KAUTILYA ON THE SCOPE AND METHODOLOGY OF ACCOUNTING, ORGANIZATIONAL DESIGN AND THE ROLE OF ETHICS IN ANCIENT INDIA

2004 ◽  
Vol 31 (2) ◽  
pp. 125-148 ◽  
Author(s):  
Balbir S. Sihag
Keyword(s):  
Economic Development ◽  
Economic Performance ◽  
Organizational Design ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Ethical Values ◽  
Allocation Of Resources ◽  
Economic Data ◽  
Ancient India

Kautilya, a 4th century B.C.E. economist, recognized the importance of accounting methods in economic enterprises. He realized that a proper measurement of economic performance was absolutely essential for efficient allocation of resources, which was considered an important source of economic development. He viewed philosophy and political science as separate disciplines but considered accounting an integral part of economics. He specified a very broad scope for accounting and considered explanation and prediction as its proper objectives. Kautilya developed bookkeeping rules to record and classify economic data, emphasized the critical role of independent periodic audits and proposed the establishment of two important but separate offices - the Treasurer and Comptroller-Auditor, to increase accountability, specialization, and above all to reduce the scope for conflicts of interest. He also linked the successful enforcement of rules and regulations to their clarity, consistency and completeness. Kautilya believed that such measures were necessary but not sufficient to eliminate fraudulent accounting. He also emphasized the role of ethics, considering ethical values as the glue which binds society and promotes economic development.

scholarly journals New approaches to achieve sustainable regional development

2013 ◽  
Vol 2 (2) ◽  
pp. 50-52
Author(s):  
József Káposzta
Keyword(s):  
Economic Development ◽  
Regional Development ◽  
Global Market ◽  
The Self ◽  
Allocation Of Resources ◽  
Resource Concentration ◽  
Global Challenges ◽  
Development Processes ◽  
Sustainable Regional Development

Abstract We are facing a transnational future. Globalization is getting more and more important in economic development, processes are becoming global, and the allocation of goods, capital and resources is carried out on the global market. In such transnational system, the role of large business centers of resource concentration is getting more significant and the ability of nations to balance the allocation of resources is getting poorer. Consequently, the micro-regions, counties and settlements need to face direct global challenges and the self-generated competition as well. Micro-regions, which are not able to adapt to the global resource market and competition, fall out of this allocation space and surely lag behind. Their future greatly depends on how they can represent their interests and how they can improve their positions.

The Industrial Politics of the Kreditbanken, 1880–1914

1977 ◽  
Vol 51 (2) ◽  
pp. 190-207 ◽  
Author(s):  
Hugh Neuburger
Keyword(s):  
Economic Development ◽  
World War I ◽  
Critical Role ◽  
Electrical Equipment ◽  
Investment Banks ◽  
German Industry ◽  
World War ◽  
Financial Strength

One of the most durable theories explaining the remarkable rise of German industry in the generation before World War I was that of the critical role of the Kreditbanken, the great commercial and investment banks of which the Deutsche Bank was the most prominent. Recently, however, historians have begun to question the power of the banks, and even to suggest that they were a drag on German economic development. In this brief study of how Georg Siemens, of the Deutsche Bank, kept the peace between the two leading German electrical equipment manufacturers, Professor Neuburger shows that the crucial factors were not merely the financial strength or weakness of the Bank, but also the diplomatic skill with which its leaders navigated the rapidly shifting currents of the era.

Axiological analysis for the role of values in person-centered healthcare

2020 ◽  
Vol 8 (2) ◽  
pp. 183
Author(s):  
James Marcum
Keyword(s):  
Human Dignity ◽  
Essential Role ◽  
Critical Role ◽  
Clinical Encounter ◽  
Vital Role ◽  
Biomedical Model ◽  
Ethical Values ◽  
Epistemic Values ◽  
Aesthetic Values

In this paper, an axiological analysis for the role of values in person-centered healthcare is undertaken from aesthetic, epistemic, and ethical perspectives, given the backdrop of a robust notion of personhood. To that end, personhood is first analyzed and conceptualized to provide a practical framework for situating the axiological analysis for the role of values, especially the value of human dignity, in healthcare. In terms of aesthetic values, beauty plays an essential role within person-centered healthcare, especially with respect to the value of wellbeing, and for providing a platform to analyze further both epistemic and ethical values in healthcare. With respect to epistemic values, truth - particularly in terms of the value of competence - plays a critical role in providing effective healthcare. In terms of ethical values, the good, especially with respect to the value of caring, plays a vital role in shaping how both clinicians and patients comport themselves in the clinical encounter. In a concluding section, the significance of the axiological analysis for the role of values in person-centered healthcare, in contrast to healthcare based on the biomedical model, is briefly discussed.

