Aurora, What Causes the Northern Lights?

This color brochure answers common questions about the aurora, including its cause and explanations of its colors, shapes, and location. It lists resources for further study. Educational levels: Informal education

Prognostic significance of endogenous erythropoietin in long-term outcome of patients with acute decompensated heart failure

Aims Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear. Methods and results We examined 539 consecutive ADHF patients with EPO measurement on admission from our registry. During a median follow-up period of 329 days, a higher EPO level on admission was independently associated with worse clinical outcomes [hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.06–1.48, P = 0.008], and haemoglobin level was the strongest determinant of EPO level (P < 0.001), whereas estimated glomerular filtration rate (eGFR) was not significant in multivariate regression analysis. In the anaemic subgroup of 318 patients, a higher EPO level than expected on the basis of their haemoglobin level was related to increased adverse events (HR 1.63, 95% CI 1.05–2.49, P = 0.028). Moreover, estimated plasma volume excess rate was positively associated with EPO level (P = 0.003), and anaemic patients with a higher than expected EPO level tended to have a higher estimated plasma volume excess rate and plasma lactate level, and lower systemic oxygen saturation level with the preservation of the reticulocyte production index than those with a lower than expected EPO level. Conclusion A high EPO level predicts long-term worse clinical outcomes in ADHF patients, independent of anaemia and impaired renal function. Anaemia and hypoxia due to severe congestion may synergistically contribute to a high EPO level in high-risk HF patients

Age-dependent expression of the erythropoietin gene in rat liver and kidneys

Using RNAse protection, we have made quantitative measurements of erythropoietin (EPO) mRNA in liver and kidneys of developing rats (days 1-54), to determine the relative contribution of both organs to the total EPO mRNA, to monitor changes which occur with development, and to compare the hypoxia-induced accumulation of EPO mRNA with the changes in serum EPO concentrations. To determine whether developmental and organ-specific responsiveness is related to the type of hypoxic stimulus, normobaric hypoxia was compared with exposure to carbon monoxide (functional anemia). Under both stimuli EPO mRNA concentration in liver was maximal on day 7 and declined during development. In contrast, EPO mRNA concentration in kidney increased during development from day 1 when it was 30-65% the hepatic concentration to day 54 when it was 12-fold higher than in liver. When organ weight was considered the liver was found to contain the majority of EPO mRNA in the first three to four weeks of life, and although, in stimulated animals, the hepatic proportion declined from 85-91% on day 1, it remained approximately 33% at day 54 and was similar for the two types of stimuli. When normalized for body weight the sum of renal and hepatic EPO mRNA in animals of a particular age was related linearly to serum hormone concentrations. However, the slope of this regression increased progressively with development, suggesting age-dependent alterations in translational efficiency or EPO metabolism

Increased plasma viscosity as a reason for inappropriate erythropoietin formation

The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenström's disease. We found that the EPO formation in response to anemia in these patients was inversely related to plasma viscosity. A similar inverse relationship between plasma viscosity and EPO production was seen in rats in which EPO formation had been stimulated by exchange transfusion and the plasma viscosity of which was thereby altered by using exchange solutions of different composition to alter plasma viscosity and thus whole blood viscosity independently from hematocrit. Raising the gammaglobulin concentration to approximately 40 mg/ml plasma in the rats almost totally blunted the rise in serum EPO levels despite a fall of the hematocrit to 20%. Determination of renal EPO mRNA levels by RNase protection revealed that the reductions in serum EPO levels at higher plasma viscosities were paralleled by reductions in renal EPO mRNA levels. Taken together, our findings suggest that plasma viscosity may be a significant inhibitory modulator of anemia-induced EPO formation. The increased plasma viscosity in patients with hypergammaglobulinemias may therefore contribute to the inappropriate EPO production, which is a major reason for the anemia developing in these patients

Post-Issue Patent "Quality Control": A Comparative Study of US Patent Re-examinations and European Patent Oppositions

We report the results of the first comparative study of the determinants and effects of patent oppositions in Europe and of re- examinations on corresponding patents issued in the United States. The analysis is based on a dataset consisting of matched EPO and US patents. Our analysis focuses on two broad technology categories - biotechnology and pharmaceuticals, and semiconductors and computer software. Within these fields, we collect data on all EPO patents for which oppositions were filed at the EPO. We also construct a random sample of EPO patents with no opposition in these technologies. We match these EPO patents with the “equivalent” US patents covering the same invention in the United States. Using the matched sample of USPTO and EPO patents, we compare the determinants of opposition and of reexamination. Our results indicate that valuable patents are more likely to be challenged in both jurisdictions. But the rate of opposition at the EPO is more than thirty times higher than the rate of reexamination at the USPTO.

