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Can queer theory proceed without an allegiance to antinormativity? The introduction to this special issue establishes the value of this question by staging an encounter with the most widely held assumption in queer theory today: that the political value of the field lies in its antinormative commitments. The first section of this introduction demonstrates how profoundly the history of queer theorizing has been shaped by an antinormative sensibility, one that has organized the multiple and at times discordant itineraries of analysis that comprise the queer theoretical archive into a field-forming synthesis. In part 2, the authors offer a more studied consideration of the character of norms. By articulating the difference between a norm and the terms that often define it—domination, homogenization, exclusion, hegemony, identity, or more colloquially, the familiar, status quo, or routine—this section demonstrates the importance of renewing queer theoretical attention to the conceptual and political particularity of normativity as a distinct object of inquiry. The authors’ aim is not to dismiss the political agenda that antinormativity has come to represent for queer inquiry, but to channel some of the field’s energies toward analyzing the critical authority it now wields. This entails promoting scholarship that not only rethinks the meaning of norms, normalization, and the normal but that also imagines new ways to approach the politics of queer criticism altogether. In the final section, the authors describe the specific contribution of each of the volume’s essays to this endeavor.

This study described the development of the Social Skills Improvement System Social Emotional Learning Edition Rating Forms (SSIS SEL RF) for teachers, parents, and students. This new multirater assessment is a reconfiguration of the SSIS Rating Scales items inspired by the CASEL Social Emotional Competency framework. The internal structure and score reliability estimates were examined across three raters for a common sample of more than 200 individual children ages 3 to 18 years. Confirmatory factor analyses tested against the CASEL five-dimensional SEL theoretical model demonstrated adequate fit for the SSIS SEL Parent and Student RFs and mediocre fit of the Teacher RF. Internal consistency, test-retest, and interrater reliability estimates for scores on each of the SSIS SEL RFs all met or exceeded acceptable criteria. Thus, researchers and practitioners interested in measuring the social–emotional behavior of children ages 3 to 18 can expect reliable scores and structurally meaningful behavior content within the Collaborative on Academic Social Emotional Learning (CASEL) SEL competency framework. Limitations to the present findings and suggestions for future research conclude the report.

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Tamoxifen is widely used as an adjuvant therapy for patients with estrogen receptor (ERa)-positive tumors. However, the clinical benefit is often limited because of the emergence of drug resistance. In this study, overexpression of ribonucleotide reductase M2 (RRM2) in MCF-7 breast cancer cells resulted in a reduction in the effectiveness of tamoxifen, through downregulation of ERa66 and upregulation of the 36-kDa variant of ER (ERa36). We identified that NF-kB, HIF1a, and MAPK/JNK are the major pathways that are affected by RRM2 overexpression and result in increased NF-kB activity and increased protein levels of EGFR, HER2, IKKs, Bcl-2, RelB, and p50. RRM2-overexpressing cells also exhibited higher migratory and invasive properties. Through time-lapse microscopy and protein profiling studies of tamoxifen-treated MCF-7 and T-47D cells, we have identified that RRM2, along with other key proteins, is altered during the emergence of acquired tamoxifen resistance. Inhibition of RRM2 using siRRM2 or the ribonucleotide reductase (RR) inhibitor didox not only eradicated and effectively prevented the emergence of tamoxifen-resistant populations but also led to the reversal of many of the proteins altered during the process of acquired tamoxifen resistance. Because didox also appears to be a potent inhibitor of NF-kB activation, combining didox with tamoxifen treatment cooperatively reverses ER-a alterations and inhibits NF-kB activation. Finally, inhibition of RRM2 by didox reversed tamoxifenresistant in vivo tumor growth and decreased in vitro migratory and invasive properties, revealing a beneficial effect of combination therapy that includes RRM2 inhibition to delay or abrogate tamoxifen resistance.

These findings identify a previously unknown function of Sema4A in the developing visual system and provide a useful model for understanding cell-cell interactions that occur between photoreceptors and the RPE.

TX 77843, U.S.A. With 11 figures and 7 tablesAbstract. The protozoan Perkinsus (= Dermocystidium) marinus is the most important pathogen of eastern oysters (Crassostrea vzrginicu) in the Gulf of Mexico. Prevalence of P. marinus has been related to salinity and temperature, with low temperatures and salinities usually limiting infection. In 1986, a yearly monitoring program was begun to describe the regional distribution and yearly trends in P. marinus prevalence and infection intensity in the Gulf of Mexico in connection with NOAA's Mussel Watch program. Between 1986 and 1989, prevalence and infection intensity dropped in the southeastern and southwestern Gulf, infection intensity most strongly, and rose in the Florida panhandle, prevalence most strongly. Infection intensity fell but prevalence rose on both sides of the Mississippi delta; centraynorth Texas remained essentially unchanged. The regional and temporal distribution of P. marinus in the Gulf of Mexico can be considered a product of two spatiotemporal phenomena. (1) A relatively stable spatial pattern exists each year with centers of infection on the order of 300 km. (2) A concordance in yearly shifts in prevalence and infection intensity occurs among sites on a scale of 1,000km. The spatial scale of concordant yearly changes is much larger than the scale of centers of infection, and probably originates in broad shifts in weather patterns as they affect temperature and salinity (via rainfall and river runoff). Long-term climatic changes are most likely responsible for these spatio-temporal shifts and, as such, P. marinus prevalence and infection intensity may eventually be predictable from climatic models. Our data demonstrate the importance of multi-year cycles, not just seasonal cycles and occasional heavy rains, in determining P. marinus prevalence and implicate salinity as the primary mediating factor. ProblemThe protozoan Perkinsus (= Dermocystidium) marinus (see PERKINS, 1988) is the most important pathogen of eastern oysters (Crassostrea virginica) in the U. S.

The hydrophobicity of many chemotherapeutic agents usually results in their nonselective passive distribution into healthy cells and organs causing collateral toxicity. Ligand-targeted drugs (LTDs) are a promising class of targeted anticancer agents. The hydrophilicity of the targeting ligands in LTDs limits its nonselective passive tissue distribution and toxicity to healthy cells. In addition, the small size of LTDs allows for better tumor penetration, especially in the case of solid tumors. However, the short circulation half-life of LTDs, due to their hydrophilicity and small size, remains a significant challenge for achieving their full therapeutic potential. Therefore, extending the circulation half-life of targeted chemotherapeutic agents while maintaining their hydrophilicity and small size will represent a significant advance toward effective and safe cancer treatment. Here, we present a new approach for enhancing the safety and efficacy of targeted chemotherapeutic agents. By endowing hydrophobic chemotherapeutic agents with a targeting moiety and a hydrophilic small molecule that binds reversibly to the serum protein transthyretin, we generated small hydrophilic drug conjugates that displayed enhanced circulation half-life in rodents and selectivity to cancer cells. To the best of our knowledge, this is the first demonstration of a successful approach that maintains the small size and hydrophilicity of targeted anticancer agents containing hydrophobic payloads while at the same time extending their circulation half-life. This was demonstrated by the superior in vivo efficacy and lower toxicity of our conjugates in xenograft mouse models of metastatic prostate cancer.