The "Pittsburgh Renaissance," an urban renewal effort launched in the late 1940s, transformed the smoky rust belt city's downtown. Working-class residents and people of color saw their neighborhoods ...cleared and replaced with upscale, white residents and with large corporations housed in massive skyscrapers. Pittsburgh's Renaissance's apparent success quickly became a model for several struggling industrial cities, including St. Louis, Cleveland, Detroit, Chicago, and Philadelphia. In A Good Place to Do Business, Roger Biles and Mark Rose chronicle these urban "makeovers" which promised increased tourism and fashionable shopping as well as the development of sports stadiums, convention centers, downtown parks, and more. They examine the politics of these government-funded redevelopment programs and show how city politics (and policymakers) often dictated the level of success. As city officials and business elites determined to reorganize their downtowns, a deeply racialized politics sacrificed neighborhoods and the livelihoods of those pushed out. Yet, as A Good Place to Do Business demonstrates, more often than not, costly efforts to bring about the hoped-for improvements failed to revitalize those cities, or even their downtowns.
Upon nutrient limitation, budding yeasts like Saccharomyces cerevisiae can be induced to adopt alternate filament-like growth patterns called diploid pseudohyphal or invasive haploid growth. Here, we ...report a novel constitutive pseudohyphal growth state, sharing some characteristics with classic forms of filamentous growth, but differing in crucial aspects of morphology, growth conditions and genetic regulation. The constitutive pseudohyphal state is observed in fus3 mutants containing various septin assembly defects, which we refer to as sadF growth (septin assembly defect induced filamentation) to distinguish it from classic filamentation pathways. Similar to other filamentous states, sadF cultures comprise aggregated chains of highly elongated cells. Unlike the classic pathways, sadF growth occurs in liquid rich media, requiring neither starvation nor the key pseudohyphal proteins, Flo8p and Flo11p. Moreover sadF growth occurs in haploid strains of S288C genetic background, which normally cannot undergo pseudohyphal growth. The sadF cells undergo highly polarized bud growth during prolonged G2 delays dependent on Swe1p. They contain septin structures distinct from classical pseudo-hyphae and FM4-64 labeling at actively growing tips similar to the Spitzenkörper observed in true hyphal growth. The sadF growth state is induced by synergism between Kss1p-dependent signaling and septin assembly defects; mild disruption of mitotic septins activates Kss1p-dependent gene expression, which exacerbates the septin defects, leading to hyper-activation of Kss1p. Unlike classical pseudo-hyphal growth, sadF signaling requires Ste5, Ste4 and Ste18, the scaffold protein and G-protein β and γ subunits from the pheromone response pathway, respectively. A swe1 mutation largely abolished signaling, breaking the positive feedback that leads to amplification of sadF signaling. Taken together, our findings show that budding yeast can access a stable constitutive pseudohyphal growth state with very few genetic and regulatory changes.
Purpose
The SRS MapCHECK®, a recently developed patient‐specific quality assurance (PSQA) tool for end‐to‐end testing of stereotactic radiosurgery (SRS) and stereotactic body radiation therapy ...(SBRT), was evaluated in a multi‐institution study and compared with radiochromic film.
Methods
The SRS MapCHECK was used to collect data on 84 SBRT or SRS PSQA plans/fields at nine institutions on treatment delivery devices (TDD) manufactured by Varian and Elekta. PSQA plans from five different treatment planning software (TPS) were selected and executed on TDDs operating at beam energies of 6 and 10 MV with and without a flattening filter. The patient plans were all VMAT except for ten conformal arc therapy fields. The plans were selected to encompass a range of size and tumor sites including brain, lung, spine, abdomen, ear, pancreas, and liver. Corresponding radiochromic film data was acquired in 50 plans/fields. Results were evaluated using gamma analysis with absolute dose criterion of 3% global dose‐difference (DD) and 1 mm distance‐to‐agreement (DTA).
Results
The mean 3% DD/1 mm DTA Gamma pass rate of SRS MapCHECK in comparison to film was 95.9%, whereas comparison of SRS MapCHECK to the treatment planning software was 94.7%. 80% of SRS MapCHECK comparisons against film exceed 95% pass rate, and about 30% of SRS MapCHECK comparisons against film exceed 99% pass rate. To maintain good agreement between SRS MapCHECK and film or TPS, authors recommend avoiding plans with a modified modulation complexity score (MMCS) <0.1 arbitrary units (a.u.). In the examples presented, this coincides with avoiding plans with a mu/dose limit of >3 µ/cGy.