Hypoxia enhances the tissue protective effect of erythropoietin and its analogues in an endothelial cell injury model

PO has tissue protective activities in ischemic disease but also has prothrombotic, erythropoietic effects. Carbamylated EPO (CEPO) retains the protective actions without the erythropoietic effects. To assess the potential of these molecules in atherosclerosis (an ischemic heart disease), we investigated EPO and CEPO in an in vitro model of injury using bovine aortic endothelial cells (BAEC) in hypoxia and normoxia.. BAECs were grown to confluence in 10% FBS in 12 well culture plates. They were then cultured under normoxia (21% oxygen) or hypoxia (5% oxygen) 24 h prior to their use in an injury model using the ‘scratch assay.’ The effects of EPO and CEPO on endothelial closure were assessed using a range of concentrations (0-10 ng/mL). In separate experiments, the effects of EPO and CEPO on BAEC proliferation and chemotaxis were also assessed under similar hypoxic conditions. Gene expression of the receptors that may be involved in their protective pathway [EPOR and the β common chain receptor (βCR)] were assessed using quantitative PCR. The effects of both EPO and CEPO were enhanced under hypoxic conditions (13 ± 2.6 %, and 10 ± 1.69 %, p0.05). Whilst, the expression of EPOR gene increased by 2.1 ± 0.8 folds (p<0.05) In hypoxia, βCR expression was not affected by the change in oxygen tension. The effects of EPO and CEPO in the scratch assay appeared to be mediated by enhancing cell proliferation and migration of BAECs (p<0.05). In conclusion, the enhanced effects of EPO and CEPO on endothelial cells under hypoxia requires further investigation in processes in which hypoxia may play a role, e.gfor example. in atherogenesis and re-stensosis following angioplasty

Poverty Reduction in Cameroon, 1996-2001: The Role of Growth and Income Redistribution

This paper appeals to the Shapley Value decomposition rule to account for the retreat in the FGT class of poverty measures in Cameroon between 1996 and 2001. In particular, the paper examines the evolution of poverty in Cameroon, simulates budgetary outlays necessary to eradicate poverty assuming perfect targeting, and decomposes changes in poverty into growth and redistribution components. The ECAM I and ECAM II household consumption surveys collected by the Governments Statistics Office together with the software DAD4.4 were used to generate the results. The incidence, depth and severity of poverty retreated significantly the period under study. The growth component contributed significantly more in explaining the fall in levels of poverty than the redistribution component in both rural and urban areas. The overall situation however clouds regional tendencies, which attribute varying importance to the two factors. The indication, however, clearly portrays the important role to be attributed to growth if long term poverty reduction is valued high in the policy menu as articulated in Cameroon’s Poverty Reduction Strategy Paper. The government needs to allocate more budgetary outlays in rural areas to fill the income gap relative to the poverty line. In spite of the importance of growth in eradicating poverty, it will be much more effective if it benefits the poor disproportionately.Poverty decomposition; Shapley Value; Household Surveys; Cameroon

Post-Issue Patent "Quality Control": A Comparative Study of US Patent Re-examinations and European Patent Oppositions

