150813 research outputs found
Sort by
Even Parity Perturbations of the Janis-Newman-Winicour Singularity
No full textIn this paper we build upon previous works on odd-parity perturbations to the Janis-Newman-Winicour singularity by extending the analysis to even-parity perturbations. Perturbations to the metric can be decomposed using tensor spherical harmonics and Fourier decomposition, and are further reduced by gauge transformations. By calculating the Einstein field equations and the divergence of the stress-energy tensor, one obtains 8 independent radial equations for the first-order metric perturbations and scalar field perturbation. Through a suitable functional transformation, one can determine a coupled wave equation between a perturbing function and the scalar field, which is most naturally solved using numerical integration techniques. Following this analysis, we briefly discuss the notion of boundary conditions for a globally naked singularity which are essential to proposing a well-defined perturbation problem.S.B
Automated reaction kinetics and network exploration (Arkane): A statistical mechanics, thermodynamics, transition state theory, and master equation software
No full textThe open-source statistical mechanics software described here, Arkane–Automated Reaction Kinetics and Network Exploration–facilitates computations of thermodynamic properties of chemical species, high-pressure limit reaction rate coefficients, and pressure-dependent rate coefficient over multi-well molecular potential energy surfaces (PES) including the effects of collisional energy transfer on phenomenological kinetics. Arkane can use estimates to fill in information for molecules or reactions where quantum chemistry information is missing. The software solves the internal energy master equation for complex unimolecular reaction systems. Inputs to the software include converged electronic structure computations performed by the user using a variety of supported software packages (Gaussian, Molpro, Orca, TeraChem, Q-Chem, Psi4). The software outputs high-pressure limit rate coefficients and pressure-dependent phenomenological rate coefficients, as well as computed thermodynamic properties (enthalpy, entropy, and constant pressure heat capacity) with added energy corrections. Some of the key features of Arkane include treatment of 1D, 2D or ND hindered internal rotation modes, treatment of free internal rotation modes, quantum tunneling effect consideration, transition state theory (TST) and Rice-Ramsperger-Kassel-Marcus (RRKM) rate coefficient computations, master equation solution with four implemented methods, inverse-Laplace transform of high-pressure limit rate coefficients into the energy domain, energy corrections based on bond-additivity or isodesmic reactions, automated and efficient PES exploration, and PES sensitivity analysis. The present work describes the design of Arkane, how it should be used, and refers to the theory that it employs. Arkane is distributed via the RMG-Py software suite (https://github.com/ReactionMechanismGenerator/RMG-Py)
Hampshire Sheep as a Large-Animal Model for Cochlear Implantation
No full textBackground Sheep have been proposed as a large-animal model for studying cochlear implantation. However, prior sheep studies report that the facial nerve (FN) obscures the round window membrane (RWM), requiring FN sacrifice or a retrofacial opening to access the middle-ear cavity posterior to the FN for cochlear implantation. We investigated surgical access to the RWM in Hampshire sheep compared to Suffolk-Dorset sheep and the feasibility of Hampshire sheep for cochlear implantation via a facial recess approach. Methods Sixteen temporal bones from cadaveric sheep heads (ten Hampshire and six Suffolk-Dorset) were dissected to gain surgical access to the RWM via an extended facial recess approach. RWM visibility was graded using St. Thomas’ Hospital (STH) classification. Cochlear implant (CI) electrode array insertion was performed in two Hampshire specimens. Micro-CT scans were obtained for each temporal bone, with confirmation of appropriate electrode array placement and segmentation of the inner ear structures. Results Visibility of the RWM on average was 83% in Hampshire specimens and 59% in Suffolk-Dorset specimens (p = 0.0262). Hampshire RWM visibility was Type I (100% visibility) for three specimens and Type IIa (> 50% visibility) for seven specimens. Suffolk-Dorset RWM visibility was Type IIa for four specimens and Type IIb (< 50% visibility) for two specimens. FN appeared to course more anterolaterally in Suffolk-Dorset specimens. Micro-CT confirmed appropriate CI electrode array placement in the scala tympani without apparent basilar membrane rupture. Conclusions Hampshire sheep appear to be a suitable large-animal model for CI electrode insertion via an extended facial recess approach without sacrificing the FN. In this small sample, Hampshire specimens had improved RWM visibility compared to Suffolk-Dorset. Thus, Hampshire sheep may be superior to other breeds for ease of cochlear implantation, with FN and facial recess anatomy more similar to humans
