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Journal articles on the topic "HBF 4"
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Alsultan, Abdulrahman, Duyen A. Ngo, John J. Farrell, et al. "Co-Inheritance of Delta Thalassemia Might Contribute to the High Fetal Hemoglobin in Sickle Cell Anemia Patients with the Saudi-Indian Haplotype." Blood 118, no. 21 (2011): 1056. http://dx.doi.org/10.1182/blood.v118.21.1056.1056.
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Abstract Abstract 1056 Most sickle cell anemia patients (HBB glu6val homozygotes) indigenous to the Eastern Province of Saudi Arabia have a fetal hemoglobin (HbF) level of about 20% that is associated with a mild clinical phenotype. Their HbS gene is on the Saudi-Indian (SI) haplotype characterized by an Xmn1 restriction site at position −158 5' to HBG2 (rs7482144), a Hinc2 site 5' to HBE (rs3834466) and other polymorphisms in the HBB gene-like cluster. However, the functional elements within the HBB gene-like cluster and elsewhere in the genome causing high HbF are yet to be determined. In a previous study we found that Saudi HbS homozygotes with the SI haplotype had a common region of autozygosity that spanned about 126 kb and included the complete HBB cluster. We have sequenced 13.6 kb in the HBD-HBG1 intergenic region (chr11:5255683-5269326, HG19), the region of the Corfu deletion. We found a SNP at position −68 bp 5' to HBD (c.-118 C>T) only in individuals with a SI haplotype. This SNP was not present in dbSNP build 132 or the 1000 Genomes databases. No other mutation in HBD was identified. This same SNP was recently associated with δ thalassemia (Phylipsen et al. Int. J. Lab. Hematol. 2011, 33: 85–91). Homozygotes for the −68 HBD SNP, who were not on hydroxyurea, had a mean HbF of 23%, range 12.1%-33.4% and mean HbA2 of 2.1%, range 1.2%-3%. We did not find the −68 HBD SNP in 15 African Americans with sickle cell anemia selected because of their unusually high HbF (mean HbF 17.2%, range 11%-28.9%). Parents and sickle cell trait carriers from the families of Saudi Eastern Province patients were heterozygous for the −68 HBD mutation (mean HbF 1.6%, range 0–4.2% and mean HbA2 2.7%, range 2.4%-3.2%) and one normal sibling did not carry this mutation (HbF 0 and HbA2 2.9%). Thirty patients with sickle cell disease indigenous to the Southwestern Province of Saudi Arabia, with the HbS gene on an African origin haplotype, (mean HbF 15.5%, range 4.5%-23% and mean HbA2 2.9%, range 2.1%-3.4% in HbS homozygotes) and 13 normal Saudi controls were examined and none carried the −68 HBD mutation. We also sequenced HBD and its promoter in 8 Southwestern Province HbS homozygotes with a Benin haplotype, 4 with HbF <5% and 4 with HbF >15%, and none had the −68 HBD SNP or any other mutation in HBD. Inverse relationships between percent HbF level and percent HbA2 was seen in 3 groups of HbS homozygotes:1) SI haplotype homozygotes; 2) Benin haplotype homozygotes from the Southwestern Province; 3) African Americans with diverse HbS haplotypes. The increased HbF in sickle cell anemia with δ thalassemia might involve both post-translational and transcriptional mechanisms. Increased HbF levels might in part be due to the preferential post-translational assembly of αγ dimers compared with αδ and αβS dimers. When δ thalassemia reduces available δ-globin chains, this might further favor preferential binding of less positively charged γ-globin subunits to positively charged α-globin compared with more positively charged δ-globin subunits. Perhaps more importantly, at the transcriptional level, the −68 HBD δ+-thalassemia promoter mutation might favor the interactions of transcription complexes with HBG promoters. The stimulus of hemolytic anemia and expanded erythropoiesis might be required before the favorable genetic milieu for increased HbF production can be fully utilized with the achievement of clinically significant increases in HbF that modulates the course of disease. For example, increased HbF levels of only 3.3%-4.7% have been reported in some hematologically normal individuals with homozygous δ0 thalassemia (Ohta et al. Hemoglobin 1980, 4: 417–425). High HbF levels in SI haplotype HbS homozygotes might involve the interactions of one or more HBG regulatory regions linked to the HBB gene-like cluster, like the −68 HBD SNP, perhaps with trans acting elements. Although the −68 HBD δ+-thalassemia mutation is associated with the SI haplotype and high HbF, functional studies are needed to establish causation. Disclosures: No relevant conflicts of interest to declare.
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Kesuma, Suryanata, and Elita Octavia. "Gambaran Fraksi Hemoglobin Penderita Talasemia Menggunakan Metode Elektroforesis Kapiler." Meditory : The Journal of Medical Laboratory 6, no. 2 (2019): 116–24. http://dx.doi.org/10.33992/m.v6i2.450.
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Thalassemia is a hereditary blood disease that is found in Indonesia. One method of examining modern thalassemia is the examination of hemoglobin fraction using the Capillary Electrophoresis. This method has a high level of accuracy and precision for quantification of hemoglobin variants.The purpose of this study was to determine the hemoglobin fraction in thalassemia patients using the Capillary Electrophoresis method. This type of research is descriptive research. The sample of this study was 3 blood specimens from thalassemia sufferers.The results showed that the first specimen, age 4 years had HbA levels of 59.9%, HbA2 levels of 4.3%, HbF levels of 14.7% and HbE levels of 21.1%. In the second specimen, 8 years of age had 88.7% HbA, 2.5% HbA2, 3.2% HbF and 5.6% HbE. In the third specimen, the age of 13 years had HbA levels of 93.8%, HbA2 levels of 4.9% and HbF levels of 1.3%.The conclusion of this study was the first specimen, HbA levels decreased, HbA2 levels increased and HbF levels increased and hemoglobin variants were found, namely HbE. In the second specimen, HbA levels decreased from the normal range, HbA2 levels were in the normal range and HbF levels increased and hemoglobin variants were found, namely HbE. In the third specimen, HbA levels decreased from the normal range, HbA2 levels and HbF levels increased, but no hemoglobin variants were found in this specimen.
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Sverrisson, Kristinn, Josefin Axelsson, Anna Rippe та ін. "Extracellular fetal hemoglobin induces increases in glomerular permeability: inhibition with α1-microglobulin and tempol". American Journal of Physiology-Renal Physiology 306, № 4 (2014): F442—F448. http://dx.doi.org/10.1152/ajprenal.00502.2013.
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Extracellular fetal hemoglobin (HbF) and adult hemoglobin (HbA) are proinflammatory and generate ROS. Increased plasma levels of extracellular HbF have recently been reported to occur in early preeclampsia. α1-Microglobulin (A1M) is a physiological heme-binding protein and radical scavenger that has been shown to counteract vascular permeability increases induced by HbA in the perfused placenta. The present study was performed to investigate whether HbF and HbA will increase glomerular permeability in vivo and to test whether A1M and tempol, a ROS scavenger, can prevent their effects. Anesthetized Wistar rats were continuously infused intravenously with either HbA, HbF, or cyano-inactivated HbF together with FITC-Ficoll-70/400, inulin, and 51Cr-labeled EDTA for 2 h. Plasma samples and urine samples (left ureter) were taken repeatedly and analyzed by high-performance size exclusion chromatography to assess glomerular sieving coefficients for Ficoll of radius 10–80 Å. In separate experiments, A1M or tempol was given before and during Hb infusions. Extracellular HbF caused rapid, transient increases in glomerular permeability to large Ficoll molecules (50–80Å), contrary to the effects of HbA and cyano-inactivated HbF. For HbF, glomerular sieving coefficients for Ficoll of radius 60Å increased from 3.85 ± 0.85 × 10−5 to 2.60 ± 0.96 × 10−4 at 15 min, changes that were abrogated by tempol and reduced by A1M. In conclusion, our data demonstrate that extracellular HbF, infused systemically, can acutely increase glomerular permeability through inducing oxidative stress.
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Alsultan, Abdulrahman, Idowu Akinsheye, Nadia Solovieff, et al. "Fetal Hemoglobin In Sickle Cell Anemia: Molecular Characterization of Saudi Patients From the Eastern Province." Blood 116, no. 21 (2010): 1627. http://dx.doi.org/10.1182/blood.v116.21.1627.1627.
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Abstract Abstract 1627 In the Eastern Province of Saudi Arabia, sickle cell anemia (HbSS) is associated with the Saudi Indian (SI) HBB-gene cluster haplotype, high levels of fetal hemoglobin (HbF) and milder disease, when compared with Southwestern Province HbSS patients who have lower HbF levels and different HBB haplotypes. An association between HbF and the Xmn1 restriction site in the HBG2 promoter present in both the SI and African-derived Senegal haplotypes is well known, but the causal elements of this association are unknown. Moreover, among individuals with the SI haplotype, only HbSS patients have high HbF while individuals with sickle cell trait (HbAS) or normal hemoglobin (HbAA) do not. Furthermore, HbF levels are far higher in SI haplotype patients, as shown below, compared with Senegal haplotype homozygotes. For example African patients homozygous for the Senegal haplotype had 12.3±5.3% HbF. To better understand the genetic basis for high HbF in SI haplotype HbSS cases, we compared sequences in the HBB gene cluster in patients with SI and Senegal haplotypes. We hypothesized that the causal elements that modify HbF in Saudi patients are in linkage disequilibrium (LD) with the βS globin gene in this population. Accordingly, we studied 5 Saudi families from the Eastern Province. Seven SI haplotype patients with HbSS (median age 5 yrs, range 2.5–49 yrs) were homozygous for the Xmn I site and had Hb 9.7 ± 1.6 g/dL, MCV 76.5 ± 8.3 fl and median Hb F 30.3 (range 18–41). Seventeen SI haplotype individuals had HbAS (median HbF 1.2, range 0–4.2); and 2 were normal. We first determined the genotypes of 3 known HbF QTLs, BCL11A (rs766432); HBS1L-MYB (rs7775698 and rs9399137); and OR51B5/6 (rs5006884). There were no consistent genotypes among these 7 patients to explain their universal high HbF. Next, we performed homozygosity mapping using Illumina Human610-Quad SNP array and identified runs of homozygosity (RoH) of variable length (from 160 kb to nearly 2 mb) within and surrounding the HBB cluster only in HbSS patients. RoH were absent elsewhere in the genome in HbSS. The RoH that was shared by all HbSS patients was 126.6 kb in chr11:5153026-5279647 (NCBI36/hg18) and contains SNPs from rs11036090 to rs7118113 of the Illumina Human610-Quad SNP array. This region contains: OR51B4, the complete HBB cluster, and OR51V1. Homozygosity mapping in 6 Senegal haplotype homozygotes showed a slightly larger RoH from chr11:4909490-5314457 and SNPs rs840713-rs10837822. Both the Saudi patients and Senegal homozygotes had the same homozygous genotypes for the overlapping region of chr11:5205580-5235931 ranging from rs11036364 to rs5010981.To identify potential genetic modifiers of HbF level in the region detected in the Saudi cases, we sequenced areas within or near the Corfu deletion that is known to cause HPFH, the HBD-HBG1 intergenic region, and core regions of HS- 2, 3, and 4 in the LCR. Core regions of HS-3 and HS-4 were identical to the reference sequences. In the core of HS-2, the 10TA.2CA.2TA.CG.12TA motif was present. This motif is known to be associated with the SI haplotype but not with any other haplotypes. Within the region of the Corfu deletion, many polymorphisms were identified highlighting the complexity of SI haplotype and HBB haplotypes in general. Many of these polymorphisms lead to creation or abolition of transcription factor binding sites when this was examined in silico using the TFBS search program ConSite (consite.genereg.net). Some of these putative sites bind transcription factors presumed to have regulatory roles in globin gene expression. Complete sequencing of the 126.6 kb interval with comparison to other HBB haplotypes associated with high and low HbF might focus attention on areas of interest that can be examined in functional studies. Disclosures: No relevant conflicts of interest to declare.
