7,664 research outputs found
Exact Statistical Characterization of Gram Matrices with Arbitrary Variance Profile
This paper is concerned with the statistical properties of the Gram matrix
, where is a
complex central Gaussian matrix whose elements have arbitrary variances. With
such arbitrary variance profile, this random matrix model fundamentally departs
from classical Wishart models and presents a significant challenge as the
classical analytical toolbox no longer directly applies. We derive new exact
expressions for the distribution of and that of its eigenvalues by
means of an explicit parameterization of the group of unitary matrices. Our
results yield remarkably simple expressions, which are further leveraged to
study the outage data rate of a dual-antenna communication system under
different variance profiles.Comment: 6 pages, 1 figure, 1 tabl
Incentive Effects of Retirement Income Transfers
The paper explores the incentive effects of retirement income transfers – essentially, non-contributory cash transfers aimed at reducing poverty among the elderly. A literature review reveals how little academic analysis of the impact of these transfers has been completed. We begin with a taxonomy of retirement income transfers, differentiating between ex-ante and ex-post interventions and universal and targeted arrangements. This distinction allows important differences across designs to be highlighted. We then provide a simple framework for thinking about what the incentive impacts of the transfers might be, distinguishing between effects related to the transfer itself and those related to the financing mechanism. Thus, from theory and available empirical evidence we derive a few policy relevant findings. First, incentive effects will depend on the level of the transfer relative to average earnings and the degree of integration between the formal and informal sectors in the economy. In general, for modest transfers, negative impacts on savings and labor supply would be contained. Second, we highlight the tradeoff between maintaining low effective marginal tax rates (EMTRs) to reduce distortions and keeping the program costs at affordable levels. This tradeoff suggests that universal programs are suboptimal. Third, in terms of design features, we emphasize the importance of implementing a gradual withdrawal of the benefit to avoid crowding-out contributory pensions among low income individuals and of indexing the eligibility age with life expectancy to contain costs. Finally we find that matching contributions can be a promising instrument to promote savings among individuals with limited savings capacity.Social pensions, Pension coverage, Retirement Insurance, matching contributions
Social Protection of Older People
Social protection is a major arena of government activity aimed at ensuring that vulnerable population groups receive appropriate and effective public support to ensure their financial security and to safeguard their health. However, despite the growth and extent of social protection programs in both developed and developing countries, most emerging economies have nascent systems and only a small portion of all such efforts address the specific vulnerabilities and needs of older people. This paper (a) discusses the vulnerabilities of older people and the benefits of crafting social programs to address them; (b) describes the nature of social protection and the forms it can take to address those vulnerabilities; (c) reports descriptive evidence on the availability and use of social protection programs; and (d) delineates steps that can be taken to remedy the shortfalls experienced by older people.aging, social protection
Recent Developments: State v. Williams: A Traffic Stop Will Be Constitutionally Permissible if It Is Based on Observations of a Police Officer That Give Reasonable Articulable Suspicion That a Traffic Law Has Been Violated
Recent Developments: State v. Williams: A Traffic Stop Will Be Constitutionally Permissible if It Is Based on Observations of a Police Officer That Give Reasonable Articulable Suspicion That a Traffic Law Has Been Violated
Transcriptional inhibition of type I collagen gene expression in scleroderma fibroblasts by the antineoplastic drug ecteinascidin 743.