Building confidence in models for complex barrier systems for radionuclides
No full textThe modeling and simulation of the Cement–clay Interaction–Diffusion field (CI-D) experiment at the Mont Terri site in Switzerland presented here demonstrates that it is possible to capture the multiscale physical and chemical features of natural and engineered barrier systems for radionuclides. The simulations are successfully carried out with the newly developed CrunchODiTi high-performance computing software that accounts for multiple continua, including a continuum representing the electrical double layer (EDL) developed along negatively charged clay particles in clay rock. The simulation also accounts for both the complex three-dimensional (3D) geometry, expected as the norm in a geological waste repository, and the anisotropy of the geological formation. In addition, the high resolution of the model makes it possible to include “skin effects” developed at the interface between highly reactive materials, in this case between the high pH cement and the circumneutral but electrostatic Opalinus Clay. The successful history matching with the field experiment demonstrates that the distinct geochemical and physical properties of the cement and the Opalinus Clay in the CI-D experiment can be accounted for. Such analyses are essential for developing a defensible safety case for the underground storage of radioactive waste.Department of Energy (DOE
Characteristics of two polarized groups in online social networks’ controversial discourse
No full textIn today’s interconnected world, online social networks play a pivotal role in facilitating global communication. These platforms often host discussions on contentious topics such as climate change, vaccines, and war, leading to the formation of two distinct groups: deniers and believers. Understanding the characteristics of these groups is crucial for predicting information flow and managing the diffusion of information. Moreover, such understanding can enhance machine learning algorithms designed to automatically detect these groups, thereby contributing to the development of strategies to curb the spread of disinformation, including fake news and rumors. In this study, we employ social network analysis measures to extract the characteristics of these groups, conducting experiments on three large-scale datasets of over 22 million tweets. Our findings indicate that, based on network science measures, the denier (anti) group exhibits greater coherence than the believer (pro) group
Modeling Mesoscale Eddies: the Effects of Resolution onOcean Turbulence
No full textWe describe a non-adiabatic idealized model for studying mesoscale turbulence in the global ocean. Using the ocean model Oceananigans, we perform a grid refinement study to determine the minimal resolution required to represent mesoscale eddies in the primitive equations. Convergence is evaluated through several metrics, including surface and depth-integrated kinetic energy, spectra, and zonally-averaged temperature, in order to establish quantitative resolution thresholds for physical fidelity. We find that while coarse-resolution simulations capture large-scale flow features, key mesoscale dynamics—including vertical stratification gradients and kinetic energy spectra—only converge at resolutions finer than 1/4°. Differences between the 1/8° and 1/16° simulations are small, suggesting that 1/8° resolution may be sufficient for resolving the mesoscale eddy field for many diagnostic purposes in idealized setups.S.B
Report to the President for year ended June 30, 2025, MIT-IBM Watson AI Lab
No full textThis report contains the following sections: Goals and Priorities, Industry Research Collaborations, Selected Research Overview, Student and Young Researcher Engagement, Community Outreach and Events, Communications, and Administration and Governance
Transforming ovarian cancer care by targeting minimal residual disease
No full textFrontline treatment and resultant cure rates in patients with advanced ovarian cancer have changed little over the past several decades. Here, we outline a multidisciplinary approach aimed at gaining novel therapeutic insights by focusing on the poorly understood minimal residual disease phase of ovarian cancer that leads to eventual incurable recurrences