Stimulation of the Mineralocorticoid Receptor by Aldosterone Leads to Activation of HL-60 Neutrophils,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3206-3206
Author(s):  
Carlos E Vazquez ◽  
Gregory N Prado ◽  
Enrique R Maldonado ◽  
Gabriela Saca ◽  
Iren M Ortiz ◽  
...  
Keyword(s):  
Western Blot ◽  
Respiratory Burst ◽  
Mineralocorticoid Receptor ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Neutrophil Activation ◽  
Human Neutrophils ◽  
Dead Cell ◽  
Cardiovascular Morbidity And Mortality

Abstract Abstract 3206 Blockade of the mineralocorticoid receptor (MR), the receptor for aldosterone (ALDO), improves cardiovascular morbidity and mortality. There is growing evidence for a critical role of ALDO in inflammation in addition to its well-described effects on sodium homeostasis. However, the role of ALDO on neutrophil activation is not entirely clear. We studied the role of ALDO on HL-60, a human promyelocytic cell line, induced to differentiate into neutrophil-like cells by incubation for 3 days with 1.3% DMSO. We detected the presence of the mineralocorticoid receptor (MR), the receptor for ALDO, by western blot analyses and MR transcript by quantitative RT-PCR using TaqMan detection probes in these cells. Cells incubated with ALDO (10−8-10−7 M) showed a dose-dependent rise in cytosolic Ca2+ that peaked within 3 min using FURA-2AM fluorescence; an event not observed when cells were incubated with 10−8 M dexamethasone (DEXA). Consistent with these results, incubation with 10−8 M ALDO led to increases in the oxidative-respiratory burst [superoxide production] (P<0.01, n=3); an event not observed when cells were incubated with either 10−8 or 10−7 M dexamethasone. The oxidative responses to ALDO were blunted by pre-incubation of cells with 1 uM canrenoic acid (CA), a well-described MR antagonist (P<0.03, n=3). We then studied the effect of ALDO on HL-60 transmigration and observed that 2 hr incubation at 37C with 10−8 M ALDO led to augmented migration (P<0.03, n=2) when compared to vehicle as estimated by CyQuant cell migration assays. We then isolated untouched circulating human neutrophils by immunomagnetic isolation following density gradient sedimentation with PolymorphPrep from otherwise healthy subjects. Flow cytometric analyses showed greater than 97% neutrophils as these cells were positive for CD45, CD16 and CD66b. Live/dead cell automated analyses shows greater than 90% cell viability by acridine orange and propidium iodide fluorescence. These cells likewise express MR as determined by western blot analyses for MR as reported in kidney and endothelial cells. Cells incubated with ALDO (10−8 M) showed a rise in cytosolic Ca2+ and an increase in the oxidative-respiratory burst (P<0.01, n=3); a response that was sensitive to 1 uM CA. We also observed that 4 hr 10−9M ALDO incubation led to augmented neutrophil transmigration (P<0.03, n=2). Thus our results suggest that activation of MR by ALDO leads to neutrophil activation that may contribute to the inflammatory responses associated with MR activation in vivo. Disclosures: No relevant conflicts of interest to declare.

ProatherogenIc Inflamatory mRNAs Have structural Features for Being Regulated by MicroRNAs

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5316-5316
Author(s):  
Xiao-Feng Yang ◽  
Anthony Virtue ◽  
Jietang Mai ◽  
Ying Yin ◽  
Xiaohua Jiang ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Critical Role ◽  
Structural Features ◽  
Database Mining ◽  
Mirna Regulation ◽  
Inflammatory Gene Expression ◽  
Inflammatory Genes ◽  
Mining Technique ◽  
Atherosclerotic Lesions

