Effect of Iron Overload and Iron Deficiency on Liver Hemojuvelin Protein

INTRODUCTION: Hemojuvelin (Hjv) is a key component of the signaling cascade that regulates liver hepcidin (Hamp) expression. The purpose of this study was to determine Hjv protein levels in mice and rats subjected to iron overload and iron deficiency. METHODS: C57BL/6 mice were injected with iron (200 mg/kg); iron deficiency was induced by feeding of an iron-deficient diet, or by repeated phlebotomies. Erythropoietin (EPO)-treated mice were administered recombinant EPO at 50 U/mouse. Wistar rats were injected with iron (1200 mg/kg), or fed an iron-deficient diet. Hjv protein was determined by immunoblotting, liver samples from Hjv-/- mice were used as negative controls. Mouse plasma Hjv content was determined by a commercial ELISA kit. RESULTS: Liver crude membrane fraction from both mice and rats displayed a major Hjv-specific band at 35 kDa, and a weaker band of 20 kDa. In mice, the intensity of these bands was not changed following iron injection, repeated bleeding, low iron diet or EPO administration. No change in liver crude membrane Hjv protein was observed in iron-treated or iron-deficient rats. ELISA assay for mouse plasma Hjv did not show significant difference between Hjv+/+ and Hjv-/- mice. Liver Hamp mRNA, Bmp6 mRNA and Id1 mRNA displayed the expected response to iron overload and iron deficiency. EPO treatment decreased Id1 mRNA, suggesting possible participation of the bone morphogenetic protein pathway in EPO-mediated downregulation of Hamp mRNA. DISCUSSION: Since no differences between Hjv protein levels were found following various experimental manipulations of body iron status, the results indicate that, in vivo, substantial changes in Hamp mRNA can occur without noticeable changes of membrane hemojuvelin content. Therefore, modulation of hemojuvelin protein content apparently does not represent the limiting step in the control of Hamp gene expression

Agile manufacturing practices: the role of big data and business analytics with multiple case studies

The purpose of this study was to examine the role of big data and business analytics (BDBA) in agile manufacturing practices. Literature has discussed the benefits and challenges related to the deployment of big data within operations and supply chains, but there has not been a study of the facilitating roles of BDBA in achieving an enhanced level of agile manufacturing practices. As a response to this gap, and drawing upon multiple qualitative case studies undertaken among four U.K. organizations, we present and validate a framework for the role of BDBA within agile manufacturing. The findings show that market turbulence has negative universal effects and that agile manufacturing enablers are being progressively deployed and aided by BDBA to yield better competitive and business performance objectives. Further, the level of intervention was found to differ across companies depending on the extent of deployment of BDBA, which accounts for variations in outcomes

Evidence for a lack of a direct transcriptional suppression of the iron regulatory peptide hepcidin by hypoxia-inducible factors.

BACKGROUND: Hepcidin is a major regulator of iron metabolism and plays a key role in anemia of chronic disease, reducing intestinal iron uptake and release from body iron stores. Hypoxia and chemical stabilizers of the hypoxia-inducible transcription factor (HIF) have been shown to suppress hepcidin expression. We therefore investigated the role of HIF in hepcidin regulation. METHODOLOGY/PRINCIPAL FINDINGS: Hepcidin mRNA was down-regulated in hepatoma cells by chemical HIF stabilizers and iron chelators, respectively. In contrast, the response to hypoxia was variable. The decrease in hepcidin mRNA was not reversed by HIF-1alpha or HIF-2alpha knock-down or by depletion of the HIF and iron regulatory protein (IRP) target transferrin receptor 1 (TfR1). However, the response of hepcidin to hypoxia and chemical HIF inducers paralleled the regulation of transferrin receptor 2 (TfR2), one of the genes critical to hepcidin expression. Hepcidin expression was also markedly and rapidly decreased by serum deprivation, independent of transferrin-bound iron, and by the phosphatidylinositol 3 (PI3) kinase inhibitor LY294002, indicating that growth factors are required for hepcidin expression in vitro. Hepcidin promoter constructs mirrored the response of mRNA levels to interleukin-6 and bone morphogenetic proteins, but not consistently to hypoxia or HIF stabilizers, and deletion of the putative HIF binding motifs did not alter the response to different hypoxic stimuli. In mice exposed to carbon monoxide, hypoxia or the chemical HIF inducer N-oxalylglycine, liver hepcidin 1 mRNA was elevated rather than decreased. CONCLUSIONS/SIGNIFICANCE: Taken together, these data indicate that hepcidin is neither a direct target of HIF, nor indirectly regulated by HIF through induction of TfR1 expression. Hepcidin mRNA expression in vitro is highly sensitive to the presence of serum factors and PI3 kinase inhibition and parallels TfR2 expression

Golden Rule of Forecasting: Be Conservative

This article proposes a unifying theory, or the Golden Rule, or forecasting. The Golden Rule of Forecasting is to be conservative. A conservative forecast is consistent with cumulative knowledge about the present and the past. To be conservative, forecasters must seek out and use all knowledge relevant to the problem, including knowledge of methods validated for the situation. Twenty-eight guidelines are logically deduced from the Golden Rule. A review of evidence identified 105 papers with experimental comparisons; 102 support the guidelines. Ignoring a single guideline increased forecast error by more than two-fifths on average. Ignoring the Golden Rule is likely to harm accuracy most when the situation is uncertain and complex, and when bias is likely. Non-experts who use the Golden Rule can identify dubious forecasts quickly and inexpensively. To date, ignorance of research findings, bias, sophisticated statistical procedures, and the proliferation of big data, have led forecasters to violate the Golden Rule. As a result, despite major advances in evidence-based forecasting methods, forecasting practice in many fields has failed to improve over the past half-century

SSR-Based Analysis of Genetic Diversity and Structure of Sweet Cherry (Prunus avium L.) from 19 Countries in Europe

Sweet cherry (Prunus avium L.) is a temperate fruit species whose production might be highly impacted by climate change in the near future. Diversity of plant material could be an option to mitigate these climate risks by enabling producers to have new cultivars well adapted to new environmental conditions. In this study, subsets of sweet cherry collections of 19 European countries were genotyped using 14 SSR. The objectives of this study were (i) to assess genetic diversity parameters, (ii) to estimate the levels of population structure, and (iii) to identify germplasm redundancies. A total of 314 accessions, including landraces, early selections, and modern cultivars, were monitored, and 220 unique SSR genotypes were identified. All 14 loci were confirmed to be polymorphic, and a total of 137 alleles were detected with a mean of 9.8 alleles per locus. The average number of alleles (N = 9.8), PIC value (0.658), observed heterozygosity (Ho = 0.71), and expected heterozygosity (He = 0.70) were higher in this study compared to values reported so far. Four ancestral populations were detected using STRUCTURE software and confirmed by Principal Coordinate Analysis (PCoA), and two of them (K1 and K4) could be attributed to the geographical origin of the accessions. A N-J tree grouped the 220 sweet cherry accessions within three main clusters and six subgroups. Accessions belonging to the four STRUCTURE populations roughly clustered together. Clustering confirmed known genealogical data for several accessions. The large genetic diversity of the collection was demonstrated, in particular within the landrace pool, justifying the efforts made over decades for their conservation. New sources of diversity will allow producers to face challenges, such as climate change and the need to develop more sustainable production systems

Physical and mechanical properties and deformation behavior of porous ceramics based on plasma chemical powders Al[2]O[3], ZrO[2](MgO)

This work investigates the behavior of porous alumina and zirconia stabilized with magnesium oxide (within the porosity range of 18% to 70%) ceramics when subjected to deformation by compression and shearing. The analysis of strain-deformation curves showed that there was a transition from a typically brittle state for relatively dense ceramics, to a pseudo-plastic one with a high rate of porosity. The values of the effective elasticity modulus, effective shear modulus and Poisson's ratio decrease with an increase in volume in the pore space of ceramics, which correlates with the appearance of plural cracking during the deformation of ceramics with a high level of porosity. There was made analysis of the nature of the destruction of ceramics with the same level of porosity. The difference in the deformation behavior of the ZrO[2]-MgO compared to the Al[2]O[3] ceramic was the fact that the transition from a typically brittle to tively dense ceramics to the pseudo -plastic at a high level of porosity is implemented with a lower level of porosity

Phase structure of ceramics Al[2]O[3]-ZrW[2]O[8]

In the course of work the phase composition of the ceramic composite material Al[2]O[3] - 50 % ZrW[2]O[8] was studied. On the polished surface of the Al[2]O[3]-ZrW[2]O[8] sintered composite can be allocated three areas: dark gray matrix, white inclusions of an irregular form and spherical inclusions. The average size of spherical inclusions was equal to 15 [mu]m. The phase structure of ceramic composite was presented by trigonal modification of aluminum oxide, cubic zirconium tungstate, monoclinic modification of zirconium oxide and tungsten oxide

Spin alignment of leading K∗(892)0K^{*}(892)^{0} mesons in hadronic Z0Z^0 decays

Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K ∗ (892) 0 mesons from hadronic Z 0 decays have been measured over the full range of K ∗ 0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x p values above 0.3, with the matrix element ϱ 00 rising to 0.66 ± 0.11 for x p > 0.7. The values of the real part of the off-diagonal element ϱ 1 - 1 are negative at large x p , with a weighted average value of −0.09 ± 0.03 for x p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the q q system from the Z 0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x p range. The K ∗ 0 fragmentation function has also been measured and the total rate determined to be 0.74 ± 0.02 ± 0.02 K ∗ (892) 0 mesons per hadronic Z 0 decay

A search for neutral Higgs bosons in the MSSM and models with two scalar field doublets

A search is described for the neutral Higgs bosons h^0 and A^0 predicted by models with two scalar field doublets and, in particular, the Minimal Supersymmetric Standard Model (MSSM). The search in the Z^0 h^0 and h^0 A^0 production channels is based on data corresponding to an integrated luminosity of 25 pb^{-1} from e^+e^- collisions at centre-of-mass energies between 130 and 172GeV collected with the OPAL detector at LEP. The observation of a number of candidates consistent with Standard Model background expectations is used in combination with earlier results from data collected at the Z^0 resonance to set limits on m_h and m_A in general models with two scalar field doublets and in the MSSM. For example, in the MSSM, for tan(beta) > 1, minimal and maximal scalar top quark mixing and soft SUSY-breaking masses of 1 TeV, the 95% confidence level limits m_h > 59.0 GeV and m_A > 59.5 GeV are obtained. For the first time, the MSSM parameter space is explored in a detailed scan.A search is described for the neutral Higgs bosons h^0 and A^0 predicted by models with two scalar field doublets and, in particular, the Minimal Supersymmetric Standard Model (MSSM). The search in the Z^0 h^0 and h^0 A^0 production channels is based on data corresponding to an integrated luminosity of 25 pb^{-1} from e^+e^- collisions at centre-of-mass energies between 130 and 172 GeV collected with the OPAL detector at LEP. The observation of a number of candidates consistent with Standard Model background expectations is used in combination with earlier results from data collected at the Z^0 resonance to set limits on m_h and m_A in general models with two scalar field doublets and in the MSSM. For example, in the MSSM, for tan(beta) > 1, minimal and maximal scalar top quark mixing and soft SUSY-breaking masses of 1 TeV, the 95% confidence level limits m_h > 59.0 GeV and m_A > 59.5 GeV are obtained. For the first time, the MSSM parameter space is explored in a detailed scan

Разработка дизайна оболочки велотренажера для людей с ограниченными физическими возможностями

Объектом исследования является велотренажер для людей с ограниченными физическими возможностями. Цель работы – проектирование оболочки велотренажера для людей с ограниченными физическими возможностями. В процессе проектирования проводилась разработка вариантов дизайнерских решений оболочки корпуса. В результате проектирования была разработана велотренажера для людей с ограниченными физическими возможностями.The object of the study is an exercise bike for people with disabilities. The aim of the work is to design the shell of an exercise bike for people with disabilities. In the design process, the development of variants of the design solutions of the hull shell was carried out. As a result of the design, an exercise bike was developed for people with disabilities