Feminist and Queer Legal Theory Fineman, Martha Albertson; Jackson, Jack E; Romero, Adam P
2009, 20160415, 2016-04-15, 2009-11-01, 2013-02-28, 20090101
eBook
Feminist and Queer Legal Theory: Intimate Encounters, Uncomfortable Conversations is a groundbreaking collection that brings together leading scholars in contemporary legal theory. The volume ...explores, at times contentiously, convergences and departures among a variety of feminist and queer political projects. These explorations - foregrounded by legal issues such as marriage equality, sexual harassment, workers' rights, and privacy - re-draw and re-imagine the alliances and antagonisms constituting feminist and queer theory. The essays cross a spectrum of disciplinary matrixes, including jurisprudence, political philosophy, literary theory, critical race theory, women's studies, and gay and lesbian studies. The authors occupy a variety of political positions vis-Ã -vis questions of identity, rights, the state, cultural normalization, and economic liberalism. The richness and vitality of feminist and queer theory, as well as their relevance to matters central to the law and politics of our time, are on full display in this volume.
The treatment of cutaneous melanoma has been revolutionized by the development of small-molecule inhibitors targeting the MAPK pathway, including inhibitors of BRAF (BRAFi) and MEK (MEKi), and immune ...checkpoint blockade antibodies, occurring in tandem. Despite these advances, the 5-year survival rate for patients with advanced melanoma remains only around 50%. Although not designed to alter immune responses within the tumor microenvironment (TME), MAPK pathway inhibitors (MAPKi) exert a range of effects on the host immune compartment that may offer opportunities for therapeutic interventions.
We review the effects of MAPKi, especially BRAFi, on the TME, focusing on alterations in inflammatory cytokine secretion, recruitment of immune cells and their functions, both during response to BRAFi treatment and as resistance develops. We outline potential combinations of MAPKi with established and experimental treatments.
MAPKi in combination or in sequence with established treatments such as checkpoint inhibitors, anti-angiogenic agents, or new therapies such as adoptive cell therapies, may augment their immunological effects, reverse tumor-associated immune suppression, and offer the prospect of longer-lived clinical responses. Refining therapeutic tools at our disposal and embracing 'old friends' in the melanoma treatment arsenal, alongside new target identification, may improve the chances of therapeutic success.
Advances with implantation of synthetic biomaterials in the setting of orthopedic surgery have clearly resulted in improvements in patient outcomes. However, all implants have been shown to have ...associated risks. For example, ionic and particulate debris from implants have been shown to engage in biological interactions with the native tissue, and have been associated with a wide range of metabolic, bacteriologic, immunologic, and oncogenic effects. The propensity of synthetic biomaterials to undergo degradation, producing an inflammatory reaction or other sequelae, has been well recognized. The use of porous implants, which allow for a greater interface area between native tissue and the prosthesis, may magnify the interaction between biologically active tissue and synthetic devices in some situations, giving rise to new and intriguing issues concerning biocorrosion and biocompatibility. In this article, we report the case of a high-grade conventional osteosarcoma occurring at the site of a modular porous-surfaced titanium and cobalt alloy total hip prosthesis 3 years after device implantation. Detailed spectroscopic trace metal analysis was performed and elevated levels of both vanadium and chromium, but not aluminum, nickel, or titanium were identified in the tumor. Ann Diagn Pathol 7:35-46, 2003. Copyright 2003, Elsevier Science (USA). All rights reserved.
Menogaril is an antitumor agent of the anthracycline type which is less cardiotoxic than doxorubicin in a chronic rabbit model and is active in experimental tumor systems when given by p.o. or ...parenteral routes. It is currently undergoing i.v. and p.o. Phase II clinical evaluation. We report here the results of pharmacokinetic and systemic bioavailability studies of menogaril in three species (mouse, dog, and monkey). Upon i.v. administration, menogaril plasma concentration-time curves declined in a biexponential (dog) or triexponential (mouse and monkey) manner, with the terminal disposition half-life (t1/2) being considerably shorter in the dog (2.86 +/- 0.47 h) than in the mouse and monkey (21.6 and 19.0 +/- 3.7 h, respectively). The systemic clearance (CL, in liters/h/kg) was highest in mouse (6.2), followed by dog (2.9) and then monkey (1.4). The drug was extensively distributed in all three species, with steady state volumes of distribution being 88.5, 9.8, and 27.9 liters/kg in the mouse, dog, and monkey, respectively. One, two, and three metabolites were detected in the plasma of mice, monkeys, and dogs, respectively, using reverse phase high performance liquid chromatography. The major fluorescent metabolite in all species coeluted with authentic N-demethyl-menogaril; the other two metabolites were present at low concentrations relative to unchanged menogaril and its putative N-demethylated metabolite. One of these metabolites, which was found in both the dog and monkey, eluted with authentic (7R)-nogarol. Mean maximum plasma concentrations of the putative N-demethylmenogaril metabolite were approximately one-tenth those of menogaril in all three species following i.v. drug administration. Upon p.o. treatment, first-pass metabolism or incomplete absorption reduced the systemic bioavailability to 12% in the dog and 33% in the mouse and monkey. N-Demethylmenogaril was the major fluorescent metabolite observed in the plasma of p.o. treated animals. Interspecies comparison of menogaril pharmacokinetic parameters in mice, dogs, monkeys, and humans using allometric techniques indicated that the parameters for mice, monkeys, and humans were highly correlated; in each of these species presystemic metabolism of p.o. administered menogaril reduced its systemic bioavailability to an equivalent extent (30-35%). To determine if metabolically formed N-demethylmenogaril might contribute to the overall antitumor activity of menogaril, we determined the effect of synthetic N-demethylmenogaril on the life span of mice bearing P388 leukemia. Results indicated that the metabolite is marginally active compared to menogaril itself.
The federally assisted public housing program was launched with enactment of the US Housing Act of 1937 and has evolved over 4 decades of piecemeal legislation. As a welfare conveyor, public housing ...is a straightforward attempt to reduce the number of people living in substandard housing. This study provides an estimate of the cash outlay that would be required to make families moving into Little Rock, Arkansas, public housing during the 1979 fiscal year equally well off. These households could then contract for housing service in the private sector. The discussion also considers: 1. a determination of how efficiently federal expenditures are transformed into an increase in tenant welfare, and 2. net-tenant-benefit equity implications. The analysis reveals that the average federal dollar's worth of Little Rock public housing increased the average tenant welfare of families moving into these dwelling units during 1979 by about $.88. It is argued that the Cobb-Douglas specification overestimates the benefits.
Knowledge of genetic diversity and population structure is critical for conservation and management planning at the population level within a species' range. Many brown bear populations in Central ...Asia are small and geographically isolated, yet their phylogeographic relationships, genetic diversity, and contemporary connectivity are poorly understood. To address this knowledge gap, we collected brown bear samples from the Gobi Desert (n = 2360), Altai, Sayan, Khentii, and Ikh Khyangan mountains of Mongolia (n = 79), and Deosai National Park in the Himalayan Mountain Range of Pakistan (n = 5) and generated 927 base pairs of mitochondrial DNA (mtDNA) sequence data and genotypes at 13 nuclear DNA microsatellite loci. We documented high levels of mtDNA and nDNA diversity in the brown bear populations of northern Mongolia (Altai, Sayan, Buteeliin nuruu and Khentii), but substantially lower diversity in brown bear populations in the Gobi Desert and Himalayas of Pakistan. We detected 3 brown bear mtDNA phylogeographic groups among bears of the region, with clade 3a1 in Sayan, Khentii, and Buteeliin nuruu mountains, clade 3b in Altai, Sayan, Buteeliin nuruu, Khentii, and Ikh Khyangan, and clade 6 in Gobi and Pakistan. Our results also clarified the phylogenetic relationships and divergence times with other brown bear mtDNA clades around the world. The nDNA genetic structure analyses revealed distinctiveness of Gobi bears and different population subdivisions compared to mtDNA results. For example, genetic distance for nDNA microsatellite loci between the bears in Gobi and Altai (FST = 0.147) was less than that of the Gobi and Pakistan (FST = 0.308) suggesting more recent male-mediated nuclear gene flow between Gobi and Altai than between Gobi and the Pakistan bears. Our results provide valuable information for conservation and management of bears in this understudied region of Central Asia and highlight the need for special protection and additional research on Gobi brown bears.
The quest for Earth-like planets is a major focus of current exoplanet research. Although planets that are Earth-sized and smaller have been detected, these planets reside in orbits that are too ...close to their host star to allow liquid water on their surfaces. We present the detection of Kepler-186f, a 1.11 ± 0.14 Earth-radius planet that is the outermost of five planets, all roughly Earth-sized, that transit a 0.47 ± 0.05 solar-radius star. The intensity and spectrum of the star's radiation place Kepler-186f in the stellar habitable zone, implying that if Kepler-186f has an Earth-like atmosphere and water at its surface, then some of this water is likely to be in liquid form.
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