Intra-Household Consumption Patterns: Issues, Evidence and Implications for Human Development

human development, consumption, globalization

Financing strategy for achievement of the MDGs and implementation of the Tenth Five Year Plan.

This working paper presents an analysis of the strategy required to generate the required resources for investment in various services necessary to achieve the MDGs. The analysis attempts to quantify the fiscal space to finance the MDGs and identify the necessary fiscal reforms required to finance the MDGs in a sustainable manner. The next section outlines the analytical framework used to determine the potential for expanding fiscal space in an economy. Section 3 makes an assessment of overall financing requirements for achieving the MDGs and compares it with the Tenth Plan outlay. Section 4 explores the prospects of domestic revenue mobilisation. Section 5 analyses expenditure trends, its consistency with MDG costing requirements and explores the scope for creating fiscal space by improving efficiency and reprioritisation. Section 6 considers the role of ODA and examines the scope for borrowings (both external and domestic) and section 7 deals with the possibilities of enhancing fiscal space through private sources (FDI, households, public-private partnerships). The last section presents the concluding remarks.

Financing Strategy for Achievement of the MDGs and Implementation of the Tenth Five Year Plan

This report presents an analysis of the strategy required to generate the required resources for investment in various services necessary to achieve the MDGs. The analysis attempts to quantify the fiscal space to finance the MDGs and identify the necessary fiscal reforms required to finance the MDGs in a sustainable manner. The next section outlines the analytical framework used to determine the potential for expanding fiscal space in an economy. Section 3 makes an assessment of overall financing requirements for achieving the MDGs and compares it with the Tenth Plan outlay. Section 4 explores the prospects of domestic revenue mobilisation. Section 5 analyses expenditure trends, its consistency with MDG costing requirements and explores the scope for creating fiscal space by improving efficiency and reprioritisation. Section 6 considers the role of ODA and examines the scope for borrowings (both external and domestic) and section 7 deals with the possibilities of enhancing fiscal space through private sources (FDI, households, public-private partnerships). The last section presents the concluding remarks.MDGs, Fiscal Space Diamond, Domestic Revenue Mobilisation, public expenditure

Macroeconomic vulnerability in developing countries: Approaches and issues

Economic vulnerability is approached from micro- and macroeconomic perspectives. While the microeconomic perspective is concerned with the impact of shocks on the well-being of individual households, the macroeconomic perspective focuses on the impact of these shocks on economic growth. This paper reviews the literature on macroeconomic vulnerability and finds that there is no single approach to understanding macroeconomic vulnerability in the context of financial and economic crises in developing countries. It identifies the critical contributions of different studies on macroeconomic vulnerability and appraises their main differences. The paper then proposes elements for a more comprehensive framework of macroeconomic vulnerability for developing countries. In a world where shocks and crises are becoming more frequent, the imperative for countries to build resilience and protect themselves from development reversals has become all the more urgent. Not surprisingly, addressing macroeconomic vulnerability has become an important aspect of the international development agenda

Identification of novel small molecule Beclin 1 mimetics activating autophagy

Anti-apoptotic proteins Bcl-2 and Bcl-xL could block autophagy by binding to Beclin 1 protein, an essential inducer of autophagy. Compounds mimicking Beclin 1 might be able to disrupt Bcl-xL/2-Beclin 1 interaction, free out Beclin 1, and thus trigger autophagy. In order to identify small molecule Beclin 1 mimetics, a fluorescence polarization-based high-throughput screening of 50,316 compounds was carried out with a Z’ score of 0.82 ± 0.05, and an outcome of 58 hits. After the structure analysis, three acridine analogues were unveiled and confirmed using the fluorescence polarization assay and the surface plasmon resonance assay. Moreover, a set of 17 additional acridine analogues was prepared and tested. Compound 7 showed selectivity for Bcl-xL (KD = 6.5 μM) over Bcl-2 (KD = 160 μM) protein, and potent cytotoxicity (nanomolar scale) in PC-3, PC-3a and DU145 prostate cancer cells. Furthermore, induction of autophagy was also demonstrated in PC-3 and PC-3a cells treated with some acridine compounds by LC3 conversion immunoblotting and LC3 fluorescence microscopy. These Beclin 1 mimetics will be invaluable tools for developing novel autophagy inducers, better understanding the roles of autophagy in cancer, and will contribute to cancer therapy

Type I interferons modulate vascular function, repair, thrombosis, and plaque progression in murine models of lupus and atherosclerosis

Objective Patients with systemic lupus erythematosus (SLE) have a notable increase in atherothrombotic cardiovascular disease (CVD) which is not explained by the Framingham risk equation. In vitro studies indicate that type I interferons (IFNs) may play prominent roles in increased CV risk in SLE. However, the in vivo relevance of these findings, with regard to the development of CVD, has not been characterized. This study was undertaken to examine the role of type I IFNs in endothelial dysfunction, aberrant vascular repair, and atherothrombosis in murine models of lupus and atherosclerosis. Methods Lupus‐prone New Zealand mixed 2328 (NZM) mice and atherosclerosis‐prone apolipoprotein E– knockout (apoE −/− ) mice were compared to mice lacking type I IFN receptor (INZM and apoE −/− IFNAR −/− mice, respectively) with regard to endothelial vasodilatory function, endothelial progenitor cell (EPC) function, in vivo neoangiogenesis, plaque development, and occlusive thrombosis. Similar experiments were performed using NZM and apoE −/− mice exposed to an IFNα‐containing or empty adenovirus. Results Loss of type I IFN receptor signaling improved endothelium‐dependent vasorelaxation, lipoprotein parameters, EPC numbers and function, and neoangiogenesis in lupus‐prone mice, independent of disease activity or sex. Further, acute exposure to IFNα impaired endothelial vasorelaxation and EPC function in lupus‐prone and non–lupus‐prone mice. Decreased atherosclerosis severity and arterial inflammatory infiltrates and increased neoangiogenesis were observed in apoE −/− IFNAR −/− mice, compared to apoE −/− mice, while NZM and apoE −/− mice exposed to IFNα developed accelerated thrombosis and platelet activation. Conclusion These results support the hypothesis that type I IFNs play key roles in the development of premature CVD in SLE and, potentially, in the general population, through pleiotropic deleterious effects on the vasculature.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93543/1/34504_ftp.pd

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin