Sample records for proximal mlh1 promoter

  1. Coexisting somatic promoter hypermethylation and pathogenic MLH1 germline mutation in Lynch syndrome. (United States)

    Rahner, N; Friedrichs, N; Steinke, V; Aretz, S; Friedl, W; Buettner, R; Mangold, E; Propping, P; Walldorf, C


    Somatic epimutations in the MLH1 promoter mimic the phenotype of Lynch syndrome. To date, no somatic hypermethylation of the MLH1 promoter in the carrier of a pathogenic MLH1 germline mutation has been identified, prompting the recommendation that a germline mutation in MLH1 should only be sought in the absence of tumour tissue methylation. We aimed to determine whether methylation of the MLH1 promoter may coexist in carriers of a pathogenic germline mutation in MLH1. We examined the methylation status of the MLH1 promoter in 123 tumour tissue samples, demonstrating high microsatellite instability and loss of expression of a mismatch repair protein (60 cases with MLH1 germline mutation, 25 cases without mutation, 38 cases with MSH2 mutations), using combined bisulphite restriction analysis (COBRA) and SNaPshot analysis. Methylation of the MLH1 promoter was found in two patients with pathogenic germline mutations, one a carrier of a MLH1 mutation and the other a carrier of a MSH2 mutation. Our results demonstrate that methylation of the MLH1 promoter region does not exclude the presence of a germline mutation in a mismatch repair (MMR) gene. Hypermethylation of the MLH1 promoter may be present in most cases of sporadic colorectal cancers, but this does not exclude a diagnosis of Lynch syndrome.

  2. Vitamin and antioxidant rich diet increases MLH1 promoter DNA methylation in DMT2 subjects

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    Switzeny Olivier J


    Full Text Available Abstract Background Oxidative stress may lead to an increased level of unrepaired cellular DNA damage, which is discussed as one risk for tumor initiation. Mismatch repair (MMR enzymes act as proofreading complexes that maintain the genomic integrity and MMR-deficient cells show an increased mutation rate. One important gene in the MMR complex is the MutL homolog 1 (MLH1 gene. Since a diet rich in antioxidants has the potential to counteract harmful effects by reactive oxygen species (ROS, we investigated the impact of an antioxidant, folate, and vitamin rich diet on the epigenetic pattern of MLH1. These effects were analyzed in individuals with non-insulin depended diabetes mellitus type 2 (NIDDM2 and impaired fasting glucose (IFG. Methods In this post-hoc analysis of a randomized trial we analyzed DNA methylation of MLH1, MSH2, and MGMT at baseline and after 8 weeks of intervention, consisting of 300 g vegetables and 25 ml plant oil rich in polyunsaturated fatty acids per day. DNA methylation was quantified using combined bisulfite restriction enzyme analysis (COBRA and pyrosequencing. MLH1 and DNMT1 mRNA expression were investigated by qRT-PCR. DNA damage was assessed by COMET assay. Student’s two-tailed paired t test and one-way ANOVA with Scheffé corrected Post hoc test was used to determine significant methylation and expression differences. Two-tailed Pearson test was used to determine correlations between methylation level, gene expression, and DNA strand break amount. Results The intervention resulted in significantly higher CpG methylation in two particular MLH1 promoter regions and the MGMT promoter. DNA strand breaks and methylation levels correlated significantly. The expression of MLH1, DNMT1, and the promoter methylation of MSH2 remained stable. CpG methylation levels and gene expression did not correlate. Conclusion This vitamin and antioxidant rich diet affected the CpG methylation of MLH1. The higher methylation might be a

  3. Regulation of MLH1 mRNA and protein expression by promoter methylation in primary colorectal cancer

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    Jensen, Lars Henrik; Rasmussen, Anders Aamann; Byriel, Lene


    In colorectal cancer MLH1 deficiency causes microsatellite instability, which is relevant for the patient's prognosis and treatment, and its putative heredity. Dysfunction of MLH1 is caused by sporadic gene promoter hypermethylation or by hereditary mutations as seen in Lynch Syndrome. The aim...

  4. Effects of dietary intake and genetic factors on hypermethylation of the hMLH1 gene promoter in gastric cancer (United States)

    Nan, Hong-Mei; Song, Young-Jin; Yun, Hyo-Yung; Park, Joo-Seung; Kim, Heon


    AIM: Hypermethylation of the promoter of the hMLH1 gene, which plays an important role in mismatch repair during DNA replication, occurs in more than 30% of human gastric cancer tissues. The purpose of this study was to investigate the effects of environmental factors, genetic polymorphisms of major metabolic enzymes, and microsatellite instability on hypermethylation of the promoter of the hMLH1 gene in gastric cancer. METHODS: Data were obtained from a hospital-based, case-control study of gastric cancer. One hundred and ten gastric cancer patients and 220 age- and sex-matched control patients completed a structured questionnaire regarding their exposure to environmental risk factors. Hypermethylation of the hMLH1 gene promoter, polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2 and L-myc genes, microsatellite instability and mutations of p53 and Ki-ras genes were investigated. RESULTS: Both smoking and alcohol consumption were associated with a higher risk of gastric cancer with hypermethylation of the hMLH1 gene promoter. High intake of vegetables and low intake of potato were associated with increased likelihood of gastric cancer with hypermethylation of the hMLH1 gene promoter. Genetic polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2, and L-myc genes were not significantly associated with the risk of gastric cancer either with or without hypermethylation in the promoter of the hMLH1 gene. Hypermethylation of the hMLH1 promoter was significantly associated with microsatellite instability (MSI): 10 of the 14 (71.4%) MSI-positive tumors showed hypermethylation, whereas 28 of 94 (29.8%) the MSI-negative tumors were hypermethylated at the hMLH1 promoter region. Hypermethylation of the hMLH1 gene promoter was significantly inversely correlated with mutation of the p53 gene. CONCLUSION: These results suggest that cigarette smoking and alcohol consumption may influence the development of hMLH1-positive gastric cancer. Most dietary factors and

  5. Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel. (United States)

    Vilkin, Alex; Niv, Yaron; Nagasaka, Takeshi; Morgenstern, Sarah; Levi, Zohar; Fireman, Zvi; Fuerst, Florentine; Goel, Ajay; Boland, C Richard


    The molecular mechanisms that underlie colorectal cancer (CRC) include microsatellite instability (MSI), chromosomal instability, and the CpG island methylator phenotype. There is evidence to suggest that CRC incidence varies among different ethnic populations worldwide. The authors of this report hypothesized that environmental factors and lifestyle differences among various ethnic groups may differentially influence the epigenetic regulation of tumor suppressor genes in CRC. In the current study, microdissection and DNA extraction were performed on 128 samples of CRC from Israeli patients (85 Jews and 43 Arabs). MSI analysis, mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) protein expression levels, and MLH1 promoter methylation were investigated by combined bisulfite restriction analysis. The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) valine-to-glutamic acid mutation at residue 600 was investigated by direct DNA sequencing. High MSI (MSI-H), MLH1 methylation, and BRAF mutations were observed in 11.6%, 9.4%, and 23.5% of Jews, respectively, and in 16.2%, 17.6%, and 20.9% of Arabs, respectively (P value nonsignificant). MLH1 promoter methylation was observed in 22.6% of microsatellite-stable (MSS) tumors and in 53.8% of MSI-H tumors (P < .015). Extensive methylation (covering both 5' and 3' promoter regions) was present in all MSI-H tumors with loss of MLH1 expression. BRAF mutation was observed in 15.6% and 46.1% of MSS tumors and MSI-H tumors, respectively (P < .007). BRAF mutation was observed in 66%, 22.2%, and 14.7% of patients who had tumors with extensive MLH1 promoter methylation, methylation of the 5' region alone, or without methylation, respectively (P < .006). There was no difference in molecular signatures examined between Jewish and Arab patients with CRC in Israel. Extensive promoter methylation was associated with MLH1 inactivation, MSI, and BRAF mutation. (c) 2009 American Cancer Society.

  6. Further evidence for heritability of an epimutation in one of 12 cases with MLH1 promoter methylation in blood cells clinically displaying HNPCC. (United States)

    Morak, Monika; Schackert, Hans Konrad; Rahner, Nils; Betz, Beate; Ebert, Matthias; Walldorf, Constanze; Royer-Pokora, Brigitte; Schulmann, Karsten; von Knebel-Doeberitz, Magnus; Dietmaier, Wolfgang; Keller, Gisela; Kerker, Brigitte; Leitner, Gertraud; Holinski-Feder, Elke


    Germline mutations in mismatch repair (MMR) genes, tumours with high microsatellite instability (MSI-H) and loss of MMR protein expression are the hallmarks of HNPCC (Lynch syndrome). While somatic MLH1 promoter hypermethylation is generally accepted in the tumorigenesis of sporadic tumours, abnormal MLH1 promoter methylation in normal body cells is controversially discussed as a mechanism predisposing patients to HNPCC. In all 94 patients suspected of HNPCC-syndrome with a mean age of onset of 45.5 years, MLH1-deficiency in their tumours but no germline mutation, underwent methylation-specific PCR-screening for MLH1 promoter methylation. In peripheral blood cells of 12 patients an MLH1 promoter methylation, in seven informative cases allele-specific, was found. Normal colonic tissue, buccal mucosa, and tumour tissue available from three patients also presented abnormal methylation in the MLH1 promoter. The heredity of aberrant methylation is questionable. Pro: MLH1 promoter methylation was found in a patient and his mother giving evidence for a familial predisposition for an epimutation in MLH1. Contra: a de novo set-up of methylation in one patient, a mosaic or incomplete methylation pattern in six patients, and no evidence for inheritance of MLH1 promoter methylation in the remaining families. Our findings provide strong evidence that MLH1 promoter methylation in normal body cells mimics HNPCC and constitutes a pathogenic pre-lesion in MLH1. The identification of hypermethylation as an epigenetic defect has important implications for surveillance recommendations, as these patients should be treated like Lynch syndrome patients, whereas the heritability of methylation is still under investigation.

  7. Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review. (United States)

    Metcalf, Alexander M; Spurdle, Amanda B


    Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

  8. Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability. (United States)

    Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide


    It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

  9. Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM-exposed workers

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    Fen Wu


    Full Text Available Objective: To explore the association of the methylation status of MGMT and hMLH1 with chromosome damage induced by vinyl chloride monomer (VCM. Materials and Methods: Methylation of MGMT and hMLH1 was measured in 101 VCM-exposed workers by methylation-specifi c PCR. Chromosome damage in peripheral blood lymphocytes was measured by the cytokinesis-block micronucleus assay. The subjects were divided into chromosome damaged and non-damaged groups based on the normal reference value of micronuclei frequencies determined for two control groups. Results: MGMT promoter methylation was detectable in 5 out of 49 chromosome damaged subjects, but not in the chromosome non-damaged subjects; there was a signifi cant difference in MGMT methylation between the two groups (p < 0.05. Conclusions: We detected aberrant promoter methylation of MGMT in a small number of chromosome damaged VCM-exposed workers, but not in the chromosome non-damaged subjects. This preliminary observation warrants further investigation in a larger study.

  10. Promoter methylation of MGMT, MLH1 and RASSF1A tumor suppressor genes in head and neck squamous cell carcinoma: pharmacological genome demethylation reduces proliferation of head and neck squamous carcinoma cells. (United States)

    Koutsimpelas, Dimitrios; Pongsapich, Warut; Heinrich, Ulf; Mann, Sylvia; Mann, Wolf J; Brieger, Jürgen


    Promoter hypermethylation of tumor suppressor genes (TSGs) is a common feature of primary cancer cells. However, to date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis have not been well-defined. In the present study, we analyzed the promoter methylation status of the genes mutL homolog 1 (MLH1), Ras-association domain family member 1 (RASSF1A) and O-6-methylguanine-DNA methyltransferase (MGMT) in 23 HNSCC samples, three control tissues and one HNSCC cell line (UM-SCC 33) using methylation-specific PCR (MSP). The expression of the three proteins was quantified by semi-quantitative immunohistochemical analysis. The cell line was treated with the demethylating agent 5-azacytidine (5-Aza) and the methylation status after 5-Aza treatment was analyzed by MSP and DNA sequencing. Proliferation was determined by Alamar blue staining. We found that the MGMT promoter in 57% of the analyzed primary tumor samples and in the cell line was hypermethylated. The MLH promoter was found to be methylated in one out of 23 (4%) tumor samples while in the examined cell line the MLH promoter was unmethylated. The RASSF1A promoter showed methylation in 13% of the tumor samples and in the cell line. MGMT expression in the group of tumor samples with a hypermethylated promoter was statistically significantly lower compared to the group of tumors with no measured hypermethylation of the MGMT promoter. After treatment of the cell line with the demethylating agent 5-Aza no demethylation of the methylated MGMT and RASSF1A genes were determined by MSP. DNA sequencing verified the MSP results, however, increased numbers of unmethylated CpG islands in the promoter region of MGMT and RASSF1A were observed. Proliferation was significantly (pproliferation of the tumor cells suggesting further evaluation of 5-Aza for HNSCC treatment.

  11. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers (United States)

    Veigl, Martina L.; Kasturi, Lakshmi; Olechnowicz, Joseph; Ma, AiHong; Lutterbaugh, James D.; Periyasamy, Sumudra; Li, Guo-Min; Drummond, James; Modrich, Paul L.; Sedwick, W. David; Markowitz, Sanford D.


    Mutations of DNA mismatch repair genes, including the hMLH1 gene, have been linked to human colon and other cancers in which defective DNA repair is evidenced by the associated instability of DNA microsatellite sequences (MSI). Germ-line hMLH1 mutations are causally associated with inherited MSI colon cancer, and somatic mutations are causally associated with sporadic MSI colon cancer. Previously however, we demonstrated that in many sporadic MSI colon cancers hMLH1 and all other DNA mismatch repair genes are wild type. To investigate this class of tumors further, we examined a group of MSI cancer cell lines, most of which were documented as established from antecedent MSI-positive malignant tumors. In five of six such cases we found that hMLH1 protein was absent, even though hMLH1-coding sequences were wild type. In each such case, absence of hMLH1 protein was associated with the methylation of the hMLH1 gene promoter. Furthermore, in each case, treatment with the demethylating agent 5-azacytidine induced expression of the absent hMLH1 protein. Moreover, in single cell clones, hMLH1 expression could be turned on, off, and on again by 5-azacytidine exposure, washout, and reexposure. This epigenetic inactivation of hMLH1 additionally accounted for the silencing of both maternal and paternal tumor hMLH1 alleles, both of which could be reactivated by 5-azacytidine. In summary, substantial numbers of human MSI cancers appear to arise by hMLH1 silencing via an epigenetic mechanism that can inactivate both of the hMLH1 alleles. Promoter methylation is intimately associated with this epigenetic silencing mechanism. PMID:9671741

  12. Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence? (United States)

    Lobo, João; Pinto, Carla; Freitas, Micaela; Pinheiro, Manuela; Vizcaino, Rámon; Oliva, Esther; Teixeira, Manuel R; Jerónimo, Carmen; Bartosch, Carla


    Currently, uveal melanoma is not considered within the Lynch syndrome tumor spectrum. However, there are studies suggesting a contribution of microsatellite instability in sporadic uveal melanoma tumorigenesis. We report a 45-year-old woman who was referred for genetic counseling due to a family history of Lynch syndrome caused by a MLH1 mutation. She originally underwent enucleation of the right eye secondary to a uveal spindle cell melanoma diagnosed at age 25. The tumor recurred 22 years later presenting as an ovarian metastasis and concurrently a microscopic endometrial endometrioid carcinoma, grade 1/3 was diagnosed. Subsequent studies highlighted that the uveal melanoma showed high microsatellite instability and loss of MLH1 and PMS2 protein expression, with no MLH1 promoter methylation or BRAF mutation. Additionally, a GNAQ mutation was found. We conclude that our patient's uveal melanoma is most likely related to MLH1 germline mutation and thus Lynch syndrome related. To the best of our knowledge, this is the first report of uveal melanoma showing MLH1/PMS2 protein loss in the context of Lynch syndrome.

  13. Specific Variants in the MLH1 Gene Region May Drive DNA Methylation, Loss of Protein Expression, and MSI-H Colorectal Cancer


    Mrkonjic, Miralem; Roslin, Nicole M.; Greenwood, Celia M.; Raptis, Stavroula; Pollett, Aaron; Laird, Peter W.; Pethe, Vaijayanti V.; Chiang, Theodore; Daftary, Darshana; Dicks, Elizabeth; Thibodeau, Stephen N.; Gallinger, Steven; Parfrey, Patrick S.; Younghusband, H. Banfield; Potter, John D.


    Background We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734) and microsatellite unstable (MSI-H) colorectal cancers (CRCs) in two samples. The current study expanded on this finding as we explored the genetic basis of DNA methylation in this region of chromosome 3. We hypothesized that specific polymorphisms in the MLH1 gene region predispose it to DNA methylation, resulting in the loss of MLH1 gene expression, mismatch-repair function, and...

  14. Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

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    Hudler Petra


    Full Text Available Abstract Background Loss of DNA mismatch repair (MMR in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC. Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Methods Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. Results The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Conclusion Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

  15. Specific Variants in the MLH1 Gene Region May Drive DNA Methylation, Loss of Protein Expression, and MSI-H Colorectal Cancer (United States)

    Mrkonjic, Miralem; Roslin, Nicole M.; Greenwood, Celia M.; Raptis, Stavroula; Pollett, Aaron; Laird, Peter W.; Pethe, Vaijayanti V.; Chiang, Theodore; Daftary, Darshana; Dicks, Elizabeth; Thibodeau, Stephen N.; Gallinger, Steven; Parfrey, Patrick S.; Younghusband, H. Banfield; Potter, John D.; Hudson, Thomas J.; McLaughlin, John R.; Green, Roger C.; Zanke, Brent W.; Newcomb, Polly A.; Paterson, Andrew D.; Bapat, Bharati


    Background We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734) and microsatellite unstable (MSI-H) colorectal cancers (CRCs) in two samples. The current study expanded on this finding as we explored the genetic basis of DNA methylation in this region of chromosome 3. We hypothesized that specific polymorphisms in the MLH1 gene region predispose it to DNA methylation, resulting in the loss of MLH1 gene expression, mismatch-repair function, and consequently to genome-wide microsatellite instability. Methodology/Principal Findings We first tested our hypothesis in one sample from Ontario (901 cases, 1,097 controls) and replicated major findings in two additional samples from Newfoundland and Labrador (479 cases, 336 controls) and from Seattle (591 cases, 629 controls). Logistic regression was used to test for association between SNPs in the region of MLH1 and CRC, MSI-H CRC, MLH1 gene expression in CRC, and DNA methylation in CRC. The association between rs1800734 and MSI-H CRCs, previously reported in Ontario and Newfoundland, was replicated in the Seattle sample. Two additional SNPs, in strong linkage disequilibrium with rs1800734, showed strong associations with MLH1 promoter methylation, loss of MLH1 protein, and MSI-H CRC in all three samples. The logistic regression model of MSI-H CRC that included MLH1-promoter-methylation status and MLH1 immunohisotchemistry status fit most parsimoniously in all three samples combined. When rs1800734 was added to this model, its effect was not statistically significant (P-value  = 0.72 vs. 2.3×10−4 when the SNP was examined alone). Conclusions/Significance The observed association of rs1800734 with MSI-H CRC occurs through its effect on the MLH1 promoter methylation, MLH1 IHC deficiency, or both. PMID:20967208

  16. Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancer.

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    Miralem Mrkonjic

    Full Text Available We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734 and microsatellite unstable (MSI-H colorectal cancers (CRCs in two samples. The current study expanded on this finding as we explored the genetic basis of DNA methylation in this region of chromosome 3. We hypothesized that specific polymorphisms in the MLH1 gene region predispose it to DNA methylation, resulting in the loss of MLH1 gene expression, mismatch-repair function, and consequently to genome-wide microsatellite instability.We first tested our hypothesis in one sample from Ontario (901 cases, 1,097 controls and replicated major findings in two additional samples from Newfoundland and Labrador (479 cases, 336 controls and from Seattle (591 cases, 629 controls. Logistic regression was used to test for association between SNPs in the region of MLH1 and CRC, MSI-H CRC, MLH1 gene expression in CRC, and DNA methylation in CRC. The association between rs1800734 and MSI-H CRCs, previously reported in Ontario and Newfoundland, was replicated in the Seattle sample. Two additional SNPs, in strong linkage disequilibrium with rs1800734, showed strong associations with MLH1 promoter methylation, loss of MLH1 protein, and MSI-H CRC in all three samples. The logistic regression model of MSI-H CRC that included MLH1-promoter-methylation status and MLH1 immunohistochemistry status fit most parsimoniously in all three samples combined. When rs1800734 was added to this model, its effect was not statistically significant (P-value  = 0.72 vs. 2.3×10(-4 when the SNP was examined alone.The observed association of rs1800734 with MSI-H CRC occurs through its effect on the MLH1 promoter methylation, MLH1 IHC deficiency, or both.

  17. Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols

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    Seppälä, Toni; Pylvänäinen, Kirsi; Evans, Dafydd Gareth


    We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic MLH1 variants (path_MLH1) despite follow-up with colonoscopy including polypectomy.......We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic MLH1 variants (path_MLH1) despite follow-up with colonoscopy including polypectomy....

  18. Clinical Significance of Epigenetic Inactivation of hMLH1 and BRCA1 in Tunisian Patients with Invasive Breast Carcinoma

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    Sondes Karray-Chouayekh


    Full Text Available Aberrant hypermethylation of gene promoter regions is one of the mechanisms for inactivation of tumour suppressor genes in many human cancers including breast carcinoma. In the current study, we aimed to assess by MSP, the methylation pattern of two cancer-related genes involved in DNA repair: hMLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli and BRCA1 (breast cancer 1, early onset in 78 primary breast cancers from Tunisian patients. The methylation frequencies were 24.36% for hMLH1 and 46% for BRCA1. BRCA1 methylation correlated with age at diagnosis (P=.015 and 5-years disease free survival (P=.016 while hMLH1 methylation was more frequent in larger tumors (P=.002 and in presence of distant metastasis (P=.004. Furthermore, methylation of hMLH1 significantly correlated with high level of P53 expression (P=.006 and with overall survival (P=.015 suggesting that silencing of hMLH1 through aberrant promoter methylation could be used as a poor prognosis indicator in breast cancer.

  19. [Histone H3 lysine 9 methylation is associated with the expression of hMLH1 and DNA methylation in gastric cancer cells]. (United States)

    Meng, Chun-Feng; Zhu, Xin-Jiang; Peng, Guo


    To identify the association of his tone H3 lysine 9 (H3-K9) methylation with DNA methylation and the expression of the mismatch repair gene hMLH1 in human gastric cancer cells. Gastric cancer cells of the lines BGC-823 and MGC-803 were cultured and treated with 5-Aza-2'-deoxycytidine (5-Aza-dC), a demethylation agent, for 72 hour. Chromatin immunoprecipitation (ChIP) assay was used to assess the status of histone H3 lysine 9 methylation in the promoter regions of hMLH1 gene. Methylation-specific PCR (MSP) was used to evaluate the effect of 5-Aza-dC on DNA methylation status. RT-PCR was used to examine the hMLH1 gene expression. In the MGC-803 cells, silenced hMLH1 gene was characterized by DNA methylation and histone H3-K9 hypermethylation; 5-Aza-dC demethylated the DNA and reduced the histone H3-K9 methylation at silenced loci and resulted in reactivation of hMLH1 gene therein. Contrary to the MGC-803 cells, BGC-823 cells expressed hMLH1 gene with DNA demethylation and histone H3-K9 hypomethylation; and 5-Aza-dC had no effects on the gene expression, DNA methylation, and histone H3-K9 methylation therein. Hypermethylation of DNA in the promoter region is related to transcriptional silencing of hMLH1 gene. Histone H3-K9 methylation in different regions of the promoter studied correlates with DNA methylation status of hMLH1 gene in gastric cancer cells. Alteration of DNA methylation affects histone H3-K9 methylation. 5-Aza-dC can control hMLH1 expression, DNA methylation, and histone H3-K9 methylation in the promoter.

  20. Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1 (United States)


    Introduction Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated. Methods Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively. Results MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability. Conclusions These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be

  1. Association between MLH1 -93G>a polymorphism and risk of colorectal cancer.

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    Ting Wang

    Full Text Available BACKGROUND: The -93G>A (rs1800734 polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC risk. However, the results remain conflicting rather than conclusive. OBJECTIVE: The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC. METHODS: To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls was performed. Odds ratios (ORs and 95% confidence intervals (CIs were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC. RESULTS: The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01-1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01-1.11. This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94-3.28; AG versus GG: OR = 1.29, 95% CI = 1.10-1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24-1.68; AA versus AG/GG: OR = 2.29, 95% CI = 1.78-2.96. Egger's test did not show any evidence of publication bias. CONCLUSION: Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.

  2. The association between methylenetetrahydrofolate reductase polymorphism and promoter methylation in proximal colon cancer. (United States)

    Oyama, Kaeko; Kawakami, Kazuyuki; Maeda, Kazuya; Ishiguro, Kaname; Watanabe, Go


    Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in folate metabolism, which is an important pathway of the methyl donor for DNA methylation. The MTHFR gene has genetic variants (C667T and A1298C), which cause reduced enzyme activity. Impaired folate metabolism by these genetic variants of MTHFR could change the methylation pattern of DNA including promoter hypermethylation, which has been frequently observed in cancer. In this study, we compared the MTHFR genotypes and haplotype to the features of colorectal cancer focusing on the promoter methylation of tumor DNA. Genomic DNA was isolated from 194 colorectal cancer tissues and subjected to MTHFR genotyping by PCR-based restriction fragment length polymorphism analysis. The MTHFR haplotype was determined by combination of C667T and A1298C genotype and classified into 2 groups, high (H-haplotype) or low (L-haplotype) enzymatic activity of MTHFR. The methylation level of tumor suppressor genes (CDKN2A, hMLH1, ARF and TIMP3) was measured by a fluorescence-based, real-time methylation specific PCR method. There was no significant association of the clinicopathological features with either C667T genotype, A1298C genotype or haplotype of MTHFR. The methylation level of CDKN2A was higher in cancer with the L-haplotype of MTHFR than in that with the H-haplotype when cancers of proximal origin were considered (p=0.029). hMLH1 methylation also tended to be higher in proximal colon cancers of MTHFR L-haplotype (p=0.059). In addition, the proximal colon cancers showing CpG island methylator phenotype (CIMP) were significantly more frequent in L-haplotype than in H-haplotype. These results suggest that the haplotype with low enzymatic activity of MTHFR is linked with promoter hypermethylation and consequently modifies the risk of CIMP(+) proximal colon cancer development in the Japanese people. The relationship between MTHFR polymorphism and DNA methylation in the Japanese is contrary to the previous results

  3. Promoting proximal formative assessment with relational discourse (United States)

    Scherr, Rachel E.; Close, Hunter G.; McKagan, Sarah B.


    The practice of proximal formative assessment - the continual, responsive attention to students' developing understanding as it is expressed in real time - depends on students' sharing their ideas with instructors and on teachers' attending to them. Rogerian psychology presents an account of the conditions under which proximal formative assessment may be promoted or inhibited: (1) Normal classroom conditions, characterized by evaluation and attention to learning targets, may present threats to students' sense of their own competence and value, causing them to conceal their ideas and reducing the potential for proximal formative assessment. (2) In contrast, discourse patterns characterized by positive anticipation and attention to learner ideas increase the potential for proximal formative assessment and promote self-directed learning. We present an analysis methodology based on these principles and demonstrate its utility for understanding episodes of university physics instruction.

  4. Functional characterization of MLH1 missaense variants identified in lynch syndrome patients

    DEFF Research Database (Denmark)

    Andersen, Sofie Dabros; Liberti, Sascha Emilie; Lützen, Anne


    Germline mutations in the human DNA mismatch repair (MMR) genes MSH2 and MLH1 are associated with the inherited cancer disorder Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer or HNPCC. A proportion of MSH2 and MLH1 mutations found in suspected LS patients give rise t...

  5. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); Kerr, Iain D., E-mail: [Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108 (United States); Min, Jinrong, E-mail: [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); University of Toronto, Toronto, ON M5G 1L7 (Canada)


    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

  6. Temporal Proximity Promotes Integration of Overlapping Events. (United States)

    Zeithamova, Dagmar; Preston, Alison R


    Events with overlapping elements can be encoded as two separate representations or linked into an integrated representation, yet we know little about the conditions that promote one form of representation over the other. Here, we tested the hypothesis that the proximity of overlapping events would increase the probability of integration. Participants first established memories for house-object and face-object pairs; half of the pairs were learned 24 hr before an fMRI session, and the other half 30 min before the session. During scanning, participants encoded object-object pairs that overlapped with the initial pairs acquired on the same or prior day. Participants were also scanned as they made inference judgments about the relationships among overlapping pairs learned on the same or different day. Participants were more accurate and faster when inferring relationships among memories learned on the same day relative to those acquired across days, suggesting that temporal proximity promotes integration. Evidence for reactivation of existing memories-as measured by a visual content classifier-was equivalent during encoding of overlapping pairs from the two temporal conditions. In contrast, evidence for integration-as measured by a mnemonic strategy classifier from an independent study [Richter, F. R., Chanales, A. J. H., & Kuhl, B. A. Predicting the integration of overlapping memories by decoding mnemonic processing states during learning. Neuroimage, 124, 323-335, 2016]-was greater for same-day overlapping events, paralleling the behavioral results. During inference itself, activation patterns further differentiated when participants were making inferences about events acquired on the same day versus across days. These findings indicate that temporal proximity of events promotes integration and further influences the neural mechanisms engaged during inference.

  7. Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants. (United States)

    Pagenstecher, Constanze; Wehner, Maria; Friedl, Waltraut; Rahner, Nils; Aretz, Stefan; Friedrichs, Nicolaus; Sengteller, Marlies; Henn, Wolfram; Buettner, Reinhard; Propping, Peter; Mangold, Elisabeth


    Single base substitutions in DNA mismatch repair genes which are predicted to lead either to missense or silent mutations, or to intronic variants outside the highly conserved splicing region are often found in hereditary nonpolyposis colorectal cancer (HNPCC) families. In order to use the variants for predictive testing in persons at risk, their pathogenicity has to be evaluated. There is growing evidence that some substitutions have a detrimental influence on splicing. We examined 19 unclassified variants (UVs) detected in MSH2 or MLH1 genes in patients suspected of HNPCC for expression at RNA level. We demonstrate that 10 of the 19 UVs analyzed affect splicing. For example, the substitution MLH1,c.2103G > C in the last position of exon 18 does not result in a missense mutation as theoretically predicted (p.Gln701His), but leads to a complete loss of exon 18. The substitution MLH1,c.1038G > C (predicted effect p.Gln346His) leads to complete inactivation of the mutant allele by skipping of exons 10 and 11, and by activation of a cryptic intronic splice site. Similarly, the intronic variant MLH1,c.306+2dupT results in loss of exon 3 and a frameshift mutation due to a new splice donor site 5 bp upstream. Furthermore, we confirmed complete exon skipping for the mutations MLH1,c.1731G > A and MLH1,c.677G > A. Partial exon skipping was demonstrated for the mutations MSH2,c.1275A > G, MLH1,c.588+5G > A, MLH1,c.790+4A > G and MLH1,c.1984A > C. In contrast, five missense mutations (MSH2,c.4G > A, MSH2,c.2123T > A, MLH1,c.464T > G, MLH1,c.875T > C and MLH1,c.2210A > T) were found in similar proportions in the mRNA as in the genomic DNA. We conclude that the mRNA examination should precede functional tests at protein level.

  8. Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch syndrome founder mutation

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Isinger-Ekstrand, Anna; Ladelund, Steen


    Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register...... to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation families with comparison to 47 other MLH1 mutant families. The founder mutation conferred comparable risks for colorectal cancer (relative risks, RR, of 0.99 for males and 0.79 for females) and lower risks...... in 68 % with extensive inter-tumor variability despite the same underlying germline mutation. In conclusion, the Danish MLH1 founder mutation that accounts for a significant proportion of Lynch syndrome and is associated with a lower risk for extracolonic cancers....

  9. De novo constitutional MLH1 epimutations confer early-onset colorectal cancer in two new sporadic Lynch syndrome cases, with derivation of the epimutation on the paternal allele in one. (United States)

    Goel, Ajay; Nguyen, Thuy-Phuong; Leung, Hon-Chiu E; Nagasaka, Takeshi; Rhees, Jennifer; Hotchkiss, Erin; Arnold, Mildred; Banerji, Pia; Koi, Minoru; Kwok, Chau-To; Packham, Deborah; Lipton, Lara; Boland, C Richard; Ward, Robyn L; Hitchins, Megan P


    Lynch syndrome is an autosomal dominant cancer predisposition syndrome classically caused by germline mutations of the mismatch repair genes, MLH1, MSH2, MSH6 and PMS2. Constitutional epimutations of the MLH1 gene, characterized by soma-wide methylation of a single allele of the promoter and allelic transcriptional silencing, have been identified in a subset of Lynch syndrome cases lacking a sequence mutation in MLH1. We report two individuals with no family history of colorectal cancer who developed that disease at age 18 and 20 years. In both cases, cancer had arisen because of the de novo occurrence of a constitutional MLH1 epimutation and somatic loss-of-heterozygosity of the functional allele in the tumors. We show for the first time that the epimutation in one case arose on the paternally inherited allele. Analysis of 13 tumors from seven individuals with constitutional MLH1 epimutations showed eight tumors had lost the second MLH1 allele, two tumors had a novel pathogenic missense mutation and three had retained heterozygosity. Only 1 of 12 tumors demonstrated the BRAF V600E mutation and 3 of 11 tumors harbored a mutation in KRAS. The finding that epimutations can originate on the paternal allele provides important new insights into the mechanism of origin of epimutations. It is clear that the second hit in MLH1 epimutation-associated tumors typically has a genetic not epigenetic basis. Individuals with mismatch repair-deficient cancers without the BRAF V600E mutation are candidates for germline screening for sequence or methylation changes in MLH1. Copyright © 2010 UICC.

