284 research outputs found
Corruption and bicameral reforms
During the last decade unicameral proposals have been put forward in fourteen US states. In this paper we analyze the effects of the proposed constitutional reforms, in a setting where decision making is subject to ‘hard time constraints’, and lawmakers face the opposing interests of a lobby and the electorate. We show that bicameralism might lead to a decline in the lawmakers’ bargaining power vis-a-vis the lobby, thus compromising their accountability to voters. Hence, bicameralism is not a panacea against the abuse of power by elected legislators and the proposed unicameral reforms could be effective in reducing corruption among elected representatives
Enhanced cartilage regeneration in MIA/CD-RAP deficient mice
Melanoma inhibitory activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from chondrocytes. It was identified as the prototype of a family of extracellular proteins adopting an SH3 domain-like fold. In order to study the consequences of MIA/CD-RAP deficiency in detail we used mice with a targeted gene disruption of MIA/CD-RAP (MIA−/−) and analyzed cartilage organisation and differentiation in in vivo and in vitro models. Cartilage formation and regeneration was determined in models for osteoarthritis and fracture healing in vivo, in addition to in vitro studies using mesenchymal stem cells of MIA−/− mice. Interestingly, our data suggest enhanced chondrocytic regeneration in the MIA−/− mice, modulated by enhanced proliferation and delayed differentiation. Expression analysis of cartilage tissue derived from MIA−/− mice revealed strong downregulation of nuclear RNA-binding protein 54-kDa (p54nrb), a recently described modulator of Sox9 activity. In this study, we present p54nrb as a mediator of MIA/CD-RAP to promote chondrogenesis. Taken together, our data indicate that MIA/CD-RAP is required for differentiation in cartilage potentially by regulating signaling processes during differentiation
Presence of HER4 associates with increased sensitivity to Herceptin™ in patients with metastatic breast cancer
Proportional Payoffs in Legislative Bargaining with Weighted Voting: A Characterization
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A practitioner's guide to Bayesian estimation of discrete choice dynamic programming models
This paper provides a step-by-step guide to estimating infinite horizon discrete choice dynamic programming (DDP) models using a new Bayesian estimation algorithm (Imai et al., Econometrica 77:1865–1899, 2009a) (IJC). In the conventional nested fixed point algorithm, most of the information obtained in the past iterations remains unused in the current iteration. In contrast, the IJC algorithm extensively uses the computational results obtained from the past iterations to help solve the DDP model at the current iterated parameter values. Consequently, it has the potential to significantly alleviate the computational burden of estimating DDP models. To illustrate this new estimation method, we use a simple dynamic store choice model where stores offer “frequent-buyer” type rewards programs. Our Monte Carlo results demonstrate that the IJC method is able to recover the true parameter values of this model quite precisely. We also show that the IJC method could reduce the estimation time significantly when estimating DDP models with unobserved heterogeneity, especially when the discount factor is close to 1
Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients
INTRODUCTION: The HER (human EGFR related) family of receptor tyrosine kinases (HER1/EGFR (epidermal growth factor receptor)/c-erbB1, HER2/c-erbB2, HER3/c-erbB3 and HER4/c-erbB4) shares a high degree of structural and functional homology. It constitutes a complex network, coupling various extracellular ligands to intracellular signal transduction pathways resulting in receptor interaction and cross-activation. The most famous family member is HER2, which is a target in Herceptin therapy in metastatic status and also in adjuvant therapy of breast cancer in the event of dysregulation as a result of gene amplification and resulting protein overexpression. The HER2-related HER receptors have been shown to interact directly with HER2 receptors and thereby mutually affect their activity and subsequent malignant growth potential. However, the clinical outcome with regard to total HER receptor state remains largely unknown. METHODS: We investigated HER1-HER4, at both the DNA and the protein level, using fluorescence in situ hybridisation (FISH) probes targeted to all four receptor loci and also immunohistochemistry in tissue microarrays derived from 278 breast cancer patients. RESULTS: We retrospectively found HER3 gene amplification with a univariate negative impact on disease-free survival (hazard ratio 2.35, 95% confidence interval 1.08 to 5.11, p = 0.031), whereas HER4 amplification showed a positive trend in overall and disease-free survival. Protein expression revealed no additional information. CONCLUSION: Overall, the simultaneous quantification of HER3 and HER4 receptor genes by means of FISH might enable the rendering of a more precise stratification of breast cancer patients by providing additional prognostic information. The continuation of explorative and prospective studies on all HER receptors will be required for an evaluation of their potential use for specific therapeutic targeting with respect to individualised therapy
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