. Hence, the limit to concentric electrohydrodynamic analysis of compound drops needs to be established. In this paper, we attempt to resolve so by creating a three-dimensional analytical model of a circular compound drop subjected to electrostatic field with varied orientation of electric field. In order to establish the demarcating limit between analysis for concentric and eccentric regime, critical assessment of viscosity, permittivity and conductivity of the phases, electric field application direction, and relative size of the shell and core on the involved electrohydrodynamic settling are also carried out. According to our research, the compound drop's directional divergence from the path of gravity can be effectively controlled by adjusting the conductivity and permittivity ratio. Moreover, the shell and core drop may attempt to deviate laterally in different directions at high viscosity ratios. This finally paves the way to establish that the validity of analysis for concentric and eccentric regime of compound drop is dictated by the polynomial relation between viscosity ratio and radius ratio of the two drops.

The thinness of GenAI: body size in relation to the construction of the normate through GenAI image models

Abstract While generative AI (genAI) image models are increasingly popular, they are not without critique for their biased outputs. Building on assessments of Dall-E’s prejudiced and homogenising production of race, this paper seeks to understand how fat bodies are presented compared to straight-size bodies in 649 images created by nine different, free-to-use genAI image models. The images are examined through critical visual analysis and reflexive thematic analysis. In the first instance, auditing highlights that, if not explicitly prompted to show larger bodies, none of the models create fatness or disability. Secondly, in the outputs with a larger body-size prompt, the models produced images which contravened their own content guidelines, showed fewer positive facial expressions, and had higher rates of mistakes and anomalies compared to images without a body-size prompt. This paper argues that the social imaginaries created through genAI images are foreclosing on difference and forming new normate standards of personhood, which explicitly exclude people who exist in socially deviant bodies.

MOLECULAR GENETIC CLASSIFICATION OF THE SPECIES G. OSCULATA (GOEZE, 1782) BELONGING TO THE GENUS GLANITAENIA (CESTODA: PROTEOCEPHALIDAE)

In this article, nucleotides belonging to the ITS region of the ribosomal DNA of Glanitaenia osculata (Goeze, 1782) found in the flounder (Silurus glanis. Linnaeus, 1758) were analyzed and the phylogenetic relationships of this species were studied. Glanitaenia was differentiated from the other genera of the subfamily Proteocephalinae by the possession of a well-developed, functional apical sucker with a deep cavity (the apical sucker in different species of the Proteocephalus-aggregate is vestigial, without any cavity, or completely absent – see Scholz et al., 1998). However, some morphological details, including characteristics that are recently considered to be of potential taxonomic and phylogenetic importance, such as the development of the uterus, the relative size of the ovary, the morphology of the eggs and terminal genitalia (the distal part of the vaginal canal), and the course of osmoregulatory canals were not provided. Keywords: Cestoda, genus, species, ribosomal DNA, ITS, phylogeny, Glanitaenia osculata, Silurus glanis, bioinformatic. Financial Support. This work was carried out by the Khorezm Mamun Academy under the state program.

Laboratory study of the enhanced wave-induced drift of large rectangular floating objects

Surface gravity waves induce a drift on objects floating on the water’s surface. This study presents laboratory experiments investigating the drift of large two-dimensional floating objects on deep-water, unidirectional, regular waves, with wave steepness ranging from 0.04 to 0.31 (0.04 $\lt k{a_w}\lt$ 0.31, where $k$ is the wavenumber and $a_w$ the wave amplitude). The objects were carefully designed to have a rectangular cross-section with a constant aspect ratio; their size varied from 2.6 $\%$ to 27 $\%$ of the incident wavelength. We observed Lagrangian behaviour for small objects. Small and large objects exhibited fundamentally different drift behaviour at high compared with low wave steepness, with a regime shift observed at a certain size and wave steepness. The scaling of object drift with steepness depends on the relative size of the object. For small objects, drift scales with steepness squared, whereas drift becomes a linear function of steepness as the object size increases. For objects that are relatively large but smaller than 13–16% of a wavelength (low to high steepness), we provide experimental evidence supporting the mechanisms of drift enhancement recently identified by Xiao et al. (J. Fluid Mech., vol. 980, 2024, p. A27) and termed the ‘diffraction-modified Stokes drift’. This enhanced drift behaviour, compared with the theoretical Stokes drift for infinitely small fluid parcels, is attributed to changes in the objects’ oscillatory motion and local wave amplitude distribution (standing wave pattern) due to the presence of the object. In the case of larger objects, similar to Harms (J. Waterw. Port Coast. Ocean Eng., vol. 113(6), 1987, pp. 606–622), we relate the critical size at which drift is maximised to their vertical bobbing motion. We determine the domain of validity for both Stokes drift and the diffraction-modified Stokes drift model of Xiao et al. (J. Fluid Mech., vol. 980, 2024, A27) in terms of relative size and wave steepness and propose an empirical parametrisation based on our experimental data.