  10. Characterization of a highly conserved binding site of Mlh1 required for exonuclease I-dependent mismatch repair

    DEFF Research Database (Denmark)

    Dherin, Claudine; Gueneau, Emeric; Francin, Mathilde


    Mlh1 is an essential factor of mismatch repair (MMR) and meiotic recombination. It interacts through its C-terminal region with MutL homologs and proteins involved in DNA repair and replication. In this study, we identified the site of yeast Mlh1 critical for the interaction with Exo1, Ntg2, and ...

  11. Completion of meiosis in male zebrafish (Danio rerio) despite lack of DNA mismatch repair gene mlh1.

    NARCIS (Netherlands)

    Leal, M.C.; Feitsma, H.; Cuppen, E.; Franca, L.R.; Schulz, R.W.


    Mlh1 is a member of DNA mismatch repair (MMR) machinery and is also essential for the stabilization of crossovers during the first meiotic division. Recently, we have shown that zebrafish mlh1 mutant males are completely infertile because of a block in metaphase I, whereas females are fertile but

  12. Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis

    DEFF Research Database (Denmark)

    Hinrichsen, Inga; Brieger, Angela; Trojan, Jörg


    Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance. The functionality of these variants can be tested in the laboratory, but the results c...... cannot be used for clinical diagnosis. We therefore aimed to establish a laboratory test that can be applied clinically.......Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance. The functionality of these variants can be tested in the laboratory, but the results...

  13. Novel Mutations in MLH1 and MSH2 Genes in Mexican Patients with Lynch Syndrome

    Directory of Open Access Journals (Sweden)

    Jose Miguel Moreno-Ortiz


    Full Text Available Background. Lynch Syndrome (LS is characterized by germline mutations in the DNA mismatch repair (MMR genes MLH1, MSH2, MSH6, and PMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC and extracolonic tumors. The aim of this study was to identify mutations in MMR genes in three Mexican patients with LS. Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC, and Sanger sequencing complemented the analysis. Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found in MLH1 gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del and c.1852_1853delinsGC (p.K618A in exon 16. In the MSH2 gene, we identified mutation c.638dupT (p.L213fs in exon 3. Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel.

  14. A Mononucleotide Markers Panel to Identify hMLH1/hMSH2 Germline Mutations

    Directory of Open Access Journals (Sweden)

    M. Pedroni


    Full Text Available Hereditary NonPolyposis Colorectal Cancer (Lynch syndrome is an autosomal dominant disease caused by germline mutations in a class of genes deputed to maintain genomic integrity during cell replication, mutations result in a generalized genomic instability, particularly evident at microsatellite loci (Microsatellite Instability, MSI. MSI is present in 85–90% of colorectal cancers that occur in Lynch Syndrome. To standardize the molecular diagnosis of MSI, a panel of 5 microsatellite markers was proposed (known as the “Bethesda panel”. Aim of our study is to evaluate if MSI testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients with hMLH1/hMSH2 germline mutations. We tested 105 tumours for MSI using both the Bethesda markers and the two mononucleotide markers BAT25 and BAT26. Moreover, immunohistochemical evaluation of MLH1 and MSH2 proteins was executed on the tumours with at least one unstable microsatellite, whereas germline hMLH1/hMSH2 mutations were searched for all cases showing two or more unstable microsatellites.

  15. Functional characterization of rare missense mutations in MLH1 and MSH2 identified in Danish colorectal cancer patients

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Kariola, Reetta; Korhonen, Mari K


    Recently, we have performed a population based study to analyse the frequency of colorectal cancer related MLH1 and MSH2 missense mutations in the Danish population. Half of the analyzed mutations were rare and most likely only present in the families where they were identified originally. Some...... of the missense mutations were located in conserved regions in the MLH1 and MSH2 proteins indicating a relation to disease development. In the present study, we functionally characterized 10 rare missense mutations in MLH1 and MSH2 identified in 13 Danish CRC families. To elucidate the pathogenicity...

  16. A positioned +1 nucleosome enhances promoter-proximal pausing


    Jimeno-Gonz?lez, Silvia; Ceballos-Ch?vez, Mar?a; Reyes, Jos? C.


    Chromatin distribution is not uniform along the human genome. In most genes there is a promoter-associated nucleosome free region (NFR) followed by an array of nucleosomes towards the gene body in which the first (+1) nucleosome is strongly positioned. The function of this characteristic chromatin distribution in transcription is not fully understood. Here we show in vivo that the +1 nucleosome plays a role in modulating RNA polymerase II (RNAPII) promoter-proximal pausing. When a +1 nucleoso...

  17. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    Directory of Open Access Journals (Sweden)

    de Bruïne Adriaan P


    Full Text Available Abstract Background The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1 and Ras (K-ras pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. Methods In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Results Mutations at the phosphorylation sites (codons 31, 33, 37, and 45 in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656 and 36% (235/656, respectively. Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656. Nine percent of all tumours (58/656 lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. Conclusion CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency.

  18. Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients

    DEFF Research Database (Denmark)

    Petersen, S. M.; Dandanell, M.; Rasmussen, L. J.


    to asses the effect on splicing. Results: We describe in silico and in vitro characterization of nine intronic MLH1, MSH2, or MSH6 mutations identified in Danish colorectal cancer patients, of which four mutations are novel. The analysis revealed aberrant splicing of five mutations (MLH1 c. 588 + 5G > A......Background: Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well...... as large genomic rearrangements. However, a large number of mutations, including missense, silent, and intronic variants, are classified as variants of unknown clinical significance. Methods: Intronic MLH1, MSH2, or MSH6 variants were investigated using in silico prediction tools and mini-gene assay...

  19. Immunohistochemical and DNA sequencing analysis on human mismatch repair gene MLH1 in cervical squamous cell carcinoma with LOH of this gene

    NARCIS (Netherlands)

    Hu, X.; Guo, Z.; Pang, T.; Li, Q.; Afink, G.; Pontén, J.


    BACKGROUND: The human MLH1 gene (hMLH1) is one of the DNA mismatch repair genes. Defects in these genes are believed to be the underlying cause of microsatellite instability (MSI). MSI has been demonstrated in many human cancers such as colon cancer and some female-specific tumors. The hMLH1 gene

  20. Repair genes expression profile of MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers. (United States)

    Alves, Mônica Ghislaine Oliveira; Carta, Celina Faig Lima; de Barros, Patrícia Pimentel; Issa, Jaqueline Scholz; Nunes, Fábio Daumas; Almeida, Janete Dias


    The aim of this study was to evaluate the effect of chronic smoking on the expression profile of the repair genes MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers and never smokers. The sample consisted of thirty exfoliative cytology smears per group obtained from Smokers and Never Smokers. Total RNA was extracted and expression of the MLH1, MSH2 and ATM genes were evaluated by quantitative real-time and immunocytochemistry. The gene and protein expression data were correlated to the clinical data. Gene expression was analyzed statistically using the Student t-test and Pearson's correlation coefficient, with pATM genes were downregulated in the smoking group compared to the control with significant values for MLH1 (p=0.006), MSH2 (p=0.0001) and ATM (p=0.0001). Immunocytochemical staining for anti-MLH1, anti-MSH2 and anti-ATM was negative in Never Smokers; in Smokers it was rarely positive. No significant correlation was observed among the expression of MLH1, MSH2, ATM and age, number of cigarettes consumed per day, time of smoking during life, smoking history or levels of CO in expired air. The expression of genes and proteins related to DNA repair mechanism MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers was reduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Spectrum of MLH1 and MSH2 mutations in Chilean families with suspected Lynch syndrome. (United States)

    Alvarez, Karin; Hurtado, Claudia; Hevia, Montserrat A; Wielandt, Ana Maria; de la Fuente, Marjorie; Church, James; Carvallo, Pilar; López-Köstner, Francisco


    Lynch syndrome is the most common inherited syndrome of colorectal cancer, caused principally by germline mutations in MLH1 and MSH2. We report our experience with genetic screening in the diagnosis of Lynch syndrome in Chile, a country previously underserved in the capacity to diagnose hereditary colorectal cancer. Families from our Familial Colorectal Cancer Registry were selected for this study if they fulfilled either Amsterdam I/II or Bethesda criteria for classification of Lynch syndrome. Analysis of colorectal tumors from probands included a microsatellite instability study and immunohistochemical evaluation for MLH1 and MSH2. Screening of germline mutations was performed by single-strand conformation polymorphism analysis and DNA sequencing. A total of 21 families were evaluated, 14 meeting Amsterdam criteria and 7 meeting Bethesda criteria. Tumors in 20 families (95%) showed microsatellite instability (19 high and 1 low) and 9 of these 20 families (45%) harbored a germline mutation (7 of 13 Amsterdam and 2 of 7 Bethesda families). Of the 9 mutations identified, 6 were in MLH1 and 3 in MSH2. Two of the mutations were novel, 3 were previously found in 1 to 2 European populations, and 4 were previously found in various ethnic populations worldwide. Only 2 mutations were previously found in another Latin American population (Colombia). In our probands, colorectal cancer was located mainly (57%) in the right or transverse colon. Pedigree information from 104 family affected members of 21 studied families showed endometrial cancer to be the most frequent primary extracolonic tumor, accounting for 15.1% of total cases, followed by stomach (13.2%) and breast cancer (11.3%). Analysis of mitochondrial DNA haplotypes showed a strong Amerindian genetic component in 15 (71.4%) of the 21 families analyzed. The study of Lynch syndrome in families of different ethnic origins contributes to the definition of genetic and clinical differences among populations. Wide

  2. High rate of CAD gene amplification in human cells deficient in MLH1 or MSH6 (United States)

    Chen, Sihong; Bigner, Sandra H.; Modrich, Paul


    MutS and MutL homologs have been implicated in multiple genetic stabilization pathways. The activities participate in the correction of DNA biosynthetic errors, are involved in cellular responses to certain types of DNA damage, and serve to ensure the fidelity of genetic recombination. We show here that the rate of CAD (carbamyl-P synthetase/aspartate transcarbamylase/dihydroorotase) gene amplification is elevated 50- to 100-fold in human cell lines deficient in MLH1 or MSH6, as compared with mismatch repair-proficient control cells. Fluorescence in situ hybridization indicates that these amplification events are the probable consequence of unequal sister chromatid exchanges involving chromosome 2, as well as translocation events involving other chromosomes. These results implicate MutSα and MutLα in the suppression of gene amplification and suggest that defects in this genetic stabilization function may contribute to the cancer predisposition associated with mismatch repair deficiency. PMID:11717437

  3. Prevalence of pathological germline mutations of hMLH1 and hMSH2 genes in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Dandan Li

    Full Text Available The prevalence of pathological germline mutations in colorectal cancer has been widely studied, as germline mutations in the DNA mismatch repair genes hMLH1 and hMSH2 confer a high risk of colorectal cancer. However, because the sample size and population of previous studies are very different from each other, the conclusions still remain controversial. In this paper, Databases such as PubMed were applied to search for related papers. The data were imported into Comprehensive Meta-Analysis V2, which was used to estimate the weighted prevalence of hMLH1 and hMSH2 pathological mutations and compare the differences of prevalence among different family histories, ethnicities and related factors. This study collected and utilized data from 102 papers. In the Amsterdam-criteria positive group, the prevalence of pathological germline mutations of the hMLH1 and hMSH2 genes was 28.55% (95%CI 26.04%-31.19% and 19.41% (95%CI 15.88%-23.51%, respectively, and the prevalence of germline mutations in hMLH1/hMSH2 was 15.44%/10.02%, 20.43%/13.26% and 15.43%/11.70% in Asian, American multiethnic and European/Australian populations, respectively. Substitution mutations accounted for the largest proportion of germline mutations (hMLH1: 52.34%, hMSH2: 43.25%. The total prevalence of mutations of hMLH1 and hMSH2 in Amsterdam-criteria positive, Amsterdam-criteria negative and sporadic colorectal cancers was around 45%, 25% and 15%, respectively, and there were no obvious differences in the prevalence of germline mutations among different ethnicities.

  4. Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Drost, Mark; Therkildsen, Christina


    In clinical genetic diagnostics, it is difficult to predict whether genetic mutations that do not greatly alter the primary sequence of the encoded protein causing unknown functional effects on cognate proteins lead to development of disease. Here, we report the clinical identification of c.2038 T......>C missense mutation in exon 18 of the human MLH1 gene and biochemically characterization of the p.Cys680Arg mutant MLH1 protein to implicate it in the pathogenicity of the Lynch syndrome (LS). We show that the mutation is deficient in DNA mismatch repair and, therefore, contributing to LS in the carriers....

  5. Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.

    NARCIS (Netherlands)

    Weijenberg, M.P.; Luchtenborg, M.; Goeij, A.F. de; Brink, M.; Muijen, G.N.P. van; Bruine, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den


    OBJECTIVE: To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat

  6. Fruits, vegetables, and hMLH1 protein-deficient and -proficient colon cancer: The Netherlands cohort study

    NARCIS (Netherlands)

    Wark, P.A.; Weijenberg, M.P.; Veer, P. van 't; Wijhe, G. van; Luchtenborg, M.; Muijen, G.N.P. van; Goeij, A.F.P.M. de; Goldbohm, R.A.; Brandt, P.A. van den


    Background: Clinical and pathologic differences exist between colon carcinomas deficient and proficient in the mismatch repair protein hMLH1. Animal and in vitro studies suggest that fruits, vegetables, folate, and antioxidants are associated with colonic expression of mismatch repair genes.

  7. Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort. (United States)

    Rosty, Christophe; Clendenning, Mark; Walsh, Michael D; Eriksen, Stine V; Southey, Melissa C; Winship, Ingrid M; Macrae, Finlay A; Boussioutas, Alex; Poplawski, Nicola K; Parry, Susan; Arnold, Julie; Young, Joanne P; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loïc; Newcomb, Polly A; Potter, John D; DeRycke, Melissa; Lindor, Noralane M; Thibodeau, Stephen N; Baron, John A; Win, Aung Ko; Hopper, John L; Jenkins, Mark A; Buchanan, Daniel D


    Immunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation in PMS2, previous studies reported MLH1 mutation in some cases. We determined the prevalence of MLH1 germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss of PMS2 expression. This cohort study included 88 individuals affected with a PMS2-deficient CRC from the Colon Cancer Family Registry Cohort. Germline PMS2 mutation analysis (long-range PCR and multiplex ligation-dependent probe amplification) was followed by MLH1 mutation testing (Sanger sequencing and multiplex ligation-dependent probe amplification). Of the 66 individuals with complete mutation screening, we identified a pathogenic PMS2 mutation in 49 (74%), a pathogenic MLH1 mutation in 8 (12%) and a MLH1 variant of uncertain clinical significance predicted to be damaging by in silico analysis in 3 (4%); 6 (9%) carried variants likely to have no clinical significance. Missense point mutations accounted for most alterations (83%; 9/11) in MLH1. The MLH1 c.113A> G p.Asn38Ser mutation was found in 2 related individuals. One individual who carried the MLH1 intronic mutation c.677+3A>G p.Gln197Argfs*8 leading to the skipping of exon 8, developed 2 tumours, both of which retained MLH1 expression. A substantial proportion of CRCs with solitary loss of PMS2 expression are associated with a deleterious MLH1 germline mutation supporting the screening for MLH1 in individuals with tumours of this immunophenotype, when no PMS2 mutation has been identified. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  8. Vitamin E Modifies High-Fat Diet-Induced Increase of DNA Strand Breaks, and Changes in Expression and DNA Methylation of Dnmt1 and MLH1 in C57BL/6J Male Mice

    Directory of Open Access Journals (Sweden)

    Marlene Remely


    Full Text Available Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD or a control diet (CD with and without vitamin E supplementation (4.5 mg/kg body weight (b.w. for four months. DNA damage, DNA promoter methylation and gene expression of Dnmt1 and a DNA repair gene (MLH1 were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important Dnmt1 gene, and the DNA repair gene MLH1. Vitamin E reduced DNA damage and showed organ-specific effects on MLH1 and Dnmt1 gene expression and methylation. These results suggest that interventions with antioxidants and epigenetic active food ingredients should be developed as an effective prevention for obesity—and oxidative stress—induced health risks.

  9. Nine novel pathogenic germline mutations in MLH1, MSH2, MSH6 and PMS2 in families with Lynch syndrome. (United States)

    Rahner, Nils; Friedrichs, Nicolaus; Wehner, Maria; Steinke, Verena; Aretz, Stefan; Friedl, Waltraut; Buettner, Reinhard; Mangold, Elisabeth; Propping, Peter; Walldorf, Constanze


    Many germline mutations in the DNA mismatch repair genes have been described so far leading to the clinical phenotype of Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC). Most mutations are private mutations. We report on nine novel pathogenic germline mutations that have been found in families meeting either the Amsterdam or the Bethesda criteria. These findings include the mutations MLH1,c.884+4A>G, MLH1,c.1377_1378insA;p.Glu460ArgfsX19, MLH1,c.1415_1416delGA;p.Arg472ThrfsX5, MSH2,c.301G>T;p.Glu101X, MSH2,c.638_639delTG;p.Leu213GlnfsX18, MSH2,c.842C>A;p.Ser281X, MSH2,c.859G>T;p.Gly287X, MSH6,c.2503C>T;p.Gln835X and a large genomic deletion of exons 1-10 of the PMS2 gene. The mutation MLH1,c.884+4A>G detected in two families results in a complete skipping of exon 10 on mRNA level and thus has been considered as pathogenic. In all cases the tumor tissue of the index patient revealed high microsatellite instability (MSI-H) and showed a complete loss of expression of the affected protein in the tumor cells by immunohistochemistry (IHC). The findings underline the importance of a pre-screening of tumor tissue for an efficient definition of conspicuous cases.

  10. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

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    Ricardo Mouro Pinto


    Full Text Available The Huntington's disease gene (HTT CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111 than on a 129 background (129.Hdh(Q111 . Linkage mapping in (B6x129.Hdh(Q111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3 complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3. The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest

  11. Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

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    Catherine E Smith


    Full Text Available Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.

  12. No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine. (United States)

    Camargo, Elaine Aparecida de; da Silva, Glenda Nicioli; Gobette, Camila Pereira; Marcondes, Joao Paulo de Castro; Salvadori, Daisy Maria Favero


    Tumor response to antineoplastic drugs is not always predictable. This is also true for bladder carcinoma, a highly recurrent neoplasia. Currently, the combination of cisplatin and gemcitabine is well accepted as a standard protocol for treating bladder carcinoma. However, in some cases, this treatment protocol causes harmful side effects. Therefore, we investigated the roles of the genes TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53 status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A and hMLH1 expression in the two cell lines. Increased DNA damage was observed in both cell lines after treatment with cisplatin or gemcitabine and with the two drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A expression and hypermethylation of its promoter were observed before and after treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated to methylation status, was observed in RT4 cells after treatment with cisplatin or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells, hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the three treatment protocols were genotoxic, independent of TP53 status. However, cisplatin was the most effective, causing the highest level of DNA damage in both wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in both cell lines. Furthermore, no relationship was observed between the amount of DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other alternative pathways might be involved in cisplatin and gemcitabine genotoxicity in these two bladder cancer cell

  13. Missense variants in hMLH1 identified in patients from the German HNPCC consortium and functional studies. (United States)

    Hardt, Karin; Heick, Sven Boris; Betz, Beate; Goecke, Timm; Yazdanparast, Haniyeh; Küppers, Robin; Servan, Kati; Steinke, Verena; Rahner, Nils; Morak, Monika; Holinski-Feder, Elke; Engel, Christoph; Möslein, Gabriela; Schackert, Hans-Konrad; von Knebel Doeberitz, Magnus; Pox, Christian; Hegemann, Johannes H; Royer-Pokora, Brigitte


    Missense mutations of the DNA mismatch repair gene MLH1 are found in a significant fraction of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) and their pathogenicity often remains unclear. We report here all 88 MLH1 missense variants identified in families from the German HNPCC consortium with clinical details of these patients/families. We investigated 23 MLH1 missense variants by two functional in vivo assays in yeast; seven map to the ATPase and 16 to the protein interaction domain. In the yeast-2-hybrid (Y2H) assay three variants in the ATPase and twelve variants in the interaction domain showed no or a reduced interaction with PMS2; seven showed a normal and one a significantly higher interaction. Using the Lys2A (14) reporter system to study the dominant negative mutator effect (DNE), 16 variants showed no or a low mutator effect, suggesting that these are nonfunctional, three were intermediate and four wild type in this assay. The DNE and Y2H results were concordant for all variants in the interaction domain, whereas slightly divergent results were obtained for variants in the ATPase domain. Analysis of the stability of the missense proteins in yeast and human embryonic kidney cells (293T) revealed a very low expression for seven of the variants in yeast and for nine in human cells. In total 15 variants were classified as deleterious, five were classified as variants of unclassified significance (VUS) and three were basically normal in the functional assays, P603R, K618R, Q689R, suggesting that these are neutral.

  14. Human MLH1 protein participates in genomic damage checkpoint signaling in response to DNA interstrand crosslinks, while MSH2 functions in DNA repair.

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    Qi Wu


    Full Text Available DNA interstrand crosslinks (ICLs are among the most toxic types of damage to a cell. For this reason, many ICL-inducing agents are effective therapeutic agents. For example, cisplatin and nitrogen mustards are used for treating cancer and psoralen plus UVA (PUVA is useful for treating psoriasis. However, repair mechanisms for ICLs in the human genome are not clearly defined. Previously, we have shown that MSH2, the common subunit of the human MutSalpha and MutSbeta mismatch recognition complexes, plays a role in the error-free repair of psoralen ICLs. We hypothesized that MLH1, the common subunit of human MutL complexes, is also involved in the cellular response to psoralen ICLs. Surprisingly, we instead found that MLH1-deficient human cells are more resistant to psoralen ICLs, in contrast to the sensitivity to these lesions displayed by MSH2-deficient cells. Apoptosis was not as efficiently induced by psoralen ICLs in MLH1-deficient cells as in MLH1-proficient cells as determined by caspase-3/7 activity and binding of annexin V. Strikingly, CHK2 phosphorylation was undetectable in MLH1-deficient cells, and phosphorylation of CHK1 was reduced after PUVA treatment, indicating that MLH1 is involved in signaling psoralen ICL-induced checkpoint activation. Psoralen ICLs can result in mutations near the crosslinked sites; however, MLH1 function was not required for the mutagenic repair of these lesions, and so its signaling function appears to have a role in maintaining genomic stability following exposure to ICL-induced DNA damage. Distinguishing the genetic status of MMR-deficient tumors as MSH2-deficient or MLH1-deficient is thus potentially important in predicting the efficacy of treatment with psoralen and perhaps with other ICL-inducing agents.

  15. Reduced frequency of extracolonic cancers in hereditary nonpolyposis colorectal cancer families with monoallelic hMLH1 expression.


    Jäger, A C; Bisgaard, M L; Myrhøj, T; Bernstein, I; Rehfeld, J F; Nielsen, F C


    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease caused by mutations in one of at least four different DNA mismatch repair genes, hMLH1, hMSH2, hPMS1, and hPMS2. Phenotypically, HNPCC is characterized by the early onset of colorectal cancers and various extracolonic cancers. Depending on the presence or absence of extracolonic tumors, HNPCG-has been divided into two syndromes (Lynch syndrome I and Lynch syndrome II), but, so far, no correlation to distinct ge...

  16. Expression of the mismatch repair gene hMLH1 is enhanced in non-small cell lung cancer with EGFR mutations.

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    Mei Li

    Full Text Available Mismatch repair (MMR plays a pivotal role in keeping the genome stable. MMR dysfunction can lead to carcinogenesis by gene mutation accumulation. HMSH2 and hMLH1 are two key components of MMR. High or low expression of them often mark the status of MMR function. Mutations (EGFR, KRAS, etc are common in non-small cell lung cancer (NSCLC. However, it is not clear what role MMR plays in NSCLC gene mutations. The expression of MMR proteins hMSH2 and hMLH1, and the proliferation markers PCNA and Ki67 were measured by immunohistochemistry in 181 NSCLCs. EGFR and KRAS mutations were identified by high resolution melting analysis. Stronger hMLH1 expression correlated to a higher frequency of EGFR mutations in exon 19 and 21 (p<0.0005. Overexpression of hMLH1 and the adenocarcinoma subtype were both independent factors that related to EGFR mutations in NSCLCs (p=0.013 and p<0.0005. The expression of hMLH1, hMSH2 and PCNA increased, while Ki67 expression significantly decreased (p=0.030 in NSCLCs with EGFR mutations. Overexpression of hMLH1 could be a new molecular marker to predict the response to EGFR-TKIs in NSCLCs. Furthermore, EGFR mutations might be an early event of NSCLC that occur before MMR dysfunction.

  17. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, Anette; Hillingsø, J; Bukhave, Klaus


    experiments. Also the combination of omeprazole and ranitidine increased (p=0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid......The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H-2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether...... this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n=17) and after pretreatment with high...

  18. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K


    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether...... this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment...... with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid...

  19. Meat and fish consumption, APC gene mutations and hMLH1 expression in colon and rectal cancer: a prospective cohort study (the Netherlands)

    NARCIS (Netherlands)

    Luchtenborg, M.; Weijenberg, M.P.; Goeij, de A.F.P.M.; Wark, P.A.; Brink, M.; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Bruine, de A.P.; Goldbohm, R.A.; Veer, van 't P.; Brandt, van den P.A.


    Objective:The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. Methods:The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer

  20. MSH2 and MLH1 mutations in sporadic replication error-positive colorectal carcinoma as assessed by two-dimensional DNA electrophoresis

    NARCIS (Netherlands)

    Wu, Y; NystromLahti, M; Osinga, J; Looman, MWG; Peltomaki, P; Aaltonen, LA; delaChapelle, A; Hofstra, RMW; Buys, CHCM

    Replication errors (RER) are frequently seen in both sporadic and hereditary forms of colorectal cancer. In hereditary nonpolyposis colorectal cancer (HNPCC), RER is associated with defects in DNA mismatch repair genes. Two of these genes, MSH2 and MLH1, account for a major share of this cancer

  1. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva


    deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...

  2. MLH1 and MSH2 protein expression as a pre-screening marker in hereditary and non-hereditary endometrial hyperplasia and cancer

    NARCIS (Netherlands)

    Berends, MJW; Hollema, H; Wu, Y; van der Sluis, T; Mensink, RGJ; ten Hoor, KA; Sijmons, RH; de Vries, EGE; Pras, E; Mourits, MJE; Hofstra, RMW; Buys, CHCM; Kleibeuker, JH; van der Zee, AGJ


    The predictive value of MLH1 or MSH2 protein expression for the presence of truncating germline mutations was examined in benign and (pre)malignant endometrial samples from 3 patient groups: (1) 10 endometrial cancer patients from hereditary non-polyposis colorectal cancer (HNPCC) families with (n =

  3. Distinct patterns of KRAS mutations in colorectal carcinomas according to germline mismatch repair defects and hMLH1 methylation status

    NARCIS (Netherlands)

    Oliveira, C; Westra, JL; Arango, D; Ollikainen, M; Domingo, E; Ferreira, A; Velho, S; Niessen, R; Lagerstedt, K; Alhopuro, P; Laiho, P; Veiga, [No Value; Teixeira, MR; Ligtenberg, M; Kleibeuker, JH; Sijmons, RH; Plukker, JT; Imai, K; Lage, P; Hamelin, R; Albuquerque, C; Schwartz, S; Lindblom, A; Peltomaki, P; Yamamoto, H; Aaltonen, LA; Seruca, R; Hofstra, RMW


    In sporadic colorectal tumours the BRAF(V600E) is associated with microsatellite instability (MSI-H) and inversely associated to KRAS mutations. Tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients carrying germline mutations in hMSH2 or hMLH1 do not show BRAF(V600E), however no

  4. Meat and fish consumption, APC gene mutations and hMLH1 expression in colon and rectal cancer: A prospective cohort study (The Netherlands)

    NARCIS (Netherlands)

    Lüchtenborg, M.; Weijenberg, M.P.; Goeij, A.F.P.M. de; Wark, P.A.; Brink, M.; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Bruïne, A.P. de; Goldbohm, R.A.; Veer, P. van 't; Brandt, P.A. van den


    Objective: The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. Methods: The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer

  5. A founder MLH1 mutation in Lynch syndrome families from Piedmont, Italy, is associated with an increased risk of pancreatic tumours and diverse immunohistochemical patterns. (United States)

    Borelli, Iolanda; Casalis Cavalchini, Guido C; Del Peschio, Serena; Micheletti, Monica; Venesio, Tiziana; Sarotto, Ivana; Allavena, Anna; Delsedime, Luisa; Barberis, Marco A; Mandrile, Giorgia; Berchialla, Paola; Ogliara, Paola; Bracco, Cecilia; Pasini, Barbara


    The MLH1 c.2252_2253delAA mutation was found in 11 unrelated families from a restricted area south-west of Turin among 140 families with mutations in the mismatch repair genes. The mutation is located in the highly conserved C-terminal region, responsible for dimerization with the PMS2 protein. Twenty-five tumour tissues from 61 individuals with the c.2252_2253delAA mutation were tested for microsatellite instability (MSI) and protein expression. We compared the clinical features of these families versus the rest of our cohort and screened for a founder effect. All but one tumours showed the MSI-high mutator phenotype. Normal, focal and lack of MLH1 staining were observed in 16, 36 and 48 % of tumours, respectively. PMS2 expression was always lost. The mutation co-segregated with Lynch syndrome-related cancers in all informative families. All families but one fulfilled Amsterdam criteria, a frequency higher than in other MLH1 mutants. This was even more evident for AC II (72.7 vs. 57.5 %). Moreover, all families had at least one colon cancer diagnosed before 50 years and one case with multiple Lynch syndrome-related tumours. Interestingly, a statistically significant (p = 0.0057) higher frequency of pancreatic tumours was observed compared to families with other MLH1 mutations: 8.2 % of affected individuals versus 1.6 %. Haplotype analysis demonstrated a common ancestral origin of the mutation, which originated about 1,550 years ago. The mutation is currently classified as having an uncertain clinical significance. Clinical features, tissue analysis and co-segregation with disease strongly support the hypothesis that the MLH1 c.2252_2253delAA mutation has a pathogenic effect.

  6. Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver and kidney specific expression and promoter activity predict variation.

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    Stephanie E Hesselson


    Full Text Available Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (-250 to +50 bp and flanking 5' sequence of 107 transporters in the ATP Binding Cassette (ABC and Solute Carrier (SLC superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (pi was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response.

  7. [Lynch Syndrome Caused by Germline Alteration of MLH1 in a Young Patient Who Developed Colon and Endometrial Cancer - A Case Report]. (United States)

    Yamamoto, Azusa; Suzuki, Okihide; Chika, Noriyasu; Ito, Tetsuya; Tajima, Yusuke; Kumamoto, Kensuke; Eguchi, Hidetaka; Kumagai, Youichi; Ishibashi, Keiichiro; Mochiki, Erito; Okazaki, Yasushi; Ishida, Hideyuki


    A 39-year-old woman underwent right colectomy for type-3 transverse colon cancer, which was histologically identified as well-differentiated stage II A adenocarcinoma with a mucinous component and tumor-infiltrating lymphocytes. The patient was suspected of having Lynch syndrome(LS)since she fulfilled 2 of the revised Bethesda criteria, even though there was no family history of LS. Twelve months after colectomy, abdominal CT revealed thickening of the uterine endometrium. Histopathological examination of biopsy specimens revealed well-differentiated endometrioid carcinoma. Extended hysterectomy with bilateral oophorectomy was performed. Histological examination of the resected specimen revealed well-differentiated endometrioid carcinoma of stage I . Immunohistochemistry analysis of mismatch repair proteins demonstrated loss of MLH1/ PMS2 expression in the colon cancer, but normal expression in the uterine cancer. Genetic testing identified duplication of exons 10-15 of the MLH1 gene, leading to a definitive diagnosis of LS. The patient has not shown any evidence of recurrence or new LS-associated tumors in the 12 years since the last surgery. There is an ongoing debate regarding the pathogenesis of endometrioid cancer, and this case emphasizes the importance of surveillance for gynecological malignancies after colon cancer surgery in female LS patients.

