Justice Kennedy\u27s Prose – Style and Substance

Supreme Court Justice Anthony Kennedy\u27s retirement in June 2018 sent shockwaves throughout America. After Justice Sandra Day O\u27Connor left the Court in 2005, Justice Kennedy became the Court\u27s all-important swing vote in virtually every important area of constitutional law. His views on affirmative action, abortion, campaign finance reform, free speech, and the separation of church and state (among many other constitutional issues) were the ones that mattered the most among the Justices. Lawyers prepared arguments and filed briefs in the Supreme Court for the main purpose of persuading Justice Kennedy to rule for their clients. He was, quite simply, the most important and powerful judge in the United States. On October 15, 2018, the Georgia State University College of Law, along with the Georgia State University Law Review, held a conference devoted to Justice Kennedy\u27s judicial legacy. Some of this country\u27s most prominent constitutional law professors from all over the political spectrum gathered to discuss and debate many different aspects of Justice Kennedy\u27s thirty-year career, including his unique prose, his status as the Court\u27s swing vote, and his important opinions

Monitoring Replication Protein A (RPA) Dynamics in Homologous Recombination Through Site-specific Incorporation of Non-canonical Amino Acids

An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA. Upon binding to ssDNA, this fluorescent RPA (RPAf) generates a quantifiable change in fluorescence, thus serving as a reporter of its dynamics on DNA in the presence of multiple other DNA binding proteins. Using RPAf, we describe the kinetics of facilitated self-exchange and exchange by Rad51 and mediator proteins during various stages in homologous recombination. RPAf is widely applicable to investigate its mechanism of action in processes such as DNA replication, repair and telomere maintenance

A change of view: Homologous recombination at single-molecule resolution

Genetic recombination occurs in all organisms and is vital for genome stability. Indeed, in humans, aberrant recombination can lead to diseases such as cancer. Our understanding of homologous recombination is built upon more than a century of scientific inquiry, but achieving a more complete picture using ensemble biochemical and genetic approaches is hampered by population heterogeneity and transient recombination intermediates. Recent advances in single-molecule and super-resolution microscopy methods help to overcome these limitations and have led to new and refined insights into recombination mechanisms, including a detailed understanding of DNA helicase function and synaptonemal complex structure. The ability to view cellular processes at single-molecule resolution promises to transform our understanding of recombination and related processes.Fil: Kaniecki, Kyle. Columbia University; Estados UnidosFil: de Tullio, Luisina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Greene, Eric C.. Columbia University; Estados Unido

Optimal MRI sequences for 68Ga-PSMA-11 PET/MRI in evaluation of biochemically recurrent prostate cancer.

BackgroundPET/MRI can be used for the detection of disease in biochemical recurrence (BCR) patients imaged with 68Ga-PSMA-11 PET. This study was designed to determine the optimal MRI sequences to localize positive findings on 68Ga-PSMA-11 PET of patients with BCR after definitive therapy. Fifty-five consecutive prostate cancer patients with BCR imaged with 68Ga-PSMA-11 3.0T PET/MRI were retrospectively analyzed. Mean PSA was 7.9 ± 12.9 ng/ml, and mean PSA doubling time was 7.1 ± 6.6 months. Detection rates of anatomic correlates for prostate-specific membrane antigen (PSMA)-positive foci were evaluated on small field of view (FOV) T2, T1 post-contrast, and diffusion-weighted images. For prostate bed recurrences, the detection rate of dynamic contrast-enhanced (DCE) imaging for PSMA-positive foci was evaluated. Finally, the detection sensitivity for PSMA-avid foci on 3- and 8-min PET acquisitions was compared.ResultsPSMA-positive foci were detected in 89.1% (49/55) of patients evaluated. Small FOV T2 performed best for lymph nodes and detected correlates for all PSMA-avid lymph nodes. DCE imaging performed the best for suspected prostate bed recurrence, detecting correlates for 87.5% (14/16) of PSMA-positive prostate bed foci. The 8-min PET acquisition performed better than the 3-min acquisition for lymph nodes smaller than 1 cm, detecting 100% (57/57) of lymph nodes less than 1 cm, compared to 78.9% (45/57) for the 3-min acquisition.ConclusionPSMA PET/MRI performed well for the detection of sites of suspected recurrent disease in patients with BCR. Of the MRI sequences obtained for localization, small FOV T2 images detected the greatest proportion of PSMA-positive abdominopelvic lymph nodes and DCE imaging detected the greatest proportion of PSMA-positive prostate bed foci. The 8-min PET acquisition was superior to the 3 min acquisition for detection of small lymph nodes

Telomere Recognition and Assembly Mechanism of Mammalian Shelterin

Shelterin is a six-subunit protein complex that plays crucial roles in telomere length regulation, protection, and maintenance. Although several shelterin subunits have been studied in vitro, the biochemical properties of the fully assembled shelterin complex are not well defined. Here, we characterize shelterin using ensemble biochemical methods, electron microscopy, and single-molecule imaging to determine how shelterin recognizes and assembles onto telomeric repeats. We show that shelterin complexes can exist in solution and primarily locate telomeric DNA through a three-dimensional diffusive search. Shelterin can diffuse along non-telomeric DNA but is impeded by nucleosomes, arguing against extensive one-dimensional diffusion as a viable assembly mechanism. Our work supports a model in which individual shelterin complexes rapidly bind to telomeric repeats as independent functional units, which do not alter the DNA-binding mode of neighboring complexes but, rather, occupy telomeric DNA in a "beads on a string" configuration