We previously showed that COL1A1 expression is up-regulated at the transcriptional level in systemic sclerosis (SSc) fibroblasts and that the CCAAT-binding factor (CBF) is involved in this increased expression. Ecteinascidin 743 (ET-743) is a chemotherapeutic agent that binds with sequence specificity to the minor groove of DNA and inhibits CBF-mediated transcriptional activation of numerous genes. Therefore, we examined the effects of ET-743 on the increased COL1A1 expression in SSc fibroblasts. The drug caused a potent and dose-dependent inhibition of type I collagen biosynthesis, which reached 70-90% at 700 pM without affecting cell viability. The same drug concentration caused 60-80% reduction in COL1A1 mRNA levels. The stability of the corresponding transcripts was not affected. In vitro nuclear transcription assays demonstrated a 54% down-regulation of COL1A1 transcription. Transient transfections with COL1A1 promoter constructs containing the specific CBF binding sequence into SSc cells previously treated with 700 pM ET-743 failed to show an effect on COL1A1 promoter activity. Furthermore, ET-743 did not affect the binding of CBF or Sp1 transcription factors to their cognate COL1A1 elements. However, treatment with 700 pM ET-743 of stably transfected NIH 3T3 cells expressing a human type II procollagen gene under the control of the human COL1A1 promoter caused a greater than 50% reduction in the production of type II procollagen and a similar decrease in the corresponding type II procollagen transcripts. These results indicate that ET-743 is a potent inhibitor of COL1A1 transcription. However, this effect cannot be explained by a direct effect on CBF binding to the COL1A1 promoter. Although the exact mechanisms responsible for the transcriptional inhibition of COL1A1 by ET-743 are not apparent, our observations suggest that the drug may be an effective agent to decrease collagen overproduction in SSc and other fibrotic diseases
Modulation of TGF-beta signaling by proinflammatory cytokines in articular chondrocytes.
OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways occurs through regulation of activity and availability of mothers against DPP (Drosophila) human homologue (Smad) proteins.
METHODS: Human articular chondrocytes isolated from knee joints from patients with osteoarthritis (OA) or normal bovine chondrocytes were cultured in suspension in poly-(2-hydroxyethyl methacrylate)-coated dishes with either 10% fetal bovine serum media or serum-deprived media 6h before treatment with IL-1beta alone, TNF-alpha alone or IL-1beta followed by TGF-beta. Nuclear extracts were examined by electrophoretic mobility-shift assays (EMSA) for nuclear factor-kappa B (NF-kappaB) and Smad3/4 deoxyribonucleic acid (DNA) binding. Nuclear extracts were also subjected to the TranSignal Protein/DNA array (Panomics, Redwood City, CA) enabling the simultaneous semiquantitative assessment of DNA-binding activity of 54 different transcription factors. Nuclear phospho-Smad2/3 and total Smad7 protein expression in whole cell lysates were studied by Western blot. Cytoplasmic Smad7, type II collagen alpha 1 (COL2A1), aggrecan and SRY-related high mobility group-Box gene 9 (SOX-9) mRNA expression were measured by real-time polymerase chain reaction (PCR).
RESULTS: The DNA-binding activity of Smad3/4 in the TranSignal Protein/DNA array was downregulated by TNF-alpha (46%) or IL-1beta treatment (42%). EMSA analysis showed a consistent reduction in Smad3/4 DNA-binding activity in human articular chondrocytes treated with IL-1beta or TNF-alpha. TGF-beta-induced Smad3/4 DNA-binding activity and Smad2/3 phosphorylation were also reduced following pretreatment with IL-1beta in human OA and bovine chondrocytes. Real-time PCR and Western blot analysis showed that IL-1beta partially reversed the TGF-beta stimulation of Smad7 mRNA and protein levels in TGF-beta-treated human OA cells. In contrast, TGF-beta-stimulated COL2A1, aggrecan, and SOX-9 mRNA levels were abrogated by IL-1beta.
CONCLUSIONS: IL-1beta or TNF-alpha exerted a suppressive effect on Smad3/4 DNA-binding activity in human articular chondrocytes, as well as on TGF-beta-induced stimulation of Smad3/4 DNA-binding activity and Smad2/3 phosphorylation in human OA and bovine articular chondrocytes. IL-1beta partially reversed the increase in TGF-beta-stimulated Smad7 mRNA or protein levels suggesting that Smad7 may not be involved in the suppression of TGF-beta signaling induced by IL-1beta or TNF-alpha in articular chondrocytes. The balance between the IL-1beta or TNF-alpha and the TGF-beta signaling pathways is crucial for maintenance of articular cartilage homeostasis and its disruption likely plays a substantial role in the pathogenesis of OA
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