Abstract Abstract 5316 The current literature focusing on miRNAs has failed to adequately address two important questions - how miRNAs modulate atherogenic inflammatory genes from a panoramic viewpoint and whether the augmented expression of the atherogenic inflammatory genes is the result of miRNAs suppression. To resolve these knowledge gaps, we have employed a novel database mining technique in conjunction with statistical analysis criteria established from experimentally verified miRNAs. Utilizing this strategy we were able to conclude that the expression of 33 inflammatory genes is upregulated in atherosclerotic lesions and that these genes contain structural features in the 3'UTR of their mRNA for potential miRNAs regulation. Additionally, the binding features governing the interactions between the miRNAs and the inflammatory genes were statistically identical to the features of experimentally verified miRNAs. It was also determined that 21 (64%) of the 33 inflammatory genes were targeted by highly expressed miRNAs while the remaining 12 genes (36%) were targeted by normally expressed miRNAs. In addition, 10 of the 21 highly expressed miRNA-targeted inflammatory genes (48%) were targeted by a single miRNA, suggesting miRNA regulation specificity. Furthermore, 12 (48%) out of the 25 miRNAs found to meet our criteria targeted individual inflammatory genes while the other 13 miRNAs targeted multiple inflammatory genes. These results indicate a critical role of miRNAs in regulating proatherogenic inflammatory gene expression. Disclosures: No relevant conflicts of interest to declare.

A Critical Role of Mir-9 in Myelopoesis and EVI1-Induced Leukemogenesis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2332-2332
Author(s):  
Vitalyi Senyuk ◽  
Yunyuan Zhang ◽  
Yang Liu ◽  
Ming Ming ◽  
Jianjun Chen ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Ectopic Expression ◽  
Myeloid Differentiation ◽  
Dna Hypermethylation ◽  
Hematopoietic Stem

Abstract Abstract 2332 MicroRNA-9 (miR-9) is required for normal neurogenesis and organ development. The expression of miR-9 is altered in several types of solid tumors suggesting that it may have a function in cell transformation. However the role of this miR in normal hematopoiesis and leukemogenesis is unknown. Here we show that miR-9 is expressed at low levels in hematopoietic stem/progenitor cells (HSCs/HPCs), and that it is upregulated during hematopoietic differentiation. Ectopic expression of miR-9 strongly accelerates terminal myelopoiesis, while promoting apoptosis in vitro and in vivo. In addition, the inhibition of miR-9 in HPC with a miRNA sponge blocks myelopoiesis. EVI1, required for normal embryogenesis, and is considered an oncogene because inappropriate upregulation induces malignant transformation in solid and hematopoietic cancers. In vitro, EVI1 severely affects myeloid differentiation. Here we show that EVI1 binds to the promoter of miR-9–3 leading to DNA hypermethylation of the promoter as well as repression of miR-9. We also show that ectopic miR-9 reverses the myeloid differentiation block that is induced by EVI1. Our findings suggest that inappropriately expressed EVI1 delays or blocks myeloid differentiation, at least in part by DNA hypermethylation and downregulation of miR-9. It was previously reported that FoxOs genes inhibit myeloid differentiation and prevent differentiation of leukemia initiating cells. Here we identify FoxO3 and FoxO1 as new direct targets of miR-9 in hematopoietic cells, and we find that upregulation of FoxO3 in miR-9-positive cells reduces the acceleration of myelopoiesis. These results reveal a novel role of miR-9 in myelopoiesis and in the pathogenesis of EVI1-induced myeloid neoplasms. They also provide new insights on the potential chromatin-modifying role of oncogenes in epigenetic changes in cancer cells. Disclosures: No relevant conflicts of interest to declare.

PRMT5 Methyltransferase Activity Is Required to Sustain Adult Hematopoiesis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4335-4335
Author(s):  
Fan LIU ◽  
Guoyan Cheng ◽  
Fabiana Perna ◽  
Xu Haiming ◽  
Pierre-Jacques Hamard ◽  
...  
Keyword(s):  
Cell Biology ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Conditional Knockout ◽  
Major Type ◽  
Cytokine Signaling ◽  
Methyltransferase Activity ◽  
Hematopoietic Stem ◽  
Arginine Residues

Abstract Epigenetic regulators have been shown to play critical roles in normal hematopoiesis, and their activity is frequently altered in hematopoietic cancers. Protein arginine methyltransferase 5 (PRMT5) is the major type II PRMTs, catalyzing the symmetric di-methylation of arginine residues in histones (H2A, H3 and H4) and non-histone proteins. PRMT5 is over-expressed in several cancers, including acute leukemia and non-Hodgkin’s lymphoma. To define the role of PRMT5 in normal adult hematopoiesis, we generated PRMT5 conditional knockout mice using Mx1-cre. The induced deletion of both alleles of PRMT5 leads to severe pancytopenia and bone marrow aplasia with subsequent lethality in two weeks. First, loss of PRMT5 triggers the impaired proliferation and rapid disappearance of progenitor cells. At the same time, PRMT5 deficient HSCs show increased cell cycling and a transient HSC accumulation, which is rapidly followed by stem cell exhaustion. Mechanistically, we show that deletion of PRMT5 severely impairs cytokine signaling. It also up-regulates p53 protein level and the expression of p53 target genes. These effects likely account for the critical role of PRMT5 in HSPCs. We have conducted many additional experiments to show that these effects of PRMT5 deletion on hematopoiesis are cell autonomous; and also that the methyltransferase activity of PRMT5 is required to sustain normal hematopoiesis. Thus, we identify PRMT5 as a critical regulator of normal hematopoietic stem and progenitor cell biology. Disclosures No relevant conflicts of interest to declare.

scholarly journals M6PR-Specific Targeting of Lysosomal Heparanase Regulates Platelet Hemostatic Function in Mice

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1059-1059
Author(s):  
Nathan Eaton ◽  
Caleb Drew ◽  
Theresa A. Dlugi ◽  
Karin M. Hoffmeister ◽  
Hervé Falet
Keyword(s):  
Platelet Function ◽  
Conflicts Of Interest ◽  
Blood Platelets ◽  
Critical Role ◽  
Fluorescent Microscopy ◽  
Type I ◽  
Dense Granules ◽  
Specific Targeting

Besides α-granules and dense granules, which play critical roles in and beyond hemostasis, circulating blood platelets and their precursor cells megakaryocytes contain lysosomes, the contents of which are also secreted during platelet activation. In their delivery to the lysosome, acid hydrolases bearing phosphomannosyl residues are trafficked from the trans-Golgi network to the acidic late-endosomal compartment via the mannose 6-phosphate receptor (M6PR) pathway. To determine the role of M6PR-specific targeting of lysosomal enzymes in platelet function, platelet parameters were investigated in M6pr-/- mice lacking the 46-kDa M6PR, the physiological role of which is unclear. M6pr-/- mice had normal platelet count but displayed an increased number of distinct proplatelet-like cells compared to control mice, as determined by immunofluorescent microscopy. Moreover, transmission electron microscopy revealed the presence of abnormal membrane tubulations, elongated and electron-dense granules, and large vacuole-like structures within resting M6pr-/- platelets. M6pr-/- platelets expressed normally major glycoproteins on their surface and von Willebrand factor and fibrinogen in their α-granules. M6pr-/- mice were hyper-thrombotic, as assessed by tail bleeding time, and M6pr-/- platelets adhered to type I collagen with a significantly greater propensity than control platelets under arterial shear in in vitro flow experiments. Heparanase, an endo-β-glucuronidase that cleaves extracellular matrix heparan sulfate proteoglycans, is the most abundant lysosomal enzyme in platelets. Thus, its contribution to the phenotype of M6pr-/- mice was investigated further. Heparanase expression was decreased in the bone marrow megakaryocytes and blood platelets of M6pr-/- mice and increased in M6pr-/- plasma, as evidenced by immunoblot and fluorescent microscopy analysis, consistent with its mistargeting in the absence of M6PR. Interestingly, pharmacological inhibition of heparanase with OGT 2115 normalized the adhesion of M6pr-/- platelets to collagen in vitro, indicating that increased plasma heparanase contributes to the thrombotic phenotype of M6pr-/- mice. Taken together, the data suggest that the M6PR-specific targeting of lysosomal heparanase plays a critical role in platelet function, thereby regulating hemostasis. Disclosures No relevant conflicts of interest to declare.

The Role of Local and Regional Institutions

2014 ◽  
pp. 112-121
Author(s):  
John Tomaney
Keyword(s):  
Economic Development ◽  
Case Studies ◽  
Economic Performance ◽  
Regional Scale ◽  
Local Institutions ◽  
Economic Wealth ◽  
Major Field ◽  
Regional Institutions ◽  
New Thinking

This chapter explores the ways in which regions that are remote from the main concentrations of economic wealth and power can achieve development in a high cost environment. The role of effective institutions in creating the conditions for economic development has become a major field of scholarship. Recently, these insights have been applied to the urban and regional scale. This chapter pays particular attention to the role that regional and local institutions play in shaping patterns of economic performance, especially in high cost environments. The chapter examines ways in which this new thinking is informing regional policy. It provides some case studies of regions that have succeeded in the high cost environment of Europe. It concludes by stressing the importance of effective and adept local and regional institutions in ensuring the prosperity of cities and regions.

The Role of Microtubule Regulatory Protein Stathmin (STMN1) in Megakaryopoiesis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4591-4591
Author(s):  
Camelia Iancu-Rubin ◽  
Joseph Tripodi ◽  
Vesna Najfeld ◽  
George F. Atweh
Keyword(s):  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Critical Role ◽  
Regulatory Protein ◽  
Active Form ◽  
Fish Analysis ◽  
Ploidy Levels ◽  
Significant Difference

Abstract Abstract 4591 Megakaryopoiesis is a complex process in which hematopoietic progenitor cells proliferate and acquire megakaryocyte (MK)-specific markers then undergo polyploidization (i.e. acquisition of DNA content >2n) and cytoplasmic maturation, and start producing platelets. Polyploidization and platelet formation are highly dependent on microtubule (MT) function. To become polyploid, MK undergo abortive mitosis that is mediated by a mitotic spindle that consists of MT. Mature polyploid MK extend cytoplasmic extensions (i.e. proplatelets) into the vascular space and release platelets into the circulation. MT provide the structural scaffold for the proplatelets and mediate the transport of organelles and specific granules into nascent platelets. Despite the critical role of MT in MK biology, the regulation of MT in MK is poorly defined. Stathmin (STMN1) is a cytosolic phosphoprotein whose major function is to regulate MT function by promoting their depolymerization. We had previously shown that STMN1 is expressed at high levels early during megakaryopoiesis and is downregulated later during MK maturation. We also showed that inhibition of STMN1 expression increased ploidy while its overexpression decreased ploidy of MK-like cell lines. Thus, we hypothesized that the dynamic regulation of STMN1 expression may be necessary for megakaryopoiesis and that perturbing its expression may impair MK polyploidization and platelet production. To test this hypothesis, we developed feline immunodeficiency virus (FIV)-based lentiviruses that express STMN1 to investigate the effects of overexpression in primary MK. Since the depolymerizing activity of STMN1 can be inactivated by a variety of cellular kinases, we generated a STMN1 vectors that expresses wild-type (WT) and another that expresses a contitutively active phosphorylation-deficient mutant of STMN1 (MT). We also developed a vector that expresses GFP as a negative control. Human MK generated ex vivo in liquid culture from CD34+ cells were infected with these different lentiviruses. After ectopic STMN1 expression by RT-PCR and flow cytometry was confirmed, MK differentiation was assessed in the presence or absence of STMN1 overexpression. Uninfected MK and MK infected with GFP lentiviruses differentiated and matured into large, easily recognizable cells with typical nuclear morphology and expressed similar levels of CD41 and CD42b by flow cytometry. The numbers of MK generated in the presence of WT-STMN1 expressing lentiviruses was similar to that generated in the cultures infected with control lentiviruses, while the number of MK generated in the presence of phosphorylation-deficient MT-STMN1 was drasticaly reduced. Similarly, the numbers of CD41+ and CD42b+ MK generated in the presence of MT-STMN1 was reduced two and three times, respectively, suggesting that overexpression of a contitutively active form of STMN1 prevents MK differentiation and maturation. We then evaluated the effects of STMN1 overexpression on MK polyploidization by determining the number X and Y chromosomes by FISH analysis. While a normal diploid cell has one copy of each chromosome, cells with ploidy levels of 4N, 8N and 16N will have 2, 4 and 8 copies, respectively. There was no significant difference between the fraction of polyploid MK infected with control-GFP and those infected with WT-STMN1 lentiviruses. In contrast, the fraction of polyploid MK infected with MT-STMN1 lentiviruses was reduced by approximately 50%, suggesting that STMN1 overexpression impairs the ability of MK to become polyploid. In conclusion, we demonstrated that perturbing the normal downregulation of STMN1 in primary human MK impairs differentiation and polyploidization. Since STMN1 is expressesd at extremely high levels in a variety of human leukemias, we have started assessing STMN1 expression expression in patients with hematological malignancies characterized by striking abnormalities in their MK lineage. Such studies might validate the role of MT regulation in MK biology in vivo and support the development of potential therapeutic strategies to target MT and/or STMN1 function in MK and platelet disorders. Disclosures: No relevant conflicts of interest to declare.

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