The CACCC-Binding Protein KLF3/BKLF Represses a Subset of KLF1/EKLF Target Genes and Is Required for Proper Erythroid Maturation In Vivo

PubMed Central

Funnell, Alister P. W.; Norton, Laura J.; Mak, Ka Sin; Burdach, Jon; Artuz, Crisbel M.; Twine, Natalie A.; Wilkins, Marc R.; Power, Carl A.; Hung, Tzong-Tyng; Perdomo, José; Koh, Philip; Bell-Anderson, Kim S.; Orkin, Stuart H.; Fraser, Stuart T.; Perkins, Andrew C.; Pearson, Richard C. M.

2012-01-01

The CACCC-box binding protein erythroid Krüppel-like factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of the gene for a second KLF, basic Krüppel-like factor, or KLF3. We have now tested the in vivo role of KLF3 in erythroid cells by examining Klf3 knockout mice. KLF3-deficient adults exhibit a mild compensated anemia, including enlarged spleens, increased red pulp, and a higher percentage of erythroid progenitors, together with elevated reticulocytes and abnormal erythrocytes in the peripheral blood. Impaired erythroid maturation is also observed in the fetal liver. We have found that KLF3 levels rise as erythroid cells mature to become TER119+. Consistent with this, microarray analysis of both TER119− and TER119+ erythroid populations revealed that KLF3 is most critical at the later stages of erythroid maturation and is indeed primarily a transcriptional repressor. Notably, many of the genes repressed by KLF3 are also known to be activated by EKLF. However, the majority of these are not currently recognized as erythroid-cell-specific genes. These results reveal the molecular and physiological function of KLF3, defining it as a feedback repressor that counters the activity of EKLF at selected target genes to achieve normal erythropoiesis. PMID:22711990

Hemozoin (Malarial Pigment) Directly Promotes Apoptosis of Erythroid Precursors

PubMed Central

Lamikanra, Abigail A.; Theron, Michel; Kooij, Taco W. A.; Roberts, David J.

2009-01-01

Severe malarial anemia is the most common syndrome of severe malaria in endemic areas. The pathophysiology of chronic malaria is characterised by a striking degree of abnormal development of erythroid precursors (dyserythropoiesis) and an inadequate erythropoietic response in spite of elevated levels of erythropoietin. The cause of dyserythropoiesis is unclear although it has been suggested that bone-marrow macrophages release cytokines, chemokines or lipo-peroxides after exposure to hemozoin, a crystalloid form of undigested heme moieties from malarial infected erythrocytes, and so inhibit erythropoiesis. However, we have previously shown that hemozoin may directly inhibit erythroid development in vitro and the levels of hemozoin in plasma from patients with malarial anemia and hemozoin within the bone marrow was associated with reduced reticulocyte response. We hypothesized that macrophages may reduce, not enhance, the inhibitory effect of hemozoin on erythropoiesis. In an in vitro model of erythropoiesis, we now show that inhibition of erythroid cell development by hemozoin isolated from P. falciparum is characterised by delayed expression of the erythroid markers and increased apoptosis of progenitor cells. Crucially, macrophages appear to protect erythroid cells from hemozoin, consistent with a direct contribution of hemozoin to the depression of reticulocyte output from the bone marrow in children with malarial anemia. Moreover, hemozoin isolated from P. falciparum in vitro inhibits erythroid development independently of inflammatory mediators by inducing apoptotic pathways that not only involve activation of caspase 8 and cleavage of caspase 3 but also loss of mitochondrial potential. Taken together these data are consistent with a direct effect of hemozoin in inducing apoptosis in developing erythroid cells in malarial anemia. Accumulation of hemozoin in the bone marrow could therefore result in inadequate reticulocytosis in children that have adequate

Histologic and cytologic bone marrow findings in dogs with suspected precursor-targeted immune-mediated anemia and associated phagocytosis of erythroid precursors.

PubMed

Lucidi, Cynthia de A; de Rezende, Christian L E; Jutkowitz, L Ari; Scott, Michael A

2017-09-01

Precursor-targeted immune-mediated anemia (PIMA) has been suspected in dogs with nonregenerative anemia and bone marrow findings varying from erythroid hyperplasia to pure red cell aplasia. Phagocytosis of erythroid precursors/rubriphagocytosis (RP) reported in some affected dogs suggests a destructive component to the pathogenesis of PIMA. The purpose of the study was to characterize laboratory and clinical findings in dogs with suspected PIMA and RP, with emphasis on cytologic and histologic bone marrow findings. Dogs with PIMA and RP were identified by review of paired bone marrow aspirate and core biopsy slides collected over a 4-year period. Samples were systematically assessed and characterized along with other pertinent laboratory data and clinical findings. Twenty-five dogs met criteria for PIMA and had RP that was relatively stage-selective. Erythropoiesis was expanded to the stage of erythroid precursors undergoing most prominent phagocytosis, yielding patterns characterized by a hypo-, normo-, or hypercellular erythroid lineage. A 4 th pattern involved severe collagen myelofibrosis, and there was a spectrum of mild to severe collagen myelofibrosis overall. Evidence of immune-mediated hemolysis was rare. Immunosuppressive therapy was associated with remission in 77% of dogs treated for at least the median response time of 2 months. Bone marrow patterns in dogs fulfilling criteria for PIMA were aligned with stage-selective phagocytosis of erythroid precursors and the development of collagen myelofibrosis, common in dogs with PIMA. Recognition of these patterns and detection of RP facilitates diagnosis of PIMA, and slow response to immunosuppressive therapy warrants further investigation into its pathogenesis. © 2017 American Society for Veterinary Clinical Pathology.

The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xiao-Fei; Wu, Xiao-Rong; Xue, Ming

2012-11-15

Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catecholmore » enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes. -- Highlights: ► Catechol enhanced hemin-induced hemoglobin accumulation. ► Exposure to catechol resulted in up-regulated expression of erythroid genes. ► Catechol reduced methylation levels at some CpG sites in erythroid genes.« less

Hls5 regulated erythroid differentiation by modulating GATA-1 activity.

PubMed

Endersby, Raelene; Majewski, Ian J; Winteringham, Louise; Beaumont, Jennifer G; Samuels, Amy; Scaife, Robin; Lim, Esther; Crossley, Merlin; Klinken, S Peter; Lalonde, Jean-Philippe

2008-02-15

Hemopoietic lineage switch (Hls) 5 and 7 were originally isolated as genes up-regulated during an erythroid-to-myeloid lineage switch. We have shown previously that Hls7/Mlf1 imposes a monoblastoid phenotype on erythroleukemic cells. Here we show that Hls5 impedes erythroid maturation by restricting proliferation and inhibiting hemoglobin synthesis; however, Hls5 does not influence the morphology of erythroid cells. Under the influence of GATA-1, Hls5 relocates from cytoplasmic granules to the nucleus where it associates with both FOG-1 and GATA-1. In the nucleus, Hls5 is able to suppress GATA-1-mediated transactivation and reduce GATA-1 binding to DNA. We conclude that Hls5 and Hls7/Mlf1 act cooperatively to induce biochemical and phenotypic changes associated with erythroid/myeloid lineage switching.

Antisense myb inhibition of purified erythroid progenitors in development and differentiation is linked to cycling activity and expression of DNA polymerase alpha

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valtieri, M.; Venturelli, D.; Care, A.

These studies aimed to determine the expression and functional role of c-myb in erythroid progenitors with different cycling activities. In the first series of experiments the erythroid burst-forming unit (BFU-E) and colony-forming unit (CFU-E) populations from adult peripheral blood (PB), bone marrow (BM), and embryonic-fetal liver (FL) were treated with either c-myb antisense oligomers or 3H-thymidine (3H-TdR). A direct correlation was always observed between the inhibitory effect of anti-myb oligomers and the level of cycling activity. Thus, the inhibitory effect of antisense c-myb on the number of BFU-E colonies was 28.3% +/- 15.8% in PB, 53.4% +/- 9.3% in BM,more » and 68.2% +/- 24.5% in FL. Both adult and embryonic CFU-E were markedly inhibited. Using purified PB progenitors, we observed a similar pattern, although with slightly lower inhibitory effects. In the 3H-TdR suicide assay the killing index of BFU-E was 8.9% +/- 4.2% in PB, 29.4% +/- 6.5% in BM, and 40.1% +/- 9.6% in FL. The values for adult and embryonic CFU-E were 55.7% +/- 7.9% and 60.98% +/- 6.6%, respectively. We then investigated the kinetics of c-myb mRNA level during the erythroid differentiation of purified adult PB and FL BFU-E, as evaluated in liquid-phase culture by reverse transcription-polymerase chain reaction. Adult erythroid precursors showed a gradual increase of c-myb mRNA from day 4 through day 8 of culture and a sharp decrease at later times, whereas the expression of c-myb mRNA and protein in differentiation embryonic precursors peaked 2 days earlier. In both cases, c-myb mRNA level peaked at the CFU-E stage of differentiation. Finally, highly purified adult PB BFU-E were stimulated into cycling by a 3-day treatment with interleukin-3 in liquid phase: both the sensitivity to c-myb antisense oligomers and the 3H-TdR suicide index showed a gradual, strictly parallel increase.« less

Calcium Signaling Is Required for Erythroid Enucleation

PubMed Central

Russell, Sarah M.; Humbert, Patrick O.

2016-01-01

Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM) pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation. PMID:26731108

Context-dependent EKLF responsiveness defines the developmental specificity of the human ɛ-globin gene in erythroid cells of YAC transgenic mice

PubMed Central

Tanimoto, Keiji; Liu, Qinghui; Grosveld, Frank; Bungert, Jörg; Engel, James Douglas

2000-01-01

We explored the mechanism of definitive-stage ɛ-globin transcriptional inactivity within a human β-globin YAC expressed in transgenic mice. We focused on the globin CAC and CAAT promoter motifs, as previous laboratory and clinical studies indicated a pivotal role for these elements in globin gene activation. A high-affinity CAC-binding site for the erythroid krüppel-like factor (EKLF) was placed in the ɛ-globin promoter at a position corresponding to that in the adult β-globin promoter, thereby simultaneously ablating a direct repeat (DR) element. This mutation led to EKLF-independent ɛ-globin transcription during definitive erythropoiesis. A second 4-bp substitution in the ɛ-globin CAAT sequence, which simultaneously disrupts a second DR element, further enhanced ectopic definitive erythroid activation of ɛ-globin transcription, which surprisingly became EKLF dependent. We finally examined factors in nuclear extracts prepared from embryonic or adult erythroid cells that bound these elements in vitro, and we identified a novel DR-binding protein (DRED) whose properties are consistent with those expected for a definitive-stage ɛ-globin repressor. We conclude that the suppression of ɛ-globin transcription during definitive erythropoiesis is mediated by the binding of a repressor that prevents EKLF from activating the ɛ-globin gene. PMID:11069894

Holoprosencephaly and Pure Red Cell Aplasia in a Feline Leukaemia Virus-Positive Kitten.

PubMed

Southard, T L; Rodriguez-Ramos Fernandez, J; Priest, H; Stokol, T

2016-01-01

A 9-month-old, female, domestic longhair cat with severe anaemia tested positive for feline leukaemia virus (FeLV) and was humanely destroyed and submitted for necropsy examination. Gross findings included a non-divided rostral telencephalon, consistent with semilobar holoprosencephaly. Histological examination of the bone marrow revealed an almost complete absence of erythroid precursor cells, consistent with pure red cell aplasia, and mild to moderate myelofibrosis. This case demonstrates a very unusual central nervous system defect, as well as an atypical presentation of pure red cell aplasia, in a FeLV-positive kitten. Copyright © 2016 Elsevier Ltd. All rights reserved.

Erythroid colony induction without erythropoietin by Friend leukemia virus in vitro.

PubMed

Clarke, B J; Axelrad, A A; Shreeve, M M; McLeod, D L

1975-09-01

Erythroid colonies could be produced without the addition of erythropeietin in plasma cultures seeded with bone marrow cells from normal C3Hf/Bi mice by exposure of the cells in vitro to medium from a cell line (IS) that continuously produces Friend leukemia virus in culture. The activity in the culture medium was viral rather than erythropoietin-like, since it was sedimentable by high-speed centrifugation and heat labile. Erythroid colonies did not develop when the bone marrow cells exposed to virus-containing medium were from mice genetically resistant to Friend virus. IS culture medium contained both Friend spleen focus-forming and XC-plaque-forming activities. No erythroid colonies were induced when genetically sensitive cells were exposed to a preparation from which the spleen focus-forming activity had been removed, but which contained XC plaque-forming activity in high concentration. Thus the spleen focus-forming component of Friend virus appeared to be responsible for inducing erythroid colony formation without erythropoietin in vitro. Some erythroid colonies were also found in control cultures to which neither virus nor erythropoietin had been added. Reduction in the concentration of fetal calf serum in the culture medium substantially decreased the number of these colonies but had only a minor effect on the number of virus-induced colonies. The number of erythroid colonies produced after 2 days of culture without erythropoietin or fetal calf serum was approximately proportional to the titer of Friend spleen focus-forming virus to whcih the bone marrow cells had been exposed. This system should prove useful for investigation in vitro of Friend virus--host cell interactions which lead to erythropoietin-independent erythropoiesis.

TMEM14C is required for erythroid mitochondrial heme metabolism

PubMed Central

Yien, Yvette Y.; Robledo, Raymond F.; Schultz, Iman J.; Takahashi-Makise, Naoko; Gwynn, Babette; Bauer, Daniel E.; Dass, Abhishek; Yi, Gloria; Li, Liangtao; Hildick-Smith, Gordon J.; Cooney, Jeffrey D.; Pierce, Eric L.; Mohler, Kyla; Dailey, Tamara A.; Miyata, Non; Kingsley, Paul D.; Garone, Caterina; Hattangadi, Shilpa M.; Huang, Hui; Chen, Wen; Keenan, Ellen M.; Shah, Dhvanit I.; Schlaeger, Thorsten M.; DiMauro, Salvatore; Orkin, Stuart H.; Cantor, Alan B.; Palis, James; Koehler, Carla M.; Lodish, Harvey F.; Kaplan, Jerry; Ward, Diane M.; Dailey, Harry A.; Phillips, John D.; Peters, Luanne L.; Paw, Barry H.

2014-01-01

The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias. PMID:25157825

The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suriguga,; Li, Xiao-Fei; Li, Yang

2013-12-15

Catechol is widely used in pharmaceutical and chemical industries. Catechol is also one of phenolic metabolites of benzene in vivo. Our previous study showed that catechol improved erythroid differentiation potency of K562 cells, which was associated with decreased DNA methylation in erythroid specific genes. Catechol is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation. In the present study, the role of COMT in catechol-enhanced erythroid differentiation of K562 cells was investigated. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced mRNA expression of erythroid specific genes in K562 cells. Treatment with catechol caused a time- and concentration-dependentmore » increase in guaiacol concentration in the medium of cultured K562 cells. When COMT expression was knocked down by COMT shRNA expression in K562 cells, the production of guaiacol significantly reduced, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increased. Knockdown of COMT expression by COMT shRNA expression also eliminated catechol-enhanced erythroid differentiation of K562 cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine or its demethylated product S-adenosyl-L-homocysteine induced a significant increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of erythroid specific genes. These findings indicated that O-methylation catalyzed by COMT acted as detoxication of catechol and involved in catechol-enhanced erythroid differentiation of K562 cells, and the production of S-adenosyl-L-homocysteine partly explained catechol-enhanced erythroid differentiation. - Highlights: • Catechol enhanced hemin-induced hemoglobin accumulation. • COMT-catalyzed methylation acted as detoxication of catechol. • COMT involved in catechol-enhanced erythroid differentiation.« less

The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells.

PubMed

Suriguga; Li, Xiao-Fei; Li, Yang; Yu, Chun-Hong; Li, Yi-Ran; Yi, Zong-Chun

2013-12-15

Catechol is widely used in pharmaceutical and chemical industries. Catechol is also one of phenolic metabolites of benzene in vivo. Our previous study showed that catechol improved erythroid differentiation potency of K562 cells, which was associated with decreased DNA methylation in erythroid specific genes. Catechol is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation. In the present study, the role of COMT in catechol-enhanced erythroid differentiation of K562 cells was investigated. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced mRNA expression of erythroid specific genes in K562 cells. Treatment with catechol caused a time- and concentration-dependent increase in guaiacol concentration in the medium of cultured K562 cells. When COMT expression was knocked down by COMT shRNA expression in K562 cells, the production of guaiacol significantly reduced, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increased. Knockdown of COMT expression by COMT shRNA expression also eliminated catechol-enhanced erythroid differentiation of K562 cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine or its demethylated product S-adenosyl-L-homocysteine induced a significant increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of erythroid specific genes. These findings indicated that O-methylation catalyzed by COMT acted as detoxication of catechol and involved in catechol-enhanced erythroid differentiation of K562 cells, and the production of S-adenosyl-L-homocysteine partly explained catechol-enhanced erythroid differentiation. © 2013.

Genome Editing of Erythroid Cell Culture Model Systems.

PubMed

Yik, Jinfen J; Crossley, Merlin; Quinlan, Kate G R

2018-01-01

Genome editing to introduce specific mutations or to knock out genes in model cell systems has become an efficient platform for research in the fields of molecular biology, genetics, and cell biology. With recent rapid improvements in genome editing techniques, bench-top manipulation of the genome in cell culture has become progressively easier. The application of this knowledge to erythroid cell culture systems now allows the rapid analysis of the downstream effects of virtually any engineered gene disruption or modification in cell systems. Here, we describe a CRISPR/Cas9-based approach to making genomic modifications in erythroid lineage cells which we have successfully used in both murine (MEL) and human (K562) erythroleukaemia immortalized cell lines.

Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation

PubMed Central

2012-01-01

Background The fetal and adult globin genes in the human β-globin cluster on chromosome 11 are sequentially expressed to achieve normal hemoglobin switching during human development. The pharmacological induction of fetal γ-globin (HBG) to replace abnormal adult sickle βS-globin is a successful strategy to treat sickle cell disease; however the molecular mechanism of γ-gene silencing after birth is not fully understood. Therefore, we performed global gene expression profiling using primary erythroid progenitors grown from human peripheral blood mononuclear cells to characterize gene expression patterns during the γ-globin to β-globin (γ/β) switch observed throughout in vitro erythroid differentiation. Results We confirmed erythroid maturation in our culture system using cell morphologic features defined by Giemsa staining and the γ/β-globin switch by reverse transcription-quantitative PCR (RT-qPCR) analysis. We observed maximal γ-globin expression at day 7 with a switch to a predominance of β-globin expression by day 28 and the γ/β-globin switch occurred around day 21. Expression patterns for transcription factors including GATA1, GATA2, KLF1 and NFE2 confirmed our system produced the expected pattern of expression based on the known function of these factors in globin gene regulation. Subsequent gene expression profiling was performed with RNA isolated from progenitors harvested at day 7, 14, 21, and 28 in culture. Three major gene profiles were generated by Principal Component Analysis (PCA). For profile-1 genes, where expression decreased from day 7 to day 28, we identified 2,102 genes down-regulated > 1.5-fold. Ingenuity pathway analysis (IPA) for profile-1 genes demonstrated involvement of the Cdc42, phospholipase C, NF-Kβ, Interleukin-4, and p38 mitogen activated protein kinase (MAPK) signaling pathways. Transcription factors known to be involved in γ-and β-globin regulation were identified. The same approach was used to generate profile-2

Expression of transcription factors during sodium phenylacetate induced erythroid differentiation in K562 cells.

PubMed

Rath, A V; Schmahl, G E; Niemeyer, C M

1997-01-01

During 15 days of treatment of K562 cells with sodium phenylacetate, we observed an increase in the cellular hemoglobin concentration with a similar increase in the expression of gamma-globin mRNA. Morphological studies demonstrated characteristic features of erythroid differentiation and maturation. At the same time there was no change in the level of expression of the cell surface antigenes CD33, CD34, CD45, CD71 and glycophorin A. Likewise, the level of expression of the erythroid transcription factors GATA-1, GATA-2, NF-E2, SCL and RBTN2, all expressed in untreated K562 cells, did not increase during sodium phenylacetate induced erythroid differentiation. The expression of the nuclear factors Evi-1 and c-myb, known to inhibit erythroid differentiation, did not decrease. We conclude that sodium phenylacetate treatment of K562 cells increases gamma-globin mRNA and induces cell maturation as judged by morphology without affecting the expression of the erythroid transcription factors, some of which are known to be involved in the regulation of beta-like globin genes.

Acute erythroid leukemia as defined in the World Health Organization classification is a rare and pathogenetically heterogeneous disease.

PubMed

Kasyan, Armen; Medeiros, L Jeffrey; Zuo, Zhuang; Santos, Favio P; Ravandi-Kashani, Farhad; Miranda, Roberto; Vadhan-Raj, Saroj; Koeppen, Hartmut; Bueso-Ramos, Carlos E

2010-08-01

The diagnostic criteria for acute erythroid leukemia have been controversial since this disease was initially described. Using the current World Health Organization classification criteria, we retrospectively reviewed cases of acute myeloid leukemia or myelodysplastic syndrome in which erythroid precursors were >or=50% of the bone marrow nucleated cell population and the diagnosis of erythroleukemia was considered using older classification schemes. We collected 90 cases and separated them into four diagnostic groups: acute erythroid leukemia, erythroleukemia or erythroid/myeloid type (n=20); acute myeloid leukemia with myelodysplasia-related changes (n=22); therapy-related acute myeloid leukemia (n=32); and refractory anemia with excess blasts and preceding or concurrent history of erythropoietin therapy for anemia (n=16). Patients with acute erythroid leukemia were the youngest patient group and had the best overall survival. There was a statistically significant difference in overall survival between patients with acute erythroid leukemia versus acute myeloid leukemia with myelodysplasia-related changes (P=0.003) and between patients with acute erythroid leukemia versus therapy-related acute myeloid leukemia (P<0.0001). The presence of complex cytogenetic abnormalities (>3) was the only statistically significant independent variable that adversely affected survival in the acute erythroid leukemia group. Monosomy 5/del(5q) and monosomy 7/del(7q) were overrepresented in the context of complex chromosomal abnormalities. Our data suggest that acute erythroid leukemia, as currently defined in the World Health Organization classification, has become a rare disease. A majority of the cases reported previously as erythroleukemia are now classified as other entities. In addition, our data suggest that the current definition of acute erythroid leukemia, erythroleukemia type remains heterogeneous. One subset of acute erythroid leukemia patients has relatively low blast

Interleukin-6 Directly Impairs the Erythroid Development of Human TF-1 Erythroleukemic Cells

PubMed Central

McCranor, Bryan J.; Kim, Min Jung; Cruz, Nicole M.; Xue, Qian-Li; Berger, Alan E.; Walston, Jeremy D.; Civin, Curt I.; Roy, Cindy N.

2013-01-01

Anemia of inflammation or chronic disease is a highly prevalent form of anemia. The inflammatory cytokine interleukin-6 (IL-6) negatively correlates with hemoglobin concentration in many disease states. The IL-6-hepcidin antimicrobial peptide axis promotes iron-restricted anemia; however the full role of IL-6 in anemia of inflammation is not well-defined. We previously reported that chronic inflammation had a negative impact on maturation of erythroid progenitors in a mouse model. We hypothesized that IL-6 may be responsible for impaired erythropoiesis, independent of iron restriction. To test the hypothesis we utilized the human erythroleukemia TF-1 cell line to model erythroid maturation and exposed them to varying doses of IL-6 over six days. At 10 ng/ml, IL-6 significantly repressed erythropoietin-dependent TF-1 erythroid maturation. While IL-6 did not decrease the expression of genes associated with hemoglobin synthesis, we observed impaired hemoglobin synthesis as demonstrated by decreased benzidine staining. We also observed that IL-6 down regulated expression of the gene SLC4a1 which is expressed late in erythropoiesis. Those findings suggested that IL-6-dependent inhibition of hemoglobin synthesis might occur. We investigated the impact of IL-6 on mitochondria. IL-6 decreased the mitochondrial membrane potential at all treatment doses, and significantly decreased mitochondrial mass at the highest dose. Our studies indicate that IL-6 may impair mitochondrial function in maturing erythroid cells resulting in impaired hemoglobin production and erythroid maturation. Our findings may indicate a novel pathway of action for IL-6 in the anemia of inflammation, and draw attention to the potential for new therapeutic targets that affect late erythroid development. PMID:24119518

Erythroid Kruppel-like factor (EKLF) is recruited to the γ-globin gene promoter as a co-activator and is required for γ-globin gene induction by short-chain fatty acid derivatives

PubMed Central

Perrine, Susan P.; Mankidy, Rishikesh; Boosalis, Michael S.; Bieker, James J.; Faller, Douglas V.

2011-01-01

Objectives The erythroid Kruppel-like factor (EKLF) is an essential transcription factor for β-type globin gene switching, and specifically activates transcription of the adult β-globin gene promoter. We sought to determine if EKLF is also required for activation of the γ-globin gene by short-chain fatty acid (SCFA) derivatives, which are now entering clinical trials. Methods The functional and physical interaction of EKLF and co-regulatory molecules with the endogenous human globin gene promoters was studied in primary human erythroid progenitors and cell lines, using chromatin immunoprecipitation (ChIP) assays and genetic manipulation of the levels of EKLF and co-regulators. Results and conclusions Knockdown of EKLF prevents SCFA-induced expression of the γ-globin promoter in a stably expressed μLCRβprRlucAγprFluc cassette, and prevents induction of the endogenous γ-globin gene in primary human erythroid progenitors. EKLF is actively recruited to endogenous γ-globin gene promoters after exposure of primary human erythroid progenitors, and murine hematopoietic cell lines, to SCFA derivatives. The core ATPase BRG1 subunit of the human SWI/WNF complex, a ubiquitous multimeric complex that regulates gene expression by remodeling nucleosomal structure, is also required for γ-globin gene induction by SCFA derivatives. BRG1 is actively recruited to the endogenous γ-globin promoter of primary human erythroid progenitors by exposure to SCFA derivatives, and this recruitment is dependent upon the presence of EKLF. These findings demonstrate that EKLF, and the co-activator BRG1, previously demonstrated to be required for definitive or adult erythropoietic patterns of globin gene expression, are co-opted by SCFA derivatives to activate the fetal globin genes. PMID:19220418

Control of developmentally primed erythroid genes by combinatorial co-repressor actions

PubMed Central

Stadhouders, Ralph; Cico, Alba; Stephen, Tharshana; Thongjuea, Supat; Kolovos, Petros; Baymaz, H. Irem; Yu, Xiao; Demmers, Jeroen; Bezstarosti, Karel; Maas, Alex; Barroca, Vilma; Kockx, Christel; Ozgur, Zeliha; van Ijcken, Wilfred; Arcangeli, Marie-Laure; Andrieu-Soler, Charlotte; Lenhard, Boris; Grosveld, Frank; Soler, Eric

2015-01-01

How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2–IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation. PMID:26593974

Brief report: ectopic expression of NUP98-HOXA10 augments erythroid differentiation of human embryonic stem cells.

PubMed

Ji, Junfeng; Risueño, Ruth M; Hong, Seokho; Allan, David; Rosten, Patty; Humphries, Keith; Bhatia, Mickie

2011-04-01

Hox genes encode highly conserved transcription factors that have been implicated in hematopoietic development and self-renewal of hematopoietic stem cells (HSCs) and hematopoietic development. The potency of NUP98-HOXA10hd (NA10) on adult murine bone marrow HSC self-renewal prompted us to examine its effect on specification and proliferation of hematopoietic cells derived from human embryonic stem cells (hESCs). Here, we demonstrate that expression of NA10 in hESCs influences the hematopoietic differentiation program. The specific effect of NA10 is dependent on the developmental stage of hematopoietic emergence from hESCs. Overexpression of NA10 in either undifferentiated hESCs or early hemogenic precursors augmented the frequency of CD45(-) GlycophorinA(+) cells and erythroid progenitors (blast-forming unit-erythrocyte). In contrast, targeted NA10 expression in primitive CD34+ cells committed to the hematopoietic lineage had no effect on erythropoietic capacity but instead increased hematopoietic progenitor proliferation. Our study reveals a novel neomorphic effect of NA10 in early human erythroid development from pluripotent stem cells. Copyright © 2011 AlphaMed Press.

Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2013-02-01

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Umbilical cord CD71+ erythroid cells are reduced in neonates born to women in spontaneous preterm labor.

PubMed

Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Miller, Derek; Unkel, Ronald; C MacKenzie, Tippi; Frascoli, Michela; Hassan, Sonia S

2016-10-01

Preterm neonates are highly susceptible to infection. Neonatal host defense against infection seems to be maintained by the temporal presence of immunosuppressive CD71+ erythroid cells. The aim of this study was to investigate whether umbilical cord CD71+ erythroid cells are reduced in neonates born to women who undergo spontaneous preterm labor/birth. Umbilical cord blood samples (n=155) were collected from neonates born to women who delivered preterm with (n=39) and without (n=12) spontaneous labor or at term with (n=82) and without (n=22) spontaneous labor. Time-matched maternal peripheral blood samples were also included (n=111). Mononuclear cells were isolated from these samples, and CD71+ erythroid cells were identified and quantified as CD3-CD235a+CD71+ cells by flow cytometry. (i) The proportion of CD71+ erythroid cells was 50-fold higher in cord blood than in maternal blood; (ii) a reduced number and frequency of umbilical cord CD71+ erythroid cells were found in neonates born to women who underwent spontaneous preterm labor compared to those born to women who delivered preterm without labor; (iii) umbilical cord CD71+ erythroid cells were fewer in neonates born to term pregnancies, regardless of the process of labor, than in those born to women who delivered preterm without labor; and (iv) no differences were seen in umbilical cord CD71+ erythroid cells between neonates born to women who underwent spontaneous preterm labor and those born to women who delivered at term with labor. Umbilical cord CD71+ erythroid cells are reduced in neonates born to women who had undergone spontaneous preterm labor. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Role of Phosphatidylinositol 3-Kinase in Friend Spleen Focus-Forming Virus-Induced Erythroid Disease▿

PubMed Central

Umehara, Daigo; Watanabe, Shinya; Ochi, Haruyo; Anai, Yukari; Ahmed, Nursarat; Kannagi, Mari; Hanson, Charlotte; Ruscetti, Sandra; Nishigaki, Kazuo

2010-01-01

Infection of erythroid cells by Friend spleen focus-forming virus (SFFV) leads to acute erythroid hyperplasia in mice due to expression of its unique envelope glycoprotein, gp55. Erythroid cells expressing SFFV gp55 proliferate in the absence of their normal regulator, erythropoietin (Epo), because of interaction of the viral envelope protein with the erythropoietin receptor and a short form of the receptor tyrosine kinase Stk (sf-Stk), leading to constitutive activation of several signal transduction pathways. Our previous in vitro studies showed that phosphatidylinositol 3-kinase (PI3-kinase) is activated in SFFV-infected cells and is important in mediating the biological effects of the virus. To determine the role of PI3-kinase in SFFV-induced disease, mice deficient in the p85α regulatory subunit of class IA PI3-kinase were inoculated with different strains of SFFV. We observed that p85α status determined the extent of erythroid hyperplasia induced by the sf-Stk-dependent viruses SFFV-P (polycythemia-inducing strain of SFFV) and SFFV-A (anemia-inducing strain of SFFV) but not by the sf-Stk-independent SFFV variant BB6. Our data also indicate that p85α status determines the response of mice to stress erythropoiesis, consistent with a previous report showing that SFFV uses a stress erythropoiesis pathway to induce erythroleukemia. We further showed that sf-Stk interacts with p85α and that this interaction depends upon sf-Stk kinase activity and tyrosine 436 in the multifunctional docking site. Pharmacological inhibition of PI3-kinase blocked proliferation of primary erythroleukemia cells from SFFV-infected mice and the erythroleukemia cell lines derived from them. These results indicate that p85α may regulate sf-Stk-dependent erythroid proliferation induced by SFFV as well as stress-induced erythroid hyperplasia. PMID:20504929

Inadequate erythroid response to hypoxia in cystic fibrosis.

PubMed

Vichinsky, E P; Pennathur-Das, R; Nickerson, B; Minor, M; Kleman, K; Higashino, S; Lubin, B

1984-07-01

An increase in hemoglobin concentration characterizes the normal compensatory response to chronic tissue hypoxia. We observed no such increase in 42 chronically hypoxic patients with cystic fibrosis, in whom the mean concentration was 12.6 gm/dl; one third of the patients were anemic. Compared with patients with cyanotic heart disease, patients with cystic fibrosis did not have a compensatory increase in P50 or 2,3-diphosphoglycerate. Despite anemia, erythropoietin levels in patients with cystic fibrosis were not significantly different from normal control values. The growth of colony-forming units-erythroid in patients with cystic fibrosis was similar to that in control subjects, and there was no inhibition of growth with the addition of autologous serum. Erythropoietin sensitivity, determined by measuring the CFUe dose response curve, was normal in both patients and controls. Results of iron studies were consistent with iron deficiency in the majority of patients. Impaired absorption of iron was observed in six of 13 iron-deficient patients with cystic fibrosis. An inverse correlation between erythrocyte sedimentation rate and peak serum iron was obtained during the iron absorption study. Eight patients who underwent a therapeutic trial of iron demonstrated a 1.8 gm/dl rise in hemoglobin concentration. Two patients with previously documented iron malabsorption responded to parenteral iron therapy after failure to respond to oral supplementation. These studies demonstrate that patients with cystic fibrosis not only have an impaired erythroid response to hypoxia, but are frequently anemic. Their inadequate erythroid response to hypoxia results in part from disturbances in erythropoietin regulation and iron availability.

Generation of erythroid cells from polyploid giant cancer cells: re-thinking about tumor blood supply.

PubMed

Yang, Zhigang; Yao, Hong; Fei, Fei; Li, Yuwei; Qu, Jie; Li, Chunyuan; Zhang, Shiwu

2018-04-01

During development and tumor progression, cells need a sufficient blood supply to maintain development and rapid growth. It is reported that there are three patterns of blood supply for tumor growth: endothelium-dependent vessels, mosaic vessels, and vasculogenic mimicry (VM). VM was first reported in highly aggressive uveal melanomas, with tumor cells mimicking the presence and function of endothelial cells forming the walls of VM vessels. The walls of mosaic vessels are randomly lined with both endothelial cells and tumor cells. We previously proposed a three-stage process, beginning with VM, progressing to mosaic vessels, and eventually leading to endothelium-dependent vessels. However, many phenomena unique to VM channel formation remain to be elucidated, such as the origin of erythrocytes before VM vessels connect with endothelium-dependent vessels. In adults, erythroid cells are generally believed to be generated from hematopoietic stem cells in the bone marrow. In contrast, embryonic tissue obtains oxygen through formation of blood islands, which are largely composed of embryonic hemoglobin with a higher affinity with oxygen, in the absence of mature erythrocytes. Recent data from our laboratory suggest that embryonic blood-forming mechanisms also exist in cancer tissue, particularly when these tissues are under environmental stress such as hypoxia. We review the evidence from induced pluripotent stem cells in vitro and in vivo to support this previously underappreciated cell functionality in normal and cancer cells, including the ability to generate erythroid cells. We will also summarize the current understanding of tumor angiogenesis, VM, and our recent work on polyploid giant cancer cells, with emphasis on their ability to generate erythroid cells and their association with tumor growth under hypoxia. An alternative embryonic pathway to obtain oxygen in cancer cells exists, particularly when they are under hypoxic conditions.

Assessment of Erythroid and Granulocytic Hematopoietic Lineages in Patients with Non-Small-Cell Lung Carcinoma.

PubMed

Goldberg, V E; Polyakova, T Yu; Popova, N O; Vysotskaya, V V; Simolina, E I; Belevich, Yu V; Tuzikova, T P; Goldberg, A V; Zhdanov, V V; Miroshnichenko, L A; Udut, E V; Simanina, E V; Dygai, A M; Zyuz'kov, G N

2017-08-01

The toxic effects of combined cisplatin/docetaxel therapy cycles on erythroid and granulocytic hematopoietic lineages as well as their intercycle recovery were examined in patients with stage III-IV non-small-cell lung carcinoma. Responsiveness of the blood system to this therapy remained at a high level. Combined therapy pronouncedly activated the key elements of the erythroid and granulocytic hematopoietic lineages leading to accumulation of immature and mature myelokaryocytes in the bone marrow, enlargement of the medullary pool of mature neutrophils, and increase in the count of medullary erythroid and granulocytic precursor cells under conditions of their accelerated maturation.

PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis

PubMed Central

Ryu, Moon-Suhn; Zhang, Deliang; Protchenko, Olga; Shakoury-Elizeh, Minoo

2017-01-01

Developing erythrocytes take up exceptionally large amounts of iron, which must be transferred to mitochondria for incorporation into heme. This massive iron flux must be precisely controlled to permit the coordinated synthesis of heme and hemoglobin while avoiding the toxic effects of chemically reactive iron. In cultured animal cells, iron chaperones poly rC–binding protein 1 (PCBP1) and PCBP2 deliver iron to ferritin, the sole cytosolic iron storage protein, and nuclear receptor coactivator 4 (NCOA4) mediates the autophagic turnover of ferritin. The roles of PCBP, ferritin, and NCOA4 in erythroid development remain unclear. Here, we show that PCBP1, NCOA4, and ferritin are critical for murine red cell development. Using a cultured cell model of erythroid differentiation, depletion of PCBP1 or NCOA4 impaired iron trafficking through ferritin, which resulted in reduced heme synthesis, reduced hemoglobin formation, and perturbation of erythroid regulatory systems. Mice lacking Pcbp1 exhibited microcytic anemia and activation of compensatory erythropoiesis via the regulators erythropoietin and erythroferrone. Ex vivo differentiation of erythroid precursors from Pcbp1-deficient mice confirmed defects in ferritin iron flux and heme synthesis. These studies demonstrate the importance of ferritin for the vectorial transfer of imported iron to mitochondria in developing red cells and of PCBP1 and NCOA4 in mediating iron flux through ferritin. PMID:28375153

In vitro culture of stress erythroid progenitors identifies distinct progenitor populations and analogous human progenitors.

PubMed

Xiang, Jie; Wu, Dai-Chen; Chen, Yuanting; Paulson, Robert F

2015-03-12

Tissue hypoxia induces a systemic response designed to increase oxygen delivery to tissues. One component of this response is increased erythropoiesis. Steady-state erythropoiesis is primarily homeostatic, producing new erythrocytes to replace old erythrocytes removed from circulation by the spleen. In response to anemia, the situation is different. New erythrocytes must be rapidly made to increase hemoglobin levels. At these times, stress erythropoiesis predominates. Stress erythropoiesis is best characterized in the mouse, where it is extramedullary and utilizes progenitors and signals that are distinct from steady-state erythropoiesis. In this report, we use an in vitro culture system that recapitulates the in vivo development of stress erythroid progenitors. We identify cell-surface markers that delineate a series of stress erythroid progenitors with increasing maturity. In addition, we use this in vitro culture system to expand human stress erythroid progenitor cells that express analogous cell-surface markers. Consistent with previous suggestions that human stress erythropoiesis is similar to fetal erythropoiesis, we demonstrate that human stress erythroid progenitors express fetal hemoglobin upon differentiation. These data demonstrate that similar to murine bone marrow, human bone marrow contains cells that can generate BMP4-dependent stress erythroid burst-forming units when cultured under stress erythropoiesis conditions. © 2015 by The American Society of Hematology.

Recombinant Human Parvovirus B19 Vectors: Erythroid Cell-Specific Delivery and Expression of Transduced Genes

PubMed Central

Ponnazhagan, Selvarangan; Weigel, Kirsten A.; Raikwar, Sudhanshu P.; Mukherjee, Pinku; Yoder, Mervin C.; Srivastava, Arun

1998-01-01

A novel packaging strategy combining the salient features of two human parvoviruses, namely the pathogenic parvovirus B19 and the nonpathogenic adeno-associated virus type 2 (AAV), was developed to achieve erythroid cell-specific delivery as well as expression of the transduced gene. The development of such a chimeric vector system was accomplished by packaging heterologous DNA sequences cloned within the inverted terminal repeats of AAV and subsequently packaging the DNA inside the capsid structure of B19 virus. Recombinant B19 virus particles were assembled, as evidenced by electron microscopy as well as DNA slot blot analyses. The hybrid vector failed to transduce nonerythroid human cells, such as 293 cells, as expected. However, MB-02 cells, a human megakaryocytic leukemia cell line which can be infected by B19 virus following erythroid differentiation with erythropoietin (N. C. Munshi, S. Z. Zhou, M. J. Woody, D. A. Morgan, and A. Srivastava, J. Virol. 67:562–566, 1993) but lacks the putative receptor for AAV (S. Ponnazhagan, X.-S. Wang, M. J. Woody, F. Luo, L. Y. Kang, M. L. Nallari, N. C. Munshi, S. Z. Zhou, and A. Srivastava, J. Gen. Virol. 77:1111–1122, 1996), were readily transduced by this vector. The hybrid vector was also found to specifically target the erythroid population in primary human bone marrow cells as well as more immature hematopoietic progenitor cells following erythroid differentiation, as evidenced by selective expression of the transduced gene in these target cells. Preincubation with anticapsid antibodies against B19 virus, but not anticapsid antibodies against AAV, inhibited transduction of primary human erythroid cells. The efficiency of transduction of primary human erythroid cells by the recombinant B19 virus vector was significantly higher than that by the recombinant AAV vector. Further development of the AAV-B19 virus hybrid vector system should prove beneficial in gene therapy protocols aimed at the correction of inherited

Unimpaired terminal erythroid differentiation and preserved enucleation capacity in myelodysplastic 5q(del) clones: a single cell study

PubMed Central

Garderet, Laurent; Kobari, Ladan; Mazurier, Christelle; De Witte, Caroline; Giarratana, Marie-Catherine; Pérot, Christine; Gorin, Norbert Claude; Lapillonne, Hélène; Douay, Luc

2010-01-01

Background Anemia is a characteristic of myelodysplastic syndromes, such as the rare 5q- syndrome, but its mechanism remains unclear. In particular, data are lacking on the terminal phase of differentiation of erythroid cells (enucleation) in myelodysplastic syndromes. Design and Methods We used a previously published culture model to generate mature red blood cells in vitro from human hematopoietic progenitor cells in order to study the pathophysiology of the 5q- syndrome. Our model enables analysis of cell proliferation and differentiation at a single cell level and determination of the enucleation capacity of erythroid precursors. Results The erythroid commitment of 5q(del) clones was not altered and their terminal differentiation capacity was preserved since they achieved final erythroid maturation (enucleation stage). The drop in red blood cell production was secondary to the decrease in the erythroid progenitor cell pool and to impaired proliferative capacity. RPS14 gene haploinsufficiency was related to defective erythroid proliferation but not to differentiation capacity. Conclusions The 5q- syndrome should be considered a quantitative rather than qualitative bone marrow defect. This observation might open the way to new therapeutic concepts. PMID:19815832

Erythroid differentiation ability of butyric acid analogues: identification of basal chemical structures of new inducers of foetal haemoglobin.

PubMed

Bianchi, Nicoletta; Chiarabelli, Cristiano; Zuccato, Cristina; Lampronti, Ilaria; Borgatti, Monica; Amari, Gabriele; Delcanale, Maurizio; Chiavilli, Francesco; Prus, Eugenia; Fibach, Eitan; Gambari, Roberto

2015-04-05

Several investigations have demonstrated a mild clinical status in patients with β-globin disorders and congenital high persistence of foetal haemoglobin. This can be mimicked by a pharmacological increase of foetal γ-globin genes expression and foetal haemoglobin production. Our goal was to apply a multistep assay including few screening methods (benzidine staining, RT-PCR and HPLC analyses) and erythroid cellular model systems (the K562 cell line and erythroid precursors collected from peripheral blood) to select erythroid differentiation agents with foetal haemoglobin inducing potential. With this methodology, we have identified a butyric acid derivative, namely the 4174 cyclopropanecarboxylic acid compound, able to induce erythroid differentiation without antiproliferative effect in K562 cells and increase of γ-globin gene expression in erythroid precursor cells. The results are relevant for pharmacological treatments of haemoglobinopathies, including β-thalassaemia and sickle cell anaemia. Copyright © 2015 Elsevier B.V. All rights reserved.

The Asymmetric Cell Division Regulators Par3, Scribble and Pins/Gpsm2 Are Not Essential for Erythroid Development or Enucleation

PubMed Central

Wölwer, Christina B.; Gödde, Nathan; Pase, Luke B.; Elsum, Imogen A.; Lim, Krystle Y. B.; Sacirbegovic, Faruk; Walkley, Carl R.; Ellis, Sarah; Ohno, Shigeo; Matsuzaki, Fumio; Russell, Sarah M.; Humbert, Patrick O.

2017-01-01

Erythroid enucleation is the process by which the future red blood cell disposes of its nucleus prior to entering the blood stream. This key event during red blood cell development has been likened to an asymmetric cell division (ACD), by which the enucleating erythroblast divides into two very different daughter cells of alternate molecular composition, a nucleated cell that will be removed by associated macrophages, and the reticulocyte that will mature to the definitive erythrocyte. Here we investigated gene expression of members of the Par, Scribble and Pins/Gpsm2 asymmetric cell division complexes in erythroid cells, and functionally tested their role in erythroid enucleation in vivo and ex vivo. Despite their roles in regulating ACD in other contexts, we found that these polarity regulators are not essential for erythroid enucleation, nor for erythroid development in vivo. Together our results put into question a role for cell polarity and asymmetric cell division in erythroid enucleation. PMID:28095473

Hepatocyte growth factor induces proliferation and differentiation of multipotent and erythroid hemopoietic progenitors.

PubMed

Galimi, F; Bagnara, G P; Bonsi, L; Cottone, E; Follenzi, A; Simeone, A; Comoglio, P M

1994-12-01

Hepatocyte growth factor (HGF) is a mesenchymal derived growth factor known to induce proliferation and "scattering" of epithelial and endothelial cells. Its receptor is the tyrosine kinase encoded by the c-MET protooncogene. Here we show that highly purified recombinant HGF stimulates hemopoietic progenitors to form colonies in vitro. In the presence of erythropoietin, picomolar concentrations of HGF induced the formation of erythroid burst-forming unit colonies from CD34-positive cells purified from human bone marrow, peripheral blood, or umbilical cord blood. The growth stimulatory activity was restricted to the erythroid lineage. HGF also stimulated the formation of multipotent CFU-GEMM colonies. This effect is synergized by stem cell factor, the ligand of the tyrosine kinase receptor encoded by the c-KIT protooncogene, which is active on early hemopoietic progenitors. By flow cytometry analysis, the receptor for HGF was found to be expressed on the cell surface in a fraction of CD34+ progenitors. Moreover, in situ hybridization experiments showed that HGF receptor mRNA is highly expressed in embryonic erythroid cells (megaloblasts). HGF mRNA was also found to be produced in the embryonal liver. These data show that HGF plays a direct role in the control of proliferation and differentiation of erythroid progenitors, and they suggest that it may be one of the long-sought mediators of paracrine interactions between stromal and hemopoietic cells within the hemopoietic microenvironment.

MLF1IP promotes normal erythroid proliferation and is involved in the pathogenesis of polycythemia vera.

PubMed

Feng, Gege; Zhang, Tianjiao; Liu, Jinqin; Ma, Xiaotang; Li, Bing; Yang, Lin; Zhang, Yue; Xu, Zefeng; Qin, Tiejun; Zhou, Jiaxi; Huang, Gang; Shi, Lihong; Xiao, Zhijian

2017-03-01

Myelodysplasia/myeloid leukemia factor 1-interacting protein (MLF1IP) appears to be an erythroid lineage-specific gene in mice; however, its role in normal erythropoiesis and erythropoietic disorders have not yet been elucidated. Here, we found that MLF1IP is abundantly expressed in human erythroid progenitor cells and that MLF1IP-deficiency reduces cell proliferation resulting from cell cycle arrest. Moreover, MLF1IP expression is exclusively elevated in CFU-E cells from polycythemia vera (PV) patients, and MLF1IP transgenic mice develop a PV-like disorder. Further analyses revealed that the erythroid progenitors and early-stage erythroblasts from these transgenic mice expand by up-regulating cyclin D2 and down-regulating p27 and p21. Thus, our data demonstrate that MLF1IP promotes erythroid proliferation and is involved in the pathogenesis of PV, suggesting that it might be a novel molecular target for erythropoietic disorders. © 2017 Federation of European Biochemical Societies.

Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells.

PubMed

Kurita, Ryo; Suda, Noriko; Sudo, Kazuhiro; Miharada, Kenichi; Hiroyama, Takashi; Miyoshi, Hiroyuki; Tani, Kenzaburo; Nakamura, Yukio

2013-01-01

Transfusion of red blood cells (RBCs) is a standard and indispensable therapy in current clinical practice. In vitro production of RBCs offers a potential means to overcome a shortage of transfusable RBCs in some clinical situations and also to provide a source of cells free from possible infection or contamination by microorganisms. Thus, in vitro production of RBCs may become a standard procedure in the future. We previously reported the successful establishment of immortalized mouse erythroid progenitor cell lines that were able to produce mature RBCs very efficiently. Here, we have developed a reliable protocol for establishing immortalized human erythroid progenitor cell lines that are able to produce enucleated RBCs. These immortalized cell lines produce functional hemoglobin and express erythroid-specific markers, and these markers are upregulated following induction of differentiation in vitro. Most importantly, these immortalized cell lines all produce enucleated RBCs after induction of differentiation in vitro, although the efficiency of producing enucleated RBCs remains to be improved further. To the best of our knowledge, this is the first demonstration of the feasibility of using immortalized human erythroid progenitor cell lines as an ex vivo source for production of enucleated RBCs.

An erythroid-specific ATP2B4 enhancer mediates red blood cell hydration and malaria susceptibility

PubMed Central

Lessard, Samuel; Gatof, Emily Stern; Schupp, Patrick G.; Sher, Falak; Ali, Adnan; Prehar, Sukhpal; Kurita, Ryo; Nakamura, Yukio; Baena, Esther; Oceandy, Delvac; Bauer, Daniel E.

2017-01-01

The lack of mechanistic explanations for many genotype-phenotype associations identified by GWAS precludes thorough assessment of their impact on human health. Here, we conducted an expression quantitative trait locus (eQTL) mapping analysis in erythroblasts and found erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of red blood cells (rbc). The same SNPs were previously associated with mean corpuscular hemoglobin concentration (MCHC) and susceptibility to severe malaria infection. We showed that Atp2b4–/– mice demonstrate increased MCHC, confirming ATP2B4 as the causal gene at this GWAS locus. Using CRISPR-Cas9, we fine mapped the genetic signal to an erythroid-specific enhancer of ATP2B4. Erythroid cells with a deletion of the ATP2B4 enhancer had abnormally high intracellular calcium levels. These results illustrate the power of combined transcriptomic, epigenomic, and genome-editing approaches in characterizing noncoding regulatory elements in phenotype-relevant cells. Our study supports ATP2B4 as a potential target for modulating rbc hydration in erythroid disorders and malaria infection. PMID:28714864

An erythroid-specific ATP2B4 enhancer mediates red blood cell hydration and malaria susceptibility.

PubMed

Lessard, Samuel; Gatof, Emily Stern; Beaudoin, Mélissa; Schupp, Patrick G; Sher, Falak; Ali, Adnan; Prehar, Sukhpal; Kurita, Ryo; Nakamura, Yukio; Baena, Esther; Ledoux, Jonathan; Oceandy, Delvac; Bauer, Daniel E; Lettre, Guillaume

2017-08-01

The lack of mechanistic explanations for many genotype-phenotype associations identified by GWAS precludes thorough assessment of their impact on human health. Here, we conducted an expression quantitative trait locus (eQTL) mapping analysis in erythroblasts and found erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of red blood cells (rbc). The same SNPs were previously associated with mean corpuscular hemoglobin concentration (MCHC) and susceptibility to severe malaria infection. We showed that Atp2b4-/- mice demonstrate increased MCHC, confirming ATP2B4 as the causal gene at this GWAS locus. Using CRISPR-Cas9, we fine mapped the genetic signal to an erythroid-specific enhancer of ATP2B4. Erythroid cells with a deletion of the ATP2B4 enhancer had abnormally high intracellular calcium levels. These results illustrate the power of combined transcriptomic, epigenomic, and genome-editing approaches in characterizing noncoding regulatory elements in phenotype-relevant cells. Our study supports ATP2B4 as a potential target for modulating rbc hydration in erythroid disorders and malaria infection.

Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy.

PubMed

Zhao, Yang; Dong, Daoyin; Reece, E Albert; Wang, Ashley R; Yang, Peixin

2018-01-01

Maternal diabetes induces neural tube defects, and oxidative stress is a causal factor for maternal diabetes-induced neural tube defects. The redox gene nuclear factor erythroid 2-related factor 2 is the master regulator of the cellular antioxidant system. In this study, we aimed to determine whether maternal diabetes inhibits nuclear factor erythroid 2-related factor 2 expression and nuclear factor erythroid 2-related factor 2-controlled antioxidant genes through the redox-sensitive miR-27a. We used a well-established type 1 diabetic embryopathy mouse model induced by streptozotocin for our in vivo studies. Embryos at embryonic day 8.5 were harvested for analysis of nuclear factor erythroid 2-related factor 2, nuclear factor erythroid 2-related factor 2-controlled antioxidant genes, and miR-27a expression. To determine if mitigating oxidative stress inhibits the increase of miR-27a and the decrease of nuclear factor erythroid 2-related factor 2 expression, we induced diabetic embryopathy in superoxide dismutase 2 (mitochondrial-associated antioxidant gene)-overexpressing mice. This model exhibits reduced mitochondria reactive oxygen species even in the presence of hyperglycemia. To investigate the causal relationship between miR-27a and nuclear factor erythroid 2-related factor 2 in vitro, we examined C17.2 neural stem cells under normal and high-glucose conditions. We observed that the messenger RNA and protein levels of nuclear factor erythroid 2-related factor 2 were significantly decreased in embryos on embryonic day 8.5 from diabetic dams compared to those from nondiabetic dams. High-glucose also significantly decreased nuclear factor erythroid 2-related factor 2 expression in a dose- and time-dependent manner in cultured neural stem cells. Our data revealed that miR-27a was up-regulated in embryos on embryonic day 8.5 exposed to diabetes, and that high glucose increased miR-27a levels in a dose- and time-dependent manner in cultured neural stem cells. In

Involvement of H-ras in erythroid differentiation of TF1 and human umbilical cord blood CD34 cells.

PubMed

Ge, Y; Li, Z H; Marshall, M S; Broxmeyer, H E; Lu, L

1998-06-01

To investigate the role of the ras gene in erythroid differentiation, a human erythroleukemic cell line, TF1, was transduced with a selectable retroviral vector carrying a mammalian wild type H-ras gene or a cytoplasmic dominant negative RAS1 gene. Transduction of TF1 cells with the wild type H-ras gene resulted in changes of cell types and up-regulation of erythroid-specific gene expression similar to that seen in differentiating erythroid cells. The number of red blood cell containing colonies derived from TF1 cells transduced with wild type H-ras cDNA was significantly increased and the cells in the colonies were more hemoglobinized as estimated by a deeper red color compared to those colony cells from mock or dominant negative RAS1 gene transduced TF1 cells, suggesting increased erythroid differentiation of TF1 cells after transduction of wild type H-ras in vitro. The mRNA levels of beta- and gamma-, but not alpha-, globin genes were significantly higher in H-ras transduced TF1 cells than those in TF1 cells transduced with mock or dominant negative RAS1 gene. Moreover, a 4kb pre-mRNA of the Erythropoietin receptor (EpoR) was highly expressed only in H-ras transduced TF1 cells. Additionally, human umbilical cord blood (CB) CD34 cells which are highly enriched for hematopoietic stem/progenitor cells were transduced with the same retroviral vectors to evaluate in normal primary cells the activities of H-ras in erythroid differentiation. Increased numbers of erythroid cell containing colonies (BFU-E and CFU-GEMM) were observed in CD34 cells transduced with the H-ras cDNA, compared to that from mock transduced cells. These data suggest a possible role for ras in erythroid differentiation.

Production of β-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous β039 thalassemia patients

PubMed Central

Salvatori, Francesca; Breveglieri, Giulia; Zuccato, Cristina; Finotti, Alessia; Bianchi, Nicoletta; Borgatti, Monica; Feriotto, Giordana; Destro, Federica; Canella, Alessandro; Brognara, Eleonora; Lampronti, Ilaria; Breda, Laura; Rivella, Stefano; Gambari, Roberto

2013-01-01

In several types of thalassemia (including β039-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying β-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the β039- thalassemia globin gene under control of the β-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of β-globin by K562 cell clones expressing the β039-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from β039-thalassemia patients were demonstrated to be able to produce β-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of β0-thalassemia caused by stop codon mutations. PMID:19810011

Efficient Generation of β-Globin-Expressing Erythroid Cells Using Stromal Cell-Derived Induced Pluripotent Stem Cells from Patients with Sickle Cell Disease.

PubMed

Uchida, Naoya; Haro-Mora, Juan J; Fujita, Atsushi; Lee, Duck-Yeon; Winkler, Thomas; Hsieh, Matthew M; Tisdale, John F

2017-03-01

Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent an ideal source for in vitro modeling of erythropoiesis and a potential alternative source for red blood cell transfusions. However, iPS cell-derived erythroid cells predominantly produce ε- and γ-globin without β-globin production. We recently demonstrated that ES cell-derived sacs (ES sacs), known to express hemangioblast markers, allow for efficient erythroid cell generation with β-globin production. In this study, we generated several iPS cell lines derived from bone marrow stromal cells (MSCs) and peripheral blood erythroid progenitors (EPs) from sickle cell disease patients, and evaluated hematopoietic stem/progenitor cell (HSPC) generation after iPS sac induction as well as subsequent erythroid differentiation. MSC-derived iPS sacs yielded greater amounts of immature hematopoietic progenitors (VEGFR2 + GPA-), definitive HSPCs (CD34 + CD45+), and megakaryoerythroid progenitors (GPA + CD41a+), as compared to EP-derived iPS sacs. Erythroid differentiation from MSC-derived iPS sacs resulted in greater amounts of erythroid cells (GPA+) and higher β-globin (and βS-globin) expression, comparable to ES sac-derived cells. These data demonstrate that human MSC-derived iPS sacs allow for more efficient erythroid cell generation with higher β-globin production, likely due to heightened emergence of immature progenitors. Our findings should be important for iPS cell-derived erythroid cell generation. Stem Cells 2017;35:586-596. © 2016 AlphaMed Press.

The role of ROS in hydroquinone-induced inhibition of K562 cell erythroid differentiation.

PubMed

Yu, Chun Hong; Suriguga; Li, Yang; Li, Yi Ran; Tang, Ke Ya; Jiang, Liang; Yi, Zong Chun

2014-03-01

The role of ROS in hydroquinone-induced inhibition of K562 cell erythroid differentiation was investigated. After K562 cells were treated with hydroquinone for 24 h, and hemin was later added to induce erythroid differentiation for 48 h, hydroquinone inhibited hemin-induced hemoglobin synthesis and mRNA expression of γ-globin in K562 cells in a concentration-dependent manner. The 24-h exposure to hydroquinone also caused a concentration-dependent increase at an intracellular ROS level, while the presence of N- acetyl-L-cysteine prevented hydroquinone- induced ROS production in K562 cells. The presence of N-acetyl-L-cysteine also prevented hydroquinone inhibiting hemin-induced hemoglobin synthesis and mRNA expression of γ-globin in K562 cells. These evidences indicated that ROS production played a role in hydroquinone-induced inhibition of erythroid differentiation. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Late stage erythroid precursor production is impaired in mice with chronic inflammation.