  8. The MLH1 c.1852_1853delinsGC (p.K618A variant in colorectal cancer: genetic association study in 18,723 individuals.

    Directory of Open Access Journals (Sweden)

    Anna Abulí

    Full Text Available Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance", being the c.1852_1853delinsGC (p.K618A variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

  9. Mutation affecting the proximal promoter of Endoglin as the origin of hereditary hemorrhagic telangiectasia type 1. (United States)

    Albiñana, Virginia; Zafra, Ma Paz; Colau, Jorge; Zarrabeitia, Roberto; Recio-Poveda, Lucia; Olavarrieta, Leticia; Pérez-Pérez, Julián; Botella, Luisa M


    Hereditary hemorrhagic telangiectasia (HHT) is a vascular multi-organ system disorder. Its diagnostic criteria include epistaxis, telangiectases in mucocutaneous sites, arteriovenous malformations (AVMs), and familial inheritance. HHT is transmitted as an autosomal dominant condition, caused in 85% of cases by mutations in either Endoglin (ENG) or Activin receptor-like kinase (ACVRL1/ACVRL1/ALK1) genes. Pathogenic mutations have been described in exons, splice junctions and, in a few cases with ENG mutations, in the proximal promoter, which creates a new ATG start site. However, no mutations affecting transcription regulation have been described to date in HHT, and this type of mutation is rarely identified in the literature on rare diseases. Sequencing data from a family with HHT lead to single nucleotide change, c.-58G > A. The functionality and pathogenicity of this change was analyzed by in vitro mutagenesis, quantitative PCR and Gel shift assay. Student t test was used for statistical significance. A single nucleotide change, c.-58G > A, in the proximal ENG promoter co-segregated with HHT clinical features in an HHT family. This mutation was present in the proband and in 2 other symptomatic members, whereas 2 asymptomatic relatives did not harbor the mutation. Analysis of RNA from activated monocytes from the probands and the healthy brother revealed reduced ENG mRNA expression in the HHT patient (p = 0.005). Site-directed mutagenesis of the ENG promoter resulted in a three-fold decrease in luciferase activity of the mutant c.-58A allele compared to wild type (p = 0.005). Finally, gel shift assay identified a DNA-protein specific complex. The novel ENG c.-58G > A substitution in the ENG promoter co-segregates with HHT symptoms in a family and appears to affect the transcriptional regulation of the gene, resulting in reduced ENG expression. ENG c.-58G > A may therefore be a pathogenic HHT mutation leading to haploinsufficiency of

  10. Frequent LOH at hMLH1, a highly variable SNP in hMSH3, and negligible coding instability in ovarian cancer

    DEFF Research Database (Denmark)

    Arzimanoglou, I.I.; Hansen, L.L.; Chong, D.


    the mismatch DNA repair genes in ovarian cancer (OC), using a sensitive, accurate and reliable protocol we have developed. MATERIALS AND METHODS: A combination of high-resolution GeneScan software analysis and automated DNA cycle sequencing was used. RESULTS: Negligible coding MSI was observed in selected...... sequences of mismatch DNA repair genes in our series of sixty-two ovarian tumors and matched blood DNAs. Unlike MSI, loss of one hMLH1 allele was scored in almost half (47%) of the informative cases. In addition, an SNP in hMSH3/intron 5 was found to be highly variable in OC patients. CONCLUSION: 1) Coding...... mismatch DNA repair and/or critical genes....

  11. Avaliação da expressão tecidual do gene de reparo MLH1 e dos níveis de dano oxidativo ao DNA em doentes com câncer colorretal Evaluation of expression of mismatch repair gene MLH1 and levels of oxidative DNA damage in normal and neoplastic tissues of patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Carlos Augusto Real Martinez


    Full Text Available O dano oxidativo ao DNA provocado por radicais livres de oxigênio representa um dos principais mecanismos responsáveis pelas etapas iniciais da carcinogênese colorretal. O estresse oxidativo ocasiona erros de pareamento de bases possibilitando o aparecimento de mutações em genes controladores do ciclo celular. As células possuem um sistema de defesa representado pelos genes de reparo do DNA que corrigindo os erros de pareamento impedem o desenvolvimento de mutações. Poucos estudos avaliaram a relação entre dano oxidativo ao DNA e a expressão tecidual do gene de reparo MLH1. OBJETIVO: O objetivo do presente estudo foi avaliar os níveis de estresse oxidativo ao DNA e a expressão tecidual do gene de reparo MLH1 nas células da mucosa cólica normal e neoplásica de doentes com câncer colorretal. MATERIAL E MÉTODO: Foram estudados 44 doentes com diagnóstico de adenocarcinoma colorretal. Foram excluídos os doentes com câncer colorretal hereditário, portadores de câncer relacionado às doenças inflamatórias intestinais e os submetidos à radioquimioterapia neoadjuvante. Para a avaliação dos níveis de dano oxidativo ao DNA utilizou-se a técnica da eletroforese alcalina em gel de célula isolada (ensaio do cometa avaliando 100 células obtidas dos tecidos normal e neoplásico. Para a avaliação da expressão do gene MLH1 utilizou-se a técnica de reação de polimerase em cadeia em tempo real (RT-PCR com primer especificamente desenhados para amplificação do gene. A comparação dos resultados encontrados para os níveis de estresse oxidativo ao DNA, e expressão do gene MLH1 nos tecidos normais e neoplásicos foi feito pelo teste t de Student, adotando-se nível de significância de 5% (pThe oxidative DNA damage caused by oxygen free radicals is one of the most important mechanisms responsible for the initial steps of colorectal carcinogenesis. The oxidative stress can cause errors in the pairing of nitrogenous bases that

  12. ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells. (United States)

    Lima, Wânia R; Parreira, Kleber S; Devuyst, Olivier; Caplanusi, Adrian; N'kuli, Francisca; Marien, Benoit; Van Der Smissen, Patrick; Alves, Pedro M S; Verroust, Pierre; Christensen, Erik I; Terzi, Fabiola; Matter, Karl; Balda, Maria S; Pierreux, Christophe E; Courtoy, Pierre J


    Epithelial polarization modulates gene expression. The transcription factor zonula occludens 1 (ZO-1)-associated nucleic acid binding protein (ZONAB) can shuttle between tight junctions and nuclei, promoting cell proliferation and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA), but whether it also represses epithelial differentiation is unknown. Here, during mouse kidney ontogeny and polarization of proximal tubular cells (OK cells), ZONAB and PCNA levels decreased in parallel and inversely correlated with increasing apical differentiation, reflected by expression of megalin/cubilin, maturation of the brush border, and extension of the primary cilium. Conversely, ZONAB reexpression and loss of apical differentiation markers provided a signature for renal clear cell carcinoma. In confluent OK cells, ZONAB overexpression increased proliferation and PCNA while repressing megalin/cubilin expression and impairing differentiation of the brush border and primary cilium. Reporter and chromatin immunoprecipitation assays demonstrated that megalin and cubilin are ZONAB target genes. Sparsely plated OK cells formed small islands composed of distinct populations: Cells on the periphery, which lacked external tight junctions, strongly expressed nuclear ZONAB, proliferated, and failed to differentiate; central cells, surrounded by continuous junctions, lost nuclear ZONAB, stopped proliferating, and engaged in apical differentiation. Taken together, these data suggest that ZONAB is an important component of the mechanisms that sense epithelial density and participates in the complex transcriptional networks that regulate the switch between proliferation and differentiation.

  13. Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome

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    Llor Xavier


    Full Text Available Abstract Background Lynch syndrome (LS is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls. Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%, seven were suspected of having hereditary CRC (2.8% and 11 were controls (2.68%. There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both

  14. Comparative study of mutations in SNP loci of K-RAS, hMLH1 and hMSH2 genes in neoplastic intestinal polyps and colorectal cancer. (United States)

    Yan, Zhi-Hui; Cui, Li-Hong; Wang, Xiao-Hui; Li, Chao; He, Xing


    To clarify the molecular mechanism involved in pathogenesis of colorectal cancer as well as clinical significance of genetic analysis of histological samples. A total of 480 blood and tissue specimens were collected in our hospital from January 2011 to October 2012. In the observation group, there were 120 blood specimens and 120 intestinal tract tissue specimens collected from patients with neoplastic intestinal polyps. In the control group I there were 80 blood specimens and 80 intestinal tract tissue specimens collected from patients with colorectal cancer. In the control group II there were 40 blood specimens and 40 intestinal tract tissue specimens collected from healthy individuals. The gene segments were amplified using PCR and DNA gel electrophoresis along with DNA sequence analysis were employed for the detection of the following single nucleotide polymorphisms (SNPs): K-RAS codons 12 and 13; hMLH1 (human mutS homolog 1) gene missense mutation at Va1384Asp; hMSH2 (human mutS homolog 2) gene missense mutation at 2783C/A. The mutation rate of the SNP at Va1384Asp locus of the hMLH1 gene from blood and tissue specimens in the observation group showed no statistical difference from those in the control group I. The mutation rates of SNPs in codons 12 and 13 of K-RAS and at 2783C/A locus of the hMSH2 gene were significantly lower in the observation group than in the control group I (χ(2) = 15.476, 29.670, 10.811, 16.618, 33.538, 7.898, P gene was significantly higher in the observation group when compared to the control group II (χ(2) = 10.486, 4.876, P RAS and at 2783C/A locus of the hMSH2 gene did not show any statistical difference from those in the control group II. There may be important clinical significance and relevance between neoplastic intestinal polyps and colorectal cancer in terms of the mechanisms involved in the pathogenesis.

  15. Comparison between two experimental protocols to promote osteoporosis in the maxilla and proximal tibia of female rats

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    Teófilo Juliana Mazzonetto


    Full Text Available The effects of two experimental protocols (ovariectomy associated or not with a low calcium diet used to promote osteoporosis in the rat maxilla and proximal tibia were compared 5 and 11 weeks after surgery. Female Wistar rats were ovariectomized or sham-operated. Half of the ovariectomized rats were fed a low Ca++ diet (ovx* and the remaining ovariectomized (ovx and sham animals received a standard chow. At sacrifice, the proximal metaphysis was excised from the tibia and the molars were extracted from the hemi-maxilla. Dry (60°C overnight and ash (700°C/14 h weights were measured and the ashes were used for Ca++ measurement by means of a colorimetric method. After 5 weeks, ovx caused no alteration while ovx* decreased proximal metaphysis (17% and maxilla (35% bone mass. After 11 weeks, ovx caused a 14% bone mass reduction in the proximal metaphysis but not in the maxilla, while ovx* caused a comparable bone mass reduction (30% in both bone segments. Calcium concentration was not altered in any experimental condition. The results show that estrogen deficiency is insufficient to cause maxillary osteoporosis in rats over an 11-week period and a long-term ovariectomy is needed to exert deleterious effect on proximal metaphysis bone mass. When a low Ca++ diet is associated with estrogen deficiency, however, a relatively precocious harmful effect is observed, twice as pronounced in the maxilla than in the proximal metaphysis. On a long-term basis, ovariectomy associated with a low Ca++ diet seems to be equally injurious to both proximal metaphysis and maxilla.

  16. Far infrared radiation promotes rabbit renal proximal tubule cell proliferation and functional characteristics, and protects against cisplatin-induced nephrotoxicity. (United States)

    Chiang, I-Ni; Pu, Yeong-Shiau; Huang, Chao-Yuan; Young, Tai-Horng


    Far infrared radiation, a subdivision of the electromagnetic spectrum, is beneficial for long-term tissue healing, anti-inflammatory effects, growth promotion, sleep modulation, acceleration of microcirculation, and pain relief. We investigated if far infrared radiation is beneficial for renal proximal tubule cell cultivation and renal tissue engineering. We observed the effects of far infrared radiation on renal proximal tubules cells, including its effects on cell proliferation, gene and protein expression, and viability. We also examined the protective effects of far infrared radiation against cisplatin, a nephrotoxic agent, using the human proximal tubule cell line HK-2. We found that daily exposure to far infrared radiation for 30 min significantly increased rabbit renal proximal tubule cell proliferation in vitro, as assessed by MTT assay. Far infrared radiation was not only beneficial to renal proximal tubule cell proliferation, it also increased the expression of ATPase Na+/K+ subunit alpha 1 and glucose transporter 1, as determined by western blotting. Using quantitative polymerase chain reaction, we found that far infrared radiation enhanced CDK5R1, GNAS, NPPB, and TEK expression. In the proximal tubule cell line HK-2, far infrared radiation protected against cisplatin-mediated nephrotoxicity by reducing apoptosis. Renal proximal tubule cell cultivation with far infrared radiation exposure resulted in better cell proliferation, significantly higher ATPase Na+/K+ subunit alpha 1 and glucose transporter 1 expression, and significantly enhanced expression of CDK5R1, GNAS, NPPB, and TEK. These results suggest that far infrared radiation improves cell proliferation and differentiation. In HK-2 cells, far infrared radiation mediated protective effects against cisplatin-induced nephrotoxicity by reducing apoptosis, as indicated by flow cytometry and caspase-3 assay.

  17. Aberrant DNA Methylation of P16, MGMT, and hMLH1 Genes in Combination with MTHFR C677T Genetic Polymorphism in gastric cancer. (United States)

    Song, Binbin; Ai, Jiang; Kong, Xianghong; Liu, Dexin; Li, Jun


    We aimed to explore the association of P16, MGMT and HMLH1 with gastric cancer and their relation with Methylenetetrahydrofolate reductase (MTHFR). 322 gastric patients who were confirmed with pathological diagnosis were included in our study. Aberrant DNA methylation of P16, MGMT and HMLH1 and polymorphisms of MTHFR C677T and A1298C were detected using PCR-RFLP. The proportions of DNA hypermethylation in P16, MGMT and hMLH1 genes in gastric cancer tissues were 75.2% (242/322), 27.6% (89/322) and 5.3% (17/322), respectively. In the remote normal-appearing tissues, 29.5% (95/322) and 16.1%(52/322) showed hypermethylation in P16 and MGMT genes, respectively. We found a significantly higher proportion of DNA hypermethylation of P16 in patients with N1 TNM stage in cancer tissues and remote normal-appearing tissues (P<0.05). Similarly, we found DNA hypermethylation of MGMT had significantly higher proportion in N1 and M1 TNM stage (P<0.05). Individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues [OR (95% CI)=4.27(1.76-7.84)], and a significant risk was also found in those carrying MTHFR 677CT/TT genotype [OR (95% CI)= 3.27(1.21-4.77)]. We found the aberrant hypermethylation of cancer-related genes, such as P16, MGMT and HMLH1, could be predictive biomarkers for detection of gastric cancer.

  18. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    DEFF Research Database (Denmark)

    Soravia, E; Grebe, A; De Luca, P


    have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes......The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we...

  19. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spink, Barbara C. [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Bloom, Michael S. [Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Wu, Susan [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Sell, Stewart; Schneider, Erasmus [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Ding, Xinxin [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Spink, David C., E-mail: [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States)


    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung

  20. Promoting Metapragmatic Development through Assessment in the Zone of Proximal Development (United States)

    van Compernolle, Remi A.; Kinginger, Celeste


    The assessment of second language (L2) pragmatic competence typically involves questionnaires, such as discourse completion tasks. This article describes a novel approach to using questionnaires to assess L2 metapragmatic capacities while simultaneously promoting their development: engaging learners in cooperative interaction as they complete the…

  1. Differential Expression and Clinical Significance of DNA Methyltransferase 3B (DNMT3B), Phosphatase and Tensin Homolog (PTEN) and Human MutL Homologs 1 (hMLH1) in Endometrial Carcinomas. (United States)

    Li, Wenting; Wang, Ying; Fang, Xinzhi; Zhou, Mei; Li, Yiqun; Dong, Ying; Wang, Ruozheng


    BACKGROUND The aim of this study was to investigate the expression and the clinicopathologic significance of DNA methyltransferase 3B (DNMT3B), phosphatase and tensin homolog (PTEN) and human MutL homologs 1 (hMLH1) in endometrial carcinomas between Han and Uygur women in Xinjiang. MATERIAL AND METHODS The expression of DNMT3B, PTEN, and hMLH1 in endometrial carcinomas were assessed by immunohistochemistry, followed by an analysis of their relationship to clinical-pathological features and prognosis. RESULTS There were a 61.7% (95/154) overexpression of DNMT3B, 50.0% (77/154) loss of PTEN expression and 18.2% (28/154) loss of hMLH1 expression. The expression of DNMT3B and PTEN in endometrial carcinomas was statistically significantly different between Uygur women and Han women (p=0.001, p=0.010, respectively). DNMT3B expression was statistically significant based on the grade of endometrial carcinomas (p=0.031). PTEN loss was statistically significant between endometrioid carcinomas (ECs) and non endometrioid carcinomas (NECs) (p=0.040). DNMT3B expression was statistically significant in different myometrial invasion groups in Uygur women (p=0.010). Furthermore, the correlation of DNMT3B and PTEN expression was significant in endometrial carcinomas (p=0.021). PTEN expression was statistically significant in the overall survival (OS) rate of women with endometrial cancers (p=0.041). CONCLUSIONS Our findings suggest that PTEN and DNMT3B possess common regulation features as well as certain ethnic differences in expression between Han women and Uygur women. An interaction may exist in the pathogenesis of endometrial carcinoma. DNMT3B was expressed differently in cases of myometrial invasion and PTEN was associated with OS, which suggested that these molecular markers may be useful in the evaluation of the biological behavior of endometrial carcinomas and may be useful indicators of prognosis in women with endometrial carcinomas.

  2. An Alphavirus E2 Membrane-Proximal Domain Promotes Envelope Protein Lateral Interactions and Virus Budding

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    Emily A. Byrd


    Full Text Available Alphaviruses are members of a group of small enveloped RNA viruses that includes important human pathogens such as Chikungunya virus and the equine encephalitis viruses. The virus membrane is covered by a lattice composed of 80 spikes, each a trimer of heterodimers of the E2 and E1 transmembrane proteins. During virus endocytic entry, the E1 glycoprotein mediates the low-pH-dependent fusion of the virus membrane with the endosome membrane, thus initiating virus infection. While much is known about E1 structural rearrangements during membrane fusion, it is unclear how the E1/E2 dimer dissociates, a step required for the fusion reaction. A recent Alphavirus cryo-electron microscopy reconstruction revealed a previously unidentified D subdomain in the E2 ectodomain, close to the virus membrane. A loop within this region, here referred to as the D-loop, contains two highly conserved histidines, H348 and H352, which were hypothesized to play a role in dimer dissociation. We generated Semliki Forest virus mutants containing the single and double alanine substitutions H348A, H352A, and H348/352A. The three D-loop mutations caused a reduction in virus growth ranging from 1.6 to 2 log but did not significantly affect structural protein biosynthesis or transport, dimer stability, virus fusion, or specific infectivity. Instead, growth reduction was due to inhibition of a late stage of virus assembly at the plasma membrane. The virus particles that are produced show reduced thermostability compared to the wild type. We propose the E2 D-loop as a key region in establishing the E1-E2 contacts that drive glycoprotein lattice formation and promote Alphavirus budding from the plasma membrane.

  3. Kmt5a Controls Hepatic Metabolic Pathways by Facilitating RNA Pol II Release from Promoter-Proximal Regions

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    Kostas C. Nikolaou


    Full Text Available H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. Here, we show that, in non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene bodies and dynamically regulated by the antagonistic action of Kmt5a methylase and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release. Downregulation of glycolytic genes resulted in an energy starvation condition partially compensated by AMP-activated protein kinase (AMPK activation and increased mitochondrial activity. This metabolic reprogramming generated a highly sensitized state that, upon different metabolic stress conditions, quickly aggravated into a senescent phenotype due to ROS overproduction-mediated oxidative DNA damage. The results illustrate how defects in the general process of RNA Pol II transition into a productive elongation phase can trigger specific metabolic changes and genome instability.

  4. An Ebox element in the proximal Gata4 promoter is required for Gata4 expression in vivo.

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    Alain Boulende Sab

    Full Text Available GATA4 is an essential transcription factor required for the development and function of multiple tissues, including a major role in gonadogenesis. Despite its crucial role, the molecular mechanisms that regulate Gata4 expression in vivo remain poorly understood. We recently found that the Gata4 gene is expressed as multiple transcripts with distinct 5' origins. These co-expressed alternative transcripts are generated by different non-coding first exons with transcripts E1a and E1b being the most prominent. Moreover, we previously showed that an Ebox element, located in Gata4 5' flanking sequences upstream of exon 1a, is important for the promoter activity of these sequences in cell lines. To confirm the importance of this element in vivo, we generated and characterized Gata4 Ebox knockout mice. Quantitative PCR analyses realized on gonads, heart and liver at three developmental stages (embryonic, pre-pubertal and adult revealed that the Ebox mutation leads to a robust and specific decrease (up to 89% of Gata4 E1a transcript expression in all tissues and stages examined. However, a detailed characterization of the gonads revealed normal morphology and GATA4 protein levels in these mutants. Our qPCR data further indicate that this outcome is most likely due to the presence of Gata4 E1b mRNA, whose expression levels were not decreased by the Ebox mutation. In conclusion, our work clearly confirms the importance of the proximal Ebox element and suggests that adequate GATA4 protein expression is likely protected by a compensation mechanism between Gata4 E1a and E1b transcripts operating at the translational level.

  5. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men

    DEFF Research Database (Denmark)

    van der Beek, Christina M; Canfora, Emanuel E; Lenaerts, Kaatje


    in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were......Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men....... In this randomized, double-blind crossover trial, six overweight/obese men [body mass index (BMI) 25-35 kg/m(2)] underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions. A feeding catheter was endoscopically positioned at the beginning of each period and remained...

  6. Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4.

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    Daniela Verzola

    Full Text Available Mild hyperuricemia has been linked to the development and progression of tubulointerstitial renal damage. However the mechanisms by which uric acid may cause these effects are poorly explored. We investigated the effect of uric acid on apoptosis and the underlying mechanisms in a human proximal tubule cell line (HK-2. Increased uric acid concentration decreased tubule cell viability and increased apoptotic cells in a dose dependent manner (up to a 7-fold increase, p<0.0001. Uric acid up-regulated Bax (+60% with respect to Ctrl; p<0.05 and down regulated X-linked inhibitor of apoptosis protein. Apoptosis was blunted by Caspase-9 but not Caspase-8 inhibition. Uric acid induced changes in the mitochondrial membrane, elevations in reactive oxygen species and a pronounced up-regulation of NOX 4 mRNA and protein (p<0.05. In addition, both reactive oxygen species production and apoptosis was prevented by the NADPH oxidase inhibitor DPI as well as by Nox 4 knockdown. URAT 1 transport inhibition by probenecid and losartan and its knock down by specific siRNA, blunted apoptosis, suggesting a URAT 1 dependent cell death. In summary, our data show that uric acid increases the permissiveness of proximal tubule kidney cells to apoptosis by triggering a pathway involving NADPH oxidase signalling and URAT 1 transport. These results might explain the chronic tubulointerstitial damage observed in hyperuricaemic states and suggest that uric acid transport in tubular cells is necessary for urate-induced effects.

  7. The additive effect of p53 Arg72Pro and RNASEL Arg462Gln genotypes on age of disease onset in Lynch syndrome patients with pathogenic germline mutations in MSH2 or MLH1. (United States)

    Krüger, Stefan; Engel, Christoph; Bier, Andrea; Silber, Ann-Sophie; Görgens, Heike; Mangold, Elisabeth; Pagenstecher, Constanze; Holinski-Feder, Elke; von Knebel Doeberitz, Magnus; Royer-Pokora, Brigitte; Dechant, Stefan; Pox, Christian; Rahner, Nils; Müller, Annegret; Schackert, Hans K


    p53 and the prostate-cancer-susceptibility gene RNASEL are tumour suppressor genes involved in apoptosis. We have previously reported that the common, functionally different variants Arg72Pro in p53 and Arg462Gln in RNASEL are associated with the age of disease onset of colorectal cancer in Lynch syndrome patients. To assess the combined effect of both variants, we screened 246 unrelated Lynch syndrome patients with a pathogenic germline mutation either in MSH2 (n=138) or in MLH1 (n=108) and colorectal cancer as first tumour, and 245 healthy controls. The global log rank test revealed significant differences in the age of disease onset for the genotypes of each variant (p=0.0176 for p53 and p=0.0358 for RNASEL) and for the combined genotypes of both variants (p=0.0174). The highest difference in median age of disease onset was seen between homozygotes for the wild-types in both genes (42years [range 22-75]) and homozygotes for the variant alleles in both genes (30years [range 26-47]). A multivariate Cox regression model indicated that only the p53 and RNASEL genotypes had a significant influence on age of disease onset (p=0.016 for p53 and p=0.014 for RNASEL) in an additive mode of inheritance, and that the effects of both variants are purely additive, which supports the notion that the p53 and RNaseL pathways do not interact. These findings may be relevant for preventive strategies in Lynch syndrome.

  8. A Leader Intron of a Soybean Elongation Factor 1A (eEF1A Gene Interacts with Proximal Promoter Elements to Regulate Gene Expression in Synthetic Promoters.

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    Ning Zhang

    Full Text Available Introns, especially the first intron in the 5' untranslated region (5'UTR, can significantly impact gene expression via intron-mediated enhancement (IME. In this study, we demonstrate the leader intron of a soybean elongation factor 1A (eEF1A gene (GmScreamM8 was essential for the high activity of the native promoter. Furthermore, the interaction of the GmScreamM8 leader intron with regulatory element sequences from several soybean eEF1A promoters was studied using synthetic promoters, which consisted of element tetramers upstream of a core promoter used to regulate a green fluorescent protein (gfp reporter gene. Element tetramers, placed upstream of a GmScreamM8 core promoter, showed very high activity using both transient expression in lima bean cotyledons and stable expression in soybean hairy roots, only if the native leader intron was included, suggesting an interaction between intronic sequences and promoter elements. Partial deletions of the leader intron showed that a 222 bp intronic sequence significantly contributed to very high levels of GFP expression. Generation of synthetic intron variants with a monomeric or trimeric repeat of the 222 bp intronic sequence, yielded almost two-fold higher expression compared to the original intron, while partial deletion of the 222 bp intronic repeated sequence significantly decreased gene expression, indicating that this intronic sequence was essential for the intron-element interaction enhancement.

  9. RET Recognition of GDNF-GFRα1 Ligand by a Composite Binding Site Promotes Membrane-Proximal Self-Association

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    Kerry M. Goodman


    Full Text Available The RET receptor tyrosine kinase is essential to vertebrate development and implicated in multiple human diseases. RET binds a cell surface bipartite ligand comprising a GDNF family ligand and a GFRα coreceptor, resulting in RET transmembrane signaling. We present a hybrid structural model, derived from electron microscopy (EM and low-angle X-ray scattering (SAXS data, of the RET extracellular domain (RETECD, GDNF, and GFRα1 ternary complex, defining the basis for ligand recognition. RETECD envelopes the dimeric ligand complex through a composite binding site comprising four discrete contact sites. The GFRα1-mediated contacts are crucial, particularly close to the invariant RET calcium-binding site, whereas few direct contacts are made by GDNF, explaining how distinct ligand/coreceptor pairs are accommodated. The RETECD cysteine-rich domain (CRD contacts both ligand components and makes homotypic membrane-proximal interactions occluding three different antibody epitopes. Coupling of these CRD-mediated interactions suggests models for ligand-induced RET activation and ligand-independent oncogenic deregulation.

  10. Zinc ions upregulate the hormone gastrin via an E-box motif in the proximal gastrin promoter. (United States)

    Xiao, Lin; Kovac, Suzana; Chang, Mike; Shulkes, Arthur; Baldwin, Graham S; Patel, Oneel


    Gastrin and its precursors act as growth factors for the normal and neoplastic gastrointestinal mucosa. As the hypoxia mimetic cobalt chloride upregulates the gastrin gene, the effect of other metal ions on gastrin promoter activity was investigated. Gastrin mRNA was measured by real-time PCR, gastrin peptides by RIA, and gastrin promoter activity by dual-luciferase reporter assay. Exposure to Zn(2)(+) ions increased gastrin mRNA concentrations in the human gastric adenocarcinoma cell line AGS in a dose-dependent manner, with a maximum stimulation of 55 ± 14-fold at 100 μM (Pgastrin induction by Zn(2)(+). Deletional mutation of the gastrin promoter identified an 11 bp DNA sequence, which contained an E-box motif, as necessary for Zn(2)(+)-dependent gastrin induction. The fact that E-box binding transcription factors play a crucial role in the epithelial-mesenchymal transition (EMT), together with our observation that Zn(2)(+) ions upregulate the gastrin gene in AGS cells by an E-box-dependent mechanism, suggests that Zn(2)(+) ions may induce an EMT, and that gastrin may be involved in the transition.

  11. Characterization of the cis elements in the proximal promoter regions of the anthocyanin pathway genes reveals a common regulatory logic that governs pathway regulation. (United States)

    Zhu, Zhixin; Wang, Hailong; Wang, Yiting; Guan, Shan; Wang, Fang; Tang, Jingyu; Zhang, Ruijuan; Xie, Lulu; Lu, Yingqing


    Cellular activities such as compound synthesis often require the transcriptional activation of an entire pathway; however, the molecular mechanisms underlying pathway activation have rarely been explained. Here, the cis regulatory architecture of the anthocyanin pathway genes targeted by the transcription factor (TF) complex including MYB, bHLH, and WDR was systematically analysed in one species and the findings extended to others. In Ipomoea purpurea, the IpMYB1-IpbHLH2-IpWDR1 (IpMBW) complex was found to be orthologous to the PAP1-GL3-TTG1 (AtPGT) complex of Arabidopsis thaliana, and interacted with a 7-bp MYB-recognizing element (MRE) and a 6-bp bHLH-recognizing element (BRE) at the proximal promoter region of the pathway genes. There was little transcription of the gene in the absence of the MRE or BRE. The cis elements identified experimentally converged on two syntaxes, ANCNNCC for MREs and CACN(A/C/T)(G/T) for BREs, and our bioinformatic analysis showed that these were present within anthocyanin gene promoters in at least 35 species, including both gymnosperms and angiosperms. For the anthocyanin pathway, IpMBW and AtPGT recognized the interspecific promoters of both early and later genes. In A. thaliana, the seed-specific TF complex (TT2, TT8, and TTG1) may regulate all the anthocyanin pathway genes, in addition to the proanthocyanidin-specific BAN. When multiple TF complexes in the anthocyanin pathway were compared, the cis architecture played a role larger than the TF complex in determining the variation in promoter activity. Collectively, a cis logic common to the pathway gene promoters was found, and this logic is essential for the trans factors to regulate the pathway. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  12. Intron DNA Sequences Can Be More Important Than the Proximal Promoter in Determining the Site of Transcript Initiation. (United States)

    Gallegos, Jenna E; Rose, Alan B


    To more precisely define the positions from which certain intronic regulatory sequences increase mRNA accumulation, the effect of a UBIQUITIN intron on gene expression was tested from six different positions surrounding the transcription start site (TSS) of a reporter gene fusion in Arabidopsis thaliana The intron increased expression from all transcribed positions but had no effect when upstream of the 5'-most TSS. While this implies that the intron must be transcribed to increase expression, the TSS changed when the intron was located in the 5'-untranslated region (UTR), suggesting that the intron affects transcription initiation. Remarkably, deleting 303 nucleotides of the promoter including all known TSSs and all but 18 nucleotides of the 5'-UTR had virtually no effect on the level of gene expression as long as an intron containing stimulatory sequences was included. Instead, transcription was initiated in normally untranscribed sequences the same distance upstream of the intron as when the promoter was intact. These results suggest that certain intronic DNA sequences play unexpectedly large roles in directing transcription initiation and constitute a previously unrecognized type of downstream regulatory element for genes transcribed by RNA polymerase II. © 2017 American Society of Plant Biologists. All rights reserved.

  13. Evidence for TGF-beta1 and bleomycin intracellular signaling through autocrine regulation of Smad 3 binding to the proximal promoter of the Smad 7 gene. (United States)

    Cutroneo, Kenneth R


    Both Bleomycin and TGF-beta1 increase the transcription of the COL1A1 gene. Bleomycin acts through TGF-beta1. Bleomycin stimulates the COL1A1 promoter through the distal TGF-beta response element by intracellular and extracellular signaling. As demonstrated in this manuscript, Bleomycin's intracellular signaling can be explained by a decrease of Smad 3 transcription factor binding to the SBE located in the proximal promoter of the inhibitory Smad 7 gene. This would result in TGF-beta1-induced activated SMADS, which would result in more collagen. Bleomycin's extracellular signaling results from the secretion of more latent TGF-beta produced by lung fibroblasts and cleaved to active TGF-beta extracellularly. Since the TGF-beta genes are auto-induced in human embryonic IMR-90 lung fibroblasts, this study indicates an autocrine mechanism to maintain homeostasis in vivo for fibroblasts and other cell types, which produce TGF-beta1 to limit the fibrogenic response to TGF-beta1 and Bleomycin. (c) 2005 Wiley-Liss, Inc.

  14. Proximal Hypospadias (United States)

    Kraft, Kate H.; Shukla, Aseem R.; Canning, Douglas A.


    Hypospadias results from abnormal development of the penis that leaves the urethral meatus proximal to its normal glanular position. Meatal position may be located anywhere along the penile shaft, but more severe forms of hypospadias may have a urethral meatus located at the scrotum or perineum. The spectrum of abnormalities may also include ventral curvature of the penis, a dorsally redundant prepuce, and atrophic corpus spongiosum. Due to the severity of these abnormalities, proximal hypospadias often requires more extensive reconstruction in order to achieve an anatomically and functionally successful result. We review the spectrum of proximal hypospadias etiology, presentation, correction, and possible associated complications. PMID:21516286

  15. Detección de mutaciones de los genes hMLH1 y hMSH2 del sistema de reparación de malos apareamientos del ADN en familias colombianas sospechosas de cancer colorrectal no polipósico hereditario (síndrome de Lynch.

    Directory of Open Access Journals (Sweden)

    Andrea Gómez


    Full Text Available Introducción. El cáncer colorrectal es la segunda causa de morbilidad y mortalidad por cáncer en los países desarrollados. En Colombia es la quinta causa de muerte entre los diferentes cánceres. Cerca del 75% de éstos corresponde a cánceres esporádicos, alrededor del 25% son familiares, y son claramente hereditarios el 5%. De éstos, el más importantes es el cáncer colorrectal no polipósico hereditario o síndrome de Lynch. Objetivo. Analizar los dos genes más importantes involucrados en el síndrome de Lynch, el hMLH1 y el hMSH2. Materiales y métodos. En 17 familias colombianas que cumplían con los criterios de Ámsterdam II o las pautas de Bethesda, se analizaron por SSCP los 35 exones de estos dos genes y las variantes electroforéticas se secuenciaron. Resultados. Se detectaron 8 mutaciones de línea germinal en las familias analizadas, 7 en el gen hMLH1 y 1 en hMSH2, y se encontró una tasa de detección de mutaciones del 47%. Seis de las 8 mutaciones encontradas en este estudio han sido previamente reportadas en la literatura. Un cambio de una base en el sitio donador de empalme en el exón 9 del gen hMLH1 (G>A (dos familias, un cambio A>G en el codón 755 del exón 17, y un cambio G>A en el exón 18. Se detectaron dos nuevas mutaciones, una en el exón 17, un cambio C>T en el codón 640, y una deleción de TG en el codón 184 del exón 3 del gen hMSH2. También se detectó en dos familias un polimorfismo del intrón 13 del hMLH1. Conclusión. Este es el primer estudio realizado en Colombia que detecta mutaciones en el síndrome de Lynch y pretende establecer un programa integral de manejo y prevención.

  16. A protein binding AT-rich sequence in the soybean leghemoglobin c3 promoter is a general cis element that requires proximal DNA elements to stimulate transcription

    DEFF Research Database (Denmark)

    Laursen, N B; Larsen, K; Knudsen, J Y


    A nodule nuclear factor, NAT2, interacts with two AT-rich binding sites (NAT2 BS1 and NAT2 BS2) in the soybean leghemoglobin (lb) c3 promoter. In transgenic Lotus corniculatus nodules, an oligonucleotide containing NAT2 BS1 activated an inactive -159 lbc3 promoter when placed immediately upstream...

  17. Proximal renal tubular acidosis (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  18. Multiset proximity spaces

    Directory of Open Access Journals (Sweden)

    A. Kandil


    Full Text Available A multiset is a collection of objects in which repetition of elements is essential. This paper is an attempt to explore the theoretical aspects of multiset by extending the notions of compact, proximity relation and proximal neighborhood to the multiset context. Examples of new multiset topologies, open multiset cover, compact multiset and many identities involving the concept of multiset have been introduced. Further, an integral examples of multiset proximity relations are obtained. A multiset topology induced by a multiset proximity relation on a multiset M has been presented. Also the concept of multiset δ- neighborhood in the multiset proximity space which furnishes an alternative approach to the study of multiset proximity spaces has been mentioned. Finally, some results on this new approach have been obtained and one of the most important results is: every T4- multiset space is semi-compatible with multiset proximity relation δ on M (Theorem 5.10.

  19. VE-statin/egfl7 expression in endothelial cells is regulated by a distal enhancer and a proximal promoter under the direct control of Erg and GATA-2.

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    Alexandra Le Bras

    Full Text Available Angiogenesis is the process by which new blood vessels arise from existing ones by the budding out of endothelial cell capillaries from the luminal side of blood vessels. Blood vessel formation is essential for organ development during embryogenesis and is associated with several physiological and pathological processes, such as wound healing and tumor development. The VE-statin/egfl7 gene is specifically expressed in endothelial cells during embryonic development and in the adult. We studied here the regulatory mechanisms that control this tissue-specific expression. RT-qPCR analyses showed that the specificity of expression of VE-statin/egfl7 in endothelial cells is not shared with its closest neighbor genes notch1 and agpat2 on the mouse chromosome 2. Chromatin-immunoprecipitation analysis of histone modifications at the VE-statin/egfl7 locus showed that the chromatin is specifically opened in endothelial cells, but not in fibroblasts at the transcription start sites. A 13 kb genomic fragment of promoter was cloned and analyzed by gene reporter assays which showed that two conserved regions are important for the specific expression of VE-statin/egfl7 in endothelial cells; a -8409/-7563 enhancer and the -252/+38 region encompassing the exon-1b transcription start site. The latter contains essential GATA and ETS-binding sites, as assessed by linker-scanning analysis and site-directed mutagenesis. An analysis of expression of the ETS and GATA transcription factors showed that Erg, Fli-1 and GATA-2 are the most highly expressed factors in endothelial cells. Erg and GATA-2 directly control the expression of the endogenous VE-statin/egfl7 while Fli-1 probably exerts an indirect control, as assessed by RNA interference and chromatin immunoprecipitation. This first detailed analysis of the mechanisms that govern the expression of the VE-statin/egfl7 gene in endothelial cells pinpoints the specific importance of ETS and GATA factors in the specific

  20. Proximal Probes Facility (United States)

    Federal Laboratory Consortium — The Proximal Probes Facility consists of laboratories for microscopy, spectroscopy, and probing of nanostructured materials and their functional properties. At the...

  1. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick


    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... RNA polymerase II-transcribed genes use specialized termination mechanisms to maintain high transcription levels....

  2. Capacitive proximity sensor (United States)

    Kronberg, James W.


    A proximity sensor based on a closed field circuit. The circuit comprises a ring oscillator using a symmetrical array of plates that creates an oscillating displacement current. The displacement current varies as a function of the proximity of objects to the plate array. Preferably the plates are in the form of a group of three pair of symmetric plates having a common center, arranged in a hexagonal pattern with opposing plates linked as a pair. The sensor produces logic level pulses suitable for interfacing with a computer or process controller. The proximity sensor can be incorporated into a load cell, a differential pressure gauge, or a device for measuring the consistency of a characteristic of a material where a variation in the consistency causes the dielectric constant of the material to change.

  3. Neighborhoods and manageable proximity

    Directory of Open Access Journals (Sweden)

    Stavros Stavrides


    Full Text Available The theatricality of urban encounters is above all a theatricality of distances which allow for the encounter. The absolute “strangeness” of the crowd (Simmel 1997: 74 expressed, in its purest form, in the absolute proximity of a crowded subway train, does not generally allow for any movements of approach, but only for nervous hostile reactions and submissive hypnotic gestures. Neither forced intersections in the course of pedestrians or vehicles, nor the instantaneous crossing of distances by the technology of live broadcasting and remote control give birth to places of encounter. In the forced proximity of the metropolitan crowd which haunted the city of the 19th and 20th century, as well as in the forced proximity of the tele-presence which haunts the dystopic prospect of the future “omnipolis” (Virilio 1997: 74, the necessary distance, which is the stage of an encounter between different instances of otherness, is dissipated.

  4. Atrofia muscular proximal familiar

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    José Antonio Levy


    Full Text Available Os autores relatam dois casos de atrofia muscular proximal familiar, moléstia caracterizada por déficit motor e atrofias musculares de distribuição proximal, secundárias a lesão de neurônios periféricos. Assim, como em outros casos descritos na literatura, foi feito inicialmente o diagnóstico de distrofia muscular progressiva. O diagnóstico correto foi conseguido com auxílio da eletromiografia e da biopsia muscular.

  5. [Experimental proximal carpectomy. Biodynamics]. (United States)

    Kuhlmann, J N


    Proximal carpectomy was performed in 10 fresh cadavre wrists. Dynamic x-rays were taken and the forces necessary to obtain different movements before and after the operation were measured. Comparison of these parameters clearly defines the advantages and limitations of carpectomy and indicates the reasons.

  6. Proximate Analysis of Coal (United States)

    Donahue, Craig J.; Rais, Elizabeth A.


    This lab experiment illustrates the use of thermogravimetric analysis (TGA) to perform proximate analysis on a series of coal samples of different rank. Peat and coke are also examined. A total of four exercises are described. These are dry exercises as students interpret previously recorded scans. The weight percent moisture, volatile matter,…

  7. Proximal Tibial Bone Graft (United States)

    ... the Big Toe Ailments of the Smaller Toes Diabetic Foot Treatments Currently selected Injections and other Procedures Treatments ... from which the bone was taken if the foot/ankle surgeries done at the same time allow for it. ... problems after a PTBG include infection, fracture of the proximal tibia and pain related ...

  8. Renal fibrosis: Primacy of the proximal tubule. (United States)

    Gewin, Leslie S


    Tubulointerstitial fibrosis (TIF) is the hallmark of chronic kidney disease and best predictor of renal survival. Many different cell types contribute to TIF progression including tubular epithelial cells, myofibroblasts, endothelia, and inflammatory cells. Previously, most of the attention has centered on myofibroblasts given their central importance in extracellular matrix production. However, emerging data focuses on how the response of the proximal tubule, a specialized epithelial segment vulnerable to injury, plays a central role in TIF progression. Several proximal tubular responses such as de-differentiation, cell cycle changes, autophagy, and metabolic changes may be adaptive initially, but can lead to maladaptive responses that promote TIF both through autocrine and paracrine effects. This review discusses the current paradigm of TIF progression and the increasingly important role of the proximal tubule in promoting TIF both in tubulointerstitial and glomerular injuries. A better understanding and appreciation of the role of the proximal tubule in TIF has important implications for therapeutic strategies to halt chronic kidney disease progression. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  9. Proximal femoral fractures

    DEFF Research Database (Denmark)

    Palm, Henrik; Teixidor, Jordi


    -displaced femoral neck fractures and prosthesis for displaced among the elderly; and sliding hip screw for stabile- and intramedullary nails for unstable- and sub-trochanteric fractures) but they are based on a variety of criteria and definitions - and often leave wide space for the individual surgeons' subjective...... guidelines for hip fracture surgery and discuss a method for future pathway/guideline implementation and evaluation. METHODS: By a PubMed search in March 2015 six studies of surgical treatment pathways covering all types of proximal femoral fractures with publication after 1995 were identified. Also we...... searched the homepages of the national heath authorities and national orthopedic societies in West Europe and found 11 national or regional (in case of no national) guidelines including any type of proximal femoral fracture surgery. RESULTS: Pathway consensus is outspread (internal fixation for un...

  10. Proximal humeral fractures


    Mauro, Craig S.


    Proximal humeral fractures may present with many different configurations in patients with varying co-morbities and expectations. As a result, the treating physician must understand the fracture pattern, the quality of the bone, other patient-related factors, and the expanding range of reconstructive options to achieve the best functional outcome and to minimize complications. Current treatment options range from non-operative treatment with physical therapy to fracture fixation using percuta...

  11. Mechanisms of microsatellite instability in colorectal cancer patients in different age groups. (United States)

    Yiu, Raymond; Qiu, Hongming; Lee, Suk-Hwan; García-Aguilar, Julio


    The proportion of colorectal cancers located proximal to the splenic flexure increases with age. Colorectal cancers of the microsatellite instability phenotype are preferentially located in the proximal colon. We investigated the location of colorectal cancer with this phenotype in different age groups to determine whether different molecular mechanisms could account for the changes in distribution of colorectal cancers. A representative sample of 230 colorectal cancers from three age groups (87 years) was selected from a subset of The Upper Midwest Oncology Medical Registries database. Microsatellite instability was determined by polymerase chain reaction using a panel of five microsatellite markers. The presence of new microsatellite alleles at two or more loci was scored as microsatellite instability. Tumors were otherwise considered microsatellite stable. MLH1 and MSH2 expression was determined by immunohistochemistry. Methylation of the MLH1 gene promotor was determined by methylation-specific polymerase chain reaction assay. The proportion of tumors of the microsatellite instability phenotype was 21 percent in the young group, 15 percent in the middle group, and 33 percent in the old group. More tumors of the microsatellite instability phenotype were proximal compared with microsatellite-stable tumors in all three age groups, but the differences were significant only for the old group. Tumors of the microsatellite instability phenotype in the older group were associated with MLH1 inactivation (24/29 or 83 percent), MLH1 promoter methylation (18/29 or 62 percent), and proximal location (25/29 or 86 percent), while tumors in the young group were associated with MSH2 inactivation (8/18 or 44 percent) and distal location (11/18 or 62 percent). The age-related proximal shift of colorectal cancers is associated with the microsatellite instability phenotype, MLH1 inactivation, and MLH1 promoter hypermethylation.

  12. Some Properties of Fuzzy Soft Proximity Spaces (United States)

    Demir, İzzettin; Özbakır, Oya Bedre


    We study the fuzzy soft proximity spaces in Katsaras's sense. First, we show how a fuzzy soft topology is derived from a fuzzy soft proximity. Also, we define the notion of fuzzy soft δ-neighborhood in the fuzzy soft proximity space which offers an alternative approach to the study of fuzzy soft proximity spaces. Later, we obtain the initial fuzzy soft proximity determined by a family of fuzzy soft proximities. Finally, we investigate relationship between fuzzy soft proximities and proximities. PMID:25793224


    Directory of Open Access Journals (Sweden)

    Ion Dorin BUMBENECI


    Full Text Available The purpose of this study is to evaluate the level of assimilation for the terms "Proximity Management" and "Proximity Manager", both in the specialized literature and in practice. The study has two parts: the theoretical research of the two terms, and an evaluation of the use of Proximity management in 32 companies in Gorj, Romania. The object of the evaluation resides in 27 companies with less than 50 employees and 5 companies with more than 50 employees.

  14. Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development

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    Sarah Derks


    Full Text Available Background: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed adenomas, 41 progressed adenomas (malignant polyps, 38 colorectal carcinomas and 18 paired normal tissues, we evaluated promoter methylation status of hMLH1, O6MGMT, APC, p14ARF, p16INK4A, RASSF1A, GATA-4, GATA-5, and CHFR using methylation-specific PCR. Mutation status of TP53, APC and KRAS were studied by p53 immunohistochemistry and sequencing of the APC and KRAS mutation cluster regions. Chromosomal alterations were evaluated by comparative genomic hybridization. Results: Our data demonstrate that nonprogressed adenomas, progressed adenomas and carcinomas show similar frequencies of promoter methylation for the majority of the genes. Normal tissues showed significantly lower frequencies of promoter methylation of APC, p16INK4A, GATA-4, and GATA-5 (P-values: 0.02, 0.02, 1.1×10−5 and 0.008 respectively. P53 immunopositivity and chromosomal abnormalities occur predominantly in carcinomas (P values: 1.1×10−5 and 4.1×10−10. Conclusions: Since promoter methylation was already present in nonprogressed adenomas without chromosomal alterations, we conclude that promoter methylation can be regarded as an early event preceding TP53 mutation and chromosomal abnormalities in colorectal cancer development.

  15. Age-related Changes in DNA Methylation Status of hTERT Gene Promoter of Oral Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Stephane Flaviane de Oliveira Bezerra


    Full Text Available The purpose of this study was to investigate the effect of aging on the DNA methylation status of two genes involved in tumorigenesis (telomerase gene hTERT and DNA repair gene- MLH1 and one in metabolism (methylenetetrahydrofolate reductase gene- MTHFR in oral epithelial cells. DNA methylation analysis was performed by Methylation Sensitive Restriction Enzymes (MSRE of healthy oral epithelial cells of child (6-10 years, n=21, young (20-25 years, n=19 and elderly (over 60 years, n=25. The results for the hTERT gene showed significant variation in the methylation frequency at CpG dinucleotides among the groups (p=0.0001, with the methylated condition more frequently in children and young people. In relation to MLH1 and MTHFR, no differences were observed among the groups and the unmethylated condition were present in most individuals (p>0.05. Thus, it was concluded that aging of oral epithelial cells was associated with hypomethylation of the hTERT gene promoter and this could be a promising marker for screening a set of age-related alterations.

  16. Proximity of Radiation Desiccation Response Motif to the core promoter is essential for basal repression as well as gamma radiation-induced gyrB gene expression in Deinococcus radiodurans. (United States)

    Anaganti, Narasimha; Basu, Bhakti; Mukhopadhyaya, Rita; Apte, Shree Kumar


    The radioresistant D. radiodurans regulates its DNA damage regulon (DDR) through interaction between a 17bp palindromic cis-regulatory element called the Radiation Desiccation Response Motif (RDRM), the DdrO repressor and a protease IrrE. The role of RDRM in regulation of DDR was dissected by constructing RDRM sequence-, position- or deletion-variants of Deinococcal gyrB gene (DR0906) promoter and by RDRM insertion in the non-RDRM groESL gene (DR0606) promoter, and monitoring the effect of such modifications on the basal as well as gamma radiation inducible promoter activity by quantifying fluorescence of a GFP reporter. RDRM sequence-variants revealed that the conservation of sequence at the 5th and 13th position and the ends of RDRM is essential for basal repression by interaction with DdrO. RDRM position-variants showed that the sequence acts as a negative regulatory element only when located around transcription start site (TSS) and within the span of RNA polymerase (RNAP) binding region. RDRM deletion-variants indicated that the 5' sequence of RDRM possibly possesses an enhancer-like element responsible for higher expression yields upon repressor clearance post-irradiation. The results suggest that RDRM plays both a negative as well as a positive role in the regulation of DDR in D. radiodurans. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes

    DEFF Research Database (Denmark)

    Ek, Jakob; Hansen, Sara P; Lajer, Maria


    Recently, it has been shown that mutations in the P2 promoter of the hepatocyte nuclear factor (HNF)-4 alpha gene (HNF4A) cause maturity-onset diabetes of the young (MODY), while single nucleotide polymorphisms in this locus are associated with type 2 diabetes. In this study, we examined 1,189 bp......,812 glucose-tolerant subjects for the -192c/g mutation and identified 5 diabetic and 1 glucose-tolerant mutation carriers (P=0.004). Examination of the families showed that carriers of the -192c/g mutation had a significantly impaired glucose-stimulated insulin release and lower levels of serum total...

  18. Fractures of the proximal humerus

    DEFF Research Database (Denmark)

    Brorson, Stig


    . The bandages were further supported by splints made of wood or coarse grass. Healing was expected in forty days. Different fracture patterns have been discussed and classified since Ancient Greece. Current classification of proximal humeral fractures mainly relies on the classifications proposed by Charles......, classification of proximal humeral fractures remains a challenge for the conduct, reporting, and interpretation of clinical trials. The evidence for the benefits of surgery in complex fractures of the proximal humerus is weak. In three systematic reviews I studied the outcome after locking plate osteosynthesis......Fractures of the proximal humerus have been diagnosed and managed since the earliest known surgical texts. For more than four millennia the preferred treatment was forceful traction, closed reduction, and immobilization with linen soaked in combinations of oil, honey, alum, wine, or cerate...

  19. The infrastructure of psychological proximity

    DEFF Research Database (Denmark)

    Nickelsen, Niels Christian Mossfeldt


    ). The experience of psychological proximity between patient and nurse is provided through confidence, continuity and the practical set-up. This constitutes an important enactment of skillfulness, which may render telemedicine a convincing health service in the future. Methodology: The study draws on a pilot...... (Langstrup & Winthereik 2008). This study contributes by showing the infrastructure of psychological proximity, which is provided by way of device, confidence, continuity and accountability....

  20. Renal proximal tubule angiotensin AT1A receptors regulate blood pressure


    Li, Huiping; Weatherford, Eric T.; Davis, Deborah R.; Keen, Henry L.; Grobe, Justin L.; Daugherty, Alan; Cassis, Lisa A.; Allen, Andrew M.; Sigmund, Curt D.


    All components of the renin angiotensin system necessary for ANG II generation and action have been reported to be present in renal proximal convoluted tubules. Given the close relationship between renal sodium handling and blood pressure regulation, we hypothesized that modulating the action of ANG II specifically in the renal proximal tubules would alter the chronic level of blood pressure. To test this, we used a proximal tubule-specific, androgen-dependent, promoter construct (KAP2) to ge...

  1. Effect of electroacupuncture at distal–proximal acupoint combinations on spinal interleukin-1 beta in a rat model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Huili Jiang


    Conclusion: EA at distal + proximal acupoints, distal points, as well as proximal points attenuated upregulation of spinal IL-1β, alleviated the extent of neuropathic pain hypersensitivity, and promoted mechanical withdrawal threshold, resulting in EA analgesia.

  2. The sooner, the better: exercise outcome proximity and intrinsic motivation. (United States)

    Evans, M Blair; Cooke, Lisa M; Murray, Robyn A; Wilson, Anne E


    Despite evidence that outcomes are highly valued when they are expected sooner rather than further into the future (Ainslie, 1975), limited research effort has been devoted to understanding the role of exercise outcome proximity. The purpose of this study was to examine how temporal proximity to positive outcomes influences exercisers' intrinsic motivation. We expected that focusing people on temporally proximal exercise outcomes would increase intrinsic motivation, especially among low-frequency exercisers. This online experimental study was completed by 135 community exercisers (Mage  = 31.11, SD = 10.29; 62% female) who reported an average of 4.86 exercise bouts per week (SD = 2.12). Participants were randomly assigned to a condition that primed temporally proximal positive exercise outcomes (i.e. experienced during or directly following an exercise bout) or temporally distal outcomes (i.e. experienced after days, months, or years of regular exercise). Participants then reported perceptions of behavioral regulation in exercise. As expected, the proximal exercise outcome condition elicited increased intrinsic regulation among those participants who exercised less frequently (i.e. 1 SD below the mean). This study reveals the importance of considering proximity as an important dimension of exercise outcomes-particularly when promoting intrinsic motivation among relatively infrequent exercisers. © 2014 The International Association of Applied Psychology.

  3. Cubesat Proximity Operations Demonstration (CPOD) (United States)

    Villa, Marco; Martinez, Andres; Petro, Andrew


    The CubeSat Proximity Operations Demonstration (CPOD) project will demonstrate rendezvous, proximity operations and docking (RPOD) using two 3-unit (3U) CubeSats. Each CubeSat is a satellite with the dimensions 4 inches x 4 inches x 13 inches (10 centimeters x 10 centimeters x 33 centimeters) and weighing approximately 11 pounds (5 kilograms). This flight demonstration will validate and characterize many new miniature low-power proximity operations technologies applicable to future missions. This mission will advance the state of the art in nanosatellite attitude determination,navigation and control systems, in addition to demonstrating relative navigation capabilities.The two CPOD satellites are scheduled to be launched together to low-Earth orbit no earlier than Dec. 1, 2015.


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    SHORT COMMUNICATION. PROXIMATE COMPOSITION, MINERAL CONTENT AND ANTINUTRITIONAL. FACTORS OF SOME CAPSICUM (Capsicum annum) VARIETIES GROWN IN. ETHIOPIA. Esayas K.1, Shimelis A.2, Ashebir F.3, Negussie R.3, Tilahun B.4 and Gulelat D.4*. 1Hawassa University, Department of Food ...

  5. Mouse model of proximal tubule endocytic dysfunction. (United States)

    Weyer, Kathrin; Storm, Tina; Shan, Jingdong; Vainio, Seppo; Kozyraki, Renata; Verroust, Pierre J; Christensen, Erik I; Nielsen, Rikke


    Several studies have indicated the central role of the megalin/cubilin multiligand endocytic receptor complex in protein reabsorption in the kidney proximal tubule. However, the poor viability of the existing megalin-deficient mice precludes further studies and comparison of homogeneous groups of mice. Megalin- and/or cubilin-deficient mice were generated using a conditional Cre-loxP system, where the Cre gene is driven by the Wnt4 promoter. Kidney tissues from the mice were analysed for megalin and cubilin expression by quantitative reverse transcription-polymerase chain reaction, western blotting and immunohistochemistry. Renal albumin uptake was visualized by immunohistochemistry. Twenty-four-hour urine samples were collected in metabolic cages and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blotting. Urinary albumin/creatinine ratios were measured by ELISA and the alkaline picrate method. The Meg(lox/lox);Cre(+), Cubn(lox/lox);Cre(+) and Meg(lox/lox), Cubn(lox/lox);Cre(+) mice were all viable, fertile and developed normal kidneys. Megalin and/or cubilin expression, assessed by immunohistology and western blotting, was reduced by >89%. Consistent with this observation, the mice excreted megalin and cubilin ligands such as transferrin and albumin in addition to low-molecular weight proteins. We further show that megalin/cubilin double-deficient mice excrete albumin with an average of 1.45 ± 0.54 mg/day, suggesting a very low albumin concentration in the glomerular ultrafiltrate. We report here the efficient genetic ablation of megalin, cubilin or both, using a Cre transgene driven by the Wnt4 promoter. The viable megalin/cubilin double-deficient mice now allow for detailed large-scale group analysis, and we anticipate that the mice will be of great value as an animal model for proximal tubulopathies with disrupted endocytosis.

  6. Small suitability of the DLEC1, MLH1 and TUSC4 mRNA expression ...

    Indian Academy of Sciences (India)


    Jun 18, 2017 ... According to the latest data, lung cancer is one of the most common cancer worldwide, men contributing nearly 21.2% and women 8.6% of all diagnosed cancers. Late detection of tumour drastically reduces the chance for a cure.Thus, it is important to search for candidate biomarkers for screening of early ...

  7. RESEARCH ARTICLE Small suitability of the DLEC1,MLH1 and ...

    Indian Academy of Sciences (India)


    Accordingly to the newest data, lung cancer is one of the most common cancers: it stands for. 21.2% of all diagnosed cancers in men, and 8.6% in women. Late detection of tumor drastically reduces the chance for a cure. Thus it is important to search for candidate biomarkers for Non-Small Cell Lung Carcinoma (NSCLC) ...

  8. Small suitability of the DLEC1, MLH1 and TUSC4 mRNA expression ...

    Indian Academy of Sciences (India)



    Jun 18, 2017 ... Abstract. According to the latest data, lung cancer is one of the most common cancer worldwide, men contributing nearly. 21.2% and women 8.6% of all diagnosed cancers. Late detection of tumour drastically reduces the chance for a cure. Thus, it is important to search for candidate biomarkers for ...

  9. ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes.

    Directory of Open Access Journals (Sweden)

    Marco Barchi


    Full Text Available During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm-/- spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm(-/- meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/-Atm-/- spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics.

  10. Photoactivated In Vivo Proximity Labeling. (United States)

    Beck, David B; Bonasio, Roberto


    Identification of molecular interactions is paramount to understanding how cells function. Most available technologies rely on co-purification of a protein of interest and its binding partners. Therefore, they are limited in their ability to detect low-affinity interactions and cannot be applied to proteins that localize to difficult-to-solubilize cellular compartments. In vivo proximity labeling (IPL) overcomes these obstacles by covalently tagging proteins and RNAs based on their proximity in vivo to a protein of interest. In IPL, a heterobifunctional probe comprising a photoactivatable moiety and biotin is recruited by a monomeric streptavidin tag fused to a protein of interest. Following UV irradiation, candidate interacting proteins and RNAs are covalently biotinylated with tight spatial and temporal control and subsequently recovered using biotin as an affinity handle. Here, we describe experimental protocols to discover novel protein-protein and protein-RNA interactions using IPL. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  11. Prox-1 Automated Proximity Operations (United States)


    on demonstrating the functionality required to meet minimum mission success criteria. The minimum mission includes on- orbit spacecraft checkout of...also includes deployment of LightSail-B from the P-POD, and imaging of LightSail-B for 20 minutes as it recedes from Prox-1. small satellite ; proximity...criteria. The minimum mission includes on- orbit spacecraft checkout of all spacecraft subsystems, including flight qualification of the following new


    African Journals Online (AJOL)


    PROXIMATE AND ELEMENTAL COMPOSITION OF WHITE GRUBS. 1 Alhassan, A. J. 1M .S. Sule, 1J. ... ABSTRACT. This study determined the proximate and mineral element composition of whole white grubs using standard methods of analysis. Proximate ... days, before pulverized to powder and kept in plastic container.

  13. Finger Proximal Interphalangeal Joint Dislocation. (United States)

    Ramponi, Denise; Cerepani, Mary Jo


    Finger dislocations are common injuries that are often managed by emergency nurse practitioners. A systematic physical examination following these injuries is imperative to avoid complications. Radiographic views, including the anteroposterior, lateral, and oblique views, are imperative to evaluate these finger dislocations. A dorsal dislocation of the proximal interphalangeal (PIP) joint is the most common finger dislocation type often easily reduced. A volar PIP dislocation can often be difficult to reduce and may result in finger deformity. Finger dislocations should be reduced promptly. Referral to an orthopedic hand specialist is required if the dislocation is unable to be reduced or if the finger joint is unstable following reduction attempts.

  14. Equilibrium properties of proximity effect

    Energy Technology Data Exchange (ETDEWEB)

    Esteve, D.; Pothier, H.; Gueron, S.; Birge, N.O.; Devoret, M.


    The proximity effect in diffusive normal-superconducting (NS) nano-structures is described by the Usadel equations for the electron pair correlations. We show that these equations obey a variational principle with a potential which generalizes the Ginzburg-Landau energy functional. We discuss simple examples of NS circuits using this formalism. In order to test the theoretical predictions of the Usadel equations, we have measured the density of states as a function of energy on a long N wire in contact with a S wire at one end, at different distances from the NS interface. (authors). 12 refs.

  15. Aberrant promoter CpG methylation as a molecular marker for disease monitoring in natural killer cell lymphomas. (United States)

    Siu, Lisa L P; Chan, John K C; Wong, Kit F; Choy, Carolyn; Kwong, Yok L


    Natural killer (NK) cell lymphomas lack suitable clonal markers for tumour cell detection, making the monitoring of minimal residual lymphoma difficult. Aberrant promoter CpG methylation occurs frequently in NK cell lymphomas. The objective of this study was to assess the potential of aberrant methylation as a surrogate tumour marker. Twenty-five primary tumours and 105 serial biopsies taken at various time points after treatment were examined using a methylation-specific polymerase chain reaction (MSP) for a panel of genes, comprising p73, p16, hMLH1, RARbeta and p15, previously shown to be methylated in NK cell lymphomas. All samples underwent independent morphological examination, supplemented by immunostaining for CD56 and in-situ hybridization for Epstein-Barr-virus-encoded RNA. Primary tumours showed the frequent methylation of the genes p73 (92%), p16 (71%), hMLH1 (61%), RARbeta (56%) and p15 (48%). MSP results in serial post-treatment biopsies were correlated with clinicopathological findings. Results were concordant in 89 follow-up samples (18 samples, histology positive/MSP positive; 71 samples, histology negative/MSP negative) and discordant in 16. Fifteen samples were histology negative/MSP positive, and tumour involvement was subsequently confirmed (positive re-biopsies or relapses at the same sites), indicating that MSP was more sensitive for minimal lymphoma detection. One sample was histology positive/MSP negative; a subsequent histological review and continuous clinical remission of the patient did not support tumour involvement. Our findings suggest that MSP for aberrantly methylated genes is a potentially valuable molecular marker for detecting either residual or relapsed disease in NK cell lymphoma patients.

  16. Complications in proximal humeral fractures. (United States)

    Calori, Giorgio Maria; Colombo, Massimiliano; Bucci, Miguel Simon; Fadigati, Piero; Colombo, Alessandra Ines Maria; Mazzola, Simone; Cefalo, Vittorio; Mazza, Emilio


    Necrosis of the humeral head, infections and non-unions are among the most dangerous and difficult-to-treat complications of proximal humeral fractures. The aim of this work was to analyse in detail non-unions and post-traumatic bone defects and to suggest an algorithm of care. Treatment options are based not only on the radiological frame, but also according to a detailed analysis of the patient, who is classified using a risk factor analysis. This method enables the surgeon to choose the most suitable treatment for the patient, thereby facilitating return of function in the shortest possible time. The treatment of such serious complications requires the surgeon to be knowledgeable about the following possible solutions: increased mechanical stability; biological stimulation; and reconstructive techniques in two steps, with application of biotechnologies and prosthetic substitution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Proximity sensor technology for manipulator end effectors (United States)

    Johnston, A. R.


    Optical proximity sensing techniques which could be used to help control the critical grasping phase of a remote manipulation are described. The proximity sensors described use a triangulation geometry to detect a surface located in a pre-determined region. The design of the proximity sensors themselves is discussed, as well as their application to manipulator control with a local control loop, and possibilities for future development are discussed.

  18. Proximate composition and antinutrient content of pumpkin ...

    African Journals Online (AJOL)

    Proximate composition and antinutrient content of pumpkin ( Cucurbita pepo ) and sorghum ( Sorghum bicolor ) flour blends fermented with Lactobacillus plantarum , Aspergillus niger and Bacillus subtilis.

  19. Functional outcome following proximal humeral interlocking system plating for displaced proximal humeral fractures


    Thyagarajan David; Haridas Samarth; Jones Denise; Dent Colin; Evans Richard; Williams Rhys


    Aim: To assess the functional outcome following internal fixation with the PHILOS (proximal humeral interlocking system) for displaced proximal humeral fractures. Patients and Methods: We reviewed 30 consecutive patients treated surgically with the proximal humeral locking plate for a displaced proximal humeral fracture. Functional outcome was determined using the American Shoulder and Elbow Society (ASES) score and Constant Murley score. Results: Average age of the patients was 58 years...

  20. Best Proximity Points for a New Class of Generalized Proximal Mappings

    Directory of Open Access Journals (Sweden)

    Tayyab Kamran


    Full Text Available The best proximity points are usually used to find the optimal approximate solution of the operator equation Tx = x, when T has no fixed point. In this paper, we prove some best proximity point theorems for nonself multivalued operators, following the foot steps of Basha and Shahzad [Best proximity point theorems for generalized proximal contractions, Fixed Point Theory Appl., 2012, 2012:42].

  1. Preliminary phytochemical screening, proximate and elemental ...

    African Journals Online (AJOL)

    The seed powder of Moringa oleifera was analysed for its phytochemical, proximate and elemental composition using Folin-Denis spectrophotometric method, gravimetric method and energy dispersing X-ray fluorescence (EDXRF) transmission emission technique respectively. The seed powder had the following proximate ...

  2. Bimalleolar ankle fracture with proximal fibular fracture

    NARCIS (Netherlands)

    Colenbrander, R. J.; Struijs, P. A. A.; Ultee, J. M.


    A 56-year-old female patient suffered a bimalleolar ankle fracture with an additional proximal fibular fracture. This is an unusual fracture type, seldom reported in literature. It was operatively treated by open reduction and internal fixation of the lateral malleolar fracture. The proximal fibular

  3. Grouping by Proximity in Haptic Contour Detection (United States)

    Overvliet, Krista E.; Krampe, Ralf Th.; Wagemans, Johan


    We investigated the applicability of the Gestalt principle of perceptual grouping by proximity in the haptic modality. To do so, we investigated the influence of element proximity on haptic contour detection. In the course of four sessions ten participants performed a haptic contour detection task in which they freely explored a haptic random dot display that contained a contour in 50% of the trials. A contour was defined by a higher density of elements (raised dots), relative to the background surface. Proximity of the contour elements as well as the average proximity of background elements was systematically varied. We hypothesized that if proximity of contour elements influences haptic contour detection, detection will be more likely when contour elements are in closer proximity. This should be irrespective of the ratio with the proximity of the background elements. Results showed indeed that the closer the contour elements were, the higher the detection rates. Moreover, this was the case independent of the contour/background ratio. We conclude that the Gestalt law of proximity applies to haptic contour detection. PMID:23762364

  4. Proximate analysis on four edible mushrooms ADEDAYO ...

    African Journals Online (AJOL)

    Michael Horsfall

    Vol. 15 (1) 9 - 11. Full-text Available Online at Proximate analysis on four edible mushrooms. ADEDAYO, MAJEKODUNMI RACHEL. Nigerian Stored Product Research Institute, P.M.B.3032, Kano. ABSTRACT: Proximate study was conducted on four edible mushrooms commonly found in farmlands in.

  5. Proximate Sources of Collective Teacher Efficacy (United States)

    Adams, Curt M.; Forsyth, Patrick B.


    Purpose: Recent scholarship has augmented Bandura's theory underlying efficacy formation by pointing to more proximate sources of efficacy information involved in forming collective teacher efficacy. These proximate sources of efficacy information theoretically shape a teacher's perception of the teaching context, operationalizing the difficulty…

  6. Phytochemical screening, proximate analysis and anticonvulsant ...

    African Journals Online (AJOL)

    Spigelia anthelmia is used traditionally in Southern Nigeria for the treatment of infant convulsion and epilepsy. This study investigated the phytochemical constituents, proximate analysis and anticonvulsant effect of the methanolic extract of Spigelia anthelmia. Phytochemical evaluation and proximate analysis was carried ...

  7. Intramedullary compression device for proximal ulna fracture. (United States)

    Hong, Choon Chiet; Han, Fucai; Decruz, Joshua; Pannirselvam, Vinodhkumar; Murphy, Diarmuid


    Proximal ulna fractures account for 20% of all proximal forearm fractures. Many treatment options are available for such fractures, such as cast immobilisation, plate and screw fixation, tension band wiring and intramedullary screw fixation, depending on the fracture pattern. Due to the subcutaneous nature of the proximal forearm, it is vulnerable to open injuries over the dorsal aspect of the proximal ulna. This may in turn prove challenging, as it is critical to obtain adequate soft tissue coverage to reduce the risk of implant exposure and bony infections. We herein describe a patient with a Gustillo III-B open fracture of the proximal ulna, treated with minimally invasive intramedullary screw fixation using a 6.0-mm cannulated headless titanium compression screw (FusiFIX, Péronnas, France).

  8. Proximal Alternating Direction Method with Relaxed Proximal Parameters for the Least Squares Covariance Adjustment Problem

    Directory of Open Access Journals (Sweden)

    Minghua Xu


    Full Text Available We consider the problem of seeking a symmetric positive semidefinite matrix in a closed convex set to approximate a given matrix. This problem may arise in several areas of numerical linear algebra or come from finance industry or statistics and thus has many applications. For solving this class of matrix optimization problems, many methods have been proposed in the literature. The proximal alternating direction method is one of those methods which can be easily applied to solve these matrix optimization problems. Generally, the proximal parameters of the proximal alternating direction method are greater than zero. In this paper, we conclude that the restriction on the proximal parameters can be relaxed for solving this kind of matrix optimization problems. Numerical experiments also show that the proximal alternating direction method with the relaxed proximal parameters is convergent and generally has a better performance than the classical proximal alternating direction method.

  9. The Life Saving Effects of Hospital Proximity

    DEFF Research Database (Denmark)

    Bertoli, Paola; Grembi, Veronica

    We assess the lifesaving effect of hospital proximity using data on fatality rates of road-traffic accidents. While most of the literature on this topic is based on changes in distance to the nearest hospital triggered by hospital closures and use OLS estimates, our identification comes from......) increases the fatality rate by 13.84% on the sample average. This is equal to a 0.92 additional death per every 100 accidents. We show that OLS estimates provide a downward biased measure of the real effect of hospital proximity because they do not fully solve spatial sorting problems. Proximity matters...

  10. Proximal Multitask Learning Over Networks With Sparsity-Inducing Coregularization (United States)

    Nassif, Roula; Richard, Cedric; Ferrari, Andre; Sayed, Ali H.


    In this work, we consider multitask learning problems where clusters of nodes are interested in estimating their own parameter vector. Cooperation among clusters is beneficial when the optimal models of adjacent clusters have a good number of similar entries. We propose a fully distributed algorithm for solving this problem. The approach relies on minimizing a global mean-square error criterion regularized by non-differentiable terms to promote cooperation among neighboring clusters. A general diffusion forward-backward splitting strategy is introduced. Then, it is specialized to the case of sparsity promoting regularizers. A closed-form expression for the proximal operator of a weighted sum of $\\ell_1$-norms is derived to achieve higher efficiency. We also provide conditions on the step-sizes that ensure convergence of the algorithm in the mean and mean-square error sense. Simulations are conducted to illustrate the effectiveness of the strategy.

  11. Immunohistochemical staining for p16 and BRAFV600E is useful to distinguish between sporadic and hereditary (Lynch syndrome-related) microsatellite instable colorectal carcinomas. (United States)

    Boissière-Michot, Florence; Frugier, Hélène; Ho-Pun-Cheung, Alexandre; Lopez-Crapez, Evelyne; Duffour, Jacqueline; Bibeau, Frédéric


    DNA mismatch repair (MMR) protein analysis by immunohistochemistry (IHC) can identify colorectal cancer (CRC) with microsatellite instability (MSI). As MLH1-deficient CRC can be hereditary or sporadic, markers to distinguish between them are needed. MLH1 promoter methylation assay is the reference method; however, sometimes, it is challenging on formalin-fixed paraffin-embedded tissue samples. We assessed by IHC the expression of BRAFV600E, p16, MGMT, and CDX2 in 55 MLH1-deficient MSI CRC samples (of which 8 had a germline MLH1 mutation) to determine whether this panel differentiates between sporadic and hereditary CRCs. We also analyzed MLH1 promoter methylation by methylation-specific PCR and pyrosequencing and BRAF status by genotyping. None of the hereditary CRCs showed MLH1 methylation, BRAF mutation, BRAFV600E-positive immunostaining, or loss of p16 expression. We detected MLH1 promoter methylation in 67 % and a BRAF mutation in 42 % of CRC, all showing MLH1 promoter methylation. BRAFV600E IHC and BRAF genotyping gave concordant results in all but two samples. Loss of expression of p16 was found in 30 % of CRC with methylation of the MLH1 promoter, but its expression was retained in all non-methylated and part of MLH1-methylated tumors (100 % specificity, 30 % sensitivity). CDX2 and MGMT expression was not associated with MLH1 status. Thus, BRAFV600E and p16 IHC may help in differentiating sporadic from hereditary MLH1-deficient CRC with MSI. Specifically, p16 IHC might be used as a surrogate marker for MLH1 promoter methylation, because all p16-negative CRCs displayed MLH1 methylation, whereas hereditary CRCs were all p16-positive.

  12. Regulatory Focus, Proximity to Goal Weight, and Weight Loss Maintenance. (United States)

    Fuglestad, Paul T; Rothman, Alexander J; Jeffery, Robert W; Sherwood, Nancy E


    Regulatory focus theory proposes 2 self-regulatory orientations: promotion focus - related to achieving aspirations and positive outcomes - and prevention focus - related to fulfilling responsibilities and preventing negative outcomes. The investigation examined whether regulatory focus and proximity to goal weight moderated the effectiveness of a weight-loss maintenance intervention. Participants who lost ≥10% of their weight were assigned to guided or self-directed treatments and completed regulatory focus and weight goal measures. Across treatment groups, people who were more promotion-focused had better 2-year maintenance rates (defined as regain focused, especially if far from their goal weight (.59 versus .44). In the guided group, people who were more prevention-focused had better maintenance rates than people who were less prevention-focused if closer to their goal weight (.69 versus .42), but poorer maintenance rates if farther from their goal (.36 versus .72). In the self-directed group, prevention focus was unrelated to maintenance. Regulatory focus and proximity to goal weight moderated intervention effectiveness. Maintenance may be enhanced by tailoring treatments to regulatory focus and goal weight (eg, prevention-focused people far from their goals may need extra weight-loss support before focusing on maintenance).

  13. Proximity and Collaboration in European Nanotechnology

    NARCIS (Netherlands)

    Cunningham, S.W.; Werker, C.


    Collaborations are particularly important for the development and deployment of technology. We analyze the influence of organizational, technological and geographical proximity on European nanotechnology collaborations with the help of a publication dataset and additional geographical information.

  14. Ammonia transport in the proximal tubule. (United States)

    Hamm, L L; Simon, E E


    The transport of ammonia in the proximal tubule is a complex interaction of a number of processes. Ammonia transport in the proximal tubule is clearly bidirectional; ammonia is secreted into the early proximal tubule lumen, but later in the proximal tubule, efflux out of the lumen may result in net ammonia reabsorption. Two mechanisms of ammonia transport have clearly been established: NH3 diffusion and NH4+ transport on the Na(+)-H+ exchanger. The relative contribution of these pathways to ammonia transport is still unsettled. Other pathways for ammonia transport, particularly NH4+ efflux out of the lumen, may be important as well. A variety of factors may modulate ammonia transport: plasma, cell and luminal pH, luminal flow rate, luminal potassium, and angiotensin II. Each of these factors also alters ammonia production rates and in most circumstances, ammonia transport appears to follow ammonia production rates.

  15. Proximate composition and cholesterol concentrations of ...

    African Journals Online (AJOL)



    DWB) for raw and fried samples, respectively, but decreased to 295.20 ... Key words: Rhynchophorus phoenicis, Oryctes monoceros, proximate composition, cholesterol, heat treatment. INTRODUCTION. Insects have played ...


    African Journals Online (AJOL)

    Babatunde Emmanuel


    Oct 6, 2011 ... Fish allows for protein improved nutrition in that it has a high biological value in terms of high ... marine algae upon which the fish feed [11]. ... Proximate composition of catfish Clarias gariepinus and Tarpon atlanticus were.

  17. Phytochemical screening, proximate analysis and acute toxicity ...

    African Journals Online (AJOL)

    Phytochemical screening, proximate analysis and acute toxicity studies were carried out on the leaf extract of Cola lepidota, in accordance with established standard procedures. The proximate analysis reveals a moisture content of 27.43 ± 3.11 % w/w, total ash value 9.32 ± 0.27 % w/w, acid insoluble ash 3.12 ± 1.05 % w/w ...

  18. Proximate, Mineral and Phytochemical Composition of Dioscorea ...

    African Journals Online (AJOL)


    ABSTRACT: Proximate, mineral and phytochemical composition of Dioscorea dumetorum tubers was investigated using standard procedures. Proximate analysis included in g% dry weight: crude protein (6.44 ± 0.32), crude fat (0.75 ± 0.04), crude fibre (15.00 ± 0.56), total ash. (3.45 ± 0.20) and a moisture content of 70.04 ...

  19. Painful Spastic Hip Dislocation: Proximal Femoral Resection


    Albiñana, Javier; Gonzalez-Moran, Gaspar


    The dislocated hip in a non-ambulatory child with spastic paresis tends to be a painful interference to sleep, sitting upright, and perineal care. Proximal femoral resection-interposition arthroplasty is one method of treatment for this condition. We reviewed eight hips, two bilateral cases, with a mean follow-up of 30 months. Clinical improvement was observed in all except one case, with respect to pain relief and sitting tolerance. Some proximal migration was observed in three cases, despit...

  20. Proximity sensor system development. CRADA final report

    Energy Technology Data Exchange (ETDEWEB)

    Haley, D.C. [Oak Ridge National Lab., TN (United States); Pigoski, T.M. [Merrit Systems, Inc. (United States)


    Lockheed Martin Energy Research Corporation (LMERC) and Merritt Systems, Inc. (MSI) entered into a Cooperative Research and Development Agreement (CRADA) for the development and demonstration of a compact, modular proximity sensing system suitable for application to a wide class of manipulator systems operated in support of environmental restoration and waste management activities. In teleoperated modes, proximity sensing provides the manipulator operator continuous information regarding the proximity of the manipulator to objects in the workspace. In teleoperated and robotic modes, proximity sensing provides added safety through the implementation of active whole arm collision avoidance capabilities. Oak Ridge National Laboratory (ORNL), managed by LMERC for the United States Department of Energy (DOE), has developed an application specific integrated circuit (ASIC) design for the electronics required to support a modular whole arm proximity sensing system based on the use of capacitive sensors developed at Sandia National Laboratories. The use of ASIC technology greatly reduces the size of the electronics required to support the selected sensor types allowing deployment of many small sensor nodes over a large area of the manipulator surface to provide maximum sensor coverage. The ASIC design also provides a communication interface to support sensor commands from and sensor data transmission to a distributed processing system which allows modular implementation and operation of the sensor system. MSI is a commercial small business specializing in proximity sensing systems based upon infrared and acoustic sensors.

  1. Transformations through Proximity Flying: A Phenomenological Investigation (United States)

    Holmbom, Maria; Brymer, Eric; Schweitzer, Robert D.


    Participation in extreme sports has been linked to personal transformations in everyday life. Descriptions of lived experience resulting from transformative experiences are limited. Proximity flying, a relatively new discipline involving BASE jumping with a wingsuit where participants fly close to solid structures, is arguably one of the most extreme of extreme sports. The aim of this paper, part of a larger phenomenological study on the lived experience of proximity flying, is to explicate the ways in which participating in proximity flying influences the everyday lives of participants. Interpretative phenomenological analysis was used to explicate the lived experience of six proximity pilots. An analysis of interview transcripts revealed three significant themes describing the lived experience of participants. First, experiences of change were described as positive and skills developed through proximity flying were transferable into everyday life. Second, transformative experiences were considered fundamental to participants’ perspectives on life. Third, experience of transformation influenced their sense of personal identity and facilitated flourishing in other aspects of everyday life. Participants were clear that their experiences in proximity flying facilitated a profound process of transformation which manifest as changes in everyday capabilities and behaviors, values and sense of identity. PMID:29104552

  2. Adult and Child Development in the Zone of Proximal Development: Socratic Dialogue in a Playworld (United States)

    Ferholt, Beth; Lecusay, Robert


    This article analyses adult and child development in the zone of proximal development in an educational practice based in Vygotsky's theories of play: the playworld educational practice. The playworld educational practice is a central component of a Scandinavian play pedagogy that promotes shared responsibility amongst adults and children for…

  3. Treatment of three- and four-part proximal humeral fractures with locking proximal humerus plate. (United States)

    Sun, Jing-Cheng; Li, Yu-Lin; Ning, Guang-Zhi; Wu, Qiang; Feng, Shi-Qing


    The purpose of this study was to evaluate the effectiveness and complications of the locking proximal humerus plate to treat proximal humerus fractures. A retrospective clinical trial. Department of Orthopaedics, Tianjin Medical University General Hospital. Sixty-eight consecutive patients with three- or four-part fractures of the proximal humerus were treated with locking proximal humerus plates. The deltopectoral anterolateral acromial approach was used to the proximal humerus; open reduction and locking proximal humerus plate were applied. Constant Score was used to measure the shoulder functional recovery, and Visual Analog Scale (VAS) was used to measure subjective evaluation of pain. The radiology was observed. After average 26.7 months, the average Constant Score was 72.6 ± 13.2 points and the average VAS was 1.2 ± 0.8 points. All the complications such as screw perforation into the glenohumeral joint, screws loosening, soft tissue infections, avascular necrosis and delayed union occurred in eight cases (11.8 %). The effectiveness of the locking proximal humerus plate was similar to other published literatures on treating fractures of the proximal humerus; however, a lower complications rate in short follow-up time was observed in this study. It may potentially provide a favorable option for treating three- or four-part fractures of the proximal humerus. Dealing with each particular fracture pattern, surgeons should have a decision of appropriate way to internal fixation.

  4. Locking plate fixation for proximal humerus fractures.

    LENUS (Irish Health Repository)

    Burke, Neil G


    Locking plates are increasingly used to surgically treat proximal humerus fractures. Knowledge of the bone quality of the proximal humerus is important. Studies have shown the medial and dorsal aspects of the proximal humeral head to have the highest bone strength, and this should be exploited by fixation techniques, particularly in elderly patients with osteoporosis. The goals of surgery for proximal humeral fractures should involve minimal soft tissue dissection and achieve anatomic reduction of the head complex with sufficient stability to allow for early shoulder mobilization. This article reviews various treatment options, in particular locking plate fixation. Locking plate fixation is associated with a high complication rate, such as avascular necrosis (7.9%), screw cutout (11.6%), and revision surgery (13.7%). These complications are frequently due to the varus deformation of the humeral head. Strategic screw placement in the humeral head would minimize the possibility of loss of fracture reduction and potential hardware complications. Locking plate fixation is a good surgical option for the management of proximal humerus fractures. Complications can be avoided by using better bone stock and by careful screw placement in the humeral head.

  5. Targeting the FANCJ–BRCA1 interaction promotes a switch from recombination to polη-dependent bypass (United States)

    Xie, J; Litman, R; Wang, S; Peng, M; Guillemette, S; Rooney, T; Cantor, SB


    BRCA1 and the DNA helicase FANCJ (also known as BACH1 or BRIP1) have common functions in breast cancer suppression and DNA repair. However, the functional significance of the direct interaction between BRCA1 and FANCJ remains unclear. Here, we have discovered that BRCA1 binding to FANCJ regulates DNA damage repair choice. Thus, when FANCJ binding to BRCA1 is ablated, the molecular mechanism chosen for the repair of damaged DNA is dramatically altered. Specifically, a FANCJ protein that cannot be phosphorylated at serine 990 or bind BRCA1 inhibits DNA repair via homologous recombination and promotes polη-dependent bypass. Furthermore, the polη-dependent bypass promoted by FANCJ requires the direct binding to the mismatch repair (MMR) protein, MLH1. Together, our findings implicate that in human cells BRCA1 binding to FANCJ is critical to regulate DNA repair choice and promote genomic stability. Moreover, unregulated FANCJ function could be associated with cancer and/or chemoresistance. PMID:20173781

  6. Industrial Computed Tomography using Proximal Algorithm

    KAUST Repository

    Zang, Guangming


    In this thesis, we present ProxiSART, a flexible proximal framework for robust 3D cone beam tomographic reconstruction based on the Simultaneous Algebraic Reconstruction Technique (SART). We derive the proximal operator for the SART algorithm and use it for minimizing the data term in a proximal algorithm. We show the flexibility of the framework by plugging in different powerful regularizers, and show its robustness in achieving better reconstruction results in the presence of noise and using fewer projections. We compare our framework to state-of-the-art methods and existing popular software tomography reconstruction packages, on both synthetic and real datasets, and show superior reconstruction quality, especially from noisy data and a small number of projections.

  7. Correlation between social proximity and mobility similarity. (United States)

    Fan, Chao; Liu, Yiding; Huang, Junming; Rong, Zhihai; Zhou, Tao


    Human behaviors exhibit ubiquitous correlations in many aspects, such as individual and collective levels, temporal and spatial dimensions, content, social and geographical layers. With rich Internet data of online behaviors becoming available, it attracts academic interests to explore human mobility similarity from the perspective of social network proximity. Existent analysis shows a strong correlation between online social proximity and offline mobility similarity, namely, mobile records between friends are significantly more similar than between strangers, and those between friends with common neighbors are even more similar. We argue the importance of the number and diversity of common friends, with a counter intuitive finding that the number of common friends has no positive impact on mobility similarity while the diversity plays a key role, disagreeing with previous studies. Our analysis provides a novel view for better understanding the coupling between human online and offline behaviors, and will help model and predict human behaviors based on social proximity.

  8. [Disorders of sex development and proximal hypospadias]. (United States)

    Oswald, J


    Children with ambiguous genitalia due to different chromosome or gonadal sex are a particular challenge concerning the diagnostic and therapeutic implications. Proximal hypospadias patients with normal gonadal development should be distinguished from children with DSD (disorders of sex development) to guarantee normal gender identity and the best possible surgical therapy. This paper focuses on the terminology, embryology, and pathophysiology of the different manifestations of DSD. The state of knowledge about this disease pattern with particular emphasis on proximal hypospadias based on national and international scientific discussions is presented. The different clinical pictures as well as therapeutic options of DSD with a special focus on recent literature and giving particular attention to patients with proximal hypospadias are presented. Because of the complexity of patients suffering from disorders of sex development an interdisciplinary DSD healthcare team including a paediatric endocrinologist as well as paediatric urologist should be provided. These specialists enable an accurate diagnosis in severe hypospadias patients without reference to DSD diseases patterns.

  9. Infiltrating/sealing proximal caries lesions

    DEFF Research Database (Denmark)

    Martignon, S; Ekstrand, K R; Gomez, J


    This randomized split-mouth controlled clinical trial aimed at assessing the therapeutic effects of infiltration vs. sealing for controlling caries progression on proximal surfaces. Out of 90 adult students/patients assessed at university clinics and agreeing to participate, 39, each with 3...... differences in lesion progression between infiltration and placebo (P = 0.0012) and between sealing and placebo (P = 0.0269). The study showed that infiltration and sealing are significantly better than placebo treatment for controlling caries progression on proximal lesions. No significant difference...... proximal lesions identified radiographically around the enamel-dentin junction to the outer third of the dentin, were included. Lesions were randomly allocated for treatment to test-A (Infiltration: ICON-pre-product; DMG), test-B (Sealing: Prime-Bond-NT; Dentsply), or control-C (Placebo). Primary outcome...

  10. Knowledge networks in the Dutch aviation industry: The proximity paradox

    NARCIS (Netherlands)

    Broekel, T.; Boschma, R.A.


    The importance of geographical proximity for interaction and knowledge sharing has been discussed extensively in recent years. There is increasing consensus that geographical proximity is just one out of many types of proximities that might be relevant. We argue that proximity may be a crucial

  11. The developmental spectrum of proximal radioulnar synostosis

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Alison M. [University of Manitoba, Winnipeg Regional Health Association Program of Genetics and Metabolism, Winnipeg, MB (Canada); University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, WRHA Program of Genetics and Metabolism, Departments of Paediatrics and Child Health, Biochemistry and Medical Genetics, Winnipeg, MB (Canada); Kibria, Lisa [University of Manitoba, Department of School of Medical Rehabilitation, Winnipeg, MB (Canada); Reed, Martin H. [University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, Department of Diagnostic Imaging, Winnipeg, MB (Canada)


    Proximal radioulnar synostosis is a rare upper limb malformation. The elbow is first identifiable at 35 days (after conception), at which stage the cartilaginous anlagen of the humerus, radius and ulna are continuous. Subsequently, longitudinal segmentation produces separation of the distal radius and ulna. However, temporarily, the proximal ends are united and continue to share a common perichondrium. We investigated the hypothesis that posterior congenital dislocation of the radial head and proximal radioulnar fusion are different clinical manifestations of the same primary developmental abnormality. Records were searched for ''proximal radioulnar fusion/posterior radial head dislocation'' in patients followed at the local Children's Hospital and Rehabilitation Centre for Children. Relevant radiographic, demographic and clinical data were recorded. Ethics approval was obtained through the University Research Ethics Board. In total, 28 patients met the inclusion criteria. The majority of patients (16) had bilateral involvement; eight with posterior dislocation of the radial head only; five had posterior radial head dislocation with radioulnar fusion and two had radioulnar fusion without dislocation. One patient had bilateral proximal radioulnar fusion and posterior dislocation of the left radial head. Nine patients had only left-sided involvement, and three had only right-sided involvement.The degree of proximal fusion varied, with some patients showing 'complete' proximal fusion and others showing fusion that occurred slightly distal to the radial head: 'partially separated.' Associated disorders in our cohort included Poland syndrome (two patients), Cornelia de Lange syndrome, chromosome anomalies (including tetrasomy X) and Cenani Lenz syndactyly. The suggestion of a developmental relationship between posterior dislocation of the radial head and proximal radioulnar fusion is supported by the fact that both anomalies

  12. Uncemented allograft-prosthetic composite reconstruction of the proximal femur

    Directory of Open Access Journals (Sweden)

    Li Min


    Full Text Available Background: Allograft-prosthetic composite can be divided into three groups names cemented, uncemented, and partially cemented. Previous studies have mainly reported outcomes in cemented and partially cemented allograft-prosthetic composites, but have rarely focused on the uncemented allograft-prosthetic composites. The objectives of our study were to describe a surgical technique for using proximal femoral uncemented allograft-prosthetic composite and to present the radiographic and clinical results. Materials and Methods: Twelve patients who underwent uncemented allograft-prosthetic composite reconstruction of the proximal femur after bone tumor resection were retrospectively evaluated at an average followup of 24.0 months. Clinical records and radiographs were evaluated. Results: In our series, union occurred in all the patients (100%; range 5-9 months. Until the most recent followup, there were no cases with infection, nonunion of the greater trochanter, junctional bone resorption, dislocation, allergic reaction, wear of acetabulum socket, recurrence, and metastasis. But there were three periprosthetic fractures which were fixed using cerclage wire during surgery. Five cases had bone resorption in and around the greater trochanter. The average Musculoskeletal Tumor Society (MSTS score and Harris hip score (HHS were 26.2 points (range 24-29 points and 80.6 points (range 66.2-92.7 points, respectively. Conclusions: These results showed that uncemented allograft-prosthetic composite could promote bone union through compression at the host-allograft junction and is a good choice for proximal femoral resection. Although this technology has its own merits, long term outcomes are yet not validated.

  13. preliminary phytochemical screening, proximate and elemental

    African Journals Online (AJOL)


    ABSTRACT. The seed powder of Moringa oleifera was analysed for its phytochemical, proximate and elemental composition using Folin-Denis spectrophotometric method, gravimetric method and energy dispersing X-ray fluorescence (EDXRF) transmission emission technique respectively. The seed powder had the ...

  14. Proximate, mineral composition, antioxidant activity, and total ...

    African Journals Online (AJOL)

    Four varieties of the red pepper fruits (Capsicum species) were evaluated for chemical composition, antioxidant activity and total phenolic contents using standard analytical technique, ferric-ion reducing antioxidant potential (FRAP) assay and Folin-Colcalteau method respectively. The proximate composition values ...

  15. 9__43 - 50__Tijjani_Proximate

    African Journals Online (AJOL)


    Sena et al., 1998). In Nigeria, the plant is commonly consumed by the Hausa speaking communities as a spice and a sauce (Ibrahim et al., 2012). However, during preparation the leaves and stem are not carefully separated before processing of food. Thus, the present study was aimed at evaluating the proximate, minerals ...

  16. Phytochemistry and proximate composition of ginger ( Zingiber ...

    African Journals Online (AJOL)

    ... a little crude fibre content of 0.92 %. The results indicated that ginger rhizome is an excellent natural remedy for a wide range of ailments. Keywords: Zingiber officinale, spice, rhizome, phytochemistry, proximate analysis, Zingiberaceae, zingerone, methanolic extraction. Journal of Pharmaceutical and Allied Sciences, Vol.


    African Journals Online (AJOL)



    Oct 24, 2012 ... opinions are analyzed and it revealed that the site has major impacts on the residents perceived quality of life, security and ... Key words: Landfill, Property value, Health and safety, Residential property, Solous. Introduction. The location ... Proximity to landfills and hazardous waste sites can severely affect ...

  18. 182 179 Comparative Study on the Proximate

    African Journals Online (AJOL)


    Dec 2, 2008 ... Key words: Annona squamosa, Fruits, Proximate, Minerals, nutrient density. INTRODUCTION. Sugar apple (Annona squamosa) also called. “Gwanda masar” in Hausa belong to the family. Annonacae. The most widely grown of all the species are A. muricata, A. cherimola, A reticulata, A. senegalensis and ...

  19. Phytochemical Screening, Proximate and Mineral Composition of ...

    African Journals Online (AJOL)

    Leaves of sweet potato (Ipomoea batatas) grown in Tepi area was studied for their class of phytochemicals, mineral and proximate composition using standard analytical methods. The phytochemical screening revealed the presence of alkaloids, flavonoid, terpenoids, saponins, quinones, phenol, tannins, amino acid and ...

  20. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    Citrus sinensis was screened for its phytochemical composition and was evaluated for the proximate and elemental analysis. The phytochemical analysis indicated the presence of reducing sugar, saponins, cardiac glycosides, tannins and flavonoids. The elemental analysis indicated the presence of the following mineral ...

  1. Phytochemical Screening and Proximate Analysis of Newbouldia ...

    African Journals Online (AJOL)

    The study was conducted to assess the phytochemical and proximate composition of Newboudia laevis leaves and Allium sativum bulb extracts. The leaves and bulbs extracts were analyzed for their chemical composition and antinutritional factors (ANFs) which include moisture, crude protein, crude fat, crude fiber, total ash ...

  2. Disability occurrence and proximity to death

    NARCIS (Netherlands)

    Klijs, Bart; Mackenbach, Johan P.; Kunst, Anton E.


    Purpose. This paper aims to assess whether disability occurrence is related more strongly to proximity to death than to age. Method. Self reported disability and vital status were available from six annual waves and a subsequent 12-year mortality follow-up of the Dutch GLOBE longitudinal study.

  3. [Four family members with proximal myotonic myopathy

    NARCIS (Netherlands)

    Tieleman, A.A.; Velden, M.P. van der; Visser, M.C.; Wokke, J.H.J.; Scheffer, H.; Engelen, B.G.M. van


    A 41-year-old woman had a 15-year history of pain in her thighs and arms, which also became weaker, and a decrease in visual acuity. Her 35-year-old brother, their 38-year-old sister and their 64-year-old mother also had myalgia, myotonia and proximal muscle weakness, and the women also had

  4. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    ... was about 0.01 in concentration. Proximate analysis also shows that it has a high nutritional value such as carbohydrate, fibre, Ash, fat and protein. These results recommended the consumption of these peels of desired physiochemical properties as sources of food fibres or low-calorie bulk ingredients in food applications ...

  5. Proximate composition and consumer acceptability of African ...

    African Journals Online (AJOL)

    The aim of the study was to assess the organoleptic differences of Clarias gariepinus smoked with two different energy sources, Anogeissus leiocarpus and Tamarindus indica with the help of a hedonic scale and to determine possible proximate composition difference between the smoked products. Smoking of the fishes ...

  6. Controllable proximity effect in superconducting hybrid devices

    NARCIS (Netherlands)

    Bakurskiy, S.V.


    This thesis is devoted to the study of controllable proximity effects in superconductors, both in terms of fundamental aspects and applications. As a part of this thesis theoretical description was suggested for a number of structures with superconducting electrodes and multiple interlayers. These

  7. Proximate, chemical compositions and sulphur concentrations on ...

    African Journals Online (AJOL)

    0, 10, 20, 50, 100, 150, 200, 250 and 300 ppm) on the nutritional value and the proximate composition of six selected mango cultivars (Tommy Atkins, Peach, Saber, Sunshine, Keitt and Vhavenda) grown in South Africa. The study shows that ...

  8. Proximate composition, bread characteristics and sensory ...

    African Journals Online (AJOL)

    This study was carried out to investigate proximate composition, bread characteristics and sensory evaluation of cocoyam-wheat composite breads at different levels of cocoyam flour substitution for human consumption.A whole wheat bread (WWB) and cocoyam-composite breads (CCB1,CCB 2 and CCB 3) were prepared ...

  9. Evaluation of the Proximate, Chemical and Phytochemical ...

    African Journals Online (AJOL)

    The increased interest in the utilization of the leaves of Moringa oleifera necessitated this study which evaluated the proximate, chemical and phytochemical composition, especially the presence of anti- physiological and toxic factors in the leaves. The results of the phytochemical analyses were: alkaloid 1.24 ± 0.141%; ...

  10. comparative proximate composition and antioxidant vitamins

    African Journals Online (AJOL)


    ABSTRACT. The proximate composition and antioxidant vitamins analysis of two varieties of honey (dark amber and light amber) were carried out using standard methods. The values for moisture, ash, crude lipid, crude protein and crude carbohydrate contents of the two honeys, (light amber and dark amber) are 9.39 ...

  11. Proximate composition and cholesterol concentrations of ...

    African Journals Online (AJOL)

    Proximate composition and cholesterol concentrations of Rhynchophorus phoenicis and Oryctes monoceros larvae subjected to different heat treatments. ... 514.63 mg/100g dry weight basis (DWB) for raw and fried samples, respectively, but decreased to 295.20 mg/100 g DWB in the smoke-dried samples. Similarly, the ...

  12. Preliminary Phytochemical Screening, Elemental and Proximate ...

    African Journals Online (AJOL)

    The study aimed at phytochemical screening, elemental and proximate composition of two varieties of Cyperus esculentus (tiger nut) big yellow and small brown nuts using standard methods. The phytochemicals tested for were alkaloid, saponin, tannin, glycoside, flavonoid, steroid and resin. All the aforementioned ...

  13. Protein biomarker validation via proximity ligation assays. (United States)

    Blokzijl, A; Nong, R; Darmanis, S; Hertz, E; Landegren, U; Kamali-Moghaddam, M


    The ability to detect minute amounts of specific proteins or protein modifications in blood as biomarkers for a plethora of human pathological conditions holds great promise for future medicine. Despite a large number of plausible candidate protein biomarkers published annually, the translation to clinical use is impeded by factors such as the required size of the initial studies, and limitations of the technologies used. The proximity ligation assay (PLA) is a versatile molecular tool that has the potential to address some obstacles, both in validation of biomarkers previously discovered using other techniques, and for future routine clinical diagnostic needs. The enhanced specificity of PLA extends the opportunities for large-scale, high-performance analyses of proteins. Besides advantages in the form of minimal sample consumption and an extended dynamic range, the PLA technique allows flexible assay reconfiguration. The technology can be adapted for detecting protein complexes, proximity between proteins in extracellular vesicles or in circulating tumor cells, and to address multiple post-translational modifications in the same protein molecule. We discuss herein requirements for biomarker validation, and how PLA may play an increasing role in this regard. We describe some recent developments of the technology, including proximity extension assays, the use of recombinant affinity reagents suitable for use in proximity assays, and the potential for single cell proteomics. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. © 2013.

