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Analyticity, Superoscillations and Supershifts in Several Variables
Get PDFSuperoscillations have roots in various scientific disciplines, including optics, signal processing, radar theory, and quantum mechanics. This intriguing mathematical phenomenon permits specific functions to oscillate at a rate surpassing their highest Fourier component. A different way of thinking about superoscillations consists in realizing that it is possible to reproduce the exponential function far away from the origin by only knowing its value in a countable set of points near the origin. By using this perspective, one can extend the idea of superoscillations to functions that are not a sum of exponential functions, namely to the notion of supershift. The study of time evolution for superoscillations (and supershifts) has naturally lead to their extension to the case of several variables. In this paper, however, we take a different approach and use the theory of Bernstein and Lagrange approximation of analytic functions in Cn to obtain deeper results for the several variables case. We provide specific examples related to harmonic analysis where the variables vary in multi-dimensional frequency (space, or scale) domains
Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors
Get PDFBackground and Objectives: Neuronal nitric oxide synthase (nNOS) overexpressed in melanoma plays a critical role in disease progression. Our previous studies demonstrated that nNOS inhibitors exhibited potent anti-melanoma activity and regulated PD-L1 expressions in the presence of interferon-gamma (IFN-γ). However, the role of nNOS in the melanoma immune response has not been well defined. Methods: Changes in gene expression profiles after nNOS inhibitor treatment were determined by transcriptomic analysis. A melanoma mouse model was used to determine the effects of nNOS inhibition on peripheral T cells and the in vivo anti-tumor activity of combining nNOS inhibitors with immune checkpoint blockade. Changes in human T cell activation through interleukin-2 (IL-2) production were investigated using an ex vivo co-culture system with human melanoma cells. Results: Cellular RNA analysis revealed significant changes in the genes involved in key signaling pathways after nNOS inhibitor HH044 treatment. Immunophenotyping of mouse peripheral blood mononuclear cells (PBMCs) after prolonged HH044 treatment showed marked increases in CD4+ and CD8+PD-1+ T cells. Ex vivo studies demonstrated that co-culturing human PBMCs with melanoma cells inhibited T cell activation, decreasing IL-2-secreting T cells both in the presence and absence of IFN-γ. PBMCs from a significant portion of donors (7/11, 64%), however, were reactivated by nNOS inhibitor pretreatment, displaying a significant increase in IL-2+ T cells. Distinctive T cell characteristics were noted at baseline among the responders with increased CD4+RORγt+ and reduced CD4 naïve T cells. In vivo mouse studies demonstrated that nNOS inhibitors, when combined with PD-1 blockade, significantly reduced tumor growth more effectively than monotherapy. Additionally, the median survival was extended from 43 days in the control mice to 176.5 days in mice co-treated with HH044 and anti-PD-1. Conclusions: Targeting nNOS is a promising approach to enhancing the anti-melanoma activity of immune checkpoint inhibitors, not only interfering with melanoma biological activities but also regulating the tumor microenvironment, which subsequently affects T cell activation and tumor immune response
An Exploratory Pharmacogenetic Pilot Study of Two Reverse Transcriptase Inhibitors, Tenofovir Alafenamide Fumarate and Tenofovir Disoproxil Fumarate
Get PDFBackground and Objectives
The nucleoside reverse transcriptase inhibitors tenofovir alafenamide fumarate and tenofovir disoproxil fumarate are frequently employed in treating human immunodeficiency virus. Further, each form of tenofovir requires laboratory monitoring to determine efficacy and tolerability among patients. This study sought to investigate the relationship, if any, of single nucleotide polymorphisms (SNPs) and selected clinical parameters. Methods
The study population, predominantly Caucasian males with a median age of 53.0 years [interquartile range 46.0–59.0], was assayed for genetic variations using an iPLEX ADME PGx Pro v1.0 Panel. Results
Although several SNP relationships were found with both forms of tenofovir, many of the reported SNPs were displayed only in the comprehensive regimen grouping, making it difficult to distinguish between the two prodrug forms. Conclusions
Being an exploratory study, the findings of this substudy serve as potential avenues for further research
Breaking the Bind: Rethinking Non-Compete Agreements in a Federal Framework
Get PDFIn April 2024, the Federal Trade Commission (FTC) adopted a sweeping rule that bans most non-compete agreements nationwide. Though well-intentioned, the FTC’s categorical prohibition neglects the complex interplay between worker mobility, employer investment, and the protection of legitimate business interests. This Article contends that the United States must move beyond the current false binary of complete prohibition or unregulated enforcement. Drawing on comparative legal analysis, it proposes a federal framework modeled on Germany’s Karenzentschädigung system, under which employers must provide post-employment compensation—typically fifty percent of prior salary—to enforce non-competes.
After tracing the evolution of non-compete doctrine in American law, this Article critiques the FTC’s rule on constitutional, statutory, and federalism grounds. It then offers a detailed roadmap for legislative reform, demonstrating how a structured compensatory approach can promote innovation, protect trade secrets, and ensure economic security for workers. The proposal includes statutory minimums on compensation and duration, administrative enforcement through the Department of Labor, and judicial review grounded in proportionality and business necessity. Empirical evidence from Germany supports the model’s efficacy in reducing litigation, enhancing labor mobility, and preserving competitive markets.