Retrospective analyses to understand how wolf territory density impacts moose quotas, harvest and observation rate

The ever-growing human population along with the expansion of settlements and land use, and effective hunting methods increasingly influence wildlife populations. Knowledge of management responses to re-establishing large carnivores is important to understand the overall impact of humans on large carnivores and their prey populations. We examined the response of moose (Alces alces) harvest, but also population size and composition in relation to wolf (Canis lupus) territory density along a latitudinal gradient in two bordering countries in northern Europe. Moose harvest density was negatively related to wolf territory density with model estimates showing that harvest was 35% (Norway) to 39% (Sweden) lower in moose management units (MMUs) with average wolf territory density, compared to MMUs without wolves during the previous five years. The corresponding model estimates for moose observation rate was 21% lower in Sweden and 1% lower in Norway. In both countries, management actions were taken to reduce the total moose mortality (reduced harvest) as well as to maximize productivity in the population (reduced harvest of adult females) in response to increased wolf territory density. Annual changes in quotas were related to fulfilment of last year´s quota and wolf territory density in the previous two years. The annual change in harvest were affected by actual harvest the previous year and by set quotas, showing that harvest followed management plans. Abilities to adjust to new conditions is a key in wildlife management where conflicting societal objectives such as forestry, sustainable ungulate harvest yield, and carnivore conservation should be balanced.

Is counting a bad idea? Complex relations among children's fraction knowledge, eye movements, and performance in visual fraction comparisons.

Understanding fraction magnitudes is crucial for mathematical development but is challenging for many children. Visualizations, such as tape diagrams, are thought to leverage children's early proportional reasoning skills. However, depending on children's prior knowledge, these visualizations may encourage various strategies. Children with lower fraction knowledge might rely on counting, leading to natural number bias and low performance, whereas those with higher knowledge might rely on more efficient strategies based on magnitude. This study explores the relationship between students' general fraction knowledge and their ability to visually compare fraction magnitudes represented with tape diagrams. A total of 67 children completed a fraction knowledge test and a set of comparison tasks with discretized and continuous tape diagrams while their eye movements, accuracy, and response times were recorded. Cluster analysis identified three groups. The first group, high-achieving and applying magnitude-based strategies, showed high accuracy and short response times, indicating efficiency. A second high-achieving group frequently used counting strategies, which was unexpected. This group achieved the highest accuracy but the longest response times, indicating less efficiency. The third group, low-achieving and rarely using counting strategies, had the lowest accuracy and short response times. These students tended to compare absolute sizes rather than relative sizes (i.e., showing a size bias). None of the groups exhibited a natural number bias. The study suggests that counting, although inefficient, does not necessarily lead to bias or low performance. Instead, biased reasoning with fraction visualizations can originate from reliance on absolute sizes.

Long-term treatment with haloperidol modulates angiotensin I-converting enzyme (ACE) activity in transgenic animal model with construct validity for schizophrenia studies.

Long-term treatment with haloperidol modulates angiotensin I-converting enzyme (ACE) activity in transgenic animal model with construct validity for schizophrenia studies.

Evidence of self-care tooling and phylogenetic modeling reveal parrot tool use is not rare.

Putatively rare behaviors like tool use are difficult to study because absence of evidence can arise from a species' inability to produce the behavior or from insufficient research. We combine data from digital platforms and phylogenetic modeling to estimate rates of tool use in parrots. Videos on YouTube revealed novel instances of self-care tooling in 17 parrot species, more than doubling the number of tool-using parrots from 11 (3%) to 28 (7%). Phylogenetic modeling suggests 11-17% of extant parrot species may be capable of tool use and identifies likely candidates. These discoveries impact our understanding of the evolution of tool use in parrots, revealing associations with relative brain size and feeding generalism and indicating likely ancestral tool use in several genera. Our findings challenge the assumption that current sampling efforts fully capture the distribution of putatively rare animal behaviors and offer a fruitful approach for investigating other rare behaviors.

CO2 uptake – Relative humidity – Pore size relationship: A new tool for the design of amine-containing adsorbents

CO2 uptake – Relative humidity – Pore size relationship: A new tool for the design of amine-containing adsorbents

Dynamic Duos: Coacervate-Lipid Membrane Interactions in Regulating Membrane Transformation and Condensate Size.