  14. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    Michael Horsfall

    2009). The aim of this study was to analyses the extract of. Citrus sinensis peels for the phytochemical, proximate and elemental composition. MATERIALS AND METHODS. Plant materials Fresh peels of Citrus sinensis were collected from Uselu market in Benin City, Edo. State, Nigeria. It was identified and authenticated by.

  15. Keldysh proximity action for disordered superconductors

    Indian Academy of Sciences (India)

    Abstract. We review a novel approach to the superconductive proximity effect in dis- ordered normal–superconducting (N–S) structures. The method is based on the multi- charge Keldysh action and is suitable for the treatment of interaction and fluctuation effects. As an application of the formalism, we study the subgap ...

  16. Goal-Proximity Decision-Making (United States)

    Veksler, Vladislav D.; Gray, Wayne D.; Schoelles, Michael J.


    Reinforcement learning (RL) models of decision-making cannot account for human decisions in the absence of prior reward or punishment. We propose a mechanism for choosing among available options based on goal-option association strengths, where association strengths between objects represent previously experienced object proximity. The proposed…

  17. Cigarette smoking and colorectal cancer: APC mutations, hMLH1 Expression and GSTM1 and GSTT1 Polymorphisms

    NARCIS (Netherlands)

    Luchtenborg, M.; Weijenberg, M.P.; Kampman, E.; Muijen, van G.N.P.; Roemen, G.M.J.M.; Zeegers, M.; Goldbohm, R.A.; Veer, van 't P.; Goeij, de A.F.P.M.; Brandt, van den P.A.


    The contribution of cigarette smoking to sporadic colorectal cancer may differ according to molecular aspects of the tumor or according to glutathione S-transferase M1 (GSTM1) or glutathione S-transferase T1 (GSTT1) genotype. In the prospective Netherlands Cohort Study on Diet and Cancer, adjusted

  18. Cigarette smoking and colorectal cancer: APC mutations, hMLH1 expression, and GSTM1 and GSTT1 polymorphisms.

    NARCIS (Netherlands)

    Luchtenborg, M.; Weijenberg, M.P.; Kampman, E.; Muijen, G.N.P. van; Roemen, G.M.; Zeegers, M.P.; Goldbohm, R.A.; Veer, P. van 't; Goeij, A.F. de; Brandt, P.A. van den


    The contribution of cigarette smoking to sporadic colorectal cancer may differ according to molecular aspects of the tumor or according to glutathione S-transferase M1 (GSTM1) or glutathione S-transferase T1 (GSTT1) genotype. In the prospective Netherlands Cohort Study on Diet and Cancer, adjusted

  19. Role of Cell Cycle Regulation and MLH1, A Key DNA Mismatch Repair Protein, In Adaptive Survival Responses. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    David A. Boothman


    Due to several interesting findings on both adaptive survival responses (ASRs) and DNA mismatch repair (MMR), this grant was separated into two discrete Specific Aim sets (each with their own discrete hypotheses). The described experiments were simultaneously performed.

  20. Internal fixation of proximal humerus fractures using the T2-proximal humeral nail. (United States)

    Popescu, Dragos; Fernandez-Valencia, Jenaro A; Rios, Moisés; Cuñé, Jordi; Domingo, Anna; Prat, Salvi


    Surgical management of proximal humerus fractures remains controversial and there is an increasing interest in intramedullary nailing. Created to improve previous designs, the T2-proximal humeral nail (PHN) (Stryker) has been recently released, and the English literature lacks a series evaluating its results. We present a clinical prospective study evaluating this implant for proximal humeral fractures. We evaluated the functional and radiological results and possible complications. Twenty-nine patients with displaced fractures of the proximal humerus were treated with this nail. One patient was lost right after surgery and excluded from the assessment. Eighteen patients were older than 70 years. There were 21 fractures of the proximal part of the humerus and 7 fractures that also involved the shaft; 15 of the fractures were two-part fractures (surgical neck), 5 were three-part fractures, and 1 was a four-part fracture. All fractures healed in a mean period of 2.7 months. There was one delayed union that healed in 4 months. One case of avascular necrosis of the humeral head was observed (a four-part fracture), but remained asymptomatic and did not require further treatment. In one case a back-out of one proximal screw was observed. A final evaluation with a minimum 1 year follow-up was performed by an independent observer; in 18 patients, the mean Constant score was 65.7 or 76.1% with the adjustment of age and gender; in 19 patients, the mean Oxford Shoulder Score was 21.7. The results obtained with the T2-PHN nail indicate that it represents a safe and reliable method in the treatment of two- and three-part fractures of the proximal humerus. The proximal fixation mechanism diminishes the rate of back-out of the screws, a frequent complication described in the literature. Better functional results were obtained from the patients younger than 70 years, but these were not statistically significant.

  1. Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria.

    Directory of Open Access Journals (Sweden)

    Ana Tobar

    Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity

  2. Renal proximal tubule angiotensin AT1A receptors regulate blood pressure. (United States)

    Li, Huiping; Weatherford, Eric T; Davis, Deborah R; Keen, Henry L; Grobe, Justin L; Daugherty, Alan; Cassis, Lisa A; Allen, Andrew M; Sigmund, Curt D


    All components of the renin angiotensin system necessary for ANG II generation and action have been reported to be present in renal proximal convoluted tubules. Given the close relationship between renal sodium handling and blood pressure regulation, we hypothesized that modulating the action of ANG II specifically in the renal proximal tubules would alter the chronic level of blood pressure. To test this, we used a proximal tubule-specific, androgen-dependent, promoter construct (KAP2) to generate mice with either overexpression of a constitutively active angiotensin type 1A receptor transgene or depletion of endogenous angiotensin type 1A receptors. Androgen administration to female transgenic mice caused a robust induction of the transgene in the kidney and increased baseline blood pressure. In the receptor-depleted mice, androgen administration to females resulted in a Cre recombinase-mediated deletion of angiotensin type 1A receptors in the proximal tubule and reduced blood pressure. In contrast to the changes observed at baseline, there was no difference in the blood pressure response to a pressor dose of ANG II in either experimental model. These data, from two separate mouse models, provide evidence that ANG II signaling via the type 1A receptor in the renal proximal tubule is a regulator of systemic blood pressure under baseline conditions.

  3. [Arthroscopic fracture management in proximal humeral fractures]. (United States)

    Lill, H; Katthagen, C; Jensen, G; Voigt, C


    Arthroscopy has become increasingly more established in the treatment of proximal humeral fractures. In addition to the known advantages of minimally invasive surgery fracture and implant positioning can be optimized and controlled arthroscopically and relevant intra-articular concomitant pathologies (e.g. biceps tendon complex and rotator cuff) can be diagnosed and treated. Arthroscopic techniques have proven to be advantageous in the treatment of various entities of greater tuberosity fractures, lesser tuberosity fractures (suture bridging technique) and subcapital humeral fractures (arthroscopic nailing). This article presents an overview on innovative arthroscopic modalities for treating proximal humeral fractures, describes the surgical techniques and the advantages compared to open procedures as well as initial clinical results.

  4. SINA: A test system for proximity fuses (United States)

    Ruizenaar, M. G. A.


    SINA, a signal generator that can be used for testing proximity fuses, is described. The circuitry of proximity fuses is presented; the output signal of the RF circuit results from a mixing of the emitted signal and received signal that is Doppler shifted in frequency by the relative motion of the fuse with respect to the reflecting target of surface. With SINA, digitized and stored target and clutter signals (previously measured) can be transformed to Doppler signals, for example during a real flight. SINA can be used for testing fuse circuitry, for example in the verification of results of computer simulations of the low frequency Doppler signal processing. The software of SINA and its use are explained.

  5. Tunable Magnetic Proximity Effects in Graphene Junctions (United States)

    Lazic, Predrag; Belashchenko, Kirill; Zutic, Igor


    The characteristic length of the magnetic proximity effects exceed the thickness of a graphene layer leading to an important, but typically overlooked, modifications of equilibrium and transport properties, as well as the implications for graphene spintronics. Using the first-principles studies that integrate a real space density functional theory (GPAW) with the state-of-the art boundary elements electrostatic code based on the Robin Hood method, we explore tunable electronic structure and magnetic proximity effects in the ferromagnet/insulator/graphene junctions. We show that the inclusion of a finite-size gate electrodes and van der Walls interaction lead to nontrivial effects that could also be important in other two-dimensional materials beyond graphene. Work supported by US ONR, NSF-DMR and Nebraska NSF MRSEC.

  6. Management of Proximal Third Arm Replantation

    Directory of Open Access Journals (Sweden)

    Süleyman Taş


    Full Text Available Notwithstanding the recent success in major limb replantation achieved through the advancements in microsurgical techniques, the viability of the extremity is still relatively low at the transhumeral level following a replantation. There are no exact guidelines for deciding whether to undertake a stump repair or a replantation in such amputations at the proximal level. However, a highly motivated patient with realistic expectations and protected shoulder function can be a candidate to undergo replantation. The replanted arm may help the uninjured arm in daily activities. In this report we present the case of a 47-year-old man whose arm was amputated at proximal third level by an asphalt machine and successfully replanted together with the encountered problems and their solutions. The roadmap followed in this rare case may be a guide for hand surgeons.

  7. Dedifferentiated chondrosarcoma of right proximal femur

    Directory of Open Access Journals (Sweden)

    Sachin A Badge


    Full Text Available Dedifferentiated chondrosarcoma (DDCS comprises approximately 10% of all chondrosarcomas. The tumor generally occurs after the age of 50 years, with equal distribution among males and females. It is most often located in the bones of the pelvis, the proximal femur or humerus, the distal femur, and the ribs. Regardless of treatment, the prognosis is ominous with 90% of patients dying with distant metastases within 2 years. We report a case of DDCS of right proximal femur in a 73-year-old woman. The most important factors affecting survival are early recognition of the radiographic features, adequate histological sampling, and wide-margin resection of the lesion. So for the correct histopathological diagnosis the biopsy sample should be adequate to visualize both cartilaginous and noncartilaginous sarcomatous component which helps to increase the survival of patients before the distant metastasis occurs.

  8. Management of Acute Proximal Humeral Fractures. (United States)

    Kancherla, Vamsi Krishna; Singh, Anshuman; Anakwenze, Oke A


    Proximal humeral fractures, which typically occur in elderly persons, are among the most common fractures. A myriad of nonsurgical and surgical treatment options exist for these injuries, including short-term immobilization and early physical therapy, percutaneous fixation, plate osteosynthesis, intramedullary nailing, hemiarthroplasty, and reverse shoulder arthroplasty. The choice of treatment depends on the fracture type and severity, surgeon expertise, patient age, and patient health status.

  9. Superconducting proximity effect in clean ferromagnetic layers


    Zareyan, M.; Belzig, W.; Nazarov, Yu. V.


    We investigate the superconducting proximity effect in clean ferromagnetic layers with rough boundaries. The subgap density of states is formed by Andreev bound states at energies which depend on trajectory length and the ferromagnetic exchange field. At energies above the gap, the spectrum is governed by resonant scattering states. The resulting density of states, measurable by tunneling spectroscopy, exhibits a rich structure, which allows us to connect the theoretical parameters from exper...

  10. Alternating proximal algorithm for blind image recovery


    Bolte, Jérôme; Combettes, Patrick Louis; Pesquet, Jean-Christophe


    International audience; We consider a variational formulation of blind image recovery problems. A novel iterative proximal algorithm is proposed to solve the associated nonconvex minimization problem. Under suitable assumptions, this algorithm is shown to have better convergence properties than standard alternating minimization techniques. The objective function includes a smooth convex data fidelity term and nonsmooth convex regularization terms modeling prior information on the data and on ...

  11. Transverse Stress Fracture of the Proximal Patella (United States)

    Atsumi, Satoru; Arai, Yuji; Kato, Ko; Nishimura, Akinobu; Nakazora, Shigeto; Nakagawa, Shuji; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Sudo, Akihiro; Kubo, Toshikazu


    Abstract Among stress fractures associated with sports activities, patellar stress fracture is rare. Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella. We describe an extremely rare case of transverse stress fracture of proximal patella in a 9-year-old athlete. A 9-year old boy, who participated in sports (sprints and Kendo) presented with left knee pain without any external injury. In plain radiographs, a fracture line was observed in the proximal 1/3 of the left patella, and a patella stress fracture was diagnosed. For treatment, because 7 months of conservative therapy showed no improvement, internal fixation was carried out using Acutrak screws, and bone union was thus achieved. Three months after the operation, he was able to return to his previous level of athletic sports activity. Regarding the mechanism of onset, it is believed that the causes are longitudinal traction force and patellofemoral contact pressure. On the other hand, the contact region of the patella with the femur changes with the flexion angle of the knee. In the current case, the fracture occurred at a site where the patella was in contact with the femur at a flexion angle of >90°, so it is believed that it occurred as a clinical condition from being subjected to repeated longitudinal traction force and patellofemoral contact pressure at a flexion angle of >90°, during the sports activities of sprints and Kendo. The nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using Acutrak screws. PMID:26871789

  12. Isolated Proximal Tibiofibular Dislocation during Soccer

    Directory of Open Access Journals (Sweden)

    Casey Chiu


    Full Text Available Proximal tibiofibular dislocations are rarely encountered in the Emergency Department (ED. We present a case involving a man presenting to the ED with left knee pain after making a sharp left turn on the soccer field. His physical exam was only remarkable for tenderness over the lateral fibular head. His X-rays showed subtle abnormalities of the tibiofibular joint. The dislocation was reduced and the patient was discharged from the ED with orthopedic follow-up.

  13. Capacitive Proximity Sensor Has Longer Range (United States)

    Vranish, John M.


    Capacitive proximity sensor on robot arm detects nearby object via capacitive effect of object on frequency of oscillator. Sensing element part of oscillator circuit operating at about 20 kHz. Total capacitance between sensing element and ground constitutes tuning capacitance of oscillator. Sensor circuit includes shield driven by replica of alternating voltage applied to sensing element. Driven shield concentrates sensing electrostatic field in exterior region to enhance sensitivity to object. Sensitivity and dynamic range has corresponding 12-to-1 improvement.


    African Journals Online (AJOL)


    The proximate analysis (moisture, crude protein, crude fat, mineral ash and total carbohydrates) in the kernels and flour of African Bush Mango (. ) were investigated. The results revealed that the kernels contained moisture (2.5 g/100 g), crude protein (8.9 g/100 g), crude fat (68.4 g/100 g), mineral ash (2.3 g/100 g) and total ...

  15. [Proximity and breastfeeding at the maternity hospital]. (United States)

    Fradin-Charrier, Anne-Claire


    The establishment of breastfeeding, as well as its duration, are facilitated through the proximity of the mother with her new baby. However, in maternity hospitals, breastfeeding mothers very often leave their baby in the nursery at night time. A study carried out in 2014 in several maternity hospitals put forward suggestions and highlighted areas to improve in everyday practice. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Proximal Gastrojejunal Reconstruction after Pancreaticoduodenal Resection

    Directory of Open Access Journals (Sweden)

    M. Wayne


    Full Text Available Introduction. Reconstruction by proximal gastrojejunostomy, and distal biliary and pancreatic anastomoses is infrequently used after resection of the head of the pancreas because of fear of fistulas and cholangitis. Pancreaticoduodenectomy is being performed more frequently for cystic malignant and premalignant lesions. Because of this there is a need for endoscopic visualization and biopsy of the residual pancreatic duct, since multi-centricity is characteristic of some of these malignancies. Since endoscopic access of the bile duct and pancreatic duct is difficult and unsuccessful in 50–70% after B II or Roux Y reconstruction, we prospectively studied the merit and complications (early and late of proximal gastrojejunal (PGJ reconstruction after pancreaticoduodenal resection. Material and Methods. Thirty nine consecutive, non-radomized patients underwent pancreaticoduodenectomy and PGJ reconstruction over 14 mos. There were 21 males and 18 females. Results. 7 patients with IPMN have undergone repeat CT scanning for surveillance, with 3 requiring repeat EUS and ERCP. There were no technical difficulties accessing the pancreas or the pancreatic duct, supporting the PGJ reconstruction. Conclusion. Proximal gastrojejunal reconstruction following pancreaticoduodenal resection may be safely done with similar morbidity to traditional pancreaticojejunal reconstructions. PGJ reconstruction may be of greater value when direct visual access to the bile duct or pancreatic duct is necessary, and should be considered when doing resection for mucinous cysts or IPMN of the head of the pancreas.

  17. Bilateral, atraumatic, proximal tibiofibular joint instability. (United States)

    Morrison, Troy D; Shaer, James A; Little, Jill E


    Dislocation of the tibiofibular joint is rare and usually results from a traumatic event. Only 1 case of atraumatic proximal tibiofibular joint instability in a 14-year-old girl has been reported in the literature, however this condition might occur more frequently than once thought. A wide range of treatment options exist for tibiofibular dislocations. Currently, the first choice is a conservative approach, and when this fails, surgical means such as resection of the fibula head, arthrodesis, and reconstruction are considered. However, no consensus exists on the most effective treatment. This article reports a unique case of bilateral, atraumatic, proximal tibia and fibular joint instability involving a 30-year-old man with a 20-year history of pain and laxity in the right knee. The patient had no trauma to his knees; he reported 2 immediate family members with similar complaints, which suggests that this case is likely congenital. After conservative approaches proved to be ineffective, the patient underwent capsular reconstruction using free autologous gracilis tendon. At 6-month postoperative follow-up, the patient was pain free with no locking and instability. He then underwent surgery on the left knee. At 1-year follow-up after the second surgery, the patient had no symptoms or restrictions in mobility. We provide an alternative surgical approach to arthrodesis and resection for the treatment of chronic proximal tibiofibular instability. In the treatment of chronic tibiofibular instability, we believe that reconstruction of the tibiofibular joint is a safe and effective choice. Copyright 2011, SLACK Incorporated.

  18. Annexin A10 expression correlates with serrated pathway features in colorectal carcinoma with microsatellite instability. (United States)

    Kim, Jung Ho; Rhee, Ye-Young; Kim, Kyung-Ju; Cho, Nam-Yun; Lee, Hye Seung; Kang, Gyeong Hoon


    Annexin A10 (ANXA10) has recently been identified as a marker of sessile serrated adenomas/polyps of the colorectum. Although the serrated neoplasia pathway is thought to be involved in the majority of microsatellite instability-high (MSI-H) sporadic colorectal carcinomas (CRCs), the clinicopathological implications of ANXA10 expression in CRC are unknown. Here, we evaluated ANXA10 expression status in 168 MSI-H CRCs by immunohistochemistry. Among 168 MSI-H CRCs, nuclear staining for ANXA10 in tumor cells revealed 28 cases (17%) with ANXA10-positive (ANXA10+) tumors. Most of the ANXA10+ tumors were located in the proximal colon (96%, p < 0.001). The ANXA10+ phenotype in MSI-H CRC was significantly associated with female gender (68%, p = 0.016), CpG island methylator phenotype-high (CIMP-H) (68%, p < 0.001), MLH1 promoter hypermethylation (61%, p < 0.001), loss of MLH1 expression (82%, p = 0.019), and wild-type KRAS status (96%, p = 0.023). Survival analysis revealed no prognostic significance of ANXA10 expression in MSI-H CRC. In conclusion, ANXA10+ MSI-H colon carcinomas are characterized by serrated pathway features, including proximal location, female predominance, and high frequencies of CIMP-H status and MLH1 methylation. © 2014 APMIS. Published by John Wiley & Sons Ltd.

  19. Calibrating animal-borne proximity loggers. (United States)

    Rutz, Christian; Morrissey, Michael B; Burns, Zackory T; Burt, John; Otis, Brian; St Clair, James J H; James, Richard


    Growing interest in the structure and dynamics of animal social networks has stimulated efforts to develop automated tracking technologies that can reliably record encounters in free-ranging subjects. A particularly promising approach is the use of animal-attached 'proximity loggers', which collect data on the incidence, duration and proximity of spatial associations through inter-logger radio communication. While proximity logging is based on a straightforward physical principle - the attenuation of propagating radio waves with distance - calibrating systems for field deployment is challenging, since most study species roam across complex, heterogeneous environments.In this study, we calibrated a recently developed digital proximity-logging system ('Encounternet') for deployment on a wild population of New Caledonian crows Corvus moneduloides. Our principal objective was to establish a quantitative model that enables robust post hoc estimation of logger-to-logger (and, hence, crow-to-crow) distances from logger-recorded signal-strength values. To achieve an accurate description of the radio communication between crow-borne loggers, we conducted a calibration exercise that combines theoretical analyses, field experiments, statistical modelling, behavioural observations, and computer simulations.We show that, using signal-strength information only, it is possible to assign crow encounters reliably to predefined distance classes, enabling powerful analyses of social dynamics. For example, raw data sets from field-deployed loggers can be filtered at the analysis stage to include predominantly encounters where crows would have come to within a few metres of each other, and could therefore have socially learned new behaviours through direct observation. One of the main challenges for improving data classification further is the fact that crows - like most other study species - associate across a wide variety of habitats and behavioural contexts, with different signal

  20. Commercial Property Value and Proximity to Light Rail: A Hedonic Price Application


    Weinberger, Rachel R.


    When the public sector sponsors projects to promote general welfare, disproportionate benefits or disproportionate burdens often fall on individuals. In Santa Clara County, California, private property owners claimed a burden due to the existence of a light rail transit system (LRT). Looking at rental rates for commercial property this research tests several hedonic specifications to determine what effect, if any, the LRT has on proximate property values; it compares transit accessibility wit...

  1. Proximate chemical composition and fatty acid profiles of ...

    African Journals Online (AJOL)

    Proximate chemical composition and fatty acid profiles of Longissimus Proximate chemical composition and fatty acid profiles of Longissimus thoracis from pasture fed LHRH immunocastrated, castrated and intact Bos indicus bulls.

  2. Proximate Analysis and Total Lycopene Content of Some Tomato ...

    African Journals Online (AJOL)



    Jun 5, 2017 ... Standard analytical techniques were employed to determine the proximate composition and lycopene content of three tomato cultivars namely: ... Keywords: Antioxidant, lycopene content, proximate composition, tomato cultivars. INTRODUCTION ..... from oranges, tomatoes and carrots. African. Journal of ...

  3. A Regularized Algorithm for the Proximal Split Feasibility Problem

    Directory of Open Access Journals (Sweden)

    Zhangsong Yao


    Full Text Available The proximal split feasibility problem has been studied. A regularized method has been presented for solving the proximal split feasibility problem. Strong convergence theorem is given.

  4. The regional dimension of intergenerational proximity in the Netherlands

    NARCIS (Netherlands)

    van der Pers, Marieke; Mulder, Clara H.

    Previous research has shown the impact of individual characteristics on intergenerational proximity but has largely ignored the regional dimension of such proximity. In this paper, we examine the regional variation in intergenerational proximity in the Netherlands. We address this issue by

  5. Quality Assessment and Proximate Analysis of Amaranthus hybridus ...

    African Journals Online (AJOL)

    The aim of this research is to determine the quality and proximate composition of Amaranthus hybridus, Celosia argentea, and Talinum triangulare obtained from open markets in Benin City, Nigeria. Microbiological and proximate analysis were carried out using standard methods. Results of the proximate analysis revealed ...

  6. Proximal femur geometry in the adult Kenyan femur and its ...

    African Journals Online (AJOL)

    Background: Numerous orthopaedic procedures are carried out on the proximal femur. For optimal hip function, these procedures must restore the anatomy of the proximal femur to as near normal as possible. There are currently no local studies that have described in detail the normal anatomy of the proximal femur and its ...

  7. Minimally Invasive Fixation for Proximal Humeral Fracture: A Review on the use of T2 Proximal Humeral Nail

    Directory of Open Access Journals (Sweden)

    Sze-Ling Iris Ngai


    Discussion and conclusion: With the proper surgical technique high union rate, good functional recovery, and low complication rate can be achieved by using T2 Proximal Humeral Nail in managing traumatic proximal humeral fracture.

  8. Delayed homicides and the proximate cause. (United States)

    Lin, Peter; Gill, James R


    Delayed homicides result from complications of remote injuries inflicted by "the hands of another." The investigation of delayed homicides may be a challenge due to a number of factors including: failure to report the death to the proper authorities, lack of ready and adequate documentation of the original injury and circumstances, and jurisdictional differences between the places of injury and death. The certification of these deaths also requires the demonstration of a pathophysiologic link between the remote injury and death. In sorting through these issues, it is helpful to rely upon the definition of the proximate cause of death. Over a 2-year period in New York City, there were 1211 deaths certified as homicide of which 42 were due to injuries sustained greater than 1 year before death. The survival interval ranged from 1.3 to 43.2 years. The most common immediate causes of death were: infections (22), seizures (7), and intestinal obstructions/hernias (6). Common patterns of complications included infection following a gunshot wound of the spinal cord, seizure disorder due to blunt head trauma, and intestinal obstruction/hernia due to adhesions from an abdominal stab wound. Spinal cord injuries resulted in paraplegia in 14 instances and quadriplegia in 8. The mean survival interval for paraplegics was 20.3 years and 14.8 years for quadriplegics; infections were a frequent immediate cause of death in both groups, particularly infections due to chronic bladder catheterization. The definition of proximate cause originated with civil law cases and was later applied to death certification as the proximate cause of death. The gradual extinction of the "year and a day rule" for the limitation of bringing homicide charges in delayed deaths may result in more of these deaths going to trial. Medical examiners/coroners must be able to explain the reasoning behind these death certifications and maintain consistent standards for the certification of all delayed deaths due

  9. Laparoscopic proximal gastrectomy with oblique jejunogastrostomy. (United States)

    Tanaka, Kimitaka; Ebihara, Yuma; Kurashima, Yo; Nakanishi, Yoshitsugu; Asano, Toshimichi; Noji, Takehiro; Murakami, Soichi; Nakamura, Toru; Tsuchikawa, Takahiro; Okamura, Keisuke; Shichinohe, Toshiaki; Hirano, Satoshi


    Proximal early gastric cancer is a good indication for totally laparoscopic proximal gastrectomy (TLPG) with double-tract reconstruction (DTR). However, when most of the dietary intake passes through the escape route of the jejunum, the functional benefits of proximal gastrectomy might be similar to those after total gastrectomy. Our DTR procedure was improved for easy passage through the remnant stomach. The purposes of this study were to present a novel technique for intracorporeal DTR using linear staplers after TLPG and to investigate surgical outcomes. DTR was performed using linear staplers only. A side-to-side jejunogastrostomy with twisting of both the remnant stomach and the anal jejunum was performed for the purpose of passing meals through the remnant stomach (an oblique jejunogastrostomy technique). The ten patients who underwent TLPG with DTR from January 2011 to August 2016 in Hokkaido University Hospital were retrospectively reviewed. Their clinicopathological characteristics and surgical and postoperative outcomes were collected and analyzed. The median duration of operation was 285 (range 146-440) min. No patients required blood transfusions. The number of dissected lymph nodes was 32 (range 22-56). There were no intraoperative complications, and no cases were converted to open surgery. All the patients were pT1N0M0 stage IA. No anastomotic leakage or complications were detected. Postoperative gastrography after reconstruction showed that contrast medium flowed mainly to the remnant stomach. The average percentage body weight loss was 14.0 ± 7.1% at 10 months. The average percentage decrease in serum hemoglobin was 5.4 ± 10.4% at 12 months. This novel technique for intracorporeal DTR provided a considerable advantage by the passage of dietary intake to the remnant stomach after LPG.

  10. Bicarbonate secretion by rabbit proximal colon. (United States)

    Sullivan, S K; Smith, P L


    Stripped segments of proximal colon (1-6 cm distal to the ampulla caecalis coli) were studied in vitro in Ussing chambers under short-circuit conditions using the pH-stat technique. With glucose and HCO3-CO2 present in the serosal bathing solution only, proximal colon alkalinizes the luminal bathing solution at a rate of 2.1 +/- 0.2 mu eq X h-1 X cm-2 (n = 36). With HCO3-CO2 present in the luminal bathing solution alone, proximal colon does not significantly acidify or alkalinize the serosal bathing solution. Addition of glucose (10 mM) to the luminal bathing solution abolished luminal alkalinization. Removal of HCO3 and CO2 from the serosal bathing solution or replacement of O2 with N2 also abolished luminal alkalinization. Acetazolamide (0.1 mM) added to both bathing solutions did not alter the rate of luminal alkalinization. Ion-replacement studies revealed that the alkalinization process was highly dependent on the presence of Na in the bathing solutions and much less dependent on the presence of Cl. Furthermore, ouabain (0.1 mM) significantly reduced luminal alkalinization. As in rabbit ileum, serosal epinephrine (0.1 mM) did not alter luminal alkalinization but increased serosal alkalinization by a Na-dependent mechanism. These results suggest that luminal alkalinization results from a Na-dependent, active transcellular HCO3 transport process and that a Na-dependent HCO3 absorptive process is activated by adrenergic stimuli.

  11. [Angle-stable intramedullary nailing of proximal humerus fractures with the PHN (proximal humeral nail)]. (United States)

    Blum, Jochen; Hansen, Matthias; Rommens, Pol Maria


    Stable fixation of two- and three-part fractures of the proximal humerus through minimally invasive operative technique and rapid bone healing as well as restoration of original anatomy. Early functional training with the goal of restoration of former mobility and daily activities. Unstabile two- and three-part fractures of the proximal humerus (AO classification: 11-A2, 11-A3, 11-B1, 11-B2, 11-B3). Subcapital nonunion of the humerus. Pathologic fractures. Pediatric fractures of the proximal humerus. Fractures of the proximal humerus types 11-C2 und 11-C3 according to the AO classification. Active local infection, e.g., after former operation. Closed reduction. Anterior acromial incision, splitting of the deltoid muscle and the rotator cuff. Opening of the medullary canal with the awl. Nail introduction. Spiral blade introduction in cannulated technique through stab incision. Distal interlocking through aiming device, angle-stable blocking of nail and blade through end cap. Postoperative fixation in Gilchrist sling until 2nd postoperative day; then physiotherapy respecting fracture type and stability, local swelling, patient's age and compliance, and concomitant injuries. 151 proximal humeral fractures were treated with a proximal humeral nail (PHN). 108 patients could be followed up 1 year postoperatively. Significant complications were perforation of the articular surface through bolts or blades (n = 8), implant-related pain (n = 10), fragment dislocation (n = 2), nonunion (n = 2), humeral head necrosis (n = 3), and superficial infection (n = 1). 1 year after the operation, the Constant-Murley Score showed a median value of 75.3 in the injured shoulder and of 89.9 in the uninjured shoulder. The DASH (Disability of the Arm, Shoulder and Hand) Score was 5.9 preoperatively and 9.3 at 1 year postoperatively. The worst results regarding the Constant-Murley Score as well as the DASH Score were found in C-type fractures.

  12. Impacted valgus fractures of the proximal humerus

    Directory of Open Access Journals (Sweden)

    Fabiano Rebouças Ribeiro


    Full Text Available Impacted valgus fractures of the proximal humerus are considered to be a special type fracture, since impaction of the humeral head on the metaphysis with maintenance of the posteromedial periosteum improves the prognosis regarding occurrences of avascular necrosis. This characteristic can also facilitate the reduction maneuver and increase the consolidation rate of these fractures, even in more complex cases. The studies included were obtained by searching the Bireme, Medline, PubMed, Cochrane Library and Google Scholar databases for those published between 1991 and 2013. The objective of this study was to identify the most common definitions, classifications and treatment methods used for these fractures in the orthopedic medical literature.

  13. Management of posttraumatic proximal interphalangeal joint contracture. (United States)

    Houshian, Shirzad; Jing, Shan Shan; Chikkamuniyappa, Chandrasekar; Kazemian, Gholam Hussein; Emami-Moghaddam-Tehrani, Mohammad


    Chronic flexion contracture of the proximal interphalangeal (PIP) joint presents a common yet challenging problem to hand surgeons. Over the years, multiple treatment modalities have been described for this problem, producing limited results. Nonoperative treatment using serial casting and splints should be tried before attempting open surgical release, which should be done in selected patients. The use of external fixation for treating PIP contracture has been encouraging and can be a useful alterative. This review provides an update on the current management of PIP joint contractures and presents a flowchart of treatment to aid decision making. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  14. Proximal iliotibial band syndrome: case report

    Directory of Open Access Journals (Sweden)

    Guilherme Guadagnini Falotico


    Full Text Available OBJECTIVE: The overuse injuries in the hip joint occur commonly in sports practitioners and currently due to technical advances in diagnostic imaging, especially magnetic resonance imaging (MRI, are often misdiagnosed. Recently, a group of people were reported, all female, with pain and swelling in the pelvic region.T2-weighted MRI showed increased signal in the enthesis of the iliotibial band (ITB along the lower border of the iliac tubercle. We report a case of a 34 year old woman, non-professional runner, with pain at the iliac crest with no history of trauma and whose MRI was compatible with the proximal iliotibial band syndrome.