PubMed

Prince, Olivier D; Langdon, Jacqueline M; Layman, Andrew J; Prince, Ian C; Sabogal, Miguel; Mak, Howard H; Berger, Alan E; Cheadle, Chris; Chrest, Francis J; Yu, Qilu; Andrews, Nancy C; Xue, Qian-Li; Civin, Curt I; Walston, Jeremy D; Roy, Cindy N

2012-11-01

We and others have shown previously that over-expression of hepcidin antimicrobial peptide, independently of inflammation, induces several features of anemia of inflammation and chronic disease, including hypoferremia, sequestration of iron stores and iron-restricted erythropoiesis. Because the iron-restricted erythropoiesis evident in hepcidin transgenic mice differs from the normocytic, normochromic anemia most often observed in anemia of inflammation, we tested the hypothesis that chronic inflammation may contribute additional features to anemia of inflammation which continue to impair erythropoiesis following the acute phase of inflammation in which hepcidin is active. We compared erythropoiesis and iron handling in mice with turpentine-induced sterile abscesses with erythropoiesis and iron handling in hepcidin transgenic mice. We compared erythrocyte indices, expression of genes in the hepcidin regulatory pathway, tissue iron distribution, expression of heme and iron transport genes in splenic macrophages, the phenotype of erythroid maturation and chloromethyl dichlorodihydrofluorescein diacetate, acetyl ester fluorescence. Mice with sterile abscesses exhibited an intense, acute inflammatory phase followed by a mild to moderate chronic inflammatory phase. We found that erythrocytes in mice with sterile abscesses were normocytic and normochromic in contrast to those in hepcidin transgenic mice. We also observed that although hypoferremia resolved in the late phases of inflammation, erythropoiesis remained suppressed, with evidence of inefficient maturation of erythroid precursors in the bone marrow of mice with sterile abscesses. Finally, we observed increased oxidative stress in erythroid progenitors and circulating erythrocytes of mice with sterile abscesses which was not evident in hepcidin transgenic mice. Our results suggest that chronic inflammation inhibits late stages of erythroid production in the turpentine-induced sterile abscess model and induces

Late stage erythroid precursor production is impaired in mice with chronic inflammation

PubMed Central

Prince, Olivier D.; Langdon, Jacqueline M.; Layman, Andrew J.; Prince, Ian C.; Sabogal, Miguel; Mak, Howard H.; Berger, Alan E.; Cheadle, Chris; Chrest, Francis J.; Yu, Qilu; Andrews, Nancy C.; Xue, Qian-Li; Civin, Curt I.; Walston, Jeremy D.; Roy, Cindy N.

2012-01-01

Background We and others have shown previously that over-expression of hepcidin antimicrobial peptide, independently of inflammation, induces several features of anemia of inflammation and chronic disease, including hypoferremia, sequestration of iron stores and iron-restricted erythropoiesis. Because the iron-restricted erythropoiesis evident in hepcidin transgenic mice differs from the normocytic, normochromic anemia most often observed in anemia of inflammation, we tested the hypothesis that chronic inflammation may contribute additional features to anemia of inflammation which continue to impair erythropoiesis following the acute phase of inflammation in which hepcidin is active. Design and Methods We compared erythropoiesis and iron handling in mice with turpentine-induced sterile abscesses with erythropoiesis and iron handling in hepcidin transgenic mice. We compared erythrocyte indices, expression of genes in the hepcidin regulatory pathway, tissue iron distribution, expression of heme and iron transport genes in splenic macrophages, the phenotype of erythroid maturation and chloromethyl dichlorodihydrofluorescein diacetate, acetyl ester fluorescence. Results Mice with sterile abscesses exhibited an intense, acute inflammatory phase followed by a mild to moderate chronic inflammatory phase. We found that erythrocytes in mice with sterile abscesses were normocytic and normochromic in contrast to those in hepcidin transgenic mice. We also observed that although hypoferremia resolved in the late phases of inflammation, erythropoiesis remained suppressed, with evidence of inefficient maturation of erythroid precursors in the bone marrow of mice with sterile abscesses. Finally, we observed increased oxidative stress in erythroid progenitors and circulating erythrocytes of mice with sterile abscesses which was not evident in hepcidin transgenic mice. Conclusions Our results suggest that chronic inflammation inhibits late stages of erythroid production in the

Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

PubMed

Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang

2017-07-01

Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-alpha-induced apoptosis.

PubMed

Vittori, Daniela; Vota, Daiana; Callero, Mariana; Chamorro, María E; Nesse, Alcira

2010-05-04

The TNF-alpha (tumour necrosis factor) affects a wide range of biological activities, such as cell proliferation and apoptosis. Cell life or death responses to this cytokine might depend on cell conditions. This study focused on the modulation of factors that would affect the sensitivity of erythroid-differentiated cells to TNF-alpha. Hemin-differentiated K562 cells showed higher sensitivity to TNF-induced apoptosis than undifferentiated cells. At the same time, hemin-induced erythroid differentiation reduced c-FLIP (cellular FLICE-inhibitory protein) expression. However, this negative effect was prevented by prior treatment with Epo (erythropoietin), which allowed the cell line to maintain c-FLIP levels. On the other hand, erythroid-differentiated UT-7 cells - dependent on Epo for survival - showed resistance to TNF-alpha pro-apoptotic action. Only after the inhibition of PI3K (phosphatidylinositol-3 kinase)-mediated pathways, which was accompanied by negative c-FLIP modulation and increased erythroid differentiation, were UT-7 cells sensitive to TNF-alpha-triggered apoptosis. In summary, erythroid differentiation might deregulate the balance between growth promotion and death signals induced by TNF-alpha, depending on cell type and environmental conditions. The role of c-FLIP seemed to be critical in the protection of erythroid-differentiated cells from apoptosis or in the determination of their sensitivity to TNF-mediated programmed cell death. Epo, which for the first time was found to be involved in the prevention of c-FLIP down-regulation, proved to have an anti-apoptotic effect against the pro-inflammatory factor. The identification of signals related to cell life/death switching would have significant implications in the control of proliferative diseases and would contribute to the understanding of mechanisms underlying the anaemia associated with inflammatory processes.

Hypoxia-inducible factor 1–mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions

PubMed Central

Zhang, Feng-Lin; Shen, Guo-Min; Liu, Xiao-Ling; Wang, Fang; Zhao, Ying-Ze; Zhang, Jun-Wu

2012-01-01

Abstract Hypoxia-inducible factor promotes erythropoiesis through coordinated cell type–specific hypoxia responses. GATA1 is essential to normal erythropoiesis and plays a crucial role in erythroid differentiation. In this study, we show that hypoxia-induced GATA1 expression is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased GATA1 mRNA and protein levels were detected in K562 cells and erythroid induction cultures of CD34+ haematopoietic stem/progenitor cells. Enforced HIF1α expression increased GATA1 expression, while HIF1α knockdown by RNA interference decreased GATA1 expression. In silico analysis revealed one potential hypoxia response element (HRE). The results from reporter gene and mutation analysis suggested that this element is necessary for hypoxic response. Chromatin immunoprecipitation (ChIP)-PCR showed that the putative HRE was recognized and bound by HIF1 in vivo. These results demonstrate that the up-regulation of GATA1 during hypoxia is directly mediated by HIF1.The mRNA expression of some erythroid differentiation markers was increased under hypoxic conditions, but decreased with RNA interference of HIF1α or GATA1. Flow cytometry analysis also indicated that hypoxia, desferrioxamine or CoCl2 induced expression of erythroid surface markers CD71 and CD235a, while expression repression of HIF1α or GATA1 by RNA interference led to a decreased expression of CD235a. These results suggested that HIF1-mediated GATA1 up-regulation promotes erythropoiesis in order to satisfy the needs of an organism under hypoxic conditions. PMID:22050843

Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

PubMed

Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

2015-01-01

Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. Copyright© Ferrata Storti Foundation.

Probing Conformational Stability and Dynamics of Erythroid and Nonerythroid Spectrin: Effects of Urea and Guanidine Hydrochloride

PubMed Central

Patra, Malay; Mukhopadhyay, Chaitali; Chakrabarti, Abhijit

2015-01-01

We have studied the conformational stability of the two homologous membrane skeletal proteins, the erythroid and non-erythroid spectrins, in their dimeric and tetrameric forms respectively during unfolding in the presence of urea and guanidine hydrochloride (GuHCl). Fluorescence and circular dichroism (CD) spectroscopy have been used to study the changes of intrinsic tryptophan fluorescence, anisotropy, far UV-CD and extrinsic fluorescence of bound 1-anilinonapthalene-8-sulfonic acid (ANS). Chemical unfolding of both proteins were reversible and could be described as a two state transition. The folded erythroid spectrin and non-erythroid spectrin were directly converted to unfolded monomer without formation of any intermediate. Fluorescence quenching, anisotropy, ANS binding and dynamic light scattering data suggest that in presence of low concentrations of the denaturants (up-to 1M) hydrogen bonding network and van der Waals interaction play a role inducing changes in quaternary as well as tertiary structures without complete dissociation of the subunits. This is the first report of two large worm like, multi-domain proteins obeying twofold rule which is commonly found in small globular proteins. The free energy of stabilization (ΔGu H 2 0) for the dimeric spectrin has been 20 kcal/mol lesser than the tetrameric from. PMID:25617632

mNotch1 signaling and erythropoietin cooperate in erythroid differentiation of multipotent progenitor cells and upregulate beta-globin.

PubMed

Henning, Konstanze; Schroeder, Timm; Schwanbeck, Ralf; Rieber, Nikolaus; Bresnick, Emery H; Just, Ursula

2007-09-01

In many developing tissues, signaling mediated by activation of the transmembrane receptor Notch influences cell-fate decisions, differentiation, proliferation, and cell survival. Notch receptors are expressed on hematopoietic cells and cognate ligands on bone marrow stromal cells. Here, we investigate the role of mNotch1 signaling in the control of erythroid differentiation of multipotent progenitor cells. Multipotent FDCP-mix cell lines engineered to permit the conditional induction of the constitutively active intracellular domain of mNotch1 (mN1(IC)) by the 4-hydroxytamoxifen (OHT)-inducible system were used to analyze the effects of activated mNotch1 on erythroid differentiation and on expression of Gata1, Fog1, Eklf, NF-E2, and beta-globin. Expression was analyzed by Northern blotting and real-time polymerase chain reaction. Enhancer activity of reporter constructs was determined with the dual luciferase system in transient transfection assays. Induction of mN1(IC) by OHT resulted in increased and accelerated differentiation of FDCP-mix cells along the erythroid lineage. Erythroid maturation was induced by activated Notch1 also under conditions that normally promote self-renewal, but required the presence of erythropoietin for differentiation to proceed. While induction of Notch signaling rapidly upregulated Hes1 and Hey1 expression, the expression of Gata1, Fog1, Eklf, and NF-E2 remained unchanged. Concomitantly with erythroid differentiation, activated mNotch1 upregulated beta-globin RNA. Notch signaling transactivated a reporter construct harboring a conserved RBP-J (CBF1) binding site in the hypersensitive site 2 (HS2) of human beta-globin. Transactivation by activated Notch was completely abolished when this RBP-J site was mutated to prevent RBP-J binding. Our results show that activation of mNotch1 induces erythroid differentiation in cooperation with erythropoietin and upregulates beta-globin expression.

The leukemia associated ETO nuclear repressor gene is regulated by the GATA-1 transcription factor in erythroid/megakaryocytic cells

PubMed Central

2010-01-01

Background The Eight-Twenty-One (ETO) nuclear co-repressor gene belongs to the ETO homologue family also containing Myeloid Translocation Gene on chromosome 16 (MTG16) and myeloid translocation Gene-Related protein 1 (MTGR1). By chromosomal translocations ETO and MTG16 become parts of fusion proteins characteristic of morphological variants of acute myeloid leukemia. Normal functions of ETO homologues have as yet not been examined. The goal of this work was to identify structural and functional promoter elements upstream of the coding sequence of the ETO gene in order to explore lineage-specific hematopoietic expression and get hints to function. Results A putative proximal ETO promoter was identified within 411 bp upstream of the transcription start site. Strong ETO promoter activity was specifically observed upon transfection of a promoter reporter construct into erythroid/megakaryocytic cells, which have endogeneous ETO gene activity. An evolutionary conserved region of 228 bp revealed potential cis-elements involved in transcription of ETO. Disruption of the evolutionary conserved GATA -636 consensus binding site repressed transactivation and disruption of the ETS1 -705 consensus binding site enhanced activity of the ETO promoter. The promoter was stimulated by overexpression of GATA-1 into erythroid/megakaryocytic cells. Electrophoretic mobility shift assay with erythroid/megakaryocytic cells showed specific binding of GATA-1 to the GATA -636 site. Furthermore, results from chromatin immunoprecipitation showed GATA-1 binding in vivo to the conserved region of the ETO promoter containing the -636 site. The results suggest that the GATA -636 site may have a role in activation of the ETO gene activity in cells with erythroid/megakaryocytic potential. Leukemia associated AML1-ETO strongly suppressed an ETO promoter reporter in erythroid/megakaryocytic cells. Conclusions We demonstrate that the GATA-1 transcription factor binds and transactivates the ETO proximal

Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies

PubMed Central

Mirabelli, Peppino; Di Noto, Rosa; Lo Pardo, Catia; Morabito, Paolo; Abate, Giovanna; Gorrese, Marisa; Raia, Maddalena; Pascariello, Caterina; Scalia, Giulia; Gemei, Marica; Mariotti, Elisabetta; Del Vecchio, Luigi

2008-01-01

Background Aldehyde dehydrogenase (ALDH) is a cytosolic enzyme highly expressed in hematopoietic precursors from cord blood and granulocyte-colony stimulating factor mobilized peripheral blood, as well as in bone marrow from patients with acute myeloblastic leukemia. As regards human normal bone marrow, detailed characterization of ALDH+ cells has been addressed by one single study (Gentry et al, 2007). The goal of our work was to provide new information about the dissection of normal bone marrow progenitor cells based upon the simultaneous detection by flow cytometry of ALDH and early hematopoietic antigens, with particular attention to the expression of ALDH on erythroid precursors. To this aim, we used three kinds of approach: i) multidimensional analytical flow cytometry, detecting ALDH and early hematopoietic antigens in normal bone marrow; ii) fluorescence activated cell sorting of distinct subpopulations of progenitor cells, followed by in vitro induction of erythroid differentiation; iii) detection of ALDH+ cellular subsets in bone marrow from pure red cell aplasia patients. Results In normal bone marrow, we identified three populations of cells, namely ALDH+CD34+, ALDH-CD34+ and ALDH+CD34- (median percentages were 0.52, 0.53 and 0.57, respectively). As compared to ALDH-CD34+ cells, ALDH+CD34+ cells expressed the phenotypic profile of primitive hematopoietic progenitor cells, with brighter expression of CD117 and CD133, accompanied by lower display of CD38 and CD45RA. Of interest, ALDH+CD34- population disclosed a straightforward erythroid commitment, on the basis of three orders of evidences. First of all, ALDH+CD34- cells showed a CD71bright, CD105+, CD45- phenotype. Secondly, induction of differentiation experiments evidenced a clear-cut expression of glycophorin A (CD235a). Finally, ALDH+CD34- precursors were not detectable in patients with pure red cell aplasia (PRCA). Conclusion Our study, comparing surface antigen expression of ALDH+/CD34+, ALDH

Eos Negatively Regulates Human γ-globin Gene Transcription during Erythroid Differentiation

PubMed Central

Yu, Hai-Chuan; Zhao, Hua-Lu; Wu, Zhi-Kui; Zhang, Jun-Wu

2011-01-01

Background Human globin gene expression is precisely regulated by a complicated network of transcription factors and chromatin modifying activities during development and erythropoiesis. Eos (Ikaros family zinc finger 4, IKZF4), a member of the zinc finger transcription factor Ikaros family, plays a pivotal role as a repressor of gene expression. The aim of this study was to examine the role of Eos in globin gene regulation. Methodology/Principal Findings Western blot and quantitative real-time PCR detected a gradual decrease in Eos expression during erythroid differentiation of hemin-induced K562 cells and Epo-induced CD34+ hematopoietic stem/progenitor cells (HPCs). DNA transfection and lentivirus-mediated gene transfer demonstrated that the enforced expression of Eos significantly represses the expression of γ-globin, but not other globin genes, in K562 cells and CD34+ HPCs. Consistent with a direct role of Eos in globin gene regulation, chromatin immunoprecipitaion and dual-luciferase reporter assays identified three discrete sites located in the DNase I hypersensitivity site 3 (HS3) of the β-globin locus control region (LCR), the promoter regions of the Gγ- and Aγ- globin genes, as functional binding sites of Eos protein. A chromosome conformation capture (3C) assay indicated that Eos may repress the interaction between the LCR and the γ-globin gene promoter. In addition, erythroid differentiation was inhibited by enforced expression of Eos in K562 cells and CD34+ HPCs. Conclusions/Significance Our results demonstrate that Eos plays an important role in the transcriptional regulation of the γ-globin gene during erythroid differentiation. PMID:21829552

GATA1 and PU.1 Bind to Ribosomal Protein Genes in Erythroid Cells: Implications for Ribosomopathies

PubMed Central

Amanatiadou, Elsa P.; Papadopoulos, Giorgio L.; Strouboulis, John; Vizirianakis, Ioannis S.

2015-01-01

The clear connection between ribosome biogenesis dysfunction and specific hematopoiesis-related disorders prompted us to examine the role of critical lineage-specific transcription factors in the transcriptional regulation of ribosomal protein (RP) genes during terminal erythroid differentiation. By applying EMSA and ChIP methodologies in mouse erythroleukemia cells we show that GATA1 and PU.1 bind in vitro and in vivo the proximal promoter region of the RPS19 gene which is frequently mutated in Diamond-Blackfan Anemia. Moreover, ChIPseq data analysis also demonstrates that several RP genes are enriched as potential GATA1 and PU.1 gene targets in mouse and human erythroid cells, with GATA1 binding showing an association with higher ribosomal protein gene expression levels during terminal erythroid differentiation in human and mouse. Our results suggest that RP gene expression and hence balanced ribosome biosynthesis may be specifically and selectively regulated by lineage specific transcription factors during hematopoiesis, a finding which may be clinically relevant to ribosomopathies. PMID:26447946

Interferon-gamma exerts its negative regulatory effect primarily on the earliest stages of murine erythroid progenitor cell development.

PubMed

Wang, C Q; Udupa, K B; Lipschitz, D A

1995-01-01

Interferon-gamma (INF-gamma) has been shown to suppress erythropoiesis and perhaps to contribute to the anemia of chronic disease. In this study we demonstrated that the concentration of INF gamma required to suppress murine burst forming unit-erythroid (BFU-E) growth was significantly less than that required to suppress colony forming unit-erythroid (CFU-E) growth. INF gamma acted at the most primitive step in erythroid progenitor cell differentiation and proliferation, as inhibition was maximal when added at the time of BFU-E culture initiation. Inhibition was progressively less if INF gamma addition was delayed after culture initiation. The effects of INF gamma on BFU-E did not require the presence of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF alpha), or granulocyte macrophage colony stimulating factor (GM-CSF), as its effects were not neutralized by monoclonal antibodies against IL-1 alpha, TNF alpha, or GM-CSF. This applied whether INF gamma was added to culture with individual antibodies or with a combination of all three antibodies. INF gamma was not required for IL-1 alpha- or TNF alpha-induced suppression of BFU-E, as their effects were not neutralized by a monoclonal anti-INF gamma antibody. In contrast, GM-CSF-induced suppression of BFU-E was negated by the simultaneous addition of anti-INF gamma. We have previously shown that the addition of TNF alpha does not suppress BFU-E growth in cultures from marrow depleted of macrophages. Suppression did occur, however, if a small concentration of INF gamma that does not inhibit and increasing concentration of TNF alpha were added to culture, suggesting a synergistic effect between INF-gamma and TNF alpha. These observations suggest that INF gamma is a potent direct inhibitor of erythroid colony growth in vitro. It exerts its negative regulatory effect primarily on the earliest stages of erythroid progenitor cell differentiation and proliferation, as much higher doses are required to

miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2.

PubMed

Gao, Ming; Liu, Yun; Chen, Yue; Yin, Chunyang; Chen, Jane-Jane; Liu, Sijin

2016-03-01

Nuclear factor (erythroid-derived 2) like 2 (Nrf2) is a key regulator in protecting cells against stress by targeting many anti-stress response genes. Recent evidence also reveals that Nrf2 functions partially by targeting mircroRNAs (miRNAs). However, the understanding of Nrf2-mediated cytoprotection through miRNA-dependent mechanisms is largely unknown. In the current study, we identified a direct Nrf2 targeting miRNA, miR-214, and demonstrated a protective role of miR-214 in erythroid cells against oxidative stresses generated by radiation, excess iron and arsenic (As) exposure. miR-214 expression was transcriptionally repressed by Nrf2 through a canonical antioxidant response element (ARE) within its promoter region, and this repression is ROS-dependence. The suppression of miR-214 by Nrf2 could antagonize oxidative stress-induced cell death in erythroid cells by two ways. First, miR-214 directly targeted ATF4, a crucial transcriptional factor involved in anti-stress responses, down regulation of miR-214 releases the repression of ATF4 translation and leads to increased ATF4 protein content. Second, miR-214 was able to prevent cell death by targeting EZH2, the catalytic core component of PRC2 complex that is responsible for tri-methylation reaction at lysine 27 (K27) of histone 3 (H3) (H3K27me3), by which As-induced miR-214 reduction resulted in an increased global H3K27me3 level and a compromised overexpression of a pro-apoptotic gene Bim. These two pathways downstream of miR-214 synergistically cooperated to antagonize erythroid cell death upon oxidative stress. Our combined data revealed a protective role of miR-214 signaling in erythroid cells against oxidative stress, and also shed new light on Nrf2-mediated cytoprotective machinery. Copyright © 2016 Elsevier Inc. All rights reserved.

Myelo-erythroid commitment after burn injury is under β-adrenergic control via MafB regulation.

PubMed

Hasan, Shirin; Johnson, Nicholas B; Mosier, Michael J; Shankar, Ravi; Conrad, Peggie; Szilagyi, Andrea; Gamelli, Richard L; Muthumalaiappan, Kuzhali

2017-03-01

Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in a high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by β-adrenergic stimulation leading to anemia. In a mouse model of scald burn injury, we observed, along with a threefold increase in bone marrow LSK cells (lin neg Sca1 + cKit + ), that the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs). β-Blocker administration (propranolol) for 6 days after burn, not only reduced the number of LSKs and MafB + cells in multipotent progenitors, but also influenced myelo-erythroid bifurcation by increasing the MEPs and reducing the granulocyte monocyte progenitors in the bone marrow of burn mice. Furthermore, similar results were observed in burn patients' peripheral blood mononuclear cell-derived ex vivo culture system, demonstrating that commitment stage of erythropoiesis is impaired in burn patients and intervention with propranolol (nonselective β1,2-adrenergic blocker) increases MEPs. Also, MafB + cells that were significantly increased following standard burn care could be mitigated when propranolol was administered to burn patients, establishing the mechanistic regulation of erythroid commitment by myeloid regulatory transcription factor MafB. Overall, results demonstrate that β-adrenergic blockers following burn injury can redirect the hematopoietic commitment toward erythroid lineage by lowering MafB expression in multipotent progenitors and be of potential therapeutic value to increase erythropoietin responsiveness in burn patients. Copyright © 2017 the American Physiological Society.

Myelo-erythroid commitment after burn injury is under β-adrenergic control via MafB regulation

PubMed Central

Hasan, Shirin; Johnson, Nicholas B.; Mosier, Michael J.; Shankar, Ravi; Conrad, Peggie; Szilagyi, Andrea; Gamelli, Richard L.

2017-01-01

Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in a high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by β-adrenergic stimulation leading to anemia. In a mouse model of scald burn injury, we observed, along with a threefold increase in bone marrow LSK cells (linneg Sca1+cKit+), that the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs). β-Blocker administration (propranolol) for 6 days after burn, not only reduced the number of LSKs and MafB+ cells in multipotent progenitors, but also influenced myelo-erythroid bifurcation by increasing the MEPs and reducing the granulocyte monocyte progenitors in the bone marrow of burn mice. Furthermore, similar results were observed in burn patients’ peripheral blood mononuclear cell-derived ex vivo culture system, demonstrating that commitment stage of erythropoiesis is impaired in burn patients and intervention with propranolol (nonselective β1,2-adrenergic blocker) increases MEPs. Also, MafB+ cells that were significantly increased following standard burn care could be mitigated when propranolol was administered to burn patients, establishing the mechanistic regulation of erythroid commitment by myeloid regulatory transcription factor MafB. Overall, results demonstrate that β-adrenergic blockers following burn injury can redirect the hematopoietic commitment toward erythroid lineage by lowering MafB expression in multipotent progenitors and be of potential therapeutic value to increase erythropoietin responsiveness in burn patients. PMID:28031160

Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8/S100A9

PubMed Central

Schneider, Rebekka K.; Schenone, Monica; Ferreira, Monica Ventura; Kramann, Rafael; Joyce, Cailin E.; Hartigan, Christina; Beier, Fabian; Brümmendorf, Tim H.; Gehrming, Ulrich; Platzbecker, Uwe; Büsche, Guntram; Knüchel, Ruth; Chen, Michelle C.; Waters, Christopher S.; Chen, Edwin; Chu, Lisa P.; Novina, Carl D.; Lindsley, R. Coleman; Carr, Steven A.; Ebert, Benjamin L.

2016-01-01

Heterozygous deletion of RPS14 occurs in del(5q) MDS and has been linked to impaired erythropoiesis, characteristic of this disease subtype. We generated a murine model with conditional inactivation of Rps14 and demonstrated a p53-dependent erythroid differentiation defect with apoptosis at the transition from polychromatic to orthochromatic erythroblasts resulting in age-dependent progressive anemia, megakaryocyte dysplasia, and loss of hematopoietic stem cell (HSC) quiescence. Using quantitative proteomics, we identified significantly increased expression of proteins involved in innate immune signaling, particularly the heterodimeric S100a8/S100a9 proteins in purified erythroblasts. S100a8 expression was significantly increased in erythroblasts, monocytes and macrophages and recombinant S100a8 was sufficient to induce an erythroid differentiation defect in wild-type cells. We rescued the erythroid differentiation defect in Rps14 haploinsufficient HSCs by genetic inactivation of S100a8 expression. Our data link Rps14 haploinsufficiency to activation of the innate immune system via induction of S100A8/A9 and the p53-dependant erythroid differentiation defect in del(5q) MDS. PMID:26878232

Productive Parvovirus B19 Infection of Primary Human Erythroid Progenitor Cells at Hypoxia Is Regulated by STAT5A and MEK Signaling but not HIFα

PubMed Central

Chen, Aaron Yun; Kleiboeker, Steve; Qiu, Jianming

2011-01-01

Human parvovirus B19 (B19V) causes a variety of human diseases. Disease outcomes of bone marrow failure in patients with high turnover of red blood cells and immunocompromised conditions, and fetal hydrops in pregnant women are resulted from the targeting and destruction of specifically erythroid progenitors of the human bone marrow by B19V. Although the ex vivo expanded erythroid progenitor cells recently used for studies of B19V infection are highly permissive, they produce progeny viruses inefficiently. In the current study, we aimed to identify the mechanism that underlies productive B19V infection of erythroid progenitor cells cultured in a physiologically relevant environment. Here, we demonstrate an effective reverse genetic system of B19V, and that B19V infection of ex vivo expanded erythroid progenitor cells at 1% O2 (hypoxia) produces progeny viruses continuously and efficiently at a level of approximately 10 times higher than that seen in the context of normoxia. With regard to mechanism, we show that hypoxia promotes replication of the B19V genome within the nucleus, and that this is independent of the canonical PHD/HIFα pathway, but dependent on STAT5A and MEK/ERK signaling. We further show that simultaneous upregulation of STAT5A signaling and down-regulation of MEK/ERK signaling boosts the level of B19V infection in erythroid progenitor cells under normoxia to that in cells under hypoxia. We conclude that B19V infection of ex vivo expanded erythroid progenitor cells at hypoxia closely mimics native infection of erythroid progenitors in human bone marrow, maintains erythroid progenitors at a stage conducive to efficient production of progeny viruses, and is regulated by the STAT5A and MEK/ERK pathways. PMID:21698228

Effect of Midmorning Puree Snacks on Subjective Appetite, Food Intake, and Glycemic and Insulin Responses in Healthy Adults.

PubMed

Guo, Qing; Totosy de Zepetnek, Julia; Chang, Jennifer; Hayden, Julia; Crozier, Stephen J; Mongia, Gagan; Rousseau, Dérick; Bellissimo, Nick

2018-04-27

Dietary pattern changes, as a part of a healthy lifestyle, may improve weight management. The objective of this study was to examine the effect of midmorning puree snacks varying in macronutrient composition and energy content on subjective appetite, food intake, and glycemic and insulin responses in healthy adults. In a randomized, repeated measures crossover design, 6 treatments (snack skipping and purees: control [186 kcal], maltodextrin [272 kcal], whey protein [201 kcal], oat [276 kcal], and coconut oil [276 kcal]) were administered to 23 normal weight adults (n = 14 males, n = 9 females). Subjective appetite, blood glucose, and insulin responses were measured at regular intervals for 2 hours immediately followed by an ad libitum pizza lunch. In vitro digestion experiments were conducted to corroborate results of the human trial. Compared to snack skipping, all snack treatments similarly reduced subjective average appetite (net area under the curve), but only oat (p < 0.032) and coconut oil (p < 0.031) purees significantly decreased test meal food intake. However, caloric compensation did not differ among snack treatments (p < 0.73). Both blood glucose (incremental area under the curve [iAUC]; p < 0.0001) and serum insulin (iAUC; p < 0.0001) were affected by treatment. A positive correlation was found between blood glucose iAUC and in vitro glucose release (r = 0.993, p < 0.0001). The release of free fatty acids (FFAs) was sustained, and oats were difficult to disintegrate during in vitro digestion. Compared with snack skipping, coconut oil and oat puree snacks suppressed short-term food intake, which was likely due to the sustained release of FFA and slowly digestible oats, respectively. Our in vitro digestion model predicted the relative differences in the glycemic response in vivo.

Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

ClinicalTrials.gov

2015-06-18

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

ClinicalTrials.gov

2014-09-04

Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

ClinicalTrials.gov

2018-04-23

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2017-04-25

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML

ClinicalTrials.gov

2015-01-22

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

ClinicalTrials.gov

2013-01-08

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Receptor for macrophage colony-stimulating factor transduces a signal decreasing erythroid potential in the multipotent hematopoietic EML cell line.

PubMed

Pawlak, G; Grasset, M F; Arnaud, S; Blanchet, J P; Mouchiroud, G

2000-10-01

To test the hypothesis that hematopoietic growth factors may influence lineage choice in pluripotent progenitor cells, we investigated the effects of macrophage colony-stimulating factor (M-CSF) on erythroid and myeloid potentials of multipotent EML cells ectopically expressing M-CSF receptor (M-CSFR). EML cells are stem cell factor (SCF)-dependent murine cells that give rise spontaneously to pre-B cells, burst-forming unit erythroid (BFU-E), and colony-forming unit granulocyte macrophage (CFU-GM). We determined BFU-E and CFU-GM frequencies among EML cells transduced with murine M-CSFR, human M-CSFR, or chimeric receptors, and cultivated in the presence of SCF, M-CSF, or both growth factors. Effects of specific inhibitors of signaling molecules were investigated. EML cells transduced with murine M-CSFR proliferated in response to M-CSF but also exhibited a sharp and rapid decrease in BFU-E frequency associated with an increase in CFU-GM frequency. In contrast, EML cells expressing human M-CSFR proliferated in response to M-CSF without any changes in erythroid or myeloid potential. Using chimeric receptors between human and murine M-CSFR, we showed that the effects of M-CSF on EML cell differentiation potential are mediated by a large region in the intracellular domain of murine M-CSFR. Furthermore, phospholipase C (PLC) inhibitor U73122 interfered with the negative effects of ligand-activated murine M-CSFR on EML cell erythroid potential. We propose that signaling pathways activated by tyrosine kinase receptors may regulate erythroid potential and commitment decisions in multipotent progenitor cells and that PLC may play a key role in this process.

Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory AML and MDS

ClinicalTrials.gov

2017-02-14

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

ClinicalTrials.gov

2018-04-20

Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Effect of deferasirox + erythropoietin vs erythropoietin on erythroid response in Low/Int-1-risk MDS patients: Results of the phase II KALLISTO trial.

PubMed

Gattermann, Norbert; Coll, Rosa; Jacobasch, Lutz; Allameddine, Allameddine; Azmon, Amin; DeBonnett, Laurie; Bruederle, Andreas; Jin, Jie

2018-05-19

Erythropoiesis-stimulating agents (ESAs) remain first-choice to treat symptomatic anemia and delay transfusion dependence in most patients with lower-risk myelodysplastic syndromes (MDS) without del(5q). Deferasirox increased erythroid responses in some lower-risk MDS patients in clinical trials, and adding low-dose deferasirox to ESA treatment may further improve erythroid response. KALLISTO (NCT01868477) was a randomized, open-label, multicenter, phase II study. Lower-risk MDS patients received deferasirox at 10 mg/kg/day (dispersible tablets) or 7 mg/kg/day (film-coated tablets) plus erythropoietin (n=11), or erythropoietin alone (n=12) for 24 weeks. The primary endpoint was the between-group difference in erythroid response within 12 weeks. Erythroid response occurred in 27.3% of patients receiving deferasirox plus erythropoietin versus 41.7% of patients receiving erythropoietin alone within 12 weeks (difference 14.4%; 95% CI -24.0, 48.16). Within 24 weeks, the hematologic response rate was 27.3% with deferasirox plus erythropoietin versus 50% with erythropoietin alone, and hematologic improvement rates were 45.5% versus 100%. Deferasirox plus erythropoietin was generally well tolerated. In this small pilot study, combining low-dose deferasirox with erythropoietin did not improve erythroid response. It remains of interest to investigate early chelation approaches with even lower deferasirox doses plus erythropoietin in lower-risk MDS patients before the onset of transfusion dependence. Deferasirox, erythropoietin, myelodysplastic syndromes, anemia, therapy, hematologic response, erythroid response, clinical trials This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Monomethylfumarate Induces γ-Globin Expression and Fetal Hemoglobin Production in Cultured Human Retinal Pigment Epithelial (RPE) and Erythroid Cells, and in Intact Retina

PubMed Central

Promsote, Wanwisa; Makala, Levi; Li, Biaoru; Smith, Sylvia B.; Singh, Nagendra; Ganapathy, Vadivel; Pace, Betty S.; Martin, Pamela M.

2014-01-01

Purpose. Sickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina. Methods. Human globin gene expression was evaluated by RT–quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase–qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous βs mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed. Results. Retinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation. Conclusions. The production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment. PMID:24825111

Erythroid cells in vitro: from developmental biology to blood transfusion products.

PubMed

Migliaccio, Anna Rita; Whitsett, Carolyn; Migliaccio, Giovanni

2009-07-01

Red blood cells (RBCs) transfusion plays a critical role in numerous therapies. Disruption of blood collection by political unrest, natural disasters and emerging infections and implementation of restrictions on the use of erythropoiesis-stimulating agents in cancer may impact blood availability in the near future. These considerations highlight the importance of developing alternative blood products. Knowledge about the processes that control RBC production has been applied to the establishment of culture conditions allowing ex-vivo generation of RBCs in numbers close to those (2.5 x 10 cells/ml) present in a transfusion, from cord blood, donated blood units or embryonic stem cells. In addition, experimental studies demonstrate that such cells protect mice from lethal bleeding. Therefore, erythroid cells generated ex vivo may be suitable for transfusion provided they can be produced safely in adequate numbers. However, much remains to be done to translate a theoretical production of approximately 2.5 x 10 RBCs in the laboratory into a 'clinical grade production process'. This review summarizes the state-of-the-art in establishing ex-vivo culture conditions for erythroid cells and discusses the most compelling issues to be addressed to translate this progress into a clinical grade transfusion product.

Leukemic blast cell colony formation in semisolid culture with erythropoietin: a case report of acute poorly differentiated erythroid leukemia.

PubMed

Tomonaga, M; Jinnai, I; Tagawa, M; Amenomori, T; Nishino, K; Yao, E; Nonaka, H; Kuriyama, K; Yoshida, Y; Matsuo, T

1987-02-01

The bone marrow of a patient with acute undifferentiated leukemia developed unique colonies after a 14-day culture in erythropoietin (EPO)-containing methylcellulose. The colonies consisted of 20 to 200 nonhemoglobinized large blast cells. Cytogenetic analysis of single colonies revealed hypotetraploid karyotypes with several marker chromosomes that were identical to those found in directly sampled bone marrow. The concurrently formed erythroid bursts showed only normal karyotypes. No leukemic colony formation was observed in other culture systems with either colony-stimulating activity (CSA) or phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). The leukemic colonies exhibited a complete EPO-dose dependency similar to that of the patient's normal BFU-E. Although cytochemical and immunologic marker studies of the bone marrow cells failed to clarify the cell lineage of the leukemic cells with extraordinarily large cell size, ultrastructural study revealed erythroid differentiation such as siderosome formation in the cytoplasm and ferritin particles in the rhophecytosis invaginations. These findings indicate that the patient had poorly differentiated erythroid leukemia and that some of the clonogenic cells might respond to EPO in vitro. Corresponding to this biological feature, the leukemic cells were markedly decreased in number in response to repeated RBC transfusions, and partial remission was obtained. These observations suggest that erythroid leukemia distinct from erythroleukemia (M6) with a myeloblastic component, can develop as a minor entity of human acute leukemia.

New insights into the mechanisms of mammalian erythroid chromatin condensation and enucleation.

PubMed

Ji, Peng

2015-01-01

A unique feature in mammalian erythropoiesis is the dramatic chromatin condensation followed by enucleation. This step-by-step process starts at the beginning of terminal erythropoiesis after the hematopoietic stem cells are committed to erythroid lineage. Although this phenomenon is known for decades, the mechanisms of chromatin condensation and enucleation remain elusive. Recent advances in cell and molecular biology have started to reveal the molecular pathways in the regulation of chromatin condensation, the establishment of nuclear polarity prior enucleation, and the rearrangement of actin cytoskeleton in enucleation. However, many challenging questions, especially whether and how the apoptotic mechanisms are involved in chromatin condensation and how to dissect the functions of many actin cytoskeleton proteins in cytokinesis and enucleation, remain to be answered. Here I review our current understanding of mammalian erythroid chromatin condensation and enucleation during terminal differentiation with a focus on more recent studies. I conclude with my perspective of future works in this rising topic in developmental and cell biology. Copyright © 2015 Elsevier Inc. All rights reserved.

Massive splenomegaly in acute erythroid leukaemia (FAB Class-M6): an unusual presentation.

PubMed

Sherazi, Syed Furqan Haider; Butt, Zeeshan

2012-09-01

AML-M6 has a peak incidence in the seventh decade with slight male preponderance, and can also present at a younger age. The usual features are anaemia, thrombocytopenia, malaise, fatigue, easy bruising, epistaxis and petechiae. Splenomegaly may occur in 20-40 % of the cases but massive splenomegaly is rare presentation and have been only reported once in humans and once in animals. A 22 year Asian female, presented with fatigue, pallor, mild jaundice, exertional dyspnoea, epigastric pain, tender right hypochondrium and massive splenomegaly. Investigations revealed anaemia and thrombocytopenia, tear drop cells, basophilic stippling, piokilocytosis and anisochromia; increased uric acid and LDH. Abdominal ultrasound showed enlarged liver (22cm) and spleen (20cm). Bone marrow aspiration revealed 51% erythroid and 24% non-erythroid precursors, depressed leukopoeisis and megakarypoeisis. Erythroblasts were PAS and CD71 positive and also reacted to Antihaemoglobin-Antibody. This report highlights characteristic features and diagnostic criteria of erythroleukaemia, differential diagnosis of massive splenomegaly and their rare association.

Aclacinomycin A Sensitizes K562 Chronic Myeloid Leukemia Cells to Imatinib through p38MAPK-Mediated Erythroid Differentiation

PubMed Central

Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

2013-01-01

Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and

Aclacinomycin A sensitizes K562 chronic myeloid leukemia cells to imatinib through p38MAPK-mediated erythroid differentiation.

PubMed

Lee, Yueh-Lun; Chen, Chih-Wei; Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

2013-01-01

Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and

Murine recessive hereditary spherocytosis, sph/sph, is caused by a mutation in the erythroid alpha-spectrin gene.

PubMed

Wandersee, N J; Birkenmeier, C S; Gifford, E J; Mohandas, N; Barker, J E

2000-01-01

Spectrin, a heterodimer of alpha- and beta-subunits, is the major protein component of the red blood cell membrane skeleton. The mouse mutation, sph, causes an alpha-spectrin-deficient hereditary spherocytosis with the severe phenotype typical of recessive hereditary spherocytosis in humans. The sph mutation maps to the erythroid alpha-spectrin locus, Spna1, on Chromosome 1. Scanning electron microscopy, osmotic gradient ektacytometry, cDNA cloning, RT-PCR, nucleic acid sequencing, and Northern blot analyses were used to characterize the wild type and sph alleles of the Spna1 locus. Our results confirm the spherocytic nature of sph/sph red blood cells and document a mild spherocytic transition in the +/sph heterozygotes. Sequencing of the full length coding region of the Spna1 wild type allele from the C57BL/6J strain of mice reveals a 2414 residue deduced amino acid sequence that shows the typical 106-amino-acid repeat structure previously described for other members of the spectrin protein family. Sequence analysis of RT-PCR clones from sph/sph alpha-spectrin mRNA identified a single base deletion in repeat 5 that would cause a frame shift and premature termination of the protein. This deletion was confirmed in sph/sph genomic DNA. Northern blot analyses of the distribution of Spna1 mRNA in non-erythroid tissues detects the expression of 8, 2.5 and 2.0 kb transcripts in adult heart. These results predict the heart as an additional site where alpha-spectrin mutations may produce a phenotype and raise the possibility that a novel functional class of small alpha-spectrin isoforms may exist.

Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

ClinicalTrials.gov

2014-07-25

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

AML Therapy With Irradiated Allogeneic Cells

ClinicalTrials.gov

2017-02-01

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

ClinicalTrials.gov

2017-02-14

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

ClinicalTrials.gov

2018-01-02

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2018-05-16

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2017-06-27

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

ClinicalTrials.gov

2017-05-30

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

A new molecular link between defective autophagy and erythroid abnormalities in chorea-acanthocytosis.

PubMed

Lupo, Francesca; Tibaldi, Elena; Matte, Alessandro; Sharma, Alok K; Brunati, Anna Maria; Alper, Seth L; Zancanaro, Carlo; Benati, Donatella; Siciliano, Angela; Bertoldi, Mariarita; Zonta, Francesca; Storch, Alexander; Walker, Ruth H; Danek, Adrian; Bader, Benedikt; Hermann, Andreas; De Franceschi, Lucia

2016-12-22

Chorea-acanthocytosis is one of the hereditary neurodegenerative disorders known as the neuroacanthocytoses. Chorea-acanthocytosis is characterized by circulating acanthocytes deficient in chorein, a protein of unknown function. We report here for the first time that chorea-acanthocytosis red cells are characterized by impaired autophagy, with cytoplasmic accumulation of active Lyn and of autophagy-related proteins Ulk1 and Atg7. In chorea-acanthocytosis erythrocytes, active Lyn is sequestered by HSP90-70 to form high-molecular-weight complexes that stabilize and protect Lyn from its proteasomal degradation, contributing to toxic Lyn accumulation. An interplay between accumulation of active Lyn and autophagy was found in chorea-acanthocytosis based on Lyn coimmunoprecipitation with Ulk1 and Atg7 and on the presence of Ulk1 in Lyn-containing high-molecular-weight complexes. In addition, chorein associated with Atg7 in healthy but not in chorea-acanthocytosis erythrocytes. Electron microscopy detected multivesicular bodies and membrane remnants only in circulating chorea-acanthocytosis red cells. In addition, reticulocyte-enriched chorea-acanthocytosis red cell fractions exhibited delayed clearance of mitochondria and lysosomes, further supporting the impairment of authophagic flux. Because autophagy is also important in erythropoiesis, we studied in vitro CD34 + -derived erythroid precursors. In chorea-acanthocytosis, we found (1) dyserythropoiesis; (2) increased active Lyn; (3) accumulation of a marker of autophagic flux and autolysososme degradation; (4) accumlation of Lamp1, a lysosmal membrane protein, and LAMP1-positive aggregates; and (5) reduced clearance of lysosomes and mitochondria. Our results uncover in chorea-acanthocytosis erythroid cells an association between accumulation of active Lyn and impaired autophagy, suggesting a link between chorein and autophagic vesicle trafficking in erythroid maturation.

Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

ClinicalTrials.gov

2017-07-03

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

ClinicalTrials.gov

2015-03-19

Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

cAMP and in vivo hypoxia induce tob, ifr1, and fos expression in erythroid cells of the chick embryo.

PubMed

Dragon, Stefanie; Offenhäuser, Nina; Baumann, Rosemarie

2002-04-01

During avian embryonic development, terminal erythroid differentiation occurs in the circulation. Some of the key events, such as the induction of erythroid 2,3-bisphosphoglycerate (2,3-BPG), carbonic anhydrase (CAII), and pyrimidine 5'-nucleotidase (P5N) synthesis are oxygen dependent (Baumann R, Haller EA, Schöning U, and Weber M, Dev Biol 116: 548-551, 1986; Dragon S and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 280: R870-R878, 2001; Dragon S, Carey C, Martin K, and Baumann R, J Exp Biol 202: 2787-2795, 1999; Dragon S, Glombitza S, Götz R, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996; Dragon S, Hille R, Götz R, and Baumann R, Blood 91: 3052-3058, 1998; Million D, Zillner P, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 261: R1188-R1196, 1991) in an indirect way: hypoxia stimulates the release of norepinephrine (NE)/adenosine into the circulation (Dragon et al., J Exp Biol 202: 2787-2795, 1999; Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996). This leads via erythroid beta-adrenergic/adenosine A(2) receptor activation to a cAMP signal inducing several proteins in a transcription-dependent manner (Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996; Dragon et al., Blood 91: 3052-3058, 1998; Glombitza S, Dragon S, Berghammer M, Pannermayr M, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R973-R981, 1996). To understand how the cAMP-dependent processes are initiated, we screened an erythroid cDNA library for cAMP-regulated genes. We detected three genes that were strongly upregulated (>5-fold) by cAMP in definitive and primitive red blood cells. They are homologous to the mammalian Tob, Ifr1, and Fos proteins. In addition, the genes are induced in the intact embryo during short-term hypoxia. Because the genes are regulators of proliferation and differentiation in other cell types, we suggest that c

Erythroid cell growth and differentiation in vitro in the simulated microgravity environment of the NASA rotating wall vessel bioreactor

NASA Technical Reports Server (NTRS)

Sytkowski, A. J.; Davis, K. L.

2001-01-01

Prolonged exposure of humans and experimental animals to the altered gravitational conditions of space flight has adverse effects on the lymphoid and erythroid hematopoietic systems. Although some information is available regarding the cellular and molecular changes in lymphocytes exposed to microgravity, little is known about the erythroid cellular changes that may underlie the reduction in erythropoiesis and resultant anemia. We now report a reduction in erythroid growth and a profound inhibition of erythropoietin (Epo)-induced differentiation in a ground-based simulated microgravity model system. Rauscher murine erythroleukemia cells were grown either in tissue culture vessels at 1 x g or in the simulated microgravity environment of the NASA-designed rotating wall vessel (RWV) bioreactor. Logarithmic growth was observed under both conditions; however, the doubling time in simulated microgravity was only one-half of that seen at 1 x g. No difference in apoptosis was detected. Induction with Epo at the initiation of the culture resulted in differentiation of approximately 25% of the cells at 1 x g, consistent with our previous observations. In contrast, induction with Epo at the initiation of simulated microgravity resulted in only one-half of this degree of differentiation. Significantly, the growth of cells in simulated microgravity for 24 h prior to Epo induction inhibited the differentiation almost completely. The results suggest that the NASA RWV bioreactor may serve as a suitable ground-based microgravity simulator to model the cellular and molecular changes in erythroid cells observed in true microgravity.

The locus control region is required for association of the murine β-globin locus with engaged transcription factories during erythroid maturation

PubMed Central

Ragoczy, Tobias; Bender, M.A.; Telling, Agnes; Byron, Rachel; Groudine, Mark

2006-01-01

We have examined the relationship between nuclear localization and transcriptional activity of the endogenous murine β-globin locus during erythroid differentiation. Murine fetal liver cells were separated into distinct erythroid maturation stages by fluorescence-activated cell sorting, and the nuclear position of the locus was determined at each stage. We find that the β-globin locus progressively moves away from the nuclear periphery with increasing maturation. Contrary to the prevailing notion that the nuclear periphery is a repressive compartment in mammalian cells, βmajor-globin expression begins at the nuclear periphery prior to relocalization. However, relocation of the locus to the nuclear interior with maturation is accompanied by an increase in βmajor-globin transcription. The distribution of nuclear polymerase II (Pol II) foci also changes with erythroid differentiation: Transcription factories decrease in number and contract toward the nuclear interior. Moreover, both efficient relocalization of the β-globin locus from the periphery and its association with hyperphosphorylated Pol II transcription factories require the locus control region (LCR). These results suggest that the LCR-dependent association of the β-globin locus with transcriptionally engaged Pol II foci provides the driving force for relocalization of the locus toward the nuclear interior during erythroid maturation. PMID:16705039

Comparison of adult age differences in verbal and visuo-spatial memory: the importance of 'pure', parallel and validated measures.

PubMed

Kemps, Eva; Newson, Rachel

2006-04-01

The study compared age-related decrements in verbal and visuo-spatial memory across a broad elderly adult age range. Twenty-four young (18-25 years), 24 young-old (65-74 years), 24 middle-old (75-84 years) and 24 old-old (85-93 years) adults completed parallel recall and recognition measures of verbal and visuo-spatial memory from the Doors and People Test (Baddeley, Emslie & Nimmo-Smith, 1994). These constituted 'pure' and validated indices of either verbal or visuo-spatial memory. Verbal and visuo-spatial memory declined similarly with age, with a steeper decline in recall than recognition. Unlike recognition memory, recall performance also showed a heightened decline after the age of 85. Age-associated memory loss in both modalities was largely due to working memory and executive function. Processing speed and sensory functioning (vision, hearing) made minor contributions to memory performance and age differences in it. Together, these findings demonstrate common, rather than differential, age-related effects on verbal and visuo-spatial memory. They also emphasize the importance of using 'pure', parallel and validated measures of verbal and visuo-spatial memory in memory ageing research.

[Effect of ATRA on the expression of genes Hoxb2 and Hoxb4 in cord blood erythroid progenitors].

PubMed

DU, Cui-Qiong; Huang, Mei-Xian; Liu, Wen-Jun

2009-12-01

This study was aimed to investigate the expressions of genes hoxb2 and hoxb4 after interference of the proliferation and differentiation of hematopoietic stem cells (HSC) to the erythroid progenitors (CFU-E) in vitro by using all-trans retinoic acid (ATRA). The cord blood was collected from 12 cases of fetal placenta umbilical vein and cultured by using culture technique of HSC in vitro. The proliferation and differentiation of HSC to CFU-E were interfered with 6 x 10(-8) mol/L of ATRA. The expression levels of genes hoxb2 and hoxb4 in blank control and ATRA groups were detected by FQ-RT-PCR on day 3, 7 and 10 of culture. The results showed that the expressions of genes Hoxb2 and hoxb4 were a little on day 3, obviously increased on day 7 and reached highest level on day 10 in 2 groups. The expression level of hoxb4 on day 3, 7 and 10 in blank control group was obviously higher than expression level of hoxb2. As compared with blank control group, the expressions of genes hoxb2 and hoxb4 in the ATRA group were significantly up-regulated. It is concluded that the genes hoxb2 and hoxb4 all expressed in process of proliferation and differentiation to erythroid progenitors, which suggests that hoxb2 and hoxb4 relate to erythroid hematopoiesis, and the hoxb4 has more great relevance to erythroid hematopoiesis as compared with hoxb2. The ATRA (6 x 10(-8) mol/L) can up-regulate the expression of hoxb2 and hoxb4 significantly.

Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

ClinicalTrials.gov

2013-06-03

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

ClinicalTrials.gov

2017-02-01

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2016-04-04

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML

ClinicalTrials.gov

2017-09-12

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy

ClinicalTrials.gov

2015-02-05

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex.

PubMed

Ganaie, Safder S; Zou, Wei; Xu, Peng; Deng, Xuefeng; Kleiboeker, Steve; Qiu, Jianming

2017-05-01

Productive infection of human parvovirus B19 (B19V) exhibits high tropism for burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) progenitor cells in human bone marrow and fetal liver. This exclusive restriction of the virus replication to human erythroid progenitor cells is partly due to the intracellular factors that are essential for viral DNA replication, including erythropoietin signaling. Efficient B19V replication also requires hypoxic conditions, which upregulate the signal transducer and activator of transcription 5 (STAT5) pathway, and phosphorylated STAT5 is essential for virus replication. In this study, our results revealed direct involvement of STAT5 in B19V DNA replication. Consensus STAT5-binding elements were identified adjacent to the NS1-binding element within the minimal origins of viral DNA replication in the B19V genome. Phosphorylated STAT5 specifically interacted with viral DNA replication origins both in vivo and in vitro, and was actively recruited within the viral DNA replication centers. Notably, STAT5 interacted with minichromosome maintenance (MCM) complex, suggesting that STAT5 directly facilitates viral DNA replication by recruiting the helicase complex of the cellular DNA replication machinery to viral DNA replication centers. The FDA-approved drug pimozide dephosphorylates STAT5, and it inhibited B19V replication in ex vivo expanded human erythroid progenitors. Our results demonstrated that pimozide could be a promising antiviral drug for treatment of B19V-related diseases.

Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex

PubMed Central

Ganaie, Safder S.; Zou, Wei; Xu, Peng; Deng, Xuefeng; Kleiboeker, Steve

2017-01-01

Productive infection of human parvovirus B19 (B19V) exhibits high tropism for burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) progenitor cells in human bone marrow and fetal liver. This exclusive restriction of the virus replication to human erythroid progenitor cells is partly due to the intracellular factors that are essential for viral DNA replication, including erythropoietin signaling. Efficient B19V replication also requires hypoxic conditions, which upregulate the signal transducer and activator of transcription 5 (STAT5) pathway, and phosphorylated STAT5 is essential for virus replication. In this study, our results revealed direct involvement of STAT5 in B19V DNA replication. Consensus STAT5-binding elements were identified adjacent to the NS1-binding element within the minimal origins of viral DNA replication in the B19V genome. Phosphorylated STAT5 specifically interacted with viral DNA replication origins both in vivo and in vitro, and was actively recruited within the viral DNA replication centers. Notably, STAT5 interacted with minichromosome maintenance (MCM) complex, suggesting that STAT5 directly facilitates viral DNA replication by recruiting the helicase complex of the cellular DNA replication machinery to viral DNA replication centers. The FDA-approved drug pimozide dephosphorylates STAT5, and it inhibited B19V replication in ex vivo expanded human erythroid progenitors. Our results demonstrated that pimozide could be a promising antiviral drug for treatment of B19V-related diseases. PMID:28459842

Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

ClinicalTrials.gov

2018-05-24

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

ClinicalTrials.gov

2016-04-05

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

ClinicalTrials.gov

2017-12-07

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

[The induction and cryopreservation of erythroid progenitor cells derived from umbilical cord blood mononuclear cells].

PubMed

Chen, Lin; Xie, Xiaoyan; Xi, Jiafei; Lyu, Yang; Tian, Yu; Liu, Daqing; Yue, Wen; Li, Yanhua; Nan, Xue; Li, Siting; Fan, Zeng; Pei, Xuetao

2016-01-01

To discover the techniques for ex vivo generation and cryopreservation of erythroid progenitor cells (EPCs)derived from umbilical cord blood (UCB)mononuclear cells (MNCs). UCB was chosen as the source of EPCs. Erythrocytes were precipitated by hydroxyethyl starch (HES). MNCs were separated by Ficoll density gradient centrifugation. Erythroid progenitor cell were generated from MNC ex vivo in suspension culture supplemented with stem cell growth factor, insulin growth factor, erythropoietin, Fms- liketyrosinekinase ligand, transferrin and dexamethasone. Cell maturation was evaluated by morphologic analysis and CD71/CD235a expression profiling. In vitro induced cells were cryopreserved using different cryopreservation media. The cell survival rate, phenotype and proliferation curves were detected after cell thawing. With the extension of culture time, the total number of cells increased significantly accompanied with the elevation of CD71 and CD235 positive populations. After 14- day inducing, the cells reached to approximately 110 times of the starting number with the cell viability as (88.92±0.95)%. The percentages of cell surface markers were (86.77±9.11)% for CD71 and (64.47±16.67)% for CD71/CD235, respectively. With the extension of inducing time, wright- Giemsa staining showed that the middle erythroblasts appeared mostly at day 10, and the late erythroblasts were seen at day 14. The red pellets were present at day 14, which indicated the more production of hemoglobin. Colony forming assay showed that erythroid colonies at induction day 7 were higher than that for non-induced cells (326.00±97.96vs 61.60±20.03 per 2 000 cells). With the extension of culture time, the number of erythroid colonies decreased. Induced EPCs were preserved with different cryopreservation solutions, in which 10% DMSO were better than 5% DMSO. Additionally, 10% DMSO + 2% HSA showed no different with 10% DMSO + 5% HSA. Combined 50% plasma with 2% HSA was more effective. This non

Identification of a human erythroid progenitor cell population which expresses the CD34 antigen and binds the plant lectin Ulex europaeus I.

PubMed

Unverzagt, K L; Martinson, J; Lee, W; Stiff, P J; Williams, S; Bender, J G

1996-01-01

Two and three color flow cytometry of normal human bone marrow was used to identify CD34+ progenitor cells and examine their binding to the plant lectin Ulex europaeus I (Ulex). In normal bone marrow, 48.48 +/- 17.4% of the CD34+ cells bind to Ulex. Two color flow cytometry was used to sort CD34 + cells, and subsets of CD34+ cells, CD34+ Ulex+ and CD34+ Ulex-. These populations were sorted into colony assays to assess myeloid (CFU-GM) and erythroid (BFU-E) progenitors. The CD34+ Ulex+ subset was 84 +/- 14% BFU-E colonies (mean +/- S.D.) and had the highest cloning efficiency of 28 +/- 13%. Three color analysis of CD34+ Ulex+ cells showed staining with other erythroid (CD71, GlyA) antibodies and lack of stain. ing with myeloid (CD13, CD45RA) antibodies. These studies confirmed the erythroid characteristics of this subpopulation.

Aid is a key regulator of myeloid/erythroid differentiation and DNA methylation in hematopoietic stem/progenitor cells

PubMed Central

Kunimoto, Hiroyoshi; McKenney, Anna Sophia; Meydan, Cem; Shank, Kaitlyn; Nazir, Abbas; Rapaport, Franck; Durham, Benjamin; Garrett-Bakelman, Francine E.; Pronier, Elodie; Shih, Alan H.; Melnick, Ari; Chaudhuri, Jayanta

2017-01-01

Recent studies have reported that activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies, and hematopoietic-specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated. Here, we show that Aid loss in mice leads to expansion of myeloid cells and reduced erythroid progenitors resulting in anemia, with dysregulated expression of Cebpa and Gata1, myeloid/erythroid lineage-specific transcription factors. Consistent with data in the murine context, silencing of AID in human bone marrow cells skews differentiation toward myelomonocytic lineage. However, in contrast to Tet2 loss, Aid loss does not contribute to enhanced HSC self-renewal or cooperate with Flt3-ITD to induce myeloid transformation. Genome-wide transcription and differential methylation analysis uncover the critical role of Aid as a key epigenetic regulator. These results indicate that AID and TET2 share common effects on myeloid and erythroid lineage differentiation, however, their role is nonredundant in regulating HSC self-renewal and in myeloid transformation. PMID:28077417

Enhanced erythropoiesis in Hfe-KO mice indicates a role for Hfe in the modulation of erythroid iron homeostasis

PubMed Central

Ramos, Pedro; Guy, Ella; Chen, Nan; Proenca, Catia C.; Gardenghi, Sara; Casu, Carla; Follenzi, Antonia; Van Rooijen, Nico; Grady, Robert W.; de Sousa, Maria

2011-01-01

In hereditary hemochromatosis, mutations in HFE lead to iron overload through abnormally low levels of hepcidin. In addition, HFE potentially modulates cellular iron uptake by interacting with transferrin receptor, a crucial protein during erythropoiesis. However, the role of HFE in this process was never explored. We hypothesize that HFE modulates erythropoiesis by affecting dietary iron absorption and erythroid iron intake. To investigate this, we used Hfe-KO mice in conditions of altered dietary iron and erythropoiesis. We show that Hfe-KO mice can overcome phlebotomy-induced anemia more rapidly than wild-type mice (even when iron loaded). Second, we evaluated mice combining the hemochromatosis and β-thalassemia phenotypes. Our results suggest that lack of Hfe is advantageous in conditions of increased erythropoietic activity because of augmented iron mobilization driven by deficient hepcidin response. Lastly, we demonstrate that Hfe is expressed in erythroid cells and impairs iron uptake, whereas its absence exclusively from the hematopoietic compartment is sufficient to accelerate recovery from phlebotomy. In summary, we demonstrate that Hfe influences erythropoiesis by 2 distinct mechanisms: limiting hepcidin expression under conditions of simultaneous iron overload and stress erythropoiesis, and impairing transferrin-bound iron uptake by erythroid cells. Moreover, our results provide novel suggestions to improve the treatment of hemochromatosis. PMID:21059897

Effects of human recombinant erythropoietin on differentiation and distribution of erythroid progenitor cells on murine medullary and splenic erythropoiesis during hypoxia and post-hypoxia.

PubMed

Mide, S M; Huygens, P; Bozzini, C E; Fernandez Pol, J A

2001-01-01

Hemopoietic cells, the extracellular matrix, growth factors and the microenvironment are involved in the regulation of hemopoiesis. Although the regulation of erythropoiesis is well understood at the cellular level in vivo and in vitro, the role of hemopoietic sites of erythroid progenitors production has not been well defined in both steady state conditions and in stress erythropoiesis. In this study we examined the qualitative erythroid differentiation and quantitative changes of the erythroid progenitors in different erythropoietic organs during erythropoiesis of stress in a hypoxia-induced polycythemia and post-hypoxic changes in a mice model. Chronic intermittent exposure to hypobaric hypoxia induced polycythemia in mice and the post-hypoxic period was characterized by total suppression of erythropoiesis. The number and distribution in hemopoietic sites of Immature Erythroid Burst (BFU-EI), Mature Erythroid Burst (BFU-EM) and Erythroid Colony Forming Units (CFU-E) was evaluated in bone marrow and spleen of hypoxic and post-hypoxic mice after removal from the chamber. The number of BFU-EI and CFU-E, was evaluated in both femoral bone marrow and spleen of ex-hypoxic polycythemic mice, at two times intervals after the end of hypoxia. We found that in both bone marrow and spleen, the kinetics of the CFU-E pool was characterized by a sharp fall from above normal to lower than normal levels. BFU-EM increased from normal to higher than normal levels. These results have been correlated with both erythropoietin (EPO) and the erythropoietic activity. The results show that EPO levels largely control both the differentiation and the amplification of the CFU-E pool and they suggest that EPO may acts as a "survival factor" at the CFU-E level and/or increase the flow of cells from BFU-E to CFU-E. After the termination of the period of hypoxia and during post-hypoxia there was a reduction in EPO production which subsequently caused a depletion of the CFU-E population

Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

ClinicalTrials.gov

2014-08-13

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Treatment for Relapsed/Refractory AML Based on a High Throughput Drug Sensitivity Assay

ClinicalTrials.gov

2018-04-11

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

ClinicalTrials.gov

2017-10-16

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia

Binding of polarity-sensitive hydrophobic ligands to erythroid and nonerythroid spectrin: fluorescence and molecular modeling studies.

PubMed

Patra, Malay; Mitra, Madhurima; Chakrabarti, Abhijit; Mukhopadhyay, Chaitali

2014-01-01

We have used three polarity-sensitive fluorescence probes, 6-propionyl 2-(N,N-dimethyl-amino) naphthalene (Prodan), pyrene and 8-anilino 1-naphthalene sulphonic acid, to study their binding with erythroid and nonerythroid spectrin, using fluorescence spectroscopy. We have found that both bind to prodan and pyrene with high affinities with apparent dissociation constants (Kd) of .50 and .17 μM, for prodan, and .04 and .02 μM, for pyrene, respectively. The most striking aspect of these bindings have been that the binding stoichiometry have been equal to 1 in erythroid spectrin, both in dimeric and tetrameric form, and in tetrameric nonerythroid spectrin. From an estimate of apparent dielectric constants, the polarity of the binding site in both erythroid and nonerythroid forms have been found to be extremely hydrophobic. Thermodynamic parameters associated with such binding revealed that the binding is favored by positive change in entropy. Molecular docking studies alone indicate that both prodan and pyrene bind to the four major structural domains, following the order in the strength of binding to the Ankyrin binding domain > SH3 domain > Self-association domain > N-terminal domain of α-spectrin of both forms of spectrin. The binding experiments, particularly with the tetrameric nonerythroid spectrin, however, indicate more toward the self association domain in offering the unique binding site, since the binding stoichiometry have been 1 in all forms of dimeric and tetrameric spectrin, so far studied by us. Further studies are needed to characterize the hydrophobic binding sites in both forms of spectrin.

Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission

ClinicalTrials.gov

2018-03-20

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Myelodysplastic Syndrome With Excess Blasts; Recurrent Adult Acute Myeloid Leukemia

Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion.

PubMed

Falchi, Mario; Varricchio, Lilian; Martelli, Fabrizio; Masiello, Francesca; Federici, Giulia; Zingariello, Maria; Girelli, Gabriella; Whitsett, Carolyn; Petricoin, Emanuel F; Moestrup, Søren Kragh; Zeuner, Ann; Migliaccio, Anna Rita

2015-02-01

Cultures of human CD34(pos) cells stimulated with erythroid growth factors plus dexamethasone, a model for stress erythropoiesis, generate numerous erythroid cells plus a few macrophages (approx. 3%; 3:1 positive and negative for CD169). Interactions occurring between erythroblasts and macrophages in these cultures and the biological effects associated with these interactions were documented by live phase-contrast videomicroscopy. Macrophages expressed high motility interacting with hundreds/thousands of erythroblasts per hour. CD169(pos) macrophages established multiple rapid 'loose' interactions with proerythroblasts leading to formation of transient erythroblastic island-like structures. By contrast, CD169(neg) macrophages established 'tight' interactions with mature erythroblasts and phagocytosed these cells. 'Loose' interactions of CD169(pos) macrophages were associated with proerythroblast cytokinesis (the M phase of the cell cycle) suggesting that these interactions may promote proerythroblast duplication. This hypothesis was tested by experiments that showed that as few as 103 macrophages significantly increased levels of 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide incorporation frequency in S/G2/M and cytokinesis expressed by proerythroblasts over 24 h of culture. These effects were observed also when macrophages were co-cultured with dexamethasone directly conjugated to a macrophage-specific CD163 antibody. In conclusion, in addition to promoting proerythroblast proliferation directly, dexamethasone stimulates expansion of these cells indirectly by stimulating maturation and cytokinesis supporting activity of macrophages. Copyright© Ferrata Storti Foundation.

Expression of sialosyl-Tn in colony-forming unit-erythroid, erythroblasts, B cells, and a subset of CD4+ cells.

PubMed

Muroi, K; Suda, T; Nakamura, M; Okada, S; Nojiri, H; Amemiya, Y; Miura, Y; Hakomori, S

1994-01-01

The epitopes Tn and sialosyl-Tn are expressed on erythrocytes of individuals with a very rare blood group, who often suffer from "Tn syndrome." We surveyed expression of Tn and sialosyl-Tn in normal blood cells, malignant transformed cells, and progenitor stem cells from bone marrow (BM). An anti-Tn antibody, IE3, and an anti-sialosyl-Tn antibody, TKH2, were used in this study. TKH2 reacted with erythroblasts, B cells, and a subset of CD4+ cells; but not with erythrocytes. Erythroblastic cell lines (K562, HEL, and UT7/EPO) and B-cell lines (Daudi, Raji, and B-cell lines transformed by Epstein-Barr virus) showed reactivity to TKH2. Similar results from the reactivity of TKH2 with transformed cells from leukemia patients and lymphoma patients were obtained; TKH2 reacted with blasts from erythroleukemia (M6; for 4 of 4 cases) and with lymphocytes from B-cell chronic lymphocytic leukemia (3 of 3), B-cell lymphoma (5 of 5), and CD4+ adult T-cell leukemia (4 of 4), but did not react with blasts from acute myeloid leukemia (M0 to M5; 0 of 22) or acute lymphoid leukemia (B-lymphoid leukemia, 0 of 11; T-lymphoid leukemia, 0 of 2; undifferentiated leukemia, 0 of 1). IE3 did not react with all of the tested cells. CD2-CD19-TKH2+ normal BM cells (BMC) contained blasts and various maturation stages of erythroblasts. The TKH2+ cells produced a large number of colony-forming unit-erythroid (CFU-E) colonies, whereas they produced a small number of burst-forming unit-erythroid colonies and CFU-granulocyte-macrophage colonies. CD34+ normal BMC did not express Tn and sialosyl-Tn. These findings suggest that sialosyl-Tn expresses in CFU-E to erythroblasts.

Transcription factor GATA-1 regulates human HOXB2 gene expression in erythroid cells.

PubMed

Vieille-Grosjean, I; Huber, P

1995-03-03

The human HOXB2 gene is a member of the vertebrate Hox gene family that contains genes coding for specific developmental stage DNA-binding proteins. Remarkably, within the hematopoietic compartment, genes of the HOXB complex are expressed specifically in erythromegakaryocytic cell lines and, for some of them, in hematopoietic progenitors. Here, we report the study of HOXB2 gene transcriptional regulation in hematopoietic cells, an initial step in understanding the lineage-specific expression of the whole HOXB complex in these cells. We have isolated the HOXB2 5'-flanking sequence and have characterized a promoter fragment extending 323 base pairs upstream from the transcriptional start site, which, in transfection experiments, was sufficient to direct the tissue-specific expression of HOXB2 in the erythroid cell line K562. In this fragment, we have identified a potential GATA-binding site that is essential to the promoter activity as demonstrated by point mutation experiments. Gel shift analysis revealed the formation of a specific complex in both erythroleukemic lines K562 and HEL that could be prevented by the addition of a specific antiserum raised against GATA-1 protein. These findings suggest a regulatory hierarchy in which GATA-1 is upstream of the HOXB2 gene in erythroid cells.

The MNS glycophorin variant GP.Mur affects differential erythroid expression of Rh/RhAG transcripts.

PubMed

Hsu, K; Kuo, M-S; Yao, C-C; Cheng, H-C; Lin, H-J; Chan, Y-S; Lin, M

2017-10-01

The band 3 macrocomplex (also known as the ankyrin-associated complex) on the red cell membrane comprises two interacting subcomplexes: a band 3/glycophorin A subcomplex, and a Rh/RhAG subcomplex. Glycophorin B (GPB) is a component of the Rh/RhAG subcomplex that is also structurally associated with glycophorin A (GPA). Expression of glycophorin B-A-B hybrid GP.Mur enhances band 3 expression and is associated with lower levels of Rh-associated glycoprotein (RhAG) and Rh polypeptides. The goal of this study was to determine whether GP.Mur influenced erythroid Rh/RhAG expression at the transcript level. GP.Mur was serologically determined in healthy participants from Taitung County, Taiwan. RNA was extracted from the reticulocyte-enriched fraction of peripheral blood, followed by reverse transcription and quantitative PCR for RhAG, RhD and RhCcEe. Quantification by real-time PCR revealed significantly fewer RhAG and RhCcEe transcripts in the reticulocytes from subjects with homozygous GYP*Mur. Independent from GYP.Mur, both RhAG and RhD transcript levels were threefold or higher than that of RhCcEe. Also, in GYP.Mur and the control samples alike, direct quantitative associations were observed between the transcript levels of RhAG and RhD, but not between that of RhAG and RhCcEe. Erythroid RhD and RhCcEe were differentially expressed at the transcript levels, which could be related to their different degrees of interaction or sensitivity to RhAG. Further, the reduction or absence of glycophorin B in GYP.Mur erythroid cells affected transcript expressions of RhAG and RhCcEe. Thus, GPB and GP.Mur differentially influenced Rh/RhAG expressions prior to protein translation. © 2017 International Society of Blood Transfusion.

Induction of Erythroid Differentiation in Human Erythroleukemia Cells by Depletion of Malic Enzyme 2

PubMed Central

Everett, Peter; Clish, Clary B.; Sukhatme, Vikas P.

2010-01-01

Malic enzyme 2 (ME2) is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and CO2 and uses NAD as a cofactor. Higher expression of this enzyme correlates with the degree of cell de-differentiation. We found that ME2 is expressed in K562 erythroleukemia cells, in which a number of agents have been found to induce differentiation either along the erythroid or the myeloid lineage. We found that knockdown of ME2 led to diminished proliferation of tumor cells and increased apoptosis in vitro. These findings were accompanied by differentiation of K562 cells along the erythroid lineage, as confirmed by staining for glycophorin A and hemoglobin production. ME2 knockdown also totally abolished growth of K562 cells in nude mice. Increased ROS levels, likely reflecting increased mitochondrial production, and a decreased NADPH/NADP+ ratio were noted but use of a free radical scavenger to decrease inhibition of ROS levels did not reverse the differentiation or apoptotic phenotype, suggesting that ROS production is not causally involved in the resultant phenotype. As might be expected, depletion of ME2 induced an increase in the NAD+/NADH ratio and ATP levels fell significantly. Inhibition of the malate-aspartate shuttle was insufficient to induce K562 differentiation. We also examined several intracellular signaling pathways and expression of transcription factors and intermediate filament proteins whose expression is known to be modulated during erythroid differentiation in K562 cells. We found that silencing of ME2 leads to phospho-ERK1/2 inhibition, phospho-AKT activation, increased GATA-1 expression and diminished vimentin expression. Metabolomic analysis, conducted to gain insight into intermediary metabolic pathways that ME2 knockdown might affect, showed that ME2 depletion resulted in high orotate levels, suggesting potential impairment of pyrimidine metabolism. Collectively our data point to ME2 as a potentially novel metabolic target for

Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia

ClinicalTrials.gov

2014-05-09

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

MBD2 is a critical component of a methyl cytosine-binding protein complex isolated from primary erythroid cells

PubMed Central

Kransdorf, Evan P.; Wang, Shou Zhen; Zhu, Sheng Zu; Langston, Timothy B.; Rupon, Jeremy W.; Ginder, Gordon D.

2006-01-01

The chicken embryonic β-type globin gene, ρ, is a member of a small group of vertebrate genes whose developmentally regulated expression is mediated by DNA methylation. Previously, we have shown that a methyl cytosine-binding complex binds to the methylated ρ-globin gene in vitro. We have now chromatographically purified and characterized this complex from adult chicken primary erythroid cells. Four components of the MeCP1 transcriptional repression complex were identified: MBD2, RBAP48, HDAC2, and MTA1. These 4 proteins, as well as the zinc-finger protein p66 and the chromatin remodeling factor Mi2, were found to coelute by gel-filtration analysis and pull-down assays. We conclude that these 6 proteins are components of the MeCPC. In adult erythrocytes, significant enrichment for MBD2 is seen at the inactive ρ-globin gene by chromatin immunoprecipitation assay, whereas no enrichment is observed at the active βA-globin gene, demonstrating MBD2 binds to the methylated and transcriptionally silent ρ-globin gene in vivo. Knock-down of MBD2 resulted in up-regulation of a methylated ρ-gene construct in mouse erythroleukemic (MEL)-ρ cells. These results represent the first purification of a MeCP1-like complex from a primary cell source and provide support for a role for MBD2 in developmental gene regulation. PMID:16778143

Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch

PubMed Central

Hwang, Yung; Futran, Melinda; Hidalgo, Daniel; Pop, Ramona; Iyer, Divya Ramalingam; Scully, Ralph; Rhind, Nicholas; Socolovsky, Merav

2017-01-01

Cell cycle regulators are increasingly implicated in cell fate decisions, such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. We studied an S phase–dependent cell fate switch, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. We found that progenitors are dependent on p57KIP2-mediated slowing of replication forks for self-renewal, a novel function for cyclin-dependent kinase inhibitors. The switch to differentiation entails rapid down-regulation of p57KIP2 with a consequent global increase in replication fork speed and an abruptly shorter S phase. Our work suggests that cell cycles with specialized global DNA replication dynamics are integral to the maintenance of specific cell states and to cell fate decisions. PMID:28560351

Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

ClinicalTrials.gov

2013-09-27

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

ClinicalTrials.gov

2018-03-05

Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

Veliparib and Topotecan With or Without Carboplatin in Treating Patients With Relapsed or Refractory Acute Leukemia, High-Risk Myelodysplasia, or Aggressive Myeloproliferative Disorders

ClinicalTrials.gov

2018-04-20

Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Hematopoietic and Lymphoid Cell Neoplasm; Myelodysplastic Syndrome; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Myelodysplastic Syndrome

Erythroid dysplasia, megaloblastic anemia, and impaired lymphopoiesis arising from mitochondrial dysfunction

PubMed Central

Chen, Michael L.; Logan, T. Daniel; Hochberg, Maryann L.; Shelat, Suresh G.; Yu, Xiang; Wilding, Gregory E.; Tan, Wei; Kujoth, Gregory C.; Prolla, Tomas A.; Selak, Mary A.; Kundu, Mondira; Carroll, Martin

2009-01-01

Recent reports describe hematopoietic abnormalities in mice with targeted instability of the mitochondrial genome. However, these abnormalities have not been fully described. We demonstrate that mutant animals develop an age-dependent, macrocytic anemia with abnormal erythroid maturation and megaloblastic changes, as well as profound defects in lymphopoiesis. Mice die of severe fatal anemia at 15 months of age. Bone-marrow transplantation studies demonstrate that these abnormalities are intrinsic to the hematopoietic compartment and dependent upon the age of donor hematopoietic stem cells. These abnormalities are phenotypically similar to those found in patients with refractory anemia, suggesting that, in some cases, the myelodysplastic syndromes are caused by abnormalities of mitochondrial function. PMID:19734452

Transduction of human IL-9 receptor cDNA into TF1 cells induces IL-9 dependency and erythroid differentiation.

PubMed

Xiao, M; Luo, Z; Mantel, C; Broxmeyer, H E; Lu, L

2000-02-01

Human growth factor-dependent cell line TF1, which lacks interleukin (IL)-9 receptors (R) and does not grow in IL-9, was transduced with a retroviral vector containing human IL-9R cDNA and a selection marker. An IL-9-dependent TF1 cell line, which could also grow in other cytokines, was established after selection in G418 and could produce mature RBC in response to cytokine stimulation. TF1 cells transduced with the same viral vector without the IL-9R insert cDNA (mock control) and then selected responded the same as nontransduced TF1 cells. They failed to grow in response to IL-9 and did not generate RBC. An increased number and size of burst-forming units-erythroid (BFU-E)-like colonies were detected from IL-9R-transduced TF1 cells, compared with mock-transduced cells, in response to erythropoietin (EPO) and IL-9. To evaluate self-renewal and differentiation capacity, colony-replating assays were performed in the presence of IL-3, GM-CSF, IL-9, and EPO. After four replatings, the cloning efficiency of IL-9R-transduced TF1 cells decreased from 98% to 38%, most likely due to terminal erythroid cell differentiation. In contrast, no change in replating efficiency was detected in mock-transduced cells. TF1 cells stably expressing IL-9R and responding to IL-9 can serve as a cell line model to study the intracellular signals mediating IL-9-induced erythroid cell proliferation and differentiation.

Otoacoustic emissions in the general adult population of Nord-Trøndelag, Norway: III. Relationships with pure-tone hearing thresholds.

PubMed

Engdahl, Bo; Tambs, Kristian; Borchgrevink, Hans M; Hoffman, Howard J

2005-01-01

This study aims to describe the association between otoacoustic emissions (OAEs) and pure-tone hearing thresholds (PTTs) in an unscreened adult population (N =6415), to determine the efficiency by which TEOAEs and DPOAEs can identify ears with elevated PTTs, and to investigate whether a combination of DPOAE and TEOAE responses improves this performance. Associations were examined by linear regression analysis and ANOVA. Test performance was assessed by receiver operator characteristic (ROC) curves. The relation between OAEs and PTTs appeared curvilinear with a moderate degree of non-linearity. Combining DPOAEs and TEOAEs improved performance. Test performance depended on the cut-off thresholds defining elevated PTTs with optimal values between 25 and 45 dB HL, depending on frequency and type of OAE measure. The unique constitution of the present large sample, which reflects the general adult population, makes these results applicable to population-based studies and screening programs.

Hemoglobin switching in sheep and goats. VI. Commitment of erythroid colony-forming cells to the synthesis of betaC globin

PubMed Central

1976-01-01

Bone marrow from mature goats and sheep was cultured in plasma clots, and three erythropoietin (ESF)-dependent responses-growth (colony formation), differentiation (globin production), and initiation of hemoglobin C (alpha2beta2C) synthesis--were quantitated. ESF concentrations below 0.01 U/ml supported colony growth and adult hemoglobin production in cultures of goat marrow, while maximal hemoglobin C synthesis (70%), as measured between 72 and 96 h in culture, required a 100-fold higher ESF concentration. Sheep marrow was cultured in a medium enriched to enhance growth and to permit complete maturation of colonies. These colonies active in hemoglobin synthesis between 24 and 96 h produced mainly adult hemoglobin, and only between 96 and 120 h did sheep colonies develop which produced mainly hemoglobin C (up to 70%). A similar heterogeneity may exist among goat colonies. Thus, when goat bone marrow was fractionated by unit gravity sedimentation, more hemoglobin C synthesis was observed in colonies derived from cells of intermediate sedimentation velocity than in colonies derived from the most rapidly sedimenting cells. Brief exposure of sheep (in vivo) and goat (in vitro) bone marrow to a high ESF concentration committed precursor cells to the generation of colonies which, even at low ESF concentration, produced hemoglobin C. Committment to hemoglobin phenotype appears to be an early and probably irreversible event in the development of an erythroid cell. PMID:993267

Erythroid cell mitochondria receive endosomal iron by a "kiss-and-run" mechanism.

PubMed

Hamdi, Amel; Roshan, Tariq M; Kahawita, Tanya M; Mason, Anne B; Sheftel, Alex D; Ponka, Prem

2016-12-01

In erythroid cells, more than 90% of transferrin-derived iron enters mitochondria where ferrochelatase inserts Fe 2+ into protoporphyrin IX. However, the path of iron from endosomes to mitochondrial ferrochelatase remains elusive. The prevailing opinion is that, after its export from endosomes, the redox-active metal spreads into the cytosol and mysteriously finds its way into mitochondria through passive diffusion. In contrast, this study supports the hypothesis that the highly efficient transport of iron toward ferrochelatase in erythroid cells requires a direct interaction between transferrin-endosomes and mitochondria (the "kiss-and-run" hypothesis). Using a novel method (flow sub-cytometry), we analyze lysates of reticulocytes after labeling these organelles with different fluorophores. We have identified a double-labeled population definitively representing endosomes interacting with mitochondria, as demonstrated by confocal microscopy. Moreover, we conclude that this endosome-mitochondrion association is reversible, since a "chase" with unlabeled holotransferrin causes a time-dependent decrease in the size of the double-labeled population. Importantly, the dissociation of endosomes from mitochondria does not occur in the absence of holotransferrin. Additionally, mutated recombinant holotransferrin, that cannot release iron, significantly decreases the uptake of 59 Fe by reticulocytes and diminishes 59 Fe incorporation into heme. This suggests that endosomes, which are unable to provide iron to mitochondria, cause a "traffic jam" leading to decreased endocytosis of holotransferrin. Altogether, our results suggest that a molecular mechanism exists to coordinate the iron status of endosomal transferrin with its trafficking. Besides its contribution to the field of iron metabolism, this study provides evidence for a new intracellular trafficking pathway of organelles. Copyright © 2016 Elsevier B.V. All rights reserved.

Single dose of filgrastim (rhG-CSF) increases the number of hematopoietic progenitors in the peripheral blood of adult volunteers.

PubMed

Schwinger, W; Mache, C; Urban, C; Beaufort, F; Töglhofer, W

1993-06-01

Hematopoietic progenitor cell levels were monitored in the peripheral blood of ten healthy adults receiving a single dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF). The objective was to determine the time and number of progenitor cells released into the peripheral blood, induced by a single dose of 15 micrograms/kg rhG-CSF administered intravenously. In all cases the absolute number of circulating progenitor cells including granulocyte-macrophage and erythroid lineages increased up to 12-fold (median 9.4-fold) 4 days after treatment. These findings were based on flow cytometric quantification of CD34+ cells and on progenitor assays. The relative distribution of granulocyte/macrophage and erythroid progenitors remained unchanged. rhG-CSF was well tolerated; mild to moderate bone pain was the most common side-effect and was noted in 6 of 10 subjects. Thus a single dose of rhG-CSF is effective in mobilizing progenitor cells into the peripheral blood in healthy adults. If these progenitors are capable of reconstituting bone marrow, peripheral progenitor cell separation following rhG-CSF administration could be a reasonable alternative to conventional bone marrow harvest in healthy adults.

Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection

NASA Astrophysics Data System (ADS)

Elahi, Shokrollah; Ertelt, James M.; Kinder, Jeremy M.; Jiang, Tony T.; Zhang, Xuzhe; Xin, Lijun; Chaturvedi, Vandana; Strong, Beverly S.; Qualls, Joseph E.; Steinbrecher, Kris A.; Kalfa, Theodosia A.; Shaaban, Aimen F.; Way, Sing Sing

2013-12-01

Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71+ cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with L-arginine overrides immunosuppression. In addition, the ablation of CD71+ cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli. However, CD71+ cell-mediated susceptibility to infection is counterbalanced by CD71+ cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition. Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71+ cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these

Engineered U7 snRNA mediates sustained splicing correction in erythroid cells from β-thalassemia/HbE patients.

PubMed

Preedagasamzin, Sarinthip; Nualkaew, Tiwaporn; Pongrujikorn, Tanjitti; Jinawath, Natini; Kole, Ryszard; Fucharoen, Suthat; Jearawiriyapaisarn, Natee; Svasti, Saovaros

2018-04-30

Repair of a splicing defect of β-globin pre-mRNA harboring hemoglobin E (HbE) mutation was successfully accomplished in erythroid cells from patients with β-thalassemia/HbE disorder by a synthetic splice-switching oligonucleotide (SSO). However, its application is limited by short-term effectiveness and requirement of lifelong periodic administration of SSO, especially for chronic diseases like thalassemias. Here, we engineered lentiviral vectors that stably express U7 small nuclear RNA (U7 snRNA) carrying the splice-switching sequence of the SSO that restores correct splicing of β E -globin pre-mRNA and achieves a long-term therapeutic effect. Using a two-step tiling approach, we systematically screened U7 snRNAs carrying splice-switching SSO sequences targeted to the cryptic 5' splice site created by HbE mutation. We tested this approach and identified the most responsive element for mediating splicing correction in engineered U7 snRNAs in HeLa-β E cell model cell line. Remarkably, the U7 snRNA lentiviral vector (U7 βE4+1) targeted to this region effectively restored the correctly-spliced β E -globin mRNA for at least 5 months. Moreover, the effects of the U7 βE4+1 snRNA lentiviral vector were also evident as upregulation of the correctly-spliced β E -globin mRNA in erythroid progenitor cells from β-thalassemia/HbE patients treated with the vector, which led to improvements of pathologies in erythroid progenitor cells from thalassemia patients. These results suggest that the splicing correction of β E -globin pre-mRNA by the engineered U7 snRNA lentiviral vector provides a promising, long-term treatment for β-thalassemia/HbE. Copyright © 2018 Elsevier Inc. All rights reserved.

7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

ClinicalTrials.gov

2013-09-27

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

ClinicalTrials.gov

2017-06-16

Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

ClinicalTrials.gov

2013-01-10

Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

Identification of Cell Type-Specific Differences in Erythropoietin Receptor Signaling in Primary Erythroid and Lung Cancer Cells

PubMed Central

Salopiata, Florian; Depner, Sofia; Wäsch, Marvin; Böhm, Martin E.; Mücke, Oliver; Plass, Christoph; Lehmann, Wolf D.; Kreutz, Clemens; Timmer, Jens; Klingmüller, Ursula

2016-01-01

Lung cancer, with its most prevalent form non-small-cell lung carcinoma (NSCLC), is one of the leading causes of cancer-related deaths worldwide, and is commonly treated with chemotherapeutic drugs such as cisplatin. Lung cancer patients frequently suffer from chemotherapy-induced anemia, which can be treated with erythropoietin (EPO). However, studies have indicated that EPO not only promotes erythropoiesis in hematopoietic cells, but may also enhance survival of NSCLC cells. Here, we verified that the NSCLC cell line H838 expresses functional erythropoietin receptors (EPOR) and that treatment with EPO reduces cisplatin-induced apoptosis. To pinpoint differences in EPO-induced survival signaling in erythroid progenitor cells (CFU-E, colony forming unit-erythroid) and H838 cells, we combined mathematical modeling with a method for feature selection, the L1 regularization. Utilizing an example model and simulated data, we demonstrated that this approach enables the accurate identification and quantification of cell type-specific parameters. We applied our strategy to quantitative time-resolved data of EPO-induced JAK/STAT signaling generated by quantitative immunoblotting, mass spectrometry and quantitative real-time PCR (qRT-PCR) in CFU-E and H838 cells as well as H838 cells overexpressing human EPOR (H838-HA-hEPOR). The established parsimonious mathematical model was able to simultaneously describe the data sets of CFU-E, H838 and H838-HA-hEPOR cells. Seven cell type-specific parameters were identified that included for example parameters for nuclear translocation of STAT5 and target gene induction. Cell type-specific differences in target gene induction were experimentally validated by qRT-PCR experiments. The systematic identification of pathway differences and sensitivities of EPOR signaling in CFU-E and H838 cells revealed potential targets for intervention to selectively inhibit EPO-induced signaling in the tumor cells but leave the responses in erythroid

Parvovirus B19 Replication and Expression in Differentiating Erythroid Progenitor Cells

PubMed Central

Bua, Gloria; Manaresi, Elisabetta; Bonvicini, Francesca; Gallinella, Giorgio

2016-01-01

The pathogenic Parvovirus B19 (B19V) is characterized by a strict adaptation to erythroid progenitor cells (EPCs), a heterogeneous population of differentiating cells with diverse phenotypic and functional properties. In our work, we studied the dynamics of B19V infection in EPCs in dependence on the cell differentiation stage, in terms of distribution of infected cells, synthesis of viral nucleic acids and production of infectious virus. EPCs at early differentiation stage led to an abortive infection, without viral genome replication and a very low transcriptional activity. EPCs at later stages were permissive, with highest levels of viral replicative activity at day 9 (+3.0 Log from 2 to 48 hpi) and lower levels at day 18 (+1.5 Log from 2 to 48 hpi). B19V DNA increment was in accordance with the percentage of cells positive to flow-FISH assay (41.4% at day 9, 1.1% at day 18). Quantitation of total RNA indicated a close association of genome replication and transcription with viral RNA accumulation within infected cells related to viral DNA increase during the course of infection. Analysis of the different classes of mRNAs revealed two distinct pattern of genome expression profile with a fine regulation in the frequency utilization of RNA processing signals: an early phase, when cleavage at the proximal site leading to a higher relative production of mRNA for NS protein, and a late phase, when cleavage at the distal site was more frequent leading to higher relative abundance of mRNA for VP and 11 kDA proteins. Infectious virus was released from cells at day 6–15, but not at day 18. Our results, providing a detailed description of B19V replication and expression profile in differentiating EPCs, highlight the very tight adaptation of B19V to a specific cellular target defined both by its erythroid lineage and its differentiation stage. PMID:26845771

Therapeutic levels of fetal hemoglobin in erythroid progeny of β-thalassemic CD34+ cells after lentiviral vector-mediated gene transfer

PubMed Central

Wilber, Andrew; Hargrove, Phillip W.; Kim, Yoon-Sang; Riberdy, Janice M.; Sankaran, Vijay G.; Papanikolaou, Eleni; Georgomanoli, Maria; Anagnou, Nicholas P.; Orkin, Stuart H.; Nienhuis, Arthur W.

2011-01-01

β-Thalassemia major results from severely reduced or absent expression of the β-chain of adult hemoglobin (α2β2;HbA). Increased levels of fetal hemoglobin (α2γ2;HbF), such as occurs with hereditary persistence of HbF, ameliorate the severity of β-thalassemia, raising the potential for genetic therapy directed at enhancing HbF. We used an in vitro model of human erythropoiesis to assay for enhanced production of HbF after gene delivery into CD34+ cells obtained from mobilized peripheral blood of normal adults or steady-state bone marrow from patients with β-thalassemia major. Lentiviral vectors encoding (1) a human γ-globin gene with or without an insulator, (2) a synthetic zinc-finger transcription factor designed to interact with the γ-globin gene promoters, or (3) a short-hairpin RNA targeting the γ-globin gene repressor, BCL11A, were tested. Erythroid progeny of normal CD34+ cells demonstrated levels of HbF up to 21% per vector copy. For β-thalassemic CD34+ cells, similar gene transfer efficiencies achieved HbF production ranging from 45% to 60%, resulting in up to a 3-fold increase in the total cellular Hb content. These observations suggest that both lentiviral-mediated γ-globin gene addition and genetic reactivation of endogenous γ-globin genes have potential to provide therapeutic HbF levels to patients with β-globin deficiency. PMID:21156846

All of the human beta-type globin genes compete for LCR enhancer activity in embryonic erythroid cells of yeast artificial chromosome transgenic mice.

PubMed

Okamura, Eiichi; Matsuzaki, Hitomi; Campbell, Andrew D; Engel, James Douglas; Fukamizu, Akiyoshi; Tanimoto, Keiji

2009-12-01

In primitive erythroid cells of human beta-globin locus transgenic mice (TgM), the locus control region (LCR)-proximal epsilon- and gamma-globin genes are transcribed, whereas the distal delta- and beta-globin genes are silent. It is generally accepted that the beta-globin gene is competitively suppressed by gamma-globin gene expression at this developmental stage. Previously, however, we observed that epsilon-globin gene expression was severely attenuated when its distance from the LCR was extended, implying that beta-globin gene might also be silenced because of its great distance from the LCR. Here, to clarify the beta-globin gene silencing mechanism, we established TgM lines carrying either gamma- or epsilon- plus gamma-globin promoter deletions, without significantly altering the distance between the beta-globin gene and the LCR. Precocious expression of delta- and beta-globin genes was observed in primitive erythroid cells of mutant, but not wild-type TgM, which was most evident when both the epsilon and gamma promoters were deleted. Thus, we clearly demonstrated that the repression of the delta- and beta-globin genes in primitive erythroid cells is dominated by competitive silencing by the epsilon- and gamma-globin gene promoters, and that epsilon- and the other beta-like globin genes might be activated by two distinct mechanisms by the LCR.

Disruption of the 5S RNP-Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia.

PubMed

Jaako, P; Debnath, S; Olsson, K; Zhang, Y; Flygare, J; Lindström, M S; Bryder, D; Karlsson, S

2015-11-01

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress response. However, the mechanisms of p53 activation and its relevance for the erythroid defect remain elusive. Previous studies have indicated that activation of p53 is caused by the inhibition of mouse double minute 2 (Mdm2), the main negative regulator of p53, by the 5S ribonucleoprotein particle (RNP). Meanwhile, it is not clear whether this mechanism solely mediates the p53-dependent component found in DBA. To approach this question, we crossed our mouse model for RPS19-deficient DBA with Mdm2(C305F) knock-in mice that have a disrupted 5S RNP-Mdm2 interaction. Upon induction of the Rps19 deficiency, Mdm2(C305F) reversed the p53 response and improved expansion of hematopoietic progenitors in vitro, and ameliorated the anemia in vivo. Unexpectedly, disruption of the 5S RNP-Mdm2 interaction also led to selective defect in erythropoiesis. Our findings highlight the sensitivity of erythroid progenitor cells to aberrations in p53 homeostasis mediated by the 5S RNP-Mdm2 interaction. Finally, we provide evidence indicating that physiological activation of the 5S RNP-Mdm2-p53 pathway may contribute to functional decline of the hematopoietic system in a cell-autonomous manner over time.

Prospective identification of erythroid elements in cultured peripheral blood.

PubMed

Miller, J L; Njoroge, J M; Gubin, A N; Rodgers, G P

1999-04-01

We have developed a prospective approach to identify the generation of erythroid cells derived from cultured peripheral blood mononuclear cells (PBMC) by monitoring the expression of the cell surface protein CD48. Unpurified populations of PBMC obtained from the buffy coats of normal volunteers were grown in suspension culture in the absence or presence of erythropoietin. A profile of surface CD48 expression permitted a flow cytometric identification of erythropoietin responsive populations at various stages of their maturation. In the absence of erythropoietin (EPO) supplemented media, the CD48- cells represented <5% of the total population of PBMC remaining in culture. In cultures supplemented with 1 U/mL EPO, the mean percentage of CD48- cells increased to 34.7 + 14.9% (p < 0.01) after 14 days in culture. Coordinated CD34 and CD71 (transferrin receptor) expression, morphology, gamma-globin transcription, and colony formation in methylcellulose were observed during the 14-day culture period. Flow cytometric monitoring of bulk cultured PBMC provides a simple and reliable means for the prospective or real-time study of human erythropoiesis.

Enhanced inhibition of parvovirus B19 replication by cidofovir in extendedly exposed erythroid progenitor cells.

PubMed

Bonvicini, Francesca; Bua, Gloria; Manaresi, Elisabetta; Gallinella, Giorgio

2016-07-15

Human parvovirus B19 (B19V) commonly induces self-limiting infections but can also cause severe clinical manifestations in patients with underlying haematological disorders or with immune system deficits. Currently, therapeutic options for B19V entirely rely on symptomatic and supportive treatments since a specific antiviral therapy is not yet available. Recently a first step in the research for active compounds inhibiting B19V replication has allowed identifying the acyclic nucleoside phosphonate cidofovir (CDV). Herein, the effect of CDV against B19V replication was characterized in human erythroid progenitor cells (EPCs) cultured and infected following different experimental approaches to replicate in vitro the infection of an expanding erythroid cell population in the bone marrow. B19V replication was selectively inhibited both in infected EPCs extendedly exposed to CDV 500μM (viral inhibition 82%) and in serially infected EPCs cultures with passage of the virus progeny, constantly under drug exposure (viral inhibition 99%). In addition, a potent inhibitory effect against B19V (viral inhibition 92%) was assessed in a short-term infection of EPCs treated with CDV 500μM 1day before viral infection. In the evaluated experimental conditions, the enhanced effect of CDV against B19V might be ascribed both to the increased intracellular drug concentration achieved by extended exposure, and to a progressive reduction in efficiency of the replicative process within treated EPCs population. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

PubMed Central

Min, Xu; Xu, Xiaohong

2017-01-01

Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies. PMID:28512642

Erythroid pyrimidine 5'-nucleotidase: cloning, developmental expression, and regulation by cAMP and in vivo hypoxia.

PubMed

Mass, Markus; Simo, Erika; Dragon, Stefanie

2003-12-01

A characteristic process of terminal erythroid differentiation is the degradation of ribosomal RNA into mononucleotides. The pyrimidine mononucleotides can be dephosphorylated by pyrimidine 5'-nucleotidase (P5N-I). In humans, a lack of this enzyme causes hemolytic anemia with ribosomal structures and trinucleotides retained in the red blood cells (RBCs). Although the protein/nucleotide sequence of P5N-I is known in mammals, the onset and regulation of P5N-I during erythroid maturation is unknown. However, in circulating chicken embryonic RBCs, the enzyme is induced together with carbonic anhydrase (CAII) and 2,3-bisphosphoglycerate (2,3-BPG) by norepinephrine (NE) and adenosine, which are released by the embryo under hypoxic conditions. Here, we present the chicken P5N-I sequence and the gene expression of P5N-I during RBC maturation; the profile of gene expression follows the enzyme activity with a rise between days 13 and 16 of embryonic development. The p5n-I expression is induced (1) in definitive but not primitive RBCs by stimulation of beta-adrenergic/adenosine receptors, and (2) in definitive RBCs by hypoxic incubation of the chicken embryo. Since embryonic RBCs increase their hemoglobin-oxygen affinity by degradation of nucleotides such as uridine triphosphate (UTP) and cytidine triphosphate (CTP), the induction of p5n-I expression can be seen as an adaptive response to hypoxia.

Clinical features of pure obsessive-compulsive disorder.

PubMed

Torres, Albina R; Shavitt, Roseli G; Torresan, Ricardo C; Ferrão, Ygor A; Miguel, Euripedes C; Fontenelle, Leonardo F

2013-10-01

Psychiatric comorbidity is the rule in obsessive-compulsive disorder (OCD); however, very few studies have evaluated the clinical characteristics of patients with no co-occurring disorders (non-comorbid or "pure" OCD). The aim of this study was to estimate the prevalence of pure cases in a large multicenter sample of OCD patients and compare the sociodemographic and clinical characteristics of individuals with and without any lifetime axis I comorbidity. A cross-sectional study with 955 adult patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC). Assessment instruments included the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, The USP-Sensory Phenomena Scale and the Brown Assessment of Beliefs Scale. Comorbidities were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders. Bivariate analyses were followed by logistic regression. Only 74 patients (7.7%) presented pure OCD. Compared with those presenting at least one lifetime comorbidity (881, 92.3%), non-comorbid patients were more likely to be female and to be working, reported less traumatic experiences and presented lower scores in the Y-BOCS obsession subscale and in total DY-BOCS scores. All symptom dimensions except contamination-cleaning and hoarding were less severe in non-comorbid patients. They also presented less severe depression and anxiety, lower suicidality and less previous treatments. In the logistic regression, the following variables predicted pure OCD: sex, severity of depressive and anxious symptoms, previous suicidal thoughts and psychotherapy. Pure OCD patients were the minority in this large sample and were characterized by female sex, less severe depressive and anxious symptoms, less suicidal thoughts and less use of psychotherapy as a treatment modality. The implications of these findings for clinical practice are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Chromatin structure of the LCR in the human β-globin locus transcribing the adult δ- and β-globin genes.

PubMed

Kim, Seoyeon; Kim, Yea Woon; Shim, Sung Han; Kim, Chul Geun; Kim, Aeri

2012-03-01

The β-like globin genes are transcribed in a developmental stage specific fashion in erythroid cells. The specific transcription of globin genes is conferred by the locus control region (LCR), but the chromatin structure of the LCR in the human adult β-globin locus transcribing the δ- and β-globin genes is not clear. Here, we employed hybrid MEL cells that contain a human chromosome 11. The δ- and β-globin genes were highly transcribed in hybrid MEL/ch11 cells after transcriptional induction. LCR HS3 and HS2 were strongly occupied by erythroid specific transcriptional activators and co-factors in the induced locus. These HSs, but not HS4 and HS1, were in close proximity with the active globin genes as revealed by high resolution 3C experiments. The active features at HS3 were markedly established after transcriptional induction, while HS2 was in a relatively active conformation before the induction. Unexpectedly, HS1 did not show notable active features except histone hyperacetylation. Taken together, the LCR of the human β-globin locus transcribing the adult δ- and β-globin genes has HS specific chromatin structure. The structure at each HS, which is different from the locus transcribing the fetal globin genes, might relate to its role in transcribing the adult genes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Use of Nandrolone Decanoate in Treatment of Pure Red Cell Aplasia Secondary to Diclofenac Administration: A Case Report.

PubMed

de Marchi, Paula Nassar; Sueur Vieira, André Nanny Le; Antunes Ribeiro, José Francisco; Geraldes, Silvano Salgueiro; Rodrigues Ramos, Paulo Roberto; Melchert, Alessandra; Guimarães-Okamoto, Priscylla Tatiana Chalfun

2017-03-01

Pure red cell aplasia (PRCA) is a disorder that leads to a nonregenerative anemia that results from erythroid precursors failing to reach maturity in the bone marrow, whereas the numbers of mature myeloid and megakaryocytic cells remain normal. PRCA can be induced by autoimmune processes, infections, drugs, toxins, and radiation, and is diagnosed by a bone marrow cytology examination after excluding the most common causes of nonregenerative anemia. Immunosuppressive therapies are used to treat PRCA, and usually involve the use of glucocorticoids, cyclosporin, or azathioprine. Alternatively, although little studied in veterinary medicine, drugs which stimulate bone marrow (e.g., nandrolone decanoate) have been mentioned as possible therapeutic agents. A case of PRCA that presented at the Veterinary Teaching Hospital of the Faculty of Veterinary Medicine and Animal Science (UNESP)-Botucatu, Brazil showed a good therapeutic response to weekly administration of nandrolone decanoate. Therefore, it was concluded that bone marrow stimulants might improve the quality of life of PRCA patients, provided they are used with caution and under close clinical supervision. Copyright © 2017 Elsevier Inc. All rights reserved.

Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

ClinicalTrials.gov

2013-05-01

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

[Pure Amnesia].

PubMed

Tagawa, Koichi; Tokida, Haruki

2017-06-01

Pure amnesia (amnesic syndrome) is an organic brain syndrome characterized by impairment in episodic memory, with either an anterograde or sometimes retrograde loss of memories. Although episodic memory is impaired, semantic memory, immediate memory, and procedural memory are preserved. The Papez circuit is a network of nerve fibers and nerve centers that starts and ends in the hippocampus travelling by way of the fornix, mammillary bodies, anterior thalamic nuclei, cingulate gyrus, and parahippocampal gyrus. A lesion restricted to this circuit often produces pure amnesia. Regions concerned with the Yakovlev circuit also have an important role in memory. Clinical cases of pure amnesia caused by cerebrovascular disease presented following brain imaging and resulted from various different lesions. The cases identified were predominantly thalamic amnesia and hippocampal amnesia. Thalamic amnesia often resulted from an infarction in the territory of the thalamotuberal artery and paramedian thalamic artery although thalamic hemorrhage in medial portion of thalamus also produced pure amnesia. Hippocampal amnesia usually occurred following an infarction in the temporal branches of posterior cerebral artery. Cases of retrosplenial amnesia caused by subcortical hematoma and infarction in the retrosplenial region are also described. In addition, cases of pure amnesia resulting from an infarction in the fornix, mammillary body hemorrhage, and caudate hemorrhage are also shown.

Defense Mechanisms in "Pure" Anxiety and "Pure" Depressive Disorders.

PubMed

Colovic, Olga; Lecic Tosevski, Dusica; Perunicic Mladenovic, Ivana; Milosavljevic, Maja; Munjiza, Ana

2016-10-01

Our study was intended to test whether there are any differences in the way defense mechanisms are used by patients suffering from pure anxiety and those with pure depressive disorders. The sample size was as follows: depressive disorders without psychotic symptoms 30, anxiety disorders 30, and the healthy control group 30. The assessment of defense mechanisms was made using the DSQ-40 questionnaire. Our findings show that "pure" anxiety disorders differ from "pure" depressive disorders only in the use of immature defense mechanisms. The group with depressive disorders was significantly more prone to use immature defense mechanisms than the group with anxiety disorders (p = 0.005), primarily projection (p = 0.001) and devaluation (p = 0.003). These defense mechanisms may therefore be used both to differentiate between anxiety and depressive disorders and also to determine which symptoms (anxiety or depressive disorders) are dominant at any given stage of treatment.

cDNA cloning and functional characterization of the mouse Ca2+-gated K+ channel, mIK1. Roles in regulatory volume decrease and erythroid differentiation.

PubMed

Vandorpe, D H; Shmukler, B E; Jiang, L; Lim, B; Maylie, J; Adelman, J P; de Franceschi, L; Cappellini, M D; Brugnara, C; Alper, S L

1998-08-21

We have cloned from murine erythroleukemia (MEL) cells, thymus, and stomach the cDNA encoding the Ca2+-gated K+ (KCa) channel, mIK1, the mouse homolog of hIK1 (Ishii, T. M., Silvia, C., Hirschberg, B., Bond, C. T., Adelman, J. P., and Maylie, J. (1997) Proc. Natl. Acad. Sci.(U. S. A. 94, 11651-11656). mIK1 mRNA was detected at varied levels in many tissue types. mIK1 KCa channel activity expressed in Xenopus oocytes closely resembled the Kca of red cells (Gardos channel) and MEL cells in its single channel conductance, lack of voltage-sensitivity of activation, inward rectification, and Ca2+ concentration dependence. mIK1 also resembled the erythroid channel in its pharmacological properties, mediating whole cell and unitary currents sensitive to low nM concentrations of both clotrimazole (CLT) and its des-imidazolyl metabolite, 2-chlorophenyl-bisphenyl-methanol, and to low nM concentrations of iodocharybdotoxin. Whereas control oocytes subjected to hypotonic swelling remained swollen, mIK1 expression conferred on oocytes a novel, Ca2+-dependent, CLT-sensitive regulatory volume decrease response. Hypotonic swelling of voltage-clamped mIK1-expressing oocytes increased outward currents that were Ca2+-dependent, CLT-sensitive, and reversed near the K+ equilibrium potential. mIK1 mRNA levels in ES cells increased steadily during erythroid differentiation in culture, in contrast to other KCa mRNAs examined. Low nanomolar concentrations of CLT inhibited proliferation and erythroid differentiation of peripheral blood stem cells in liquid culture.

Cotransduction with MGMT and Ubiquitous or Erythroid-Specific GFP Lentiviruses Allows Enrichment of Dual-Positive Hematopoietic Progenitor Cells In Vivo

PubMed Central

Roth, Justin C.; Ismail, Mourad; Reese, Jane S.; Lingas, Karen T.; Ferrari, Giuliana; Gerson, Stanton L.

2012-01-01

The P140K point mutant of MGMT allows robust hematopoietic stem cell (HSC) enrichment in vivo. Thus, dual-gene vectors that couple MGMT and therapeutic gene expression have allowed enrichment of gene-corrected HSCs in animal models. However, expression levels from dual-gene vectors are often reduced for one or both genes. Further, it may be desirable to express selection and therapeutic genes at distinct stages of cell differentiation. In this regard, we evaluated whether hematopoietic cells could be efficiently cotransduced using low MOIs of two separate single-gene lentiviruses, including MGMT for dual-positive cell enrichment. Cotransduction efficiencies were evaluated using a range of MGMT : GFP virus ratios, MOIs, and selection stringencies in vitro. Cotransduction was optimal when equal proportions of each virus were used, but low MGMT : GFP virus ratios resulted in the highest proportion of dual-positive cells after selection. This strategy was then evaluated in murine models for in vivo selection of HSCs cotransduced with a ubiquitous MGMT expression vector and an erythroid-specific GFP vector. Although the MGMT and GFP expression percentages were variable among engrafted recipients, drug selection enriched MGMT-positive leukocyte and GFP-positive erythroid cell populations. These data demonstrate cotransduction as a mean to rapidly enrich and evaluate therapeutic lentivectors in vivo. PMID:22888445

Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3-3ζ

PubMed Central

Patrick, David M.; Zhang, Cheng C.; Tao, Ye; Yao, Huiyu; Qi, Xiaoxia; Schwartz, Robert J.; Jun-Shen Huang, Lily; Olson, Eric N.

2010-01-01

Erythrocyte formation occurs throughout life in response to cytokine signaling. We show that microRNA-451 (miR-451) regulates erythropoiesis in vivo. Mice lacking miR-451 display a reduction in hematrocrit, an erythroid differentiation defect, and ineffective erythropoiesis in response to oxidative stress. 14-3-3ζ, an intracellular regulator of cytokine signaling that is repressed by miR-451, is up-regulated in miR-451−/− erythroblasts, and inhibition of 14-3-3ζ rescues their differentiation defect. These findings reveal an essential role of 14-3-3ζ as a mediator of the proerythroid differentiation actions of miR-451, and highlight the therapeutic potential of miR-451 inhibitors. PMID:20679397

Comparison of different methods for erythroid differentiation in the K562 cell line.

PubMed

Shariati, Laleh; Modaress, Mehran; Khanahmad, Hossein; Hejazi, Zahra; Tabatabaiefar, Mohammad Amin; Salehi, Mansoor; Modarressi, Mohammad Hossein

2016-08-01

To compare methods for erythroid differentiation of K562 cells that will be promising in the treatment of beta-thalassemia by inducing γ-globin synthesis. Cells were treated separately with: RPMI 1640 medium without glutamine, RPMI 1640 medium without glutamine supplemented with 1 mM sodium butyrate, RPMI 1640 medium supplemented with 1 mM sodium butyrate, 25 µg cisplatin/ml, 0.1 µg cytosine arabinoside/ml. The highest differentiation (84 %) with minimum toxicity was obtained with cisplatin at 15 µg /ml. Real-time RT-PCR showed that expression of the γ-globin gene was significantly higher in the cells differentiated with cisplatin compared to undifferentiated cells (P < 0.001). Cisplatin is useful in the experimental therapy of ß-globin gene defects and can be considered for examining the basic mechanism of γ-reactivation.

S-1 induced secondary acute erythroid leukemia with a chromosome inv(12)(p13;q13)

PubMed Central

Matsumoto, Kensuke; Kitanaka, Akira; Uemura, Makiko; Waki, Fusako; Fukumoto, Tetsuya; Ohnishi, Hiroaki; Kubota, Yoshitsugu; Ishida, Toshihiko

2011-01-01

Adjuvant chemotherapy by S-1 following gastrectomy is considered standard treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1 administration, and that hematological adverse events were relatively rare. Pyrimidine anti-metabolites, including S-1, have shown relatively lower risks for secondary hematological malignancies in comparison to alkylating agents and topoisomerase-II inhibitors. We here report a case of therapy-related leukemia after S-1 administration. A patient who had received S-1as the sole adjuvant chemotherapy was diagnosed with acute erythroid leukemia. To the best of our knowledge, our patient represents the first report of S-1 induced acute leukemia. PMID:22147971

Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

ClinicalTrials.gov

2017-11-13

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Pure-quartic solitons

PubMed Central

Blanco-Redondo, Andrea; Martijn, de Sterke C.; Sipe, J.E.; Krauss, Thomas F.; Eggleton, Benjamin J.; Husko, Chad

2016-01-01

Temporal optical solitons have been the subject of intense research due to their intriguing physics and applications in ultrafast optics and supercontinuum generation. Conventional bright optical solitons result from the interaction of anomalous group-velocity dispersion and self-phase modulation. Here we experimentally demonstrate a class of bright soliton arising purely from the interaction of negative fourth-order dispersion and self-phase modulation, which can occur even for normal group-velocity dispersion. We provide experimental and numerical evidence of shape-preserving propagation and flat temporal phase for the fundamental pure-quartic soliton and periodically modulated propagation for the higher-order pure-quartic solitons. We derive the approximate shape of the fundamental pure-quartic soliton and discover that is surprisingly Gaussian, exhibiting excellent agreement with our experimental observations. Our discovery, enabled by precise dispersion engineering, could find applications in communications, frequency combs and ultrafast lasers. PMID:26822758

Effect of human cytomegalovirus infection on the expression of Hoxb2 and Hoxb4 genes in the developmental process of cord blood erythroid progenitors.

PubMed

Liu, Wen-Jun; Huang, Mei-Xian; Guo, Qu-Lian; Chen, Jun-Hong; Shi, Han

2011-01-01

The aim of the present study was to investigate the role of Hoxb2 and Hoxb4 gene expression induced by human cytomegalovirus (HCMV) and/or all-trans retinoic acid (ATRA) on the proliferation and committed differentiation process of human cord blood hematopoietic stem cells (HSCs) to colony-forming erythroid progenitor cells (CFU-Es) in vitro. Cord blood was collected from the fetal placenta umbilical vein in 12 cases and cultured using hematopoietic stem cell culture technique in vitro. The proliferation and differentiation of cord blood HSCs to CFU-Es were continuously disrupted with HCMV-AD169 and/or 6 x 10⁻⁸ mol/l of ATRA. Expression levels of the Hoxb2 and Hoxb4 genes in the blank, ATRA, HCMV-AD169 and ATRA + HCMV treatment groups of CFU-Es were detected on day 3, 7 and 10 of culture by fluorescent quantitative reverse transcriptase-polymerase chain reaction method. Hoxb2 and Hoxb4 gene expression in each group began on day 3, obviously increased on day 7 and reached a peak on day 10. The expression levels of the Hoxb2 and Hoxb4 genes in the HCMV group were obviously down-regulated compared with the level in the blank group. However, expression levels of the Hoxb2 and Hoxb4 genes were significantly up-regulated in the HCMV + ATRA group compared with the HCMV group (P<0.05). Abnormal expression of the Hoxb2 and Hoxb4 genes induced by HCMV may play important roles in abnormal hematopoietic damage. They were also correlated with the process of erythroid hematopoiesis. ATRA (6 x 10⁻⁸ mol/l) significantly up-regulated expression of the Hoxb2 and Hoxb4 genes in the normal erythroid progenitor cells and in those cells infected with HCMV as well.

Reactive oxygen species levels control NF-κB activation by low dose deferasirox in erythroid progenitors of low risk myelodysplastic syndromes.

PubMed

Meunier, Mathieu; Ancelet, Sarah; Lefebvre, Christine; Arnaud, Josiane; Garrel, Catherine; Pezet, Mylène; Wang, Yan; Faure, Patrice; Szymanski, Gautier; Duployez, Nicolas; Preudhomme, Claude; Biard, Denis; Polack, Benoit; Cahn, Jean-Yves; Moulis, Jean Marc; Park, Sophie

2017-12-01

Anemia is a frequent cytopenia in myelodysplastic syndromes (MDS) and most patients require red blood cell transfusion resulting in iron overload (IO). Deferasirox (DFX) has become the standard treatment of IO in MDS and it displays positive effects on erythropoiesis. In low risk MDS samples, mechanisms improving erythropoiesis after DFX treatment remain unclear. Herein, we addressed this question by using liquid cultures with iron overload of erythroid precursors treated with low dose of DFX (3μM), which corresponds to DFX 5 mg/kg/day, an unusual dose used for iron chelation. We highlight a decreased apoptosis rate and an increased proportion of cycling cells, both leading to higher proliferation rates. The iron chelation properties of low dose DFX failed to activate the Iron Regulatory Proteins and to support iron depletion, but low dose DFX dampers intracellular reactive oxygen species. Furthermore low concentrations of DFX activate the NF-κB pathway in erythroid precursors triggering anti-apoptotic and anti-inflammatory signals. Establishing stable gene silencing of the Thioredoxin (TRX) 1 genes, a NF-κB modulator, showed that fine-tuning of reactive oxygen species (ROS) levels regulates NF-κB. These results justify a clinical trial proposing low dose DFX in MDS patients refractory to erythropoiesis stimulating agents.

Reactive oxygen species levels control NF-κB activation by low dose deferasirox in erythroid progenitors of low risk myelodysplastic syndromes

PubMed Central

Meunier, Mathieu; Ancelet, Sarah; Lefebvre, Christine; Arnaud, Josiane; Garrel, Catherine; Pezet, Mylène; Wang, Yan; Faure, Patrice; Szymanski, Gautier; Duployez, Nicolas; Preudhomme, Claude; Biard, Denis; Polack, Benoit; Cahn, Jean-Yves; Moulis, Jean Marc; Park, Sophie

2017-01-01

Anemia is a frequent cytopenia in myelodysplastic syndromes (MDS) and most patients require red blood cell transfusion resulting in iron overload (IO). Deferasirox (DFX) has become the standard treatment of IO in MDS and it displays positive effects on erythropoiesis. In low risk MDS samples, mechanisms improving erythropoiesis after DFX treatment remain unclear. Herein, we addressed this question by using liquid cultures with iron overload of erythroid precursors treated with low dose of DFX (3μM), which corresponds to DFX 5 mg/kg/day, an unusual dose used for iron chelation. We highlight a decreased apoptosis rate and an increased proportion of cycling cells, both leading to higher proliferation rates. The iron chelation properties of low dose DFX failed to activate the Iron Regulatory Proteins and to support iron depletion, but low dose DFX dampers intracellular reactive oxygen species. Furthermore low concentrations of DFX activate the NF-κB pathway in erythroid precursors triggering anti-apoptotic and anti-inflammatory signals. Establishing stable gene silencing of the Thioredoxin (TRX) 1 genes, a NF-κB modulator, showed that fine-tuning of reactive oxygen species (ROS) levels regulates NF-κB. These results justify a clinical trial proposing low dose DFX in MDS patients refractory to erythropoiesis stimulating agents. PMID:29285268

Tropomodulin3-null mice are embryonic lethal with anemia due to impaired erythroid terminal differentiation in the fetal liver

PubMed Central

Sui, Zhenhua; Nowak, Roberta B.; Bacconi, Andrea; Kim, Nancy E.; Liu, Hui; Li, Jie; Wickrema, Amittha; An, Xiu-li

2014-01-01

Tropomodulin (Tmod) is a protein that binds and caps the pointed ends of actin filaments in erythroid and nonerythoid cell types. Targeted deletion of mouse tropomodulin3 (Tmod3) leads to embryonic lethality at E14.5-E18.5, with anemia due to defects in definitive erythropoiesis in the fetal liver. Erythroid burst-forming unit and colony-forming unit numbers are greatly reduced, indicating defects in progenitor populations. Flow cytometry of fetal liver erythroblasts shows that late-stage populations are also decreased, including reduced percentages of enucleated cells. Annexin V staining indicates increased apoptosis of Tmod3−/− erythroblasts, and cell-cycle analysis reveals that there are more Ter119hi cells in S-phase in Tmod3−/− embryos. Notably, enucleating Tmod3−/− erythroblasts are still in the process of proliferation, suggesting impaired cell-cycle exit during terminal differentiation. Tmod3−/− late erythroblasts often exhibit multilobular nuclear morphologies and aberrant F-actin assembly during enucleation. Furthermore, native erythroblastic island formation was impaired in Tmod3−/− fetal livers, with Tmod3 required in both erythroblasts and macrophages. In conclusion, disruption of Tmod3 leads to impaired definitive erythropoiesis due to reduced progenitors, impaired erythroblastic island formation, and defective erythroblast cell-cycle progression and enucleation. Tmod3-mediated actin remodeling may be required for erythroblast-macrophage adhesion, coordination of cell cycle with differentiation, and F-actin assembly and remodeling during erythroblast enucleation. PMID:24159174

H-Ferritin Is Preferentially Incorporated by Human Erythroid Cells through Transferrin Receptor 1 in a Threshold-Dependent Manner

PubMed Central

Sakamoto, Soichiro; Kawabata, Hiroshi; Masuda, Taro; Uchiyama, Tatsuki; Mizumoto, Chisaki; Ohmori, Katsuyuki; Koeffler, H. Phillip; Kadowaki, Norimitsu; Takaori-Kondo, Akifumi

2015-01-01

Ferritin is an iron-storage protein composed of different ratios of 24 light (L) and heavy (H) subunits. The serum level of ferritin is a clinical marker of the body’s iron level. Transferrin receptor (TFR)1 is the receptor not only for transferrin but also for H-ferritin, but how it binds two different ligands and the blood cell types that preferentially incorporate H-ferritin remain unknown. To address these questions, we investigated hematopoietic cell-specific ferritin uptake by flow cytometry. Alexa Fluor 488-labeled H-ferritin was preferentially incorporated by erythroid cells among various hematopoietic cell lines examined, and was almost exclusively incorporated by bone marrow erythroblasts among human primary hematopoietic cells of various lineages. H-ferritin uptake by erythroid cells was strongly inhibited by unlabeled H-ferritin but was only partially inhibited by a large excess of holo-transferrin. On the other hand, internalization of labeled holo-transferrin by these cells was not inhibited by H-ferritin. Chinese hamster ovary cells lacking functional endogenous TFR1 but expressing human TFR1 with a mutated RGD sequence, which is required for transferrin binding, efficiently incorporated H-ferritin, indicating that TFR1 has distinct binding sites for H-ferritin and holo-transferrin. H-ferritin uptake by these cells required a threshold level of cell surface TFR1 expression, whereas there was no threshold for holo-transferrin uptake. The requirement for a threshold level of TFR1 expression can explain why among primary human hematopoietic cells, only erythroblasts efficiently take up H-ferritin. PMID:26441243

Social inequalities in pure-tone hearing assessed using occupational stratification schemes.

PubMed

von Gablenz, Petra; Holube, Inga

2017-07-01

The objective of this study is to analyse the performance of two occupational stratification approaches and the impact of social position on adult hearing. The prevalence of hearing impairment, pure-tone averages (PTA) and prevalence ratios (PR) for relative hearing loss, which focuses on the position of one's PTA in the age- and gender-specific distribution, were compared in groups defined by ISCO Skill Level and the International Socio-Economic Index (ISEI). About 1571 subjects aged 30-89, including 677 highly screened adults, from the cross-sectional study HÖRSTAT. ISCO Skill Level and ISEI yielded qualitatively the same results. The prevalence difference between the socially least and most advantaged group ranges between 10 and 16%, varying with the scheme applied. Low- and high-frequency PTA and PR for relative hearing loss confirm the gradient. Screening reduced, but did not negate the social differences. The prevalence difference dropped to 6-7% in the otologically normal subsample. Social groups defined by hierarchical, occupational measures differ in their pure-tone hearing, even if the main risk factors are controlled for. This underlines the need for population-based sampling, the relevance of reporting the study group's social composition and the importance of advancing the discussion on appropriate social measures in hearing research.

Pure-tone Audiometer

NASA Astrophysics Data System (ADS)

Kapul, A. A.; Zubova, E. I.; Torgaev, S. N.; Drobchik, V. V.

2017-08-01

The research focuses on a pure-tone audiometer designing. The relevance of the study is proved by high incidence of an auditory analyser in older people and children. At first, the article provides information about subjective and objective audiometry methods. Secondly, we offer block-diagram and basic-circuit arrangement of device. We decided to base on STM32F407VG microcontroller and use digital pot in the function of attenuator. Third, we implemented microcontroller and PC connection. C programming language is used for microcontroller’s program and PC’s interface. Fourthly, we created the pure-tone audiometer prototype. In the future, we will implement the objective method ASSR in addition to pure-tone audiometry.

Reference ranges of handgrip strength from 125,462 healthy adults in 21 countries: a prospective urban rural epidemiologic (PURE) study.

PubMed

Leong, Darryl P; Teo, Koon K; Rangarajan, Sumathy; Kutty, V Raman; Lanas, Fernando; Hui, Chen; Quanyong, Xiang; Zhenzhen, Qian; Jinhua, Tang; Noorhassim, Ismail; AlHabib, Khalid F; Moss, Sarah J; Rosengren, Annika; Akalin, Ayse Arzu; Rahman, Omar; Chifamba, Jephat; Orlandini, Andrés; Kumar, Rajesh; Yeates, Karen; Gupta, Rajeev; Yusufali, Afzalhussein; Dans, Antonio; Avezum, Álvaro; Lopez-Jaramillo, Patricio; Poirier, Paul; Heidari, Hosein; Zatonska, Katarzyna; Iqbal, Romaina; Khatib, Rasha; Yusuf, Salim

2016-12-01

The measurement of handgrip strength (HGS) has prognostic value with respect to all-cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high-income countries. There is a paucity of information on normative HGS values in non-Caucasian populations from low- or middle-income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions. HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35-70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25 th -75 th percentile) 50 kg (43-56 kg) in men <40 years from Europe/North America to 18 kg (14-20 kg) in women >60 years from South East Asia. Reference ranges by ethnicity and body-mass index are also reported. Individual HGS measurements should be interpreted using region/ethnic-specific reference ranges.

Anemia in new congenital adult type polycystic kidney mice.

PubMed

Koumegawa, J; Nagano, N; Arai, H; Wada, M; Kusaka, M; Takahashi, H

1991-12-01

Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit-erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r-HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure.

pureS2HAT: S 2HAT-based Pure E/B Harmonic Transforms

NASA Astrophysics Data System (ADS)

Grain, J.; Stompor, R.; Tristram, M.

2011-10-01

The pS2HAT routines allow efficient, parallel calculation of the so-called 'pure' polarized multipoles. The computed multipole coefficients are equal to the standard pseudo-multipoles calculated for the apodized sky maps of the Stokes parameters Q and U subsequently corrected by so-called counterterms. If the applied apodizations fullfill certain boundary conditions, these multipoles correspond to the pure multipoles. Pure multipoles of one type, i.e., either E or B, are ensured not to contain contributions from the other one, at least to within numerical artifacts. They can be therefore further used in the estimation of the sky power spectra via the pseudo power spectrum technique, which has to however correctly account for the applied apodization on the one hand, and the presence of the counterterms, on the other. In addition, the package contains the routines permitting calculation of the spin-weighted apodizations, given an input scalar, i.e., spin-0 window. The former are needed to compute the counterterms. It also provides routines for maps and window manipulations. The routines are written in C and based on the S2HAT library, which is used to perform all required spherical harmonic transforms as well as all inter-processor communication. They are therefore parallelized using MPI and follow the distributed-memory computational model. The data distribution patterns, pixelization choices, conventions etc are all as those assumed/allowed by the S2HAT library.

17-N-Allylamino-17-Demethoxygeldanamycin and Bortezomib in Treating Patients With Relapsed or Refractory Hematologic Cancer

ClinicalTrials.gov

2013-06-03

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Mixtures of maximally entangled pure states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flores, M.M., E-mail: mflores@nip.up.edu.ph; Galapon, E.A., E-mail: eric.galapon@gmail.com

We study the conditions when mixtures of maximally entangled pure states remain entangled. We found that the resulting mixed state remains entangled when the number of entangled pure states to be mixed is less than or equal to the dimension of the pure states. For the latter case of mixing a number of pure states equal to their dimension, we found that the mixed state is entangled provided that the entangled pure states to be mixed are not equally weighted. We also found that one can restrict the set of pure states that one can mix from in order tomore » ensure that the resulting mixed state is genuinely entangled. Also, we demonstrate how these results could be applied as a way to detect entanglement in mixtures of the entangled pure states with noise.« less

Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities

PubMed Central

Wilber, Andrew; Nienhuis, Arthur W.

2011-01-01

In humans, embryonic, fetal, and adult hemoglobins are sequentially expressed in developing erythroblasts during ontogeny. For the past 40 years, this process has been the subject of intensive study because of its value to enlighten the biology of developmental gene regulation and because fetal hemoglobin can significantly ameliorate the clinical manifestations of both sickle cell disease and β-thalassemia. Understanding the normal process of loss of fetal globin expression and activation of adult globin expression could potentially lead to new therapeutic approaches for these hemoglobin disorders. Herein, we briefly review the history of the study of hemoglobin switching and then focus on recent discoveries in the field that now make new therapeutic approaches seem feasible in the future. Erythroid-specific knockdown of fetal gene repressors or enforced expression of fetal gene activators may provide clinically applicable approaches for genetic treatment of hemoglobin disorders that would benefit from increased fetal hemoglobin levels. PMID:21321359

Effects of a water-soluble curcumin protein conjugate vs. pure curcumin in a diabetic model of erectile dysfunction.

PubMed

Abdel Aziz, Mohamed Talaat; Motawi, Tarek; Rezq, Ameen; Mostafa, Taymour; Fouad, Hanan H; Ahmed, Hanan H; Rashed, Laila; Sabry, Dina; Senbel, Amira; Al-Malki, A; El-Shafiey, Raghda

2012-07-01

Curcumin is involved in erectile signaling via elevation of cyclic guanosine monophosphate (cGMP). Assessment of the effects of water-soluble curcumin in erectile dysfunction (ED). One hundred twenty male white albino rats were divided into: 1st and 2nd control groups with or without administration of Zinc protoporphyrin (ZnPP), 3rd and 4th diabetic groups with or without ZnPP, 5th diabetic group on single oral dose of pure curcumin, 6th diabetic group on pure curcumin administered daily for 12 weeks, 7th and 8th diabetic groups on single dose of water-soluble curcumin administered with or without ZnPP, 9th and 10th diabetic groups on water-soluble curcumin administered daily for 12 weeks with or without ZnPP. All curcumin dosage schedules were administered after induction of diabetes. Quantitative gene expression of endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid2 (Nrf2), NF-Кβ, and p38. Cavernous tissue levels of HO and NOS enzyme activities, cGMP and intracavernosal pressure (ICP). Twelve weeks after induction of diabetes, ED was confirmed by the significant decrease in ICP. There was a significant decrease in cGMP, NOS, HO enzymes, a significant decrease in eNOS, nNOS, HO-1 genes and a significant elevation of NF-Кβ, p38, iNOS genes. Administration of pure curcumin or its water-soluble conjugate led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in eNOS, nNOS, HO-1, and Nrf2 genes, and a significant decrease in NF-Кβ, p38, and iNOS genes. Water-soluble curcumin showed significant superiority and more prolonged duration of action. Repeated doses regimens were superior to single dose regimen. Administration of ZnPP significantly reduced HO enzyme, cGMP, ICP/ mean arterial pressure (MAP), HO-1 genes in diabetic groups. Water-soluble curcumin could enhance erectile function with more

Stimulation of globin synthesis: relative responsiveness of reticulocytes and nucleated erythroid cells

PubMed Central

Waxman, Herbert S.

1970-01-01

The effects of iron, cobalt, hemin, and plasma on hemoglobin synthesis by suspensions of rabbit reticulocytes and nucleated bone marrow cells were studied. L-Leucine-14C and sodium pyruvate-3-14C were employed to measure globin and heme synthesis, respectively. Normal plasma (or serum) was found to stimulate the rate of globin synthesis in both systems. The stimulatory effects of iron and hemin were additive to those of plasma or serum only in the reticulocytes. Cobaltous ion, at concentrations less than 1.0 mmole/liter, was found to stimulate globin synthesis by reticulocytes as effectively as ferrous ion; cobalt was inhibitory only at concentrations greater than 3.0-5.0 mmoles/liter. Heme synthesis by reticulocytes was inhibited at all concentrations employed (0.2-5.0 mmoles/liter). In bone marrow nucleated erythroid cells, globin synthesis was markedly enhanced by exogenous hemin. In contrast to reticulocytes, however, bone marrow cells were unresponsive to either cobalt or transferrin-bound iron. Possible implications of these findings on regulation of the rate and mechanism of iron uptake and hemoglobin synthesis in vivo are discussed. PMID:5443172

Beyond Sex Education: How Adults Relate to Children's Sensuality.

ERIC Educational Resources Information Center

Fogel, Alan

Current cultural attitudes toward children's sexuality resemble attitudes toward adults' sexuality; there is an emphasis on purely genital and orgasmic pleasure. Adults and children need warmth, physical contact, and a sense of belonging for which genital stimulation may be unnecessary or inappropriate. Children's sexual advances to adults, as…

Nighttime kidney transplantation is associated with less pure technical graft failure.

PubMed

Brunschot, Denise M D Özdemir-van; Hoitsma, Andries J; van der Jagt, Michel F P; d'Ancona, Frank C; Donders, Rogier A R T; van Laarhoven, Cees J H M; Hilbrands, Luuk B; Warlé, Michiel C

2016-07-01

To minimize cold ischemia time, transplantations with kidneys from deceased donors are frequently performed during the night. However, sleep deprivation of those who perform the transplantation may have adverse effects on cognitive and psychomotor performance and may cause reduced cognitive flexibility. We hypothesize that renal transplantations performed during the night are associated with an increased incidence of pure technical graft failure. A retrospective analysis of data of the Dutch Organ Transplant Registry concerning all transplants from deceased donors between 2000 and 2013 was performed. Nighttime surgery was defined as the start of the procedure between 8 p.m. and 8 a.m. The primary outcome measure was technical graft failure, defined as graft loss within 10 days after surgery without signs of (hyper)acute rejection. Of 4.519 renal transplantations in adult recipients, 1.480 were performed during the night. The incidence of pure technical graft failure was 1.0 % for procedures started during the night versus 2.6 % for daytime surgery (p = .001). In a multivariable model, correcting for relevant donor, recipient and graft factors, daytime surgery was an independent predictor of pure technical graft failure (p < .001). Limitation of this study is mainly to its retrospective design, and the influence of some relevant variables, such as the experience level of the surgeon, could not be assessed. We conclude that nighttime surgery is associated with less pure technical graft failures. Further research is required to explore factors that may positively influence the performance of the surgical team during the night.

Decryption of pure-position permutation algorithms.

PubMed

Zhao, Xiao-Yu; Chen, Gang; Zhang, Dan; Wang, Xiao-Hong; Dong, Guang-Chang

2004-07-01

Pure position permutation image encryption algorithms, commonly used as image encryption investigated in this work are unfortunately frail under known-text attack. In view of the weakness of pure position permutation algorithm, we put forward an effective decryption algorithm for all pure-position permutation algorithms. First, a summary of the pure position permutation image encryption algorithms is given by introducing the concept of ergodic matrices. Then, by using probability theory and algebraic principles, the decryption probability of pure-position permutation algorithms is verified theoretically; and then, by defining the operation system of fuzzy ergodic matrices, we improve a specific decryption algorithm. Finally, some simulation results are shown.

Hydroxyurea inhibits parvovirus B19 replication in erythroid progenitor cells.

PubMed

Bonvicini, Francesca; Bua, Gloria; Conti, Ilaria; Manaresi, Elisabetta; Gallinella, Giorgio

2017-07-15

Parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells (EPCs) of the human bone marrow, leading to transient arrest of erythropoiesis and severe complications mainly in subjects with underlying hematological disorders or with immune system deficits. Currently, there are no specific antiviral drugs for B19V treatment, but identification of compounds inhibiting B19V replication can be pursued by a drug repositioning strategy. In this frame, the present study investigates the activity of hydroxyurea (HU), the only disease-modifying therapy approved for sickle cell disease (SCD), towards B19V replication in the two relevant cellular systems, the UT7/EpoS1 cell line and EPCs. Results demonstrate that HU inhibits B19V replication with EC 50 values of 96.2µM and 147.1µM in UT7/EpoS1 and EPCs, respectively, providing experimental evidence of the antiviral activity of HU towards B19V replication, and confirming the efficacy of a drug discovery process by drug repositioning strategy. The antiviral activity occurs in vitro at concentrations lower than those affecting cellular DNA replication and viability, and at levels measured in plasma samples of SCD patients undergoing HU therapy. HU might determine a dual beneficial effect on SCD patients, not only for the treatment of the disease but also towards a virus responsible for severe complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Perspectives on the Pure-Tone Audiogram.

PubMed

Musiek, Frank E; Shinn, Jennifer; Chermak, Gail D; Bamiou, Doris-Eva

The pure-tone audiogram, though fundamental to audiology, presents limitations, especially in the case of central auditory involvement. Advances in auditory neuroscience underscore the considerably larger role of the central auditory nervous system (CANS) in hearing and related disorders. Given the availability of behavioral audiological tests and electrophysiological procedures that can provide better insights as to the function of the various components of the auditory system, this perspective piece reviews the limitations of the pure-tone audiogram and notes some of the advantages of other tests and procedures used in tandem with the pure-tone threshold measurement. To review and synthesize the literature regarding the utility and limitations of the pure-tone audiogram in determining dysfunction of peripheral sensory and neural systems, as well as the CANS, and to identify other tests and procedures that can supplement pure-tone thresholds and provide enhanced diagnostic insight, especially regarding problems of the central auditory system. A systematic review and synthesis of the literature. The authors independently searched and reviewed literature (journal articles, book chapters) pertaining to the limitations of the pure-tone audiogram. The pure-tone audiogram provides information as to hearing sensitivity across a selected frequency range. Normal or near-normal pure-tone thresholds sometimes are observed despite cochlear damage. There are a surprising number of patients with acoustic neuromas who have essentially normal pure-tone thresholds. In cases of central deafness, depressed pure-tone thresholds may not accurately reflect the status of the peripheral auditory system. Listening difficulties are seen in the presence of normal pure-tone thresholds. Suprathreshold procedures and a variety of other tests can provide information regarding other and often more central functions of the auditory system. The audiogram is a primary tool for determining type

Generalized pure Lovelock gravity

NASA Astrophysics Data System (ADS)

Concha, Patrick; Rodríguez, Evelyn

2017-11-01

We present a generalization of the n-dimensional (pure) Lovelock Gravity theory based on an enlarged Lorentz symmetry. In particular, we propose an alternative way to introduce a cosmological term. Interestingly, we show that the usual pure Lovelock gravity is recovered in a matter-free configuration. The five and six-dimensional cases are explicitly studied.

Erythroid progenitor cells (CFU-E*) from Friend virus-infected mice undergo VVFe suicide in vitro in the absence of added erythropoietin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Del Rizzo, D.F.; Axelrad, A.A.

The authors have investigated the effect of VVFe on the survival in suspension of erythropoietin (epo)-independent erythroid progenitor cells (CFU-E*) induced by Friend polycythemia virus (FV). Spleen cells from C3Hf/Bi mice previously infected with FV were exposed to carrier-free VVFe, and the survival of CFU-E* as a function of time in liquid medium was determined from the number of erythroid colonies that developed from these cells seeded in plasma cultures without added epo. The results showed that spleen CFU-E* were highly vulnerable to VVFe. Marrow CFU-E* behaved in a similar manner. The VVFe responsible for their suicide had been presentedmore » to the progenitor cells only during the 4-h period of incubation, after which they were washed and plated in excess nonradioactive iron. They therefore conclude that CFU-E* themselves, and not only their progeny, are capable of actively incorporating iron. Under the same conditions in the absence of added epo, the effect of VVFe on the survival of normal spleen or marrow CFU-E could not be assessed because two few normal CFU-E survived the incubation period. Normal bone marrow cells incubated in complete medium containing epo retained their capacity for erythrocytic colony formation, and CFU-E could then be shown to be vulnerable to VVFe. Thus, either the iron-incorporating system of normal CFU-E was inducible by epo, or else epo permitted survival of the CFU-E so that the activity of a constitutive iron-incorporating system could be recognized.« less

The Cultivation of Pure Altruism via Gratitude: A Functional MRI Study of Change with Gratitude Practice

PubMed Central

Karns, Christina M.; Moore, William E.; Mayr, Ulrich

2017-01-01

Gratitude is an emotion and a trait linked to well-being and better health, and welcoming benefits to oneself is instrumentally valuable. However, theoretical and empirical work highlights that gratitude is more fully understood as an intrinsically valuable moral emotion. To understand the role of neural reward systems in the association between gratitude and altruistic motivations we tested two hypotheses: First, whether self-reported propensity toward gratitude relates to fMRI-derived indicators of “pure altruism,” operationalized as the neural valuation of passive, private transfers to a charity versus to oneself. In young adult female participants, self-reported gratitude and altruism were associated with “neural pure altruism” in ventromedial prefrontal cortex (VMPFC) and nucleus accumbens. Second, whether neural pure altruism can be increased through practicing gratitude. In a double-blind study, we randomly assigned participants to either a gratitude-journal or active-neutral control journal group for 3 weeks. Relative to pre-test levels, gratitude journaling increased the neural pure altruism response in the VMPFC. We posit that as a context-dependent value-sensitive cortical region, the VMPFC supports change with gratitude practice, a change that is larger for benefits to others versus oneself. PMID:29375336

The Cultivation of Pure Altruism via Gratitude: A Functional MRI Study of Change with Gratitude Practice.

PubMed

Karns, Christina M; Moore, William E; Mayr, Ulrich

2017-01-01

Gratitude is an emotion and a trait linked to well-being and better health, and welcoming benefits to oneself is instrumentally valuable. However, theoretical and empirical work highlights that gratitude is more fully understood as an intrinsically valuable moral emotion. To understand the role of neural reward systems in the association between gratitude and altruistic motivations we tested two hypotheses: First, whether self-reported propensity toward gratitude relates to fMRI-derived indicators of "pure altruism," operationalized as the neural valuation of passive, private transfers to a charity versus to oneself. In young adult female participants, self-reported gratitude and altruism were associated with "neural pure altruism" in ventromedial prefrontal cortex (VMPFC) and nucleus accumbens. Second, whether neural pure altruism can be increased through practicing gratitude. In a double-blind study, we randomly assigned participants to either a gratitude-journal or active-neutral control journal group for 3 weeks. Relative to pre-test levels, gratitude journaling increased the neural pure altruism response in the VMPFC. We posit that as a context-dependent value-sensitive cortical region, the VMPFC supports change with gratitude practice, a change that is larger for benefits to others versus oneself.

Analysis of pure maple syrup consumers

Treesearch

Paul E. Sendak

1974-01-01

Virtually all of the pure maple syrup productim in the United States is in the northern states of Maine, Massachusetts, Michigan, New Hampshire, New York, Ohio, Pennsylvania, Vermont, and Wisconsin. Pure maple syrup users living in the maple production area and users living in other areas of the United States were asked a series of questions about their use of pure...

Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue

PubMed Central

de Souza, M. Cristina P.; Deschênes, Marie-Eve; Laurencelle, Suzanne; Godet, Patrick; Roy, Claude C.; Djilali-Saiah, Idriss

2016-01-01

The question about recommending pure, noncontaminated oats as part of the gluten-free diet of patients with celiac disease remains controversial. This might be due to gluten cross contamination and to the possible immunogenicity of some oat cultivars. In view of this controversy, a review of the scientific literature was conducted to highlight the latest findings published between 2008 and 2014 to examine the current knowledge on oats safety and celiac disease in Europe and North America. Results showed that regular oats consumed in Canada are largely contaminated. Overall, the consumption of pure oats has been generally considered to be safe for adults and children. However, it appears that some oat cultivars may trigger an immune response in sensitive individuals. Therefore, further long-term studies on the impact of consumption of oats identifying the cultivar(s) constitute an important step forward for drawing final recommendations. Furthermore, a closer and more accurate monitoring of the dietary intake of noncontaminated oats would be paramount to better determine what its actual contribution in the gluten-free diet of adults and children with celiac disease are in order to draw sound recommendations on the safety of pure oats as part of the gluten-free diet. PMID:27446824

Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue.

PubMed

de Souza, M Cristina P; Deschênes, Marie-Eve; Laurencelle, Suzanne; Godet, Patrick; Roy, Claude C; Djilali-Saiah, Idriss

2016-01-01

The question about recommending pure, noncontaminated oats as part of the gluten-free diet of patients with celiac disease remains controversial. This might be due to gluten cross contamination and to the possible immunogenicity of some oat cultivars. In view of this controversy, a review of the scientific literature was conducted to highlight the latest findings published between 2008 and 2014 to examine the current knowledge on oats safety and celiac disease in Europe and North America. Results showed that regular oats consumed in Canada are largely contaminated. Overall, the consumption of pure oats has been generally considered to be safe for adults and children. However, it appears that some oat cultivars may trigger an immune response in sensitive individuals. Therefore, further long-term studies on the impact of consumption of oats identifying the cultivar(s) constitute an important step forward for drawing final recommendations. Furthermore, a closer and more accurate monitoring of the dietary intake of noncontaminated oats would be paramount to better determine what its actual contribution in the gluten-free diet of adults and children with celiac disease are in order to draw sound recommendations on the safety of pure oats as part of the gluten-free diet.

Rehabilitation of pure alexia: A review

PubMed Central

Starrfelt, Randi; Ólafsdóttir, Rannveig Rós; Arendt, Ida-Marie

2013-01-01

Acquired reading problems caused by brain injury (alexia) are common, either as a part of an aphasic syndrome, or as an isolated symptom. In pure alexia, reading is impaired while other language functions, including writing, are spared. Being in many ways a simple syndrome, one would think that pure alexia was an easy target for rehabilitation efforts. We review the literature on rehabilitation of pure alexia from 1990 to the present, and find that patients differ widely on several dimensions, such as alexia severity and associated deficits. Many patients reported to have pure alexia in the reviewed studies, have associated deficits such as agraphia or aphasia and thus do not strictly conform to the diagnosis. Few studies report clear and generalisable effects of training, none report control data, and in many cases the reported findings are not supported by statistics. We can, however, tentatively conclude that Multiple Oral Re-reading techniques may have some effect in mild pure alexia where diminished reading speed is the main problem, while Tacile-Kinesthetic training may improve letter identification in more severe cases of alexia. There is, however, still a great need for well-designed and controlled studies of rehabilitation of pure alexia. PMID:23808895

Comparative in vitro biocompatibility of nickel-titanium, pure nickel, pure titanium, and stainless steel: genotoxicity and atomic absorption evaluation.

PubMed

Assad, M; Lemieux, N; Rivard, C H; Yahia, L H

1999-01-01

The genotoxicity level of nickel-titanium (NiTi) was compared to that of its pure constituents, pure nickel (Ni) and pure titanium (Ti) powders, and also to 316L stainless steel (316L SS) as clinical reference material. In order to do so, a dynamic in vitro semiphysiological extraction was performed with all metals using agitation and ISO requirements. Peripheral blood lymphocytes were then cultured in the presence of all material extracts, and their comparative genotoxicity levels were assessed using electron microscopy-in situ end-labeling (EM-ISEL) coupled to immunogold staining. Cellular chromatin exposition to pure Ni and 316L SS demonstrated a significantly stronger gold binding than exposition to NiTi, pure Ti, or the untreated control. In parallel, graphite furnace atomic absorption spectrophotometry (AAS) was also performed on all extraction media. The release of Ni atoms took the following decreasing distribution for the different resulting semiphysiological solutions: pure Ni, 316L SS, NiTi, Ti, and controls. Ti elements were detected after elution of pure titanium only. Both pure titanium and nickel-titanium specimens obtained a relative in vitro biocompatibility. Therefore, this quantitative in vitro study provides optimistic results for the eventual use of nickel-titanium alloys as surgical implant materials.

Proteasome-Mediated Proteolysis of SRSF5 Splicing Factor Intriguingly Co-occurs with SRSF5 mRNA Upregulation during Late Erythroid Differentiation

PubMed Central

Breig, Osman; Baklouti, Faouzi

2013-01-01

SR proteins exhibit diverse functions ranging from their role in constitutive and alternative splicing, to virtually all aspects of mRNA metabolism. These findings have attracted growing interest in deciphering the regulatory mechanisms that control the tissue-specific expression of these SR proteins. In this study, we show that SRSF5 protein decreases drastically during erythroid cell differentiation, contrasting with a concomitant upregulation of SRSF5 mRNA level. Proteasome chemical inhibition provided strong evidence that endogenous SRSF5 protein, as well as protein deriving from stably transfected SRSF5 cDNA, are both targeted to proteolysis as the cells undergo terminal differentiation. Consistently, functional experiments show that overexpression of SRSF5 enhances a specific endogenous pre-mRNA splicing event in proliferating cells, but not in differentiating cells, due to proteasome-mediated targeting of both endogenous and transfection-derived SRSF5. Further investigation of the relationship between SRSF5 structure and its post-translation regulation and function, suggested that the RNA recognition motifs of SRSF5 are sufficient to activate pre-mRNA splicing, whereas proteasome-mediated proteolysis of SRSF5 requires the presence of the C-terminal RS domain of the protein. Phosphorylation of SR proteins is a key post-translation regulation that promotes their activity and subcellular availability. We here show that inhibition of the CDC2-like kinase (CLK) family and mutation of the AKT phosphorylation site Ser86 on SRSF5, have no effect on SRSF5 stability. We reasoned that at least AKT and CLK signaling pathways are not involved in proteasome-induced turnover of SRSF5 during late erythroid development. PMID:23536862

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations

PubMed Central

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10–13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease. PMID:29201369

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations.

PubMed

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10-13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease.

Polarized ensembles of random pure states

NASA Astrophysics Data System (ADS)

Deelan Cunden, Fabio; Facchi, Paolo; Florio, Giuseppe

2013-08-01

A new family of polarized ensembles of random pure states is presented. These ensembles are obtained by linear superposition of two random pure states with suitable distributions, and are quite manageable. We will use the obtained results for two purposes: on the one hand we will be able to derive an efficient strategy for sampling states from isopurity manifolds. On the other, we will characterize the deviation of a pure quantum state from separability under the influence of noise.

Newly discovered orally active pure antiestrogens.

PubMed

Kanbe, Yoshitake; Kim, Myung-Hwa; Nishimoto, Masahiro; Ohtake, Yoshihito; Yoneya, Takaaki; Ohizumi, Iwao; Tsunenari, Toshiaki; Taniguchi, Kenji; Kaiho, Shin-ichi; Nabuchi, Yoshiaki; Araya, Hiroshi; Kawata, Setsu; Morikawa, Kazumi; Jo, Jae-Chon; Kwon, Hee-An; Lim, Hyun-Suk; Kim, Hak-Yeop

2006-09-15

In order to develop orally active pure antiestrogens, we incorporated the carboxy-containing side chains into the 7alpha-position of the steroid scaffold and found that 17-keto derivative CH4893237 (12b) functioned as a pure antiestrogen with its oral activity much superior to clinically used pure antiestrogen, ICI182,780. Results from the pharmacokinetic evaluation indicated that the potent antiestrogen activity at oral dosing in mice attributed to both improved absorption from the intestinal wall and metabolic stability in liver.

Tensor modes in pure natural inflation

NASA Astrophysics Data System (ADS)

Nomura, Yasunori; Yamazaki, Masahito

2018-05-01

We study tensor modes in pure natural inflation [1], a recently-proposed inflationary model in which an axionic inflaton couples to pure Yang-Mills gauge fields. We find that the tensor-to-scalar ratio r is naturally bounded from below. This bound originates from the finiteness of the number of metastable branches of vacua in pure Yang-Mills theories. Details of the model can be probed by future cosmic microwave background experiments and improved lattice gauge theory calculations of the θ-angle dependence of the vacuum energy.

ABO alleles are linked with haplotypes of an erythroid cell-specific regulatory element in intron 1 with a few exceptions attributable to genetic recombination.

PubMed

Nakajima, T; Sano, R; Takahashi, Y; Watanabe, K; Kubo, R; Kobayashi, M; Takahashi, K; Takeshita, H; Kominato, Y

2016-01-01

Recent investigation of transcriptional regulation of the ABO genes has identified a candidate erythroid cell-specific regulatory element, named the +5·8-kb site, in the first intron of ABO. Six haplotypes of the site have been reported previously. The present genetic population study demonstrated that each haplotype was mostly linked with specific ABO alleles with a few exceptions, possibly as a result of hybrid formation between common ABO alleles. Thus, investigation of these haplotypes could provide a clue to further elucidation of ABO alleles. © 2015 International Society of Blood Transfusion.

Gate-driven pure spin current in graphene

NASA Astrophysics Data System (ADS)

Lin, Xiaoyang; Su, Li; Zhang, Youguang; Bournel, Arnaud; Zhang, Yue; Klein, Jacques-Olivier; Zhao, Weisheng; Fert, Albert

An important challenge of spin current based devices is to realize long-distance transport and efficient manipulation of pure spin current without frequent spin-charge conversions. Here, the mechanism of gate-driven pure spin current in graphene is presented. Such a mechanism relies on the electrical gating of conductivity and spin diffusion length in graphene. The gate-driven feature is adopted to realize the pure spin current demultiplexing operation, which enables gate-controllable distribution of the pure spin current into graphene branches. Compared with Elliot-Yafet spin relaxation mechanism, D'yakonov-Perel spin relaxation mechanism results in more appreciable demultiplexing performance, which also implies a feasible strategy to characterize the spin relaxation mechanisms. The unique feature of the pure spin current demultiplexing operation would pave a way for ultra-low power spin logic beyond CMOS. Supported by the NSFC (61627813, 51602013) and the 111 project (B16001).

Hepatoblastoma with pure fetal epithelial differentiation in a 10-year-old boy

PubMed Central

Zhong, Shanshan; Zhao, Yang; Fan, Chuifeng

2018-01-01

Abstract Rationale: Hepatoblastoma is a rare malignant embryonal tumor that only accounts for approximately 1% of all pediatric cancers and mostly develops in children younger than 5 years old. Moreover, the occurrence of hepatoblastoma in adults is extremely rare. Patient concerns: Herein, we present a rare case of hepatoblastoma with pure epithelial differentiation in a 10-year-old boy.Pathological examination was performed. The tumor was 15 cm × 15 cm in size with clear margins. The cut surface was multiple nodular and grey-yellow. Histologically, the small cuboidal tumor cells were arranged in trabeculae with 2–3 cell layers. The tumor cells had eosinophilic or clear cytoplasm, formed dark and light areas, and were positive for alpha-fetoprotein, CK, CK8/18, CD10, hepatocyte, and GPC3. CD34 staining revealed that the sinusoids were lined by endothelial cells in the tumor tissues. The Ki67 index was approximately 20%. Diagnoses: Based on these findings, the case was diagnosed as hepatoblastoma with pure fetal epithelial differentiation. Interventions: The tumor was completely removed. Outcomes: No recurrence was found 3 months after the operation. Lessons: Hepatoblastoma with pure epithelial differentiation can also occur in older children. Children rarely notice and report any physical abnormality, and this may be among the primary reasons for the late diagnosis of the tumor. Annual heath checks may be beneficial in the detection of these rare tumors and improvement of patient outcomes. PMID:29480877

Interference of qubits in pure dephasing and almost pure dephasing environments

NASA Astrophysics Data System (ADS)

Łobejko, Marcin; Mierzejewski, Marcin; Dajka, Jerzy

2015-07-01

Two-path interference of quantum particles with internal spin (qubits) interacting on one arm of the interferometer with bosonic environment is studied. It is assumed that the energy exchange between the qubit and its environment is either absent, which is a pure dephasing (decoherence) model, or very weak. Both the amplitude and the position of maximum of an output intensity discussed as a function of a phase shift can serve as a quantifier of parameters describing coupling between qubit and its environment. The time evolution of the qubit-environment system is analyzed in the Schrödinger picture and the output intensity for qubit-environment interaction close to pure decoherence is analyzed by means of perturbation theory. Quality of the applied approximation is verified by comparison with numerical results.

Arsenic disulfide induced apoptosis and concurrently promoted erythroid differentiation in cytokine-dependent myelodysplastic syndrome-progressed leukemia cell line F-36p with complex karyotype including monosomy 7.

PubMed

Hu, Xiao-mei; Tanaka, Sachiko; Onda, Kenji; Yuan, Bo; Toyoda, Hiroo; Ma, Rou; Liu, Feng; Hirano, Toshihiko

2014-05-01

Acute myeloid leukemia progressed from myelodysplastic syndrome (MDS/AML) is generally incurable with poor prognosis for complex karyotype including monosomy 7 (-7). Qinghuang Powder (, QHP), which includes Qing Dai (Indigo naturalis) and Xiong Huang (realgar) in the formula, is effective in treating MDS or MDS/AML even with the unfavorable karyotype, and its therapeutic efficacy could be enhanced by increasing the Xiong huang content in the formula, while Xiong huang contains > 90% arsenic disulfide (As2S2). F-36p cell line was established from a MDS/AML patient with complex karyotype including -7, and was in cytokine-dependent. The present study was to investigate the effects of As2S2 on F-36p cells. Cell proliferation was measured by an 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was identified by Annexin V-staining. Cell viability was determined by a propidium iodide (PI) exclusion. Erythroid differentiation was evaluated by the expression of cell surface antigen CD235a (GpA). After treatment with As2S2 at concentrations of 0.5 to 16 μmol/L for 72 h, As2S2 inhibited the proliferation of F-36p cells. The 50% inhibitory concentrations (IC50) of As2S2 against the proliferation of F-36p cells was 6 μmol/L. The apoptotic cells significantly increased in a dose-dependent mannar (P<0.05). The cell viabilities were significantly inhibited by As2S2 dose-dependent in a dose-dependent manner (P<0.05). Significant increases of CD235a-positive cells were concurrently observed (P<0.05) also in a dose-dependent manner. As2S2 could inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation dose-dependently in F-36p cells. As2S2 can inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation in cytokine-dependent MDS-progressed human leukemia cell line F-36p with complex karyotype including -7. The data suggest that QHP and/or As2S2 could

Differential effect of pure isoflavones and soymilk on estrogen receptor activity in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rando, Gianpaolo; Ramachandran, Balaji; Rebecchi, Monica

2009-06-15

Background: Because of the complexity of estrogen receptor (ER) physiological activity, the interaction of pure isoflavones or soy-based diets on ER needs to be clearly demonstrated. Objectives: To investigate the effects of the administration of isoflavones as a pure compound or as a component of diet on the ER transcriptional activity in adult mice. Methods: Effects of acute (6 h) and chronic (21 days) oral administration of soy milk, pure genistein and a mix of genistein and daidzein was studied in living ERE-Luc mice. In this animal model, the synthesis of luciferase is under the state of ER transcriptional activity.more » Luciferase activity was measured in living mice by daily bioluminescence imaging sessions and in tissue extracts by enzymatic assay. Results: Acute, oral administration of genistein or soymilk caused a significant increase of ER activity in liver. In a 20 day long treatment, soymilk was more potent than genistein in liver and appeared to extend its influence on ER transcriptional activity in other tissues, such as the digestive tract. A mixture of pure genistein and daidzein at the same concentration as in soymilk failed to induce significant changes during acute and chronic studies suggesting an important, uncharacterized role of the soymilk matrix. Consistent with this observation, synergistic effects of the matrix plus isoflavones were observed in MCF-7 cells stably transfected with the ERE-luc construct. Conclusions: This study underlines the limitations of the analysis of single food components in the evaluation of their effects on estrogen receptor activity and advocates the necessity to use complex organisms for the full comprehension of the effects of compounds altering the endocrine balance.« less

Plant-Produced Human Recombinant Erythropoietic Growth Factors Support Erythroid Differentiation In Vitro

PubMed Central

Musiychuk, Konstantin; Sivalenka, Rajarajeswari; Jaje, Jennifer; Bi, Hong; Flores, Rosemary; Shaw, Brenden; Jones, R. Mark; Golovina, Tatiana; Schnipper, Jacob; Khandker, Luipa; Sun, Ruiqiang; Li, Chang; Kang, Lin; Voskinarian-Berse, Vanessa; Zhang, Xiaokui; Streatfield, Stephen; Hambor, John; Abbot, Stewart

2013-01-01

Clinically available red blood cells (RBCs) for transfusions are at high demand, but in vitro generation of RBCs from hematopoietic stem cells requires significant quantities of growth factors. Here, we describe the production of four human growth factors: erythropoietin (EPO), stem cell factor (SCF), interleukin 3 (IL-3), and insulin-like growth factor-1 (IGF-1), either as non-fused proteins or as fusions with a carrier molecule (lichenase), in plants, using a Tobacco mosaic virus vector-based transient expression system. All growth factors were purified and their identity was confirmed by western blotting and peptide mapping. The potency of these plant-produced cytokines was assessed using TF1 cell (responsive to EPO, IL-3 and SCF) or MCF-7 cell (responsive to IGF-1) proliferation assays. The biological activity estimated here for the cytokines produced in plants was slightly lower or within the range cited in commercial sources and published literature. By comparing EC50 values of plant-produced cytokines with standards, we have demonstrated that all four plant-produced growth factors stimulated the expansion of umbilical cord blood-derived CD34+ cells and their differentiation toward erythropoietic precursors with the same potency as commercially available growth factors. To the best of our knowledge, this is the first report on the generation of all key bioactive cytokines required for the erythroid development in a cost-effective manner using a plant-based expression system. PMID:23517237

Characterizing commercial pureed foods: sensory, nutritional, and textural analysis.

PubMed

Ettinger, Laurel; Keller, Heather H; Duizer, Lisa M

2014-01-01

Dysphagia (swallowing impairment) is a common consequence of stroke and degenerative diseases such as Parkinson's and Alzheimer's. Limited research is available on pureed foods, specifically the qualities of commercial products. Because research has linked pureed foods, specifically in-house pureed products, to malnutrition due to inferior sensory and nutritional qualities, commercial purees also need to be investigated. Proprietary research on sensory attributes of commercial foods is available; however direct comparisons of commercial pureed foods have never been reported. Descriptive sensory analysis as well as nutritional and texture analysis of commercially pureed prepared products was performed using a trained descriptive analysis panel. The pureed foods tested included four brands of carrots, of turkey, and two of bread. Each commercial puree was analyzed for fat (Soxhlet), protein (Dumas), carbohydrate (proximate analysis), fiber (total fiber), and sodium content (Quantab titrator strips). The purees were also texturally compared with a line spread test and a back extrusion test. Differences were found in the purees for sensory attributes as well as nutritional and textural properties. Findings suggest that implementation of standards is required to reduce variability between products, specifically regarding the textural components of the products. This would ensure all commercial products available in Canada meet standards established as being considered safe for swallowing.

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

PubMed Central

Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc

2012-01-01

Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

Pure natural inflation

NASA Astrophysics Data System (ADS)

Nomura, Yasunori; Watari, Taizan; Yamazaki, Masahito

2018-01-01

We point out that a simple inflationary model in which the axionic inflaton couples to a pure Yang-Mills theory may give the scalar spectral index (ns) and tensor-to-scalar ratio (r) in complete agreement with the current observational data.

Loss of the Gata1 Gene IE Exon Leads to Variant Transcript Expression and the Production of a GATA1 Protein Lacking the N-terminal Domain*

PubMed Central

Kobayashi, Eri; Shimizu, Ritsuko; Kikuchi, Yuko; Takahashi, Satoru; Yamamoto, Masayuki

2010-01-01

GATA1 is essential for the differentiation of erythroid cells and megakaryocytes. The Gata1 gene is composed of multiple untranslated first exons and five common coding exons. The erythroid first exon (IE exon) is important for Gata1 gene expression in hematopoietic lineages. Because previous IE exon knockdown analyses resulted in embryonic lethality, less is understood about the contribution of the IE exon to adult hematopoiesis. Here, we achieved specific deletion of the floxed IE exon in adulthood using an inducible Cre expression system. In this conditional knock-out mouse line, the Gata1 mRNA level was significantly down-regulated in the megakaryocyte lineage, resulting in thrombocytopenia with a marked proliferation of megakaryocytes. By contrast, in the erythroid lineage, Gata1 mRNA was expressed abundantly utilizing alternative first exons. Especially, the IEb/c and newly identified IEd exons were transcribed at a level comparable with that of the IE exon in control mice. Surprisingly, in the IE-null mouse, these transcripts failed to produce full-length GATA1 protein, but instead yielded GATA1 lacking the N-terminal domain inefficiently. With low level expression of the short form of GATA1, IE-null mice showed severe anemia with skewed erythroid maturation. Notably, the hematological phenotypes of adult IE-null mice substantially differ from those observed in mice harboring conditional ablation of the entire Gata1 gene. The present study demonstrates that the IE exon is instrumental to adult erythropoiesis by regulating the proper level of transcription and selecting the correct transcription start site of the Gata1 gene. PMID:19854837

Method of preparing pure fluorine gas

DOEpatents

Asprey, Larned B.

1976-01-01

A simple, inexpensive system for purifying and storing pure fluorine is described. The method utilizes alkali metal-nickel fluorides to absorb tank fluorine by forming nickel complex salts and leaving the gaseous impurities which are pumped away. The complex nickel fluoride is then heated to evolve back pure gaseous fluorine.

Testing effects in mixed- versus pure-list designs.

PubMed

Rowland, Christopher A; Littrell-Baez, Megan K; Sensenig, Amanda E; DeLosh, Edward L

2014-08-01

In the present study, we investigated the role of list composition in the testing effect. Across three experiments, participants learned items through study and initial testing or study and restudy. List composition was manipulated, such that tested and restudied items appeared either intermixed in the same lists (mixed lists) or in separate lists (pure lists). In Experiment 1, half of the participants received mixed lists and half received pure lists. In Experiment 2, all participants were given both mixed and pure lists. Experiment 3 followed Erlebacher's (Psychological Bulletin, 84, 212-219, 1977) method, such that mixed lists, pure tested lists, and pure restudied lists were given to independent groups. Across all three experiments, the final recall results revealed significant testing effects for both mixed and pure lists, with no reliable difference in the magnitude of the testing advantage across list designs. This finding suggests that the testing effect is not subject to a key boundary condition-list design-that impacts other memory phenomena, including the generation effect.

Pure Maple Syrup: Nutritive Value.

PubMed

Leaf, A L

1964-02-28

Variations in concentrations of sugar, nitrogen, phosphorus, potassium, calcium, and magnesium of sap from sugar maple (Acer saccharum, Marsh.) trees are related to the time of sap collection and result in variation of the same components in pure maple syrup. Thirty milliliters (one fluid ounce) of pure maple syrup may contain 3 to 6 mg of phosphorus, 10 to 30 mg of potassium, 40 to 80 mg of calcium, and 4 to 25 mg of magnesium.

Similarities and differences between learning abilities, "pure" learning disabilities, "pure" ADHD and comorbid ADHD with learning disabilities.

PubMed

Mangina, Constantine A; Beuzeron-Mangina, Helen

2009-08-01

This research pursues the crucial question of the differentiation of preadolescents with "Pure" ADHD, comorbid ADHD with learning disabilities, "Pure" learning disabilities and age-matched normal controls. For this purpose, Topographic Mapping of Event-Related Brain Potentials (ERPs) to a Memory Workload Paradigm with visually presented words, Bilateral Electrodermal Activity during cognitive workload and Mangina-Test performance were used. The analysis of Topographic distribution of amplitudes revealed that normal preadolescents were significantly different from "Pure" ADHD (P<0.0001), "Pure" learning disabilities (P<0.0001), and comorbid ADHD with learning disabilities (P<0.0009), by displaying enhanced prefrontal and frontal negativities (N450). In contrast, preadolescents with "Pure" ADHD and comorbid ADHD with learning disabilities have shown a marked reduction of prefrontal and frontal negativities (N450). As for the "Pure" Learning Disabled preadolescents, very small positivities (P450) in prefrontal and frontal regions were obtained as compared to the other pathological groups. Bilateral Electrodermal Activity during cognitive workload revealed a significant main effect for groups (P<0.00001), Left versus Right (P=0.0029) and sessions (P=0.0136). A significant main effect for the Mangina-Test performance which separated the four groups was found (P<0.000001). Overall, these data support the existence of clear differences and similarities between the pathological preadolescent groups as opposed to age-matched normal controls. The psychophysiological differentiation of these groups, provides distinct biological markers which integrate central, autonomic and neuropsychometric variables by targeting the key features of these pathologies for diagnosis and intervention strategies and by providing knowledge for the understanding of normal neurocognitive processes and functions.

Single-lineage transcriptome analysis reveals key regulatory pathways in primitive erythroid progenitors in the mouse embryo

PubMed Central

Isern, Joan; He, Zhiyong; Fraser, Stuart T.; Nowotschin, Sonja; Ferrer-Vaquer, Anna; Moore, Rebecca; Hadjantonakis, Anna-Katerina; Schulz, Vincent; Tuck, David; Gallagher, Patrick G.

2011-01-01

Primitive erythroid (EryP) progenitors are the first cell type specified from the mesoderm late in gastrulation. We used a transgenic reporter to image and purify the earliest blood progenitors and their descendants from developing mouse embryos. EryP progenitors exhibited remarkable proliferative capacity in the yolk sac immediately before the onset of circulation, when these cells comprise nearly half of all cells of the embryo. Global expression profiles generated at 24-hour intervals from embryonic day 7.5 through 2.5 revealed 2 abrupt changes in transcript diversity that coincided with the entry of EryPs into the circulation and with their late maturation and enucleation, respectively. These changes were paralleled by the expression of critical regulatory factors. Experiments designed to test predictions from these data demonstrated that the Wnt-signaling pathway is active in EryP progenitors, which display an aerobic glycolytic profile and the numbers of which are regulated by transforming growth factor-β1 and hypoxia. This is the first transcriptome assembled for a single hematopoietic lineage of the embryo over the course of its differentiation. PMID:21263157

Requirement for erythroblast-macrophage protein (Emp) in definitive erythropoiesis.

PubMed

Soni, Shivani; Bala, Shashi; Hanspal, Manjit

2008-01-01

Emp, erythroblast-macrophage protein was initially identified as a mediator of erythroblast-macrophage interactions during erythroid differentiation. More recent studies have shown that targeted disruption of Emp leads to abnormal erythropoiesis in the fetal liver, and fetal demise. To further address the activity of Emp in the hematopoietic lineage in adult bone marrow, we conducted fetal liver HSC reconstitution assay. Emp null fetal liver cells were transplanted into lethally irradiated wild-type sibling mice, and assessed the erythropoietic activity. We found that Emp null cells rescued lethally irradiated mice with efficiency comparable to that of wild-type cells. However, the recipients of Emp null cells showed abnormal erythropoiesis as indicated by the presence of persistent anemia, extensive extramedullary erythropoiesis, and increased apoptosis of erythroid precursors. Extramedullary erythropoiesis suggests perturbed interactions between the Emp-deficient hematopoietic cells and the wild-type niche. Furthermore, in spleen colony-forming unit assays, proliferation rates of the Emp null cells were greater than those of the wild-type cells. Similarly, in vitro burst-forming unit-erythroid and colony-forming unit-erythroid assays showed increased erythroid colony numbers from Emp null livers. Morphologic examination showed that Emp null CFU-E-derived erythroblasts were immature compared to those derived from wild-type CFU-Es, suggesting that loss of Emp function in erythroid cells results in impaired proliferation and terminal differentiation. These results demonstrate that Emp plays a cell intrinsic role in the erythroid lineage.

Gate-Driven Pure Spin Current in Graphene

NASA Astrophysics Data System (ADS)

Lin, Xiaoyang; Su, Li; Si, Zhizhong; Zhang, Youguang; Bournel, Arnaud; Zhang, Yue; Klein, Jacques-Olivier; Fert, Albert; Zhao, Weisheng

2017-09-01

The manipulation of spin current is a promising solution for low-power devices beyond CMOS. However, conventional methods, such as spin-transfer torque or spin-orbit torque for magnetic tunnel junctions, suffer from large power consumption due to frequent spin-charge conversions. An important challenge is, thus, to realize long-distance transport of pure spin current, together with efficient manipulation. Here, the mechanism of gate-driven pure spin current in graphene is presented. Such a mechanism relies on the electrical gating of carrier-density-dependent conductivity and spin-diffusion length in graphene. The gate-driven feature is adopted to realize the pure spin-current demultiplexing operation, which enables gate-controllable distribution of the pure spin current into graphene branches. Compared with the Elliott-Yafet spin-relaxation mechanism, the D'yakonov-Perel spin-relaxation mechanism results in more appreciable demultiplexing performance. The feature of the pure spin-current demultiplexing operation will allow a number of logic functions to be cascaded without spin-charge conversions and open a route for future ultra-low-power devices.

Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2

PubMed Central

Furue, Masutaka; Uchi, Hiroshi; Mitoma, Chikage; Hashimoto-Hachiya, Akiko; Chiba, Takahito; Ito, Takamichi; Nakahara, Takeshi; Tsuji, Gaku

2017-01-01

Skin is the outermost part of the body and is, thus, inevitably exposed to UV rays and environmental pollutants. Oxidative stress by these hazardous factors accelerates skin aging and induces skin inflammation and carcinogenesis. Aryl hydrocarbon receptors (AHRs) are chemical sensors that are abundantly expressed in epidermal keratinocytes and mediate the production of reactive oxygen species. To neutralize or minimize oxidative stress, the keratinocytes also express nuclear factor-erythroid 2-related factor-2 (NRF2), which is a master switch for antioxidant signaling. Notably, there is fine-tuned crosstalk between AHR and NRF2, which mutually increase or decrease their activation states. Many NRF2-mediated antioxidant phytochemicals are capable of up- and downmodulating AHR signaling. The precise mechanisms by which these phytochemicals differentially affect the AHR and NRF2 system remain largely unknown and warrant future investigation. PMID:28273792

Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2.

PubMed

Furue, Masutaka; Uchi, Hiroshi; Mitoma, Chikage; Hashimoto-Hachiya, Akiko; Chiba, Takahito; Ito, Takamichi; Nakahara, Takeshi; Tsuji, Gaku

2017-03-03

Skin is the outermost part of the body and is, thus, inevitably exposed to UV rays and environmental pollutants. Oxidative stress by these hazardous factors accelerates skin aging and induces skin inflammation and carcinogenesis. Aryl hydrocarbon receptors (AHRs) are chemical sensors that are abundantly expressed in epidermal keratinocytes and mediate the production of reactive oxygen species. To neutralize or minimize oxidative stress, the keratinocytes also express nuclear factor-erythroid 2-related factor-2 (NRF2), which is a master switch for antioxidant signaling. Notably, there is fine-tuned crosstalk between AHR and NRF2, which mutually increase or decrease their activation states. Many NRF2-mediated antioxidant phytochemicals are capable of up- and downmodulating AHR signaling. The precise mechanisms by which these phytochemicals differentially affect the AHR and NRF2 system remain largely unknown and warrant future investigation.

Pure chiral optical fibres.

PubMed

Poladian, L; Straton, M; Docherty, A; Argyros, A

2011-01-17

We investigate the properties of optical fibres made from chiral materials, in which a contrast in optical activity forms the waveguide, rather than a contrast in the refractive index; we refer to such structures as pure chiral fibres. We present a mathematical formulation for solving the modes of circularly symmetric examples of such fibres and examine the guidance and polarisation properties of pure chiral step-index, Bragg and photonic crystal fibre designs. Their behaviour is shown to differ for left- and right-hand circular polarisation, allowing circular polarisations to be isolated and/or guided by different mechanisms, as well as differing from equivalent non-chiral fibres. The strength of optical activity required in each case is quantified.

The L49F mutation in alpha erythroid spectrin induces local disorder in the tetramer association region: Fluorescence and molecular dynamics studies of free and bound alpha spectrin

PubMed Central

Song, Yuanli; Pipalia, Nina H; Fung, L W-M

2009-01-01

The bundling of the N-terminal, partial domain helix (Helix C′) of human erythroid α-spectrin (αI) with the C-terminal, partial domain helices (Helices A′ and B′) of erythroid β-spectrin (βI) to give a spectrin pseudo structural domain (triple helical bundle A′B′C′) has long been recognized as a crucial step in forming functional spectrin tetramers in erythrocytes. We have used apparent polarity and Stern–Volmer quenching constants of Helix C′ of αI bound to Helices A′ and B′ of βI, along with previous NMR and EPR results, to propose a model for the triple helical bundle. This model was used as the input structure for molecular dynamics simulations for both wild type (WT) and αI mutant L49F. The simulation output structures show a stable helical bundle for WT, but not for L49F. In WT, four critical interactions were identified: two hydrophobic clusters and two salt bridges. However, in L49F, the region downstream of Helix C′ was unable to assume a helical conformation and one critical hydrophobic cluster was disrupted. Other molecular interactions critical to the WT helical bundle were also weakened in L49F, possibly leading to the lower tetramer levels observed in patients with this mutation-induced blood disorder. PMID:19593814

[The left central gyral lesion and pure anarthria].

PubMed

Tabuchi, M; Odashima, K; Fujii, T; Suzuki, K; Saitou, J; Yamadori, A

2000-05-01

We report a very rare case of pure anarthria with lesion analysis. A 44-year-old right-handed man suffered from a cerebral infarction with a mild right hemiparesis and speech disturbance. An MRI of the brain 1.5 months post onset revealed a lesion confined to the left central gyrus. One month after the onset, his spontaneous speech was dysprosodic and laborious. It was contaminated with dysarthria and phonological paraphasias. However, language comprehension, repetition and naming abilities were normal. Most remarkably he showed no impairment in writing with his left hand. Over the following months, his difficulties in verbal output showed general amelioration, but the isolated impairment in the domain of articulation characterized by dysprosody, dysarthria, and phonological paraphasia persisted. As for the symptomatology of pure anarthria resulting from precentral gyral lesions, there have been controversies about its pureness. Some argue that the so called pure anarthria always shows some degree of writing disturbances, albeit mild in degree. Others maintain there certainly exists the pure type without any signs of agraphia. In the present case lesions were limited to the central gyrus but spared the lowest opercular portion. The previous reports of pure anarthria that had mild agraphia all had lesions involving the opercular portion. We conclude the sparing of this area is most likely related with sparing of writing capacity in pure anarthria.

Anti-M Antibody Induced Prolonged Anemia Following Hemolytic Disease of the Newborn Due to Erythropoietic Suppression in 2 Siblings.

PubMed

Ishida, Atsushi; Ohto, Hitoshi; Yasuda, Hiroyasu; Negishi, Yutaka; Tsuiki, Hideki; Arakawa, Takeshi; Yagi, Yoshihito; Uchimura, Daisuke; Miyazaki, Toru; Ohashi, Wataru; Takamoto, Shigeru

2015-08-01

Hemolytic disease of the newborn (HDN) arising from MNSs incompatibility is rare, with few reports of prolonged anemia and reticulocytopenia following HDN. We report the younger of 2 male siblings, both of whom had anti-M-induced HDN and anemia persisting for over a month. Peripheral reticulocytes remained inappropriately low for the degree of anemia, and they needed multiple red cell transfusions. Viral infections were ruled out. Corticosteroids were given for suspected pure red cell aplasia. Anemia and reticulocytopenia subsequently improved. Colony-forming unit erythroid assay revealed erythropoietic suppression of M antigen-positive erythroid precursor cells cultured with maternal or infant sera containing anti-M. In conclusion, maternal anti-M caused HDN and prolonged anemia by erythropoietic suppression in 2 siblings.

The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12.

PubMed

Hall, Mark A; Curtis, David J; Metcalf, Donald; Elefanty, Andrew G; Sourris, K; Robb, Lorraine; Gothert, Joachim R; Jane, Stephen M; Begley, C Glenn

2003-02-04

Gene targeting studies have shown that the transcription factor SCL is critically important for embryonic hematopoiesis, but the early lethality of SCL null mice has precluded the genetic analysis of its function in the adult. We have now generated a conditional knockout of SCL by using CreLox technology and an IFN-inducible Cre transgenic mouse. Deletion of SCL in adult mice perturbed megakaryopoiesis and erythropoiesis with the loss of early progenitor cells in both lineages. This led to a blunted response to the hematopoietic stress induced by polyinosinic-polycytidylic acid, with a persistently low platelet count and hematocrit compared with controls. In contrast, progenitors of granulocyte and macrophage lineages were not affected, even in the setting of stress. Immature progenitor cells (day 12 colony-forming unit spleen) with multilineage capacity were still present in the SCL null bone marrow, but these progenitors had lost the capacity to generate erythroid and megakaryocyte cells, and colonies were composed of only myeloid cells. These results suggest that SCL is critical for megakaryopoiesis and erythropoiesis, but is dispensable for production of myeloid cells during adult hematopoiesis.

Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing.

PubMed

Tang, Qin; Iyer, Sowmya; Lobbardi, Riadh; Moore, John C; Chen, Huidong; Lareau, Caleb; Hebert, Christine; Shaw, McKenzie L; Neftel, Cyril; Suva, Mario L; Ceol, Craig J; Bernards, Andre; Aryee, Martin; Pinello, Luca; Drummond, Iain A; Langenau, David M

2017-10-02

Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA-protein kinase catalytic subunit ( prkdc ), interleukin-2 receptor γ a ( il2rga ), and double-homozygous-mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish. © 2017 Tang et al.

Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing

PubMed Central

Iyer, Sowmya; Lobbardi, Riadh; Chen, Huidong; Hebert, Christine; Shaw, McKenzie L.; Neftel, Cyril; Suva, Mario L.; Bernards, Andre; Aryee, Martin; Drummond, Iain A.

2017-01-01

Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA–protein kinase catalytic subunit (prkdc), interleukin-2 receptor γ a (il2rga), and double-homozygous–mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish. PMID:28878000

PSYCHE Pure Shift NMR Spectroscopy.

PubMed

Foroozandeh, Mohammadali; Morris, Gareth; Nilsson, Mathias

2018-03-13

Broadband homodecoupling techniques in NMR, also known as "pure shift" methods, aim to enhance spectral resolution by suppressing the effects of homonuclear coupling interactions to turn multiplet signals into singlets. Such techniques typically work by selecting a subset of "active" nuclear spins to observe, and selectively inverting the remaining, "passive", spins to reverse the effects of coupling. Pure Shift Yielded by Chirp Excitation (PSYCHE) is one such method; it is relatively recent, but has already been successfully implemented in a range of different NMR experiments. Paradoxically, PSYCHE is one of the trickiest of pure shift NMR techniques to understand but one of the easiest to use. Here we offer some insights into theoretical and practical aspects of the method, and into the effects and importance of the experimental parameters. Some recent improvements that enhance the spectral purity of PSYCHE spectra will be presented, and some experimental frameworks including examples in 1D and 2D NMR spectroscopy, for the implementation of PSYCHE will be introduced. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA-1 erythroid transcription factor.

PubMed

Foti, M; Omichinski, J G; Stahl, S; Maloney, D; West, J; Schweitzer, B I

1999-02-05

We investigate here the effects of the incorporation of the nucleoside analogs araC (1-beta-D-arabinofuranosylcytosine) and ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl] guanine) into the DNA binding recognition sequence for the GATA-1 erythroid transcription factor. A 10-fold decrease in binding affinity was observed for the ganciclovir-substituted DNA complex in comparison to an unmodified DNA of the same sequence composition. AraC substitution did not result in any changes in binding affinity. 1H-15N HSQC and NOESY NMR experiments revealed a number of chemical shift changes in both DNA and protein in the ganciclovir-modified DNA-protein complex when compared to the unmodified DNA-protein complex. These changes in chemical shift and binding affinity suggest a change in the binding mode of the complex when ganciclovir is incorporated into the GATA DNA binding site.

Dissociative Global and Local Task-Switching Costs Across Younger Adults, Middle-Aged Adults, Older Adults, and Very Mild Alzheimer Disease Individuals

PubMed Central

Huff, Mark J.; Balota, David A.; Minear, Meredith; Aschenbrenner, Andrew J.; Duchek, Janet M.

2015-01-01

A task-switching paradigm was used to examine differences in attentional control across younger adults, middle-aged adults, healthy older adults, and individuals classified in the earliest detectable stage of Alzheimer's disease (AD). A large sample of participants (570) completed a switching task in which participants were cued to classify the letter (consonant/vowel) or number (odd/even) task-set dimension of a bivalent stimulus (e.g., A 14), respectively. A Pure block consisting of single-task trials and a Switch block consisting of nonswitch and switch trials were completed. Local (switch vs. nonswitch trials) and global (nonswitch vs. pure trials) costs in mean error rates, mean response latencies, underlying reaction time distributions, along with stimulus-response congruency effects were computed. Local costs in errors were group invariant, but global costs in errors systematically increased as a function of age and AD. Response latencies yielded a strong dissociation: Local costs decreased across groups whereas global costs increased across groups. Vincentile distribution analyses revealed that the dissociation of local and global costs primarily occurred in the slowest response latencies. Stimulus-response congruency effects within the Switch block were particularly robust in accuracy in the very mild AD group. We argue that the results are consistent with the notion that the impaired groups show a reduced local cost because the task sets are not as well tuned, and hence produce minimal cost on switch trials. In contrast, global costs increase because of the additional burden on working memory of maintaining two task sets. PMID:26652720

Efficient production of erythroid, megakaryocytic and myeloid cells, using single cell-derived iPSC colony differentiation.

PubMed

Hansen, Marten; Varga, Eszter; Aarts, Cathelijn; Wust, Tatjana; Kuijpers, Taco; von Lindern, Marieke; van den Akker, Emile

2018-04-28

Hematopoietic differentiation of human induced pluripotent stem cells (iPSCs) provide opportunities not only for fundamental research and disease modelling/drug testing but also for large-scale production of blood effector cells for future clinical application. Although there are multiple ways to differentiate human iPSCs towards hematopoietic lineages, there is a need to develop reproducible and robust protocols. Here we introduce an efficient way to produce three major blood cell types using a standardized differentiation protocol that starts with a single hematopoietic initiation step. This system is feeder-free, avoids EB-formation, starts with a hematopoietic initiation step based on a novel single cell-derived iPSC colony differentiation and produces multi-potential progenitors within 8-10 days. Followed by lineage-specific growth factor supplementation these cells can be matured into well characterized erythroid, megakaryocytic and myeloid cells with high-purity, without transcription factor overexpression or any kind of pre-purification step. This standardized differentiation system provides a simple platform to produce specific blood cells in a reproducible manner for hematopoietic development studies, disease modelling, drug testing and the potential for future therapeutic applications. Copyright © 2018. Published by Elsevier B.V.

Pure Electron Plasmas near Thermal Equilibrium

DTIC Science & Technology

1990-11-01

I University of California, San Diego Institute of Pure and Applied Physical Sciences La Jolla, CA 92093 N 0 (V) Final Technical Report N "Pure...Research/code -..... " 1112AI. VC 1/8/91 ’ , .... i ; () -ii- r INTRODUCTION Since 1982 the plasma group at UCSD has been conducting an experimental and...scale. We have also observed an unusual I = 1 instability which the previously published theoretical literature stated unconditionally was stable. The

7 CFR 201.64 - Pure live seed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... applying the respective tolerances to the germination plus the hard seed and the pure seed. [5 FR 35, Jan... 7 Agriculture 3 2010-01-01 2010-01-01 false Pure live seed. 201.64 Section 201.64 Agriculture..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT...

7 CFR 201.64 - Pure live seed.

Code of Federal Regulations, 2011 CFR

2011-01-01

... applying the respective tolerances to the germination plus the hard seed and the pure seed. [5 FR 35, Jan... 7 Agriculture 3 2011-01-01 2011-01-01 false Pure live seed. 201.64 Section 201.64 Agriculture..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT...

New Bell inequalities for three-qubit pure states

NASA Astrophysics Data System (ADS)

Das, Arpan; Datta, Chandan; Agrawal, Pankaj

2017-12-01

We introduce a set of Bell inequalities for a three-qubit system. Each inequality within this set is violated by all generalized GHZ states. The more entangled a generalized GHZ state is, the more will be the violation. This establishes a relation between nonlocality and entanglement for this class of states. Certain inequalities within this set are violated by pure biseparable states. We also provide numerical evidence that at least one of these Bell inequalities is violated by a pure genuinely entangled state. These Bell inequalities can distinguish between separable, biseparable and genuinely entangled pure three-qubit states. We also generalize this set to n-qubit systems and may be suitable to characterize the entanglement of n-qubit pure states.

Science: Pure or Applied?

ERIC Educational Resources Information Center

Evans, Peter

1980-01-01

Through a description of some of the activities which take place in his science classroom, the author makes a strong case for the inclusion of technology, or applied science, rather than pure science in the primary curriculum. (KC)

ThermoData Engine Database - Pure Compounds and Binary Mixtures

National Institute of Standards and Technology Data Gateway

SRD 103b NIST ThermoData Engine Version 6.0 - Pure CompoThermoData Engine Database - Pure Compounds and Binary Mixtures (PC database for purchase)   This database contains property data for more than 21,000 pure compounds, 37,500 binary mixtures, 10,000 ternary mixtures, and 6,000 chemical reactions.

Internal oxidation phenomenon in pure copper

NASA Astrophysics Data System (ADS)

Rudolf, Rebeka; Anžel, Ivan

2009-04-01

This paper presents two special kinds of internal oxidation phenomenon that can take place in pure metals containing a high concentration of non-equilibrium defects. These processes are Internal Oxidation (IO) and Internal Carbonisation (IC). Both processes start with the dissolution of oxidant (O or C) into the pure metal at the free surfaces, and continue with the diffusion of oxidant atoms into the metal matrix volume, where they are trapped at numerous defects within the crystal lattice. Increasing oxidant activity at these places causes local oxidation of the matrix and, consequently, precipitation of fine oxide or graphite particles. The IO and IC processes were tested on the rapidly solidified pure copper which was produced by the Chill-Block Melt Spinning Technique. Analysis of the IO process showed the formation of Cu-Cu2O, and the formation of Cu-C composite from the IC process.

Miso. III. Pure culture fermentation with Saccharomyces rouxii.

PubMed

HESSELTINE, C W; SHIBASAKI, K

1961-11-01

Excellent miso has been prepared with soybean grits inoculated with a pure culture of Saccharomyces rouxii strain NRRL Y-2547. Pure culture inoculum of this osmophilic yeast was prepared by growing the culture in aerated flasks on a yeast extract medium with a salt concentration equal to that used in the manufacture of miso. It has also been found possible to make miso from whole beans with the above culture. The advantages of pure culture fermentation in producing miso are discussed.

Pure science and the problem of progress.

PubMed

Douglas, Heather

2014-06-01

How should we understand scientific progress? Kuhn famously discussed science as its own internally driven venture, structured by paradigms. He also famously had a problem describing progress in science, as problem-solving ability failed to provide a clear rubric across paradigm change--paradigm changes tossed out problems as well as solving them. I argue here that much of Kuhn's inability to articulate a clear view of scientific progress stems from his focus on pure science and a neglect of applied science. I trace the history of the distinction between pure and applied science, showing how the distinction came about, the rhetorical uses to which the distinction has been put, and how pure science came to be both more valued by scientists and philosophers. I argue that the distinction between pure and applied science does not stand up to philosophical scrutiny, and that once we relinquish it, we can provide Kuhn with a clear sense of scientific progress. It is not one, though, that will ultimately prove acceptable. For that, societal evaluations of scientific work are needed.

Repression of chimeric transcripts emanating from endogenous retrotransposons by a sequence-specific transcription factor

PubMed Central

2014-01-01

Background Retroviral elements are pervasively transcribed and dynamically regulated during development. While multiple histone- and DNA-modifying enzymes have broadly been associated with their global silencing, little is known about how the many diverse retroviral families are each selectively recognized. Results Here we show that the zinc finger protein Krüppel-like Factor 3 (KLF3) specifically silences transcription from the ORR1A0 long terminal repeat in murine fetal and adult erythroid cells. In the absence of KLF3, we detect widespread transcription from ORR1A0 elements driven by the master erythroid regulator KLF1. In several instances these aberrant transcripts are spliced to downstream genic exons. One such chimeric transcript produces a novel, dominant negative isoform of PU.1 that can induce erythroid differentiation. Conclusions We propose that KLF3 ensures the integrity of the murine erythroid transcriptome through the selective repression of a particular retroelement and is likely one of multiple sequence-specific factors that cooperate to achieve global silencing. PMID:24946810

The First Comparative Study of the Perioperative Outcomes Between Pure Laparoscopic Donor Hepatectomy and Laparoscopy-Assisted Donor Hepatectomy in a Single Institution.

PubMed

Takahara, Takeshi; Wakabayashi, Go; Nitta, Hiroyuki; Hasegawa, Yasushi; Katagiri, Hirokatsu; Umemura, Akira; Takeda, Daiki; Makabe, Kenji; Otsuka, Koki; Koeda, Keisuke; Sasaki, Akira

2017-07-01

In a statement from the second International Consensus Conference for Laparoscopic Liver Resection, adult-to-adult laparoscopic donor surgery was the earliest phase of development. It was recommended that the procedure be performed under institutional ethical approval and a reporting registry. At our institute, we started laparoscopy-assisted donor hepatectomy (LADH) in 2007 and changed to pure laparoscopic donor hepatectomy (PLDH) in 2012. This study included 40 living donors who underwent LADH and 14 live donors who underwent PLDH. We describe the technical aspects and outcomes of our donor hepatectomy from assist to pure and examine the liver allograft outcomes of the recipients after LADH and PLDH. There was significantly less blood loss in the PLDH group (81.07 ± 52.78 g) than that in the LADH group (238.50 ± 177.05 g), although the operative time was significantly longer in the PLDH group (454.93 ± 85.60 minutes) than in the LADH group (380.40 ± 44.08 minutes). And there were no significant differences in postoperative complication rate in the 2 groups. The liver allograft outcomes were acceptable and comparable with open living donor hepatectomy. By changing our routine approach from assist to pure, PLDH can be performed safely, with better exposure due to magnification, and with less blood loss under pneumoperitoneal pressure. PLDH, which has become our promising donor procedure, results in less blood loss, better cosmesis, and the donor's complete rehabilitation without deterioration in donor safety.

Measuring the entanglement of bipartite pure states

NASA Astrophysics Data System (ADS)

Sancho, J. M.; Huelga, S. F.

2000-04-01

The problem of the experimental determination of the amount of entanglement of a bipartite pure state is addressed. We show that measuring a single observable does not suffice to determine the entanglement of a given unknown pure state of two particles. Possible minimal local measuring strategies are discussed, and a comparison is made on the basis of their best achievable precision.

Therapeutic fetal-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms.

PubMed

Dai, Yan; Sangerman, Jose; Luo, Hong Yuan; Fucharoen, Suthat; Chui, David H K; Faller, Douglas V; Perrine, Susan P

2016-01-01

Pharmacologic augmentation of γ-globin expression sufficient to reduce anemia and clinical severity in patients with diverse hemoglobinopathies has been challenging. In studies here, representative molecules from four chemical classes, representing several distinct primary mechanisms of action, were investigated for effects on γ-globin transcriptional repressors, including components of the NuRD complex (LSD1 and HDACs 2-3), and the downstream repressor BCL11A, in erythroid progenitors from hemoglobinopathy patients. Two HDAC inhibitors (MS-275 and SB939), a short-chain fatty acid derivative (sodium dimethylbutyrate [SDMB]), and an agent identified in high-throughput screening, Benserazide, were studied. These therapeutics induced γ-globin mRNA in progenitors above same subject controls up to 20-fold, and increased F-reticulocytes up to 20%. Cellular protein levels of BCL11A, LSD-1, and KLF1 were suppressed by the compounds. Chromatin immunoprecipitation assays demonstrated a 3.6-fold reduction in LSD1 and HDAC3 occupancy in the γ-globin gene promoter with Benserazide exposure, 3-fold reduction in LSD-1 and HDAC2 occupancy in the γ-globin gene promoter with SDMB exposure, while markers of gene activation (histone H3K9 acetylation and H3K4 demethylation), were enriched 5.7-fold. These findings identify clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapeutic γ-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms

PubMed Central

Dai, Yan; Sangerman, Jose; Hong, Yuan Luo; Fuchareon, Suthat; Chui, David H.K.; Faller, Douglas V.; Perrine, Susan P.

2015-01-01

Pharmacologic augmentation of γ-globin expression sufficient to reduce anemia and clinical severity in patients with diverse hemoglobinopathies has been challenging. In studies here, representative molecules from four chemical classes, representing several distinct primary mechanisms of action, were investigated for effects on γ-globin transcriptional repressors, including components of the NuRD complex (LSD1 and HDACs 2-3), and the downstream repressor BCL11A, in erythroid progenitors from hemoglobinopathy patients. Two HDAC inhibitors (MS-275 and SB939), a short-chain fatty acid derivative (sodium dimethylbutyrate [SDMB]), and an agent identified in high-throughput screening, Benserazide, were studied. These therapeutics induced γ globin mRNA in progenitors above same subject controls up to 20-fold, and increased F-reticulocytes up to 20%. Cellular protein levels of BCL11A, LSD-1, and KLF1 were suppressed by the compounds. Chromatin immunoprecipitation assays demonstrated a 3.6-fold reduction in LSD1 and HDAC3 occupancy in the γ-globin gene promoter with Benserazide exposure, 3-fold reduction in LSD-1 and HDAC2 occupancy in the γ-globin gene promoter with SDMB exposure, while markers of gene activation (histone H3K9 acetylation and H3K4 demethylation), were enriched 5.7-fold. These findings identify clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. PMID:26603726

Role of Stem Cell Factor in the Reactivation of Human Fetal Hemoglobin

PubMed Central

Gabbianelli, Marco; Testa, Ugo

2009-01-01

In humans the switch from fetal to adult hemoglobin (HbF → HbA) takes place in the perinatal and postnatal period, determining the progressive replacement of HbF with HbA synthesis (i.e., the relative HbF content in red blood cells decreases from 80–90% to <1%). In spite of more than twenty years of intensive investigations on this classic model, the molecular mechanisms regulating the Hb switching, as well as HbF synthesis in adults, has been only in part elucidated. In adult life, the residual HbF, restricted to F cell compartment, may be reactivated up to 10–20% of total Hb synthesis in various conditions associated with “stress erythropoiesis”: this reactivation represented until now an interesting model of partial Hb switch reverse with important therapeutic implications in patients with hemoglobinopathies, and particularly in β-thalassemia. In vitro and in vivo models have led to the identification of several chemical compounds able to reactivate HbF synthesis in adult erythroid cells. Although the impact of these HbF inducers, including hypomethylating agents, histone deacetylase inhibitors and hydroxyurea, was clear on the natural history of sickle cell anemia, the benefit on the clinical course of β-thalassemia was only limited: particularly, the toxicity and the modest increase in γ-globin reactivation indicated the need for improved agents able to induce higher levels of HbF. In the present review we describe the biologic properties of Stem Cell Factor (SCF), a cytokine sustaining the survival and proliferation of erythroid cells, that at pharmacological doses acts as a potent stimulator of HbF synthesis in adult erythroid cells. PMID:21415991

No oral-cavity-only discrimination of purely olfactory odorants.

PubMed

Stephenson, Dejaimenay; Halpern, Bruce P

2009-02-01

The purely olfactory odorants coumarin, octanoic acid, phenylethyl alcohol, and vanillin had been found to be consistently identified when presented retronasally but could not be identified when presented oral-cavity only (OCO). However, OCO discrimination of these odorants was not tested. Consequently, it remained possible that the oral cavity trigeminal system might provide sufficient information to differentiate these purely olfactory odorants. To evaluate this, 20 participants attempted to discriminate vapor-phase coumarin, octanoic acid, phenylethyl alcohol, and vanillin and, as a control, the trigeminal stimulus peppermint extract, from their glycerin solvent, all presented OCO. None of the purely olfactory odorants could be discriminated OCO, but, as expected, peppermint extract was consistently discriminated. This inability to discriminate clarifies and expands the previous report of lack of OCO identification of purely olfactory odorants. Taken together with prior data, these results suggest that the oral cavity trigeminal system is fully unresponsive to these odorants in vapor phase and that coumarin, octanoic acid, phenylethyl alcohol, and vanillin are indeed purely olfactory stimuli. The OCO discrimination of peppermint extract demonstrated that the absence of discrimination for the purely olfactory odorants was odorant dependent and confirmed that the oral cavity trigeminal system will provide differential response information to some vapor-phase stimuli.

Language as Pure Potential

ERIC Educational Resources Information Center

Park, Joseph Sung-Yul

2016-01-01

Language occupies a crucial position in neoliberalism, due to the reimagination of language as commodified skill. This paper studies the role of language ideology in this transformation by identifying a particular ideology that facilitates this process, namely the ideology which views language as pure potential. Neoliberalism treats language as a…

Dahlbeck and Pure Ontology

ERIC Educational Resources Information Center

Mackenzie, Jim

2016-01-01

This article responds to Johan Dahlbeck's "Towards a pure ontology: Children's bodies and morality" ["Educational Philosophy and Theory," vol. 46 (1), 2014, pp. 8-23 (EJ1026561)]. His arguments from Nietzsche and Spinoza do not carry the weight he supposes, and the conclusions he draws from them about pedagogy would be…

Production of pure metals

NASA Technical Reports Server (NTRS)

Philipp, W. H.; Marsik, S. J.; May, C. E. (Inventor)

1974-01-01

A process for depositing elements by irradiating liquids is reported. Ultra pure elements are precipitated from aqueous solutions or suspensions of compounds. A solution of a salt of a metal to be prepared is irradiated, and the insoluble reaction product settles out. Some chemical compounds may also be prepared in this manner.

Fracture behaviors under pure shear loading in bulk metallic glasses.

PubMed

Chen, Cen; Gao, Meng; Wang, Chao; Wang, Wei-Hua; Wang, Tzu-Chiang

2016-12-23

Pure shear fracture test, as a special mechanical means, had been carried out extensively to obtain the critical information for traditional metallic crystalline materials and rocks, such as the intrinsic deformation behavior and fracture mechanism. However, for bulk metallic glasses (BMGs), the pure shear fracture behaviors have not been investigated systematically due to the lack of a suitable test method. Here, we specially introduce a unique antisymmetrical four-point bend shear test method to realize a uniform pure shear stress field and study the pure shear fracture behaviors of two kinds of BMGs, Zr-based and La-based BMGs. All kinds of fracture behaviors, the pure shear fracture strength, fracture angle and fracture surface morphology, are systematically analyzed and compared with those of the conventional compressive and tensile fracture. Our results indicate that both the Zr-based and La-based BMGs follow the same fracture mechanism under pure shear loading, which is significantly different from the situation of some previous research results. Our results might offer new enlightenment on the intrinsic deformation and fracture mechanism of BMGs and other amorphous materials.

Fracture behaviors under pure shear loading in bulk metallic glasses

NASA Astrophysics Data System (ADS)

Chen, Cen; Gao, Meng; Wang, Chao; Wang, Wei-Hua; Wang, Tzu-Chiang

2016-12-01

Pure shear fracture test, as a special mechanical means, had been carried out extensively to obtain the critical information for traditional metallic crystalline materials and rocks, such as the intrinsic deformation behavior and fracture mechanism. However, for bulk metallic glasses (BMGs), the pure shear fracture behaviors have not been investigated systematically due to the lack of a suitable test method. Here, we specially introduce a unique antisymmetrical four-point bend shear test method to realize a uniform pure shear stress field and study the pure shear fracture behaviors of two kinds of BMGs, Zr-based and La-based BMGs. All kinds of fracture behaviors, the pure shear fracture strength, fracture angle and fracture surface morphology, are systematically analyzed and compared with those of the conventional compressive and tensile fracture. Our results indicate that both the Zr-based and La-based BMGs follow the same fracture mechanism under pure shear loading, which is significantly different from the situation of some previous research results. Our results might offer new enlightenment on the intrinsic deformation and fracture mechanism of BMGs and other amorphous materials.

Purely electromagnetic spacetimes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivanov, B. V.

The Rainich's program of describing metrics induced by pure electromagnetic fields is implemented in a simpler way by using the Ernst formalism and increasing the symmetry of spacetime. Stationary metrics possessing one, two or three Killing vectors are studied and classified. Three branches of solutions exist. Electromagnetically induced mass terms appear in two of them, including a class of solutions in harmonic functions. The static subcase is discussed too. Relations to other well-known electrovacuum metrics are elucidated.

DNase I hypersensitivity and epsilon-globin transcriptional enhancement are separable in locus control region (LCR) HS1 mutant human beta-globin YAC transgenic mice.

PubMed

Shimotsuma, Motoshi; Okamura, Eiichi; Matsuzaki, Hitomi; Fukamizu, Akiyoshi; Tanimoto, Keiji

2010-05-07

Expression of the five beta-like globin genes (epsilon, Ggamma, Agamma, delta, beta) in the human beta-globin locus depends on enhancement by the locus control region, which consists of five DNase I hypersensitive sites (5'HS1 through 5'HS5). We report here a novel enhancer activity in 5'HS1 that appears to be potent in transfected K562 cells. Deletion analyses identified a core activating element that bound to GATA-1, and a two-nucleotide mutation that disrupted GATA-1 binding in vitro abrogated 5'HS1 enhancer activity in transfection experiments. To determine the in vivo role of this GATA site, we generated multiple lines of human beta-globin YAC transgenic mice bearing the same two-nucleotide mutation. In the mutant mice, epsilon-, but not gamma-globin, gene expression in primitive erythroid cells was severely attenuated, while adult beta-globin gene expression in definitive erythroid cells was unaffected. Interestingly, DNaseI hypersensitivity near the 5'HS1 mutant sequence was eliminated in definitive erythroid cells, whereas it was only mildly affected in primitive erythroid cells. We therefore conclude that, although the GATA site in 5'HS1 is critical for efficient epsilon-globin gene expression, hypersensitive site formation per se is independent of 5'HS1 function, if any, in definitive erythroid cells.

Pure Motor Stroke Secondary to Cerebral Infarction of Recurrent Artery of Heubner after Mild Head Trauma: A Case Report.

PubMed

Yilmaz, Ali; Kizilay, Zahir; Ozkul, Ayca; Çirak, Bayram

2016-03-15

The recurrent Heubner's artery is the distal part of the medial striate artery. Occlusion of the recurrent artery of Heubner, classically contralateral hemiparesis with fasciobrachiocrural predominance, is attributed to the occlusion of the recurrent artery of Heubner and is widely known as a stroke syndrome in adults. However, isolated occlusion of the deep perforating arteries following mild head trauma also occurs extremely rarely in childhood. Here we report the case of an 11-year-old boy with pure motor stroke. The brain MRI showed an acute ischemia in the recurrent artery of Heubner supply area following mild head trauma. His fasciobrachial hemiparesis and dysarthria were thought to be secondary to the stretching of deep perforating arteries leading to occlusion of the recurrent artery of Heubner. Post-traumatic pure motor ischemic stroke can be secondary to stretching of the deep perforating arteries especially in childhood.

No changes in heme synthesis in human Friedreich´s ataxia erythroid progenitor cells.

PubMed

Steinkellner, Hannes; Singh, Himanshu Narayan; Muckenthaler, Martina U; Goldenberg, Hans; Moganty, Rajeswari R; Scheiber-Mojdehkar, Barbara; Sturm, Brigitte

2017-07-20

Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the protein frataxin. Frataxin is thought to play a role in iron-sulfur cluster biogenesis and heme synthesis. In this study, we used erythroid progenitor stem cells obtained from FRDA patients and healthy donors to investigate the putative role, if any, of frataxin deficiency in heme synthesis. We used electrochemiluminescence and qRT-PCR for frataxin protein and mRNA quantification. We used atomic absorption spectrophotometry for iron levels and a photometric assay for hemoglobin levels. Protoporphyrin IX and Ferrochelatase were analyzed using auto-fluorescence. An "IronChip" microarray analysis followed by a protein-protein interaction analysis was performed. FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis. The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported. Copyright © 2017 Elsevier B.V. All rights reserved.

A determination of the external forces required to move the benchmark active controls testing model in pure plunge and pure pitch

NASA Technical Reports Server (NTRS)

Dcruz, Jonathan

1993-01-01

In view of the strong need for a well-documented set of experimental data which is suitable for the validation and/or calibration of modern Computational Fluid Dynamics codes, the Benchmark Models Program was initiated by the Structural Dynamics Division of the NASA Langley Research Center. One of the models in the program, the Benchmark Active Controls Testing Model, consists of a rigid wing of rectangular planform with a NACA 0012 profile and three control surfaces (a trailing-edge control surface, a lower-surface spoiler, and an upper-surface spoiler). The model is affixed to a flexible mount system which allows only plunging and/or pitching motion. An approximate analytical determination of the forces required to move this model, with its control surfaces fixed, in pure plunge and pure pitch at a number of test conditions is included. This provides a good indication of the type of actuator system required to generate the aerodynamic data resulting from pure plunging and pure pitching motion, in which much interest was expressed. The analysis makes use of previously obtained numerical results.

Shunting arc plasma source for pure carbon ion beam.

PubMed

Koguchi, H; Sakakita, H; Kiyama, S; Shimada, T; Sato, Y; Hirano, Y

2012-02-01

A plasma source is developed using a coaxial shunting arc plasma gun to extract a pure carbon ion beam. The pure carbon ion beam is a new type of deposition system for diamond and other carbon materials. Our plasma device generates pure carbon plasma from solid-state carbon material without using a hydrocarbon gas such as methane gas, and the plasma does not contain any hydrogen. The ion saturation current of the discharge measured by a double probe is about 0.2 mA∕mm(2) at the peak of the pulse.

Shunting arc plasma source for pure carbon ion beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koguchi, H.; Sakakita, H.; Kiyama, S.

2012-02-15

A plasma source is developed using a coaxial shunting arc plasma gun to extract a pure carbon ion beam. The pure carbon ion beam is a new type of deposition system for diamond and other carbon materials. Our plasma device generates pure carbon plasma from solid-state carbon material without using a hydrocarbon gas such as methane gas, and the plasma does not contain any hydrogen. The ion saturation current of the discharge measured by a double probe is about 0.2 mA/mm{sup 2} at the peak of the pulse.

Superposing pure quantum states with partial prior information

NASA Astrophysics Data System (ADS)

Dogra, Shruti; Thomas, George; Ghosh, Sibasish; Suter, Dieter

2018-05-01

The principle of superposition is an intriguing feature of quantum mechanics, which is regularly exploited in many different circumstances. A recent work [M. Oszmaniec et al., Phys. Rev. Lett. 116, 110403 (2016), 10.1103/PhysRevLett.116.110403] shows that the fundamentals of quantum mechanics restrict the process of superimposing two unknown pure states, even though it is possible to superimpose two quantum states with partial prior knowledge. The prior knowledge imposes geometrical constraints on the choice of input states. We discuss an experimentally feasible protocol to superimpose multiple pure states of a d -dimensional quantum system and carry out an explicit experimental realization for two single-qubit pure states with partial prior information on a two-qubit NMR quantum information processor.

Fisher-Symmetric Informationally Complete Measurements for Pure States.

PubMed

Li, Nan; Ferrie, Christopher; Gross, Jonathan A; Kalev, Amir; Caves, Carlton M

2016-05-06

We introduce a new kind of quantum measurement that is defined to be symmetric in the sense of uniform Fisher information across a set of parameters that uniquely represent pure quantum states in the neighborhood of a fiducial pure state. The measurement is locally informationally complete-i.e., it uniquely determines these parameters, as opposed to distinguishing two arbitrary quantum states-and it is maximal in the sense of a multiparameter quantum Cramér-Rao bound. For a d-dimensional quantum system, requiring only local informational completeness allows us to reduce the number of outcomes of the measurement from a minimum close to but below 4d-3, for the usual notion of global pure-state informational completeness, to 2d-1.

Faithful Transfer Arbitrary Pure States with Mixed Resources

NASA Astrophysics Data System (ADS)

Luo, Ming-Xing; Li, Lin; Ma, Song-Ya; Chen, Xiu-Bo; Yang, Yi-Xian

2013-09-01

In this paper, we show that some special mixed quantum resource experience the same property of pure entanglement such as Bell state for quantum teleportation. It is shown that one mixed state and three bits of classical communication cost can be used to teleport one unknown qubit compared with two bits via pure resources. The schemes are easily implement with model physical techniques. Moreover, these resources are also optimal and typical for faithfully remotely prepare an arbitrary qubit, two-qubit and three-qubit states with mixed quantum resources. Our schemes are completed as same as those with pure quantum entanglement resources except only 1 bit additional classical communication cost required. The success probability is independent of the form of the mixed resources.

Pure Air`s Bailly scrubber: A four-year retrospective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manavi, G.B.; Vymazal, D.C.; Sarkus, T.A.

1997-12-31

Pure Air`s Advanced Flue Gas Desulfurization (AFGD) Clean Coal Project has completed four highly successful years of operation at NIPSCO`s Bailly Station. As part of their program, Pure Air has concluded a six-part study of system performance. This paper summarizes the results of the demonstration program, including AFGD performance on coals ranging from 2.0--2.4% sulfur. The paper highlights novel aspects of the Bailly facility, including pulverized limestone injection, air rotary sparger for oxidation, wastewater evaporation system and the production of PowerChip{reg_sign} gypsum. Operations and maintenance which have led to the facility`s notable 99.47% availability record are also discussed. A projectmore » company, Pure Air on the Lake Limited Partnership, owns the AFGD facility. Pure Air was the turn key contractor and Air Products and Chemicals, Inc. is the operator of the AFGD system.« less

Production of substantially pure fructose

DOEpatents

Hatcher, Herbert J.; Gallian, John J.; Leeper, Stephen A.

1990-01-01

A process is disclosed for the production of substantially pure fructose from sucrose-containing substrates. The process comprises converting the sucrose to levan and glucose, purifying the levan by membrane technology, hydrolyzing the levan to form fructose monomers, and recovering the fructose.

Compact objects in pure Lovelock theory

NASA Astrophysics Data System (ADS)

Dadhich, Naresh; Hansraj, Sudan; Chilambwe, Brian

For static fluid interiors of compact objects in pure Lovelock gravity (involving only one Nth order term in the equation), we establish similarity in solutions for the critical odd and even d = 2N + 1, 2N + 2 dimensions. It turns out that in critical odd d = 2N + 1 dimensions, there cannot exist any bound distribution with a finite radius, while in critical even d = 2N + 2 dimensions, all solutions have similar behavior. For exhibition of similarity, we would compare star solutions for N = 1, 2 in d = 4 Einstein and d = 6 in Gauss-Bonnet theory, respectively. We also obtain the pure Lovelock analogue of the Finch-Skea model.

Pure akinesia: an atypical manifestation of progressive supranuclear palsy.

PubMed Central

Matsuo, H; Takashima, H; Kishikawa, M; Kinoshita, I; Mori, M; Tsujihata, M; Nagataki, S

1991-01-01

Two patients with "pure akinesia" who showed the characteristic changes of progressive supranuclear palsy (PSP) at necropsy are described. They had akinesia but no rigidity or tremor, and ophthalmoplegia was not observed during the course of illness. The symptoms of "pure akinesia" was not improved by levodopa therapy but was considerably improved by L-threo-3,4-dihydroxy-phenylserine. At necropsy, pathological findings were not different from those reported for PSP. It is suggested that "pure akinesia" is an atypical manifestation of PSP, and that norepinephrinergic neurons may be involved in some types of PSP. Images PMID:1865200

Magnetic nano-oscillator driven by pure spin current.

PubMed

Demidov, Vladislav E; Urazhdin, Sergei; Ulrichs, Henning; Tiberkevich, Vasyl; Slavin, Andrei; Baither, Dietmar; Schmitz, Guido; Demokritov, Sergej O

2012-12-01

With the advent of pure-spin-current sources, spin-based electronic (spintronic) devices no longer require electrical charge transfer, opening new possibilities for both conducting and insulating spintronic systems. Pure spin currents have been used to suppress noise caused by thermal fluctuations in magnetic nanodevices, amplify propagating magnetization waves, and to reduce the dynamic damping in magnetic films. However, generation of coherent auto-oscillations by pure spin currents has not been achieved so far. Here we demonstrate the generation of single-mode coherent auto-oscillations in a device that combines local injection of a pure spin current with enhanced spin-wave radiation losses. Counterintuitively, radiation losses enable excitation of auto-oscillation, suppressing the nonlinear processes that prevent auto-oscillation by redistributing the energy between different modes. Our devices exhibit auto-oscillations at moderate current densities, at a microwave frequency tunable over a wide range. These findings suggest a new route for the implementation of nanoscale microwave sources for next-generation integrated electronics.

Production of fermented chestnut purees by lactic acid bacteria.

PubMed

Blaiotta, G; Di Capua, M; Coppola, R; Aponte, M

2012-09-03

The objective of this study was to develop a new chestnut-based puree, in order to seasonally adjust the offer and use the surplus of undersized production, providing, at the same time, a response to the growing demand for healthy and environmentally friendly products. Broken dried chestnuts have been employed to prepare purees to be fermented with six different strains of Lactobacillus (Lb.) rhamnosus and Lactobacillus casei. The fermented purees were characterized by a technological and sensorial point of view, while the employed strains were tested for their probiotic potential. Conventional in vitro tests have indicated the six lactobacilli strains as promising probiotic candidates; moreover, being the strains able to grow and to survive in chestnut puree at a population level higher than 8 log₁₀ CFU/mL along 40 days of storage at 4 °C, the bases for the production of a new food, lactose-free and with reduced fat content, have been laid. Copyright © 2012 Elsevier B.V. All rights reserved.

[Current anatomical and etiological aspects of chronic or subacute, surgical, pure mitral valve insufficiency in adults. Apropos of 75 medicosurgical cases].

PubMed

Penther, P; Boschat, J; Etienne, Y; Jobic, Y

1991-04-01

Seventy five medico-surgical cases (52 men, with a mean age at surgery of 59, and 23 women, with a mean age at surgery of 59) collected between 1983 and 1989, in an ethnically homogeneous and geographically stable population (West Brittany) confirmed that the current anatomical and etiological aspects of chronic (or subacute) pure mitral incompetence (MI) have changed radically. While rates for bacterial and ischemic etiologies remain stable, the share of rheumatic MI (14 cases) has fallen considerably, to the advantage of degenerative MI (51 cases) with a heavy male predominance (39 men) with in 33 cases rupture of the main chordae, and tending to affect the lesser mitral cusp more often. A precise diagnosis in terms of lesions and etiology is possible in almost all cases on the basis of clinical history and echocardiographic findings. In a perfectly homogeneous population, chronic surgical pure MI is currently essentially a male disease, of dystrophic origin, in patients in the 6th and 7th decades of life.

Pure field theories and MACSYMA algorithms

NASA Technical Reports Server (NTRS)

Ament, W. S.

1977-01-01

A pure field theory attempts to describe physical phenomena through singularity-free solutions of field equations resulting from an action principle. The physics goes into forming the action principle and interpreting specific results. Algorithms for the intervening mathematical steps are sketched. Vacuum general relativity is a pure field theory, serving as model and providing checks for generalizations. The fields of general relativity are the 10 components of a symmetric Riemannian metric tensor; those of the Einstein-Straus generalization are the 16 components of a nonsymmetric. Algebraic properties are exploited in top level MACSYMA commands toward performing some of the algorithms of that generalization. The light cone for the theory as left by Einstein and Straus is found and simplifications of that theory are discussed.

Purely wavelength- and amplitude-modulated quartz-enhanced photoacoustic spectroscopy.

PubMed

Patimisco, Pietro; Sampaolo, Angelo; Bidaux, Yves; Bismuto, Alfredo; Scott, Marshall; Jiang, James; Muller, Antoine; Faist, Jerome; Tittel, Frank K; Spagnolo, Vincenzo

2016-11-14

We report here on a quartz-enhanced photoacoustic (QEPAS) sensor employing a quantum cascade laser (QCL) structure capable of operating in a pure amplitude or wavelength modulation configuration. The QCL structure is composed of three electrically independent sections: Gain, Phase (PS) and Master Oscillator (MO). Selective current pumping of these three sections allows obtaining laser wavelength tuning without changes in the optical power, and power modulation without emission wavelength shifts. A pure QEPAS amplitude modulation condition is obtained by modulating the PS current, while pure wavelength modulation is achieved by modulating simultaneously the MO and PS QCL sections and slowly scanning the DC current level injected in the PS section.

A Simple Protein Synthesis Model for the PURE System Operation.

PubMed

Mavelli, Fabio; Marangoni, Roberto; Stano, Pasquale

2015-06-01

The encapsulation of transcription-translation (TX-TL) cell-free machinery inside lipid vesicles (liposomes) is a key element in synthetic cell technology. The PURE system is a TX-TL kit composed of well-characterized parts, whose concentrations are fine tunable, which works according to a modular architecture. For these reasons, the PURE system perfectly fulfils the requirements of synthetic biology and is widely used for constructing synthetic cells. In this work, we present a simplified mathematical model to simulate the PURE system operations. Based on Michaelis-Menten kinetics and differential equations, the model describes protein synthesis dynamics by using 9 chemical species, 6 reactions and 16 kinetic parameters. The model correctly predicts the time course for messenger RNA and protein production and allows quantitative predictions. By means of this model, it is possible to foresee how the PURE system species affect the mechanism of proteins synthesis and therefore help in understanding scenarios where the concentration of the PURE system components has been modified purposely or as a result of stochastic fluctuations (for example after random encapsulation inside vesicles). The model also makes the determination of response coefficients for all species involved in the TX-TL mechanism possible and allows for scrutiny on how chemical energy is consumed by the three PURE system modules (transcription, translation and aminoacylation).

Auditory Repetition Priming Is Impaired in Pure Alexic Patients

ERIC Educational Resources Information Center

Swick, Diane; Miller, Kimberly M.; Larsen, Jary

2004-01-01

Alexia without agraphia, or ''pure'' alexia, is an acquired impairment in reading that leaves writing skills intact. Repetition priming for visually presented words is diminished in pure alexia. However, it is not possible to verify whether this priming deficit is modality-specific or modality independent because reading abilities are compromised.…

[Main regulatory element (MRE) of the Danio rerio α/β-globin gene domain exerts enhancer activity toward the promoters of the embryonic-larval and adult globin genes].

PubMed

Kovina, A P; Petrova, N V; Razin, S V; Yarovaia, O V

2016-01-01

In warm-blooded vertebrates, the α- and β-globin genes are organized in domains of different types and are regulated in different fashion. In cold-blooded vertebrates and, in particular, the tropical fish Danio rerio, the α- and β-globin genes form two gene clusters. A major D. rerio globin gene cluster is in chromosome 3 and includes the α- and β-globin genes of embryonic-larval and adult types. The region upstream of the cluster contains c16orf35, harbors the main regulatory element (MRE) of the α-globin gene domain in warm-blooded vertebrates. In this study, transient transfection of erythroid cells with genetic constructs containing a reporter gene under the control of potential regulatory elements of the domain was performed to characterize the promoters of the embryonic-larval and adult α- and β-globin genes of the major cluster. Also, in the 5th intron of c16orf35 in Danio reriowas detected a functional analog of the warm-blooded vertebrate MRE. This enhancer stimulated activity of the promoters of both adult and embryonic-larval α- and β-globin genes.

Self-esteem in pure bullies and bully/victims: a longitudinal analysis.

PubMed

Pollastri, Alisha R; Cardemil, Esteban V; O'Donnell, Ellen H

2010-08-01

Past research on the self-esteem of bullies has produced equivocal results. Recent studies have suggested that the inconsistent findings may be due, in part, to the failure to account for bully/victims: those children who both bully and are victims of bullying. In this longitudinal study, we examined the distinctions among pure bullies, pure victims, bully/victims, and noninvolved children in a sample of 307 middle school students. Analyses of cross-sectional and longitudinal results supported the importance of distinguishing between pure bullies and bully/victims. In addition, results revealed some interesting sex differences: girls in the pure bully and bully/victim groups reported significant increases in self-esteem over time, with girls in the pure bully group reporting the greatest increase, whereas boys in these groups reported no significant changes in self-esteem over time.

Uniform and accelerated degradation of pure iron patterned by Pt disc arrays

PubMed Central

Huang, Tao; Zheng, Yufeng

2016-01-01

Pure iron has been confirmed as a promising biodegradable metal. However, the degradation rate of pure iron should be accelerated to meet the clinical requirements. In this work, two different designs of platinum disc arrays, including sizes of Φ20 μm × S5 μm and Φ4 μm × S4 μm, have been coated on the surface of pure iron. Corrosion tests showed the platinum discs formed plenty of galvanic cells with the iron matrix which significantly accelerated the degradation of pure iron. Simultaneously, due to the designability of the shape, size as well as distribution of Pt discs, the degradation rate as well as degradation uniformity of pure iron can be effectively controlled by coating with platinum discs. The cytotoxicity test results unveiled that Pt discs patterned pure iron exhibited almost no toxicity to human umbilical vein endothelial cells, but a significant inhibition on proliferation of vascular smooth muscle cells. In addition, the hemolysis rate of Pt discs patterned pure iron was lower than 1%. Moreover, Pt discs also effectively reduced the number of adhered platelets. All these results indicated that Pt discs patterning is an effective way to accelerate degradation and improve biocompatibility of pure iron. PMID:27033380

Making Pure Fine-Grained Inorganic Powder

NASA Technical Reports Server (NTRS)

Wood, C.

1985-01-01

Sustained arc plasma chemical reactor fabricates very-fine-grained inorganic solids having low thermal conductivity. Powder fabrication method, based on plasma tube technique produces pure solids without contamination commonly produced by grinding.

Research on the Applicable Method of Valuation of Pure Electric Used vehicles

NASA Astrophysics Data System (ADS)

Cai, yun; Tan, zhengping; Wang, yidong; Mao, pan

2018-03-01

With the rapid growth in the ownership of pure electric vehicles, the research on the valuation of used electric vehicles has become the key to the development of the pure electric used vehicle market. The paper analyzed the application of the three value assessment methods, current market price method, capitalized earning method and replacement cost method, in pure electric used vehicles, and draws a conclusion that the replacement cost method is more suitable for pure electric used car. At the same time, the article also conducted a parametric correction exploration research, aiming at the characteristics of pure electric vehicles and replacement cost of the constituent factors. Through the analysis of the applicability parameters of physical devaluation, functional devaluation and economic devaluation, the revised replacement cost method can be used for the valuation of purely used electric vehicles for private use.

Redefining dermatomyositis: a description of new diagnostic criteria that differentiate pure dermatomyositis from overlap myositis with dermatomyositis features.

PubMed

Troyanov, Yves; Targoff, Ira N; Payette, Marie-Pier; Raynauld, Jean-Pierre; Chartier, Suzanne; Goulet, Jean-Richard; Bourré-Tessier, Josiane; Rich, Eric; Grodzicky, Tamara; Fritzler, Marvin J; Joyal, France; Koenig, Martial; Senécal, Jean-Luc

2014-11-01

Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM.Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival.Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high

[Pure akinesia presenting with antecollis].

PubMed

Ota, Satoru; Tsuchiya, Kuniaki

2005-10-01

We reported a 77-year-old woman having pure akinesia who presented with antecollis induced by L-threo-3, 4-dihydroxyphenylserine (L-DOPS). At the age of 70, she noticed increasing difficulty in standing up from a seat and moving. Afterward, she developed gait disturbance with difficulty in initiating walking, frozen gait, and postural instability. At 73 years of age, she came to our hospital, because she gradually fell down easily. Neurological examination disclosed mild akinesia with freezing symptom and kinésie paradoxale. No evidence of dementia, supranuclear gaze palsy, pseudobulbar palsy, rigidity, or tremor were present. As she developed akinesia, of which L-dopa therapy achieved little improvement, we clinically diagnosed as having pure akinesia. At age 74, L-DOPS was administered at a dose of 300mg per day and gradually increased up to 900mg per day, because her postural reflex was markedly disturbed and gait showed severe unsteadiness. Amelioration of frozen gait and unsteadiness were recognized, but efficacy of L-DOPS was temporal. It is well known that reported cases of pure akinesia were pathologically diagnosed as having progressive supranuclear palsy (PSP) or pallido-nigro-luysian atrophy. Therefore, the present case was suspected as having pathological changes which involved degeneration of the substantia nigra and globus pallidus. After three years of treatment with L-DOPS, at age 77, she was admitted to our hospital for abrupt onset of her dropped head. Hematological examinations were normal, cervical MRI showed no evidence of paracervical muscular atrophy, and electromyography did not demonstrate any abnormal change. In addition, her posterior cervical muscles showed abnormally high tension, so the dropped head was considered due to antecollis. After admission, antecollis disappeared rapidly following discontinuation of L-DOPS. However the mechanism of drug induced dystonia is imperfectly understood on the basis of the clinical course, L-DOPS was

Entropy for quantum pure states and quantum H theorem

NASA Astrophysics Data System (ADS)

Han, Xizhi; Wu, Biao

2015-06-01

We construct a complete set of Wannier functions that are localized at both given positions and momenta. This allows us to introduce the quantum phase space, onto which a quantum pure state can be mapped unitarily. Using its probability distribution in quantum phase space, we define an entropy for a quantum pure state. We prove an inequality regarding the long-time behavior of our entropy's fluctuation. For a typical initial state, this inequality indicates that our entropy can relax dynamically to a maximized value and stay there most of time with small fluctuations. This result echoes the quantum H theorem proved by von Neumann [Zeitschrift für Physik 57, 30 (1929), 10.1007/BF01339852]. Our entropy is different from the standard von Neumann entropy, which is always zero for quantum pure states. According to our definition, a system always has bigger entropy than its subsystem even when the system is described by a pure state. As the construction of the Wannier basis can be implemented numerically, the dynamical evolution of our entropy is illustrated with an example.

Pure E and B polarization maps via Wiener filtering

NASA Astrophysics Data System (ADS)

Bunn, Emory F.; Wandelt, Benjamin

2017-08-01

In order to draw scientific conclusions from observations of cosmic microwave background (CMB) polarization, it is necessary to separate the contributions of the E and B components of the data. For data with incomplete sky coverage, there are ambiguous modes, which can be sourced by either E or B signals. Techniques exist for producing "pure" E and B maps, which are guaranteed to be free of cross-contamination, although the standard method, which involves constructing an eigenbasis, has a high computational cost. We show that such pure maps can be thought of as resulting from the application of a Wiener filter to the data. This perspective leads to far more efficient methods of producing pure maps. Moreover, by expressing the idea of purification in the general framework of Wiener filtering (i.e., maximization of a posterior probability), it leads to a variety of generalizations of the notion of pure E and B maps, e.g., accounting for noise or other contaminants in the data as well as correlations with temperature anisotropy.

Pure state `really' informationally complete with rank-1 POVM

NASA Astrophysics Data System (ADS)

Wang, Yu; Shang, Yun

2018-03-01

What is the minimal number of elements in a rank-1 positive operator-valued measure (POVM) which can uniquely determine any pure state in d-dimensional Hilbert space H_d? The known result is that the number is no less than 3d-2. We show that this lower bound is not tight except for d=2 or 4. Then we give an upper bound 4d-3. For d=2, many rank-1 POVMs with four elements can determine any pure states in H_2. For d=3, we show eight is the minimal number by construction. For d=4, the minimal number is in the set of {10,11,12,13}. We show that if this number is greater than 10, an unsettled open problem can be solved that three orthonormal bases cannot distinguish all pure states in H_4. For any dimension d, we construct d+2k-2 adaptive rank-1 positive operators for the reconstruction of any unknown pure state in H_d, where 1≤ k ≤ d.

Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium.

PubMed

Xia, Dengning; He, Yuan; Li, Qiuxia; Hu, Cunde; Huang, Wei; Zhang, Yunhai; Wan, Feng; Wang, Chi; Gan, Yong

2018-01-10

Pure drug nanoparticles (NPs) represent a promising formulation for improved drug solubility and controlled dissolution velocity. However, limited absorption by the intestinal epithelium remains challenge to their clinical application, and little is known about how these NPs within the cells are transported. To improve cellular uptake and transport of pure nanodrug in cells, here, a lipid covered saquinavir (SQV) pure drug NP (Lipo@nanodrug) was designed by modifying a pure SQV NP (nanodrug) with a phospholipid bilayer. We studied their endocytosis, intracellular trafficking mechanism using Caco-2 cell model. Uptake of Lipo@nanodrug by Caco-2 cells was 1.91-fold greater than that of pure nanodrug via processes involving cell lipid raft. The transcellular transport of Lipo@nanodrug across Caco-2 monolayers was 3.75-fold and 1.92-fold higher than that of coarse crystals and pure nanodrug, respectively. Within cells, Lipo@nanodrug was mainly localized in the endoplasmic reticulum and Golgi apparatus, leading to transcytosis of Lipo@nanodrug across intestinal epithelial cells, whereas pure nanodrug tended to be retained and to dissolve in cell and removed by P-gp-mediated efflux. In rats, the oral bioavailability of the model drug SQV after Lipo@nanodrug administration was 4.29-fold and 1.77-fold greater than after coarse crystal and pure nanodrug administration, respectively. In conclusion, addition of a phospholipid bilayer to pure drug NP increased their cellular uptake and altered their intracellular processing, helping to improve drug transport across intestinal epithelium. To our knowledge, this is the first presentation of the novel phospholipid bilayer covered SQV pure drug NP design, and a mechanistic study on intracellular trafficking in in vitro cell models has been described. The findings provide a new platform for oral delivery of poorly water-soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase.

PubMed

Latagliata, Roberto; Montagna, Chiara; Porrini, Raffaele; Di Veroli, Ambra; Leonetti, Sabrina Crescenzi; Niscola, Pasquale; Ciccone, Fabrizio; Spadea, Antonio; Breccia, Massimo; Maurillo, Luca; Rago, Angela; Spirito, Francesca; Cedrone, Michele; De Muro, Marianna; Montanaro, Marco; Andriani, Alessandro; Bagnato, Antonino; Montefusco, Enrico; Alimena, Giuliana

2016-06-01

At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1-43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra-hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uziel, Orit, E-mail: Oritu@clalit.org.il; Kanfer, Gil; Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv

Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized thatmore » some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway.« less

Can a pure vector gravitational wave mimic a pure tensor one?

NASA Astrophysics Data System (ADS)

Allen, Bruce

2018-06-01

In the general theory of relativity, gravitational waves have two possible polarizations, which are transverse and traceless with helicity ±2 . Some alternative theories contain additional helicity 0 and helicity ±1 polarization modes. Here, we consider a hypothetical "pure vector" theory in which gravitational waves have only two possible polarizations, with helicity ±1 . We show that if these polarizations are allowed to rotate as the wave propagates, then for certain source locations on the sky, the strain outputs of three ideal interferometric gravitational wave detectors can exactly reproduce the strain outputs predicted by general relativity.

Combined Cognitive Training vs. Memory Strategy Training in Healthy Older Adults.

PubMed

Li, Bing; Zhu, Xinyi; Hou, Jianhua; Chen, Tingji; Wang, Pengyun; Li, Juan

2016-01-01

As mnemonic utilization deficit in older adults associates with age-related decline in executive function, we hypothesized that memory strategy training combined with executive function training might induce larger training effect in memory and broader training effects in non-memory outcomes than pure memory training. The present study compared the effects of combined cognitive training (executive function training plus memory strategy training) to pure memory strategy training. Forty healthy older adults were randomly assigned to a combined cognitive training group or a memory strategy training group. A control group receiving no training was also included. Combined cognitive training group received 16 sessions of training (eight sessions of executive function training followed by eight sessions of memory strategy training). Memory training group received 16 sessions of memory strategy training. The results partly supported our hypothesis in that indeed improved performance on executive function was only found in combined training group, whereas memory performance increased less in combined training compared to memory strategy group. Results suggest that combined cognitive training may be less efficient than pure memory training in memory outcomes, though the influences from insufficient training time and less closeness between trained executive function and working memory could not be excluded; however it has broader training effects in non-memory outcomes. www.chictr.org.cn, identifier ChiCTR-OON-16007793.

Combined Cognitive Training vs. Memory Strategy Training in Healthy Older Adults

PubMed Central

Li, Bing; Zhu, Xinyi; Hou, Jianhua; Chen, Tingji; Wang, Pengyun; Li, Juan

2016-01-01

As mnemonic utilization deficit in older adults associates with age-related decline in executive function, we hypothesized that memory strategy training combined with executive function training might induce larger training effect in memory and broader training effects in non-memory outcomes than pure memory training. The present study compared the effects of combined cognitive training (executive function training plus memory strategy training) to pure memory strategy training. Forty healthy older adults were randomly assigned to a combined cognitive training group or a memory strategy training group. A control group receiving no training was also included. Combined cognitive training group received 16 sessions of training (eight sessions of executive function training followed by eight sessions of memory strategy training). Memory training group received 16 sessions of memory strategy training. The results partly supported our hypothesis in that indeed improved performance on executive function was only found in combined training group, whereas memory performance increased less in combined training compared to memory strategy group. Results suggest that combined cognitive training may be less efficient than pure memory training in memory outcomes, though the influences from insufficient training time and less closeness between trained executive function and working memory could not be excluded; however it has broader training effects in non-memory outcomes. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR-OON-16007793. PMID:27375521

Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia

PubMed Central

Rinaldi, Carlo; Schmidt, Thomas; Situ, Alan J.; Johnson, Janel O.; Lee, Philip R.; Chen, Ke-lian; Bott, Laura C.; Fadó, Rut; Harmison, George H.; Parodi, Sara; Grunseich, Christopher; Renvoisé, Benoît; Biesecker, Leslie G.; De Michele, Giuseppe; Santorelli, Filippo M.; Filla, Alessandro; Stevanin, Giovanni; Dürr, Alexandra; Brice, Alexis; Casals, Núria; Traynor, Bryan J.; Blackstone, Craig; Ulmer, Tobias S.; Fischbeck, Kenneth H.

2017-01-01

IMPORTANCE The family of genes implicated in hereditary spastic paraplegias (HSPs) is quickly expanding, mostly owing to the widespread availability of next-generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains unavailable for many patients. OBJECTIVE To identify the genetic cause for a novel form of pure autosomal dominant HSP. DESIGN, SETTING, AND PARTICIPANTS We examined and followed up with a family presenting to a tertiary referral center for evaluation of HSP for a decade until August 2014. Whole-exome sequencing was performed in 4 patients from the same family and was integrated with linkage analysis. Sanger sequencing was used to confirm the presence of the candidate variant in the remaining affected and unaffected members of the family and screen the additional patients with HSP. Five affected and 6 unaffected participants from a 3-generation family with pure adult-onset autosomal dominant HSP of unknown genetic origin were included. Additionally, 163 unrelated participants with pure HSP of unknown genetic cause were screened. MAIN OUTCOME AND MEASURE Mutation in the neuronal isoform of carnitine palmitoyl-transferase (CPT1C) gene. RESULTS We identified the nucleotide substitution c.109C>T in exon 3 of CPT1C, which determined the base substitution of an evolutionarily conserved Cys residue for an Arg in the gene product. This variant strictly cosegregated with the disease phenotype and was absent in online single-nucleotide polymorphism databases and in 712 additional exomes of control participants. We showed that CPT1C, which localizes to the endoplasmic reticulum, is expressed in motor neurons and interacts with atlastin-1, an endoplasmic reticulum protein encoded by the ATL1 gene known to be mutated in pure HSPs. The mutation, as indicated by nuclear magnetic resonance spectroscopy studies, alters the protein conformation and reduces the mean (SD) number (213.0 [46.99] vs 81.9 [14.2]; P < .01) and size (0.29 [0.01] vs 0.26 [0

No Association Between Time of Onset of Hearing Loss (Childhood Versus Adulthood) and Self-Reported Hearing Handicap in Adults.

PubMed

Aarhus, Lisa; Tambs, Kristian; Engdahl, Bo

2015-12-01

This study examined the association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap in adults. This is a population-based cohort study of 2,024 adults (mean = 48 years) with hearing loss (binaural pure-tone average 0.5-4 kHz ≥ 20 dB HL) who completed a hearing handicap questionnaire. In childhood, the same persons (N = 2,024) underwent audiometry in a school investigation (at ages 7, 10, and 13 years), in which 129 were diagnosed with sensorineural hearing loss (binaural pure-tone average 0.5-4 kHz ≥ 20 dB HL), whereas 1,895 had normal hearing thresholds. Hearing handicap was measured in adulthood as the sum-score of various speech perception and social impairment items (15 items). The sum-score increased with adult hearing threshold level (p < .001). After adjustment for adult hearing threshold level, hearing aid use, adult age, sex, and socioeconomic status, there was no significant difference in hearing handicap sum-score between the group with childhood-onset hearing loss (n = 129) and the group with adult-onset hearing loss (n = 1,895; p = .882). Self-reported hearing handicap in adults increased with hearing threshold level. After adjustment for adult hearing threshold level, this cohort study revealed no significant association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap.

Effect of humidity on fretting wear of several pure metals

NASA Technical Reports Server (NTRS)

Goto, H.; Buckley, D. H.

1984-01-01

Fretting wear experiments with several pure metals were conducted in air at various relative humidity levels. The materials used were iron, aluminum, copper, silver, chromium, titanium, and nickel. Each pure metal had a maximum fretting wear volume at a specific humidity level RH sub max that was not dependent on mechanical factors such as contact load, fretting amplitude, and frequency in the ranges studied. The weight loss due to fretting wear at RH sub max for each pure metal decreased with increasing heat of oxygen adsorption on the metal, indicating that adhesive wear dominated at RH sub max.

UV-induced lethal sectoring and pure mutant clones in yeast.

PubMed

Hannan, M A; Duck, P; Nasim, A

1976-08-01

The induction of lethal sectoring and pure mutant clones by ultraviolet light has been studied in a homogeneous G1 population of Saccharomyces cerevisiae grown in a normal growth medium. At the lowest UV dose of 250 ergs, which corresponds to a shoulder in the survival curve, all mutants appeared as pure clones. At higher doses the frequency of mosaic mutants progressively increased. These results indicate a relationship between the highest frequency of complete mutants and the maximum repair activity. In addition, the frequency of lethal sectoring at all doses tested was too low to account for the origin of pure mutant clones.

Primary pure choriocarcinoma of the liver.

PubMed

Fernández Alonso, J; Sáez, C; Pérez, P; Montaño, A; Japón, M A

1992-04-01

We report a pure choriocarcinoma of the liver studied at necropsy. The tumour was diagnosed ante-mortem and treated by chemotherapy with no satisfactory response. Previous cases of hepatic choriocarcinoma are reviewed and criteria to diagnose this extragonadal neoplasm are recommended.

Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

ClinicalTrials.gov

2017-05-17

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Myeloid Leukemia in Remission; Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell

Generic pure quantum states as steady states of quasi-local dissipative dynamics

NASA Astrophysics Data System (ADS)

Karuvade, Salini; Johnson, Peter D.; Ticozzi, Francesco; Viola, Lorenza

2018-04-01

We investigate whether a generic pure state on a multipartite quantum system can be the unique asymptotic steady state of locality-constrained purely dissipative Markovian dynamics. In the tripartite setting, we show that the problem is equivalent to characterizing the solution space of a set of linear equations and establish that the set of pure states obeying the above property has either measure zero or measure one, solely depending on the subsystems’ dimension. A complete analytical characterization is given when the central subsystem is a qubit. In the N-partite case, we provide conditions on the subsystems’ size and the nature of the locality constraint, under which random pure states cannot be quasi-locally stabilized generically. Also, allowing for the possibility to approximately stabilize entangled pure states that cannot be exact steady states in settings where stabilizability is generic, our results offer insights into the extent to which random pure states may arise as unique ground states of frustration-free parent Hamiltonians. We further argue that, to a high probability, pure quantum states sampled from a t-design enjoy the same stabilizability properties of Haar-random ones as long as suitable dimension constraints are obeyed and t is sufficiently large. Lastly, we demonstrate a connection between the tasks of quasi-local state stabilization and unique state reconstruction from local tomographic information, and provide a constructive procedure for determining a generic N-partite pure state based only on knowledge of the support of any two of the reduced density matrices of about half the parties, improving over existing results.

Electron Acoustic Waves in Pure Ion Plasmas

NASA Astrophysics Data System (ADS)

Anderegg, F.; Driscoll, C. F.; Dubin, D. H. E.; O'Neil, T. M.

2009-11-01

Electron Acoustic Waves (EAW) are the low frequency branch of electrostatic plasma waves. These waves exist in neutralized plasmas, pure electron plasmas and in pure ion plasmasfootnotetextF. Anderegg et al., PRL 102, 095001 (2009) and PoP 16, 055705 (2009). (where the name is deceptive). Here, we observe standing mθ= 0 mz= 1 EAWs in a pure ion plasma column. At small amplitude, the EAWs have a phase velocity vph ˜1.4 v, and the frequencies are in close agreement with theory. At moderate amplitudes, waves can be excited over a broad range of frequencies, with observed phase velocities in the range of 1.4 v <=vph <=2.1 v. This frequency variability comes from the plasma adjusting its velocity distribution so as to make the EAW resonant with the drive frequency. Our wave-coherent laser-induced fluorescence diagnostic shows that particles slower than vph oscillate in phase with the wave, while particles moving faster than vph oscillate 180^o out of phase with the wave. From a fluid perspective, this gives an unusual negative dynamical compressibility. That is, the wave pressure oscillations are 180^o out of phase from the density oscillations, almost fully canceling the electrostatic restoring force, giving the low and malleable frequency.

Effect of Discharge Time on Plasma Electrolytic Borocarbonitriding of Pure Iron

NASA Astrophysics Data System (ADS)

Jin, Xiaoyue; Wu, Jie; Wang, Bin; Yang, Xuan; Chen, Lin; Qu, Yao; Xue, Wenbin

The plasma electrolytic borocarbonitriding (PEB/C/N) process on pure iron was carried out in 25% borax solution with glycerine and carbamide additives under different discharge time at 360V. The morphology and structure of PEB/C/N hardened layers were analyzed by SEM and XRD. The hardness profiles of hardened layers were measured by microhardness test. Corrosion behavior of PEB/C/N layers was evaluated by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). Their wear performance was carried out using a pin-disc friction and wear tester under dry sliding test. The PEB/C/N samples mainly consisted of α-Fe, Fe2B, Fe3C, FeN, FeB, Fe2O3 and Fe4N phases, and the Fe2B phase was the dominant phase in the boride layer. It was found that the thickness of boride layer increased with the discharge time and reached 14μm after 60min treatment. The microhardness of the boride layer was up to 2100HV, which was much higher than that of the bare pure iron (about 150HV). After PEB/C/N treatment, the corrosion resistance of pure iron was slightly improved. The friction coefficient of PEB/C/N treated pure iron decreased to 0.129 from 0.556 of pure iron substrate. The wear rate of the PEB/C/N layer after 60min under dry sliding against ZrO2 ball was only 1/10 of that of the bare pure iron. The PEB/C/N treatment is an effective way to improve the wear behavior of pure iron.

Measurement of generation-dependent proliferation rates and death rates during mouse erythroid progenitor cell differentiation.

PubMed

Akbarian, Vahe; Wang, Weijia; Audet, Julie

2012-05-01

Herein, we describe an experimental and computational approach to perform quantitative carboxyfluorescein diacetate succinimidyl ester (CFSE) cell-division tracking in cultures of primary colony-forming unit-erythroid (CFU-E) cells, a hematopoietic progenitor cell type, which is an important target for the treatment of blood disorders and for the manufacture of red blood cells. CFSE labeling of CFU-Es isolated from mouse fetal livers was performed to examine the effects of stem cell factor (SCF) and erythropoietin (EPO) in culture. We used a dynamic model of proliferation based on the Smith-Martin representation of the cell cycle to extract proliferation rates and death rates from CFSE time-series. However, we found that to accurately represent the cell population dynamics in differentiation cultures of CFU-Es, it was necessary to develop a model with generation-specific rate parameters. The generation-specific rates of proliferation and death were extracted for six generations (G(0) -G(5) ) and they revealed that, although SCF alone or EPO alone supported similar total cell outputs in culture, stimulation with EPO resulted in significantly higher proliferation rates from G(2) to G(5) and higher death rates in G(2) , G(3) , and G(5) compared with SCF. In addition, proliferation rates tended to increase from G(1) to G(5) in cultures supplemented with EPO and EPO + SCF, while they remained lower and more constant across generations with SCF. The results are consistent with the notion that SCF promotes CFU-E self-renewal while EPO promotes CFU-E differentiation in culture. Copyright © 2012 International Society for Advancement of Cytometry.

Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese children.

PubMed

Guiyedi, Vincent; Chanseaud, Youri; Fesel, Constantin; Snounou, Georges; Rousselle, Jean-Claude; Lim, Pharat; Koko, Jean; Namane, Abdelkader; Cazenave, Pierre-André; Kombila, Maryvonne; Pied, Sylviane

2007-04-25

Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFalpha), with the manifestation of CM in Gabonese children. To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFalpha concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFalpha concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM.

Self-Reactivities to the Non-Erythroid Alpha Spectrin Correlate with Cerebral Malaria in Gabonese Children

PubMed Central

Fesel, Constantin; Snounou, Georges; Rousselle, Jean-Claude; Lim, Pharat; Koko, Jean; Namane, Abdelkader; Cazenave, Pierre-André; Kombila, Maryvonne; Pied, Sylviane

2007-01-01

Background Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children. Methodology To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFα concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. Results/Conclusion The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFα concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM. PMID:17460756

Factors affecting sensitivity to frequency change in school-age children and adults.

PubMed

Buss, Emily; Taylor, Crystal N; Leibold, Lori J

2014-10-01

The factors affecting frequency discrimination in school-age children are poorly understood. The goal of the present study was to evaluate developmental effects related to memory for pitch and the utilization of temporal fine structure. Listeners were 5.1- to 13.6-year-olds and adults, all with normal hearing. A subgroup of children had musical training. The task was a 3-alternative forced choice in which listeners identified the interval with the higher frequency tone or the tone characterized by frequency modulation (FM). The standard was 500 or 5000 Hz, and the FM rate was either 2 or 20 Hz. Thresholds tended to be higher for younger children than for older children and adults for all conditions, although this age effect was smaller for FM detection than for pure-tone frequency discrimination. Neither standard frequency nor modulation rate affected the child/adult difference FM thresholds. Children with musical training performed better than their peers on pure-tone frequency discrimination at 500 Hz. Testing frequency discrimination using a low-rate FM detection task may minimize effects related to cognitive factors like memory for pitch or training effects. Maturation of frequency discrimination does not appear to differ across conditions in which listeners are hypothesized to rely on temporal cues and place cues.

Characteristic chromatographic fingerprint study of short-chain fatty acids in human milk, infant formula, pure milk and fermented milk by gas chromatography-mass spectrometry.

PubMed

Jiang, Zhenzuo; Liu, Yanan; Zhu, Yan; Yang, Jing; Sun, Lili; Chai, Xin; Wang, Yuefei

2016-09-01

Human milk, infant formula, pure milk and fermented milk as food products or dietary supplements provide a range of nutrients required to both infants and adults. Recently, a growing body of evidence has revealed the beneficial roles of short-chain fatty acids (SCFAs), a subset of fatty acids produced from the fermentation of dietary fibers by gut microbiota. The objective of this study was to establish a chromatographic fingerprint technique to investigate SCFAs in human milk and dairy products by gas chromatography coupled with mass spectrometry. The multivariate method for principal component analysis assessed differences between milk types. Human milk, infant formula, pure milk and fermented milk were grouped independently, mainly because of differences in formic acid, acetic acid, propionic acid and hexanoic acid levels. This method will be important for the assessment of SCFAs in human milk and various dairy products.

Endoscopic Endonasal Surgery for Purely Intrathird Ventricle Craniopharyngioma.

PubMed

Nishioka, Hiroshi; Fukuhara, Noriaki; Yamaguchi-Okada, Mitsuo; Yamada, Shozo

2016-07-01

Extended endoscopic transsphenoidal surgery (EETS) is a safe and effective treatment for many suprasellar craniopharyngiomas, including those with third-ventricle involvement. Craniopharyngioma entirely within the third ventricle (purely intraventricular type), however, is generally regarded unsuitable for treatment with EETS. Three patients underwent total removal of a purely intraventricular craniopharyngioma with inferior extension via EETS by direct incision of the bulging, stretched ventricular floor and fine dissection from the ventricular wall. In 2 patients with an anteriorly displaced chiasm, the space between the chiasm and pituitary stalk created a wide corridor to the ventricle, whereas in the third case, in which the infrachiasmal space was somewhat narrowed, partial sacrifice of the pituitary gland was necessary to obtain sufficient space. Despite preservation of the stalk in 2 patients, hypopituitarism and diabetes insipidus developed after surgery. There was no other complication including obesity. Selected patients with purely intraventricular craniopharyngioma can be treated effectively and safely with EETS. Those with inferior extension in the interpeduncular fossa and anterior displacement of the chiasm may be suitable candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

"Vague and artificial": the historically elusive distinction between pure and applied science.

PubMed

Gooday, Graeme

2012-09-01

This essay argues for the historicity of applied science as a contested category within laissez-faire Victorian British science. This distinctively pre-twentieth-century notion of applied science as a self-sustaining, autonomous enterprise was thrown into relief from the 1880s by a campaign on the part of T. H. Huxley and his followers to promote instead the primacy of "pure" science. Their attempt to relegate applied science to secondary status involved radically reconfiguring it as the mere application of pre-existing pure science. This new notion of extrinsically funded pure science that would produce only contingently future social benefits as a mere by-product came under pressure during World War I, when military priorities focused attention once again on science for immediate utility. This threatened the Cambridge-based promoters of self-referential pure science who collectively published Science and the Nation in 1917. Yet most contributors to this work discussed forms of "applied" science that had no prior "pure" form. Even the U.K.'s leading government scientist, Lord Moulton, dismissed the book's provocative distinction between pure and applied science as unhelpfully "vague and artificial."

No Association Between Time of Onset of Hearing Loss (Childhood Versus Adulthood) and Self-Reported Hearing Handicap in Adults

PubMed Central

Tambs, Kristian; Engdahl, Bo

2015-01-01

Purpose This study examined the association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap in adults. Methods This is a population-based cohort study of 2,024 adults (mean = 48 years) with hearing loss (binaural pure-tone average 0.5–4 kHz ≥ 20 dB HL) who completed a hearing handicap questionnaire. In childhood, the same persons (N = 2,024) underwent audiometry in a school investigation (at ages 7, 10, and 13 years), in which 129 were diagnosed with sensorineural hearing loss (binaural pure-tone average 0.5–4 kHz ≥ 20 dB HL), whereas 1,895 had normal hearing thresholds. Results Hearing handicap was measured in adulthood as the sum-score of various speech perception and social impairment items (15 items). The sum-score increased with adult hearing threshold level (p < .001). After adjustment for adult hearing threshold level, hearing aid use, adult age, sex, and socioeconomic status, there was no significant difference in hearing handicap sum-score between the group with childhood-onset hearing loss (n = 129) and the group with adult-onset hearing loss (n = 1,895; p = .882). Conclusion Self-reported hearing handicap in adults increased with hearing threshold level. After adjustment for adult hearing threshold level, this cohort study revealed no significant association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap. PMID:26649831

Characterization of pure and composite resorcinol formaldehyde aerogels doped with silver

NASA Astrophysics Data System (ADS)

Attia, S. M.; Abdelfatah, M. S.; Mossad, M. M.

2017-07-01

A series of Resorcinol Formaldehyde (RF) aerogels composites with nanoparticles of sliver were prepared by the sol-gel method at different concentrations doped silver. FTIR spectra of pure and composite RF aerogels show six absorption bands attributed to -OH groups bonded to the benzene ring, stretching of -CH2- bonds and aromatic ring stretching. FTIR results ensured that sliver particles do not interact with aerogel network. UV-visible spectrum of pure silver show an absorbance peak at 420 nm attributed to the surface plasmon excitation of sliver Nano spheres. UV-visible spectral of pure and composite RF aerogels shows a steep decrease of absorption with wavelength after 500 nm, making sample’s color reddish brown. TEM and SEM images of pure and composite RF aerogels revealed that the textural arrangement of RF aerogels can be described as densely packed small nodules.

Dissecting limiting factors of the Protein synthesis Using Recombinant Elements (PURE) system

PubMed Central

Li, Jun; Zhang, Chi; Huang, Poyi; Kuru, Erkin; Forster-Benson, Eliot T. C.; Church, George M.

2017-01-01

ABSTRACT Reconstituted cell-free protein synthesis systems such as the Protein synthesis Using Recombinant Elements (PURE) system give high-throughput and controlled access to in vitro protein synthesis. Here we show that compared with the commercial S30 crude extract based RTS 100 E. coli HY system, the PURE system has less mRNA degradation and produces up to ∼6-fold full-length proteins. However the majority of polypeptides PURE produces are partially translated or inactive since the signal from firefly luciferase (Fluc) translated in PURE is only ∼2/3rd of that measured using the RTS 100 E. coli HY S30 system. Both of the 2 batch systems suffer from low ribosome recycling efficiency when translating proteins from 82 kD to 224 kD. A systematic fed-batch analysis of PURE shows replenishment of 6 small molecule substrates individually or in combination before energy depletion increased Fluc protein yield by ∼1.5 to ∼2-fold, while creatine phosphate and magnesium have synergistic effects when added to the PURE system. Additionally, while adding EF-P to PURE reduced full-length protein translated, it increased the fraction of functional protein and reduced partially translated protein probably by slowing down the translation process. Finally, ArfA, rather than YaeJ or PrfH, helped reduce ribosome stalling when translating Fluc and improved system productivity in a template-dependent fashion. PMID:28702280

Dissecting limiting factors of the Protein synthesis Using Recombinant Elements (PURE) system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jun; Zhang, Chi; Huang, Poyi

Reconstituted cell-free protein synthesis systems such as the Protein synthesis Using Recombinant Elements (PURE) system give high-throughput and controlled access to in vitro protein synthesis. Here we show that compared with the commercial S30 crude extract based RTS 100 E. coli HY system, the PURE system has less mRNA degradation and produces up to ~6-fold full-length proteins. However the majority of polypeptides PURE produces are partially translated or inactive since the signal from firefly luciferase (Fluc) translated in PURE is only ~2/3 rd of that measured using the RTS 100 E. coli HY S30 system. Both of the 2 batchmore » systems suffer from low ribosome recycling efficiency when translating proteins from 82 k D to 224 k D. A systematic fed-batch analysis of PURE shows replenishment of 6 small molecule substrates individually or in combination before energy depletion increased Fluc protein yield by ~1.5 to ~2-fold, while creatine phosphate and magnesium have synergistic effects when added to the PURE system. Additionally, while adding EF-P to PURE reduced full-length protein translated, it increased the fraction of functional protein and reduced partially translated protein probably by slowing down the translation process. Finally, ArfA, rather than YaeJ or PrfH, helped reduce ribosome stalling when translating Fluc and improved system productivity in a template-dependent fashion.« less

Dissecting limiting factors of the Protein synthesis Using Recombinant Elements (PURE) system

DOE PAGES

Li, Jun; Zhang, Chi; Huang, Poyi; ...

2017-05-09

Reconstituted cell-free protein synthesis systems such as the Protein synthesis Using Recombinant Elements (PURE) system give high-throughput and controlled access to in vitro protein synthesis. Here we show that compared with the commercial S30 crude extract based RTS 100 E. coli HY system, the PURE system has less mRNA degradation and produces up to ~6-fold full-length proteins. However the majority of polypeptides PURE produces are partially translated or inactive since the signal from firefly luciferase (Fluc) translated in PURE is only ~2/3 rd of that measured using the RTS 100 E. coli HY S30 system. Both of the 2 batchmore » systems suffer from low ribosome recycling efficiency when translating proteins from 82 k D to 224 k D. A systematic fed-batch analysis of PURE shows replenishment of 6 small molecule substrates individually or in combination before energy depletion increased Fluc protein yield by ~1.5 to ~2-fold, while creatine phosphate and magnesium have synergistic effects when added to the PURE system. Additionally, while adding EF-P to PURE reduced full-length protein translated, it increased the fraction of functional protein and reduced partially translated protein probably by slowing down the translation process. Finally, ArfA, rather than YaeJ or PrfH, helped reduce ribosome stalling when translating Fluc and improved system productivity in a template-dependent fashion.« less

Concurrence of assistance and Mermin inequality on three-qubit pure states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Dong Pyo; Kim, Taewan; Lee, Kyungjin

2010-04-15

We study a relation between the concurrence of assistance and the Mermin inequality on three-qubit pure states and claim that if a three-qubit pure state has a minimal concurrence of assistance greater than 1/2 then the state violates some Mermin inequality. In this work, we analytically show that our claim holds for several classes and also find that it can be generalized to the set of all three-qubit pure states by exploiting previous numerical work [C. Emary and C. W. J. Beenakker, Phys. Rev. A 69, 032317 (2004)].

Anti-fibrotic effects of L-2-oxothiazolidine-4-carboxylic acid via modulation of nuclear factor erythroid 2-related factor 2 in rats.

PubMed

Kim, In Hee; Kim, Dae-Ghon; Hao, Peipei; Wang, Yunpeng; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik

2012-06-01

L-2-Oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione in tissues. The present study was designed to investigate anti-fibrotic and anti-oxidative effects of OTC via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in an in vivo thioacetamide (TAA)-induced hepatic fibrosis model. Treatment with OTC (80 or 160 mg/kg) improved serum liver function parameters and significantly ameliorated liver fibrosis. The OTC treatment groups exhibited significantly lower expression of α-smooth muscle actin, transforming growth factor-β 1, and collagen α 1 mRNA than that in the TAA model group. Furthermore, the OTC treatment groups showed a significant decrease in hepatic malondialdehyde level compared to that in the TAA model group. Nrf2 and heme oxygenase-1 expression increased significantly in the OTC treatment groups compared with that in the TAA model group. Taken together, these results suggest that OTC restores the anti- oxidative system by upregulating Nrf2; thus, ameliorating liver injury and a fibrotic reaction.

A Multinomial Model for Identifying Significant Pure-Tone Threshold Shifts

ERIC Educational Resources Information Center

Schlauch, Robert S.; Carney, Edward

2007-01-01

Purpose: Significant threshold differences on retest for pure-tone audiometry are often evaluated by application of ad hoc rules, such as a shift in a pure-tone average or in 2 adjacent frequencies that exceeds a predefined amount. Rules that are so derived do not consider the probability of observing a particular audiogram. Methods: A general…

CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

ClinicalTrials.gov

2017-06-12

Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

General entanglement-assisted transformation for bipartite pure quantum states

NASA Astrophysics Data System (ADS)

Song, Wei; Huang, Yan; Nai-LeLiu; Chen, Zeng-Bing

2007-01-01

We introduce the general catalysts for pure entanglement transformations under local operations and classical communications in such a way that we disregard the profit and loss of entanglement of the catalysts per se. As such, the possibilities of pure entanglement transformations are greatly expanded. We also design an efficient algorithm to detect whether a k × k general catalyst exists for a given entanglement transformation. This algorithm can also be exploited to witness the existence of standard catalysts.

Visibility in a pure model of golden spiral phyllotaxis.

PubMed

Herrmann, Burghard

2018-07-01

This paper considers the geometry of plants with golden spiral phyllotaxis, i.e. growing leaf by leaf on a spiral with golden divergence angle, via the simplest mathematical model, a cylinder with regular arrangement of points on its surface. As is well-known, Fibonacci numbers appear by means of the order of parastichies. This fact is shown to be a straightforward application of logical consequences to a particular model with respect to pure visibility. This notion is very similar to that of contact parastichies. The 3-D cylindrical model of golden spiral phyllotaxis abstracts from the form of leaves and identifies them with points. Pure visibility is specified in the 2-D representation so that common sense parastichies can be scrutinized. The main Theorem states that the orders of the purely most visible parastichies are Fibonacci numbers. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of Hearing Handicap in Adults with Auditory Neuropathy Spectrum Disorder.

PubMed

Prabhu, Prashanth

2017-08-01

The present study attempted to evaluate hearing handicap in adults with auditory neuropathy spectrum disorder (ANSD). The study also attempted to determine if gender, pure tone average, speech identification scores (SIS), and reported duration of hearing loss could predict the hearing handicap in adults with ANSD. Hearing Handicap Inventory for Adults and Hearing Handicap Questionnaire were administered to 50 adults with ANSD. Using both the scales, there was a significant hearing handicap in both the social and emotional domains in adults with ANSD. SIS was a good predictor of hearing handicap compared to other variables. The poor SIS can affect communication skills leading to higher degree of social handicap. The ignorance regarding the exact cause for their hearing problems and lack of appropriate management strategies could lead to emotional problems in individuals with ANSD. However, further studies are essential for determining hearing handicap with the use of hearing aids and cochlear implants.

Assessment of semen quality in pure and crossbred Jersey bulls

PubMed Central

Kumar, Umesh; Gawande, Ajay P.; Sahatpure, Sunil K.; Patil, Manoj S.; Lakde, Chetan K.; Bonde, Sachin W.; Borkar, Pradnyankur L.; Poharkar, Ajay J.; Ramteke, Baldeo R.

2015-01-01

Aim: To compare the seminal attributes of neat, pre-freeze (at equilibration), and post-freeze (24 h after freezing) semen in pure and crossbred Jersey bulls. Materials and Methods: Total 36 ejaculates (3 ejaculates from each bull) were collected from 6 pure Jersey and 6 crossbred Jersey bulls and evaluated for various seminal attributes during neat, pre-freeze, and post-freeze semen. Results: The mean (±standard error [SE]) values of neat semen characteristics in pure and crossbred Jersey bulls were recorded such as volume (ml), color, consistency, mass activity (scale: 0-5), and sperm concentration (millions/ml). The extended semen was further investigated at pre-freeze and post-freeze stages and the mean (±SE) values recorded at neat, pre-freeze, and post-freeze semen were compared between pure and crossbred Jersey bulls; sperm motility (80.55±1.70%, 62.77±1.35%, 46.11±1.43% vs. 80.00±1.80%, 65.00±1.66%, 47.22±1.08%), live sperm count (83.63±1.08%, 71.72±1.09%, 58.67±1.02% vs. 80.00±1.08%, 67.91±1.20%, 51.63±0.97%), total abnormal sperm count (8.38±0.32%, 12.30±0.39%, 16.75±0.42% vs. 9.00±0.45%, 12.19±0.48%, 18.11±0.64%), hypo-osmotic swelling (HOS) reacted spermatozoa (71.88±0.77%, 62.05±0.80%, 47.27±1.05% vs. 72.77±1.02%, 62.11±0.89%, 45.94±1.33%), acrosome integrity (89.05±0.83%, 81.33±0.71%, 71.94±0.86% vs. 86.55±0.57%, 78.66±0.42%, 69.38±0.53%), and DNA integrity (99.88±0.07%, 100, 99.66±0.11% vs. 99.94±0.05%, 100, 99.44±0.18%,). The volume, color, consistency, sperm concentration, and initial motility in pure and crossbred Jersey bulls did not differ significantly (p>0.05). The mass activity was significantly (p<0.05) higher in pure Jersey as compare to crossbred Jersey bulls. Live sperm percentage and acrosome integrity was significantly (p<0.01) higher in pure Jersey bulls as compared to crossbred Jersey bulls. However, no statistical difference (p>0.05) was observed in abnormal sperm; HOS reacted spermatozoa and DNA

A new nanospray drying method for the preparation of nicergoline pure nanoparticles

NASA Astrophysics Data System (ADS)

Martena, Valentina; Censi, Roberta; Hoti, Ela; Malaj, Ledjan; Di Martino, Piera

2012-06-01

Three different batches of pure nanoparticles (NPs) of nicergoline (NIC) were prepared by spray drying a water:ethanol solution by a new Nano Spray Dryer Büchi B-90. Spherical pure NPs were obtained, and several analytical techniques such as differential scanning calorimetry and X-ray powder diffractometry permitted to assess their amorphous character. A comparison of the solubility, intrinsic dissolution, and drug release of original particles and pure amorphous NPs were determined, revealing an interesting improvement of biopharmaceutical properties of amorphous NPs, due to both amorphous properties and nanosize dimensions. Since in a previous work, the high-thermodynamic stability of amorphous NIC was demonstrated, this study is addressed toward the formulation of NIC as pure amorphous NPs.

Porcine reproductive and respiratory syndrome type 1 viruses induce hypoplasia of erythroid cells and myeloid cell hyperplasia in the bone marrow of experimentally infected piglets independently of the viral load and virulence.

PubMed

Amarilla, Shyrley Paola; Gómez-Laguna, Jaime; Carrasco, Librado; Rodríguez-Gómez, Irene M; Caridad Y Ocerín, José M; Graham, Simon P; Frossard, Jean-Pierre; Steinbach, Falko; Salguero, Francisco J

2017-03-01

Porcine reproductive and respiratory syndrome viruses (PRRSV) present a wide phenotypic and genetic diversity. Experimental infections have demonstrated viral replication, including highly pathogenic strains (HP-PRRSV), in primary lymphoid organs such as the thymus. However, studies of the bone marrow are scarce but necessary to help elucidate the immunobiology of PRRSV strains of differing virulence. In this study, whereas viral RNA was detected within the bone marrow of animals experimentally infected with both low virulent Lelystad (LV) and 215-06 PRRSV-1 strains and with the highly virulent SU1-bel strain, PRRSV positive cells were only occasionally detected in one SU1-bel infected animal. PRRSV RNA levels were associated to circulating virus with the highest levels detected in LV-infected pigs. At 3 dpi, a decrease in the proportion of haematopoietic tissue and number of erythroid cells in all infected groups was associated with an increase in TUNEL or cleaved caspase 3 labelling and higher counts of myeloid cells compared to control. The expression of IL-1α and IL-6 was elevated at the beginning of the infection in all infected animals. The expression of TNF-α was increased at the end of the study in all infected groups with respect to control. Different PRRSV-1 strains induced, presummably by indirect mechanisms and independently of viral load and strain virulence, moderate and sustained hypoplasia of erythroid cells and myeloid cell hyperplasia at early stages of infection. These changes were paralleled by a peak in the local expression of IL-1α, IL-6 and TNF-α in all infected groups. Copyright © 2017 Elsevier B.V. All rights reserved.

Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5.

PubMed

Ashino, Takashi; Ohkubo-Morita, Haruyo; Yamamoto, Masayuki; Yoshida, Takemi; Numazawa, Satoshi

2014-01-01

Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2)-deficient (Nrf2(-⧸-)) mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2(-⧸-) mouse livers were lower than that in wild-type mouse livers. Nrf2(-⧸-) mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression.

Growth of erythroid burst-forming units (BFU-E) in cultures of canine bone marrow and peripheral blood cells: effect of serum from irradiated dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreja, L.; Baltschukat, K.; Nothdurft, W.

1988-08-01

Erythroid burst-forming units (BFU-E) from canine bone marrow and peripheral blood could be grown in methylcellulose in the presence of an appropriate batch of fetal calf serum (FCS), transferrin, and erythropoietin (Epo). However, improved colony formation (size and number of bursts) was obtained when serum from total body irradiated dogs was present in the culture. This serum, obtained from dogs at day 9 after total body irradiation with a dose of 3.9 Gy, reduced markedly the Epo requirement of BFU-E. Furthermore, it allowed the omission of FCS from the culture medium if cholesterol and bovine serum albumin (BSA) were usedmore » as FCS substitutes. BFU-E concentrations were found to be rather different in the peripheral blood and in bone marrow samples from different sites (i.e., iliac crest, sternum, and humerus) of normal beagles. The studies further show that canine bone marrow BFU-E can be cryopreserved in liquid nitrogen.« less

Physical and Spiritual Education within the Framework of Pure Life

ERIC Educational Resources Information Center

Bagheri Noaparast, Khosrow

2013-01-01

This paper aims at showing the dimensions of spirituality in childhood education by suggesting a new analysis of the concept of "pure life" used in the Qur'an. Putting spirituality in the framework of the pure life provides us with a rich framework in dealing with spirituality as the latter will be extended to all dimensions of a life. In the…

Heat engine driven by purely quantum information.

PubMed

Park, Jung Jun; Kim, Kang-Hwan; Sagawa, Takahiro; Kim, Sang Wook

2013-12-06

The key question of this Letter is whether work can be extracted from a heat engine by using purely quantum mechanical information. If the answer is yes, what is its mathematical formula? First, by using a bipartite memory we show that the work extractable from a heat engine is bounded not only by the free energy change and the sum of the entropy change of an individual memory but also by the change of quantum mutual information contained inside the memory. We then find that the engine can be driven by purely quantum information, expressed as the so-called quantum discord, forming a part of the quantum mutual information. To confirm it, as a physical example we present the Szilard engine containing a diatomic molecule with a semipermeable wall.

Quantum gravity in the Eddington purely affine picture

NASA Astrophysics Data System (ADS)

Martellini, M.

1984-06-01

It was shown by Kijowski and Tulczjew that pure gravity with a cosmological constant can be obtained by a covariant Legendre transformation of a purely affine Lagrangian "in the manner of Eddington" constructed from a symmetric linear connection. In this paper I prove by explicit calculations that the Eddington Lagrangian is equivalent, in the sense which gives the same field equations, to a polynomial effective Lagrangian which turns out to be power-counting renormalizable. Then a formal proof of the unitarity of this theory is stated in the Kugo-Ojima formalism on the basis of the existence of two local Becchi-Rouet-Stora symmetries. These supertransformations are related to the algebra of the diffeomorphisms of the space-time, as well as to that of the volume-preserving space-time transformations which are not fixed by the gauge fixing used for the diffeomorphism group itself. Furthermore, I find that in the purely affine picture quantum gravity exhibits an infrared freedom. Since now the self-coupling constant is given by the cosmological constant, such a property could explain the observed almost zero value of the cosmological term at very large distances, i.e., to very low energies.

Inhibition of G9a methyltransferase stimulates fetal hemoglobin production by facilitating LCR/γ-globin looping.

PubMed

Krivega, Ivan; Byrnes, Colleen; de Vasconcellos, Jaira F; Lee, Y Terry; Kaushal, Megha; Dean, Ann; Miller, Jeffery L

2015-07-30

Induction of fetal hemoglobin (HbF) production in adult erythrocytes can reduce the severity of sickle cell disease and β-thalassemia. Transcription of β-globin genes is regulated by the distant locus control region (LCR), which is brought into direct gene contact by the LDB1/GATA-1/TAL1/LMO2-containing complex. Inhibition of G9a H3K9 methyltransferase by the chemical compound UNC0638 activates fetal and represses adult β-globin gene expression in adult human hematopoietic precursor cells, but the underlying mechanisms are unclear. Here we studied UNC0638 effects on β-globin gene expression using ex vivo differentiation of CD34(+) erythroid progenitor cells from peripheral blood of healthy adult donors. UNC0638 inhibition of G9a caused dosed accumulation of HbF up to 30% of total hemoglobin in differentiated cells. Elevation of HbF was associated with significant activation of fetal γ-globin and repression of adult β-globin transcription. Changes in gene expression were associated with widespread loss of H3K9me2 in the locus and gain of LDB1 complex occupancy at the γ-globin promoters as well as de novo formation of LCR/γ-globin contacts. Our findings demonstrate that G9a establishes epigenetic conditions preventing activation of γ-globin genes during differentiation of adult erythroid progenitor cells. In this view, manipulation of G9a represents a promising epigenetic approach for treatment of β-hemoglobinopathies.

Diagnosing pure-electron plasmas with internal particle flux probes.

PubMed

Kremer, J P; Pedersen, T Sunn; Marksteiner, Q; Lefrancois, R G; Hahn, M

2007-01-01

Techniques for measuring local plasma potential, density, and temperature of pure-electron plasmas using emissive and Langmuir probes are described. The plasma potential is measured as the least negative potential at which a hot tungsten filament emits electrons. Temperature is measured, as is commonly done in quasineutral plasmas, through the interpretation of a Langmuir probe current-voltage characteristic. Due to the lack of ion-saturation current, the density must also be measured through the interpretation of this characteristic thereby greatly complicating the measurement. Measurements are further complicated by low densities, low cross field transport rates, and large flows typical of pure-electron plasmas. This article describes the use of these techniques on pure-electron plasmas in the Columbia Non-neutral Torus (CNT) stellarator. Measured values for present baseline experimental parameters in CNT are phi(p)=-200+/-2 V, T(e)=4+/-1 eV, and n(e) on the order of 10(12) m(-3) in the interior.

Fast word reading in pure alexia: "fast, yet serial".

PubMed

Bormann, Tobias; Wolfer, Sascha; Hachmann, Wibke; Neubauer, Claudia; Konieczny, Lars

2015-01-01

Pure alexia is a severe impairment of word reading in which individuals process letters serially with a pronounced length effect. Yet, there is considerable variation in the performance of alexic readers with generally very slow, but also occasionally fast responses, an observation addressed rarely in previous reports. It has been suggested that "fast" responses in pure alexia reflect residual parallel letter processing or that they may even be subserved by an independent reading system. Four experiments assessed fast and slow reading in a participant (DN) with pure alexia. Two behavioral experiments investigated frequency, neighborhood, and length effects in forced fast reading. Two further experiments measured eye movements when DN was forced to read quickly, or could respond faster because words were easier to process. Taken together, there was little support for the proposal that "qualitatively different" mechanisms or reading strategies underlie both types of responses in DN. Instead, fast responses are argued to be generated by the same serial-reading strategy.

[A study on the bond interface between low-fusing dental porcelain and pure titanium].

PubMed

Mo, A; Cen, Y; Liao, Y; Wang, J; Shi, X

2001-09-01

To evaluate the bond interface between low fusing dental porcelain and pure titanium by observing the topography and detecting the ionic diffusion in the interface area. The low fusing-porcelain La-porcelain produced by the authors or Vita Titankeramik porcelain was fused to the surfaces of pure titanium. The topography of the interface between pure titanium and porcelain, and the structure of experimental materials were observed with SEM. The state of ionic diffusion in the interface area was investigated with EPMA. Excellent permeation and diffusion of La-porcelain were observed on the surfaces of pure titanium. The diffusion of ions of stannum and silicon was discovered in the interface area. The microstructure of La-porcelain to pure titanium bond interface was finer than that of Vita Titankeramik porcelain. Excellent bond can be produced in the interface between La-porcelain and pure titanium. The bonding mechanism may involve mechanical bond and chemical bond. The ionic diffusion of stannum plays an important role in the bonding of porcelain to pure titanium.

The Socioeconomic Impact of Hearing Loss in US Adults

PubMed Central

Emmett, Susan D.; Francis, Howard W.

2014-01-01

Objective To evaluate the associations between hearing loss and educational attainment, income, and unemployment/underemployment in US adults. Study design National cross-sectional survey. Setting Ambulatory examination centers. Patients Adults aged 20-69 years who participated in the 1999-2002 cycles of the National Health and Nutrition Examination Survey (NHANES) audiometric evaluation and income questionnaire (n = 3379). Intervention(s) Pure tone audiometry, with hearing loss defined by World Health Organization criteria of bilateral pure tone average >25 decibels (0.5,1,2,4 kHz). Main outcome measure(s) Low educational attainment, defined as not completing high school; low income, defined as family income less than $20,000/year, and unemployment or underemployment, defined as not having a job or working less than 35 hours per week. Results Individuals with hearing loss had 3.21 times higher odds of low educational attainment (95% CI: 2.20-4.68) compared to normal-hearing individuals. Controlling for education, age, sex, and race, individuals with hearing loss had 1.58 times higher odds of low income (95% CI: 1.16-2.15) and 1.98 times higher odds of being unemployed or underemployed (95% CI: 1.38-2.85) compared to normal-hearing individuals. Conclusions Hearing loss is associated with low educational attainment in US adults. Even after controlling for education and important demographic factors, hearing loss is independently associated with economic hardship, including both low income and unemployment/underemployment. The societal impact of hearing loss is profound in this nationally representative study and should be further evaluated with longitudinal cohorts. PMID:25158616

Inclusive Literature in the Library and the Classroom: The Importance of Young Adult and Children's Books that Portray Characters with Disabilities

ERIC Educational Resources Information Center

Wopperer, Emily

2011-01-01

Literature for children and young adults is written for many different reasons. It is written purely to entertain, to help children and young adults understand the world they live in, or to help cope with problems they face. It can also be written to introduce new places, ideas, or situations to its readers, or to portray characters with whom…

Pure endmember extraction using robust kernel archetypoid analysis for hyperspectral imagery

NASA Astrophysics Data System (ADS)

Sun, Weiwei; Yang, Gang; Wu, Ke; Li, Weiyue; Zhang, Dianfa

2017-09-01

A robust kernel archetypoid analysis (RKADA) method is proposed to extract pure endmembers from hyperspectral imagery (HSI). The RKADA assumes that each pixel is a sparse linear mixture of all endmembers and each endmember corresponds to a real pixel in the image scene. First, it improves the re8gular archetypal analysis with a new binary sparse constraint, and the adoption of the kernel function constructs the principal convex hull in an infinite Hilbert space and enlarges the divergences between pairwise pixels. Second, the RKADA transfers the pure endmember extraction problem into an optimization problem by minimizing residual errors with the Huber loss function. The Huber loss function reduces the effects from big noises and outliers in the convergence procedure of RKADA and enhances the robustness of the optimization function. Third, the random kernel sinks for fast kernel matrix approximation and the two-stage algorithm for optimizing initial pure endmembers are utilized to improve its computational efficiency in realistic implementations of RKADA, respectively. The optimization equation of RKADA is solved by using the block coordinate descend scheme and the desired pure endmembers are finally obtained. Six state-of-the-art pure endmember extraction methods are employed to make comparisons with the RKADA on both synthetic and real Cuprite HSI datasets, including three geometrical algorithms vertex component analysis (VCA), alternative volume maximization (AVMAX) and orthogonal subspace projection (OSP), and three matrix factorization algorithms the preconditioning for successive projection algorithm (PreSPA), hierarchical clustering based on rank-two nonnegative matrix factorization (H2NMF) and self-dictionary multiple measurement vector (SDMMV). Experimental results show that the RKADA outperforms all the six methods in terms of spectral angle distance (SAD) and root-mean-square-error (RMSE). Moreover, the RKADA has short computational times in offline

A 3.0-kb deletion including an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene in an individual with the Bm phenotype.

PubMed

Sano, R; Kuboya, E; Nakajima, T; Takahashi, Y; Takahashi, K; Kubo, R; Kominato, Y; Takeshita, H; Yamao, H; Kishida, T; Isa, K; Ogasawara, K; Uchikawa, M

2015-04-01

We developed a sequence-specific primer PCR (SSP-PCR) for detection of a 5.8-kb deletion (B(m) 5.8) involving an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene. Using this SSP-PCR, we performed genetic analysis of 382 individuals with Bm or ABm. The 5.8-kb deletion was found in 380 individuals, and disruption of the GATA motif in the regulatory element was found in one individual. Furthermore, a novel 3.0-kb deletion involving the element (B(m) 3.0) was demonstrated in the remaining individual. Comparisons of single-nucleotide polymorphisms and microsatellites in intron 1 between B(m) 5.8 and B(m) 3.0 suggested that these deletions occurred independently. © 2014 International Society of Blood Transfusion.

chemf: A purely functional chemistry toolkit.

PubMed

Höck, Stefan; Riedl, Rainer

2012-12-20

Although programming in a type-safe and referentially transparent style offers several advantages over working with mutable data structures and side effects, this style of programming has not seen much use in chemistry-related software. Since functional programming languages were designed with referential transparency in mind, these languages offer a lot of support when writing immutable data structures and side-effects free code. We therefore started implementing our own toolkit based on the above programming paradigms in a modern, versatile programming language. We present our initial results with functional programming in chemistry by first describing an immutable data structure for molecular graphs together with a couple of simple algorithms to calculate basic molecular properties before writing a complete SMILES parser in accordance with the OpenSMILES specification. Along the way we show how to deal with input validation, error handling, bulk operations, and parallelization in a purely functional way. At the end we also analyze and improve our algorithms and data structures in terms of performance and compare it to existing toolkits both object-oriented and purely functional. All code was written in Scala, a modern multi-paradigm programming language with a strong support for functional programming and a highly sophisticated type system. We have successfully made the first important steps towards a purely functional chemistry toolkit. The data structures and algorithms presented in this article perform well while at the same time they can be safely used in parallelized applications, such as computer aided drug design experiments, without further adjustments. This stands in contrast to existing object-oriented toolkits where thread safety of data structures and algorithms is a deliberate design decision that can be hard to implement. Finally, the level of type-safety achieved by Scala highly increased the reliability of our code as well as the productivity of

Eco-Cities: Possible or Purely Utopian?

DTIC Science & Technology

2009-12-01

00-2009 to 00-00-2009 4. TITLE AND SUBTITLE Eco-Cities: Possible or Purely Utopian? 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...2005, Disney modified their building plans for Hong Kong Disneyland by shifting the angle of the front gate by twelve degrees in order to abide by

Relations among pure-tone sound stimuli, neural activity, and the loudness sensation

NASA Technical Reports Server (NTRS)

Howes, W. L.

1972-01-01

Both the physiological and psychological responses to pure-tone sound stimuli are used to derive formulas which: (1) relate the loudness, loudness level, and sound-pressure level of pure tones; (2) apply continuously over most of the acoustic regime, including the loudness threshold; and (3) contain no undetermined coefficients. Some of the formulas are fundamental for calculating the loudness of any sound. Power-law formulas relating the pure-tone sound stimulus, neural activity, and loudness are derived from published data.

Equivalence and test-retest reproducibility of conventional and extended-high-frequency audiometric thresholds obtained using pure-tone and narrow-band-noise stimuli.

PubMed

John, Andrew B; Kreisman, Brian M

2017-09-01

Extended high-frequency (EHF) audiometry is useful for evaluating ototoxic exposures and may relate to speech recognition, localisation and hearing aid benefit. There is a need to determine whether common clinical practice for EHF audiometry using tone and noise stimuli is reliable. We evaluated equivalence and compared test-retest (TRT) reproducibility for audiometric thresholds obtained using pure tones and narrowband noise (NBN) from 0.25 to 16 kHz. Thresholds and test-retest reproducibility for stimuli in the conventional (0.25-6 kHz) and EHF (8-16 kHz) frequency ranges were compared in a repeated-measures design. A total of 70 ears of adults with normal hearing. Thresholds obtained using NBN were significantly lower than thresholds obtained using pure tones from 0.5 to 16 kHz, but not 0.25 kHz. Good TRT reproducibility (within 2 dB) was observed for both stimuli at all frequencies. Responses at the lower limit of the presentation range for NBN centred at 14 and 16 kHz suggest unreliability for NBN as a threshold stimulus at these frequencies. Thresholds in the conventional and EHF ranges showed good test-retest reproducibility, but differed between stimulus types. Care should be taken when comparing pure-tone thresholds with NBN thresholds especially at these frequencies.

Pure akinesia: a kinematic analysis in a case responsive to rotigotine

PubMed Central

Di Fabio, Roberto; Serrao, Mariano; Pierelli, Francesco; Fragiotta, Gaia; Sandrini, Giorgio

2013-01-01

Summary A patient with pure akinesia is described. This rare gait disorder, poorly responsive to therapy, is characterized by gait impairment which may be associated with handwriting and speech difficulties, in the absence of further signs of extrapyramidal involvement. Here, we report the improvement in a patient suffering from pure akinesia after low doses of rotigotine, a non-ergolinic dopamine agonist, detailing the kinematic analysis before and after the treatment. After therapy, an improvement in all of the gait parameters, particularly gait speed, was observed with a trend toward normalization. Our case report suggests that rotigotine may be a therapeutic option in cases of pure akinesia. PMID:24125564

Implicit Reading in Chinese Pure Alexia

ERIC Educational Resources Information Center

Shan, Chunlei; Zhu, Renjing; Xu, Mingwei; Luo, Benyan; Weng, Xuchu

2010-01-01

A number of recent studies have shown that some patients with pure alexia display evidence of implicit access to lexical and semantic information about words that they cannot read explicitly. This phenomenon has not been investigated systematically in Chinese patients. We report here a case study of a Chinese patient who met the criteria for pure…

Synthesis and photoluminescence of ultra-pure germanium nanoparticles

NASA Astrophysics Data System (ADS)

Chivas, R.; Yerci, S.; Li, R.; Dal Negro, L.; Morse, T. F.

2011-09-01

We have used aerosol deposition to synthesize defect and micro-strain free, ultra-pure germanium nanoparticles. Transmission electron microscopy images show a core-shell configuration with highly crystalline core material. Powder X-ray diffraction measurements verify the presence of highly pure, nano-scale germanium with average crystallite size of 30 nm and micro-strain of 0.058%. X-ray photoelectron spectroscopy demonstrates that GeO x ( x ⩽ 2) shells cover the surfaces of the nanoparticles. Under optical excitation, these nanoparticles exhibit two separate emission bands at room temperature: a visible emission at 500 nm with 0.5-1 ns decay times and an intense near-infrared emission at 1575 nm with up to ˜20 μs lifetime.

Lattice modes of the chirally pure and racemic phases of tyrosine crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belyanchikov, M. A.; Gorelik, V. S., E-mail: gorelik@sci.lebedev.ru; Gorshunov, B. P.

High-Q librational modes have been found to be present in the infrared absorption and Raman spectra of chirally pure L-tyrosine. Such modes can serve as terahertz radiation detectors and generators in chirally pure biostructures.

Pure drug nanoparticles in tablets: what are the dissolution limitations?

NASA Astrophysics Data System (ADS)

Heng, Desmond; Ogawa, Keiko; Cutler, David J.; Chan, Hak-Kim; Raper, Judy A.; Ye, Lin; Yun, Jimmy

2010-06-01

There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 ± 2.7% to 72.3 ± 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

Tribological Properties of Surface-Textured and Plasma-Nitrided Pure Titanium Under Oil Lubrication Condition

NASA Astrophysics Data System (ADS)

Zhang, Baosen; Dong, Qiangsheng; Ba, Zhixin; Wang, Zhangzhong; Shi, Hancheng; Xue, Yanting

2018-01-01

Plasma nitriding was conducted as post-treatment for surface texture on pure titanium to obtain a continuous nitriding layer. Supersonic fine particles bombarding (SFPB) was carried out to prepare surface texture. The surface morphologies and chemical composition were analyzed using scanning electron microscope and energy disperse spectroscopy. The microstructures of modified layers were characterized by transmission electron microscope. The tribological properties of surface-textured and duplex-treated pure titanium under oil lubrication condition were systematically investigated in the ball-on-plate reciprocating mode. The effects of applied load and sliding velocity on the tribological behavior were analyzed. The results show that after duplex treatments, the grains size in modified layer becomes slightly larger, and hardness is obviously improved. Wear resistance of duplex-treated pure titanium is significantly improved referenced to untreated and surface-textured pure titanium, which is 3.22 times as much as untreated pure titanium and 2.15 times of that for surface-textured pure titanium, respectively.

In vitro degradation of pure Mg in response to glucose

NASA Astrophysics Data System (ADS)

Zeng, Rong-Chang; Li, Xiao-Ting; Li, Shuo-Qi; Zhang, Fen; Han, En-Hou

2015-08-01

Magnesium and its alloys are promising biodegradable biomaterials but are still challenging to be used in person with high levels of blood glucose or diabetes. To date, the influence of glucose on magnesium degradation has not yet been elucidated, this issue requires more attention. Herein, we present pure Mg exhibiting different corrosion responses to saline and Hank’s solutions with different glucose contents, and the degradation mechanism of pure Mg in the saline solution with glucose in comparison with mannitol as a control. On one hand, the corrosion rate of pure Mg increases with the glucose concentration in saline solutions. Glucose rapidly transforms into gluconic acid, which attacks the oxides of the metal and decreases the pH of the solution; it also promotes the absorption of chloride ions on the Mg surface and consequently accelerates corrosion. On the other hand, better corrosion resistance is obtained with increasing glucose content in Hank’s solution due to the fact that glucose coordinates Ca2+ ions in Hank’s solution and thus improves the formation of Ca-P compounds on the pure Mg surface. This finding will open up new avenues for research on the biodegradation of bio-Mg materials in general, which could yield many new and interesting results.

In vitro degradation of pure Mg in response to glucose

PubMed Central

Zeng, Rong-Chang; Li, Xiao-Ting; Li, Shuo-Qi; Zhang, Fen; Han, En-Hou

2015-01-01

Magnesium and its alloys are promising biodegradable biomaterials but are still challenging to be used in person with high levels of blood glucose or diabetes. To date, the influence of glucose on magnesium degradation has not yet been elucidated, this issue requires more attention. Herein, we present pure Mg exhibiting different corrosion responses to saline and Hank’s solutions with different glucose contents, and the degradation mechanism of pure Mg in the saline solution with glucose in comparison with mannitol as a control. On one hand, the corrosion rate of pure Mg increases with the glucose concentration in saline solutions. Glucose rapidly transforms into gluconic acid, which attacks the oxides of the metal and decreases the pH of the solution; it also promotes the absorption of chloride ions on the Mg surface and consequently accelerates corrosion. On the other hand, better corrosion resistance is obtained with increasing glucose content in Hank’s solution due to the fact that glucose coordinates Ca2+ ions in Hank’s solution and thus improves the formation of Ca-P compounds on the pure Mg surface. This finding will open up new avenues for research on the biodegradation of bio-Mg materials in general, which could yield many new and interesting results. PMID:26264413

A Hybrid Sensing Approach for Pure and Adulterated Honey Classification

PubMed Central

Subari, Norazian; Saleh, Junita Mohamad; Shakaff, Ali Yeon Md; Zakaria, Ammar

2012-01-01

This paper presents a comparison between data from single modality and fusion methods to classify Tualang honey as pure or adulterated using Linear Discriminant Analysis (LDA) and Principal Component Analysis (PCA) statistical classification approaches. Ten different brands of certified pure Tualang honey were obtained throughout peninsular Malaysia and Sumatera, Indonesia. Various concentrations of two types of sugar solution (beet and cane sugar) were used in this investigation to create honey samples of 20%, 40%, 60% and 80% adulteration concentrations. Honey data extracted from an electronic nose (e-nose) and Fourier Transform Infrared Spectroscopy (FTIR) were gathered, analyzed and compared based on fusion methods. Visual observation of classification plots revealed that the PCA approach able to distinct pure and adulterated honey samples better than the LDA technique. Overall, the validated classification results based on FTIR data (88.0%) gave higher classification accuracy than e-nose data (76.5%) using the LDA technique. Honey classification based on normalized low-level and intermediate-level FTIR and e-nose fusion data scored classification accuracies of 92.2% and 88.7%, respectively using the Stepwise LDA method. The results suggested that pure and adulterated honey samples were better classified using FTIR and e-nose fusion data than single modality data. PMID:23202033

A hybrid sensing approach for pure and adulterated honey classification.

PubMed

Subari, Norazian; Mohamad Saleh, Junita; Md Shakaff, Ali Yeon; Zakaria, Ammar

2012-10-17

This paper presents a comparison between data from single modality and fusion methods to classify Tualang honey as pure or adulterated using Linear Discriminant Analysis (LDA) and Principal Component Analysis (PCA) statistical classification approaches. Ten different brands of certified pure Tualang honey were obtained throughout peninsular Malaysia and Sumatera, Indonesia. Various concentrations of two types of sugar solution (beet and cane sugar) were used in this investigation to create honey samples of 20%, 40%, 60% and 80% adulteration concentrations. Honey data extracted from an electronic nose (e-nose) and Fourier Transform Infrared Spectroscopy (FTIR) were gathered, analyzed and compared based on fusion methods. Visual observation of classification plots revealed that the PCA approach able to distinct pure and adulterated honey samples better than the LDA technique. Overall, the validated classification results based on FTIR data (88.0%) gave higher classification accuracy than e-nose data (76.5%) using the LDA technique. Honey classification based on normalized low-level and intermediate-level FTIR and e-nose fusion data scored classification accuracies of 92.2% and 88.7%, respectively using the Stepwise LDA method. The results suggested that pure and adulterated honey samples were better classified using FTIR and e-nose fusion data than single modality data.

Too little, too late: reduced visual span and speed characterize pure alexia.

PubMed

Starrfelt, Randi; Habekost, Thomas; Leff, Alexander P

2009-12-01

Whether normal word reading includes a stage of visual processing selectively dedicated to word or letter recognition is highly debated. Characterizing pure alexia, a seemingly selective disorder of reading, has been central to this debate. Two main theories claim either that 1) Pure alexia is caused by damage to a reading specific brain region in the left fusiform gyrus or 2) Pure alexia results from a general visual impairment that may particularly affect simultaneous processing of multiple items. We tested these competing theories in 4 patients with pure alexia using sensitive psychophysical measures and mathematical modeling. Recognition of single letters and digits in the central visual field was impaired in all patients. Visual apprehension span was also reduced for both letters and digits in all patients. The only cortical region lesioned across all 4 patients was the left fusiform gyrus, indicating that this region subserves a function broader than letter or word identification. We suggest that a seemingly pure disorder of reading can arise due to a general reduction of visual speed and span, and explain why this has a disproportionate impact on word reading while recognition of other visual stimuli are less obviously affected.

Too Little, Too Late: Reduced Visual Span and Speed Characterize Pure Alexia

PubMed Central

Habekost, Thomas; Leff, Alexander P.

2009-01-01

Whether normal word reading includes a stage of visual processing selectively dedicated to word or letter recognition is highly debated. Characterizing pure alexia, a seemingly selective disorder of reading, has been central to this debate. Two main theories claim either that 1) Pure alexia is caused by damage to a reading specific brain region in the left fusiform gyrus or 2) Pure alexia results from a general visual impairment that may particularly affect simultaneous processing of multiple items. We tested these competing theories in 4 patients with pure alexia using sensitive psychophysical measures and mathematical modeling. Recognition of single letters and digits in the central visual field was impaired in all patients. Visual apprehension span was also reduced for both letters and digits in all patients. The only cortical region lesioned across all 4 patients was the left fusiform gyrus, indicating that this region subserves a function broader than letter or word identification. We suggest that a seemingly pure disorder of reading can arise due to a general reduction of visual speed and span, and explain why this has a disproportionate impact on word reading while recognition of other visual stimuli are less obviously affected. PMID:19366870

Optical characterization of pure vegetable oils and their biodiesels using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Firdous, S.; Anwar, S.; Waheed, A.; Maraj, M.

2016-04-01

Great concern regarding energy resources and environmental polution has increased interest in the study of alternative sources of energy. Biodiesels as an alternative fuel provide a suitable diesel oil substitute for internal combustion engines. The Raman spectra of pure biodiesels of soybean oil, olive oil, coconut oil, animal fats, and petroleum diesel are optically characterized for quality and biofuel as an alternative fuel. The most significant spectral differences are observed in the frequency range around 1457 cm-1 for pure petroleum diesel, 1427 for fats biodiesel, 1670 cm-1 for pure soybean oil, 1461 cm-1 for soybean oil based biodiesel, 1670 cm-1 for pure olive oil, 1666 cm-1 for olive oil based biodiesel, 1461 cm-1 for pure coconut oil, and 1460 cm-1 for coconut oil based biodiesel, which is used for the analysis of the phase composition of oils. A diode pump solid-state laser with a 532 nm wavelength is used as an illuminating light. It is demonstrated that the peak positions and relative intensities of the vibrations of the oils can be used to identify the biodiesel quality for being used as biofuel.

Nuclear factor erythroid 2-related factor-2 activity controls 4-hydroxynonenal metabolism and activity in prostate cancer cells.

PubMed

Pettazzoni, Piergiorgio; Ciamporcero, Eric; Medana, Claudio; Pizzimenti, Stefania; Dal Bello, Federica; Minero, Valerio Giacomo; Toaldo, Cristina; Minelli, Rosalba; Uchida, Koji; Dianzani, Mario Umberto; Pili, Roberto; Barrera, Giuseppina

2011-10-15

4-Hydroxynonenal (HNE) is an end product of lipoperoxidation with antiproliferative and proapoptotic properties in various tumors. Here we report a greater sensitivity to HNE in PC3 and LNCaP cells compared to DU145 cells. In contrast to PC3 and LNCaP cells, HNE-treated DU145 cells showed a smaller reduction in growth and did not undergo apoptosis. In DU145 cells, HNE did not induce ROS production and DNA damage and generated a lower amount of HNE-protein adducts. DU145 cells had a greater GSH and GST A4 content and GSH/GST-mediated HNE detoxification. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a regulator of the antioxidant response. Nrf2 protein content and nuclear accumulation were higher in DU145 cells compared to PC3 and LNCaP cells, whereas the expression of KEAP1, the main negative regulator of Nrf2 activity, was lower. Inhibition of Nrf2 expression with specific siRNA resulted in a reduction in GST A4 expression and GS-HNE formation, indicating that Nrf2 controls HNE metabolism. In addition, Nrf2 knockdown sensitized DU145 cells to HNE-mediated antiproliferative and proapoptotic activity. In conclusion, we demonstrated that increased Nrf2 activity resulted in a reduction in HNE sensitivity in prostate cancer cells, suggesting a potential mechanism of resistance to pro-oxidant therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Hepatoblastoma with pure fetal epithelial differentiation in a 10-year-old boy: A rare case report and review of the literature.

PubMed

Zhong, Shanshan; Zhao, Yang; Fan, Chuifeng

2018-01-01

Hepatoblastoma is a rare malignant embryonal tumor that only accounts for approximately 1% of all pediatric cancers and mostly develops in children younger than 5 years old. Moreover, the occurrence of hepatoblastoma in adults is extremely rare. Herein, we present a rare case of hepatoblastoma with pure epithelial differentiation in a 10-year-old boy.Pathological examination was performed. The tumor was 15 cm × 15 cm in size with clear margins. The cut surface was multiple nodular and grey-yellow. Histologically, the small cuboidal tumor cells were arranged in trabeculae with 2-3 cell layers. The tumor cells had eosinophilic or clear cytoplasm, formed dark and light areas, and were positive for alpha-fetoprotein, CK, CK8/18, CD10, hepatocyte, and GPC3. CD34 staining revealed that the sinusoids were lined by endothelial cells in the tumor tissues. The Ki67 index was approximately 20%. Based on these findings, the case was diagnosed as hepatoblastoma with pure fetal epithelial differentiation. The tumor was completely removed. No recurrence was found 3 months after the operation. Hepatoblastoma with pure epithelial differentiation can also occur in older children. Children rarely notice and report any physical abnormality, and this may be among the primary reasons for the late diagnosis of the tumor. Annual heath checks may be beneficial in the detection of these rare tumors and improvement of patient outcomes. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Regulation mechanisms in mixed and pure culture microbial fermentation.

PubMed

Hoelzle, Robert D; Virdis, Bernardino; Batstone, Damien J

2014-11-01

Mixed-culture fermentation is a key central process to enable next generation biofuels and biocommodity production due to economic and process advantages over application of pure cultures. However, a key limitation to the application of mixed-culture fermentation is predicting culture product response, related to metabolic regulation mechanisms. This is also a limitation in pure culture bacterial fermentation. This review evaluates recent literature in both pure and mixed culture studies with a focus on understanding how regulation and signaling mechanisms interact with metabolic routes and activity. In particular, we focus on how microorganisms balance electron sinking while maximizing catabolic energy generation. Analysis of these mechanisms and their effect on metabolism dynamics is absent in current models of mixed-culture fermentation. This limits process prediction and control, which in turn limits industrial application of mixed-culture fermentation. A key mechanism appears to be the role of internal electron mediating cofactors, and related regulatory signaling. This may determine direction of electrons towards either hydrogen or reduced organics as end-products and may form the basis for future mechanistic models. © 2014 Wiley Periodicals, Inc.

Purely temporal figure-ground segregation.

PubMed

Kandil, F I; Fahle, M

2001-05-01

Visual figure-ground segregation is achieved by exploiting differences in features such as luminance, colour, motion or presentation time between a figure and its surround. Here we determine the shortest delay times required for figure-ground segregation based on purely temporal features. Previous studies usually employed stimulus onset asynchronies between figure- and ground-containing possible artefacts based on apparent motion cues or on luminance differences. Our stimuli systematically avoid these artefacts by constantly showing 20 x 20 'colons' that flip by 90 degrees around their midpoints at constant time intervals. Colons constituting the background flip in-phase whereas those constituting the target flip with a phase delay. We tested the impact of frequency modulation and phase reduction on target detection. Younger subjects performed well above chance even at temporal delays as short as 13 ms, whilst older subjects required up to three times longer delays in some conditions. Figure-ground segregation can rely on purely temporal delays down to around 10 ms even in the absence of luminance and motion artefacts, indicating a temporal precision of cortical information processing almost an order of magnitude lower than the one required for some models of feature binding in the visual cortex [e.g. Singer, W. (1999), Curr. Opin. Neurobiol., 9, 189-194]. Hence, in our experiment, observers are unable to use temporal stimulus features with the precision required for these models.

Multiple pure tone noise prediction

NASA Astrophysics Data System (ADS)

Han, Fei; Sharma, Anupam; Paliath, Umesh; Shieh, Chingwei

2014-12-01

This paper presents a fully numerical method for predicting multiple pure tones, also known as “Buzzsaw” noise. It consists of three steps that account for noise source generation, nonlinear acoustic propagation with hard as well as lined walls inside the nacelle, and linear acoustic propagation outside the engine. Noise generation is modeled by steady, part-annulus computational fluid dynamics (CFD) simulations. A linear superposition algorithm is used to construct full-annulus shock/pressure pattern just upstream of the fan from part-annulus CFD results. Nonlinear wave propagation is carried out inside the duct using a pseudo-two-dimensional solution of Burgers' equation. Scattering from nacelle lip as well as radiation to farfield is performed using the commercial solver ACTRAN/TM. The proposed prediction process is verified by comparing against full-annulus CFD simulations as well as against static engine test data for a typical high bypass ratio aircraft engine with hardwall as well as lined inlets. Comparisons are drawn against nacelle unsteady pressure transducer measurements at two axial locations as well as against near- and far-field microphone array measurements outside the duct. This is the first fully numerical approach (no experimental or empirical input is required) to predict multiple pure tone noise generation, in-duct propagation and far-field radiation. It uses measured blade coordinates to calculate MPT noise.

Noni puree (Morinda citrifolia) mixed in beef patties enhanced color stability.

PubMed

Tapp, W Nathan; Yancey, Janeal W S; Apple, Jason K; Dikeman, Michael E; Godbee, Richard G

2012-06-01

Ground beef, mixed with 0, 2, 4, and 6% Noni puree, was formed into 150-g patties, aerobically packaged, and displayed in retail for 5d. After 2 and 3d, patties with higher concentrations of Noni were perceived as redder and less discolored (P<0.05) by visual panelists. Noni patties were found to have greater (P<0.05) a* values than controls, even though all patties became less red during display. After 3 and 5d of retail display, patties with higher concentrations of Noni puree also had lower TBARS (were less oxidized; P<0.05). In fresh taste panels, panelists perceived the patties to have less beef flavor and greater incidence of off-flavors (P<0.05) as Noni puree concentration increased. The potential of Noni puree to improve the color stability and shelf life of fresh ground beef is very promising, but the flavors produced by the addition of Noni in ground beef may be detrimental to its use. Copyright © 2012. Published by Elsevier Ltd.

Assessing the microstructural and rheological changes induced by food additives on potato puree.

PubMed

Dankar, Iman; Haddarah, Amira; El Omar, Fawaz; Sepulcre, Francesc; Pujolà, Montserrat

2018-02-01

The effects of agar, alginate, lecithin and glycerol on the rheological properties of commercial potato puree were investigated and interpreted in terms of starch microstructural changes, and the applicability of the Cox-Merz rule was evaluated. Each additive was applied separately at two concentrations (0.5 and 1%). Microscopic observations revealed more swollen starch aggregations in lecithin and glycerol compared with those of potato puree and agar, consequently affecting the rheological properties of potato puree. All samples exhibited shear thinning non-Newtonian behaviour. Rheological measurements were strongly concentration dependent. At 0.5% concentration, additives exerted decreases in all the rheological properties of potato puree in the order of glycerol>alginate>lecithin>agar, while at 1% concentration, the order changed to glycerol>lecithin>alginate, whereas 1% agar behaved differently, increasing all rheological values. This study also showed that agar and alginate in addition to potato puree could be valuable and advantageous for further technological processes, such as 3D printing. Copyright © 2017 Elsevier Ltd. All rights reserved.

What lies beneath: A comparison of reading aloud in pure alexia and semantic dementia

PubMed Central

Hoffman, Paul; Roberts, Daniel J.; Ralph, Matthew A. Lambon; Patterson, Karalyn E.

2014-01-01

Exaggerated effects of word length upon reading-aloud performance define pure alexia, but have also been observed in semantic dementia. Some researchers have proposed a reading-specific account, whereby performance in these two disorders reflects the same cause: impaired orthographic processing. In contrast, according to the primary systems view of acquired reading disorders, pure alexia results from a basic visual processing deficit, whereas degraded semantic knowledge undermines reading performance in semantic dementia. To explore the source of reading deficits in these two disorders, we compared the reading performance of 10 pure alexic and 10 semantic dementia patients, matched in terms of overall severity of reading deficit. The results revealed comparable frequency effects on reading accuracy, but weaker effects of regularity in pure alexia than in semantic dementia. Analysis of error types revealed a higher rate of letter-based errors and a lower rate of regularization responses in pure alexia than in semantic dementia. Error responses were most often words in pure alexia but most often nonwords in semantic dementia. Although all patients made some letter substitution errors, these were characterized by visual similarity in pure alexia and phonological similarity in semantic dementia. Overall, the data indicate that the reading deficits in pure alexia and semantic dementia arise from impairments of visual processing and knowledge of word meaning, respectively. The locus and mechanisms of these impairments are placed within the context of current connectionist models of reading. PMID:24702272

Children's and adults' judgments of the certainty of deductive inferences, inductive inferences, and guesses.

PubMed

Pillow, Bradford H; Pearson, Raeanne M; Hecht, Mary; Bremer, Amanda

2010-01-01

Children and adults rated their own certainty following inductive inferences, deductive inferences, and guesses. Beginning in kindergarten, participants rated deductions as more certain than weak inductions or guesses. Deductions were rated as more certain than strong inductions beginning in Grade 3, and fourth-grade children and adults differentiated strong inductions, weak inductions, and informed guesses from pure guesses. By Grade 3, participants also gave different types of explanations for their deductions and inductions. These results are discussed in relation to children's concepts of cognitive processes, logical reasoning, and epistemological development.

Angels and demons are among us: assessing individual differences in belief in pure evil and belief in pure good.

PubMed

Webster, Russell J; Saucier, Donald A

2013-11-01

We conducted five studies to demonstrate that individuals' beliefs in pure evil (BPE) and in pure good (BPG) are valid and important psychological constructs. First, these studies together demonstrated that BPE and BPG are reliable, unitary, and stable constructs each composed of eight theoretically interdependent dimensions. Second, these studies showed that across a wide variety of different measures, higher BPE consistently related to greater intergroup aggression (e.g., supporting the death penalty and preemptive military aggression) and less intergroup prosociality (e.g., opposing criminal rehabilitation, proracial policies, and beneficial social programs), while higher BPG consistently related to less intergroup aggression (e.g., opposing proviolent foreign relations and torture) and greater intergroup prosociality (e.g., supporting criminal rehabilitation and support for diplomacy). In sum, these studies evidence that BPE and BPG relate to aggressive and prosocial orientations toward others and have strong potential to advance current theories on prejudice, aggression, and prosociality.

Universality in volume-law entanglement of scrambled pure quantum states.

PubMed

Nakagawa, Yuya O; Watanabe, Masataka; Fujita, Hiroyuki; Sugiura, Sho

2018-04-24

A pure quantum state can fully describe thermal equilibrium as long as one focuses on local observables. The thermodynamic entropy can also be recovered as the entanglement entropy of small subsystems. When the size of the subsystem increases, however, quantum correlations break the correspondence and mandate a correction to this simple volume law. The elucidation of the size dependence of the entanglement entropy is thus essentially important in linking quantum physics with thermodynamics. Here we derive an analytic formula of the entanglement entropy for a class of pure states called cTPQ states representing equilibrium. We numerically find that our formula applies universally to any sufficiently scrambled pure state representing thermal equilibrium, i.e., energy eigenstates of non-integrable models and states after quantum quenches. Our formula is exploited as diagnostics for chaotic systems; it can distinguish integrable models from non-integrable models and many-body localization phases from chaotic phases.

For your interest? The ethical acceptability of using non-invasive prenatal testing to test 'purely for information'.

PubMed

Deans, Zuzana; Clarke, Angus J; Newson, Ainsley J

2015-01-01

Non-invasive prenatal testing (NIPT) is an emerging form of prenatal genetic testing that provides information about the genetic constitution of a foetus without the risk of pregnancy loss as a direct result of the test procedure. As with other prenatal tests, information from NIPT can help to make a decision about termination of pregnancy, plan contingencies for birth or prepare parents to raise a child with a genetic condition. NIPT can also be used by women and couples to test purely 'for information'. Here, no particular action is envisaged following the test; it is motivated entirely by an interest in the result. The fact that NIPT can be performed without posing a risk to the pregnancy could give rise to an increase in such requests. In this paper, we examine the ethical aspects of using NIPT 'purely for information', including the competing interests of the prospective parents and the future child, and the acceptability of testing for 'frivolous' reasons. Drawing on several clinical scenarios, we claim that arguments about testing children for genetic conditions are relevant to this debate. In addition, we raise ethical concerns over the potential for objectification of the child. We conclude that, in most cases, using NIPT to test for adult-onset conditions, carrier status or non-serious traits presenting in childhood would be unacceptable. © 2014 John Wiley & Sons Ltd.

Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells.

PubMed

Emara, Marwan; Turner, A Robert; Allalunis-Turner, Joan

2014-02-01

Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

Yttria Nanoparticle Reinforced Commercially Pure (CP) Titanium

DTIC Science & Technology

2011-09-01

nanoparticles as well as titanium boride (TiB) reinforcements were produced through gas atomization. After consolidation and extrusion, room temperature...pure FE iron O oxygen Ti titanium TiB titanium boride TYS tensile yield strength UTS ultimate tensile strength wt% weight percent Y2O3

Revival of pure titanium for dynamically loaded porous implants using additive manufacturing.

PubMed

Wauthle, Ruben; Ahmadi, Seyed Mohammad; Amin Yavari, Saber; Mulier, Michiel; Zadpoor, Amir Abbas; Weinans, Harrie; Van Humbeeck, Jan; Kruth, Jean-Pierre; Schrooten, Jan

2015-09-01

Additive manufacturing techniques are getting more and more established as reliable methods for producing porous metal implants thanks to the almost full geometrical and mechanical control of the designed porous biomaterial. Today, Ti6Al4V ELI is still the most widely used material for porous implants, and none or little interest goes to pure titanium for use in orthopedic or load-bearing implants. Given the special mechanical behavior of cellular structures and the material properties inherent to the additive manufacturing of metals, the aim of this study is to investigate the properties of selective laser melted pure unalloyed titanium porous structures. Therefore, the static and dynamic compressive properties of pure titanium structures are determined and compared to previously reported results for identical structures made from Ti6Al4V ELI and tantalum. The results show that porous Ti6Al4V ELI still remains the strongest material for statically loaded applications, whereas pure titanium has a mechanical behavior similar to tantalum and is the material of choice for cyclically loaded porous implants. These findings are considered to be important for future implant developments since it announces a potential revival of the use of pure titanium for additively manufactured porous implants. Copyright © 2015 Elsevier B.V. All rights reserved.

Minimally differentiated erythroleukaemia (AML M6 'variant'): a rare subset of AML distinct from AML M6. Groupe Français d'Hématologie Cellulaire.

PubMed

Garand, R; Duchayne, E; Blanchard, D; Robillard, N; Kuhlein, E; Fenneteau, O; Salomon-Nguyen, F; Grange, M J; Rousselot, P; Demur, C

1995-08-01

We describe eight cases of erythroleukaemia distinct from FAB-AML M6, which demonstrate minimal erythroid differentiation not associated with a myeloblastic component. Three infants (including a Down's syndrome) and two adults presented with a de novo leukaemia. One case was preceded by an untreated refractory anaemia with excess of blasts and one by polycythaemia vera. One case presented with an inaugural blast crisis of chronic myeloid leukaemia. In four patients the leukaemic cells showed a proerythroblast-like morphology. The four other were initially classified as undifferentiated AL (two cases) or AML MO (two cases) because of the immature aspect of the cells, their lack of myeloperoxidase activity and the absence of B, T lymphoid and myeloid (My) marker expressions apart from the CD33 antigen. Immunophenotyping in three cases showed an immature erythroblast profile (glycophorins A and B+, spectrin+). In the five others the erythroid nature was recognized by the expression of ABH blood group system on fresh cells (four cases) and glycophorin A on cells after 3 d in vitro culture with erythropoietin (EPO) + IL3 (two cases). Moreover, an erythroid colony growth of leukaemic origin was observed in three patients. In conclusion, the study of erythroid marker expression is of particular importance when immunophenotyping leukaemic cells with a proerythroblast-like morphology or an undifferentiated aspect and a HLA DR-, CD36++, B-, T-, My- (CD33 +/-) phenotype. We propose the term AML M6 'variant' for this rare type of AML.

Whole-body and multispectral photoacoustic imaging of adult zebrafish

NASA Astrophysics Data System (ADS)

Huang, Na; Xi, Lei

2016-10-01

Zebrafish is a top vertebrate model to study developmental biology and genetics, and it is becoming increasingly popular for studying human diseases due to its high genome similarity to that of humans and the optical transparency in embryonic stages. However, it becomes difficult for pure optical imaging techniques to volumetric visualize the internal organs and structures of wild-type zebrafish in juvenile and adult stages with excellent resolution and penetration depth. Even with the establishment of mutant lines which remain transparent over the life cycle, it is still a challenge for pure optical imaging modalities to image the whole body of adult zebrafish with micro-scale resolution. However, the method called photoacoustic imaging that combines all the advantages of the optical imaging and ultrasonic imaging provides a new way to image the whole body of the zebrafish. In this work, we developed a non-invasive photoacoustic imaging system with optimized near-infrared illumination and cylindrical scanning to image the zebrafish. The lateral and axial resolution yield to 80 μm and 600 μm, respectively. Multispectral strategy with wavelengths from 690 nm to 930 nm was employed to image various organs inside the zebrafish. From the reconstructed images, most major organs and structures inside the body can be precisely imaged. Quantitative and statistical analysis of absorption for organs under illumination with different wavelengths were carried out.

Augmenting The HST Pure Parallel Observations

NASA Astrophysics Data System (ADS)

Patterson, Alan; Soutchkova, G.; Workman, W.

2012-05-01

Pure Parallel (PP) programs, designated GO/PAR, are a subgroup of General Observer (GO) programs. PP execute simultaneously with prime GO observations to which they are "attached". The PP observations can be performed with ACS/WFC, WFC3/UVIS or WFC3/IR and can be attached only to GO visits in which the instruments are either COS or STIS. The current HST Parallel Observation Processing System (POPS) was introduced after the Servicing Mission 4. It increased the HST productivity by 10% in terms of the utilization of HST prime orbits and was highly appreciated by the HST observers, allowing them to design efficient, multi-orbit survey projects for collecting large amounts of data on identifiable targets. The results of the WFC3 Infrared Spectroscopic Parallel Survey (WISP), Hubble Infrared Pure Parallel Imaging Extragalactic Survey (HIPPIES), and The Brightest-of-Reionizing Galaxies Pure Parallel Survey (BoRG) exemplify this benefit. In Cycle 19, however, the full advantage of GO/PARs came under risk. Whereas each of the previous cycles provided over one million seconds of exposure time for PP, in Cycle 19 that number reduced to 680,000 seconds. This dramatic decline occurred because of fundamental changes in the construction of COS prime observations. To preserve the science output of PP, the PP Working Group was tasked to find a way to recover the lost time and maximize the total time available for PP observing. The solution was to expand the definition of a PP opportunity to allow PP exposures to span one or more primary exposure readouts. So starting in HST Cycle 20, PP opportunities will no longer be limited to GO visits with a single uninterrupted exposure in an orbit. The resulting enhancements in HST Cycle 20 to the PP opportunity identification and matching process are expected to restore the PP time to previously achieved and possibly even greater levels.

chemf: A purely functional chemistry toolkit

PubMed Central

2012-01-01

Background Although programming in a type-safe and referentially transparent style offers several advantages over working with mutable data structures and side effects, this style of programming has not seen much use in chemistry-related software. Since functional programming languages were designed with referential transparency in mind, these languages offer a lot of support when writing immutable data structures and side-effects free code. We therefore started implementing our own toolkit based on the above programming paradigms in a modern, versatile programming language. Results We present our initial results with functional programming in chemistry by first describing an immutable data structure for molecular graphs together with a couple of simple algorithms to calculate basic molecular properties before writing a complete SMILES parser in accordance with the OpenSMILES specification. Along the way we show how to deal with input validation, error handling, bulk operations, and parallelization in a purely functional way. At the end we also analyze and improve our algorithms and data structures in terms of performance and compare it to existing toolkits both object-oriented and purely functional. All code was written in Scala, a modern multi-paradigm programming language with a strong support for functional programming and a highly sophisticated type system. Conclusions We have successfully made the first important steps towards a purely functional chemistry toolkit. The data structures and algorithms presented in this article perform well while at the same time they can be safely used in parallelized applications, such as computer aided drug design experiments, without further adjustments. This stands in contrast to existing object-oriented toolkits where thread safety of data structures and algorithms is a deliberate design decision that can be hard to implement. Finally, the level of type-safety achieved by Scala highly increased the reliability of our code

[Effects of laser welding on bond of porcelain fused cast pure titanium].

PubMed

Zhu, Juan-fang; He, Hui-ming; Gao, Bo; Wang, Zhong-yi

2006-04-01

To investigate the influence of the laser welding on bond of porcelain fused to cast pure titanium. Twenty cast titanium plates were divided into two groups: laser welded group and control group. The low-fusing porcelain was fused to the laser welded cast pure titanium plates at fusion zone. The bond strength of the porcelain to laser welded cast pure titanium was measured by the three-point bending test. The interface of titanium and porcelain was investigated by scanning electron microscopy (SEM) and energy depressive X-ray detector (EDX). The non-welded titanium plates were used as comparison. No significant difference of the bond strength was found between laser-welded samples [(46.85 +/- 0.76) MPa] and the controls [(41.71 +/- 0.55) MPa] (P > 0.05). The SEM displayed the interface presented similar irregularities with a predominance. The titanium diffused to low-fusing porcelain, while silicon and aluminum diffused to titanium basement. Laser welding does not affect low-fusing porcelain fused to pure titanium.

Investigations in Pure Mathematics: A Constructivist Perspective.

ERIC Educational Resources Information Center

Hirst, Keith; Shiu, Christine

1995-01-01

Discusses an investigative, constructivist approach in the context of undergraduate mathematics, with particular reference to pure mathematics, general aims and objectives, assessment strategies, and problems of supervision that affect tutors and lecturers using this approach. Gives students' views on their experiences in this mode of working. (19…

Noninformative prior in the quantum statistical model of pure states

NASA Astrophysics Data System (ADS)

Tanaka, Fuyuhiko

2012-06-01

In the present paper, we consider a suitable definition of a noninformative prior on the quantum statistical model of pure states. While the full pure-states model is invariant under unitary rotation and admits the Haar measure, restricted models, which we often see in quantum channel estimation and quantum process tomography, have less symmetry and no compelling rationale for any choice. We adopt a game-theoretic approach that is applicable to classical Bayesian statistics and yields a noninformative prior for a general class of probability distributions. We define the quantum detection game and show that there exist noninformative priors for a general class of a pure-states model. Theoretically, it gives one of the ways that we represent ignorance on the given quantum system with partial information. Practically, our method proposes a default distribution on the model in order to use the Bayesian technique in the quantum-state tomography with a small sample.

Fundamental data on the desorption of pure interstellar ices

NASA Astrophysics Data System (ADS)

Brown, Wendy A.; Bolina, Amandeep S.

2007-01-01

The desorption of molecular ices from grain surfaces is important in a number of astrophysical environments including dense molecular clouds, cometary nuclei and the surfaces and atmospheres of some planets. With this in mind, we have performed a detailed investigation of the desorption of pure water, pure methanol and pure ammonia ices from a model dust-grain surface. We have used these results to determine the desorption energy, order of desorption and the pre-exponential factor for the desorption of these molecular ices from our model surface. We find good agreement between our desorption energies and those determined previously; however, our values for the desorption orders, and hence also the pre-exponential factors, are different to those reported previously. The kinetic parameters derived from our data have been used to model desorption on time-scales relevant to astrophysical processes and to calculate molecular residence times, given in terms of population half-life as a function of temperature. These results show the importance of laboratory data for the understanding of astronomical situations whereby icy mantles are warmed by nearby stars and by other dynamical events.

B(H) has a pure state that is not multiplicative on any masa.

PubMed

Akemann, Charles; Weaver, Nik

2008-04-08

Assuming the continuum hypothesis, we prove that Bernoulli function(H) has a pure state whose restriction to any masa is not pure. This resolves negatively old conjectures of Kadison and Singer and of Anderson.

Thermal inactivation of Botrytis cinerea conidia in synthetic medium and strawberry puree.

PubMed

Villa-Rojas, R; Sosa-Morales, M E; López-Malo, A; Tang, J

2012-04-16

Botrytis cinerea is one of the most important post-harvest molds that cause quality deterioration of strawberries and other fruits even during refrigeration storage. This research studied the effects of thermal inactivation of B. cinerea in synthetic medium and strawberry puree using hot water baths at different temperatures. These media were studied in order to determine if results obtained in a solution with the major components of the fruit (synthetic media), are comparable to the ones obtained in fruit purees. The results demonstrated that B. cinerea spores can be inactivated by heat treatments using relatively low temperatures (42-46 °C). Inactivation curves were well described by first order kinetics (R² 0.91-0.99). B. cinerea conidia inoculated in synthetic medium required less time to achieve one log reduction in population than those inoculated in the fruit puree. D values were 22, 8.5, 4 and 1.4 min at 42, 44, 46 and 48 °C, respectively, in synthetic medium; while D values in strawberry puree were 44.9, 13.8, 4.7 and 1.4 min at 42, 44, 46 and 48 °C, respectively. The z values obtained were 4.15 and 5.08 °C for the strawberry puree and synthetic medium respectively, showing higher sensitivity of B. cinerea in fruit purees than in the synthetic medium. Thus, a change in the medium composition had a marked difference in the heat inactivation of B. cinerea conidia, and the results obtained in synthetic medium are not accurate to describe the behavior of the microorganism in the fruit. Copyright © 2012 Elsevier B.V. All rights reserved.

Asperger Syndrome: a frequent comorbidity in first diagnosed adult ADHD patients?

PubMed

Roy, Mandy; Ohlmeier, Martin D; Osterhagen, Lasse; Prox-Vagedes, Vanessa; Dillo, Wolfgang

2013-06-01

Because adult ADHD is often accompanied by psychiatric comorbidities, the diagnostic process should include a thorough investigation for comorbid disorders. Asperger-Syndrome is rarely reported in adult ADHD and commonly little attention is paid to this possible comorbidity. We investigated 53 adult ADHD-patients which visited our out patient clinic for first ADHD-diagnosis (17 females, 36 males; range of age: 18-56 years) for the frequency of a comorbid Asperger-Syndrome. Diagnosis of this autism-spectrum disorder was confirmed by applying the appropriate DSM-IV-criteria. Additionally we tested the power of the two screening-instruments "Autism-spectrum quotient" (AQ) and "Empathy quotient" (EQ) by Baron-Cohen for screening Asperger-Syndrome in adult ADHD. Eight ADHD-patients were diagnosed with a comorbid Asperger-Syndrome (15.1%). The difference in AQ- and EQ-scores between pure ADHD-patients and comorbid patients was analysed, showing significantly higher scores in AQ and significant lower scores in EQ in comorbid patients. Results show that the frequency of Asperger-Syndrome seems to be substantially increased in adult ADHD (versus the prevalence of 0.06% in the general population), indicating that investigators of adult ADHD should also be attentive to autism-spectrum disorders. Especially the AQ seems to be a potential screening instrument for Asperger-Syndrome in adult ADHD-patients.

Analysis of pure and malachite green doped polysulfone sample using FT-IR technique

NASA Astrophysics Data System (ADS)

Nayak, Rashmi J.; Khare, P. K.; Nayak, J. G.

2018-05-01

The sample of pure and malachite green doped Polysulfone in the form of foil was prepared by isothermal immersion technique. For the preparation of pure sample 4 gm of Polysulfone was dissolved in 50 ml of Dimethyl farmamide (DMF) solvent, while for the preparation of doped sample 10 mg, 50 mg and 100 mg Malachite Green was mixed with 4 gm of Polysulfone respectively. For the study of structural characterization of these pure and doped sample, Fourier Transform Infra-Red Spectroscopy (FT-IR) technique was used. This study shows that the intensity of transmittance decreases as the ratio of doping increases in pure polysulfone. The reduction in intensity of transmittance is clearly apparent in the present case more over the bands were broader which indicates towards charge transfer interaction between the donar and acceptor molecule.

The origins of pure and applied science in Gilded Age America.

PubMed

Lucier, Paul

2012-09-01

"Pure science" and "applied science" have peculiar histories in the United States. Both terms were in use in the early part of the nineteenth century, but it was only in the last decades that they took on new meanings and became commonplace in the discourse of American scientists. The rise in their currency reflected an acute concern about the corruption of character and the real possibilities of commercializing scientific knowledge. "Pure" was the preference of scientists who wanted to emphasize their nonpecuniary motives and their distance from the marketplace. "Applied" was the choice of scientists who accepted patents and profits as other possible returns on their research. In general, the frequent conjoining of "pure" and "applied" bespoke the inseparable relations of science and capitalism in the Gilded Age.

Generalized Gödel universes in higher dimensions and pure Lovelock gravity

NASA Astrophysics Data System (ADS)

Dadhich, Naresh; Molina, Alfred; Pons, Josep M.

2017-10-01

The Gödel universe is a homogeneous rotating dust with negative Λ which is a direct product of a three-dimensional pure rotation metric with a line. We would generalize it to higher dimensions for Einstein and pure Lovelock gravity with only one N th-order term. For higher-dimensional generalization, we have to include more rotations in the metric, and hence we shall begin with the corresponding pure rotation odd (d =2 n +1 )-dimensional metric involving n rotations, which eventually can be extended by a direct product with a line or a space of constant curvature for yielding a higher-dimensional Gödel universe. The considerations of n rotations and also of constant curvature spaces is a new line of generalization and is being considered for the first time.

Alcohol-dependent patients with comorbid phobic disorders: a comparison between comorbid patients, pure alcohol-dependent and pure phobic patients.

PubMed

Schadé, Annemiek; Marquenie, Loes A; Van Balkom, Anton J L M; Koeter, Maarten W J; De Beurs, Edwin; Van Den Brink, Wim; Van Dyck, Richard

2004-01-01

Patients with a double diagnosis of alcohol dependence and phobic disorders are a common phenomenon in both alcohol and anxiety disorder clinics. If we are to provide optimum treatment we need to know more about the clinical characteristics of this group of comorbid patients. To answer the following questions. (1). What are the clinical characteristics of treatment-seeking alcohol-dependent patients with a comorbid phobic disorder? (2). Are alcohol dependence and other clinical characteristics of comorbid patients different from those of 'pure' alcohol-dependent patients? (3). Are the anxiety symptoms and other clinical characteristics of comorbid patients different from those of 'pure' phobic patients? Three groups of treatment-seeking patients were compared on demographic and clinical characteristics: alcohol dependent patients with a comorbid phobic disorder (n = 110), alcohol-dependent patients (n = 148) and patients with social phobia or agoraphobia (n = 106). In order to diagnose the comorbid disorders validly, the assessment took place at least 6 weeks after detoxification. Comorbid patients have high scores on depressive symptoms and general psychopathology: 25% of patients have a current and 52% a lifetime depressive disorder. The majority have no partner and are unemployed, they have a high incidence of other substance use (benzodiazepine, cocaine, cannabis) and a substantial proportion of comorbid patients have been emotionally, physically and sexually abused. They do not have a more severe, or different type of alcohol dependence or anxiety disorder than 'pure' alcohol-dependent patients and phobic patients respectively. Comorbid patients constitute a complex part of the treatment-seeking population in alcohol clinics and psychiatric hospitals. These findings should be taken into account when diagnosing and treating alcohol-dependent patients with a comorbid phobic disorder.

Ischemic Preconditioning Protects Astrocytes against Oxygen Glucose Deprivation Via the Nuclear Erythroid 2-Related Factor 2 Pathway.

PubMed

Narayanan, Srinivasan V; Dave, Kunjan R; Perez-Pinzon, Miguel A

2018-04-01

Induction of ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia by activation of adaptive pathways and modulation of mitochondria to induce ischemic tolerance to various cells and tissues. Mitochondrial dysfunction has been ascribed to contribute to numerous neurodegenerative conditions and cerebral ischemia. Nuclear erythroid 2-related factor 2 (Nrf2) is a transcription factor that has traditionally been involved in upregulating cellular antioxidant systems to combat oxidative stress in the brain; however, the association of Nrf2 with mitochondria in the brain remains unclear. In the present study, we investigated the effects of Nrf2 on (i) IPC-induced protection of astrocytes; (ii) OXPHOS protein expression; and (iii) mitochondrial supercomplex formation.Oxygen-glucose deprivation (OGD) was used as an in vitro model of cerebral ischemia and IPC in cultured rodent astrocytes derived from WT C57Bl/6J and Nrf2 -/- mice. OXPHOS proteins were probed via western blotting, and supercomplexes were determined by blue native gel electrophoresis.IPC-induced cytoprotection in wild-type, but not Nrf2 -/- mouse astrocyte cultures following a lethal duration of OGD. In addition, our results suggest that Nrf2 localizes to the outer membrane in non-synaptic brain mitochondria, and that a lack of Nrf2 in vivo produces altered supercomplex formation in mitochondria.Our findings support a role of Nrf2 in mediating IPC-induced protection in astrocytes, which can profoundly impact the ischemic tolerance of neurons. In addition, we provide novel evidence for the association of Nrf2 to brain mitochondria and supercomplex formation. These studies offer new targets and pathways of Nrf2, which may be heavily implicated following cerebral ischemia.

Pure spinor superspace action for D = 6, N = 1 super-Yang-Mills theory

NASA Astrophysics Data System (ADS)

Cederwall, Martin

2018-05-01

A Batalin-Vilkovisky action for D = 6, N = 1 super-Yang-Mills theory, including coupling to hypermultiplets, is given. The formalism involves pure spinor superfields. The geometric properties of the D = 6, N = 1 pure spinors (which differ from Cartan pure spinors) are examined. Unlike the situation for maximally supersymmetric models, the fields and antifields (including ghosts) of the vector multiplet reside in separate superfields. The formalism provides an off-shell superspace formulation for matter hypermultiplets, which in a traditional treatment are on-shell.

Chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis

PubMed Central

Vignjević, Sanja; Budeč, Mirela; Marković, Dragana; Đikić, Dragoslava; Mitrović, Olivera; Mojsilović, Slavko; Đurić, Sanja Vranješ; Koko, Vesna; Čokić, Bojana Beleslin; Čokić, Vladan; Jovčić, Gordana

2014-01-01

Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychological stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progenitors in response to stressful stimuli, and emerging evidence suggests that inappropriate activation of stress erythropoiesis may predispose to leukaemic transformation. We used a mouse model to study the influence of chronic psychological stress on erythropoiesis in the spleen and to investigate potential mediators of observed effects. Adult mice were subjected to 2 hrs daily restraint stress for 7 or 14 consecutive days. Our results showed that chronic exposure to restraint stress decreased the concentration of haemoglobin in the blood, elevated circulating levels of erythropoietin and corticosterone, and resulted in markedly increased number of erythroid progenitors and precursors in the spleen. Western blot analysis revealed significantly decreased expression of both erythropoietin receptor and glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic stress enhanced the expression of stem cell factor receptor in the red pulp. Moreover, chronically stressed animals exhibited significantly increased expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as substantially enhanced mRNA expression levels of its receptors in the spleen. These findings demonstrate for the first time that chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis and leads to the prolonged activation of stress erythropoiesis pathways. Prolonged activation of these pathways along with an excessive production of immature erythroid cells may predispose chronically stressed subjects to a higher risk of leukaemic transformation. PMID:24283209

Do all pure entangled states violate Bell's inequalities for correlation functions?

PubMed

Zukowski, Marek; Brukner, Caslav; Laskowski, Wiesław; Wieśniak, Marcin

2002-05-27

Any pure entangled state of two particles violates a Bell inequality for two-particle correlation functions (Gisin's theorem). We show that there exist pure entangled N>2 qubit states that do not violate any Bell inequality for N particle correlation functions for experiments involving two dichotomic observables per local measuring station. We also find that Mermin-Ardehali-Belinskii-Klyshko inequalities may not always be optimal for refutation of local realistic description.

Nuclear Factor (Erythroid-Derived 2)-Like 2 and Thioredoxin-1 in Atherosclerosis and Ischemia/Reperfusion Injury in the Heart

PubMed Central

Jakobs, Philipp; Serbulea, Vlad; Leitinger, Norbert; Eckers, Anna

2017-01-01

Abstract Significance: Redox signaling is one of the key elements involved in cardiovascular diseases. Two important molecules are the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and the oxidoreductase thioredoxin-1 (Trx-1). Recent Advances: During the previous years, a lot of studies investigated Nrf2 and Trx-1 as protective proteins in cardiovascular disorders. Moreover, post-translational modifications of those molecules were identified that play an important role in the cardiovascular system. This review will summarize changes in the vasculature in atherosclerosis and ischemia reperfusion injury of the heart and the newest findings achieved with Nrf2 and Trx-1 therein. Interestingly, Nrf2 and Trx-1 can act together as well as independently of each other in protection against atherosclerosis and ischemia and reperfusion injury. Critical Issues: In principle, pharmacological activation of a transcription factor-like Nrf2 can be dangerous, since a transcription regulator has multiple targets and the pleiotropic effects of such activation should not be ignored. Moreover, overactivation of Nrf2 as well as long-term treatment with Trx-1 could be deleterious for the cardiovascular system. Future Directions: Therefore, the length of treatment with Nrf2 activators and/or Trx-1 has first to be studied in more detail in cardiovascular disorders. Moreover, a combination of Nrf2 activators and Trx-1 should be investigated and taken into consideration. Antioxid. Redox Signal. 26, 630–644. PMID:27923281

76 FR 69284 - Pure Magnesium From China

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-08

... China Determination On the basis of the record \\1\\ developed in the subject five-year review, the United... China would be likely to lead to continuation or recurrence of material injury to an industry in the...), entitled Pure Magnesium from China: Investigation No. 731-TA-696 (Third Review). Issued: November 2, 2011...

Number Reading in Pure Alexia--A Review

ERIC Educational Resources Information Center

Starrfelt, Randi; Behrmann, Marlene

2011-01-01

It is commonly assumed that number reading can be intact in patients with pure alexia, and that this dissociation between letter/word recognition and number reading strongly constrains theories of visual word processing. A truly selective deficit in letter/word processing would strongly support the hypothesis that there is a specialized system or…

Development and evaluation of 'Pure Rush': An online serious game for drug education.

PubMed

Stapinski, Lexine A; Reda, Bill; Newton, Nicola C; Lawler, Siobhan; Rodriguez, Daniel; Chapman, Catherine; Teesson, Maree

2018-04-01

Learning is most effective when it is active, enjoyable and incorporates feedback. Past research demonstrates that serious games are prime candidates to utilise these principles, however the potential benefits of this approach for delivering drug education are yet to be examined in Australia, a country where drug education in schools is mandatory. The serious game 'Pure Rush' was developed across three stages. First, formative consultation was conducted with 115 students (67% male, aged 15-17 years), followed by feasibility and acceptability testing of a prototype of the game (n = 25, 68% male). In the final stage, 281 students (62% female, aged 13-16 years) were randomly allocated to receive a lesson involving Pure Rush or an active control lesson. The lessons were compared in terms of learning outcomes, lesson engagement and future intentions to use illicit drugs. Students enjoyed playing Pure Rush, found the game age-appropriate and the information useful to them. Both the Pure Rush and the active control were associated with significant knowledge increase from pre to post-test. Among females, multi-level mixed-effects regression showed knowledge gain was greater in the Pure Rush condition compared to control (β = 2.36, 95% confidence interval 0.36-4.38). There was no evidence of between condition differences in lesson engagement or future intentions to use illicit drugs. Pure Rush is an innovative online drug education game that is well received by students and feasible to implement in schools. [Stapinski LA, Reda B, Newton NC, Lawler S, Rodriguez D, Chapman C, Teesson M. Development and evaluation of 'Pure Rush': An online serious game for drug education. Drug Alcohol Rev 2017]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Modeling pure culture heterotrophic production of polyhydroxybutyrate (PHB).

PubMed

Mozumder, Md Salatul Islam; Goormachtigh, Laurens; Garcia-Gonzalez, Linsey; De Wever, Heleen; Volcke, Eveline I P

2014-03-01

In this contribution a mechanistic model describing the production of polyhydroxybutyrate (PHB) through pure-culture fermentation was developed, calibrated and validated for two different substrates, namely glucose and waste glycerol. In both cases, non-growth-associated PHB production was triggered by applying nitrogen limitation. The occurrence of some growth-associated PHB production besides non-growth-associated PHB production was demonstrated, although it is inhibited in the presence of nitrogen. Other phenomena observed experimentally and described by the model included biomass growth on PHB and non-linear product inhibition of PHB production. The accumulated impurities from the waste substrate negatively affected the obtained maximum PHB content. Overall, the developed mathematical model provided an accurate prediction of the dynamic behavior of heterotrophic biomass growth and PHB production in a two-phase pure culture system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improving quality of an innovative pea puree by high hydrostatic pressure.

PubMed

Klug, Tâmmila Venzke; Martínez-Sánchez, Ascensión; Gómez, Perla A; Collado, Elena; Aguayo, Encarna; Artés, Francisco; Artés-Hernández, Francisco

2017-10-01

The food industry is continuously innovating to fulfill consumer demand for new, healthy, ready-to-eat products. Pea purees could satisfy this trend by increasing the intake of legumes, which are an important source of nutrients. Moreover, sensorial properties like viscosity could be improved by high hydrostatic pressure (HHP). In this study the effect of a boiling treatment (10 min) followed by HHP at 550 kPa (0, 5 or 10 min) on the rheological properties, associated with enzymatic activity and particle size, as well as on the microbial and sensory quality of a pea-based puree stored for 36 days at 5 °C, has been assessed. The particle size of pea puree decreased after all processing treatments, but increased during storage in HHP-treated samples. Conversely, boiling treatment showed an increase in polygalacturonase activity at the end of the storage period, with a decrease in particle size, viscosity and stability. However, 5 min of 550 kPa HHP showed the highest mean particle size, mean surface diameter and viscosity regarding the remaining treatments. The microbial load remained low during storage. HHP treatment can be used by the food industry to improve the rheological properties, viscosity and stability of pea purees. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Underwater localization of pure tones by harbor seals (Phoca vitulina).

PubMed

Bodson, Anaïs; Miersch, Lars; Dehnhardt, Guido

2007-10-01

The underwater sound localization acuity of harbor seals (Phoca vitulina) was measured in the horizontal plane. Minimum audible angles (MAAs) of pure tones were determined as a function of frequency from 0.2 to 16 kHz for two seals. Testing was conducted in a 10-m-diam underwater half circle using a right/left psychophysical procedure. The results indicate that for both harbor seals, MAAs were large at high frequencies (13.5 degrees and 17.4 degrees at 16 kHz), transitional at intermediate frequencies (9.6 degrees and 10.1 degrees at 4 kHz), and particularly small at low frequencies (3.2 degrees and 3.1 degrees at 0.2 kHz). Harbor seals seem to be able to utilize both binaural cues, interaural time differences (ITDs) and interaural intensity differences (IIDs), but a significant decrease in the sound localization acuity with increasing frequency suggests that IID cues may not be as robust as ITD cues under water. These results suggest that the harbor seal can be regarded as a low-frequency specialist. Additionally, to obtain a MAA more representative of the species, the horizontal underwater MAA of six adult harbor seals was measured at 2 kHz under identical conditions. The MAAs of the six animals ranged from 8.8 degrees to 11.7 degrees , resulting in a mean MAA of 10.3 degrees .

The Work Softening Behavior of Pure Mg Wire during Cold Drawing.

PubMed

Sun, Liuxia; Bai, Jing; Xue, Feng; Chu, Chenglin; Meng, Jiao

2018-04-13

We performed multiple-pass cold drawing for pure Mg wire which showed excellent formability (~138% accumulative true strain) at room temperature. Different from the continuous work hardening occurring during cold drawing of Mg alloy wires, for pure Mg, an initially rapid increase in hardness and strength was followed by significant work softening and finally reached a steady-state level, approximately 40~45 HV. The work softening can be attributed to the dynamic recovery and recrystallization of pure Mg at room temperature. Meanwhile, an abrupt change in texture component also was detected with the transition from work hardening to softening in the strain range of 28~34%. During the whole drawing, the strongest texture component gradually transformed from as-extruded basal to <10 1 ¯ 0> fiber (~28% accumulative true strain), and then rapidly returned to the weak basal texture.

Analysis of corneal topography in patients with pure microphthalmia in Eastern China.

PubMed

Hu, Pei-Hong; Gao, Gui-Ping; Yu, Yao; Pei, Chong-Gang; Zhou, Qiong; Huang, Xin; Zhang, Ying; Shao, Yi

2015-12-01

To determine the typical corneal changes in pure microphthalmia using a corneal topography system and identify characteristics that may assist in early diagnosis. Patients with pure microphthalmia and healthy control subjects underwent corneal topography analysis (Orbscan IIZ® Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) to determine degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zone, and mean thickness of nine distinct corneal regions. Patients with pure microphthalmia (n = 12) had significantly higher mean K, sim K, mean A, sim A, 3.0 mm irregularity and 5.0 mm irregularity, and exhibited significantly more false keratoconus than controls (n = 12). There was a significant between-group difference in the morphology of the anterior corneal surface and the central curvature of the cornea. Changes in corneal morphology observed in this study could be useful in borderline situations to confirm the diagnosis of pure microphthalmia. © The Author(s) 2015.

Thermodynamics of a pure substance at the triple point

NASA Astrophysics Data System (ADS)

Velasco, S.; Fernández-Pineda, C.

2007-12-01

A thermodynamic study of a pure substance at the triple point is presented. In particular, we show that the mass fractions of the phases coexisting at the triple point obey lever rules in the specific entropy-specific volume diagram, and the relative changes in the mass fractions present in each phase along reversible isochoric and adiabatic processes of a pure substance at the triple point are governed by the relative sizes of the segments of the triple-point line in the pressure-specific volume diagram and in the temperature-specific entropy diagram. Applications to the ordinary triple point of water and to the triple point of Al2SiO5 polymorphs are presented.

Temporal Ventriloquism in a Purely Temporal Context

ERIC Educational Resources Information Center

Hartcher-O'Brien, Jessica; Alais, David

2011-01-01

This study examines how audiovisual signals are combined in time for a temporal analogue of the ventriloquist effect in a purely temporal context, that is, no spatial grounding of signals or other spatial facilitation. Observers were presented with two successive intervals, each defined by a 1250-ms tone, and indicated in which interval a brief…

Biocorrosion properties and blood and cell compatibility of pure iron as a biodegradable biomaterial.

PubMed

Zhang, Erlin; Chen, Haiyan; Shen, Feng

2010-07-01

Biocorrosion properties and blood- and cell compatibility of pure iron were studied in comparison with 316L stainless steel and Mg-Mn-Zn magnesium alloy to reveal the possibility of pure iron as a biodegradable biomaterial. Both electrochemical and weight loss tests showed that pure iron showed a relatively high corrosion rate at the first several days and then decreased to a low level during the following immersion due to the formation of phosphates on the surface. However, the corrosion of pure iron did not cause significant increase in pH value to the solution. In comparison with 316L and Mg-Mn-Zn alloy, the pure iron exhibited biodegradable property in a moderate corrosion rate. Pure iron possessed similar dynamic blood clotting time, prothrombin time and plasma recalcification time to 316L and Mg-Mn-Zn alloy, but a lower hemolysis ratio and a significant lower number density of adhered platelets. MTT results revealed that the extract except the one with 25% 24 h extract actually displayed toxicity to cells and the toxicity increased with the increasing of the iron ion concentration and the incubation time. It was thought there should be an iron ion concentration threshold in the effect of iron ion on the cell toxicity.

The socioeconomic impact of hearing loss in U.S. adults.

PubMed

Emmett, Susan D; Francis, Howard W

2015-03-01

To evaluate the associations between hearing loss and educational attainment, income, and unemployment/underemployment in U.S. adults. National cross-sectional survey. Ambulatory examination centers. Adults aged 20 to 69 years who participated in the 1999 to 2002 cycles of the NHANES (National Health and Nutrition Examination Survey) audiometric evaluation and income questionnaire (N = 3,379). Pure-tone audiometry, with hearing loss defined by World Health Organization criteria of bilateral pure-tone average of more than 25 dB (0.5, 1, 2, 4 kHz). Low educational attainment, defined as not completing high school; low income, defined as family income less than $20,000 per year; and unemployment or underemployment, defined as not having a job or working less than 35 hours per week. Individuals with hearing loss had 3.21 times higher odds of low educational attainment (95% confidence interval [95% CI], 2.20-4.68) compared with normal-hearing individuals. Controlling for education, age, sex, and race, individuals with hearing loss had 1.58 times higher odds of low income (95% CI, 1.16-2.15) and 1.98 times higher odds of being unemployed or underemployed (95% CI, 1.38-2.85) compared with normal-hearing individuals. Hearing loss is associated with low educational attainment in U.S. adults. Even after controlling for education and important demographic factors, hearing loss is independently associated with economic hardship, including both low income and unemployment/underemployment. The societal impact of hearing loss is profound in this nationally representative study and should be further evaluated with longitudinal cohorts. Received institutional review board approval (National Center for Health Statistics Institutional Review Board Protocol no. 98-12).

The role of macrophages in the regulation of erythroid colony growth in vitro.

PubMed

Wang, C Q; Udupa, K B; Lipschitz, D A

1992-10-01

Depletion of macrophages from murine marrow by the use of a monoclonal anti-macrophage antibody resulted in a significant increase in the number of erythroid burst forming units (BFU-E). This increase could be neutralized by the addition back to culture of macrophages or macrophage conditioned medium indicating that the suppression was mediated by soluble factors. To further characterize this effect, the addition to culture, either alone or in combination, of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the growth of BFU-E and the colony-forming unit granulocyte-macrophage (CFU-GM) was examined in macrophage-containing and macrophage-depleted cultures. The addition of IL-1 alpha to culture stimulated the release of both TNF alpha and GM-CSF and acted synergistically with both cytokines, resulting in a dose-dependent suppression of BFU-E and stimulation of CFU-GM growth. The increase in CFU-GM caused by the addition of IL-1 alpha was mediated by GM-CSF but not by TNF alpha as the increase was prevented by the addition of a monoclonal anti-GM-CSF antibody but not by anti-TNF alpha. When either TNF alpha or GM-CSF was neutralized by monoclonal antibodies the addition of IL-1 alpha resulted in a significant increase in BFU-E growth. The addition of GM-CSF to culture caused a dose-dependent suppression of BFU-E that was mediated by TNF alpha, as colony number was not reduced when GM-CSF and a monoclonal anti-TNF alpha antibody were simultaneously added to culture. TNF alpha-induced suppression of BFU-E only occurred in the presence of macrophages. In macrophage-depleted cultures, a dose-dependent suppression of BFU-E could be induced if subinhibitory concentrations of IL-1 alpha or GM-CSF were simultaneously added with increasing concentrations of TNF alpha. The effects of IL-1 alpha or GM-CSF and TNF alpha were markedly synergistic so that the doses required to induce

Changes in carotenoids during processing and storage of pumpkin puree.

PubMed

Provesi, João Gustavo; Dias, Carolinne Odebrecht; Amante, Edna Regina

2011-09-01

Changes in the contents of carotenoids and their true retentions (% TR) during the production of puree of Cucurbita moschata 'Menina Brasileira' and of Cucurbita maxima 'Exposição' pumpkins and the stability of such compounds during 180days of storage were monitored by liquid chromatography coupled with a photodiode array detector. Cooking caused higher losses than commercial sterilisation. High losses of xanthophylls such as lutein and violaxanthin were noted during processing and storage of pumpkin puree. Such losses show the low stability of these compounds. The major carotenoids, pro-vitamin A carotenes, namely, α-carotene and all-trans-β-carotene for C. moschata 'Menina Brasileira' and all-trans-β-carotene for C. maxima 'Exposição' obtained high retentions (>75%) after processing. A slight degree of isomerisation of β-carotene was noted in the puree samples, but with low concentrations of cis-isomers. Storage for 180days did not significantly affect (P⩽0.05) the concentrations of these carotenoids. Copyright © 2011 Elsevier Ltd. All rights reserved.

Techno-functional properties of tomato puree fortified with anthocyanin pigments.

