This chapter surveys sociological approaches to the study of job authority, including theoretical foundations, measurement, and emergence as an important dimension of social inequality. The focus here is mainly on studies of race and gender differences in the determinants of authority and the consequences of race and gender differences in authority for income. Despite significant advancements in the overall socioeconomic status of minorities and working women, race and gender remain important impediments to their attainment of authority. This pattern, which is consistent and robust in state-level, national, cross-national, and cross-temporal studies, is sustained net of an incumbent's human capital investments and structural location within and between several economic units. Following a review of the predominant explanations for gender and racial disparities in job authority is the conclusion that the most promising explanations for persistent racial and gender disparities in authority concern the racial and gender demography of the workplace and the tendency on the part of authority elites to reproduce themselves through both exclusionary and inclusionary processes. Suggestions for future research include additional delineation of these processes based on samples of multiple racial/ethnic groups of men and women and studies that synthesize quantitative and qualitative approaches to understanding the effects of employer and employee attitudes/preferences and practices on the authority attainment process.

Survey data support hypotheses regarding differential access to workplace power among women and minorities relative to white men. Specific findings indicate that, relative to white men, all groups encounter increasing inequality at higher levels of power, but only black women seem to experience this form of inequality as a result of direct discrimination. Further analysis indicates that network assistance is more a response to this form of discrimination than an indirect cause. Finally, analysis shows that most groups attain power through homosocial reproduction, but what differs is the opportunity to engage in such reproduction, wherein white men excel. These findings imply that while women and minorities face lower odds than white men of achieving higher levels of workplace power, the reasons for this disadvantage vary among respective groups and thus will likely require different remedies.

Sphingosine kinases (SKs) are promising new therapeutic targets for cancer because they regulate the balance between pro-apoptotic ceramides and mitogenic sphingosine-1-phosphate. The functions of the two SK isoenzymes, SK1 and SK2, are not redundant, with genetic ablation of SK2 having more pronounced anticancer effects than removal of SK1. Although several small molecule inhibitors of SKs have been described in the literature, detailed characterization of their molecular and cellular pharmacology, particularly their activities against human SK1 and SK2, have not been completed. Computational modeling of the putative active sites of SK1 and SK2 suggests structural differences that might allow isozyme-selective inhibitors. Therefore, we characterized several SK-inhibitory compounds which revealed differential inhibitory effects on SK1 and SK2 as follows: SKI-II and ABC294735 are SK1/2-dual inhibitors; CB5468139 is a SK1-selective inhibitor; and ABC294640 is a SK2-selective inhibitor. We examined the effects of the SK inhibitors on several biochemical and phenotypic processes in A498 kidney adenocarcinoma cells. The SK2-selective inhibitor ABC294640 demonstrated the most pronounced effects on SK1 and SK2 mRNA expression, decrease of S1P levels, elevation of ceramide levels, cell cycle arrest, and inhibition of proliferation, migration and invasion. ABC294640 also down-regulated the expression or activation of several signaling proteins, including STAT3, AKT, ERK, p21, p53 and FAK. These effects were equivalent or superior to responses to the SK1/2-dual inhibitors. Overall, these results suggest that inhibition of SK2 results in stronger anticancer effects than does inhibition of SK1 or both SK1 and SK2.

Research on minority authority attainment tends to stress top-down processes of social closure, whereby the dominant social group produces and preserves positions of power and in uence byOne explanation for why racial and ethnic minorities are relatively unlikely to occupy positions of authority in U.S. workplaces is that, like all groups, those in power tend to prefer others like themselves, especially when relations of trust are at stake (Baron and Pfeffer 1994;Kanter 1977; Pfeffer and Salancik 1978:146;Salancik and Pfeffer 1978). Because whites have historically been the primary decision makers in organizations, they bene t most from this ingroup preference, leaving minorities under-represented in positions of authority. Kanter (1977) refers to this process as "homosocial reproduction," whereby the group in charge reproduces its ascriptive characteristics in those they select to join them (see also, Bergmann 1986; Brewer and Brown 1998:567).While we do not dispute this "top-down" process of ascription, we believe that it is incomplete, especially when it comes to understanding opportunities for minority authority attainment. In addition to top-down ascription, we believe that pressures for "bottom-up" ascription also play a key role, whereby the race and ethnicity of lower-level supervisors are matched to the numerically dominant race and ethnicity of their subordinates. As a result, blacks are much more likely to gain authority over largely black work groups; Latinos are much more likely to gain authority over largely Latino work groups; and so forth. In drawing attention to this process, we do not claim that top-down ascription is unimportant, but rather that pressures for bottom-up ascription push against it to shape when and where authority opportunities are likely to arise for minority workers.Data for this analysis come primarily from the Multi-City Study of Urban Inequality (MCSUI) and are available from the Inter-University Consortium for Political and Social Research (ICPSR) at the University of Michigan. Direct all correspondence to: James R. Elliott, Department of Sociology, 220 Newcomb Hall, Tulane University, New Orleans, LA 70118. E-mail: jre@tulane.edu. Ethnic Matching 259Broadly speaking, our objectives in advancing this argument are twofold. First, we wish to provide further intellectual support to the idea that labor market opportunities depend not just on individual human capital, but also on group membership. In other words, we advocate a contextual approach to understanding social mobility in which the causal dynamics of authority attainment are embedded in group composition. Second, we wish to provide a corrective to the traditional assumption, based on identity theory and truncated interpretations of homosocial reproduction, that elites only reproduce themselves. We argue that the closer one gets to elite status, the more powerful forces of top-down ascription become, but that forces of bottom-up ascription can also be very powerful at lower levels of work organization, where out-group ...

