Graham v. Estuary Properties, Inc., 399 So.2d 1374 (Fla. 1981)

Environmental Regulation/Constitutional Law- TAKING JURISPRUDENCE AND ITS APPLICATION TO REGULATIONS OF SENSITIVE ECOLOGICAL ENVIRONMENT

Additive Influence of Extracellular pH, Oxygen Tension, and Pressure on Invasiveness and Survival of Human Osteosarcoma Cells

Background/Purpose: The effects of chemical and physical interactions in the microenvironment of solid tumors have not been fully elucidated. We hypothesized that acidosis, hypoxia, and elevated interstitial fluid pressure (eIFP) have additive effects on tumor cell biology and lead to more aggressive behavior during tumor progression. We investigated this phenomenon using three human osteosarcoma (OS) cell lines and a novel in vitro cell culture apparatus. Materials and Methods: U2OS, SaOS, and MG63 cell lines were cultured in media adjusted to various pH levels, oxygen tension (hypoxia 2% O(2), normoxia 20% O(2)), and hydrostatic gage pressure (0 or 50 mmHg). Growth rate, apoptosis, cell cycle parameters, and expression of mRNA for proteins associated with invasiveness and tumor microenvironment (CA IX, VEGF-A, HIF-1A, MMP-9, and TIMP-2) were analyzed. Levels of CA IX, HIF-1α, and MMP-9 were measured using immunofluorescence. The effect of pH on invasiveness was evaluated in a Matrigel chamber assay. Results: Within the acidic–hypoxic–pressurized conditions that simulate the microenvironment at a tumor’s center, invasive genes were upregulated, but the cell cycle was downregulated. The combined influence of acidosis, hypoxia, and IFP promoted invasiveness and angiogenesis to a greater extent than did pH, pO(2), or eIFP individually. Significant cell death after brief exposure to acidic conditions occurred in each cell line during acclimation to acidic media, while prolonged exposure to acidic media resulted in reduced cell death. Furthermore, 48-h exposure to acidic conditions promoted tumor invasiveness in the Matrigel assay. Conclusion: Our findings demonstrate that tumor microenvironmental parameters – particularly pH, pO(2), and eIFP – additively influence tumor proliferation, invasion, metabolism, and viability to enhance cell survival and must be controlled in OS research

Factuality Challenges in the Era of Large Language Models

The emergence of tools based on Large Language Models (LLMs), such as OpenAI's ChatGPT, Microsoft's Bing Chat, and Google's Bard, has garnered immense public attention. These incredibly useful, natural-sounding tools mark significant advances in natural language generation, yet they exhibit a propensity to generate false, erroneous, or misleading content -- commonly referred to as "hallucinations." Moreover, LLMs can be exploited for malicious applications, such as generating false but credible-sounding content and profiles at scale. This poses a significant challenge to society in terms of the potential deception of users and the increasing dissemination of inaccurate information. In light of these risks, we explore the kinds of technological innovations, regulatory reforms, and AI literacy initiatives needed from fact-checkers, news organizations, and the broader research and policy communities. By identifying the risks, the imminent threats, and some viable solutions, we seek to shed light on navigating various aspects of veracity in the era of generative AI.Comment: Our article offers a comprehensive examination of the challenges and risks associated with Large Language Models (LLMs), focusing on their potential impact on the veracity of information in today's digital landscap

Not all mitochondrial carrier proteins support permeability transition pore formation: no involvement of uncoupling protein 1

The mPTP (mitochondrial permeability transition pore) is a non-specific channel that is formed in the mitochondrial inner membrane in response to several stimuli, including elevated levels of matrix calcium. The pore is proposed to be composed of the ANT (adenine nucleotide translocase), voltage-dependent anion channel and cyclophilin D. Knockout studies, however, have demonstrated that ANT is not essential for permeability transition, which has led to the proposal that other members of the mitochondrial carrier protein family may be able to play a similar function to ANT in pore formation. To investigate this possibility, we have studied the permeability transition properties of BAT (brown adipose tissue) mitochondria in which levels of the mitochondrial carrier protein, UCP1 (uncoupling protein 1), can exceed those of ANT. Using an improved spectroscopic assay, we have quantified mPTP formation in de-energized mitochondria from wild-type and Ucp1KO (Ucp1-knockout) mice and assessed the dependence of pore formation on UCP1. When correctly normalized for differences in mitochondrial morphology, we find that calcium-induced mPTP activity is the same in both types of mitochondria, with similar sensitivity to GDP (approximately 50% inhibited), although the portion sensitive to cyclosporin A is higher in mitochondria lacking UCP1 (approximately 80% inhibited, compared with approximately 60% in mitochondria containing UCP1). We conclude that UCP1 is not a component of the cyclosporin A-sensitive mPTP in BAT and that playing a role in mPTP formation is not a general characteristic of the mitochondrial carrier protein family but is, more likely, restricted to specific members including ANT

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Convection and Retro-Convection Enhanced Delivery: Some Theoretical Considerations Related to Drug Targeting

Delivery of drugs and macromolecules into the brain is a challenging problem, due in part to the blood–brain barrier. In this article, we focus on the possibilities and limitations of two infusion techniques devised to bypass the blood–brain barrier: convection enhanced delivery (CED) and retro-convection enhanced delivery (R-CED). CED infuses fluid directly into the interstitial space of brain or tumor, whereas R-CED removes fluid from the interstitial space, which results in the transfer of drugs from the vascular compartment into the brain or tumor. Both techniques have shown promising results for the delivery of drugs into large volumes of tissue. Theoretical approaches of varying complexity have been developed to better understand and predict brain interstitial pressures and drug distribution for these techniques. These theoretical models of flow and diffusion can only be solved explicitly in simple geometries, and spherical symmetry is usually assumed for CED, while axial symmetry has been assumed for R-CED. This perspective summarizes features of these models and provides physical arguments and numerical simulations to support the notion that spherical symmetry is a reasonable approximation for modeling CED and R-CED. We also explore the potential of multi-catheter arrays for delivering and compartmentalizing drugs using CED and R-CED

Progress Towards Low Energy Charge Transfer Collision Experiments Using Pulse Sequencing

Our goal is to extend measurements of the lithium-proton charge transfer cross section to lower energies than have previously been measured. This will mimic collisions that occur near the walls of some nuclear fusion devices. To do this we require a new experimental method, called the “pulse sequencing” method. Pulse sequencing requires that the protons involved in the collisions, and the charged lithium ions which are created in the collisions, be controlled by a series of carefully timed voltage pulses. These voltage pulses will simultaneously guide lithium ions towards a detector, and remove unwanted background ions from the collision site. Using a software called SIMION, we were able to simulate the trajectories of the protons, the lithium ions, and the background ions as they move through the electric fields created by the timed voltage pulses. These simulations allowed us to maximize the expected efficiency of detecting lithium ions in our experiments. In addition to simulations, we tested the necessary equipment for our pulse sequencing experiment. This was done to determine exactly how well the equipment performs its intended functions in the pulse sequencing process. Additionally, we wrote a computer program in the LabView programming language to allow computer control of the necessary parameters in the pulse sequence