Conclusions
Stereotactic radiosurgery MapCHECK has been validated for PSQA for a variety of clinical SRS/SBRT plans in a wide range of treatment delivery conditions. The SRS MapCHECK comparison with film demonstrates near‐equivalence for analysis of patient‐specific QA deliveries comprised of small field measurements.
Display omitted
The last 25 years have seen significant growth in new therapeutic options for breast cancer, termed targeted therapies based on their ability to block specific pathways known to drive ...breast tumor growth and survival. Introduction of these drugs has been made possible through advances in the understanding of breast cancer biology.
While the promise of targeted therapy for breast cancer has been clear for some time, the experience of the clinical use of multiple drugs and drug classes allows us to now present a summary and perspective as to the success and impact of this endeavor.
Here we will review breast cancer targeted therapeutics in clinical use. We will provide the rationale for their indications and summarize clinical data in patients with different breast cancer subtypes, their impact on breast cancer progression and survival and their major adverse effects. The focus of this review will be on the development that has occurred within classes of targeted therapies and subsequent impact on breast cancer patient outcomes. We will conclude with a perspective on the role of targeted therapy in breast cancer treatment and highlight future areas of development.
Kar4p, the yeast homolog of the mammalian methyltransferase subunit METTL14, is required for efficient mRNA m.sup.6 A methylation, which regulates meiotic entry. Kar4p is also required for a second ...seemingly non-catalytic function during meiosis. Overexpression of the early meiotic transcription factor, IME1, can bypass the requirement for Kar4p in meiotic entry but the additional overexpression of the translational regulator, RIM4, is required to permit sporulation in kar4DELTA/DELTA. Using microarray analysis and RNA sequencing, we sought to determine the impact of removing Kar4p and consequently mRNA methylation on the early meiotic transcriptome in a strain background (S288c) that is sensitive to the loss of early meiotic regulators. We found that kar4DELTA/DELTA mutants have a largely wild type transcriptional profile with the exception of two groups of genes that show delayed and reduced expression: (1) a set of Ime1p-dependent early genes as well as IME1, and (2) a set of late genes dependent on the mid-meiotic transcription factor, Ndt80p. The early gene expression defect is likely the result of the loss of mRNA methylation and is rescued by overexpressing IME1, but the late defect is only suppressed by overexpression of both IME1 and RIM4. The requirement for RIM4 led us to predict that the non-catalytic function of Kar4p, like methyltransferase complex orthologs in other systems, may function at the level of translation. Mass spectrometry analysis identified several genes involved in meiotic recombination with strongly reduced protein levels, but with little to no reduction in transcript levels in kar4DELTA/DELTA after IME1 overexpression. The low levels of these proteins were rescued by overexpression of RIM4 and IME1, but not by the overexpression of IME1 alone. These data expand our understanding of the role of Kar4p in regulating meiosis and provide key insights into a potential mechanism of Kar4p's later meiotic function that is independent of mRNA methylation.
We describe the catalogs assembled and the algorithms used to populate the revised TESS Input Catalog (TIC), based on the incorporation of the Gaia second data release. We also describe a revised ...ranking system for prioritizing stars for 2 minute cadence observations, and we assemble a revised Candidate Target List (CTL) using that ranking. The TIC is available on the Mikulski Archive for Space Telescopes server, and an enhanced CTL is available through the Filtergraph data visualization portal system at http://filtergraph.vanderbilt.edu/tess_ctl.
We carry out a phase-curve analysis of the KELT-9 system using photometric observations from NASA's Transiting Exoplanet Survey Satellite (TESS). The measured secondary eclipse depth and peak-to-peak ...atmospheric brightness modulation are and 566 16 ppm, respectively. The planet's brightness variation reaches maximum 31 5 minutes before the midpoint of the secondary eclipse, indicating a 5 2 0 9 eastward shift in the dayside hot spot from the substellar point. We also detect stellar pulsations on KELT-9 with a period of 7.58695 0.00091 hr. The dayside emission of KELT-9b in the TESS bandpass is consistent with a blackbody brightness temperature of 4600 100 K. The corresponding nightside brightness temperature is 3040 100 K, comparable to the dayside temperatures of the hottest known exoplanets. In addition, we detect a significant phase-curve signal at the first harmonic of the orbital frequency and a marginal signal at the second harmonic. While the amplitude of the first harmonic component is consistent with the predicted ellipsoidal distortion modulation assuming equilibrium tides, the phase of this photometric variation is shifted relative to the expectation. Placing KELT-9b in the context of other exoplanets with phase-curve observations, we find that the elevated nightside temperature and relatively low day-night temperature contrast agree with the predictions of atmospheric models that include H2 dissociation and recombination. The nightside temperature of KELT-9b implies an atmospheric composition containing about 50% molecular and 50% atomic hydrogen at 0.1 bar, a nightside emission spectrum that deviates significantly from a blackbody, and a 0.5-2.0 m transmission spectrum that is featureless at low resolution.