Critical behavior of gravitating sphalerons

We examine the gravitational collapse of sphaleron type configurations in Einstein--Yang--Mills--Higgs theory. Working in spherical symmetry, we investigate the critical behavior in this model. We provide evidence that for various initial configurations, there can be three different critical transitions between possible endstates with different critical solutions sitting on the threshold between these outcomes. In addition, we show that within the dispersive and black hole regimes, there are new possible endstates, namely a stable, regular sphaleron and a stable, hairy black hole.Comment: Latex, 14 pages, 8 figure

Now You See It, Now You Don't: The Disappearing Central Engine of the Quasar J1011+5442

We report the discovery of a new "changing-look" quasar, SDSS J101152.98+544206.4, through repeat spectroscopy from the Time Domain Spectroscopic Survey. This is an addition to a small but growing set of quasars whose blue continua and broad optical emission lines have been observed to decline by a large factor on a time scale of approximately a decade. The 5100 Angstrom monochromatic continuum luminosity of this quasar drops by a factor of > 9.8 in a rest-frame time interval of < 9.7 years, while the broad H-alpha luminosity drops by a factor of 55 in the same amount of time. The width of the broad H-alpha line increases in the dim state such that the black hole mass derived from the appropriate single-epoch scaling relation agrees between the two epochs within a factor of 3. The fluxes of the narrow emission lines do not appear to change between epochs. The light curve obtained by the Catalina Sky Survey suggests that the transition occurs within a rest-frame time interval of approximately 500 days. We examine three possible mechanisms for this transition suggested in the recent literature. An abrupt change in the reddening towards the central engine is disfavored by the substantial difference between the timescale to obscure the central engine and the observed timescale of the transition. A decaying tidal disruption flare is consistent with the decay rate of the light curve but not with the prolonged bright state preceding the decay, nor can this scenario provide the power required by the luminosities of the emission lines. An abrupt drop in the accretion rate onto the supermassive black hole appears to be the most plausible explanation for the rapid dimming.Comment: Submitted to MNRA

Topological Orbifold Models and Quantum Cohomology Rings

We discuss the toplogical sigma model on an orbifold target space. We describe the moduli space of classical minima for computing correlation functions involving twisted operators, and show, through a detailed computation of an orbifold of ${\bf CP}^1$ by the dihedral group $D_{4},$ how to compute the complete ring of observables. Through this procedure, we compute all the rings from dihedral ${\bf CP}^1$ orbifolds; we note a similarity with rings derived from perturbed $D-$series superpotentials of the $A-D-E$ classification of $N = 2$ minimal models. We then consider ${\bf CP}^2/D_4,$ and show how the techniques of topological-anti-topological fusion might be used to compute twist field correlation functions for nonabelian orbifolds.Comment: 48 pages, harvmac, HUTP-92/A06

EXCEDE Technology Development III: First Vacuum Tests

This paper is the third in the series on the technology development for the EXCEDE (EXoplanetary Circumstellar Environments and Disk Explorer) mission concept, which in 2011 was selected by NASA's Explorer program for technology development (Category III). EXCEDE is a 0.7m space telescope concept designed to achieve raw contrasts of 1e6 at an inner working angle of 1.2 l/D and 1e7 at 2 l/D and beyond. This will allow it to directly detect and spatially resolve low surface brightness circumstellar debris disks as well as image giant planets as close as in the habitable zones of their host stars. In addition to doing fundamental science on debris disks, EXCEDE will also serve as a technological and scientific precursor for any future exo-Earth imaging mission. EXCEDE uses a Starlight Suppression System (SSS) based on the PIAA coronagraph, enabling aggressive performance. We report on our continuing progress of developing the SSS for EXCEDE, and in particular (a) the reconfiguration of our system into a more flight-like layout, with an upstream deformable mirror and an inverse PIAA system, as well as a LOWFS, and (b) testing this system in a vacuum chamber, including IWA, contrast, and stability performance. The results achieved so far are 2.9e-7 contrast between 1.2-2.0 l/D and 9.7e-8 contrast between 2.0-6.0 l/D in monochromatic light; as well as 1.4e-6 between 2.0-6.0 l/D in a 10% band, all with a PIAA coronagraph operating at an inner working angle of 1.2 l/D. This constitutes better contrast than EXCEDE requirements (in those regions) in monochromatic light, and progress towards requirements in broadband light. Even though this technology development is primarily targeted towards EXCEDE, it is also germane to any exoplanet direct imaging space-based telescopes because of the many challenges common to different coronagraph architectures and mission requirements.Comment: 12 pages, 12 figures, to be published in proceedings of SPIE Astronomical Telescopes + Instrumentation (2014

Symmetrized models of last passage percolation and non-intersecting lattice paths

It has been shown that the last passage time in certain symmetrized models of directed percolation can be written in terms of averages over random matrices from the classical groups $U(l)$, $Sp(2l)$ and $O(l)$. We present a theory of such results based on non-intersecting lattice paths, and integration techniques familiar from the theory of random matrices. Detailed derivations of probabilities relating to two further symmetrizations are also given.Comment: 21 pages, 5 figure