Regulation of Chromatin Landscape on and by the Human Sex Chromosomes
No full textSex chromosome constitution is the largest and oldest source of genetic variation in the human population. One sex chromosome—the “active X” (Xa)—is present in all individuals. The second sex chromosome differs between sexes; most males have a Y while most females have a second X, which adopts a distinct conformation from Xa and is termed the “inactive X” (Xi). Despite its name, the human Xi expresses ~20% of its genes. Xi-expressed genes and their Y homologs play critical gene regulatory roles. Examining mechanisms and effects of Xi gene expression is essential to understanding these functions. In this thesis, I investigate chromatin landscape across the human Xi to identify features of Xi-expressed and Xi-silent genes; I also interrogate the role of an Xi-expressed gene and its Y homolog in regulating chromatin genome-wide. To examine chromatin state differences between Xi-expressed and Xi-silent genes, we quantified H3K4me3, H3K27me3, and CTCF along Xi by linear modeling in cells of individuals with zero to three Xis. We demonstrate that Xi-expressed genes are enriched for H3K4me3 compared to Xi-silent genes. Moreover, Xi-silent genes near strongly Xi-expressed genes have higher H3K27me3 than other Xi-silent genes. CTCF shields strongly Xi-expressed gene promoters from surrounding heterochromatin. We propose a framework associating combinations of chromatin marks with subcategories of Xi-expressed and Xi-silent genes. A key Xi-expressed gene, KDM6A, encodes an H3K27me3 demethylase—enabling Xi to impact chromatin structure genome-wide. Its Y homolog, UTY, is thought to encode a catalytically dead enzyme. However, we demonstrate that Xi and Y copy number-dependent changes to H3K27me3 across autosomes are strongly correlated. Moreover, KDM6A knockdown results in increased H3K27me3 at similar genomic regions as UTY knockdown. We posit that KDM6A and UTY share demethylase-dependent functions. Deciphering features and genome-wide effects of Xi expression is essential to understanding fundamental mechanisms of gene regulation and the shared and differential roles of the sex chromosomes outside the reproductive tract. This work highlights critical chromatin-level differences between Xi-silent and Xi-expressed genes, the effects of an Xi-expressed gene on chromatin structure genome-wide, and striking similarities between Xi and Y in modulating autosomal chromatin structure and gene expression.Ph.D
Layer-by-Layer Polymer Functionalization Improves Nanoparticle Penetration and Glioblastoma Targeting in the Brain
No full textGlioblastoma is characterized by diffuse infiltration into surrounding healthy brain tissues, which makes it challenging to treat. Complete surgical resection is often impossible, and systemically delivered drugs cannot achieve adequate tumor exposure to prevent local recurrence. Convection-enhanced delivery (CED) offers a method for administering therapeutics directly into brain tumor tissue, but its impact has been limited by rapid clearance and off-target cellular uptake. Nanoparticle (NP) encapsulation presents a promising strategy for extending the retention time of locally delivered therapies while specifically targeting glioblastoma cells. However, the brain's extracellular structure poses challenges for NP distribution due to its narrow, tortuous pores and a harsh ionic environment. In this study, we investigated the impact of NP surface chemistry using layer-by-layer (LbL) assembly to design drug carriers for broad spatial distribution in brain tissue and specific glioblastoma cell targeting. We found that poly-l-glutamate and hyaluronate were effective surface chemistries for targeting glioblastoma cells in vitro. Coadsorbing either polymer with a small fraction of PEGylated polyelectrolytes improved the colloidal stability without sacrificing cancer cell selectivity. Following CED in vivo, gadolinium-functionalized LbL NPs enabled MRI visualization and exhibited a distribution volume up to three times larger than liposomes and doubled the retention half-time up to 13.5 days. Flow cytometric analysis of CED-treated murine orthotopic brain tumors indicated greater cancer cell uptake and reduced healthy cell uptake for LbL NPs compared to nonfunctionalized liposomes. The distinct cellular outcomes for different colayered LbL NPs provide opportunities to tailor this modular delivery system for various therapeutic applications