Abstract
AU Mic is a young (∼24 Myr), pre-main-sequence M dwarf star that was observed in the first month of science observations of the Transiting Exoplanet Survey Satellite (TESS) and reobserved 2 ...years later. This target has photometric variability from a variety of sources that is readily apparent in the TESS light curves; spots induce modulation in the light curve, flares are present throughout (manifesting as sharp rises with slow exponential decay phases), and transits of AU Mic b may be seen by eye as dips in the light curve. We present a combined analysis of both TESS Sector 1 and Sector 27 AU Mic light curves including the new 20 s cadence data from TESS Year 3. We compare flare rates between both observations and analyze the spot evolution, showing that the activity levels increase slightly from Sector 1 to Sector 27. Furthermore, the 20 s data collection allows us to detect more flares, smaller flares, and better resolve flare morphology in white light as compared to the 2 minute data collection mode. We also refine the parameters for AU Mic b by fitting three additional transits of AU Mic b from Sector 27 using a model that includes stellar activity. We show that the transits exhibit clear transit timing variations with an amplitude of ∼80 s. We also detect three transits of a 2.8
R
⊕
planet, AU Mic c, which has a period of 18.86 days.
Why isn't my professor aboriginal? Jones, Mark; Stanton, Pauline; Rose, Mark
Australian journal of management,
02/2024, Volume:
49, Issue:
1
Journal Article
Peer reviewed
This article focuses on the lived experience of a Karajarri Yawuru, First Peoples Doctoral candidate and his interactions with the Academy. This article draws on three vignettes and highlights first, ...racism that questions First Peoples' academic expertise and knowledge, second, racism that dismisses and demeans First Peoples' lived experience and third, racism that instrumentalises First Peoples' academics. We argue that despite the aspirational strategies and good intentions of Australian universities, the deeply embedded and pervasive nature of colonisation and institutional whiteness has to be identified and challenged in order for First Peoples to take their rightful place in the Academy.
Although most Americans attribute shifting practices in the financial industry to the invisible hand of the market, Mark H. Rose reveals the degree to which presidents, legislators, regulators, and ...even bankers themselves have long taken an active interest in regulating the industry.In 1971, members of Richard Nixon's Commission on Financial Structure and Regulation described the banks they sought to create as "supermarkets." Analogous to the twentieth- century model of a store at which Americans could buy everything from soft drinks to fresh produce, supermarket banks would accept deposits, make loans, sell insurance, guide mergers and acquisitions, and underwrite stock and bond issues. The supermarket bank presented a radical departure from the financial industry as it stood, composed as it was of local savings and loans, commercial banks, investment banks, mutual funds, and insurance firms. Over the next four decades, through a process Rose describes as "grinding politics, " supermarket banks became the guiding model of the financial industry. As the banking industry consolidated, it grew too large while remaining too fragmented and unwieldy for politicians to regulate and for regulators to understand—until, in 2008, those supermarket banks, such as Citigroup, needed federal help to survive and prosper once again.Rose explains the history of the financial industry as a story of individuals—some well-known, like Presidents Kennedy, Carter, Reagan, and Clinton; Treasury Secretaries Donald Regan and Timothy Geithner; and JP Morgan CEO Jamie Dimon; and some less so, though equally influential, such as Kennedy's Comptroller of the Currency James J. Saxon, Citicorp CEO Walter Wriston, and Bank of America CEOs Hugh McColl and Kenneth Lewis. Rose traces the evolution of supermarket banks from the early days of the Kennedy administration, through the financial crisis of 2008, and up to the Trump administration's attempts to modify bank rules. Deeply researched and accessibly written, Market Rules demystifies the major trends in the banking industry and brings financial policy to life.
PDF