We report the results of the first comparative study of the determinants and effects of patent oppositions in Europe and of re-examinations on corresponding patents issued in the United States. The analysis is based on a dataset consisting of matched EPO and US patents. Our analysis focuses on two broad technology categories - biotechnology and pharmaceuticals, and semiconductors and computer software. Within these fields, we collect data on all EPO patents for which oppositions were filed at the EPO. We also construct a random sample of EPO patents with no opposition in these technologies. We match these EPO patents with the 'equivalent' US patents covering the same invention in the United States. Using the matched sample of USPTO and EPO patents, we compare the determinants of opposition and of re-examination. Our results indicate that valuable patents are more likely to be challenged in both jurisdictions. But the rate of opposition at the EPO is more than thirty times higher than the rate of re-examination at the USPTO. Moreover, opposition leads to a revocation of the patent in about 41 percent of the cases, and to a restriction of the patent right in another 30 percent of the cases. Re-examination results in a cancellation of the patent right in only 12.2 percent of all cases. We also find that re-examination is frequently initiated by the patentholders themselves.

Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway

Objective. Erythropoietin (EPO) is a key regulator of erythropoiesis, playing a role in both the proliferation and differentiation of erythroid cells. One of the signal transduction molecules activated upon EPO stimulation is signal transducer and activator of transcription (STAT) 3. Besides tyrosine 705 phosphorylation of STAT3, serine 727 phosphorylation has been described upon EPO stimulation. In the present study, we investigated which molecular pathways mediate the STAT3 serine 727 phosphorylation and the functional implications of this phosphorylation. Methods. The EPO-dependent erythroid cell line ASE2 was used to investigate which signaling routes were involved in the STAT3 serine 727 phosphorylation. Western blotting using phosphospecific antibodies was used to assess the phosphorylation status of STAT3 molecules. Transfection analysis was performed to investigate the transactivational potential of STAT3, and quantitative RT-PCR was used to study the in vivo gene expression of STAT3-responsive genes. Results. Western blotting of extracts of cells exposed to various chemical inhibitors revealed that the MEK inhibitors PD98059 and U0126 abrogated the EPO-mediated STAT3 serine 727 phosphorylation without an effect on tyrosine phosphorylation. Further analysis showed that MSK1 is activated downstream of ERK, and retroviral transductions with kinase-inactive MSK1 revealed that MSK1 is necessary for STAT3 serine phosphorylation. Furthermore, the STAT3-mediated transactivation was reduced by blocking the STAT3 serine phosphorylation with the MEK inhibitor U0126 or by expression of kinase-inactive MSK1. Conclusions. The EPO-induced STAT3 serine 727 phosphorylation is mediated by a pathway involving MEK, ERK, and MSK1. Furthermore, serine phosphorylation of STAT3 augments the transactivational potential of STAT3.

Oxygen-dependent expression of the erythropoietin gene in rat hepatocytes in vitro

Since in juvenile rats the liver is the predominant site of erythropoietin (EPO) gene expression, we have used primary cultures of juvenile rat hepatocytes to establish and in vitro system for investigation of oxygen-dependent EPO formation. When isolated hepatocytes were incubated at reduced oxygen tensions for 18-48 h, we found increased secretion of EPO protein and elevated levels of EPO mRNA, as determined by RNas protection. This increase was maximal at 3% O2, where EPO mRNA levels after 18 h were approximately 15-fold higher than at 20% O2. The increase in EPO mRNA at low oxygen tensions was specific insofar as [3H]uridine incorporation, as a measure of total RNA synthesis, was reduced by approximately 50% at 3% O2, and it appeared to involve gene transcription since it was abolished in the presence of actinomycin D (35 microM). Significant increases in EPO mRNA were also observed in cells kept at 20% oxygen in the presence of cobalt chloride (50 microM) and nickel chloride (400 microM), but EPO mRNA levels achieved under these conditions were less than 7% of those in cells incubated at 3% oxygen. No increase in EPO mRNA levels was observed in cultures incubated at 20% O2 in the presence of cyclic dibutyryl-AMP (10 microM-3 mM), cyclic 8-bromoGMP (10 microM-1 mM), cyclohexyladenosine (1 microM), 5'-N-ethylcarboxamidoadenosine (1 microM) and phorbol 12-myristate 13-acetate (3 nM). In the presence of 10% carbon monoxide, used to block haem proteins in their oxy conformation, EPO mRNA levels in hepatocytes incubated at low oxygen tensions were reduced to 63%.(ABSTRACT TRUNCATED AT 250 WORDS