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Sebastiani, Paola, John J. Farrell, Shuai Wang, et al. "BCL11A enhancer Haplotypes Are Associated with the Distribution of HbF in Arab-Indian and African Haplotype Sickle Cell Anemia but Not the Different Population Levels of HbF." Blood 124, no. 21 (2014): 4066. http://dx.doi.org/10.1182/blood.v124.21.4066.4066.
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Abstract Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia. In the Middle East and India the HbS gene is often on an Arab-Indian HBB haplotype that is associated with high HbF levels. HbF is “normally” distributed in this population with a mean ~20%. In African HbS haplotypes, HbF levels are much lower (mean value ~6%) with a highly skewed distribution. BCL11A is an important modulator of γ-globin gene (HBG2 and HBG1) expression and BCL11A is regulated by erythroid specific enhancers in its 2nd intron. The enhancers consist of 3 DNase hypersensitive sites (HS) +62, +58 and +55 kb from the transcription initiation site of this gene. Polymorphisms (SNPs) in these enhancers are associated with HbF. The strongest association with HbF levels in African Americans with sickle cell anemia was with rs1427407 in HS +62 and to a lesser extent, rs7606173 in HS+55. Using the results of whole genome sequencing of 14 AI haplotype patients—half with HbF <10%, half with HbF >20%—6 SNPs in the BCL11A enhancer region, rs1427407, rs7599488, rs6706648, rs6738440, rs7565301, rs7606173 and 2 indels rs3028027 and rs142027584 (CCT, CCTCT and AAAAC respectively), were detected as possibly associated with HbF level. There were no novel polymorphisms detected. We genotyped the 6 SNPs and studied their associated haplotypes in 137 Saudi (HbF18.0±7.0%) and 44 Indian patients (HbF23.0±4.8%) with the Arab-Indian HBB haplotype; 50 African Americans with diverse African haplotypes, including 4 Senegal haplotype heterozygotes, (20 with HbF 17.2±4.6% and 30 with HbF 5.0±2.5%) and imputed genotypes for these SNPs in 847 African Americans with sickle cell anemia and diverse haplotypes (HbF 6.6±5.5%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) in the HS sites showed consistent associations with HbF levels in all 4 cohorts. Haplotype analysis of these 4 SNPs showed that there were 4 common and 10 rare haplotypes. The most common, GCAG, was found in ~54% of Arab-Indian haplotype carriers (HbF, ~20%) and in ~33% of African origin haplotype carriers (HbF, ~5.5%). Two haplotypes, GTAC and GTGC, were carried by ~40% of African American patients and were associated with lower levels of HbF (3.6%-4%). These same haplotypes were carried by 18% of Arab-Indian haplotype carriers and their average HbF level was 17%. These differences were significant. Haplotype TCAG was present in 20% of Arab-Indian and 25% of African haplotype cases, and carriers had on average higher HbF levels (~22% in the Arab-Indian haplotype, ~8% in African Americans). The analysis shows that: BCL11A enhancer haplotypes are differentially distributed among patients with the HbS gene on Arab-Indian or African origin haplotypes; haplotype pairs TCAG/TCAG and GTAC/GTGC are associated with the highest and lowest HbF levels in all the studied groups; the population-specific prevalence of HbF BCL11A enhancer haplotypes are likely to explain the different distributions of HbF in African origin and Arab-Indian haplotypes but do not account for the differences in average population levels of HbF or the high HbF of the Arab-Indian haplotype. Novel SNPs in BCL11A do not explain the high HbF of the Arab-Indian haplotype. Other important loci must have a predominant role in the differential expression of HbF among HbS Arab-Indian haplotype carriers. Disclosures No relevant conflicts of interest to declare.
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Pongpaksupasin, Phitchapa, Tiwaporn Nualkaew, Suradej Hongeng, Suthat Fucharoen, Natee Jearawiriyapaisarn та Orapan Sripichai. "Lysine-Specific Histone Demethylase 1 Inhibition Enhances Robust Fetal Hemoglobin Induction in Human β0-Thalassemia/Hemoglobin E Rrythroid Cells". Hematology Reports 13, № 4 (2021): 9215. http://dx.doi.org/10.4081/hr.2021.9215.
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Induction of fetal hemoglobin (HbF) ameliorates the clinical severity of β-thalassemias. Histone methyltransferase LSD1 enzyme removes methyl groups from the activating chromatin mark histone 3 lysine 4 at silenced genes, including the γ-globin genes. LSD1 inhibitor RN-1 induces HbF levels in cultured human erythroid cells. Here, the HbF-inducing activity of RN-1 was investigated in erythroid progenitor cells derived from β0-thalassemia/HbE patients. The significant and reproducible increases in γ-globin transcript and HbF expression upon RN-1 treatment was demonstrated in erythroid cells with divergent HbF baseline levels, the average of HbF induction was 17.7 + 0.8%. RN-1 at low concentration did not affect viability and proliferation of erythroid cells, but decreases in cell number was observed in cells treated with RN-1 at high concentration. Delayed terminal erythroid differentiation was revealed in β0-thalassemia/HbE erythroid cells treated with RN-1 as similar to other compounds that target LSD1 activity. Downregulation of repressors of γ-globin expression; NCOR1 and SOX6, was observed in RN-1 treatment. These findings provide a proof of concept that a LSD1 epigenetic enzymes is a potential therapeutic target for β0-thalassemia/HbE patients.
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Alsultan, Abdulrahman, Nadia Solovieff, Aamer Aleem, et al. "Fetal Hemoglobin In Sickle Cell Anemia: Molecular Characterization of Saudi Patients From the Southwestern Province." Blood 116, no. 21 (2010): 1621. http://dx.doi.org/10.1182/blood.v116.21.1621.1621.
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Abstract Abstract 1621 Sickle cell disease (SCD) is common in the Eastern and Southwestern (SW) Provinces of Saudi Arabia. Patients from the SW Province have many complications of this disease but they have phenotypic differences from African Americans that include a high prevalence of splenomegaly, rare CNS disease and absence of leg ulcers. In contrast, Eastern Province patients have a milder phenotype that is related to a nearly uniformly high fetal hemoglobin (HbF) level that is associated with the Saudi-Indian haplotype of the HBB gene-like cluster. SW Province patients have variable HbF levels and do not have the Saudi-Indian haplotype. We studied patients from the SW Province to determine the associations of known HbF quantitative trait loci (QTL) with HbF concentration. Seventy-seven Saudi patients, aged ≥4 yrs, with SCD were studied, 53 HbS homozygotes and 24 with HbS-β0 thalassemia. Their age was 17.7±10 (range 4–46) yrs and 45% were on hydroxyurea. HBB gene cluster haplotypes were 58 (75%) Benin, 17 (22%) Bantu, 1(1.5%) Senegal/Bantu, and 1(1.5%) Senegal. HbF level was measured by capillary electrophoresis and we used the lowest HbF level after age 4 yrs, the age where HbF levels stabilized, for analysis. Genotyping was done by TaqMan SNP genotyping assays, and included SNPs in BCL11A (rs4671393, rs766432), HBS1L-MYB (rs28384513, rs9399137, rs4895441), and OR51B5/6 (rs5006884). Results are summarized in the Table. QTLs showed similar trend in their effects on HbF level when patients on hydroxyurea were excluded from analysis. BCL11A was the sole QTL associated with HbF level in Saudi patients from the SW Province whereas the HBS1L-MYB and OR51B5/6 loci had no effect. For comparison, we selected cases from 2 studies of African American with SCD. All were HbS homozygotes and none took hydroxyurea, and we compared them to Saudi patients who were HbS homozygotes and not on hydroxyurea (n=29). Compared with African Americans with similar HBB haplotypes, and after adjusting for the BCL11A genotype, Saudi cases from SW Province had HbF levels almost twice that of African Americans (p <0.0001). Given that Saudi and African American patients had a nearly identical distribution of HBB gene cluster haplotypes, we examined ancestral origin of Saudi and African American patients. Using a genome-wide set of SNPs, we performed a principal component analysis with the Saudi, the African Americans with SCD and African, Arab, Asian and European populations from the Human Genome Diversity Project. We estimated the Fst statistic between these populations which is defined as the proportion of genetic diversity due to allele frequency differences among populations and can be interpreted as the distance between populations. African American cases were in close proximity to Yoruban, Mandenka and Bantu populations while Saudi patients resembled Arab populations. African American patients were the farthest from Saudi patients as compared with Asian and European populations. The commonality of HBB haplotypes in these Saudi cases and African Americans, coupled with the genetic distance between these populations suggest that genetic modifiers remote from the HBB cluster or unknown environmental influences are likely to account for the higher HbF in these Saudi patients. Disclosures: No relevant conflicts of interest to declare.
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Vathipadiekal, Vinod, Abdulrahman Alsultan, John Farrell, et al. "Polymorphisms Associated with the Arab-Indian Haplotype of Sickle Cell Anemia Are Candidate Fetal Hemoglobin Gene Modulators." Blood 126, no. 23 (2015): 3388. http://dx.doi.org/10.1182/blood.v126.23.3388.3388.
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Abstract Fetal hemoglobin (HbF) inhibits HbS polymerization. Because of this, sufficient HbF in most sickle erythrocytes can lead to a milder disease phenotype. HbF levels differ amongst the β-globin gene (HBB) cluster haplotypes of sickle cell anemia. In the Arab-Indian (AI) haplotype, HbF was about 20% compared with 5-10% in the Bantu, Benin, and Senegal haplotypes. Functional elements linked to the HBB haplotype are likely to regulate the expression of HbF in addition to the effects of trans-acting modulators. To identify cis-acting SNPs in the HBB gene cluster that differentiate the AI haplotype from all others, including the Senegal haplotype-the Senegal haplotype shares some SNPs with the AI haplotype but its carriers have lower HbF-we studied patients with sickle cell anemia who were homozygous for HBB haplotypes by genome-wide SNP association analysis (GWAS; Table). First, we compared the results of GWAS of 42 Saudi AI haplotype homozygotes with GWAS in 71 Saudi Benin haplotype homozygotes. The only variants distinguishing these 2 populations with genome-wide significance (p-values between 9.6E-07 and 2.7E-45) were 223 SNPs in chromosome 11p15 from positions 3.5 to 6.5 mb. This region included the HBB gene cluster, its locus control region (LCR) and the upstream and downstream olfactory receptor gene clusters. The minor allele frequency of SNPs in MYB (chr 6q23), BCL11A (chr 2p16) and KLF1 (chr 19), trans-acting loci that affect expression of the HbF genes, were similar in these 2 cohorts. A novel candidate trans-acting locus was not found, however our power to detect such an association was low. We followed-up these observations by comparing allele frequencies in 303 African American cases homozygous for the haplotypes shown in the Table. Thirteen GWAS-significant SNPs, in addition to rs7482144 and rs10128556, were present in all AI haplotype cases but not in 83 Senegal haplotype chromosomes. The allele frequency of these SNPs was replicated in 62 independent AI haplotype cases. Rs2472530 is in the coding region of OR52A5; rs16912979, rs4910743 and rs4601817 are in the HBB gene cluster LCR; rs16912979 in DNase I hypersensitive site-4 altered motifs for POLR2A, GATA1, and GATA2 binding.The minor allele of rs10837771 causes a missense mutation in OR51B4 an upstream olfactory receptor gene. To see if any of these or other alleles might sometimes be associated with HbF in the Bantu and Benin haplotyes, we selected homozygotes and compound heterozygous for these haplotypes who had unexplained and uncharacteristically high HbF. Thirty-one African Americans, aged ≥5 yrs. who had a HbF of 21% were compared with 350 similar cases who had a mean HbF of 3%. Four additional SNPs on chromosome 11, from positions ranging from 5536415 to 5543705 in the UBQLNL/HBG2, region and present in 45-48% of AI haplotype and 3-13% of other haplotypes, were found at higher frequencies in the high HbF group compared with the low HbF group. These SNPs also altered transcription factor binding motifs. Loci marked by SNPs that distinguish the AI from the Senegal and other HBB haplotypes might contain functionally important polymorphisms and account in part for high HbF in AI haplotype sickle cell anemia, independent of, or in addition to, the effects associated with rs7482144 or rs10128556. They might also be rarely associated with high HbF found in other haplotypes. These observations provide a foundation for mechanistic studies focused on the role of these variants in the expression of their linked HbF genes.Table 1.non-codedallelegenomic locationSaudi AI(n=42)Saudi ben.ben(n=71)AA ben.ben(n=264)AA ban.ban(n=31)AA sen.sen(n=8)HbF (%)1711669rs10837771Gexon OR51B410.020.0200rs4601817GLCR10.020.0400rs4910743CLCR10.010.0100rs16912979CLCR00.960.920.111rs10488675Gintron HBE110.01000rs7482144*AHBG210001rs10128556#TIntron HBBP110001rs7935470COR51V110.020.0300rs10837582GOR51V1100.0200rs11036227TOR51V110000rs10734485COR51A1P00.990.9711rs10837461AOR52A110.01000rs2472522GOR52A110.01000rs2472530Gexon OR52A510.01000rs2499948TOR52A510.020.010.020Allele frequencies in haplotypes of sickle cell anemia. * Xmn1 5' HBG 2 restriction site. This SNP, not present on the SNP microarray, was genotyped independently; # LD with rs7482144; AA designates African Americans; ben-Benin; ban-Bantu; sen-Senegal. Disclosures No relevant conflicts of interest to declare.
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Rok, M., P. Szklarz, and G. Bator. "Structures and phase transitions in molecular complexes containing tetrafluoroboric acid and tetramethylpyrazine." CrystEngComm 20, no. 38 (2018): 5772–81. http://dx.doi.org/10.1039/c8ce01231h.
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Crystals of tetrafluoroboric acid with tetramethylpyrazine, TMP + HBF<sub>4</sub> + H<sub>2</sub>O (1 : 1 : 2, A), TMP + HBF<sub>4</sub> (1 : 1, B) and TMP + HBF<sub>4</sub> (1 : 2, C) were synthesized and characterized by physicochemical experimental methods.
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Carol Illa, Ariadna, Jesper Petersen, Søren Skov, Andreas Glenthoej, and Carsten Dan Ley. "Is Epigenetic Modulation to Induce Fetal Hemoglobin Translatable in Sickle Cell Mice?" Blood 142, Supplement 1 (2023): 5261. http://dx.doi.org/10.1182/blood-2023-173922.
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Sickle cell disease (SCD) is a genetic disorder caused by a mutation in the β-globin subunit of hemoglobin, resulting in the formation of HbS. Under deoxygenation, HbS polymerizes leading to red blood cell sickling, increased hemolysis and multi-organ damage. During human fetal development, due to expression of the γ-globin gene, the predominant type of hemoglobin produced is fetal hemoglobin (HbF). However, after birth, this shifts to adult globin (HbA or HbS in SCD). This is driven by epigenetic repression of γ-globin due to an increased methylation of its gene promoters. DNA methyltransferase 1 (DNMT1) is an important enzyme for DNA methylation and is known to be pivotal in regulation of HbF expression. Reactivation of HbF provides a functional hemoglobin, and therefore has the potential to treat SCD symptoms ( Steinberg et al. JAMA 2003;289:1645-51). HbF induction is an accepted treatment strategy in SCD; even small increases result in decreased vaso-occlusive crises and mortality ( Kato et al. Nat Rev Dis Primers 2018;4:18010). Decitabine inhibits DNMT1 activity, thus promoting γ-globin expression and thereby increasing HbF levels. While inhibition of DNA methylation is known to cause HbF induction in humans and non-human primates, the effects observed in SCD mouse models are more ambiguous. This study investigated to which extent decitabine treatment could induce HbF expression in the Townes SCD model. In Townes mice, the murine globin genes have been substituted for their sickle human counterparts, HBA, HBB sickle and HBG1, and mimic many features of human SCD. Mice aged 4-5 weeks were dosed subcutaneously 3 times a week for 12 weeks with research-grade decitabine (0.6 mg/kg or 0.4 mg/kg) or vehicle. Blood samples were collected for analysis of HbF protein levels by HPLC (represented as % of total Hb) and F-cells by flow cytometry (represented as % of the total RBC population positive for HbF), complete blood counts, histology, and other markers of disease and organ damage. Results are presented as mean ± SD. Groups were compared using an ANCOVA model, adjusting for multiple comparisons (Dunnett) with p&lt;0.05 considered statistically significant. For both treatment groups, HbF was significantly elevated compared to the control group, with the maximal response observed at 12 weeks (Figure 1). F-cells at the end of the study were increased in both 0.4 mg/kg (11.4±1.5%) and 0.6 mg/kg (11.8±1.4%) groups compared to vehicle (4.5±0.6%). The same was observed for protein levels: 0.4 mg/kg group (1.2±0.3%), 0.6 mg/kg (1.4±0.3%) compared to vehicle (0.4±0.1%). Interestingly, after 12 weeks RBC and reticulocyte counts were significantly decreased in treatment groups and mean corpuscular volume (MCV) was significantly increased. No changes on LDH, bilirubin and liver markers (ALP, ALT, AST) were observed at 6 or 12 weeks. The results showed that treatment groups had significantly higher HbF levels than the vehicle group. However, the level of induction was lower than observed for inhibition of DNA methylation in humans and primates. The decrease in RBCs and reticulocytes could be partially explained by a combination of HbF induction, reduction of sickle RBC, and inhibition of erythropoiesis. The lack of changes in disease markers suggests that the increase in HbF levels in Townes mice might not be sufficient to alleviate the disease. This observation is consistent with recently published data (Woodard et al. Dis Model Mech. 2022;15(6)) that indicates that Townes mice are less suitable for studying this mechanism of action since, even though they have all human globin genes and some proximal regulatory elements, they lack key cis-acting distant DNA elements that regulate the globin genes. However, in primates the globin structure and regulation mechanisms are similar to human (Hardison. Cold Spring Harb Perspect Med. 2012;2(12)). In conclusion, although the measured levels of HbF protein were no higher than 2%, we found that decitabine can induce HbF expression in the Townes mouse model of SCD. However, within the 12-weeks, there was no clear beneficial effect on the disease markers studied. The successful induction of HbF suggests that better outcomes might be achieved with further optimization of the dosing and duration of the study. This indicates that SCD mice may be useful for preclinical studies of HbF induction, but caution is needed when extrapolating results to humans.
Dissertations / Theses on the topic "HBF 4"
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Ayari, Sami. "Implication des récepteurs nucléaires HNF-4α et HNF-4γ dans la fonction entéroendocrine et la susceptibilité à l'obésité et au diabète de type II". Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066380.
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L’obésité et le diabète de type 2 (DT2) sont des pathologies métaboliques associées à des perturbations de l’homéostasie glucidique et énergétique. Les enterohormones sont des acteurs importants de la regulation des mécanismes perturbés lors de ces pathologies. Parmi ces enterohormones, le GLP-1, sécrété par les cellules entéroendocrines de type L suite à un repas, permet d’amplifier la sécrétion d’insuline par les cellules β-pancréatiques et de diminuer la prise alimentaire. L’objectif de ma thèse a été de caractériser le rôle du récepteur nucléaire HNF-4γ dans l’homéostasie énergétique et la fonction endocrine de l’intestin.A l’aide d’un modèle murin d’invalidation totale et constitutive du facteur de transcription HNF-4γ, notre équipe a mis en évidence que l’absence de HNF-4γ induit une amélioration de la tolérance au glucose grâce à une augmentation du nombre de cellules L et de la quantité plasmatique de GLP-1 en réponse au glucose. L’ensemble de ces données démontre pour la première fois un rôle de HNF-4γ dans l’homéostasie glucidique via une modulation du lignage enteroendocrine spécifique du GLP-1 et suggère que son absence pourrait protéger les souris de l’établissement d’un DT2.Par ailleurs, la perte d’expression de HNF-4γ confère une protection vis-à-vis de la prise de poids et de l’intolérance au glucose normalement induites par six semaines d’un régime riche en lipides et en fructose grâce une perte énergétique accrue dans les fécès essentiellement due à une malabsorption des acides gras.En conclusion, cette étude met en exergue le rôle du récepteur nucléaire intestinal HNF-4γ dans la fonction enteroendocrine et la susceptibilité à l’obésité et au DT2<br>Obesity and type 2 diabetes (T2D) are metabolic pathologies associated with glucose and energy homeostasis perturbations. Enterohormones are important players in the regulation of the mechanisms disturbed during these pathologies. Among these enterohormones, GLP-1, secreted by enteroendocrine L cells in response to a meal, potentiates insulin secretion by pancreatic β cells and inhibits food intake. The aim of my thesis was to characterize the role of the nuclear receptor HNF-4γ in the energy homeostasis and the endocrine function of the intestine.By using a total and constitutive HNF-4γ knock-out mouse model, our team has highlighted that the loss of hnf-4γ induces an improved glucose tolerance. This effect is due to an increased GLP-1 cell number and GLP-1 plasma levels in response to glucose. All together these data demonstrate for the first time a role of HNF-4γ in glucose homeostasis through a modulation of the enteroendocrine lineage specific for GLP-1 and suggest that its absence could protect mice from the T2D establishment.The loss of HNF-4γ protects mice from body weight gain and glucose intolerance normally induced by six weeks of a high-fat/high-fructose diet demonstrating its involvement in obesity and T2D. HNF-4γ -/- mice are protected from obesity by a greater energy loss in faeces mainly due to lipid malabsorption. These results demonstrate that HNF-4γ is necessary for the intestinal fatty acids uptake.In conclusion, this study highlights the role of the intestinal nuclear receptor HNF-4γ in enteroendocrine function and susceptibility to obesity and T2D
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Gu, Ning. "Effects of mutant HNF-1α and HNF-1β identified in MODY3 and MODY5 on the sucrase-isomaltase and dipeptidylpeptidase-4 gene expressions". Kyoto University, 2007. http://hdl.handle.net/2433/136420.
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Kyoto University (京都大学)<br>0048<br>新制・課程博士<br>博士(人間・環境学)<br>甲第13147号<br>人博第354号<br>新制||人||88(附属図書館)<br>18||D||155(吉田南総合図書館)<br>UT51-2007-H420<br>京都大学大学院人間・環境学研究科共生人間学<br>(主査)教授 石原 昭彦, 教授 津田 謹輔, 助教授 林 達也<br>学位規則第4条第1項該当
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Wikner, Martin. "Malmölärares syn på sexuella normavvikelser i årskurs 4-6." Thesis, Malmö högskola, Lärarutbildningen (LUT), 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-27730.
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Arbetet försöker belysa och förstå hur några lärare i årskurs 4-6 i Malmö ser på frågor om homosexualitet, bisexualitet och transpersoner (HBT) ur ett queerperspektiv. Frågeställningarna handlar om hur lärarna anser att HBT-frågor hanteras bäst i mötet med eleverna i och utanför klassrummet, vilken syn de har på kollegor och föräldrar som är HBT samt grundsynen i HBT-frågor. Undersökningen genomfördes med enkäter som syftade till att ge kvalitativa svar och skickades ut till olika skolor i Malmö kommuns stadsdelar. Resultatet visar på att den allmänna synen bland lärarna är att heterosexualitet är viktigare att undervisa i än homo- och bisexualitet samt transsexualitet. Synen på HBT-personer är accepterande, men hamnar lätt i skymundan bakom heterosexuella normer.
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Dimitrova, Tatyana Stefanova [Verfasser]. "Inhibition of HIF prolyl 4-hydroxylases protect endothelial cells from apoptosis / by Tatyana Stefanova Dimitrova." Giessen : VVB Laufersweiler, 2010. http://d-nb.info/1009522264/34.
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Määttä, J. (Jenni). "Effects of the hypoxia response on metabolism in atherosclerosis and pregnancy." Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526222394.
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Abstract Oxygen is vital for human survival. To ensure its sufficient supply, the body has an intricate system, which involves the circulatory, respiratory and neuroendocrine systems. When oxygen is lacking, a state of hypoxia occurs, and adaptive changes in gene expression increase oxygen delivery to promote survival. The key regulator of the transcriptional hypoxia response is hypoxia-inducible factor (HIF) which targets over 1000 genes. The HIF prolyl 4-hydroxylases (HIF-P4Hs) govern the stability of HIF in an oxygen-dependent fashion. In our studies we investigated whether activation of the hypoxia response through inhibition of either of two distinct HIF-P4Hs, HIF-P4H-2 or P4H-TM would reduce atherosclerosis in mice. We found that inhibition of HIF-P4H-2 led to reductions in numbers of atherosclerotic plaques, and levels of serum cholesterol and inflammation in white adipose tissue and aortic plaques. In addition, HIF-P4H-2 deficient mice had elevated levels of modified LDL-targeting, atheroprotective circulating autoantibodies. The P4H-TM knockout mice also had reduced numbers of atherosclerotic plaques and increased levels of atheroprotective autoantibodies in their sera, but in contrast to the HIF-P4H-2 deficient mice, they also showed a reduction in serum triglyceride levels. To determine how hypoxia alters maternal glucose and lipid metabolism in pregnancy, we studied pregnant mice that were predisposed to a hypoxic condition (15% ambient O2). We found that they had enhanced glucose metabolism due to reduced insulin resistance and an increased flux of glucose to maternal tissues. The hypoxic dams also failed to gain weight and store adipose tissue in the anabolic phase to the same extent as normoxic control dams. These results implicate HIF-P4H inhibition as a novel therapeutic mechanism for atherosclerosis, and suggest that the small molecule HIF-P4H inhibitors currently in clinical trials for renal anemia may have further possible therapeutic applications. In addition, greater understanding of the changes in maternal metabolism that underly reduced fetal growth in hypoxic conditions, and the development of targeted interventions may allow the preservation of fetal growth in cases of maternal hypoxia<br>Tiivistelmä Happi on ihmiselle elintärkeää. Tämän vuoksi meille on kehittynyt pitkälle jalostunut verenkierto-, hengitys- ja neuroendokriininen järjestelmä sekä sellaisten geenien ilmentymisen muutoksia, jotka joko lisäävät hapen kuljetusta tai auttavat selviytymään hypoksisissa oloissa, jotta taataan riittävä hapen saanti. Hapen puutteessa hypoksiavaste, jonka tärkein säätelijä on hypoksiassa indusoituva transkriptiotekijä (HIF), aktivoituu. HIF:lla on yli 1000 kohdegeeniä joiden kautta sen vaikutukset välittyvät. HIF-prolyyli-4-hydroksylaasit (HIF-P4H:t) säätelevät HIF:n stabiilisuutta hapesta riippuvaisesti. Tutkimuksessamme selvitimme, vähentääkö hypoksiavasteen aktivointi HIF-P4H-2:n tai P4H-TM:n inhibition kautta ateroskleroosia hiirillä. Tuloksena oli, että HIF-P4H-2:n inhibitio vähensi ateroskleroottisia plakkeja, seerumin kolesterolia ja inflammaatiota valkoisessa rasvakudoksessa sekä plakeissa. Lisäksi hiirillä, joilta puuttui HIF-P4H-2, oli lisääntynyt määrä ateroskleroosilta suojaavia muokattua LDL:ää sitovia autovasta-aineita seerumissa. P4H-TM-poistogeenisillä hiirillä todettiin vastaavasti vähemmän ateroskleroottisia plakkeja ja lisääntynyt määrä ateroskleroosilta suojaavia autovasta-aineita seerumissa. Poiketen HIF-P4H-2-puutteisista hiiristä, niillä oli matalammat seerumin triglyseridi-tasot. Tutkimme raskaina olevia hiiriä, jotka altistimme hypoksisille olosuhteille (15% O2), jotta pystyisimme määrittämään, kuinka hypoksia vaikuttaa äidin sokeri- ja rasva-aineenvaihduntaan. Hypoksiassa raskaana olevilla hiirillä todettiin tehostunut sokeriaineenvaihdunta, joka oli seurausta alentuneesta insuliiniresistenssistä sekä lisääntyneestä sokerin sisäänotosta äidin kudoksiin. Hypoksiassa eivät raskaana olevien hiirten paino eivätkä rasvavarastot lisääntyneet samassa suhteessa normoksiassa raskaana olevien hiirten kanssa. Nämä tulokset tarjoavat uusia mahdollisuuksia HIF-P4H-inhibition käyttämiseen terapeuttisena vaihtoehtona ateroskleroosin hoidossa ja ehkäisemisessä. Kliinisissä kokeissa munuaisperäisen anemian hoidossa olevat HIF-P4H-estäjät voisivat näin ollen saada lisää indikaatioita. Lisäksi korkean ilmanalan aiheuttaman pienipainoisuuden takana olevien aineenvaihdunnan muutoksien ymmärtäminen voi mahdollistaa sikiön kasvun turvaamisen spesifein interventioin
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Coêlho, Harnôldo Colares. "Presença dos vírus HBV e HCV e seus fatores de riscos nos presidiários masculinos da penitenciária de Ribeirão Preto." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/17/17138/tde-15052008-140503/.
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Infecções pelos vírus da hepatite B (HBV) e vírus da hepatite C (HCV) na população prisional apresentam prevalências bastante elevadas, alcançando taxas, algumas vezes, de mais de 40%. Contribuem para isso diversos comportamentos de risco, adotados já antes do encarceramento ou desenvolvidos durante o período de reclusão. Entre eles, destacam-se o uso de drogas ilícitas intravenosas com compartilhamento de agulhas, tatuagens e atividade sexual desprotegida. Esta pesquisa objetivou estimar a prevalência dos marcadores do HBV e HCV com seus respectivos fatores de risco para estas exposições na população masculina carcerária da Penitenciária de Ribeirão Preto - SP, no período de maio a agosto de 2003. Do total de 1030 presidiários, foram sorteados 333 participantes por amostragem casual simples, os quais foram submetidos à aplicação de um questionário padronizado e tiveram coletada uma amostra de sangue. Para diagnóstico do HBV e HCV foi utilizado o ensaio imunoenzimático para detecção do HBsAG, anti-HBc total, anti-HBs e anti-HCV. A confirmação deste foi feita através de reação de polimerase em cadeia (HCV RNA). As prevalências encontradas para HBV e HCV nos presidiários foram de 19,5%% (IC 95% : 15,2 - 23,8) e 8,7% (IC 95% : 5,7 - 11,7), respectivamente . Todas as variáveis que apresentaram \"p\" abaixo de 0,25, através de análise univariada, foram submetidas a um modelo multivariado de regressão logística. Nesta análise, as variáveis que se mostraram preditoras de forma independente da infecção pelo HBV foram: idade acima de 30 anos e passado de droga injetável. Já para o HCV, as variáveis foram idade acima de 30 anos, história prévia de hepatite, tatuagem, passado de droga injetável e passado de compartilhamento de agulhas.<br>The hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in correctional settings have quite high prevalences, reaching rates of up to 40%. Several risk behaviors, adopted before or during the imprisonment, accounts for that. Among them, the use of intravenous illicit drugs, sharing of needles, tattoos and unprotect sexual activity are the most important. This survey aimed to estimate the prevalence of HBV and HCV serological marker and risk factors for these infections in men inmates at the Penitentiary of Ribeirão Preto, State of São Paulo, Brazil, between May and August 2003. Out of 1030 inmates, a simple random sample of 333 participants was chosen. The participants were interviewed in a standardized questionnaire and provided blood for serological tests. An enzyme-linked immunosorbent assay (ELISA) was used for diagnosis of HBV and HCV infection (HBsAg, anti-HBs, anti-HBc, anti-HCV). Polymerase chain reaction (HCV RNA) was used to confirm HCV infection. The overall prevalence for HBV and HCV markers in inmates was 19,5% (CI 95%: 15,2 - 23,8) and 8,7% (CI 95%: 5,7 - 11,7), respectively. The variables that displayed p<0,25, through univariate analysis, were assessed by a logistic regression multivariate model. At the level of 5%, HBV infection was associated with age > 30 years and previous injecting drug use. For HCV infection, age > 30 years, previous injecting drug use, previous sharing of needles, tattoos and previous hepatitis.
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Hao, Wei. "THE MAP KINASE AND TCF-4 SIGNALING PATHWAYS REGULATE HIF-1A TRANSCRIPTIONAL ACTIVITY IN RESPONSE TO HYPOXIA." Thesis, The University of Arizona, 2009. http://hdl.handle.net/10150/192464.
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Karsikas, S. (Sara). "Hypoxia-inducible factor prolyl 4-hydroxylase-2 in cardiac and skeletal muscle ischemia and metabolism." Doctoral thesis, Oulun yliopisto, 2015. http://urn.fi/urn:isbn:9789526207810.
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Abstract Oxygen is essential for aerobic organisms, as shortage of oxygen (hypoxia) can induce cellular dysfunctions and even cell death, leading to tissue damage and decreased viability of the organism. Oxygen homeostasis is regulated delicately by several mechanisms, the major one being the hypoxia-inducible factor (HIF) pathway that is evolutionarily conserved. HIFα subunits are regulated in an oxygen-dependent manner via three HIF prolyl 4-hydroxylases (HIF-P4Hs). In the presence of oxygen HIF-P4Hs modify HIFα, which leads to its degradation, whereas in hypoxia the HIF-P4H enzymes cannot function and HIFα is stabilized. HIF regulates more than 300 genes that enhance oxygen delivery from the lungs to tissues and reduce oxygen consumption in tissues, such as those for erythropoietin and vascular endothelial growth factor. When a tissue suffers from hypoxia caused by a circulatory restriction, the situation is called ischemia. In this study we used a genetically modified HIF-P4H-2 hypomorph mouse line that expresses 8% of the wild-type Hif-p4h-2 mRNA in the heart and 19% in skeletal muscle, and has HIFα stabilization in both tissues. We showed that chronic HIF-P4H-2 deficiency leads to protection against acute ischemic injury both in the heart and in skeletal muscle. The protection was mainly due to enlarged capillaries and better perfusion in both tissues. Hypoxia is known to decrease body weight. The observation of the HIF-P4H-2 deficient mice being leaner than their wild-type littermates led us to study their body constitution, metabolism and adipose tissue in detail. We discovered that chronic HIF-P4H-2 deficiency protects against obesity and several metabolic dysfunctions including diabetes and metabolic syndrome. These beneficial outcomes were mimicked when a pharmacological pan-HIF-P4H inhibitor was administered to wild-type mice. In these studies we showed that pharmacological HIF-P4H-2 inhibition may provide a novel treatment for diseases such as acute myocardial infarction, peripheral artery disease and metabolic disorders<br>Tiivistelmä Happi on edellytys aerobisen eliön, kuten ihmisen, elämälle; hapen niukkuus (hypoksia) voi johtaa monenlaisiin solun toimintahäiriöihin, jotka voivat edelleen aiheuttaa solun kuoleman, kyseisen kudoksen vaurion, ja lopulta eliön elinkyvyn heikkenemisen. Happitasapainoa säädellään monilla menetelmillä, joista merkittävin on hypoksiassa indusoituvasta tekijästä (HIF) riippuvainen reitti, joka on evoluutiossa säilynyt. HIFα alayksiköitä säätelee hapesta riippuvaisesti kolme HIF prolyyli 4-hydroksylaasia (HIF-P4Ht). Hapen läsnä ollessa HIF-P4H on aktiivinen ja johtaa HIFα:n hajottamiseen, kun taas hypoksiassa HIF-P4H entsyymit eivät voi toimia ja siten HIFα stabiloituu. HIF säätelee yli 300 geeniä, jotka edistävät hapen kuljetusta ja pääsyä keuhkoista kudoksiin sekä vähentävät hapenkulutusta. Näitä geenejä ovat mm. erytropoietiini sekä vaskulaarinen endoteelikasvutekijä. Kudoksen heikentyneestä verenkierrosta johtuvaa hapenpuutetta kutsutaan iskemiaksi. Tässä tutkimuksessa käytimme geneettisesti muunneltua HIF-P4H-2 hypomorfi-hiirikantaa, joka tuottaa Hif-p4h-2 lähetti-RNA:ta sydämessä vain 8 % ja luurankolihaksessa 19 % villityypin määrästä, ja jolla on HIFα stabiloituneena molemmissa kudoksissa. Osoitimme, että krooninen HIF-P4H-2:n puute suojaa sekä sydäntä että luurankolihasta akuutissa iskemiassa. Vaikutus johtui pääasiassa suuremmista kapillaareista ja paremmasta perfuusiosta molemmissa kudoksissa. Aikaisempien tutkimusten perusteella tiedetään, että hypoksia alentaa painoa. Huomio siitä, että HIF-P4H-2 puutteiset hiiret ovat hoikempia kuin villityypin sisaruksensa, johti meidät tutkimaan hiirten kehon koostumusta, aineenvaihduntaa ja rasvakudosta tarkemmin. Tutkimuksissamme selvisi, että krooninen HIF-P4H-2:n puute suojaa lihavuudelta ja monelta aineenvaihdunnan häiriöltä kuten sokeritaudilta ja metaboliselta oireyhtymältä. Nämä edulliset vaikutukset toistuivat, kun annoimme villityypin hiirille pan-HIF-P4H inhibiittoria. Kaiken kaikkiaan, näissä tutkimuksissa osoitimme, että lääkkeellinen HIF-P4H-2:n estäminen voi tarjota uuden keinon sydäninfarktin, luurankolihasiskemian ja aineenvaihdunnan häiriöiden hoitoon
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Ahmed, Raju. "Investigation of the effects of different cryopreservation parameters on the genome of 51/4 hpf zebrafish (Danio rerio) embryos." Thesis, University of Bedfordshire, 2013. http://hdl.handle.net/10547/322165.
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In recent years, numerous studies have linked cryopreservation with increased occurrence of mutations, DNA fragmentation and the event of apoptosis in biological objects. However, the evidence emerged from such studies is somewhat inconclusive. The current study, therefore, aimed to analyse the DNA damage response (DDR) from the cryopreserved cells in order to characterise the nature of the putative DNA damage. The study set out to investigate the effects of different cryopreservation parameters on the genome in terms of double strand breaks (DSBs), single strand breaks (SSBs), and various forms of sequence alteration using 5¼ hour post fertilisation (hpf) zebrafish (Danio rerio) embryos. The experimental conditions under which the investigation was carried out were short term chilling at 0˚C, treatment with two cryoprotective agents (CPA), namely, MeOH and Me2SO, and cooling to -35˚C. Assays for detecting DSB-activated DDR proteins and SSB-activated DDR proteins in 5¼ hpf zebrafish (Danio rerio) were developed and then utilised to investigate the occurrence of DSBs and SSBs in the genome of the embryos treated with the experimental conditions. The study then analysed the expression profiles of a set of genes unique to the base excision repair (BER), nucleotide excision repair (NER) and mismatch repair (MMR) pathways as indicators of the occurrence of various forms of sequence alterations in the genome of the embryos treated with the experimental conditions. It was found that chilling and CPA treatment did not induce DSBs or SSBs but up-regulated the MMR and BER, respectively. CPA treatment also down-regulated the NER and the MMR mechanisms. Cooling, on the contrary, did not induce DSBs but induced SSBs in the genome, which were repaired when the embryos were provided with a recovery time. Cooling also up-regulated the NER and the BER mechanisms in the embryos. The overall finding of the study indicated that the experimental conditions increased the occurrence of various single stranded DNA lesions in the genome of the embryos. The present study provided important insights into how eukaryotic cells respond to different cryopreservation parameters, which will significantly enhance the current knowledge of the effects of cryopreservation on the genome of biological objects.
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GUESNE, HERAUD CATHERINE. "Prevalence de l'antigene hbs chez les femmes enceintes suivies au chu de limoges : etude sur une periode de 4 ans." Limoges, 1988. http://www.theses.fr/1988LIMO0103.
Full textBooks on the topic "HBF 4"
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Daphne, Kerslake, Davies Janet, and Welsh Joint Education Committee. Cynllun Adnoddau., eds. Mathemateg HBJ: Llyfr gweithgareddau blwyddyn 4: neidio/mwy a llai. Collins Educational, 1994.
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Rißmann-Ottow, Guido, Jörg Scherz, and Sigrid Stenzel, eds. Gewerkschaftliche Jugendpolitik zwischen HBV und ver.di. VS Verlag für Sozialwissenschaften, 2001. http://dx.doi.org/10.1007/978-3-322-92227-4.
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Sun, Yabin. Research on the Radiation Effects and Compact Model of SiGe HBT. Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-10-4612-4.
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Great Britain. Welsh Office. Education Department. Inspectorate. Adroddiad ganArolygwyr ei Mawrhydi: Arolwg o hanes yng nghyfnodau allweddol 3 a 4 yng Nghymru : arolygwyd yn ystod tymor yr Hydref 1993, tymor y Gwanwyn a'r Haf 1994. Welsh Office, 1995.
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HBJ Mathematics Year 4: Activity Masters (HBJ Mathematics). HarperCollins Publishers, 1996.
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HBJ Mathematics Year 4: Children's Book (HBJ Mathematics). HarperCollins Publishers, 1991.
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Hbj Mathematics Year 4: Teacher's Resource Book (HBJ Mathematics). Collins Educational, 1995.
Find full textBook chapters on the topic "HBF 4"
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Pawlak, A., M. Schröter, and B. Ardouin. "SiGe HBT Compact Modeling." In Silicon-Germanium Heterojunction Bipolar Transistors for Mm-wave Systems Technology, Modeling and Circuit Applications. River Publishers, 2022. http://dx.doi.org/10.1201/9781003339519-4.
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Lalova, Teodora, Anastassia Negrouk, Laurent Dollé, et al. "An Overview of Belgian Legislation Applicable to Biobank Research and Its Interplay with Data Protection Rules." In GDPR and Biobanking. Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-49388-2_10.
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AbstractThis contribution aims to present in a clear and concise manner the intricate legal framework for biobank research in Belgium. In Part 1, we describe the Belgian biobank infrastructure, with a focus on the concept of biobank. In Part 2, we provide an overview of the applicable legal framework, namely the Act of 19 December 2008 on Human Body Material (HBM), and its amendments. Attention is given to an essential piece of self-regulation, namely the Compendium on biobanks issued by the Federal Agency on Medicine Products and Health (FAMPH). Furthermore, we delineate the interplay with relevant data protection rules. Part 3 is dedicated to the main research oversight bodies in the field of biobanking. In Part 4, we provides several examples of the ‘law in context’. In particular, we discuss issues pertaining to presumed consent, processing of personal data associated with HBM, and information provided to the donor of HBM. Finally, Part 5 and 6 addresses the impact of the EU General Data Protection Regulation (GDPR), suggests lines for further research, and outline the future possibilities for biobanking in Belgium.
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Kato, Yukio, Ke-Xin Liu, Tetsuya Terasaki, Toshikazu Nakamura, and Yuichi Sugiyama. "A Novel Drug Delivery System of Hepatocyte Growth Factor (HGF): Utilization of Heparin-HGF Complex." In Advanced Biomaterials in Biomedical Engineering and Drug Delivery Systems. Springer Japan, 1996. http://dx.doi.org/10.1007/978-4-431-65883-2_108.
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Cabrera-Munguia, Denis A., Horacio González, Adolfo Romero-Galarza, L. Farías-Cepeda, Lucero Rosales-Marines, and Sandra L. Castañón-Alonso. "Catalytic Routes in Biomass Conversion: Synthesis of Furfural and HMF." In Handbook of Research on Bioenergy and Biomaterials. Apple Academic Press, 2021. http://dx.doi.org/10.1201/9781003105053-4.
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Hirono, Shuichi, Kenji Nagata, Akihiro Ivioriuchi, et al. "HGF-Related Proteins in Hepatocellular Carcinoma (HCC)." In Liver Cirrhosis. Springer Japan, 2001. http://dx.doi.org/10.1007/978-4-431-68343-8_11.
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Peters, Marion. "New Antiviral Therapy: Adefovir Dipivoxil for HBV." In Therapy for Viral Hepatitis and Prevention of Hepatocellular Carcinoma. Springer Japan, 2004. http://dx.doi.org/10.1007/978-4-431-53977-3_6.
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Tanaka, Satoshi, and Nobu Hattori. "The role of HBV in hepatocellular carcinoma." In Primary Liver Cancer in Japan. Springer Japan, 1992. http://dx.doi.org/10.1007/978-4-431-68177-9_7.
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Bartz, Christopher, Konstantinos Chasapis, Michael Kuhn, Petra Nerge, and Thomas Ludwig. "A Best Practice Analysis of HDF $$5$$ 5 and NetCDF- $$4$$ 4 Using Lustre." In Lecture Notes in Computer Science. Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-20119-1_20.
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Fajans, S. S., G. I. Bell, W. H. Herman, K. S. Polonsky, and J. B. Halter. "Natural History, Genetics and Pathogenesis of HNF-4α/MODY1." In Frontiers in Diabetes. KARGER, 2000. http://dx.doi.org/10.1159/000060911.
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Coad, Alex, Anders Bornhäll, Sven-Olov Daunfeldt, and Alexander McKelvie. "In Search of Scale-ups: Empirical Analysis." In SpringerBriefs in Business. Springer Nature Singapore, 2024. http://dx.doi.org/10.1007/978-981-97-1379-0_7.
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AbstractThis chapter takes our empirical definition of scale-up to the data: Swedish register data on over 700,000 firms for the period 1997–2001. 1.28% of firms meet the HGF criteria. Among these HGFs, it is rare for a firm to satisfy all 7 scale-up conditions (in line with the idea of ‘too many exceptions’). 25.89% of HGFs satisfy 5 or more of the 7 conditions for scale-ups, while 60.75% of HGFs satisfy 4 out of 7 conditions. Our analysis highlighted how missing values can cause problems when investigating which HGFs are scale-ups.
Conference papers on the topic "HBF 4"
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Liu, Jie, Craig Ungaro, Lei Yuan, John Nord, and Ming-Jun Li. "Hollow-core Fiber Side-view Imaging for Non-destructive Clocking Angle Measurement and Structural Analysis." In Optical Fiber Communication Conference. Optica Publishing Group, 2025. https://doi.org/10.1364/ofc.2025.m2f.4.
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We report side-view images of a HCF compared with the simulated transmission interference patterns to clarify clocking angle and feasibility of side-view imaging for HCF nondestructive structural analysis.
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Roberts, Henry C., Aadil Waseem, Scott A. Wicker, et al. "Aluminum Nitride Ring Resonator-Coupled Spin Defects in Hexagonal Boron Nitride for Integrated Quantum Photonics." In CLEO: Science and Innovations. Optica Publishing Group, 2024. http://dx.doi.org/10.1364/cleo_si.2024.sm4g.4.
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We report a new approach to generate waveguide-coupled emission from deterministically implanted boron vacancy spin defects in hBN using single-crystal AlN-on-sapphire ring resonators. This facilitates the eventual development of hBN-based integrated quantum technologies.
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Zami, Thierry, Nicola Rossi, Serge Melle, and Bruno Lavigne. "Benefit of HCF for Throughput of Future WDM Networks." In Optical Fiber Communication Conference. Optica Publishing Group, 2025. https://doi.org/10.1364/ofc.2025.m3f.4.
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We quantify the benefit from Hollow Core Fibers (HCF) versus common SSMF regarding the total capacity in modern WDM transparent backbone networks for various network sizes, various fiber losses in dB/km and various span lengths
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Ge, Dawei, Siyuan Liu, Peng Li, et al. "Field Trial of Real-time 128Tb/s Co-frequency Co-time Full-duplex Transmission over Deployed 20km AR-HCFs in Urban Duct Network." In Optical Fiber Communication Conference. Optica Publishing Group, 2025. https://doi.org/10.1364/ofc.2025.w1c.4.
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We report the first real-time 128Tb/s co-frequency co-time full-duplex transmission over the first deployed 20km AR-HCFs in complex urban duct network in China by leveraging extremely low distributed Rayleigh backscattering of AR-HCF.
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You, Jeonghyeok, Hohyun Chae, Taeryeong Kim, Ji Hoon Lee, and Seong-Ook Jung. "Design and Analysis of Static-Free PAM-4 Transmitter for HBM TSV Interface." In 2025 International Conference on Electronics, Information, and Communication (ICEIC). IEEE, 2025. https://doi.org/10.1109/iceic64972.2025.10879743.
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Abudayyeh, Hamza, Zhida Liu, Kan Yao, Yuebing Zheng, and Xiaoqin Li. "Enhancement of TMD Exciton Resonances using Plasmonic Resonators." In CLEO: Applications and Technology. Optica Publishing Group, 2024. http://dx.doi.org/10.1364/cleo_at.2024.jth2a.128.
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Samples of monolayer, bilayer, trilayer and 4-layer WS2 encapsulated between two layers of hBN are embedded into plasmonic patch antennas. The resulting low mode volume leads to 1000-fold enhancement of dark resonances in the material.
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Shirshov, Yu M., A. L. Kukla, L. P. Pochekaylova, A. E. Rachkov, and S. A. Piletski. "Conductivity of HBF/sub 4/-and HCLO/sub 4/-doped emeraldine polyaniline in air and ammonia." In International Conference on Science and Technology of Synthetic Metals. IEEE, 1994. http://dx.doi.org/10.1109/stsm.1994.834840.
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Bonato, Camila, Daniane Grando Remor Canali, Gianfranco Zamperi, et al. "Avaliação analítica e clínica de hemoglobina glicada por HPLC (Analisador Lifotronic® H100Plus) em um laboratório clínico." In Resumos do 56º Congresso Brasileiro de Patologia Clínica/Medicina Laboratorial. Zeppelini Editorial e Comunicação, 2024. https://doi.org/10.5327/1516-3180.142s1.10908.
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Objetivo: Neste estudo, foram avaliadas as métricas de desempenho analítico, como imprecisão, correlação, linearidade, carreamento e detecção de variantes de hemoglobina por meio do método de cromatografia líquida de alta eficiência do analisador Lifotronic® H100 Plus para A1c. Método: Para a correlação, analisaram-se 40 amostras de pacientes variando de 4 a 15,4%. Para a imprecisão intraensaio e inter-ensaio, utilizaram-se duas concentrações de controle de qualidade interno; para linearidade, foram usadas amostras em duas concentrações, uma baixa (4,5%) e outra alta (17,2%); para avaliar carreamento, utilizaram-se amostras com concentrações baixas (4,98%), intermediárias (9,97%) e altas (14,96%) de forma intercalada. Variantes de hemoglobina encontradas na população estudada (HbS, HbF, HbC, HbE e HbD) foram avaliadas por correlação. As etapas do método de avaliação seguiram as diretrizes do CLSI. Conclusão: Correlação revelou um erro total para níveis de decisão 5,6% de 2,23% e 6,5% de 1,70%, que foram inferiores ao erro total máximo permitido de 3,3% (EFLM - EuBIVAS), e 95% dos resultados ficaram dentro dos limites aceitáveis. Viés positivo observado em sete amostras, predominantemente em amostras com concentrações acima de 6,5%. Em imprecisão intraensaio, o CV obtido foi de 0,86%, e para interensaio foi de 0,87%, ambos aceitáveis conforme especificação de 3% do fornecedor para os dois níveis. Mostrou-se linear para concentrações propostas pelo fabricante entre 3 e 18%, e não foi encontrado carreamento entre as amostras. As variantes de hemoglobina foram detectadas sem exceção, embora o tipo específico de variante de Hb não tenha sido identificado. O analisador foi aprovado com algumas observações, viés positivo em amostras com concentrações acima de 6,5%, embora não tenha sido considerado clinicamente relevante, produção de 58 testes por hora pode ser uma limitação para laboratórios com alto volume de testes e o analisador detectou a presença de variantes de Hb, embora não tenha identificado seus tipos específicos.
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Ribeiro, Edy Alyson Costa, Fabio Augusto Rodrigues Gonçalves, Evelinda Marramon Trindade, et al. "Devemos estabelecer medidas educativas e restritivas baseadas em boas práticas médicas para rastreio e seguimento de hepatite B?" In Resumos do 56º Congresso Brasileiro de Patologia Clínica/Medicina Laboratorial. Zeppelini Editorial e Comunicação, 2024. https://doi.org/10.5327/1516-3180.142s1.12228.
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Objetivo: A infecção pelo vírus da hepatite B (HBV) promove a replicação viral, resposta imune do hospedeiro e danos ao fígado. O rastreamento e o seguimento dessa infecção envolve os seguintes marcadores: anti-HBc Total, HBsAg, anti-HBs, HBeAg, anti-HBe e anti-HBc IgM. O objetivo deste estudo foi apresentar a dinâmica de solicitação de marcadores de hepatite B ao longo de 13 anos em hospital terciário universitário. Método: Estudo retrospectivo de análise de banco de dados dos marcadores de hepatite B solicitados entre janeiro de 2010 e dezembro de 2023 em hospital universitário de São Paulo. Considerou-se “evento de testagem” cada pedido médico, independentemente da quantidade de testes solicitados. Para avaliar a frequência dos marcadores positivos para rastreio e seguimento, consideraram-se quatro grupos: 1) HBsAg e HBeAg; 2) HBsAg e anti-HBc Total; 3) HBeAg e anti-HBc Total; e 4) HBeAg e anti-HBc Ig M. Conclusão: Foram avaliados 463.611 pedidos médicos (eventos de testagem), os quais totalizaram 896.563 (100%) análises de 269.198 pacientes. Os marcadores mais solicitados foram: anti-HBs (308.290; 34,3%), anti-HBc total (297.341; 33,1%) e HBsAg (245.769; 27,4%). Sem considerar a origem da solicitação, predominaram resultados negativos (686.376; 76,5%), com os seguintes números e frequências: anti-HBc Total (254.983; 85,8%); HBsAg (234.529; 95,4%); e anti-HBs (159.847; 51,8%). Os eventos de testagem diminuíram ao longo do tempo, passando de cerca de 50 mil em 2011 para próximo de 28 mil em 2022. Nota-se queda exponencial de pedidos dos grupos 1, 2 e 3 e aumento linear do grupo 4. Conclui-se que o anti-HBs foi o teste mais solicitado, sugerindo avaliação pós-vacinal. Solicitou-se mais anti-HBc total que AgHBs, contrariando a recomendação para rastreio. O aumento de biomarcadores do grupo 4 merece investigação para entender seu uso concomitante em rastreio e para adoção de ações educativas com definição de algoritmos claros para rastreio e seguimento.
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Fernandes, GS, GC Carvalho, DR Ramadan, S. Tufik, and MC Feres. "AVALIAÇÃO DE ANTICORPOS A HBSAG E MARCADORES DE FUNÇÃO HEPÁTICA EM UM LABORATÓRIO DE ANÁLISES CLÍNICAS DO BRASIL." In Resumos do 55º Congresso Brasileiro de Patologia Clínica/Medicina Laboratorial. Zeppelini Editorial e Comunicação, 2023. http://dx.doi.org/10.5327/1516-3180.141s2.7806.
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Objetivo: A infecção pelo vírus da hepatite B (HBV) pode levar à hepatite B crônica. O objetivo deste estudo é analisar os marcadores de hepatite B e a função hepática em populações com VHB positivo. Método: Foi realizada uma análise retrospectiva entre 2020 e 2022, usando um banco de dados laboratorial. Foram selecionados indivíduos com marcadores diagnósticos sorológicos para o VHB, incluindo HBsAg, anti-HBc total, IgM anti-HBc e anti-HBs. O grupo suscetível ao VHB foi identificado como negativo para todos os marcadores; o grupo naturalmente imune, com marcadores anti-HBc e anti-HBs, e o grupo vacinado, com anti-HBs apenas. A função hepática foi avaliada pelos marcadores: transferase gama glutamil (GGT), aspartato aminotransferase (AST) e alanina aminotransferase (ALT). Os testes de Mann-Whitney U e Kruskal-Wallis foram realizados e valores de p < 0,05, considerados significativos. Conclusão: Os resultados do estudo foram avaliados em 57.311 homens (32%) e 121.404 mulheres (68%). A taxa de indivíduos expostos à infecção natural foi maior no grupo de homens (9%) em comparação com o grupo de mulheres (4%). Foi observada uma concentração mais alta de anticorpos anti-Hbs na população com marcadores de infecção natural em comparação com aqueles imunizados pela vacinação contra HBV (527,5 ± 4 SEM vs 332,3 ± 1,1 mUI/ml, p < 0,001). Analisando as faixas etárias com maior suscetibilidade (31-40 e 41-50 anos), foi observada uma diminuição gradual nos anticorpos ao longo dos anos, tanto em indivíduos naturalmente infectados (p = 0,03) quanto em indivíduos imunizados (p < 0,001). GGT acima do valor de referência para os grupos naturalmente infectados foram observados para o sexo feminino (62,4 ± 5,34 EPM U/l) e masculino (86,7 ± 5,4 EPM U/l, p < 0,001). O estudo indicou que os homens foram mais suscetíveis à infecção por HBV, enquanto as mulheres apresentam níveis mais elevados de anticorpos anti-HBs. Além disso, indivíduos que tiveram infecção natural por hepatite B apresentaram níveis elevados de GGT.
Reports on the topic "HBF 4"
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สิโรตมรัตน์, สัตถาพร, เครือวัลย์ พลจันทร та อัมพร ตันประเสริฐ. การตรวจหาดีเอ็นเอไวรัสตับอักเสบบีในซีรัมหญิงตั้งครรภ์ด้วยวิธี Polymerase chain reaction. จุฬาลงกรณ์มหาวิทยาลัย, 2001. https://doi.org/10.58837/chula.res.2001.29.
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นำตัวอย่างซีรัมหญิงตั้งครรภ์ทั้งหมด 512 ตัวอย่าง มาตรวจหาดีเอ็นเอส่วน S gene ของไวรัสตับอักเสบบี (HBV-DNA) ซึ่งเป็นแถบดีเอ็นเอขนาด 431 คู่เบส ด้วยวิธี Polymerase Chain Reaction (PCR) ศึกษาควบคู่กับการตรวจหาดัชนีในซีรัม (seromarkers) อื่นๆ ด้วยวิธีทางอิมมูโนแอสเสย์ ได้แก่ แอนติเจนชนิดผิวของไวรัสตับอักเสบบี (HBsAg) ภูมิต้านทานต่อแอนติเจนชนิดผิวของไวรัส (Anti-HBs) และ ภูมิต้านทานต่อส่วยแกน (core) ของอนุภาคไวรัส (Anti-HBC) การตรวจหา HBsAgใช้ 2 วิธี คือ Chemiluminescent immunoassay : Abbott prism HBsAg ประเทศเยอรมัน และ Enzyme-Linked Immunosorbent Assay (ELISA) ซึ่งพัฒนาโดยกรมวิทยาศาสตร์ กระทรวงสาธารณสุข นนทบุรี เมื่อเปรียบเทียบผลการทดลองวิธี PCR กับ Chemiluminescence สามารถตรวจพบ HBV-DNA ในกลุ่มตัวอย่างซีรัมที่ให้ผล HBsAg เป็นลบซึ่งถือว่าเป็นกลุ่มปกติ 4 ตัวอย่าง จาก 482 ตัวอย่าง (ร้อย 0.83) และในกลุ่มที่ให้ผล HBsAg เป็นบวกกลุ่มพาหะ 10 ตัวอย่าง จาก 30 ตัวอย่างคิดเป็นร้อยละ 33.33 อีทางหนึ่งเมื่อเปรียบเทียบวิธี PCR กับวิธี ELISA สามารถตรวจพบ HBV-DNA 1 ตัวอย่างในกลุ่มที่ให้ผล HBsAg เป็นลบ จากตัวอย่างทั้งหมด 478 ตัวอย่าง (ร้อยละ 0.21) และตรวจพบ HBV-DNA ในกลุ่มที่ให้ผล HBsAg เป็นบวก 13 ตัวอย่าง จาก 34 ตัวอย่าง (ร้อยละ 38.24) อย่างไรก็ตามแม้วิธี PCR จะมีข้อจำกัดในการตรวจหาไวรัสตับอักเสบบีในซีรัม แต่เป็นวิธีที่ให้ประโยชน์มากหากใช้ควบคู่ไปกับวิธีทางอิมมิวโนแอสเสย์ในการตรวจหาผู้ที่เป็นพาหะของโรค เพื่อป้องกันการตรวจได้ผลลบลวงเนื่องจากวิธี PCR สามารถตรวจหาไวรัสตับอักเสบบีได้ แม้ว่าผลการตรวจ HBsAg เป็นลบ
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Dickson, T. L., and R. D. Cheverton. HFIR Vessel Life Extension with Enlarged HB-2 and HB-4 Beam Tubes. Office of Scientific and Technical Information (OSTI), 1998. http://dx.doi.org/10.2172/3297.
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Prevey, Paul S., N. Jayaraman, and Michael J. Shepard. Improved HCF Performance and FOD Tolerance of Surface Treated Ti-6-2-4-6 Compressor Blades. Defense Technical Information Center, 2004. http://dx.doi.org/10.21236/ada444573.
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Ruangpornvisuti, Vithaya. Investigation of conformational equilibrium and proton affinity of Thiacalix[4] arenas and their complexes with cations : research report. Chulalongkorn University, 2004. https://doi.org/10.58837/chula.res.2004.35.
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The p-tert-butylsulfonylcalix[4]arene and sulfonycalix[4]arene conformers have been obtained by AM1 geometry optimizations. The structural cavities of p-tert-butylsulfonylcalix[4]arene and sulfonylcalix[4]arene conformers of which phenol groups are bridged by sulfonyl sulfur have been compared to the calix[4]arene and thiacalix[4]arene. The conformational energies of p-tert-butylsulfonylcalix[4]arene have been compared with the energies of sulfonylcalix[4]arene, calix[4]arene and thiacalix[4]arene. The most stable conformer of sulfonylcalix[4]arene and p-tert-butylsulfonylcalix[4]arene are 1,2-alternate and 0011-AAAA 1,2-alternate conformers, respectively. Two different types of hydrogen bond presented in the sulfonyl calix[4]arene cone and partial cone conformers and p-tert-butylsulfonylcalix[4]arene cone conformer have been found. Ab initio energies of the AM1 optimized structures of sulfonylcalix[4]arene and p-tert-butylsulfonylcalix[4]arene conformers and their complexes with zinc(II) have been computed at HF/6-31G* and B3LYP/6-31G* theoretical levels. The optimized structure of complex species of p-tert-butylsulfonylcalix[4]arene with zinc(II) is in good agreement with recent x-ray geometry data.
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Attwood. PR-339-093702-R03 Human Factors Influences on Pipeline Damage Milestone 2 Identify and Define Issues. Pipeline Research Council International, Inc. (PRCI), 2010. http://dx.doi.org/10.55274/r0010700.
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The members of the Pipeline Research Council International (PRCI) have identified Human Factors (HF) as a major component influencing the number and severity of pipeline damage incidents. PRCI has initiated a two-year program whose objectives include: A) Understand the contribution of HF to pipeline damage from all sources (i.e., first, secondand third party contributions) B) Identify the most important Human Factors involved in pipeline damage Recommend HF interventions for the high priority issues that will reduce damage incidents C) Propose next steps to implement these high priority interventions and to monitor their performance D) The final project deliverable is a Guide that will identify practical ways to address potentially adverse effects of HF on the performance of damage prevention measures, including examples of how they can be implemented and continuously improved. During the period 2009 to 2010, the project will complete six milestones, including: 1. Review available Human Factors literature (2009) 2. Identify and define issues (2009) 3. Categorize and prioritize issues (2010) 4. Develop intervention strategies (2010) 5. Propose next steps to implement strategies (2010) 6. Develop guide to use HF for damage prevention (2010) This report documents the results of Milestone 2, Identify and Define Issues. Appendices posted seperate
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Tronstad, Lusha. Aquatic invertebrate monitoring at Agate Fossil Beds National Monument: 2019 data report. National Park Service, 2022. http://dx.doi.org/10.36967/nrds-2293128.
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Monitoring ecosystems is vital to understanding trends over time and key to detecting change so that managers can address perturbations. Freshwater streams are the lifeblood of the surrounding landscape, and their health is a measure of the overall watershed integrity. Streams are the culmination of upland processes and inputs. Degradation on the landscape as well as changes to the stream itself can be detected using biota living in these ecosystems. Aquatic invertebrates are excellent indicators of ecosystem quality because they are relatively long-lived, sessile, diverse, abundant and their tolerance to perturbation differs. Aquatic invertebrates were monitored at three sites along the Niobrara River at Agate Fossil Beds National Monument in 2019 completing 23 years of data using Hester-Dendy and Hess samplers. Hess samplers are artificial multi-plate samplers suspended in the water column to allow invertebrates to colonize and Hess samples collect invertebrates in a known area on natural substrate and vegetation. We identified 45 invertebrate taxa from four phyla (Annelida, Arthropoda, Mollusca, Nematoda) using both samplers in the Niobrara River (Appendix A and B). Hester-Dendy samplers collected 4 taxa not found in Hess samples and Hess samples collected 17 taxa not collected with Hester-Dendy samplers. Hess samples captured more (91%) than Hester-Dendy samples (62%). Crustacea, Diptera and Ephemeroptera were the most abundant groups of invertebrates collected in the Niobrara River. The proportion of Insecta, Annelida, Trichoptera and Diptera differed between Hester-Dendy and Hess samples (p < 0.05). EPT richness, proportion EPT taxa and Hilsenhoff’s Biotic Index (HBI) (p < 0.0001) differed between sampler types, but taxa richness, taxa diversity and evenness (p > 0.29) did not. We collected the highest density of invertebrates at the Agate Middle site. Agate Spring Ranch had the lowest taxa richness and HBI, and the highest proportion of EPT taxa. HBI at the sites ranged from 4.0 to 6.3 (very good to fair from Hilsenhoff 1987) using the Hester-Dendy and 5.2 to 6.9 (good to fairly poor from Hilsenhoff 1987) using the Hess sampler.