PubMed

Gerardi, C; Albano, C; Calabriso, N; Carluccio, M A; Durante, M; Mita, G; Renna, M; Serio, F; Blando, F

2018-02-01

This study investigates the effects of tomato puree fortification with several anthocyanin-rich food colorants on bioactive compound content (phenolics, isoprenoids), antioxidant capacity, in vitro biological activities and consumer acceptance. Tomato puree (tp) was added with different anthocyanin extracts from black carrot (Anthocarrot), grape fruit skins (Enocolor), elderberry fruits (Elderberry) or mahaleb cherry fruits (Mahaleb), thus obtaining a 'functional tomato puree' (ftp). The consumer acceptance (colour, flavor, taste, visual appearance) was at high level, except for Mahaleb-added ftp. Compared to the control (tp), the addition of colouring extracts increased significantly the total phenolic content, before pasteurization, in addition to the expected anthocyanin content. However, after pasteurization, mostly Anthocarrot-ftp preserved an increased phenolic (+53%) content, as well as a higher antioxidant capacity (50%), more than the other added-extracts. Consistently, against tp, Anthocarrot-ftp exhibited an increased anti-inflammatory capacity as showed by the reduced expression of vascular cell adhesion molecule (VCAM)-1 in human cultured endothelial cells, under inflammatory conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of impurities on the biodegradation behavior of pure magnesium

NASA Astrophysics Data System (ADS)

Lee, Ji-Young; Han, Gilsoo; Kim, Yu-Chan; Byun, Ji-Young; Jang, Jae-il; Seok, Hyun-Kwang; Yang, Seok-Jo

2009-12-01

The corrosion behavior of pure magnesium that has different content ratio of impurities (such as Fe/Mn ratio) in Hanks' solution was investigated in order to tailor the lifetime of biodegradable implant made of pure magnesium. Two distinct stages of corrosion were observed: a slow corrosion rate stage and a subsequent fast corrosion rate stage. The first stage was characterized by uniform corrosion that produced magnesium hydroxide and calcium phosphate film on a magnesium surface, resulting in a slow corrosion rate. The second stage with an abrupt increase in the corrosion rate was induced by Fe precipitates and was stimulated by an increase in the Fe/Mn ratio. This corrosion was developed to a preferred crystallographic pitting corrosion where the pits propagated along the preferred crystallographic plane and several layers of Mg planes with narrow interplanar space remained uncorroded. From this study, it is expected that the lifetime of the biodegradable implant made of pure Mg can be tailored by controlling the amount and ratio of the impurities.

Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5☆

PubMed Central

Ashino, Takashi; Ohkubo-Morita, Haruyo; Yamamoto, Masayuki; Yoshida, Takemi; Numazawa, Satoshi

2014-01-01

Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2)–deficient (Nrf2−⧸−) mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2−⧸− mouse livers were lower than that in wild-type mouse livers. Nrf2−⧸− mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression. PMID:24494203

Enhancing the Electrochemical Behavior of Pure Copper by Cyclic Potentiodynamic Passivation: A Comparison between Coarse- and Nano-Grained Pure Copper

NASA Astrophysics Data System (ADS)

Fattah-alhosseini, Arash; Imantalab, Omid; Attarzadeh, Farid Reza

2016-10-01

Electrochemical behavior of coarse- and nano-grained pure copper were modified and improved to a large extent by the application of cyclic potentiodynamic passivation. The efficacy of this method was evaluated on the basis of grain size which is of great importance in corrosion studies. In this study, the eight passes of accumulative roll bonding process at room temperature were successfully performed to produce nano-grained pure copper. Transmission electron microscopy image indicated that the average grain size reached below 100 nm after eight passes. On the basis of cyclic voltammetry and also the electrochemical tests performed after that, it was revealed that cyclic potentiodynamic passivation had a significant improving effect on the passive behavior of both coarse- and nano-grained samples. In addition, a superior behavior of nano-grained sample in comparison to coarse-grained one was distinguished by its smaller cyclic voltammogram loops, nobler free potentials, larger capacitive arcs in the Nyquist plots, and less charge carrier densities within the passive film.

Enhanced bactericidal activity against Escherichia coli in calves fed Morinda citrifolia (Noni) puree.

PubMed

Schäfer, M; Sharp, P; Brooks, V J; Xu, J; Cai, J; Keuler, N S; Peek, S F; Godbee, R G; Schultz, R D; Darien, B J

2008-01-01

Although adequate colostrum intake and properly used antibiotics can provide much protection for the bovine neonate, increased antibiotic scrutiny and consumer demand for organic products have prompted investigations of natural immunomodulators for enhancing calf health. One plant-based immunomodulator, Morinda citrifolia (noni) fruit, is a well-recognized natural product that has a broad range of immunomodulatory effects. Neonatal calves fed noni puree would demonstrate whole blood phagocytic capacity in Gram-negative and Gram-positive in vitro assays. Blood samples from 18 neonatal Holstein bull calves. Calves were divided into 2 groups: Group 1 comprised control calves, whereas Group 2 received 30 mL of noni puree twice a day in milk replacer. Day 0 blood samples were obtained between 36 and 48 hours of age before the first feeding of puree. Ethylenediaminetetraacetic acid anticoagulated blood was collected from each calf on days 0, 3, 7, and 14. Bactericidal assays were performed to estimate the percentage killing of Escherichia coli and Staphylococcus epidermidis. Blood samples from noni puree-fed calves displayed significantly more E. coli bacterial killing than did controls on day 14, and although differences were not significant on days 0, 3, and 7, bacterial killing progressively increased over time. There was no significant difference between the groups for S. epidermidis killing. The immunomodulatory effect of noni puree may prove valuable in the future as production animal antibiotic use becomes more restricted. Additional clinical trials are warranted to investigate the clinical application of noni puree in promoting calf health.

Corrosion resistance and blood compatibility of lanthanum ion implanted pure iron by MEVVA

NASA Astrophysics Data System (ADS)

Zhu, Shengfa; Huang, Nan; Shu, Hui; Wu, Yanping; Xu, Li

2009-10-01

Pure iron is a potential material applying for coronary artery stents based on its biocorrodible and nontoxic properties. However, the degradation characteristics of pure iron in vivo could reduce the mechanical stability of iron stents prematurely. The purpose of this work was to implant the lanthanum ion into pure iron specimens by metal vapor vacuum arc (MEVVA) source at an extracted voltage of 40 kV to improve its corrosion resistance and biocompatibility. The implanted fluence was up to 5 × 10 17 ions/cm 2. The X-ray photoelectron spectroscopy (XPS) was used to characterize the chemical state and depth profiles of La, Fe and O elements. The results showed lanthanum existed in the +3 oxidation state in the surface layer, most of the oxygen combined with lanthanum and form a layer of oxides. The lanthanum ion implantation layer could effectively hold back iron ions into the immersed solution and obviously improved the corrosion resistance of pure iron in simulated body fluids (SBF) solution by the electrochemical measurements and static immersion tests. The systematic evaluation of blood compatibility, including in vitro platelets adhesion, prothrombin time (PT), thrombin time (TT), indicated that the number of platelets adhesion, activation, aggregation and pseudopodium on the surface of the La-implanted samples were remarkably decreased compared with pure iron and 316L stainless steel, the PT and TT were almost the same as the original plasma. It was obviously showed that lanthanum ion implantation could effectively improve the corrosion resistance and blood compatibility of pure iron.

Investigation on the Enhanced Oxidation of Ferritic/Martensitic Steel P92 in Pure Steam

PubMed Central

Yuan, Juntao; Wu, Ximao; Wang, Wen; Zhu, Shenglong; Wang, Fuhui

2014-01-01

Oxidation of ferritic/martensitic steel P92 was investigated in pure oxygen and in pure steam at 600–800 °C by thermogravimetric analysis (TGA), optical microscopy (OM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results showed that the oxidation of P92 was significantly enhanced and multilayer scale with an outer iron oxides layer formed in pure steam. At 700 °C, the gas switch markedly influenced the scaling kinetics and scale microstructure. It was supposed that the higher affinity of iron to steam would be attributed to the enhanced oxidation of P92 in pure steam, and the much easier transport of hydroxyl would account for the significant difference induced by gas switch. PMID:28788592

Theory of Direct Optical Measurement of Pure Spin Currents in Direct-gap Semiconductors

NASA Astrophysics Data System (ADS)

Wang, Jing; Liu, Ren-Bao; Zhu, Bang-Fen

2010-01-01

We predict that a pure spin current in a semiconductor may lead to the optical circular birefingence effect without invoking magnetization. This effect may be exploited for a direct, non-destructive measurement of the pure spin current. We derive the effective coupling between a pure spin current and a polarized light beam, and point out that it originates from the inherent spin-orbit coupling in the valence bands, rather than the Rashba or Dresselhaus effects due to inversion asymmetries. The Faraday rotation angle in GaAs is estimated, which indicates that this spin current optical birefringence is experimentally observable.

Erythroid Promoter Confines FGF2 Expression to the Marrow after Hematopoietic Stem Cell Gene Therapy and Leads to Enhanced Endosteal Bone Formation

PubMed Central

Meng, Xianmei; Baylink, David J.; Sheng, Matilda; Wang, Hongjie; Gridley, Daila S.; Lau, K.-H. William; Zhang, Xiao-Bing

2012-01-01

Fibroblast growth factor-2 (FGF2) has been demonstrated to be a promising osteogenic factor for treating osteoporosis. Our earlier study shows that transplantation of mouse Sca-1+ hematopoietic stem/progenitor cells that are engineered to express a modified FGF2 leads to considerable endosteal/trabecular bone formation, but it also induces adverse effects like hypocalemia and osteomalacia. Here we report that the use of an erythroid specific promoter, β-globin, leads to a 5-fold decrease in the ratio of serum FGF2 to the FGF2 expression in the marrow cavity when compared to the use of a ubiquitous promoter spleen focus-forming virus (SFFV). The confined FGF2 expression promotes considerable trabeculae bone formation in endosteum and does not yield anemia and osteomalacia. The avoidance of anemia in the mice that received Sca1+ cells transduced with FGF2 driven by the β-globin promoter is likely due to attenuation of high-level serum FGF2-mediated stem cell mobilization observed in the SFFV-FGF2 animals. The prevention of osteomalacia is associated with substantially reduced serum Fgf23/hypophosphatemia, and less pronounced secondary hyperparathyroidism. Our improved stem cell gene therapy strategy represents one step closer to FGF2-based clinical therapy for systemic skeletal augmentation. PMID:22629419

Effect of laser soldering irradiation on covalent bonds of pure collagen.

PubMed

Constantinescu, Mihai A; Alfieri, Alex; Mihalache, George; Stuker, Florian; Ducray, Angélique; Seiler, Rolf W; Frenz, Martin; Reinert, Michael

2007-03-01

Laser tissue welding and soldering is being increasingly used in the clinical setting for defined surgical procedures. The exact induced changes responsible for tensile strength are not yet fully investigated. To further improve the strength of the bonding, a better understanding of the laser impact at the subcellular level is necessary. The goal of this study was to analyze whether the effect of laser irradiation on covalent bonding in pure collagen using irradiances typically applied for tissue soldering. Pure rabbit and equine type I collagen were subjected to laser irradiation. In the first part of the study, rabbit and equine collagen were compared using identical laser and irradiation settings. In the second part of the study, equine collagen was irradiated at increasing laser powers. Changes in covalent bonding were studied indirectly using the sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) technique. Tensile strengths of soldered membranes were measured with a calibrated tensile force gauge. In the first experiment, no differences between the species-specific collagen bands were noted, and no changes in banding were found on SDS-PAGE after laser irradiation. In the second experiment, increasing laser irradiation power showed no effect on collagen banding in SDS-PAGE. Finally, the laser tissue soldering of pure collagen membranes showed virtually no determinable tensile strength. Laser irradiation of pure collagen at typical power settings and exposure times generally used in laser tissue soldering does not induce covalent bonding between collagen molecules. This is true for both rabbit and equine collagen proveniences. Furthermore, soldering of pure collagen membranes without additional cellular components does not achieve the typical tensile strength reported in native, cell-rich tissues. This study is a first step in a better understanding of laser impact at the molecular level and might prove useful in engineering of combined

Strength tests of thin-walled elliptic duralumin cylinders in pure bending and in combined pure bending and torsion

NASA Technical Reports Server (NTRS)

Lundquist, Eugene E; Stowell, Elbridge Z

1942-01-01

An analysis is presented of the results of tests made by the Massachusetts Institute of Technology and by the National Advisory Committee for Aeronautics on an investigation of the strength of thin-walled circular and elliptic cylinders in pure bending and in combined torsion and bending. In each of the loading conditions, the bending moments were applied in the plane of the major axis of the ellipse.

Non-Born-Oppenheimer calculations of the pure vibrational spectrum of HeH+.

PubMed

Pavanello, Michele; Bubin, Sergiy; Molski, Marcin; Adamowicz, Ludwik

2005-09-08

Very accurate calculations of the pure vibrational spectrum of the HeH(+) ion are reported. The method used does not assume the Born-Oppenheimer approximation, and the motion of both the electrons and the nuclei are treated on equal footing. In such an approach the vibrational motion cannot be decoupled from the motion of electrons, and thus the pure vibrational states are calculated as the states of the system with zero total angular momentum. The wave functions of the states are expanded in terms of explicitly correlated Gaussian basis functions multipled by even powers of the internuclear distance. The calculations yielded twelve bound states and corresponding eleven transition energies. Those are compared with the pure vibrational transition energies extracted from the experimental rovibrational spectrum.

Radiation effects on beta /10.6/ of pure and europium doped KCl

NASA Technical Reports Server (NTRS)

Grimes, H. H.; Maisel, J. E.; Hartford, R. H.

1975-01-01

Changes in the optical absorption coefficient as the result of X-ray and electron bombardment of pure monocrystalline and polycrystalline KCl and of divalent europium doped polycrystalline KCl were determined. A constant heat flow calorimetric method was used to measure the optical absorption coefficients. Both 300 kV X-ray irradiation and 2 MeV electron irradiation produced increases in the optical absorption coefficient at room temperature. X-ray irradiation produced more significant changes in pure monocrystalline KCl than equivalent amounts of electron irradiation. Electron irradiation of pure and Eu-doped polycrystalline KCl produced increases in the absorption by as much as a factor of 20 over untreated material. Bleaching of the electron-irradiated doped KCl with 649 millimicron light produced a further increase.

Suppressing hillock formation in Si-supported pure Al films

NASA Astrophysics Data System (ADS)

Liu, N. Z.; Liu, Y.

2018-04-01

To suppress the hillock formation and hence improve the service performance of pure Al thin films deposited on Si substrate, dependence of hillock formation on film thickness and annealing temperature was systematically investigated. Experimental results revealed that the hillock volume increased linearly with both the film thickness and annealing temperature. While the evolution of hillock density with film thickness was complicated, strongly depending on the annealing temperature. It was evident that the hillock formation could be effectively suppressed at a critical annealing temperature especially in thinner thickness, similar to the previous findings in Mo/glass-supported pure Al films. These experimental evidences clearly demonstrated that the hillock formation should be controlled by the plastic deformation in the surrounding film, which was further rationalized by a micromechanics model.

Method of production of pure hydrogen near room temperature from aluminum-based hydride materials

DOEpatents

Pecharsky, Vitalij K.; Balema, Viktor P.

2004-08-10

The present invention provides a cost-effective method of producing pure hydrogen gas from hydride-based solid materials. The hydride-based solid material is mechanically processed in the presence of a catalyst to obtain pure gaseous hydrogen. Unlike previous methods, hydrogen may be obtained from the solid material without heating, and without the addition of a solvent during processing. The described method of hydrogen production is useful for energy conversion and production technologies that consume pure gaseous hydrogen as a fuel.

[Inhibition of Bacillus coagulans growth in laboratory media and in fruit purees].

PubMed

Cerrutti, P; Alzamora, S M; de Huergo, M S

2000-01-01

The growth of two strains of B. coagulans was inhibited in laboratory media at pH < or = 4.5, and at water activity (aw) levels of 0.96 for B. coagulans NRS 609 and 0.95 for B. coagulans ATCC 803. The growth of both strains was also inhibited in apple and strawberry purees (pH = 3.5) stored at 37 degrees C for over two months. B. coagulans was able to grow in banana puree (pH approximately equal to 5.0) but acidification of the puree at pH = 3.5 was enough to prevent growth. The addition of up to 3,000 ppm vainillin ("natural" preservative) or 1,000 ppm potassium sorbate (traditional preservative) at pH higher than the inhibitory level previously determined could not prevent growth of B. coagulans in laboratory or in fruits, but 100 ppm lysozyme retarded growth in laboratory media at different pH levels (from 4.5 to 6.7) and in banana puree. As lysozyme showed to be effective at pH < or = 6.7, it might be used to prevent growth of B. coagulans at an eventual increment of pH during storage.

Pasteurization of strawberry puree using a pilot plant pulsed electric fields (PEF) system

USDA-ARS?s Scientific Manuscript database

The processing of strawberry puree by pulsed electric fields (PEF) in a pilot plant system has never been evaluated. In addition, a method does not exist to validate the exact number and shape of the pulses applied during PEF processing. Both buffered peptone water (BPW) and fresh strawberry puree (...

Social phobia, panic disorder and suicidality in subjects with pure and depressive mania.

PubMed

Dilsaver, Steven C; Chen, Yuan-Who

2003-11-01

The objective of this study is to ascertain the rates of social phobia, panic disorder and suicidality in the midst of the manic state among subjects with pure and depressive mania. Subjects received evaluations entailing the use of serial standard clinical interviews, the Schedule for Affective Disorders and Schizophrenia (SADS) and a structured interview to determine whether they met the criteria for intra-episode social phobia (IESP) and panic disorder (IEPD). The diagnoses of major depressive disorder and mania were rendered using the Research Diagnostic Criteria. The diagnoses of IESP and IEPD were rendered using DSM-III-R criteria. Categorization as being suicidal was based on the SADS suicide subscale score. Twenty-five (56.8%) subjects had pure and 19 (43.2%) subjects had depressive mania. None of the subjects with pure and 13 (68.4%) with depressive mania had IESP (P<0.0001). One (4.0%) subject with pure and 16 (84.2%) subjects with depressive mania had IEPD (P<0.0001). One (4.0%) subject with pure and 12 (63.2%) subjects with depressive were suicidal. Twelve of 13 (92.3%) subjects with depressive mania met the criteria for IESP and IEPD concurrently (P<0.0001). All were suicidal. The study suffers limitations imposed by small sample sizes and non-blind methods of identifying subjects with IESP, IEPD and who were suicidal. Subjects with depressive but not pure mania exhibited high rates of both IESP and IEPD. Concurrence of the disorders is the rule. The findings suggest that databases disclosing a relationship between panic disorder and suicidality merit, where possible, reanalysis directed at controlling for the effect of social phobia.

Mental rotation and the human body: Children's inflexible use of embodiment mirrors that of adults.

PubMed

Krüger, Markus; Ebersbach, Mirjam

2017-12-25

Adults' mental rotation performance with body-like stimuli is enhanced if these stimuli are anatomically compatible with a human body, but decreased by anatomically incompatible stimuli. In this study, we investigated these effects for kindergartners and first-graders: When asked to mentally rotate cube configurations attached with human body parts in an anatomically compatible way, allowing for the projection of a human body, children performed better than with pure cube combinations. By contrast, when body parts were attached in an anatomically incompatible way, disallowing the projection of a human body, children performed worse than with pure combinations. This experiment is of specific interest against the background of two different theoretical approaches concerning imagery and the motor system in development: One approach assumes an increasing integration of motor processes and imagery over time that enables older children and adults to requisition motor resources for imagery processes, while the other postulates that imagery stems from early sensorimotor processes in the first place, and is disentangled from it over time. The finding that children of the two age groups tested show exactly the same effects as adults when mentally rotating anatomically compatible and incompatible stimuli is interpreted in favour of the latter approach. Statement of contribution What is already known on this subject? In mental rotation, adults perform better when rotating anatomically possible stimuli as compared to rotating standard cube combinations. Performance is worse when rotating anatomically impossible stimuli. What does this study add? The present study shows that children's mental transformations mirror those of adults in these respects. In case of the anatomically impossible stimuli, this highlights an inflexible use of embodiment in both age groups. This is in line with the Piagetian assumption of imagery being based on sensorimotor processes. © 2017 The British

Erythropoiesis from Human Embryonic Stem Cells Through Erythropoietin-Independent AKT Signaling

PubMed Central

Kim, William S.; Zhu, Yuhua; Deng, Qiming; Chin, Chee Jia; He, Chong Bin; Grieco, Amanda J.; Dravid, Gautam G.; Parekh, Chintan; Hollis, Roger P.; Lane, Timothy F.; Bouhassira, Eric E.; Kohn, Donald B.; Crooks, Gay M.

2014-01-01

Unlimited self renewal capacity and differentiation potential make human pluripotent stem cells (PSC) a promising source for the ex vivo manufacture of red blood cells (RBC) for safe transfusion. Current methods to induce erythropoiesis from PSC suffer from low yields of RBCs, most of which are immature and contain embryonic and fetal rather than adult hemoglobins. We have previously shown that homo-dimerization of the intracellular component of MPL (ic-MPL) induces erythropoiesis from human cord blood progenitors. The goal of the present study was to investigate the potential of ic-MPL dimerization to induce erythropoiesis from human embryonic stem cells (hESC) and to identify the signaling pathways activated by this strategy. We present here evidence that ic-MPL dimerization induces erythropoietin (EPO)-independent erythroid differentiation from hESC by inducing the generation of erythroid progenitors and by promoting more efficient erythroid maturation with increased RBC enucleation as well as increased gamma:epsilon globin ratio and production of beta-globin protein. ic-MPL dimerization is significantly more potent than EPO in inducing erythropoiesis and its effect is additive to EPO. Signaling studies show that dimerization of ic-MPL, unlike stimulation of the wild type MPL receptor, activates AKT in the absence of JAK2/STAT5 signaling. AKT activation upregulates the GATA-1 and FOXO3 transcriptional pathways with resulting inhibition of apoptosis, modulation of cell cycle and enhanced maturation of erythroid cells. These findings open up potential new targets for the generation of therapeutically relevant RBC products from hPSC. PMID:24677652

About being pure and natural: understandings of pre-service primary teachers

NASA Astrophysics Data System (ADS)

Lake, David

2005-04-01

In an investigation of 149 pre-service primary teachers' understanding of the terms pure and natural, the participants were asked to provide definitions of the two words, and classify various substances including drugs of abuse, pharmaceuticals, nutriceuticals, and household substances as either natural or not natural, and as pure or not pure. A common scale of purity and naturalness could be constructed consistent with the Rasch model, suggesting that the participants conflate the two terms. This conflation is consistent with the qualitative data that suggested participants associated both concepts within a common spiritual metaphor, heavily laden with emotive content. Purity was not seen as relating to the composition of a substance, but to its history. The findings may help explain the development of persistent non-scientific chemical taxonomies observed in secondary students. Furthermore, as health educators, the participants may become the source of inappropriate messages about the use of medicines, or the abuse of drugs.

Pure spin current manipulation in antiferromagnetically exchange coupled heterostructures

NASA Astrophysics Data System (ADS)

Avilés-Félix, L.; Butera, A.; González-Chávez, D. E.; Sommer, R. L.; Gómez, J. E.

2018-03-01

We present a model to describe the spin currents generated by ferromagnet/spacer/ferromagnet exchange coupled trilayer systems and heavy metal layers with strong spin-orbit coupling. By exploiting the magnitude of the exchange coupling (oscillatory RKKY-like coupling) and the spin-flop transition in the magnetization process, it has been possible to produce spin currents polarized in arbitrary directions. The spin-flop transition of the trilayer system originates pure spin currents whose polarization vector depends on the exchange field and the magnetization equilibrium angles. We also discuss a protocol to control the polarization sign of the pure spin current injected into the metallic layer by changing the initial conditions of magnetization of the ferromagnetic layers previously to the spin pumping and inverse spin Hall effect experiments. The small differences in the ferromagnetic layers lead to a change in the magnetization vector rotation that permits the control of the sign of the induced voltage components due to the inverse spin Hall effect. Our results can lead to important advances in hybrid spintronic devices with new functionalities, particularly, the ability to control microscopic parameters such as the polarization direction and the sign of the pure spin current through the variation of macroscopic parameters, such as the external magnetic field or the thickness of the spacer in antiferromagnetic exchange coupled systems.

Metastable growth of pure wurtzite InGaAs microstructures.

PubMed

Ng, Kar Wei; Ko, Wai Son; Lu, Fanglu; Chang-Hasnain, Connie J

2014-08-13

III-V compound semiconductors can exist in two major crystal phases, namely, zincblende (ZB) and wurtzite (WZ). While ZB is thermodynamically favorable in conventional III-V epitaxy, the pure WZ phase can be stable in nanowires with diameters smaller than certain critical values. However, thin nanowires are more vulnerable to surface recombination, and this can ultimately limit their performances as practical devices. In this work, we study a metastable growth mechanism that can yield purely WZ-phased InGaAs microstructures on silicon. InGaAs nucleates as sharp nanoneedles and expand along both axial and radial directions simultaneously in a core-shell fashion. While the base can scale from tens of nanometers to over a micron, the tip can remain sharp over the entire growth. The sharpness maintains a high local surface-to-volume ratio, favoring hexagonal lattice to grow axially. These unique features lead to the formation of microsized pure WZ InGaAs structures on silicon. To verify that the WZ microstructures are truly metastable, we demonstrate, for the first time, the in situ transformation from WZ to the energy-favorable ZB phase inside a transmission electron microscope. This unconventional core-shell growth mechanism can potentially be applied to other III-V materials systems, enabling the effective utilization of the extraordinary properties of the metastable wurtzite crystals.

Pure Gaussian state generation via dissipation: a quantum stochastic differential equation approach.

PubMed

Yamamoto, Naoki

2012-11-28

Recently, the complete characterization of a general Gaussian dissipative system having a unique pure steady state was obtained. This result provides a clear guideline for engineering an environment such that the dissipative system has a desired pure steady state such as a cluster state. In this paper, we describe the system in terms of a quantum stochastic differential equation (QSDE) so that the environment channels can be explicitly dealt with. Then, a physical meaning of that characterization, which cannot be seen without the QSDE representation, is clarified; more specifically, the nullifier dynamics of any Gaussian system generating a unique pure steady state is passive. In addition, again based on the QSDE framework, we provide a general and practical method to implement a desired dissipative Gaussian system, which has a structure of quantum state transfer.

Use of pure glycerol in fattening heavy pigs.

PubMed

Della Casa, G; Bochicchio, D; Faeti, V; Marchetto, G; Poletti, E; Rossi, A; Garavaldi, A; Panciroli, A; Brogna, N

2009-01-01

Eighty Italian Duroc×Italian Large White pigs (BW 42.6±3.37kg) were used to determine the effects of pure glycerol on growth performance and meat quality of heavy pigs. Pigs were divided into five groups receiving 0% (control), 5% or 10% during the growing and finishing phases (42.6-160kg BW) (G+F5,G+F10) or 5% or 10% during the finishing period (100-160kg BW) (FIN5,FIN10) of pure glycerol in substitution for maize meal (on a dry matter basis). The pigs were slaughtered at approximately 160kg BW. The growth performance of pigs fed 5% glycerol did not differ from controls regardless of feeding duration, whereas those fed 10% glycerol showed reduced growth and poorer feed:gain ratio. Fat quality and meat suitability for raw ham curing were not affected by dietary treatment. Differences were not consistent enough to draw any conclusion about the effects of feeding glycerol on sensory characteristics.

Preparation and physical characterization of pure beta-carotene.

PubMed

Laughlin, Robert G; Bunke, Gregory M; Eads, Charles D; Laidig, William D; Shelley, John C

2002-05-01

Pure all-trans beta-carotene has been prepared on the 10's of grams scale by isothermal Fractional Dissolution (FD) of commercial laboratory samples in tetrahydrofuran (THF). beta-Carotene purified in this way is black, with a faint brownish tinge. The electronic spectra of black samples extend into the near infrared, with end-absorption past 750 nm. Black samples react directly with dioxygen under mild conditions to yield the familiar orange or red powders. Pure beta-carotene rigorously obeys Beer's Law in octane over the entire UV-Vis spectral range, while commercial laboratory samples and recrystallized samples do not. NMR self-diffusion coefficient data demonstrate that beta-carotene exists as simple molecular solutions in octane and toluene. The anomalously high crystallinity of beta-carotene can be attributed (from analysis using molecular mechanics) to the facts that: (1) the number of theoretically possible conformers of beta-carotene is extremely small, and (2) only a small fraction of these (ca. 12%, or 127) may actually exist in fluid phases.

Electronic transport in pure and doped UO2

NASA Astrophysics Data System (ADS)

Massih, A. R.

2017-12-01

The thermoelectric properties of pure and doped UO2, namely the thermal and electrical conductivities and the thermopower, are assessed. We adopt the small polaron theory of the Mott type insulators, wherein the charge carriers, the electron and hole on the U3+ and U5+ ions, are treated as small polarons. For the thermal conductivity, the small polaron theory is applicable at temperatures above 1500 K. A review of the experimental data on the temperature dependence of the aforementioned transport properties is made. The data include UO2 with dopants such as Cr2O3, Gd2O3, Y2O3 and Nb2O5. We compare the applications of the theory with the data. Two limiting regimes, adiabatic and nonadiabatic, with the ensuing expressions for the conductivities and the thermoelectric power are considered. We discuss both the merits and shortcomings of the putative small polaron model and the simplification thereof as applied to pure and doped uranium dioxide.

Altered soleus responses to magnetic stimulation in pure cerebellar ataxia.

PubMed

Kurokawa-Kuroda, Tomomi; Ogata, Katsuya; Suga, Rie; Goto, Yoshinobu; Taniwaki, Takayuki; Kira, Jun-Ichi; Tobimatsu, Shozo

2007-06-01

Transcranial magnetic stimulation (TMS) over the leg motor area elicits a soleus primary response (SPR) and a soleus late response (SLR). We evaluated the influence of the cerebellofugal pathway on the SPR and SLR in patients with 'pure' cerebellar ataxia. SPRs and SLRs were recorded from 11 healthy subjects and 9 patients with 'pure' cerebellar cortical degeneration; 5 with spinocerebellar ataxia type 6 (SCA6), and 4 with late cortical cerebellar ataxia (LCCA). In addition, three patients with localized cerebellar lesions were tested. The SPR latency was significantly longer in patients than in controls, but primary responses in the tibialis anterior muscle were normal. The frequency of abnormal SLR was 38.9% in the supine position and 83.3% in the standing position. Two out of three patients with localized cerebellar lesions also showed abnormal SLR. Altered SPRs in patients may result from a dysfunction of the primary motor cortex caused by crossed cerebello-cerebral diaschisis. In addition, our results suggest that 'pure' cerebellar degeneration involves the mechanism responsible for evoking SLR which is related to the control of posture. SLR can be a useful neurophysiological parameter for evaluating cerebellofugal function.

Behavior of pure gallium in water and various saline solutions.

PubMed

Horasawa, N; Nakajima, H; Takahashi, S; Okabe, T

1997-12-01

This study investigated the chemical stability of pure gallium in water and saline solutions in order to obtain fundamental knowledge about the corrosion mechanism of gallium-based alloys. A pure gallium plate (99.999%) was suspended in 50 mL of deionized water, 0.01%, 0.1% or 1% NaCl solution at 24 +/- 2 degrees C for 1, 7, or 28 days. The amounts of gallium released into the solutions were determined by atomic absorption spectrophotometry. The surfaces of the specimens were examined after immersion by x-ray diffractometry (XRD) and x-ray photoelectron spectroscopy (XPS). In the solutions containing 0.1% or more NaCl, the release of gallium ions into the solution was lowered when compared to deionized water after 28-day immersion. Gallium oxide monohydroxide was found by XRD on the specimens immersed in deionized water after 28-day immersion. XPS indicated the formation of gallium oxide/hydroxide on the specimens immersed in water or 0.01% NaCl solution. The chemical stability of pure solid gallium was strongly affected by the presence of Cl- ions in the aqueous solution.

Synthesis of Enantiomerically Pure Anthracyclinones

NASA Astrophysics Data System (ADS)

Achmatowicz, Osman; Szechner, Barbara

The anthracycline antibiotics are among the most important clinical drugs used in the treatment of human cancer. The search for new agents with improved therapeutic efficacy and reduced cardiotoxicity stimulated considerable efforts in the synthesis of new analogues. Since the biological activity of anthracyclines depends on their natural absolute configuration, various strategies for the synthesis of enantiomerically pure anthracyclinones (aglycones) have been developed. They comprise: resolution of racemic intermediate, incorporation of a chiral fragment derived from natural and non-natural chiral pools, asymmetric synthesis with the use of a chiral auxiliary or a chiral reagent, and enantioselective catalysis. Synthetic advances towards enantiopure anthracyclinones reported over the last 17 years are reviewed.

Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of nuclear factor (erythroid-derived 2)-like 2

PubMed Central

Zhao, Hailin; Mitchell, Sian; Ciechanowicz, Sarah; Savage, Sinead; Wang, Tianlong; Ji, Xunming; Ma, Daqing

2016-01-01

Perinatal hypoxic ischaemic encephalopathy (HIE) has a high mortality rate with neuropsychological impairment. This study investigated the neuroprotective effects of argon against neonatal hypoxic-ischaemic brain injury. In vitro cortical neuronal cell cultures derived from rat foetuses were subjected to an oxygen and glucose deprivation (OGD) challenge for 90 minutes and then exposed to 70% argon or nitrogen with 5% carbon dioxide and balanced with oxygen for 2 hours. In vivo, seven-day-old rats were subjected to unilateral common carotid artery ligation followed by hypoxic (8% oxygen balanced with nitrogen) insult for 90 minutes. They were exposed to 70% argon or nitrogen balanced with oxygen for 2 hours. In vitro, argon treatment of cortical neuronal cultures resulted in a significant increase of p-mTOR and Nuclear factor (erythroid-derived 2)-like 2(Nrf2) and protection against OGD challenge. Inhibition of m-TOR through Rapamycin or Nrf2 through siRNA abolished argon-mediated cyto-protection. In vivo, argon exposure significantly enhanced Nrf2 and its down-stream effector NAD(P)H Dehydrogenase, Quinone 1(NQO1) and superoxide dismutase 1(SOD1). Oxidative stress, neuroinflammation and neuronal cell death were significantly decreased and brain infarction was markedly reduced. Blocking PI-3K through wortmannin or ERK1/2 through U0126 attenuated argon-mediated neuroprotection. These data provide a new molecular mechanism for the potential application of argon as a neuroprotectant in HIE. PMID:27016422

Comparing pure-tone audiometry and auditory steady state response for the measurement of hearing loss.

PubMed

Ahn, Joong Ho; Lee, Hyo-Sook; Kim, Young-Jin; Yoon, Tae Hyun; Chung, Jong Woo

2007-06-01

To compare pure-tone audiometry and auditory steady state response (ASSR) to measure hearing loss based on the severity of hearing loss in frequencies. A total of 105 subjects (168 ears, 64 male and 41 female) were enrolled in this study. We determined hearing level by measurement of pure-tone audiometry and ASSR on the same day for each subject. Pure-tone audiometry and ASSR were highly correlated (r=0.96). The relationship is described by the equation PTA=1.05 x mean ASSR - 7.6. When analyzed according to the frequencies, the correlation coefficients were 0.94, 0.95, 0.94, and 0.92 for 0.5, 1, 2, and 4 kHz, respectively. From this study, authors could conclude that pure-tone audiometry and ASSR showed very similar results and indicated that ASSR may be a good alternative method for the measurement of hearing level in infants and children, for whom pure-tone audiometry is not appropriate.

Coherent perfect absorber and laser modes in purely imaginary metamaterials

NASA Astrophysics Data System (ADS)

Fu, Yangyang; Cao, Yanyan; Cummer, Steven A.; Xu, Yadong; Chen, Huanyang

2017-10-01

Conjugate metamaterials, in which the permittivity and the permeability are complex conjugates of each other, possess the elements of loss and gain simultaneously. By employing a conjugate metamaterial with a purely imaginary form, we propose a mechanism for realizing both coherent perfect absorber (CPA) and laser modes. Moreover, the general conditions for obtaining CPA and laser modes, including obtaining them simultaneously, are revealed by analyzing the wave scattering properties of a slab made of purely imaginary metamaterials (PIMs). Specifically, in a PIM slab with a subunity effective refractive index, the CPA mode can be simplified as a perfect absorption mode and the incident wave from one side could be perfectly absorbed.

Pure versus mixed electrosurgical current for endoscopic biliary sphincterotomy: a meta-analysis of adverse outcomes.

PubMed

Verma, Dharmendra; Kapadia, Asha; Adler, Douglas G

2007-08-01

Endoscopic biliary sphincterotomy (ES) can cause bleeding, pancreatitis, and perforation. This has, in part, been attributed to the type of electrosurgical current used for ES. No consensus exists on the optimal type of electrosurgical current for ES to maximize safety. To compare the rates of complications in patients undergoing ES via pure current versus mixed current. A systematic review of published, prospective, randomized trials that compared pure current with mixed current for ES. Patients undergoing ES, with random assignment to either current group. Data were standardized for pancreatitis and postsphincterotomy bleeding. There were insufficient data to analyze perforation risk. A random-effects model was used. Bleeding, pancreatitis, and perforation. A total of 804 patients from 4 trials that compared pure current to mixed current were analyzed. The aggregated rate of pancreatitis was 3.8%, 95% confidence interval (CI) 1.0%-6.6%, for the pure-current group versus 7.9%, 95% CI 3.1%-12.7%, for the mixed-current group; the difference was not statistically significant. The rate of bleeding (all severity groups) for the pure-current group was 37.3% (95% CI 27.3%, 47.3%), which was significantly higher than that of the mixed-current group (12.2% [95% CI 4.1%, 20.3%]). Mild bleeding was significantly more frequent with pure current (28.9% [95% CI 16.3, 41.4]) compared with mixed current (9.4% [95% CI 2.1%, 16.8%]). Variables, including endoscopist skill and cannulation difficulty, were difficult to measure. The rate of pancreatitis in patients who underwent ES when using pure current was not significantly different from those when using mixed current. Pure current was associated with more episodes of bleeding, primarily mild bleeding. Data were insufficient to analyze the perforation risk.

The future of 'pure' medical science: the need for a new specialist professional research system.

PubMed

Charlton, Bruce G; Andras, Peter

2005-01-01

Over recent decades, medical research has become mostly an 'applied' science which implicitly aims at steady progress by an accumulation of small improvements, each increment having a high probability of validity. Applied medical science is, therefore, a social system of communications for generating pre-publication peer-reviewed knowledge that is ready for implementation. However, the need for predictability makes modern medical science risk-averse and this is leading to a decline in major therapeutic breakthroughs where new treatments for new diseases are required. There is need for the evolution of a specialized professional research system of pure medial science, whose role would be to generate and critically evaluate radically novel and potentially important theories, techniques, therapies and technologies. Pure science ideas typically have a lower probability of being valid, but the possibility of much greater benefit if they turn out to be true. The domination of medical research by applied criteria means that even good ideas from pure medical science are typically ignored or summarily rejected as being too speculative. Of course, radical and potentially important ideas may currently be published, but at present there is no formal mechanism by which pure science publications may be received, critiqued, evaluated and extended to become suitable for 'application'. Pure medical science needs to evolve to constitute a typical specialized scientific system of formal communications among a professional community. The members of this putative profession would interact via close research groupings, journals, meetings, electronic and web communications--like any other science. Pure medical science units might arise as elite grouping linked to existing world-class applied medical research institutions. However, the pure medical science system would have its own separate aims, procedures for scientific evaluation, institutional organization, funding and support

[The corrosion of pure iron in five different mediums].

PubMed

Xu, Li; Zhu, Shengfa; Huang, Nan; Li, Xinchang; Zhang, Yu

2009-08-01

The sectional test was adopted in this study to investigate the corrosion of pure iron in 0.15 mol/L NaCl solution, Ringer solution, PBS(-) solution, SBF solution and M199 cell culture medium at three different times. The result shows that different mediums have different corrosion effects on pure iron. The arrangement according to the medium's corrosion ability from the strongest to weakest is 0.15 mol/L NaCl solution (Ringer solution), PBS(-) solution, SBF solution and M199 cell culture medium. The results of scanning electron microscopy and energy dispersive X-ray spectrum analyses show that the addition of HPO4(2-), H2POC4-, Ca2+, Mg2+, SO4(2-) and the organic component can inhibit the corrosion to some degree.

Faithful teleportation with arbitrary pure or mixed resource states

NASA Astrophysics Data System (ADS)

Zhao, Ming-Jing; Li, Zong-Guo; Fei, Shao-Ming; Wang, Zhi-Xi; Li-Jost, Xianqing

2011-05-01

We study faithful teleportation systematically with arbitrary entangled states as resources. The necessary conditions of mixed states to complete perfect teleportation are proved. Based on these results, the necessary and sufficient conditions of faithful teleportation of an unknown state |phirang in { C}^d with an entangled resource ρ in { C}^m \\otimes { C}^d and { C}^d \\otimes { C}^n are derived. It is shown that for ρ in { C}^m \\otimes { C}^d, ρ must be a maximally entangled state, while for ρ in { C}^d \\otimes { C}^n, ρ must be a pure maximally entangled state. Moreover, we show that the sender's measurements must be all projectors of maximally entangled pure states. The relations between the entanglement of the formation of the resource states and faithful teleportation are also discussed.

Developmental and Individual Differences in Pure Numerical Estimation

ERIC Educational Resources Information Center

Booth, Julie L.; Siegler, Robert S.

2006-01-01

The authors examined developmental and individual differences in pure numerical estimation, the type of estimation that depends solely on knowledge of numbers. Children between kindergarten and 4th grade were asked to solve 4 types of numerical estimation problems: computational, numerosity, measurement, and number line. In Experiment 1,…

Pure connection action principle for general relativity.

PubMed

Krasnov, Kirill

2011-06-24

It has already been known for two decades that general relativity can be reformulated as a certain gauge theory, so that the only dynamical field is an SO(3) connection and the spacetime metric appears as a derived object. However, no simple action principle realizing these ideas has been available. A new elegant action principle for such a "pure connection" formulation of GR is described.

Pure Lovelock gravity and Chern-Simons theory

NASA Astrophysics Data System (ADS)

Concha, P. K.; Durka, R.; Inostroza, C.; Merino, N.; Rodríguez, E. K.

2016-07-01

We explore the possibility of finding pure Lovelock gravity as a particular limit of a Chern-Simons action for a specific expansion of the AdS algebra in odd dimensions. We derive in detail this relation at the level of the action in five and seven dimensions. We provide a general result for higher dimensions and discuss some issues arising from the obtained dynamics.

75 FR 23318 - Culturally Significant Objects Imported for Exhibition Determinations: “John Baldessari: Pure...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-03

... DEPARTMENT OF STATE [Public Notice 6983] Culturally Significant Objects Imported for Exhibition Determinations: ``John Baldessari: Pure Beauty'' SUMMARY: Notice is hereby given of the following determinations... Baldessari: Pure Beauty,'' imported from abroad for temporary exhibition within the United States, are of...

Effects of the breed, sex and age on cellular content and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel.

PubMed

Giraldo, Carlos E; López, Catalina; Álvarez, María E; Samudio, Ismael J; Prades, Marta; Carmona, Jorge U

2013-02-12

There is no information on the effects of the breed, gender and age on the cellular content and growth factor (GF) release from equine pure-platelet rich plasma (P-PRP) and pure-platelet rich gel (P-PRG). The objectives of this study were: 1) to compare the cellular composition of P-PRP with whole blood and platelet poor plasma (PPP); 2) to compare the concentration of transforming GF beta 1 (TGF-β1) and platelet derived GF isoform BB (PDGF-BB) between P-PRP treated with non-ionic detergent (P-PRP+NID), P-PRG (activated with calcium gluconate -CG-), PPP+NID, PPP gel (PPG), and plasma and; 3) to evaluate and to correlate the effect of the breed, gender and age on the cellular and GF concentration for each blood component. Forty adult horses, 20 Argentinean Creole Horses (ACH) and, 20 Colombian Creole Horses (CCH) were included. Data were analyzed by parametric (i.e.: t-test, one way ANOVA) and non parametric (Kruskal-Wallis test, Wilcoxon test) tests. Correlation analysis was also performed by using the Spearman and Pearson tests. A p ≤ 0.05 was set as significant for all tests. All the blood components were compared for platelet (PLT), leukocyte (WBC), TGF-β1 and PDGF-BB concentrations. The effect of the breed, gender and age on these variables was analyzed. A P ≤ 0.05 was accepted as significant for all the tests. PLT counts were 1.8 and 0.6 times higher in P-PRP than in whole blood and PPP, respectively; WBC counts were 0.5 and 0.1 times lower in P-PRP, in comparison with whole blood and PPP, respectively. TGF-β1 and PDGF-BB concentrations were 2.3 and 262 times higher, respectively, in P-PRG than in plasma, and 0.59 and 0.48 times higher, respectively, in P-PRG than in PPG. P-PRG derived from CCH females or young horses presented significantly (P < 0.001) higher PDGF-BB concentrations than P-PRG derived from ACH males or older horses. Our results indicated that P-PRP obtained by a manual method was affected by intrinsic factors such as the breed

Chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis.

PubMed

Vignjević, Sanja; Budeč, Mirela; Marković, Dragana; Dikić, Dragoslava; Mitrović, Olivera; Mojsilović, Slavko; Durić, Sanja Vranješ; Koko, Vesna; Cokić, Bojana Beleslin; Cokić, Vladan; Jovčić, Gordana

2014-01-01

Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychological stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progenitors in response to stressful stimuli, and emerging evidence suggests that inappropriate activation of stress erythropoiesis may predispose to leukaemic transformation. We used a mouse model to study the influence of chronic psychological stress on erythropoiesis in the spleen and to investigate potential mediators of observed effects. Adult mice were subjected to 2 hrs daily restraint stress for 7 or 14 consecutive days. Our results showed that chronic exposure to restraint stress decreased the concentration of haemoglobin in the blood, elevated circulating levels of erythropoietin and corticosterone, and resulted in markedly increased number of erythroid progenitors and precursors in the spleen. Western blot analysis revealed significantly decreased expression of both erythropoietin receptor and glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic stress enhanced the expression of stem cell factor receptor in the red pulp. Moreover, chronically stressed animals exhibited significantly increased expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as substantially enhanced mRNA expression levels of its receptors in the spleen. These findings demonstrate for the first time that chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis and leads to the prolonged activation of stress erythropoiesis pathways. Prolonged activation of these pathways along with an excessive production of immature erythroid cells may predispose chronically stressed subjects to a higher risk of leukaemic transformation. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for

Idealization in Chemistry: Pure Substance and Laboratory Product

ERIC Educational Resources Information Center

Fernández-González, Manuel

2013-01-01

This article analyzes the concept of idealization in chemistry and the role played by pure substance and laboratory product. This topic has evident repercussions in the educational contexts that are applied to the science classroom, which are highlighted throughout the text. A common structure for knowledge construction is proposed for both…

Dissociative effects of orthographic distinctiveness in pure and mixed lists: an item-order account.

PubMed

McDaniel, Mark A; Cahill, Michael; Bugg, Julie M; Meadow, Nathaniel G

2011-10-01

We apply the item-order theory of list composition effects in free recall to the orthographic distinctiveness effect. The item-order account assumes that orthographically distinct items advantage item-specific encoding in both mixed and pure lists, but at the expense of exploiting relational information present in the list. Experiment 1 replicated the typical free recall advantage of orthographically distinct items in mixed lists and the elimination of that advantage in pure lists. Supporting the item-order account, recognition performances indicated that orthographically distinct items received greater item-specific encoding than did orthographically common items in mixed and pure lists (Experiments 1 and 2). Furthermore, order memory (input-output correspondence and sequential contiguity effects) was evident in recall of pure unstructured common lists, but not in recall of unstructured distinct lists (Experiment 1). These combined patterns, although not anticipated by prevailing views, are consistent with an item-order account.

Microstructures and Dry Sliding Wear Resistance of the Laser Ceramics Composite Coating on Pure Ti

NASA Astrophysics Data System (ADS)

Liu, Peng; Zhang, Yuanbin; Luo, Hui; Huo, Yushuang

2012-06-01

In this study, Al-Ti-Co was used to improve the surface performance of pure Ti. Laser cladding is an important surface modification technique, which can be used to improve the surface performance of pure Ti. Laser cladding of the Al-Ti-Co + TiB2 pre-placed powders on pure Ti can form ceramics reinforced the composite coating, which improved the wear resistance of the substrate. Characteristics of the composite coating were investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), microhardness and wear tests. And the laser-cladded coating can also have major dilution from the substrate. Due to the action of the fine grain strengthening and the phase constituent, the wear resistance and microhardness of pure Ti surface were greatly improved.

Initial experience with purely laparoscopic living-donor right hepatectomy.

PubMed

Hong, S K; Lee, K W; Choi, Y; Kim, H S; Ahn, S W; Yoon, K C; Kim, H; Yi, N J; Suh, K S

2018-05-01

There may be concerns about purely laparoscopic donor right hepatectomy (PLDRH) compared with open donor right hepatectomy, especially when performed by surgeons accustomed to open surgery. This study aimed to describe technical tips and pitfalls in PLDRH. Data from donors who underwent PLDRH at Seoul National University Hospital between December 2015 and July 2017 were analysed retrospectively. Endpoints analysed included intraoperative events and postoperative complications. All operations were performed by a single surgeon with considerable experience in open living donor hepatectomy. A total of 26 donors underwent purely laparoscopic right hepatectomy in the study interval. No donor required transfusion during surgery, whereas two underwent reoperation. In two donors, the dissection plane at the right upper deep portion of the midplane was not correct. One donor experienced portal vein injury during caudate lobe transection, and one developed remnant left hepatic duct stenosis. One donor experienced remnant portal vein angulation owing to a different approach angle, and one experienced arterial damage associated with the use of a laparoscopic energy device. One donor had postoperative bleeding due to masking of potential bleeding foci owing to intra-abdominal pressure during laparoscopy. Two donors experienced right liver surface damage caused by a xiphoid trocar. Purely laparoscopic donor hepatectomy differs from open donor hepatectomy in terms of angle and caudal view. Therefore, surgeons experienced in open donor hepatectomy must gain adequate experience in laparoscopic liver surgery and make adjustments when performing PLDRH. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Pure Mediated Priming: A Retrospective Semantic Matching Model

ERIC Educational Resources Information Center

Jones, Lara L.

2010-01-01

Mediated priming refers to the activation of a target (e.g., "stripes") by a prime (e.g., "lion") that is related indirectly via a connecting mediator (e.g., tiger). In previous mediated priming studies (e.g., McNamara & Altarriba, 1988), the mediator was associatively related to the prime. In contrast, pure mediated…

Femtosecond pulses propagation through pure water

NASA Astrophysics Data System (ADS)

Naveira, Lucas; Sokolov, Alexei; Byeon, Joong-Hyeok; Kattawar, George

2007-10-01

Recently, considerable attention has been dedicated to the field of optical precursors, which can possibly be applied to long-distance underwater communications. Input beam intensities have been carefully adjusted to keep experiments in the linear regime, and some experiments have shown violation of the Beer-Lambert law. We are presently carrying out experiments using femtosecond laser pulses propagating through pure water strictly in the linear regime to study this interesting and important behavior. We are also employing several new and innovative schemes to more clearly define the phenomena.

Are all maximally entangled states pure?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cavalcanti, D.; Brandao, F.G.S.L.; Terra Cunha, M.O.

We study if all maximally entangled states are pure through several entanglement monotones. In the bipartite case, we find that the same conditions which lead to the uniqueness of the entropy of entanglement as a measure of entanglement exclude the existence of maximally mixed entangled states. In the multipartite scenario, our conclusions allow us to generalize the idea of the monogamy of entanglement: we establish the polygamy of entanglement, expressing that if a general state is maximally entangled with respect to some kind of multipartite entanglement, then it is necessarily factorized of any other system.

Are all maximally entangled states pure?

NASA Astrophysics Data System (ADS)

Cavalcanti, D.; Brandão, F. G. S. L.; Terra Cunha, M. O.

2005-10-01

We study if all maximally entangled states are pure through several entanglement monotones. In the bipartite case, we find that the same conditions which lead to the uniqueness of the entropy of entanglement as a measure of entanglement exclude the existence of maximally mixed entangled states. In the multipartite scenario, our conclusions allow us to generalize the idea of the monogamy of entanglement: we establish the polygamy of entanglement, expressing that if a general state is maximally entangled with respect to some kind of multipartite entanglement, then it is necessarily factorized of any other system.

76 FR 1404 - Pure Magnesium in Granular Form From the People's Republic of China: Rescission of Changed...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-10

... DEPARTMENT OF COMMERCE International Trade Administration [A-570-864] Pure Magnesium in Granular... duty order \\1\\ on pure magnesium in granular form from the People's Republic of China (``PRC'') to... circumstances review. The Department is now rescinding this CCR. \\1\\ See Antidumping Duty Order: Pure Magnesium...

Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway.

PubMed

Ha, Ae Wha; Kim, Woo Kyoung

2017-06-01

Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin F2α (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly ( P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly ( P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly ( P < 0.05) increased in the HF with BGE groups compared to those in the HF group. The improvements of blood glucose homeostasis and antioxidant systems in rats fed with black garlic extract were

Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway

PubMed Central

Ha, Ae Wha

2017-01-01

BACKGROUN/OBJECTIVES Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin F2α (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. RESULTS Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly (P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly (P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly (P < 0.05) increased in the HF with BGE groups compared to those in the HF group. CONCLUSIONS The improvements of blood glucose homeostasis and

Pure-rotational H2 thermometry by ultrabroadband coherent anti-Stokes Raman spectroscopy.

PubMed

Courtney, Trevor L; Bohlin, Alexis; Patterson, Brian D; Kliewer, Christopher J

2017-06-14

Coherent anti-Stokes Raman spectroscopy (CARS) is a sensitive technique for probing highly luminous flames in combustion applications to determine temperatures and species concentrations. CARS thermometry has been demonstrated for the vibrational Q-branch and pure-rotational S-branch of several small molecules. Practical advantages of pure-rotational CARS, such as multi-species detection, reduction of coherent line mixing and collisional narrowing even at high pressures, and the potential for more precise thermometry, have motivated experimental and theoretical advances in S-branch CARS of nitrogen (N 2 ), for example, which is a dominant species in air-fed combustion processes. Although hydrogen (H 2 ) is of interest given its prevalence as a reactant and product in many gas-phase reactions, laser bandwidth limitations have precluded the extension of CARS thermometry to the H 2 S-branch. We demonstrate H 2 thermometry using hybrid femtosecond/picosecond pure-rotational CARS, in which a broadband pump/Stokes pulse enables simultaneous excitation of the set of H 2 S-branch transitions populated at flame temperatures over the spectral region of 0-2200 cm -1 . We present a pure-rotational H 2 CARS spectral model for data fitting and compare extracted temperatures to those from simultaneously collected N 2 spectra in two systems of study: a heated flow and a diffusion flame on a Wolfhard-Parker slot burner. From 300 to 650 K in the heated flow, the H 2 and N 2 CARS extracted temperatures are, on average, within 2% of the set temperature. For flame measurements, the fitted H 2 and N 2 temperatures are, on average, within 5% of each other from 300 to 1600 K. Our results confirm the viability of pure-rotational H 2 CARS thermometry for probing combustion reactions.

Pure-rotational H2 thermometry by ultrabroadband coherent anti-Stokes Raman spectroscopy

NASA Astrophysics Data System (ADS)

Courtney, Trevor L.; Bohlin, Alexis; Patterson, Brian D.; Kliewer, Christopher J.

2017-06-01

Coherent anti-Stokes Raman spectroscopy (CARS) is a sensitive technique for probing highly luminous flames in combustion applications to determine temperatures and species concentrations. CARS thermometry has been demonstrated for the vibrational Q-branch and pure-rotational S-branch of several small molecules. Practical advantages of pure-rotational CARS, such as multi-species detection, reduction of coherent line mixing and collisional narrowing even at high pressures, and the potential for more precise thermometry, have motivated experimental and theoretical advances in S-branch CARS of nitrogen (N2), for example, which is a dominant species in air-fed combustion processes. Although hydrogen (H2) is of interest given its prevalence as a reactant and product in many gas-phase reactions, laser bandwidth limitations have precluded the extension of CARS thermometry to the H2 S-branch. We demonstrate H2 thermometry using hybrid femtosecond/picosecond pure-rotational CARS, in which a broadband pump/Stokes pulse enables simultaneous excitation of the set of H2 S-branch transitions populated at flame temperatures over the spectral region of 0-2200 cm-1. We present a pure-rotational H2 CARS spectral model for data fitting and compare extracted temperatures to those from simultaneously collected N2 spectra in two systems of study: a heated flow and a diffusion flame on a Wolfhard-Parker slot burner. From 300 to 650 K in the heated flow, the H2 and N2 CARS extracted temperatures are, on average, within 2% of the set temperature. For flame measurements, the fitted H2 and N2 temperatures are, on average, within 5% of each other from 300 to 1600 K. Our results confirm the viability of pure-rotational H2 CARS thermometry for probing combustion reactions.

Computer Pure-Tone and Operator Stress: Report III.

ERIC Educational Resources Information Center

Dow, Caroline; Covert, Douglas C.

Pure-tone sound at 15,750 Herz generated by flyback transformers in many computer and video display terminal (VDT) monitors has stress-related productivity effects in some operators, especially women. College-age women in a controlled experiment simulating half a normal work day showed responses within the first half hour of exposure to a tone…

Pure rotation of a prism on a ramp

PubMed Central

Zhao, Zhen; Liu, Caishan; Ma, Daolin

2014-01-01

In this work, we study a prism with a cross section in polygon rolling on a ramp inclined at a small angle. The prism under gravity rolls purely around each individual edge, intermittently interrupted by a sequence of face collisions between the side face of the prism and the ramp. By limiting the prism in a planar motion, we propose a mathematical model to deal with the events of the impacts. With a pair of laser-Doppler vibrometers, experiments are also conducted to measure the motions of various prisms made of different materials and with different edge number. Not only are good agreements achieved between our numerical and experimental results, but also an intriguing physical phenomenon is discovered: the purely rolling motion is nearly independent of the prism's materials, yet it is closely related to the prism's geometry. Imagine that an ideal circular section can be approximately equivalent to a polygon with a large enough edge number N, the finding presented in this paper may help discover the physical mechanism of rolling friction. PMID:25197242

Pure rotation of a prism on a ramp.

PubMed

Zhao, Zhen; Liu, Caishan; Ma, Daolin

2014-09-08

In this work, we study a prism with a cross section in polygon rolling on a ramp inclined at a small angle. The prism under gravity rolls purely around each individual edge, intermittently interrupted by a sequence of face collisions between the side face of the prism and the ramp. By limiting the prism in a planar motion, we propose a mathematical model to deal with the events of the impacts. With a pair of laser-Doppler vibrometers, experiments are also conducted to measure the motions of various prisms made of different materials and with different edge number. Not only are good agreements achieved between our numerical and experimental results, but also an intriguing physical phenomenon is discovered: the purely rolling motion is nearly independent of the prism's materials, yet it is closely related to the prism's geometry. Imagine that an ideal circular section can be approximately equivalent to a polygon with a large enough edge number N , the finding presented in this paper may help discover the physical mechanism of rolling friction.