The covalent attachment of palmitate to specific proteins by the action of palmitoyl acyltransferases (PAT) plays critical roles in the biological activities of several oncoproteins. Two PAT activities are expressed by human cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found in H-and N-Ras, and type 2 PATs that modify the myristoyl-dependent palmitoylation motif found in the Src family of tyrosine kinases. We have previously shown that the type 1 PAT HIP14 causes cellular transformation. In the current study, we show that mRNA encoding HIP14 is up-regulated in a number of types of human tumors. To assess the potential of HIP14 and other PATs as targets for new anticancer drugs, we developed three cell-based assays suitable for highthroughput screening to identify inhibitors of these enzymes. Using these screens, five chemotypes, with activity toward either type 1 or type 2 PAT activity, were identified. The activity of the hits were confirmed using assays that quantify the in vitro inhibition of PAT activity, as well as a cell-based assay that determines the abilities of the compounds to prevent the localization of palmitoylated green fluorescent proteins to the plasma membrane. Representative compounds from each chemotype showed broad antiproliferative activity toward a panel of human tumor cell lines and inhibited the growth of tumors in vivo. Together, these data show that PATs, and HIP14 in particular, are interesting new targets for anticancer compounds, and that small molecules with such activity can be identified by high-throughput screening.

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The ceramide/sphingosine-1-phosphate (S1P) rheostat has been hypothesized to play a critical role in regulating tumor cell fate, with elevated levels of ceramide inducing death and elevated levels of S1P leading to survival and proliferation. Ceramidases are key enzymes that control this rheostat by hydrolyzing ceramide to produce sphingosine, and may also confer resistance to drugs and radiation. Therefore, ceramidase inhibitors have excellent potential for development as new anticancer drugs. In this study, we identify a novel ceramidase inhibitor (Ceranib-1) by screening a small molecule library and describe the synthesis of a more potent analog (Ceranib-2). In a cell-based assay, both compounds were found to inhibit cellular ceramidase activity toward an exogenous ceramide analog, induce the accumulation of multiple ceramide species, decrease levels of sphingosine and S1P, inhibit the proliferation of cells alone and in combination with paclitaxel, and induce cell cycle arrest and cell death. In vivo, Ceranib-2 was found to delay tumor growth in a syngeneic tumor model without hematologic suppression or overt signs of toxicity. These data support the selection of ceramidases as suitable targets for anticancer drug development, and provide the first non-lipid inhibitors of human ceramidase activity.

Previous research has shown that delays in pediatric anterior cruciate ligament (ACL) reconstruction are associated with increased prevalence of concomitant knee injuries and worse outcomes following surgery. However, few studies have described factors that may contribute to these delays and adverse outcomes. This study seeks to determine the effect of socioeconomic status on clinical outcomes following ACL reconstruction.A retrospective review of patients who underwent primary ACL reconstruction at a tertiary pediatric hospital between 2009 and 2015 was conducted. Variables included chronologic, demographic, and socioeconomic data, and postoperative complications. Socioeconomic status was measured using health insurance type and median household income levels derived from 2009 to 2015 US Census Bureau.A total of 127 patients (69 male, 58 female) were included. The mean age at time of surgery was 15.0 years. Overall, 68 patients had commercial insurance and 59 patients had government-assisted insurance. The mean household median income for patients with commercial insurance was $87,767 compared to $51,366 for patients with government-assisted insurance. Patients with government-assisted insurance plans demonstrated greater delays in time from injury to initial orthopaedic evaluation (P = .0003), injury to magnetic resonance imaging (MRI) examination (P = .021), injury to surgery (P < .0001), initial orthopaedic evaluation to surgery (P = .0036), and injury to return to play clearance, P = .044. Median household income was significantly related to time from injury to MRI examination (P = .0018), injury to surgery (P = .0017), and initial orthopaedic evaluation to surgery (P = .039). Intraoperatively, 81% of patients with government-assisted insurance had concomitant meniscal injuries compared 65% of patients with commercial insurance, P = .036. Postoperatively, 22% of patients with government-assisted insurance were found to have decreased knee range of motion (“stiffness”) compared to 9% of patients with commercial insurance, P = .034.Pediatric patients who have government-assisted plans may experience delays in receiving definitive injury management and be at risk for postoperative complications. Our findings suggest a significant discrepancy in time to treatment as well as rates of concomitant knee injuries and postoperative complications between government and commercial insurance types.Level of Evidence: III