  15. Ontogeny of rabbit proximal tubule urea permeability (United States)



    Urea transport in the proximal tubule is passive and is dependent on the epithelial permeability. The present study examined the maturation of urea permeability (Purea) in in vitro perfused proximal convoluted tubules (PCT) and basolateral membrane vesicles (BLMV) from rabbit renal cortex. Urea transport was lower in neonatal than adult PCT at both 37 and 25°C. The PCT Purea was also lower in the neonates than the adults (37°C: 45.4 ± 10.8 vs. 88.5 ± 15.2 × 10−6 cm/s, P 0.05). The activation energy for PCT Purea was not different between the neonatal and adult groups. BLMV Purea was determined by measuring vesicle shrinkage, due to efflux of urea, using a stop-flow instrument. Neonatal BLMV Purea was not different from adult BLMV Purea at 37°C [1.14 ± 0.05 × 10−6 vs. 1.25 ± 0.05 × 10−6 cm/s; P = not significant (NS)] or 25°C (0.94 ± 0.06 vs. 1.05 ± 0.10 × 10−6 cm/s; P = NS). There was no effect of 250 μM phloretin, an inhibitor of the urea transporter, on Purea in either adult or neonatal BLMV. The activation energy for urea diffusion was also identical in the neonatal and adult BLMV. These findings in the BLMV are in contrast to the brush-border membrane vesicles (BBMV) where we have previously demonstrated that urea transport is lower in the neonate than the adult. Urea transport is lower in the neonatal proximal tubule than the adult. This is due to a lower rate of apical membrane urea transport, whereas basolateral urea transport is the same in neonates and adults. The lower Purea in neonatal proximal tubules may play a role in overall urea excretion and in developing and maintaining a high medullary urea concentration and thus in the ability to concentrate the urine during renal maturation. PMID:11353675

  16. Congenital anomalies and proximity to landfill sites.

    LENUS (Irish Health Repository)

    Boyle, E


    The occurrence of congenital anomalies in proximity to municipal landfill sites in the Eastern Region (counties Dublin, Kildare, Wicklow) was examined by small area (district electoral division), distance and clustering tendancies in relation to 83 landfills, five of which were major sites. The study included 2136 cases of congenital anomaly, 37,487 births and 1423 controls between 1986 and 1990. For the more populous areas of the region 50% of the population lived within 2-3 km of a landfill and within 4-5 km for more rural areas. In the area-level analysis, the standardised prevalence ratios, empirical and full Bayesian modelling, and Kulldorff\\'s spatial scan statistic found no association between the residential area of cases and location of landfills. In the case control analysis, the mean distance of cases and controls from the nearest landfill was similar. The odds ratios of cases compared to controls for increasing distances from all landfills and major landfills showed no significant difference from the baseline value of 1. The kernel and K methods showed no tendency of cases to cluster in relationship to landfills. In conclusion, congenital anomalies were not found to occur more commonly in proximity to municipal landfills.

  17. Scattering Effects in Proximity Effect Tunneling Spectroscopy. (United States)

    Gai, Wei

    PETS (Proximity Effect Tunneling Spectroscopy) technique has been applied to Niobium/Yttrium and Niobium/Lutetium bilayers. We have determined electron - phonon interaction parameter lambda_{rm e -ph} is 0.55 for Yttrium and 0.67 for Lutetium. Spin fluctuations parameter lambda_{ rm S} is 0.20 for Yttrium and 0.33 for Lutetium. We found that the large spin fluctuations in Yttrium and Lutetium has responsibility to the absence of superconductivity in them. Our results have given a reasonable explanation of high superconducting transition temperature in them under high pressure. The large reflection coefficient and strong diffuse scattering at Nb/Y and Nb/Lu interface has been discovered and it should have strong influence on the transport properties of metallic superlattices. From the modeling study of elastic scattering in proximity effect tunnel junctions, we have explained why some conventional made high {rm T_{C}} superconducting tunnel junctions give ideal like characteristics in the gap region but variable strength phonon structures in the phonon region.

  18. Proteomics of Primary Cilia by Proximity Labeling. (United States)

    Mick, David U; Rodrigues, Rachel B; Leib, Ryan D; Adams, Christopher M; Chien, Allis S; Gygi, Steven P; Nachury, Maxence V


    While cilia are recognized as important signaling organelles, the extent of ciliary functions remains unknown because of difficulties in cataloguing proteins from mammalian primary cilia. We present a method that readily captures rapid snapshots of the ciliary proteome by selectively biotinylating ciliary proteins using a cilia-targeted proximity labeling enzyme (cilia-APEX). Besides identifying known ciliary proteins, cilia-APEX uncovered several ciliary signaling molecules. The kinases PKA, AMPK, and LKB1 were validated as bona fide ciliary proteins and PKA was found to regulate Hedgehog signaling in primary cilia. Furthermore, proteomics profiling of Ift27/Bbs19 mutant cilia correctly detected BBSome accumulation inside Ift27(-/-) cilia and revealed that β-arrestin 2 and the viral receptor CAR are candidate cargoes of the BBSome. This work demonstrates that proximity labeling can be applied to proteomics of non-membrane-enclosed organelles and suggests that proteomics profiling of cilia will enable a rapid and powerful characterization of ciliopathies. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Empathy: Its ultimate and proximate bases. (United States)

    Preston, Stephanie D; de Waal, Frans B M


    There is disagreement in the literature about the exact nature of the phenomenon of empathy. There are emotional, cognitive, and conditioning views, applying in varying degrees across species. An adequate description of the ultimate and proximate mechanism can integrate these views. Proximately, the perception of an object's state activates the subject's corresponding representations, which in turn activate somatic and autonomic responses. This mechanism supports basic behaviors (e.g., alarm, social facilitation, vicariousness of emotions, mother-infant responsiveness, and the modeling of competitors and predators) that are crucial for the reproductive success of animals living in groups. The Perception-Action Model (PAM), together with an understanding of how representations change with experience, can explain the major empirical effects in the literature (similarity, familiarity, past experience, explicit teaching, and salience). It can also predict a variety of empathy disorders. The interaction between the PAM and prefrontal functioning can also explain different levels of empathy across species and age groups. This view can advance our evolutionary understanding of empathy beyond inclusive fitness and reciprocal altruism and can explain different levels of empathy across individuals, species, stages of development, and situations.

  20. Proximal femoral osteotomy in cerebral palsy. (United States)

    Tylkowski, C M; Rosenthal, R K; Simon, S R


    The purpose of this study was to examine the results of the proximal femoral osteotomy for the management of hip deformity in 32 children, aged 4 to 15 years. Twenty-two bilateral and ten unilateral procedures were performed. The indications for surgery were subluxation in 16, dislocation in two, and intoeing and femoral anteversion in 14. The average follow-up was two years and 11 months. CE angle of Wiberg, acetabular index and neck shaft angle were evaluated. The average time to regain preoperative ambulatory status was six months with intensive physical therapy. In osteotomies performed for subluxation, dislocation did not occur; roentgenographic indices showed variability in the degree of subluxation. Osteotomy performed in children older than 8 years of age produced no evidence of acetabular remodeling. THere was no recurrence with osteotomies for dislocation. In those patients with internal rotation gait, improvement resulted. Complications were few and minor. Hip dislocation in children with progressive subluxation, in spite of previous soft-tissue releases, is preventable by proximal femoral osteotomy. The inability of the roentgenographic indices to quantitate the increased stability indicates the procedure's major effect is to realign muscle forces about the hip. Treatment of the intoeing gait produced improvement of rotational deformity.

  1. Obesity and supermarket access: proximity or price? (United States)

    Drewnowski, Adam; Aggarwal, Anju; Hurvitz, Philip M; Monsivais, Pablo; Moudon, Anne V


    We examined whether physical proximity to supermarkets or supermarket price was more strongly associated with obesity risk. The Seattle Obesity Study (SOS) collected and geocoded data on home addresses and food shopping destinations for a representative sample of adult residents of King County, Washington. Supermarkets were stratified into 3 price levels based on average cost of the market basket. Sociodemographic and health data were obtained from a telephone survey. Modified Poisson regression was used to test the associations between obesity and supermarket variables. Only 1 in 7 respondents reported shopping at the nearest supermarket. The risk of obesity was not associated with street network distances between home and the nearest supermarket or the supermarket that SOS participants reported as their primary food source. The type of supermarket, by price, was found to be inversely and significantly associated with obesity rates, even after adjusting for individual-level sociodemographic and lifestyle variables, and proximity measures (adjusted relative risk=0.34; 95% confidence interval=0.19, 0.63) Improving physical access to supermarkets may be one strategy to deal with the obesity epidemic; improving economic access to healthy foods is another.

  2. Demonstration of automated proximity and docking technology (United States)

    Anderson, Robert L.; Tsugawa, Roy K.; Bryan, Thomas C.


    Automated spacecraft docking operations are being performed using a full scale motion based simulator and an optical sensor. This presentation will discuss the work in progress at TRW and MSFC facilities to study the problem of automated proximity and docking operations. The docking sensor used in the MSFC Optical Sensor and simulation runs are performed using the MSFC Flat Floor Facility. The control algorithms and six degrees of freedom (6DOF) simulation software were developed at TRW and integrated into the MSFC facility. Key issues being studied are the quantification of docking sensor requirements and operational constraints necessary to perform automated docking maneuvers, control algorithms capable of performing automated docking in the presence of sensitive and noisy sensor data, and sensor technologies for automated proximity and docking operations. As part of this study the MSFC sensor characteristics were analyzed and modeled so that off line simulation runs can be performed for control algorithm testing. Our goal is to develop and demonstrate full 6DOF docking capabilities with actual sensors on the MSFC motion based simulator. We present findings from actual docking simulation runs which show sensor and control loop performance as well as problem areas which require close attention. The evolution of various control algorithms using both phase plane and Clohessy-Wiltshire techniques are discussed. In addition, 6DOF target acquisition and control strategies are described.

  3. Pathological fractures of the proximal humerus treated with a proximal humeral locking plate and bone cement. (United States)

    Siegel, H J; Lopez-Ben, R; Mann, J P; Ponce, B A


    Bone loss secondary to primary or metastatic lesions of the proximal humerus remains a challenging surgical problem. Options include preservation of the joint with stabilisation using internal fixation or resection of the tumour with prosthetic replacement. Resection of the proximal humerus often includes the greater tuberosity and adjacent diaphysis, which may result in poor function secondary to loss of the rotator cuff and/or deltoid function. Preservation of the joint with internal fixation may reduce the time in hospital and peri-operative morbidity compared with joint replacement, and result in a better functional outcome. We included 32 patients with pathological fractures of the proximal humerus in this study. Functional and radiological assessments were performed. At a mean follow-up of 17.6 months (8 to 61) there was no radiological evidence of failure of fixation. The mean revised musculoskeletal Tumour Society functional score was 94.6% (86% to 99%). There was recurrent tumour requiring further surgery in four patients (12.5%). Of the 22 patients who were employed prior to presentation all returned to work without restrictions. The use of a locking plate combined with augmentation with cement extends the indications for salvage of the proximal humerus with good function in patients with pathological and impending pathological fractures.

  4. Metazoan promoters

    DEFF Research Database (Denmark)

    Lenhard, Boris; Sandelin, Albin Gustav; Carninci, Piero


    Promoters are crucial for gene regulation. They vary greatly in terms of associated regulatory elements, sequence motifs, the choice of transcription start sites and other features. Several technologies that harness next-generation sequencing have enabled recent advances in identifying promoters ...

  5. Health Promotion

    DEFF Research Database (Denmark)

    Povlsen, Lene; Borup, I.


    In 1953 when the Nordic School of Public Health was founded, the aim of public health programmes was disease prevention more than health promotion. This was not unusual, since at this time health usually was seen as the opposite of disease and illness. However, with the Ottawa Charter of 1986......, the World Health Organization made a crucial change to view health not as a goal in itself but as the means to a full life. In this way, health promotion became a first priority and fundamental action for the modern society. This insight eventually reached NHV and in 2002 - 50 years after the foundation...... - an associate professorship was established with a focus on health promotion. Nevertheless, the concept of health promotion had been integrated with or mentioned in courses run prior to the new post. Subsequently, a wide spectrum of courses in health promotion was introduced, such as Empowerment for Child...

  6. Digital camera resolution and proximal caries detection. (United States)

    Prapayasatok, S; Janhom, A; Verochana, K; Pramojanee, S


    To evaluate the diagnostic accuracy of proximal caries detection from digitized film images captured by a digital camera at different resolution settings. Twenty-five periapical radiographs of 50 premolar and 25 molar teeth were photographed using a digital camera, Sony Cyber-shot, DSC-S75 at three different resolution settings: 640 x 480, 1280 x 960 and 1600 x 1200. Seventy-five digital images were transferred to a computer, saved and opened using ACDSee software. In addition, a PowerPoint slide was made from each digital image. Five observers scored three groups of images (the films, the displayed 1:1 digital images on the ACDSee software, and the PowerPoint slides) for the existence of proximal caries using a 5-point confidence scale, and the depth of caries on a 4-point scale. Ground sections of the teeth were used as the gold standard. Az values under the receiver operating characteristic (ROC) curve of each group of images and at different resolutions were compared using the Friedman and Wilcoxon signed rank tests. Mean different values between the lesions' depth interpreted by the observers and that of the gold standard were analysed. Films showed the highest Az values. Only the 1280 x 960 images on the ACDSee software showed no significant difference of the Az value from the films (P=0.28). The digital images from three resolution settings on the PowerPoint slides showed no significant differences, either among each other or between them and the films. For caries depth, the 1280 x 960 images showed lower values of mean difference in enamel lesions compared with the other two resolution groups. This study showed that in order to digitize conventional films, it was not necessary to use the highest camera resolution setting to achieve high diagnostic accuracy for proximal caries detection. The 1280 x 960 resolution setting of the digital camera demonstrated comparable diagnostic accuracy with film and was adequate for digitizing radiographs for caries

  7. The non-operative resin treatment of proximal caries lesions. (United States)

    Ekstrand, Kim; Martignon, Stefania; Bakhshandeh, Azam; Ricketts, David N J


    Epidemiological data show that the prevalence of caries on proximal surfaces in need of operative treatment is very high around the world, both in the primary and the permanent dentition. This article presents two new treatment methods: proximal sealing and proximal infiltration. The indications are progressing proximal caries lesions, radiographically with a depth around the enamel-dentine junction. A small number of studies regarding the effect of sealing and infiltration on proximal caries versus the use of fluoride varnish, placebo treatment and flossing instructions have been carried out. About half of the studies disclose a not significant difference between test and control treatment. In the other half, the therapeutic effect is significant and corresponds to about 30% reduction in lesion progression. However, longitudinal studies of longer duration are lacking. Proximal sealing and proximal infiltration may have a place in the treatment of non-cavitated proximal lesions. Proximal caries is a problem in both primary and permanent dentitions. Proximal sealants or lesion infiltration are possible treatments.

  8. Rehabilitation and Prevention of Proximal Hamstring Tendinopathy. (United States)

    Beatty, Nicholas R; Félix, Ioonna; Hettler, Jessica; Moley, Peter J; Wyss, James F

    Proximal hamstring tendinopathy (PHT) comprises a small but significant portion of hamstring injuries in athletes, especially runners. PHT is a chronic condition that is clinically diagnosed but can be supported with imaging. The main presenting complaint is pain in the lower gluteal or ischial region that may or may not radiate along the hamstrings in the posterior thigh. There is little scientific evidence on which to base the rehabilitation management of PHT. Treatment is almost always conservative, with a focus on activity modification, addressing contributing biomechanical deficiencies, effective tendon loading including eccentric training, and ultrasound-guided interventional procedures which may facilitate rehabilitation. Surgery is limited to recalcitrant cases or those involving concomitant high-grade musculotendinous pathology. The keys to PHT management include early and accurate diagnosis, optimal rehabilitation to allow for a safe return to preinjury activity level, and preventative strategies to reduce risk of reinjury.

  9. DC Proximal Newton for Nonconvex Optimization Problems. (United States)

    Rakotomamonjy, Alain; Flamary, Rémi; Gasso, Gilles


    We introduce a novel algorithm for solving learning problems where both the loss function and the regularizer are nonconvex but belong to the class of difference of convex (DC) functions. Our contribution is a new general purpose proximal Newton algorithm that is able to deal with such a situation. The algorithm consists in obtaining a descent direction from an approximation of the loss function and then in performing a line search to ensure a sufficient descent. A theoretical analysis is provided showing that the iterates of the proposed algorithm admit as limit points stationary points of the DC objective function. Numerical experiments show that our approach is more efficient than the current state of the art for a problem with a convex loss function and a nonconvex regularizer. We have also illustrated the benefit of our algorithm in high-dimensional transductive learning problem where both the loss function and regularizers are nonconvex.

  10. Proximity Effects in Superconductor-Graphene Junctions (United States)

    Cuellar, Fabian A.; Perconte, David; Martin, Marie-Blandine; Dlubak, Bruno; Piquemail, Maelis; Bernard, Rozenn; Trastoy, Juan; Moreau-Luchaire, Constance; Seneor, Pierre; Villegas, Javier E.; Kidambi, Piran; Hofmann, Stephan; Robertson, John


    Superconducting proximity effects are of particular interest in graphene: because of its band structure, an unconventional (specular) Andreev reflection is expected. In this context, high-Tc superconductor-graphene junctions are especially attractive. In these, the size of the superconducting energy-gap may exceed the graphene doping inhomogeneities around the Dirac point, which should favor the observation of the specular Andreev reflection. Yet, the fabrication of high-Tc superconductor-graphene junctions is challenging: the usual growth and lithography processes in both materials are incompatible. We report here on a fabrication method that allow us to fabricate planar cuprate superconductor-graphene junctions, which we characterize via conductance spectroscopy. We analyze the features in the conductance spectra as a function of graphene doping, and discuss them in the framework of the Andreev reflection. Work supported by Labex Nanosaclay.

  11. Phonon engineering in proximity enhanced superconductor heterostructures. (United States)

    Tang, Yong-Chao; Kwon, Sangil; Mohebbi, Hamid R; Cory, David G; Miao, Guo-Xing


    In this research, we tailor the phonon density of states (DOS) in thin superconducting films to suppress quasiparticle losses. We examine a model system of a proximity-enhanced three-layered Al/Nb/Al heterostructure and show that the local quantized phonon spectrum of the ultrathin Al cladding layers in the heterostructure has a pronounced effect on the superconducting resonator's quality factors. Instead of a monotonic increase of quality factors with decreasing temperatures, we observe the quality factor reaches a maximum at 1.2 K in 5/50/5 nm Al/Nb/Al microstrip resonators, because of a quantized phonon ladder. The phonon DOS may be engineered to enhance the performance of quantum devices.

  12. Proximal and distal muscle fatigue differentially affect movement coordination. (United States)

    Cowley, Jeffrey C; Gates, Deanna H


    Muscle fatigue can cause people to change their movement patterns and these changes could contribute to acute or overuse injuries. However, these effects depend on which muscles are fatigued. The purpose of this study was to determine the differential effects of proximal and distal upper extremity muscle fatigue on repetitive movements. Fourteen subjects completed a repetitive ratcheting task before and after a fatigue protocol on separate days. The fatigue protocol either fatigued the proximal (shoulder flexor) or distal (finger flexor) muscles. Pre/Post changes in trunk, shoulder, elbow, and wrist kinematics were compared to determine how proximal and distal fatigue affected multi-joint movement patterns and variability. Proximal fatigue caused a significant increase (7°, p fatigue caused small but significant changes in trunk angles (2°, p fatigue protocols (p fatigue at either proximal or distal joints. The identified differences between proximal and distal muscle fatigue adaptations could facilitate risk assessment of occupational tasks.

  13. Proximal and distal muscle fatigue differentially affect movement coordination (United States)

    Cowley, Jeffrey C.


    Muscle fatigue can cause people to change their movement patterns and these changes could contribute to acute or overuse injuries. However, these effects depend on which muscles are fatigued. The purpose of this study was to determine the differential effects of proximal and distal upper extremity muscle fatigue on repetitive movements. Fourteen subjects completed a repetitive ratcheting task before and after a fatigue protocol on separate days. The fatigue protocol either fatigued the proximal (shoulder flexor) or distal (finger flexor) muscles. Pre/Post changes in trunk, shoulder, elbow, and wrist kinematics were compared to determine how proximal and distal fatigue affected multi-joint movement patterns and variability. Proximal fatigue caused a significant increase (7°, p fatigue caused small but significant changes in trunk angles (2°, p fatigue protocols (p fatigue at either proximal or distal joints. The identified differences between proximal and distal muscle fatigue adaptations could facilitate risk assessment of occupational tasks. PMID:28235005

  14. Proximate, mineral, and antinutrient compositions of indigenous Okra (Abelmoschus esculentus) pod accessions: implications for mineral bioavailability. (United States)

    Gemede, Habtamu Fekadu; Haki, Gulelat Desse; Beyene, Fekadu; Woldegiorgis, Ashagrie Z; Rakshit, Sudip Kumar


    The promotion and consumption of indigenous vegetables could help to mitigate food insecurity and alleviate malnutrition in developing countries. Nutrient and antinutrient compositions of eight accessions of Okra Pods were investigated. Molar ratios and mineral bioavailability of Okra pod accessions were also calculated and compared to the critical values to predict the implications for mineral bioavailability. Proximate and mineral composition of Okra pod accessions were determined using standard methods of Association of Official Analytical Chemists. The result of the study revealed that the proximate composition (g/100 g) in dry weight basis was significantly (P analysis showed that, except phytate, tannin, and oxalate contents of all the accessions were significantly (P associated with malnutrition in the country.

  15. Spatial Proximity and Intercompany Communication: Myths and Realities


    Aguilera, Anne; Lethiais, Virginie; Alain RALLET


    Spatial proximity is credited with numerous virtues in the economic literature. In particular, for a company to be located near other companies is seen as conducive to the development of business relations. Spatial proximity is also considered to contribute to the quality and efficiency of these relations by facilitating face-to-face meetings that foster the exchange of complex knowledge and, in particular, the emergence of innovation. This article explores the notion of spatial proximity in ...

  16. Diagnosis of Proximal Caries in Primary Molars with DIAGNOdent pen


    Ermler, Romy


    Proximal surfaces, together with fissures, are the areas where most primary caries occur. Due to the anatomy of the deciduous molars, proximal caries cannot be detected at an early stage in crowded teeth by simply using a mirror and probe. Therefore, additional methods to find early proximal caries have to be used. KaVo uses laser fluorescence to detect caries. Originally, the DIAGNOdent devices were able to detect only occlusal caries (56, 61, 62, 65, 66). New results are now also available ...

  17. Inexact proximal Newton methods for self-concordant functions

    DEFF Research Database (Denmark)

    Li, Jinchao; Andersen, Martin Skovgaard; Vandenberghe, Lieven


    with an application to L1-regularized covariance selection, in which prior constraints on the sparsity pattern of the inverse covariance matrix are imposed. In the numerical experiments the proximal Newton steps are computed by an accelerated proximal gradient method, and multifrontal algorithms for positive definite......We analyze the proximal Newton method for minimizing a sum of a self-concordant function and a convex function with an inexpensive proximal operator. We present new results on the global and local convergence of the method when inexact search directions are used. The method is illustrated...

  18. IGFBP3 Promoter Methylation in Colorectal Cancer: Relationship with Microsatellite Instability, CpG Island Methylator Phenotype, p53

    Directory of Open Access Journals (Sweden)

    Takako Kawasaki


    Full Text Available Insulin-like growth factor binding protein 3 (IGFBP3, which is induced by wild-type p53, regulates IGF and interacts with the TGF-β pathway. IGFBP3 promoter methylation may occur in colorectal cancer with or without the CpG island methylator phenotype (CIMP, which is associated with microsatellite instability (MSI and TGFBR2 mutation. We examined the relationship between IGFBP3 methylation, p53 expression, CIMP and MSI in 902 population-based colorectal cancers. Utilizing real-time PCR (MethyLight, we quantified promoter methylation in IGFBP3 and eight other CIMP-high-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1. IGFBP3 methylation was far more frequent in non-MSI-high CIMP-high tumors (85% = 35/41 than in MSI-high CIMPhigh (49% = 44/90, P < .0001, MSI-high non-CIMP-high (17% = 6/36, P < .0001, non-MSI-high non-CIMP-high tumors (22% = 152/680, P < .0001. Among CIMPhigh tumors, the inverse relationship between MSI and IGFBP3 methylation persisted in p53-negative tumors (P < .0001, but not in p53-positive tumors. IGFBP3 methylation was associated inversely with TGFBR2 mutation in MSI-high non-CIMP-high tumors (P = .02. In conclusion, IGFBP3 methylation is inversely associated with MSI in CIMP-high colorectal cancers, this relationship is limited to p53-negative tumors. Our data suggest complex relationship between global genomic/epigenomic phenomena (such as MSI/ CIMP, single molecular events (e.g., IGFBP3 methylation, TP53 mutation, TGFBR2 mutation, the related pathways.

  19. Promoter Hypermethylation Profiling Identifies Subtypes of Head and Neck Cancer with Distinct Viral, Environmental, Genetic and Survival Characteristics.

    Directory of Open Access Journals (Sweden)

    Javed Hussain Choudhury

    Full Text Available Epigenetic and genetic alteration plays a major role to the development of head and neck squamous cell carcinoma (HNSCC. Consumption of tobacco (smoking/chewing and human papilloma virus (HPV are also associated with an increase the risk of HNSCC. Promoter hypermethylation of the tumor suppression genes is related with transcriptional inactivation and loss of gene expression. We investigated epigenetic alteration (promoter methylation of tumor-related genes/loci in tumor tissues in the context of genetic alteration, viral infection, and tobacco exposure and survival status.The study included 116 tissue samples (71 tumor and 45 normal tissues from the Northeast Indian population. Methylation specific polymerase chain reaction (MSP was used to determine the methylation status of 10 tumor-related genes/loci (p16, DAPK, RASSF1, BRAC1, GSTP1, ECAD, MLH1, MINT1, MINT2 and MINT31. Polymorphisms of CYP1A1, GST (M1 & T1, XRCC1and XRCC2 genes were studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and multiplex-PCR respectively.Unsupervised hierarchical clustering analysis based on methylation pattern had identified two tumor clusters, which significantly differ by CpG island methylator phenotype (CIMP, tobacco, GSTM1, CYP1A1, HPV and survival status. Analyzing methylation of genes/loci individually, we have found significant higher methylation of DAPK, RASSF1, p16 and MINT31 genes (P = 0.031, 0.013, 0.031 and 0.015 respectively in HPV (+ cases compared to HPV (-. Furthermore, a CIMP-high and Cluster-1 characteristic was also associated with poor survival.Promoter methylation profiles reflecting a correlation with tobacco, HPV, survival status and genetic alteration and may act as a marker to determine subtypes and patient outcome in HNSCC.

  20. Imaging of rectus femoris proximal tendinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Pesquer, Lionel; Poussange, Nicolas; Meyer, Philippe; Dallaudiere, Benjamin; Feldis, Matthieu [Clinique du Sport de Bordeaux, Centre d' Imagerie Osteo-articulaire, Merignac (France); Sonnery-Cottet, Bertrand [Groupe Ramsay Generale de Sante - Hopital Prive Jean Mermoz, Centre Orthopedique Santy, Lyon (France); Graveleau, Nicolas [Clinique du Sport de Bordeaux, Centre de Chirurgie Orthopedique et Sportive, Merignac (France)


    The rectus femoris is the most commonly injured muscle of the anterior thigh among athletes, especially soccer players. Although the injury pattern of the muscle belly is well documented, less is known about the anatomy and specific lesions of the proximal tendons. For each head, three distinctive patterns may be encountered according to the location of the injury, which can be at the enthesis, within the tendon, or at the musculotendinous junction. In children, injuries correspond most commonly to avulsion of the anteroinferior iliac spine from the direct head and can lead to subspine impingement. Calcific tendinitis and traumatic tears may be encountered in adults. Recent studies have shown that traumatic injuries of the indirect head may be underdiagnosed and that injuries of both heads may have a surgical issue. Finally, in the case of tears, functional outcome and treatment may vary if the rupture involves one or both tendons and if the tear is partial or complete. Thus, it is mandatory for the radiologist to know the different ultrasound and magnetic resonance imaging (MRI) patterns of these lesions in order to provide accurate diagnosis and treatment. The purpose of this article is to recall the anatomy of the two heads of rectus femoris, describe a reliable method of assessment with ultrasound and MRI and know the main injury patterns, through our own experience and literature review. (orig.)

  1. Proximate industrial activity and psychological distress (United States)

    Downey, Liam; Jackson, James S.; Merrill, J. Bryce; Saint Onge, Jarron M.; Williams, David R.


    This paper examines the role that gender, occupational status, and family status play in moderating the effect of industrial activity on the psychological well-being of nearby residents. Using a unique spatial assessment of industrial activity and an environmental risk/social stressor framework in conjunction with individual-level data from the Detroit Area Study (DAS) and demographic data from the U.S. census, we find that residents of neighborhoods in close proximity to industrial activity report elevated levels of psychological distress compared to residents of neighborhoods removed from this type of activity. These influences are more pronounced among women but gender differences are also contingent upon occupational and family statuses. We show that specific combinations of work and family statuses make persons particularly vulnerable to the influence of this environmental stressor and women are two and a half times more likely than men to have these vulnerable statuses. This study makes an important contribution to the environmental health literature because it reminds researchers of the fundamental influence of social roles when examining the link between environmental risks and mental health. PMID:19444334

  2. [Ophthalmologists in the proximity of Adolf Hitler]. (United States)

    Rohrbach, J M


    Adolf Hitler met or at least knew about 5 ophthalmologists. The chair of ophthalmology in Berlin, Walther Löhlein, personally examined Hitler's eyes at least two times. The chair of ophthalmology in Breslau, Walter Dieter, developed "air raid protection spectacles" with the aid of high representatives of the NS-system and probably Adolf Hitler himself. Heinrich Wilhelm Kranz became rector of the universities of Giessen and Frankfurt/Main. He was known as a very strict advocate of the NS-race hygiene. Werner Zabel made plans for Hitler's diet and tried to interfere with Hitler's medical treatment. Finally, Hellmuth Unger was an influential representative of the medical press and a famous writer. Three of his novels with medical topics were made into a film which Hitler probably saw. Hitler had, so to say, a small "ophthalmological proximity" which, however, did not play a significant role for himself or the NS-state. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Proximity coupling in superconductor-graphene heterostructures. (United States)

    Lee, Gil-Ho; Lee, Hu-Jong


    This review discusses the electronic properties and the prospective research directions of superconductor-graphene heterostructures. The basic electronic properties of graphene are introduced to highlight the unique possibility of combining two seemingly unrelated physics, superconductivity and relativity. We then focus on graphene-based Josephson junctions, one of the most versatile superconducting quantum devices. The various theoretical methods that have been developed to describe graphene Josephson junctions are examined, together with their advantages and limitations, followed by a discussion on the advances in device fabrication and the relevant length scales. The phase-sensitive properties and phase-particle dynamics of graphene Josephson junctions are examined to provide an understanding of the underlying mechanisms of Josephson coupling via graphene. Thereafter, microscopic transport of correlated quasiparticles produced by Andreev reflections at superconducting interfaces and their phase-coherent behaviors are discussed. Quantum phase transitions studied with graphene as an electrostatically tunable two-dimensional platform are reviewed. The interplay between proximity-induced superconductivity and the quantum-Hall phase is discussed as a possible route to study topological superconductivity and non-Abelian physics. Finally, a brief summary on the prospective future research directions is given. © 2018 IOP Publishing Ltd.

  4. Semiconductor detectors with proximity signal readout

    Energy Technology Data Exchange (ETDEWEB)

    Asztalos, Stephen J. [XIA, LLC, Hayward, CA (United States)


    Semiconductor-based radiation detectors are routinely used for the detection, imaging, and spectroscopy of x-rays, gamma rays, and charged particles for applications in the areas of nuclear and medical physics, astrophysics, environmental remediation, nuclear nonproliferation, and homeland security. Detectors used for imaging and particle tracking are more complex in that they typically must also measure the location of the radiation interaction in addition to the deposited energy. In such detectors, the position measurement is often achieved by dividing or segmenting the electrodes into many strips or pixels and then reading out the signals from all of the electrode segments. Fine electrode segmentation is problematic for many of the standard semiconductor detector technologies. Clearly there is a need for a semiconductor-based radiation detector technology that can achieve fine position resolution while maintaining the excellent energy resolution intrinsic to semiconductor detectors, can be fabricated through simple processes, does not require complex electrical interconnections to the detector, and can reduce the number of required channels of readout electronics. Proximity electrode signal readout (PESR), in which the electrodes are not in physical contact with the detector surface, satisfies this need.

  5. Altruism by age and social proximity. (United States)

    Long, Mark C; Krause, Eleanor


    This study evaluates the extent to which an individual's stated altruistic sentiments can be influenced by context-most importantly, by the age and social proximity of the other person and by the nature of what is being sacrificed. We measure willingness to sacrifice own health for another person's health and willingness to sacrifice own wealth for another person's wealth. To evaluate these sentiments, two surveys were administered to representative samples of Americans which contained hypothetical scenarios with context randomly assigned; the first survey posed a dictator game question and the second survey was designed to elicit marginal rates of substitution between own and other's health/wealth. As expected, we find less altruism towards those who are more socially distant (e.g., strangers relative to family). We find individuals are more health altruistic towards young children and more wealth altruistic towards adults, and health altruism tends to be lowest for survey respondents near retirement age. We find no relationship between levels of altruism and the distance between the respondent's state of birth and state of current residence. These findings improve society's understanding of situational altruism and kinship and reciprocity as motivations for altruism, and they have practical implications concerning the economic valuation of human lives used to guide public policy-making.

