Community College of Rhode Island

Tumor cell plasticity drives metastasis and therapy resistance, yet its regulation by oncoprotein dosage dynamics remains poorly understood. In Ewing sarcoma (EwS), variations in EWS::FLI1 (EF) fusion oncoprotein activity have been associated with epithelial-mesenchymal plasticity (EMP). Using degron technology, we precisely modulated endogenous EF in EwS cells and linked phenotypic states to distinct oncoprotein dosages. Strikingly, modest EF depletion promoted a pro-metastatic phenotype that diminished upon near-complete EF loss, revealing a paradoxical effect of submaximal EF inhibition. Nascent RNA-sequencing uncovered distinct gene clusters with heterogenous transcriptional responses to graded EF loss. Genes most sensitive to subtle EF depletion harbored GGAA microsatellites within EF-bound enhancers, while chromatin profiling uncovered candidate cofactors regulating EF-repressed EMP programs. Transient EF depletion followed by rapid restoration, modelling oncoprotein fluctuations, caused persistent dysregulation of genes functionally linked to enhanced extravasation and metastatic burden in preclinical models. This study highlights the therapeutic challenge of incomplete EF elimination, serving a paradigm in which oncoprotein dosage dynamics act as non-genetic drivers of disease progression and reveal novel vulnerabilities of advanced disease.

Abstract I investigated the near-Earth response to the 2025 November 4 X1.8 solar flare (peak 17:34 UT) using seven days of GOES-18 soft X-ray, integral proton, and magnetometer data, together with one-minute scalar geomagnetic measurements from USGS/INTERMAGNET observatories and a campus Geometrics G-857. The GOES 0.1–0.8 nm channel shows a clean rise to 1.8 × 10 −4 W m −2 and decay by ≈17:51 UT, with no major SEP onset or sudden-commencement-like step in the magnetometer record. I searched for a magnetic crochet by constructing detrended total-field variations Δ F over a flare-centered window and applying timing, morphology, coherence, and amplitude criteria. No station exhibits a clear, flare-synchronous signature. At mid-latitudes, including the campus site, I place a conservative upper limit of ≲5 nT. This well-constrained non-detection complements recent high-latitude and cusp detections, indicating that radiatively strong but magnetospherically quiet X-class flares may not produce observable crochets at mid-latitudes.

Abstract Single-cell RNA-seq characterizes biological samples at unprecedented scale and detail, but data interpretation remains challenging. Here we introduce CellWhisperer, a multimodal machine learning model and software that connects transcriptomes and text for interactive single-cell RNA-seq data analysis. CellWhisperer enables the chat-based interrogation of transcriptome data in English language. To train our model, we created an AI-curated dataset with over a million pairs of RNA-seq profiles and matched textual annotations across a broad range of human biology, and we established a multimodal embedding of matched transcriptomes and text using contrastive learning. Our model enables free-text search and annotation of transcriptome datasets by cell types, states, and other properties in a zero-shot manner and without the need for reference datasets. Moreover, Cell-Whisperer answers questions about cells and genes in natural-language chats, using a biologically fluent large language model that we fine-tuned to analyze bulk and single-cell transcriptome data across various biological applications. We integrated CellWhisperer with the widely used CELLxGENE browser, allowing users to in-teractively explore RNA-seq data through an integrated graphical and chat interface. Our method demonstrates a new way of working with transcriptome data, leveraging the power of natural language for single-cell data analysis and establishing an important building block for future AI-based bioinformatics research assistants.

SummaryChildhood myelodysplastic syndrome (cMDS) is a rare clonal hematopoietic disorder characterized by peripheral cytopenia, with refractory cytopenia of childhood (RCC) being the most prevalent form. In children presenting with pancytopenia and significantly reduced bone marrow cellularity, RCC, severe aplastic anemia (SAA), and inherited bone marrow failure syndromes (IBMFS) are critical differential diagnoses, with accurate distinction being pivotal for effective treatment decisions. While histopathological analysis remains fundamental in differentiating these conditions, genetic and molecular testing are playing an increasingly important role. Reflecting this importance, two new classifications for cMDS were introduced in 2022: the WHO 5th edition and the International Consensus Classification (ICC). Both classifications have broadened the scope to include additional gene mutations, highlighting advances in understanding the genetic underpinnings of cMDS. However, significant differences in terminology persist: while the WHO 5th edition redefined RCC, replacing it with the term childhood MDS with low blasts (cMDS-LB), the ICC retained the RCC designation. This paper presents two cases that illustrate the current challenges in diagnosing and treating disorders in the spectrum of cMDS. One case describes a patient with germline GATA2 deficiency, highlighting the difficulties of distinguishing between SAA and cMDS in a timely manner. The other case underscores the importance of whole exome sequencing to differentiate between IBMFS and cMDS in the presence of a histomorphological RCC pattern.

A review of The Oxford English Literary History: Volume 5: 1645–1714: The Later Seventeenth Century by Margaret J. M. Ezell.

Abstract On the Presentation of the Physical and Mathematical Solutions Process of Problems in Physics to Engineering Students The solution to problems is both a techne and a technique. To teach and train engineering students (our future engineers and colleagues) on how to solve problems (engineers solve problems) we presented them with the solution process using two approaches. One characteristic of both approaches is that we show all the steps of the solution process so the student concentrates on understanding the application of principles than trying to guess how the various results come into existence. To distinguish the two approaches, are called the Mathematical and Physical/Mathematical. In the newly developed Mathematical approach, the mathematical steps of the solution process are organized in a diagrammatic approach. All steps of the mathematical solution process are presented logically, clearly indicating the necessary derivations and substitutions, until to get a final formula that to the left of the equality sign has the unknown quantity and to the right all the known quantities. This approach has the advantage of including interactive dialogs (questions and answers, comments) which take place during class time, but requires the presence of the instructor. The physical explanation of every step was provided during the presentation (lecture/recitation) using an interactive screen by the instructor. The presentation (video and audio) was recorded and made available to the students in the Collaborate part of Blackboard. It is ideal for class discussion. Other problems were presented using the Physical/Mathematical approach that includes both physical explanation and mathematical presentation. The one line of the text is followed by the next line corresponding equation, and so on, until to get the final formula in which to the left of the equality sign has the unknown quantity and to the right all the known quantities. This approach has the advantage that does not require the presence of the instructor. It is ideal for self-study. Both approaches were presented to the students during the past year. In class, discussions took place during the semester on the preferable and possibly more beneficial approach by the students. They embraced the physical/mathematical more because it suits for self-study. Furthermore, it does not require the need to watch the recorded lecture/recitation which takes considerably more time. But they suggested that the first approach is beneficial for fast review (preparation for examination) after they have mastered the classical solution. To assist the student in their study an effort is underway to prepare problem-solution processes that include both the above-discussed approaches; the physical/mathematical is the main solution process while the mathematical is presented under Summary. NOTE: THE FORMULAS BELOW CANNOT BE PASTED ON A TEXTBOX! Example: Let us consider a point charge Q. Determine an expression for the electric field E at every point of the space. Solution Process: Mathematical approach Physical / Mathematical approach To find the electric field intensity around a charge Q, we shall use the definition of the electric field: The force on the test charge due to the charge is given by Coulomb's law: The distance is denoted by in the spherical coordinate system we are using to solve this problem. Substituting the force equation into the electric field equation, we get: We conclude that the electric field has an component when the source charge is positive and the test charge is, by definition, positive. The force will have orientation along the line connecting the two points and sense away from the charge . Why?