Ultimately, this Article advances a middle path—“earned enforceability”—that reconciles economic dynamism with legal stability. By transforming non-compete agreements from instruments of suppression into deliberate, reciprocal contracts, a federal compensatory regime can replace the existing regulatory patchwork with a durable, constitutionally sound solution for the knowledge-based economy
Technological Change and the Evolution of Patent Rights
Get PDFThe history of patent law is characterized by a striking pattern: dramatic, recurring cycles between eras of stronger and weaker patent rights. One theory is that patent law has been adapting to waves of technological change. In periods of rapid technological progress, following major breakthroughs (like the steam engine or the microprocessor), freely granting patents tends to create thickets of overlapping claims that block innovation, and courts have reacted by weakening rights (raising the standard to obtain and enforce a patent).
Existing histories, relying on qualitative methods, have argued that this theory explains certain nineteenth-century legal developments, but have questioned whether it can explain the post-nineteenth-century period. This Article introduces new, complementary evidence that is based on a quantitative approach and covers substantially the entire two-century doctrinal history.
In particular, the Article presents a model for the correlation predicted by the technological theory (changes in the law lag behind changes in the pace of technological progress) using a dynamic ordered probit. To measure the rate of technological progress, it uses two quantitative measures from economic history: (1) the rate of productivity growth, and (2) the number of technologically significant patents issued by the United States Patent and Trademark Office. To measure changes in the law over time, it focuses on changes to an especially central doctrine—the standard of invention—and uses the judgments of doctrinal commentaries to code the law in each year.
The results both replicate the prior qualitative analyses of the nineteenth century and show that the same story extends to future periods. For nearly two centuries, courts have consistently weakened patent rights after the rate of technological progress rose, and vice versa, at a lag of roughly a decade. A one-percent rise in the rate of productivity growth, or one more technologically significant patent in force per five thousand people, has been associated with at least one step upward in the stringency of the standard of invention
Keynote Address: Is This Cultural Property Law? The Emerging Norm of Voluntary Repatriations
No full textProfessor Erin L. Thompson, Professor of Art Crime, John Jay College (CUNY
Geospatial Intelligence and Multi-criteria Analysis for Mapping Groundwater Potential Zones and Sustainable Resource Management in Wadi Qena Basin, Eastern Desert, Egypt
Get PDFGroundwater is a rare and valuable resource in arid and hyperarid areas. Over the past few decades, population growth, urbanization, and agricultural activities—particularly in developing countries like Egypt—have greatly increased the demand for water supplies. The purpose of this study is to apply a multi-criteria analytical hierarchy process (AHP) in conjunction with remote sensing and geographic information systems methodologies to identify potential zones for groundwater recharge in Wadi Qena, Eastern Desert of Egypt. This valley is considered as one of the most potential valleys for government-led land reclamation and development initiatives. Using several data sources (e.g., Landsat-8 Enhanced Thematic Mapper Plus and Shuttle Radar Topography Mission), as well as all available geologic and hydrogeological data, thematic maps were prepared and combined based on 15 spatial criteria. Using AHP-based specialized knowledge and expert judgment, the study assigned weights to spatial criteria layers and classified Wadi Qena catchment area into five zones: very high (11.75%), high (29.30%), moderate (8.86%), low (47.55%), and very low (2.50%), with the southwestern part having a very high recharge and storage capacity. The model\u27s accuracy was confirmed by comparing the obtained groundwater potential map with the available borehole data and daily productivity from the groundwater aquifers within the valley (e.g., ROC curve with AUC = 0.94). The results demonstrate that the integration of AHP, remote sensing, and GIS techniques is effective for precise groundwater resource assessment, planning, and monitoring in arid regions like Wadi Qena. These insights can assist decision-makers in water-scarce areas in making informed decisions regarding the conservation and sustainable management of groundwater resources
The Impact of Insufficient Sleep on the Serial Reproduction of Information
Get PDFStory retelling is an important form of communication, cultural practice, and message transmission. Insufficient sleep is known to affect relevant cognitive skill areas necessary for story retelling or transmission fidelity. We conducted a preregistered randomized cross-over study on n = 155 young adults with exogenously assigned nightly sleep levels experienced in their at-home environments. A serial story reproduction task was administered online, and chains of up to three retells of a given story involved varied numbers of sleep restricted (SR) versus well-rested (WR) retellers. While story content decayed with each retell, group-level analysis showed that additional SR retellers in a chain was associated with greater decay, which mostly resulted from the introduction of an initial SR reteller at the first retell. Supporting the group-level effect, individual-level analysis confirmed that the number of details and the story’s key event were significantly less preserved during a participant’s SR treatment week. Exploratory analysis showed an attenuation of this effect in those reporting a higher level of affective response (interest or surprise) in the story. This suggests that emotional engagement can combat the deleterious effects of SR on successful story retelling, and perhaps on other types of content recollection