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Farrell, K., F. B. Kam, and C. A. Baldwin. The DOS 1 neutron dosimetry experiment at the HB-4-A key 7 surveillance site on the HFIR pressure vessel. Office of Scientific and Technical Information (OSTI), 1994. http://dx.doi.org/10.2172/10130970.
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Godet, A., M. Smit, C. Guilmette, and F. Fournier-Roy. La longue vie du Batholite de Decelles, Pontiac, Québec: les grenats à notre rescousse! Natural Resources Canada/CMSS/Information Management, 2024. http://dx.doi.org/10.4095/332509.
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Les granites peralumineux sont reconnus à l'échelle mondiale comme le produit magmatique final des cratons archéens. Cependant, leur durée, les conditions thermiques de leur mise en place, leur séquence de cristallisation, ainsi que les liens avec l'évolution tectonométamorphique des roches encaissantes et les systèmes minéralisés en métaux précieux, de base, et rares sont peu connus. Le Batholite de Decelles (c. 2670-2620 Ma) exposé dans le sud-est du craton du Supérieur au Québec, Canada est l'un des plus volumineux de la région, offrant une opportunité unique dmp;gt;'améliorer notre compréhension des conditions thermiques et de la mobilité des magmas et des fluides dans la croûte moyenne et supérieure. Nous présentons des nouvelles datations Lu-Hf et des cartes dmp;gt;'éléments traces sur grenat de trois échantillons de granite du Batholite de Decelles. Les nouvelles dates de 2668 ± 4 Ma, 2663 ± 5 Ma, 2656 ± 7 Ma sont indifférenciables (considérant les incertitudes) des dates Lu-Hf sur grenat et U-Pb sur monazite des unités métasédimentaires encaissantes. La cartographie des éléments traces in situ par LA-ICP-MS révèle une zonation compositionnelle systématique. Les grenats présentent un cur avec une zonation oscillatoire concentrique en Li, P, Sc, Ti, Y, Zr, REE, Hf, Th et U; et une surcroissance marquée par des concentrations relativement élevées en MREE, HREE et V, et de faibles concentrations en Li, Ti, P, Sm, Zr, Hf et U par rapport aux curs. Les résultats indiquent une origine magmatique des grenats par opposition aux grenats métamorphiques de la source avec une histoire de cristallisation complexe. Le contenu en éléments traces du grenat semble être contrôlé par des variations cinétiques de croissance et de diffusion à l'interface grenat-matrice, ainsi que par la cristallisation de phases majeures et accessoires telles que la muscovite, la monazite, l'apatite et le zircon. Dans l'ensemble, le grenat du Batholite de Decelles date le début de la cristallisation magmatique et son contenu en éléments traces enregistre son histoire complète. Les archives géochronologiques régionales indiquent une évolution commune des niveaux de croûte moyenne et supérieure avec un refroidissement progressif entre c. 2640 et c. 2620 Ma, associé à la migration et au refroidissement de fluides minéralisateurs.
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Yahav, Shlomo, John Brake, and Noam Meiri. Development of Strategic Pre-Natal Cycling Thermal Treatments to Improve Livability and Productivity of Heavy Broilers. United States Department of Agriculture, 2013. http://dx.doi.org/10.32747/2013.7593395.bard.
Full textAbstract:
The necessity to improve broiler thermotolerance and live performance led to the following hypothesis: Appropriate comprehensive incubation treatments that include significant temperature management changes will promote angiogenesis and will improve acquisition of thermotolerance and carcass quality of heavy broilers through epigenetic adaptation. It was based on the following questions: 1. Can TM during embryogenesis of broilers induce a longer-lasting thermoregulatory memory (up to marketing age of 10 wk) that will improve acquisition of thermotolerance as well as increased breast meat yield in heavy broilers? 2. The improved sensible heat loss (SHL) suggests an improved peripheral vasodilation process. Does elevated temperature during incubation affect vasculogenesis and angiogenesis processes in the chick embryo? Will such create subsequent advantages for heavy broilers coping with adverse hot conditions? 3. What are the changes that occur in the PO/AH that induce the changes in the threshold response for heat production/heat loss based on the concept of epigenetic temperature adaptation? The original objectives of this study were as follow: a. to assess the improvement of thermotolerance efficiency and carcass quality of heavy broilers (~4 kg); b. toimproveperipheral vascularization and angiogenesis that improve sensible heat loss (SHL); c. to study the changes in the PO/AH thermoregulatory response for heat production/losscaused by modulating incubation temperature. To reach the goals: a. the effect of TM on performance and thermotolerance of broilers reared to 10 wk of age was studied. b. the effect of preincubation heating with an elevated temperature during the 1ˢᵗ 3 to 5 d of incubation in the presence of modified fresh air flow coupled with changes in turning frequency was elucidated; c.the effect of elevated temperature on vasculogenesis and angiogenesis was determined using in ovo and whole embryo chick culture as well as HIF-1α VEGF-α2 VEGF-R, FGF-2, and Gelatinase A (MMP2) gene expression. The effects on peripheral blood system of post-hatch chicks was determined with an infrared thermal imaging technique; c. the expression of BDNF was determined during the development of the thermal control set-point in the preoptic anterior hypothalamus (PO/AH). Background to the topic: Rapid growth rate has presented broiler chickens with seriousdifficulties when called upon to efficiently thermoregulate in hot environmental conditions. Being homeotherms, birds are able to maintain their body temperature (Tb) within a narrow range. An increase in Tb above the regulated range, as a result of exposure to environmental conditions and/or excessive metabolic heat production that often characterize broiler chickens, may lead to a potentially lethal cascade of irreversible thermoregulatory events. Exposure to temperature fluctuations during the perinatal period has been shown to lead to epigenetic temperature adaptation. The mechanism for this adaptation was based on the assumption that environmental factors, especially ambient temperature, have a strong influence on the determination of the “set-point” for physiological control systems during “critical developmental phases.” Recently, Piestunet al. (2008) demonstrated for the first time that TM (an elevated incubation temperature of 39.5°C for 12 h/d from E7 to E16) during the development/maturation of the hypothalamic-hypophyseal-thyroid axis (thermoregulation) and the hypothalamic-hypophyseal-adrenal axis (stress) significantly improved the thermotolerance and performance of broilers at 35 d of age. These phenomena raised two questions that were addressed in this project: 1. was it possible to detect changes leading to the determination of the “set point”; 2. Did TM have a similar long lasting effect (up to 70 d of age)? 3. Did other TM combinations (pre-heating and heating during the 1ˢᵗ 3 to 5 d of incubation) coupled with changes in turning frequency have any performance effect? The improved thermotolerance resulted mainly from an efficient capacity to reduce heat production and the level of stress that coincided with an increase in SHL (Piestunet al., 2008; 2009). The increase in SHL (Piestunet al., 2009) suggested an additional positive effect of TM on vasculogenesis and angiogensis. 4. In order to sustain or even improve broiler performance, TM during the period of the chorioallantoic membrane development was thought to increase vasculogenesis and angiogenesis providing better vasodilatation and by that SHL post-hatch.
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Friedman, Haya, Julia Vrebalov, and James Giovannoni. Elucidating the ripening signaling pathway in banana for improved fruit quality, shelf-life and food security. United States Department of Agriculture, 2014. http://dx.doi.org/10.32747/2014.7594401.bard.
Full textAbstract:
Background : Banana being a monocot and having distinct peel and pulp tissues is unique among the fleshy fruits and hence can provide a more comprehensive understanding of fruit ripening. Our previous research which translated ripening discoveries from tomato, led to the identification of six banana fruit-associated MADS-box genes, and we confirmed the positive role of MaMADS1/2 in banana ripening. The overall goal was to further elucidate the banana ripening signaling pathway as mediated by MADS-boxtranscriptional regulators. Specific objectives were: 1) characterize transcriptional profiles and quality of MaMADS1/2 repressed fruit; 2) reveal the role of additional MaMADSgenes in ripening; 3) develop a model of fruit MaMADS-box mode of action; and 4) isolate new components of the banana ripening signaling pathway. Major conclusion: The functions of the banana MaMADS1-5 have been examined by complimenting the rinor the TAGL1-suppressed lines of tomato. Only MaMADS5 exhibited partial complementation of TAGL1-suppressed and rinlines, suggesting that while similar genes play corresponding roles in ripening, evolutionary divergence makes heterologous complementation studies challenging. Nevertheless, the partial complementation of tomato TAGL1-surpessed and rinlines with MaMADS5 suggests this gene is likely an important ripening regulator in banana, worthy of further study. RNA-seqtranscriptome analysis during ripening was performed on WT and MaMADS2-suppressed lines revealing additional candidate genes contributing to ripening control mechanisms. In summary, we discovered 39 MaMADS-box genes in addition to homologues of CNR, NOR and HB-1 expressed in banana fruits, and which were shown in tomato to play necessary roles in ripening. For most of these genes the expression in peel and pulp was similar. However, a number of key genes were differentially expressed between these tissues indicating that the regulatory components which are active in peel and pulp include both common and tissue-specific regulatory systems, a distinction as compared to the more uniform tomato fruit pericarp. Because plant hormones are well documented to affect fruit ripening, the expressions of genes within the auxin, gibberellin, abscisic acid, jasmonic acid, salicylic and ethylene signal transduction and synthesis pathways were targeted in our transcriptome analysis. Genes’ expression associated with these pathways generally declined during normal ripening in both peel and pulp, excluding cytokinin and ethylene, and this decline was delayed in MaMADS2-suppressed banana lines. Hence, we suggest that normal MaMADS2 activity promotes the observed downward expression within these non-ethylene pathways (especially in the pulp), thus enabling ripening progression. In contrast, the expressions of ACSand ACOof the ethylene biosynthesis pathway increase in peel and pulp during ripening and are delayed/inhibited in the transgenic bananas, explaining the reduced ethylene production of MaMADS2-suppressed lines. Inferred by the different genes’ expression in peel and pulp of the gibberellins, salicylic acid and cytokinins pathways, it is suggested that hormonal regulation in these tissues is diverse. These results provide important insights into possible avenues of ripening control in the diverse fruit tissues of banana which was not previously revealed in other ripening systems. As such, our transcriptome analysis of WT and ripening delayed banana mutants provides a starting point for further characterization of ripening. In this study we also developed novel evidence that the cytoskeleton may have a positive role in ripening as components of this pathway were down-regulated by MaMADS2 suppression. The mode of cytoskeleton involvement in fruit ripening remains unclear but presents a novel new frontier in ripening investigations. In summary, this project yielded functional understanding of the role and mode of action of MaMADS2 during ripening, pointing to both induction of ethylene and suppression of non-ethylene hormonal singling pathways. Furthermore, our data suggest important roles for cytoskeleton components and MaMADS5 in the overall banana ripening control network. Implications: The project revealed new molecular components/genes involved in banana ripening and refines our understanding of ripening responses in the peel and pulp tissues of this important species. This information is novel as compared to that derived from the more uniform carpel tissues of other highly studied ripening systems including tomato and grape. The work provides specific target genes for potential modification through genetic engineering or for exploration of useful genetic diversity in traditional breeding. The results from the project might point toward improved methods or new treatments to improve banana fruit storage and quality.