Show Me the Money: An Empirical Analysis of Interest Group Opposition to Federal Courts of Appeals Nominees

Contemporary views of the federal judicial appointment process are grounded in themes of obstruction and gridlock. Within this environment, interest groups find fertile ground to target, and sometimes successfully oppose, judicial nominees that once automatically moved through the appointment process and ended in confirmation. While interest group involvement and influence is an accepted fact, much less is known about the efficacy of these groups in carrying out their objective of correctly identifying ideological outlier nominees. This article asks the question: Do interest groups correctly identify and target nominees who are ideological outliers? The article implements a research design that evaluates whether those nominees opposed by interest groups are substantively different than arguably similar but unopposed nominees. The article adopts alternative theories of interest group motivations within the screening role: 1) policy promotion, and 2) group maintenance. Using matched-pair cohorts from the population of Clinton and W. Bush Administration appointments to the United States Courts of Appeals the article compares the dissenting behavior of the matched pairs. The expectation is that, if interest groups are correctly opposing outlier nominees, those who are confirmed despite opposition, should demonstrate outlier behavior in decision making, particularly in their dissenting behavior. Do opposing interest groups accurately identify the most ideologically extreme nominees? The answer is a discernible no. We conclude that there are no substantive differences between the dissenting behavior of targeted and untargeted nominees. Perhaps more interesting, the true relationship might actually be reversed, and controversial nominees are less likely to dissent (and to dissent in salient policy issue areas), than similar non-controversial nominees. These findings call into question the function of interest groups in the confirmation process. The assumption is that these groups are identifying ideological outliers and taking steps to prevent those nominees from being confirmed. This article undermines that thesis and proposes that groups actually target nominees in a way that best serves to increase the membership and financial well-being of the group instead

The Effects of Survey Nonresponse and Proxy Response on Measures of Employment for Persons with Disabilities

Abstract If many people do not respond to surveys, and those who do not respond are different from those who do, then survey estimates may be biased. This study examines potential bias in employment statistics for persons with disabilities arising from differences in the survey response patterns between persons with and without disabilities. Several types of response rate are considered: contact, cooperation, and self-response (vice proxy response). Also, several types of disability are considered: mobility, mental, seeing, hearing, and MR/DD/LD. The data are from the National Health Interview Surveys of 1994 and 1995, including the National Health Interview Survey on Disability, Phase 1 and Phase 2. Based on the evidence of this study, there is little reason to believe that household survey-based employment statistics for persons with disability are significantly biased by nonresponse or proxy response of respondents with disabilities

IgG light chain-independent secretion of heavy chain dimers: consequence for therapeutic antibody production and design

Rodent monoclonal antibodies with specificity towards important biological targets are developed for therapeutic use by a process of humanisation. This process involves the creation of molecules, which retain the specificity of the rodent antibody but contain predominantly human coding sequence. Here we show that some humanised heavy chains can fold, form dimers and be secreted even in the absence of light chain. Quality control of recombinant antibody assembly in vivo is thought to rely upon folding of the heavy chain CH1 domain. This domain acts as a switch for secretion, only folding upon interaction with the light chain CL domain. We show that the secreted heavy-chain dimers contain folded CH1 domains and contribute to the heterogeneity of antibody species secreted during the expression of therapeutic antibodies. This subversion of the normal quality control process is dependent upon the heavy chain variable domain, is prevalent with engineered antibodies and can occur when only the Fab fragments are expressed. This discovery will impact on the efficient production of both humanised antibodies as well as the design of novel antibody formats

The molecular mechanisms underlying BiP-mediated gating of the Sec61 translocon of the endoplasmic reticulum

The Sec61 translocon of the endoplasmic reticulum membrane forms an aqueous pore that is gated by the lumenal Hsp70 chaperone BiP. We have explored the molecular mechanisms governing BiP-mediated gating activity, including the coupling between gating and the BiP ATPase cycle, and the involvement of the substrate-binding and J domain–binding regions of BiP. Translocon gating was assayed by measuring the collisional quenching of fluorescent probes incorporated into nascent chains of translocation intermediates engaged with microsomes containing various BiP mutants and BiP substrate. Our results indicate that BiP must assume the ADP-bound conformation to seal the translocon, and that the reopening of the pore requires an ATP binding–induced conformational change. Further, pore closure requires functional interactions between both the substrate-binding region and the J domain–binding region of BiP and membrane proteins. The mechanism by which BiP mediates translocon pore closure and opening is therefore similar to that in which Hsp70 chaperones associate with and dissociate from substrates

The ICIDH-2: Developments for a new era of outcomes research

ABSTRACT. Gray DB, Hendershot GE. The ICIDH-2: developments for a new era of outcomes research. Arch Phys Med Rehabil 2000;81 Suppl 2:S10-S14. This article reviews the important concepts that led to the development of the International Classification of Impairments, Disabilities, and Handicaps (ICIDH), explicates the International Classification of Functioning and Disability (ICIDH-2), and discusses implications of the ICIDH-2 as a conceptual framework for outcome measures. The original ICIDH opened the door to include factors outside the traditional classification boundaries of disease, illness, and functional limitations that have framed the concept of disability. The new factors in the ICIDH-2 include a dimension for participation in social activities and a listing of environmental factors that are important for understanding the complexity of disability. The ICIDH-2 offers an opportunity for building a consensus on the terms used to describe disability and on the scope of factors to include in studying disability

Targeted deletion of Hand2 in cardiac neural crest-derived cells influences cardiac gene expression and outflow tract development

AbstractThe basic helix–loop–helix DNA binding protein Hand2 has critical functions in cardiac development both in neural crest-derived and mesoderm-derived structures. Targeted deletion of Hand2 in the neural crest has allowed us to genetically dissect Hand2-dependent defects specifically in outflow tract and cardiac cushion independent of Hand2 functions in mesoderm-derived structures. Targeted deletion of Hand2 in the neural crest results in misalignment of the aortic arch arteries and outflow tract, contributing to development of double outlet right ventricle (DORV) and ventricular septal defects (VSD). These neural crest-derived developmental anomalies are associated with altered expression of Hand2-target genes we have identified by gene profiling. A number of Hand2 direct target genes have been identified using ChIP and ChIP-on-chip analyses. We have identified and validated a number of genes related to cell migration, proliferation/cell cycle and intracellular signaling whose expression is affected by Hand2 deletion in the neural crest and which are associated with development of VSD and DORV. Our data suggest that Hand2 is a multifunctional DNA binding protein affecting expression of target genes associated with a number of functional interactions in neural crest-derived cells required for proper patterning of the outflow tract, generation of the appropriate number of neural crest-derived cells for elongation of the conotruncus and cardiac cushion organization. Our genetic model has made it possible to investigate the molecular genetics of neural crest contributions to outflow tract morphogenesis and cell differentiation

Analysis and design of a slotless tubular permanent magnet actuator for high acceleration applications

This paper presents the design of a linear actuator for high acceleration applications. In the analysis, a slotless tubular permanent magnet actuator is modeled by means of semianalytical field solutions. Several slotless topologies are modeled and compared to achieve the highest acceleration. A design has been proposed and built, and measurements are conducted to verify the model