Biomolecular condensates interfacing with lipid membranes is crucial for several key cellular functions. However, the role of lipid membranes in regulating condensates in cells remains obscure. Here, in-depth interactions between condensates and lipid membranes are probed and unraveled by employing cell-mimetic systems like Giant unilamellar vesicles (GUVs). An unprecedented influence of the coacervate size and their electrostatic interaction with lipid membranes is revealed on the membrane properties and deformation. Importantly, these findings demonstrate that the large relative size of coacervates and minimal electrostatic interaction strength with membranes allow for budding transitions at the interface. Membranes act as nucleation site for coacervates when the charge-charge interaction is high, giving a wrinkled vesicle surface appearance. Molecular diffusion property of lipids, quantified using Fluorescence recovery after photobleaching (FRAP), is modulated at the coacervate-membrane interaction site restricting the coarsening of coacervates. Notably, these results reveal coacervate droplets are intertwined in between membrane folds and invaginations discerned using Transmission electron microscopy (TEM) and high-resolution imaging, which further controls the dimension of droplets resembling size distributions observed in cells. Finally, these findings provide mechanistic insights of lipid bilayers controlling condensate sizes that play a prominent role in comprehending nucleation and localization of cellular condensates.

Uncertainty Reduction for Subaerial Landslide‐Tsunami Hazards

AbstractSubaerial rock slopes may generate a tsunami by rapidly moving into the water. Large uncertainty in landslide characteristics propagates into large uncertainty in tsunami hazard, making hazard assessment more difficult for land and emergency managers. Once a potentially tsunamigenic landslide is identified, it may not be clear which landslide characteristics contribute most significantly to uncertainty in the tsunami hazard. Our aim is to document the relative worth of different landslide characteristics (e.g., size, material properties) for reducing uncertainty in landslide‐tsunami hazard assessments. Isolating the relative importance of specific landslide characteristics may inform prioritization of data collection and improve efficiency in understanding hazard. To accomplish this, we generated a set of 288 landslide‐tsunami simulations in which we systematically varied the size and material properties of possible failure extents at the Barry Arm landslide complex in northwestern Prince William Sound, Alaska, USA. We find that for landslides smaller than the receiving waterbody, the landslide volume has the strongest effect on resulting wave characteristics and thus the highest leverage on reducing uncertainty in tsunami hazard. In contrast, for landslides substantially larger than the waterbody, the duration of rapid movement of the landslide has the highest leverage. Based on our results, we propose a classification scheme for subaerial landslides based on the relative size of the landslide and waterbody. Additionally, our results support the generation of a tsunami height transfer function between existing tide gages and a nearby coastal city. These results have direct implications for the practice of operational early warning.

Epistatic impacts of cis - and trans -regulatory mutations on the distribution of mutational effects for gene expression in Saccharomyces cerevisiae.

Epistasis can influence evolution by causing the distribution of phenotypic effects for new mutations to vary among genotypes. Here, we investigate how epistatic interactions between new mutations and an existing regulatory mutation might impact the evolution of gene expression using Saccharomyces cerevisiae. We do so by estimating the distribution of mutational effects for expression of a fluorescent reporter protein driven by the S. cerevisiae TDH3 promoter in a reference strain as well as in eight mutant strains. Each of the mutant strains differed from the reference strain by a single mutation affecting expression of the focal gene. We found that half of these regulatory mutations changed the variance and/or skewness of the distribution of mutational effects. A change in variance indicates a change in mutational robustness, and we found that one initial regulatory mutation increased mutational robustness while another decreased it. A change in skewness indicates a change in the relative frequency and/or effect size of mutations increasing or decreasing expression, and we found that the initial regulatory mutation in four strains had such an effect. Strikingly, in all four of these cases, the change in skewness increased the likelihood that new mutations would at least partially compensate for the effects of the initial regulatory mutation. If this form of epistatic impact on the distribution of mutational effects is common, it could provide a neutral mechanism reducing the divergence of gene expression and help explain the prevalence of alleles with compensatory effects in natural populations of S. cerevisiae .

Quantifying retinal size and shape distortion in different ultra-widefield imaging systems

ObjectiveTo quantitatively investigate the retinal size and shape distortion in different ultra-widefield (UWF) imaging systems.Methods and analysisWe imaged the posterior segments of model eyes using Daytona, Mirante, CLARUS 500, VG2001,...