  6. Proximal spinal muscular atrophy: current orthopedic perspective

    Directory of Open Access Journals (Sweden)

    Haaker G


    Full Text Available Gerrit Haaker, Albert Fujak Department of Orthopaedic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Abstract: Spinal muscular atrophy (SMA is a hereditary neuromuscular disease of lower motor neurons that is caused by a defective "survival motor neuron" (SMN protein that is mainly associated with proximal progressive muscle weakness and atrophy. Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. Active research for possible treatment options has become possible since the disease-causing gene defect was identified in 1995. Nevertheless, a causal therapy is not available at present, and therapeutic management of SMA remains challenging; the prolonged survival is increasing, especially orthopedic, respiratory and nutritive problems. This review focuses on orthopedic management of the disease, with discussion of key aspects that include scoliosis, muscular contractures, hip joint disorders, fractures, technical devices, and a comparative approach of conservative and surgical treatment. Also emphasized are associated complications including respiratory involvement, perioperative care and anesthesia, nutrition problems, and rehabilitation. The SMA disease course can be greatly improved with adequate therapy with established orthopedic procedures in a multidisciplinary therapeutic approach. Keywords: spinal muscular atrophy, scoliosis, contractures, fractures, lung function, treatment, rehabilitation, surgery, ventilation, nutrition, perioperative management

  7. Optical proximity correction with principal component regression (United States)

    Gao, Peiran; Gu, Allan; Zakhor, Avideh


    An important step in today's Integrated Circuit (IC) manufacturing is optical proximity correction (OPC). In model based OPC, masks are systematically modified to compensate for the non-ideal optical and process effects of optical lithography system. The polygons in the layout are fragmented, and simulations are performed to determine the image intensity pattern on the wafer. Then the mask is perturbed by moving the fragments to match the desired wafer pattern. This iterative process continues until the pattern on the wafer matches the desired one. Although OPC increases the fidelity of pattern transfer to the wafer, it is quite CPU intensive; OPC for modern IC designs can take days to complete on computer clusters with thousands of CPU. In this paper, techniques from statistical machine learning are used to predict the fragment movements. The goal is to reduce the number of iterations required in model based OPC by using a fast and efficient solution as the initial guess to model based OPC. To determine the best model, we train and evaluate several principal component regression models based on prediction error. Experimental results show that fragment movement predictions via regression model significantly decrease the number of iterations required in model based OPC.

  8. Altruism by age and social proximity.

    Directory of Open Access Journals (Sweden)

    Mark C Long

    Full Text Available This study evaluates the extent to which an individual's stated altruistic sentiments can be influenced by context-most importantly, by the age and social proximity of the other person and by the nature of what is being sacrificed. We measure willingness to sacrifice own health for another person's health and willingness to sacrifice own wealth for another person's wealth. To evaluate these sentiments, two surveys were administered to representative samples of Americans which contained hypothetical scenarios with context randomly assigned; the first survey posed a dictator game question and the second survey was designed to elicit marginal rates of substitution between own and other's health/wealth. As expected, we find less altruism towards those who are more socially distant (e.g., strangers relative to family. We find individuals are more health altruistic towards young children and more wealth altruistic towards adults, and health altruism tends to be lowest for survey respondents near retirement age. We find no relationship between levels of altruism and the distance between the respondent's state of birth and state of current residence. These findings improve society's understanding of situational altruism and kinship and reciprocity as motivations for altruism, and they have practical implications concerning the economic valuation of human lives used to guide public policy-making.

  9. Altruism by age and social proximity (United States)


    This study evaluates the extent to which an individual’s stated altruistic sentiments can be influenced by context–most importantly, by the age and social proximity of the other person and by the nature of what is being sacrificed. We measure willingness to sacrifice own health for another person’s health and willingness to sacrifice own wealth for another person’s wealth. To evaluate these sentiments, two surveys were administered to representative samples of Americans which contained hypothetical scenarios with context randomly assigned; the first survey posed a dictator game question and the second survey was designed to elicit marginal rates of substitution between own and other’s health/wealth. As expected, we find less altruism towards those who are more socially distant (e.g., strangers relative to family). We find individuals are more health altruistic towards young children and more wealth altruistic towards adults, and health altruism tends to be lowest for survey respondents near retirement age. We find no relationship between levels of altruism and the distance between the respondent’s state of birth and state of current residence. These findings improve society’s understanding of situational altruism and kinship and reciprocity as motivations for altruism, and they have practical implications concerning the economic valuation of human lives used to guide public policy-making. PMID:28837557

  10. Menin and JunD regulate gastrin gene expression through proximal DNA elements (United States)

    Mensah-Osman, Edith J.; Veniaminova, Natalia A.


    Mutations in the MEN1 gene correlate with multiple endocrine neoplasia I (MEN1). Gastrinomas are the most malignant of the neuroendocrine tumors associated with MEN1. Because menin and JunD proteins interact, we examined whether JunD binds to and regulates the gastrin gene promoter. Both menin and JunD are ubiquitous nuclear proteins that we showed colocalize in the gastrin-expressing G cells of the mouse antrum. Transfection with a JunD expression vector alone induced endogenous gastrin mRNA in AGS human gastric cells, and the induction was blocked by menin overexpression. We mapped repression by menin to both a nonconsensus AP-1 site and proximal GC-rich elements within the human gastrin promoter. Chromatin immunoprecipitation assays, EMSAs, and DNA affinity precipitation assays documented that JunD and Sp1 proteins bind these two elements and are both targets for menin regulation. Consistent with menin forming a complex with histone deacetylases, we found that repression of gastrin gene expression by menin was reversed by trichostatin A. In conclusion, proximal DNA elements within the human gastrin gene promoter mediate interactions between JunD, which induces gastrin gene expression and menin, which suppresses JunD-mediated activation. PMID:21852362

  11. On the existence of best proximity points for generalized contractions

    Directory of Open Access Journals (Sweden)

    V. Vetrivel


    Full Text Available In this article we establish the existence of a unique best proximity point for some generalized non self contractions on a metric space in a simpler way using a geometric result. Our results generalize some recent best proximity point theorems and several fixed point theorems proved by various authors.

  12. Phytochemical, Proximate and Toxicity Studies of Aqueous Extract of ...

    African Journals Online (AJOL)

    Phytochemical, Proximate and Toxicity Studies of Aqueous Extract of Crinum ornatum (Toad's Onion) ... The results indicate that, the bulbs can be considered as a spice that could serve as potential sources of flavouring agent with medicinal benefits. Keywords: Crinum ornatum, Phytochemical, Proximate, Toxicity ...

  13. Proximity and inter-organizational collaboration: a literature review

    NARCIS (Netherlands)

    Knoben, J.; Oerlemans, L.A.G.


    The proximity concept is used in many different ways in the literature. These dimensions of proximity are, however, defined and measured in many different (sometimes even contradictory) ways, show large amounts of overlap, and often are under- or over-specified. The goal of this paper is to specify

  14. Proximate composition and levels of some toxicants in four ...

    African Journals Online (AJOL)

    Proximate composition and levels of some toxicants (anti-nutrients) in four commonly consumed spices were investigated. The spices were garlic (Allium sativum), ginger (Zingiber officinale), onion (Allium cepa var. cepa), and Piper guineense seeds (Ashanti pepper). Proximate analyses showed the spices to contain (on ...

  15. Proximal and distal muscle fatigue differentially affect movement coordination.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Cowley

    Full Text Available Muscle fatigue can cause people to change their movement patterns and these changes could contribute to acute or overuse injuries. However, these effects depend on which muscles are fatigued. The purpose of this study was to determine the differential effects of proximal and distal upper extremity muscle fatigue on repetitive movements. Fourteen subjects completed a repetitive ratcheting task before and after a fatigue protocol on separate days. The fatigue protocol either fatigued the proximal (shoulder flexor or distal (finger flexor muscles. Pre/Post changes in trunk, shoulder, elbow, and wrist kinematics were compared to determine how proximal and distal fatigue affected multi-joint movement patterns and variability. Proximal fatigue caused a significant increase (7°, p < 0.005 in trunk lean and velocity, reduced humeral elevation (11°, p < 0.005, and increased elbow flexion (4°, p < 0.01. In contrast, distal fatigue caused small but significant changes in trunk angles (2°, p < 0.05, increased velocity of wrench movement relative to the hand (17°/s, p < 0.001, and earlier wrist extension (4%, p < 0.005. Movement variability increased at proximal joints but not distal joints after both fatigue protocols (p < 0.05. Varying movements at proximal joints may help people adapt to fatigue at either proximal or distal joints. The identified differences between proximal and distal muscle fatigue adaptations could facilitate risk assessment of occupational tasks.

  16. Properties of Sn-Ag proximity effect bridges

    Energy Technology Data Exchange (ETDEWEB)

    Fan Hongchang; Yu Zheng


    We have measured the I-V characteristics, I/sub c/(t) and T/sub c/ of Sn-Ag proximity effect bridges, obtaining some interesting results. We have also analyzed and tried to explain the results in terms of phenomenological theories, believing that microbridge theories of Skocpol, Beasley and Tinkham (SBT) also apply to our proximity effect bridges.

  17. Determination of Proximate Composition and Amino Acid Profile of ...

    African Journals Online (AJOL)

    The proximate composition and amino acid profile of the seed of 30 Nigerian sesame genotypes were determined based on the standard methods of the Association of Official Analytical Chemists (AOAC) and the Sequential Multi- sample amino acid Analyzer (TSM). Proximate analysis showed that sesame seed contained ...

  18. Management of proximal interphalangeal joint dislocations in athletes. (United States)

    Bindra, Randy R; Foster, Brian J


    Proximal interphalangeal joint dislocations are common athletic injuries. In dislocations and fracture dislocations, the most important treatment principle is congruent joint reduction and maintenance of stability. This article reviews the relevant anatomy, injury characteristics, and treatment options for proximal interphalangeal joint dislocations and fracture dislocations. Treatment methods discussed include closed reduction, percutaneous fixation, and open reduction.

  19. Water Balance and Proximate Composition in Cowpea ( vigna ...

    African Journals Online (AJOL)

    Studying the water balance and proximate composition in plants subjected to these stresses compared the influence of drought and flooding on cowpea seedlings. In drought plants the leaf water potential, its components and the proximate composition were markedly reduced by the end of the experimental period.

  20. Cast index in predicting outcome of proximal pediatric forearm fractures

    Directory of Open Access Journals (Sweden)

    Hassaan Qaiser Sheikh


    Conclusion: Cast index is useful in predicting redisplacement of manipulated distal forearm fractures. We found that in proximal half forearm fractures it is difficult to achieve a CI of <0.8, but increased CI does not predict loss of position in these fractures. We therefore discourage the use of CI in proximal half forearm fractures.

  1. Proximate composition and mineral contents of Pebbly fish, Alestes ...

    African Journals Online (AJOL)


    The objective of this study was to determine the proximate composition and mineral contents of A. ... and also develop suitable processing method. This study determined the proximate composition and mineral contents of A. baremoze fillets based on fish size. Materials and .... moisture contents can vary with sex of the fish ...

  2. proximal femur geometry in the adult kenyan femur and its ...

    African Journals Online (AJOL)

    implications considering that the implants used to treat fractures in the proximal femur would usually traverse the neck and lodge in the femoral head. A very narrow neck may not allow adequate implant placement especially for those implants that employ two proximal locking screws. This has been shown, in a study by ...

  3. Spontaneous Healing of a Pediatric Scaphoid Proximal Pole Fracture Nonunion. (United States)

    Rupani, Neal; Riley, Nicholas; McNab, Ian


    Background  Scaphoid fractures in the pediatric population are rare. The majority of nondisplaced fractures tend to unite; however, there is an increased risk of nonunion in proximal pole fractures. Limited evidence exists in their outcomes, owing to the scarcity of the fracture pattern. Case Description  A 13-year-old boy who presented late after developing a traumatic proximal pole scaphoid fracture developed nonunion. He was treated conservatively owing to it being asymptomatic and developed union at 18 months. Literature Review  No previous case of proximal pole pediatric scaphoid fractures with established nonunion that has developed union with conservative management has been described. Clinical Relevance  The authors highlight a unique case of an established proximal pole scaphoid nonunion in a child progressing to union with nonoperative intervention. Owing to its rarity and difficulty in obtaining research, we recommend consideration of nonoperative management of asymptomatic nondisplaced proximal pole fractures in children.

  4. Nanocrystal Bioassembly: Asymmetry, Proximity, and Enzymatic Manipulation

    Energy Technology Data Exchange (ETDEWEB)

    Claridge, Shelley A. [Univ. of California, Berkeley, CA (United States)


    Research at the interface between biomolecules and inorganic nanocrystals has resulted in a great number of new discoveries. In part this arises from the synergistic duality of the system: biomolecules may act as self-assembly agents for organizing inorganic nanocrystals into functional materials; alternatively, nanocrystals may act as microscopic or spectroscopic labels for elucidating the behavior of complex biomolecular systems. However, success in either of these functions relies heavily uponthe ability to control the conjugation and assembly processes.In the work presented here, we first design a branched DNA scaffold which allows hybridization of DNA-nanocrystal monoconjugates to form discrete assemblies. Importantly, the asymmetry of the branched scaffold allows the formation of asymmetric2assemblies of nanocrystals. In the context of a self-assembled device, this can be considered a step toward the ability to engineer functionally distinct inputs and outputs.Next we develop an anion-exchange high performance liquid chromatography purification method which allows large gold nanocrystals attached to single strands of very short DNA to be purified. When two such complementary conjugates are hybridized, the large nanocrystals are brought into close proximity, allowing their plasmon resonances to couple. Such plasmon-coupled constructs are of interest both as optical interconnects for nanoscale devices and as `plasmon ruler? biomolecular probes.We then present an enzymatic ligation strategy for creating multi-nanoparticle building blocks for self-assembly. In constructing a nanoscale device, such a strategy would allow pre-assembly and purification of components; these constructs can also act as multi-label probes of single-stranded DNA conformational dynamics. Finally we demonstrate a simple proof-of-concept of a nanoparticle analog of the polymerase chain reaction.

  5. Translational Imaging Spectroscopy for Proximal Sensing. (United States)

    Rogass, Christian; Koerting, Friederike M; Mielke, Christian; Brell, Maximilian; Boesche, Nina K; Bade, Maria; Hohmann, Christian


    Proximal sensing as the near field counterpart of remote sensing offers a broad variety of applications. Imaging spectroscopy in general and translational laboratory imaging spectroscopy in particular can be utilized for a variety of different research topics. Geoscientific applications require a precise pre-processing of hyperspectral data cubes to retrieve at-surface reflectance in order to conduct spectral feature-based comparison of unknown sample spectra to known library spectra. A new pre-processing chain called GeoMAP-Trans for at-surface reflectance retrieval is proposed here as an analogue to other algorithms published by the team of authors. It consists of a radiometric, a geometric and a spectral module. Each module consists of several processing steps that are described in detail. The processing chain was adapted to the broadly used HySPEX VNIR/SWIR imaging spectrometer system and tested using geological mineral samples. The performance was subjectively and objectively evaluated using standard artificial image quality metrics and comparative measurements of mineral and Lambertian diffuser standards with standard field and laboratory spectrometers. The proposed algorithm provides highly qualitative results, offers broad applicability through its generic design and might be the first one of its kind to be published. A high radiometric accuracy is achieved by the incorporation of the Reduction of Miscalibration Effects (ROME) framework. The geometric accuracy is higher than 1 μpixel. The critical spectral accuracy was relatively estimated by comparing spectra of standard field spectrometers to those from HySPEX for a Lambertian diffuser. The achieved spectral accuracy is better than 0.02% for the full spectrum and better than 98% for the absorption features. It was empirically shown that point and imaging spectrometers provide different results for non-Lambertian samples due to their different sensing principles, adjacency scattering impacts on the signal

  6. Observer differentiation of proximal enamel mechanical defects versus natural proximal dental caries with computed dental radiography. (United States)

    Kang, B C; Farman, A G; Scarfe, W C; Goldsmith, L J


    Various models have been used to study the accuracy of imaging systems for detection of dental caries. This study compares the ability of dentists to detect mechanically created defects versus natural dental caries cavitations on the proximal surfaces of extracted teeth with Computed Dental Radiography (Schick Industries, Long Island City, N.Y.). Detection rates are investigated according to lesion depth to permit comparisons to be made between studies in the literature with other mechanical defects or natural caries models. Discrimination of natural caries versus artificial defects with Computed Dental Radiography is also compared with a previous report that used standard dental film. Fifty-two extracted molar and premolar teeth were mounted into representative sets of maxillary and mandibular posterior arches for bite-wing radiography. There were 16 proximal surfaces with natural caries and 28 proximal surfaces with mechanical defects. An optical bench was used to ensure constant beam geometry. A 1.8 cm acrylic soft tissue equivalent attenuator was placed in front of the receptor. Thirty dentists acted independently as observers to differentiate between sound proximal tooth surfaces, natural dental caries, and mechanical defects. Evaluation of intra- and interobserver variability was made with use of the kappa statistic. The Zelen test of odds ratios was used to test for homogeneity, and the Mantel-Haenszel analysis plus stratified logistic regression were used for inference about the common odds ratio. Significance was set at p detection was 74% for mechanical defects and 67% for natural caries. The odds of detecting a mechanical defect were 1.40 times the odds of finding natural dental caries cavitation of the same depth. Lesion depth did influence the probability of correctly identifying the presence of a lesion; the odds of identifying cavitation increased 1.41 times with every 0.1 mm increase in lesion depth. Correct designation of lesion type was 1.42 times

  7. Health promotion is peace promotion. (United States)

    Middleton, J D


    This paper discusses the effects of the arms race on health, in the absence of nuclear war. High levels of military expenditure are inextricably linked to unemployment, poverty, starvation and ill health. Alternatives to the escalation of military expenditure are possible; health promotion can be involved in wider public health initiatives towards economic and industrial conversion to peaceful, socially useful production. The interests of the health and scientific communities have traditionally transcended narrow chauvinism and nationalism. World Health Organization activities such as work towards primary health care and the Expanded Programme on Immunization actively involve international co-operation, demystify potential enemies and promote health and peace.

  8. Numerical Optimization of the Position in Femoral Head of Proximal Locking Screws of Proximal Femoral Nail System; Biomechanical Study. (United States)

    Konya, Mehmet Nuri; Verim, Özgür


    Proximal femoral fracture rates are increasing due to osteoporosis and traffic accidents. Proximal femoral nails are routinely used in the treatment of these fractures in the proximal femur. To compare various combinations and to determine the ideal proximal lag screw position in pertrochanteric fractures (Arbeitsgemeinschaft für Osteosynthesefragen classification 31-A1) of the femur by using optimized finite element analysis. Biomechanical study. Computed tomography images of patients' right femurs were processed with Mimics. Afterwards a solid femur model was created with SolidWorks 2015 and transferred to ANSYS Workbench 16.0 for response surface optimization analysis which was carried out according to anterior-posterior (-10°0) and posterior-anterior directions of the femur neck significantly increased these stresses. The most suitable position of the proximal lag screw was confirmed as the middle of the femoral neck by using optimized finite element analysis.

  9. Proximal-to-distal sequencing in vertical jumping with and without arm swing. (United States)

    Chiu, Loren Z F; Bryanton, Megan A; Moolyk, Amy N


    Vertical jumping performance is dependent on muscle strength and motor skill. An understanding of motor skill strategies and their influence on jumping mechanics provides insight into how to improve performance. This study aimed to determine whether kinematic sequencing strategy influenced jump height, the effect of sequencing on jumping mechanics, and whether arm swing influences sequencing strategy. Women volleyball players (n = 16) performed vertical jumps with and without arm swing on force platforms while recorded with a 6-camera motion capture system. Sequencing strategy was determined as the relative time delay between pelvis and knee extension. A long time delay indicated a proximal-to-distal strategy, whereas no time delay represented a simultaneous strategy. Longer relative time delay was correlated with higher jump height in jumps with (r = 0.82, p jump height were associated with greater hip extensor and ankle plantar flexor net joint moments (NJM), and greater ratio of concentric to eccentric knee extensor NJM (p ≤ 0.05). Longer relative time delay and higher jump height were correlated with greater thigh and leg angular accelerations (p ≤ 0.05). These kinetic and kinematic variables, along with relative time delay and jump height were greater in jumps with arm swing than without (p ≤ 0.05), indicating arm swing promotes use of a proximal-to-distal strategy. Use of a proximal-to-distal strategy is associated with greater NJM and segment accelerations, which may contribute to better vertical jump performance.

  10. Instrument access device for instrument access system, has connector member connecting proximal member with instrument seals, where proximal member and connector member are configured to retain proximal end of retractor member


    Bonadio, Frank; Vaugh, Trevor; McManus, Ronan; MacNally, Shane


    The device (203) has instrument seals sealingly arranged in a body of a patient, and a distal anchoring member located in a wound interior. A retractor member is proximally extended from a distal anchoring member to retract sides of a wound opening. A proximal member is adopted for locating an external part of the wound opening. A connector member connects the proximal member with the instrument seals. The proximal member and the connector member are configured to retain a proximal end of the...

  11. Effect of age on proximal esophageal response to swallowing

    Directory of Open Access Journals (Sweden)

    Roberto Oliveira Dantas


    Full Text Available CONTEXT: It has been demonstrated that the ageing process affects esophageal motility. OBJECTIVES: To evaluate the effect of the age on the proximal esophageal response to wet swallows. METHOD: We measured the proximal esophageal response to swallows of a 5 mL bolus of water in 69 healthy volunteers, 20 of them aged 18-30 years (group I, 27 aged 31-50 years (group II, and 22 aged 51-74 years (group III. We used the manometric method with continuous perfusion. The proximal esophageal contractions were recorded 5 cm from a pharyngeal recording site located 1 cm above the upper esophageal sphincter. The time between the onset of the pharyngeal and of the proximal esophageal recording (pharyngeal-esophageal time and the amplitude, duration and area under the curve of the proximal esophageal contraction were measured. RESULTS: The pharyngeal-esophageal time was shorter in group I subjects than in group II and III subjects (P<0.05. The duration of proximal esophageal contractions was longer in group I than in groups II and III (P<0.001. There was no differences between groups in the amplitude or area under the curve of contractions. There were no differences between groups II and III for any of the measurements. CONCLUSION: We conclude that the age may affects the response of the proximal esophagus to wet swallows.

  12. Dual pathology proximal median nerve compression of the forearm.

    LENUS (Irish Health Repository)

    Murphy, Siun M


    We report an unusual case of synchronous pathology in the forearm- the coexistence of a large lipoma of the median nerve together with an osteochondroma of the proximal ulna, giving rise to a dual proximal median nerve compression. Proximal median nerve compression neuropathies in the forearm are uncommon compared to the prevalence of distal compression neuropathies (eg Carpal Tunnel Syndrome). Both neural fibrolipomas (Refs. 1,2) and osteochondromas of the proximal ulna (Ref. 3) in isolation are rare but well documented. Unlike that of a distal compression, a proximal compression of the median nerve will often have a definite cause. Neural fibrolipoma, also called fibrolipomatous hamartoma are rare, slow-growing, benign tumours of peripheral nerves, most often occurring in the median nerve of younger patients. To our knowledge, this is the first report of such dual pathology in the same forearm, giving rise to a severe proximal compression of the median nerve. In this case, the nerve was being pushed anteriorly by the osteochondroma, and was being compressed from within by the intraneural lipoma. This unusual case highlights the advantage of preoperative imaging as part of the workup of proximal median nerve compression.

  13. Digital contrast subtraction radiography for proximal caries diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Byung Cheol; Yoon, Suk Ja [Department of Dental Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of)


    To determine whether subtraction images utilizing contrast media can improve the diagnostic performance of proximal caries diagnosis compared to conventional periapical radiographic images. Thirty-six teeth with 57 proximal surfaces were radiographied using a size no.2 RVG-ui sensor (Trophy Radiology, Marne-la-Vallee, France). The teeth immersed in water-soluble contrast media and subtraction images were taken. Each tooth was then sectioned for histologic examination. The digital radiographic images and subtraction images were examined and interpreted by three dentists for proximal caries. The results of the proximal caries diagnosis were then verified with the results of the histologic examination. The proximal caries sensitivity using digital subtraction radiography was significantly higher than simply examining a single digital radiograph. The sensitivity of the proximal dentinal carious lesion when analyzed with the subtraction radiograph and the radiograph together was higher than with the subtraction radiograph or the radiograph alone. The use of subtraction radiography with contrast media may be useful for detecting proximal dentinal carious lesions.

  14. RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation

    NARCIS (Netherlands)

    Yan, Helen H N; Lai, Jeffrey C W; Ho, Siu Lun; Leung, Wai Keung; Law, Wai Lun; Lee, Janet F Y; Chan, Anthony K W; Tsui, Wai Yin; Chan, Annie S Y; Lee, Bernard C H; Yue, Sarah S K; Man, Alice H Y; Clevers, Hans; Yuen, Siu Tsan; Leung, Suet Yi


    OBJECTIVE: Serrated polyps (hyperplastic polyps, sessile or traditional serrated adenomas), which can arise in a sporadic or polyposis setting, predispose to colorectal cancer (CRC), especially those with microsatellite instability (MSI) due to MLH1 promoter methylation (MLH1(me+)). We investigate

  15. Proximity to urban parks and mental health. (United States)

    Sturm, Roland; Cohen, Deborah


    Urban parks have received attention in recent years as a possible environmental factor that could encourage physical activity, prevent obesity, and reduce the incidence of chronic conditions. Despite long hypothesized benefits of parks for mental health, few park studies incorporate mental health measures. To test the association between proximity to urban parks and psychological distress. Cross-sectional analysis of individual health survey responses. Data were collected for a study of capital improvements of neighborhood parks in Los Angeles. A survey was fielded on a sample of residential addresses, stratified by distance from the park (within 400m, 800m, 1.6 km, and 3.2km; N=1070). We used multiple regression to estimate the relationship between the psychological distress as measured by the MHI-5 (outcome variable) and distance to parks (main explanatory variable), controlling for observed individual characteristics. Mental health is significantly related to residential distance from parks, with the highest MHI-5 scores among residents within short walking distance from the park (400m) and decreasing significantly over the next distances. The number of visits and physical activity minutes are significantly and independently related to distance, although controlling for them does not reduce the association between distance and mental health. This paper provides a new data point for an arguably very old question, but for which empirical data are sparse for the US. A nearby urban park is associated with the same mental health benefits as decreasing local unemployment rates by 2 percentage points, suggesting at least the potential of environmental interventions to improve mental health. The analysis is cross-sectional, making it impossible to control for important confounders, including residential selection. Mental health policy has traditionally focused on individual-centered interventions. Just as health policy for preventable chronic illnesses has shifted

  16. Proximal caries detection: Sirona Sidexis versus Kodak Ektaspeed Plus. (United States)

    Khan, Emad A; Tyndall, Donald A; Ludlow, John B; Caplan, Daniel


    This study compared the accuracy of intraoral film and a charge-coupled device (CCD) receptor for proximal caries detection. Four observers evaluated images of the proximal surfaces of 40 extracted posterior teeth. The presence or absence of caries was scored using a five-point confidence scale. The actual status of each surface was determined from ground section histology. Responses were evaluated by means of receiver operating characteristic (ROC) analysis. Areas under ROC curves (Az) were assessed through a paired t-test. The performance of the CCD-based intraoral sensor was not different statistically from Ektaspeed Plus film in detecting proximal caries.

  17. Closed reduction and percutaneous annulated screw fixation in the treatment of comminuted proximal humeral fractures. (United States)

    Yu, Zhe; Zheng, Lianhe; Yan, Xiaodong; Li, Xiaoxiang; Zhao, Jian; Ma, Bao'an


    Displaced proximal humeral fractures remain a challenge to orthopedic surgeons. The purpose of this study was to evaluate the functional and radiological outcomes of patients with comminuted proximal humeral fractures treated with closed reduction and percutaneous screw fixation (CRPF). The authors retrospectively reviewed 38 cases of displaced proximal humeral fractures (2-, 3- or 4-part fractures according to the Neer classification) that were treated using the CRPF technique from May 2009 to April 2013. From this group 26 patients were followed up for a period ranging from 9 to 24 months (averaging 12.9 months) and evaluated for the functional and radiological outcomes by a series of standard questionnaires and measurements. The fractures in all 26 patients were healed within an average time of 14.6 weeks (ranging from 11 to 27 weeks), and the mean interval between the operation and fully functional activity was 18.6 weeks (ranging from 15 to 32 weeks). At the final follow-up visit, no patient showed shoulder instability; the mean range of abduction motion was 146.5° (ranging from 72° to 180°). For all patients, no statistically significant difference in the functional outcomes was observed between their 6-month and final follow-up visits; or in the radiological findings between their immediate post-operative and final follow-up examinations. The CRPF technique is a safe and effective therapeutic option for comminuted proximal humeral fractures. Good stability is obtained and aggressive impairment of the soft tissue and periosteum around the fracture is avoided, which allows for an early painless range of motion. The technique promotes bone healing, prevents ischemic osteonecrosis of the head of the humerus and leads to few complications.

  18. Comparative analyses of bidirectional promoters in vertebrates

    Directory of Open Access Journals (Sweden)

    Taylor James


    Full Text Available Abstract Background Orthologous genes with deep phylogenetic histories are likely to retain similar regulatory features. In this report we utilize orthology assignments for pairs of genes co-regulated by bidirectional promoters to map the ancestral history of the promoter regions. Results Our mapping of bidirectional promoters from humans to fish shows that many such promoters emerged after the divergence of chickens and fish. Furthermore, annotations of promoters in deep phylogenies enable detection of missing data or assembly problems present in higher vertebrates. The functional importance of bidirectional promoters is indicated by selective pressure to maintain the arrangement of genes regulated by the promoter over long evolutionary time spans. Characteristics unique to bidirectional promoters are further elucidated using a technique for unsupervised classification, known as ESPERR. Conclusion Results of these analyses will aid in our understanding of the evolution of bidirectional promoters, including whether the regulation of two genes evolved as a consequence of their proximity or if function dictated their co-regulation.

  19. On Optimal Fuzzy Best Proximity Coincidence Points of Proximal Contractions Involving Cyclic Mappings in Non-Archimedean Fuzzy Metric Spaces

    Directory of Open Access Journals (Sweden)

    Manuel De la Sen


    Full Text Available The main objective of this paper is to deal with some properties of interest in two types of fuzzy ordered proximal contractions of cyclic self-mappings T integrated in a pair ( g , T of mappings. In particular, g is a non-contractive fuzzy self-mapping, in the framework of non-Archimedean ordered fuzzy complete metric spaces and T is a p -cyclic proximal contraction. Two types of such contractions (so called of type I and of type II are dealt with. In particular, the existence, uniqueness and limit properties for sequences to optimal fuzzy best proximity coincidence points are investigated for such pairs of mappings.

  20. Population Exposure Estimates in Proximity to Nuclear Power Plants, Locations (United States)

    National Aeronautics and Space Administration — The Population Exposure Estimates in Proximity to Nuclear Power Plants, Locations data set combines information from a global data set developed by Declan Butler of...

  1. Transverse Stress Fracture of the Proximal Patella: A Case Report

    National Research Council Canada - National Science Library

    Atsumi, Satoru; Arai, Yuji; Kato, Ko; Nishimura, Akinobu; Nakazora, Shigeto; Nakagawa, Shuji; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Sudo, Akihiro; Kubo, Toshikazu


    .... Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella...

  2. Genetics Home Reference: proximal 18q deletion syndrome (United States)

    ... can range from mild to severe. In particular, vocabulary and the production of speech (expressive language skills) ... Some affected individuals have an unusually large head size ( macrocephaly ). People with proximal 18q deletion syndrome often ...

  3. Perinatal mortality and residential proximity to an industrial park. (United States)

    Sarov, Batia; Bentov, Yaakov; Kordysh, Ella; Karakis, Isabella; Bolotin, Arkady; Hershkovitz, Reli; Belmaker, Ilana


    The authors' objective was to determine whether residential proximity to an industrial park (IP) is associated with increased perinatal mortality (PM). This semiecological study included 63,850 delivered births with 840 cases of PM (1995-2000). The authors categorized the study populations by ethnicity (ie, Bedouin and Jewish) and type of locality. Residential distance from the IP served as a surrogate indicator of exposure. Among Bedouin newborns, proximity to the IP was associated with increased PM rates (relative risk = 1.45; 95% confidence interval = 1.22-1.72). The excess in PM was not related to maternal or newborn physical characteristics that the authors observed. The risk of PM and its components in the Jewish localities was not associated with IP proximity. The association between residential proximity to the IP and excess in PM among only Bedouin newborns may be related to vulnerability caused by the nomadic nature of the society.

  4. Computational proximity excursions in the topology of digital images

    CERN Document Server

    Peters, James F


    This book introduces computational proximity (CP) as an algorithmic approach to finding nonempty sets of points that are either close to each other or far apart. Typically in computational proximity, the book starts with some form of proximity space (topological space equipped with a proximity relation) that has an inherent geometry. In CP, two types of near sets are considered, namely, spatially near sets and descriptivelynear sets. It is shown that connectedness, boundedness, mesh nerves, convexity, shapes and shape theory are principal topics in the study of nearness and separation of physical aswell as abstract sets. CP has a hefty visual content. Applications of CP in computer vision, multimedia, brain activity, biology, social networks, and cosmology are included. The book has been derived from the lectures of the author in a graduate course on the topology of digital images taught over the past several years. Many of the students have provided important insights and valuable suggestions. The topics in ...

  5. Proximate and Amino Acid Composition of Celosia argentea Leaves ...

    African Journals Online (AJOL)

    % respectively while ... were analyzed using flame photometer for K and ... low in methionine. Table 1: Proximate Composition of C. argentea. Parameter. Composition (%). Moisture content. Crude Fat. Crude protein. Crude fibre. Ash. Nitrogen ...

  6. [A case of proximal type epithelioid sarcoma of the perineum]. (United States)

    Murashima, Takaya; Kamibeppu, Toyoharu; Hiromasa, Tukino; Mukai, Syoichiro; Kamoto, Toshiyuki


    Epithelioid sarcomas are rare soft tissue neoplasms which occur more often in young people. They tend to relapse, metastatize and show poor prognosis. Proximal-type epithelioid sarcomas arise from the more proximal part of body and are more malignant than distal-type epithelioid sarcomas. We present a case of proximal-type epithelioid sarcoma which occurred in the perineum. A 24-year-old male visited our hospital with the chief complaint of pain in the perineum. Computed tomography and magnetic resonance imaging showed a tumor 30×23×17 mm in diameter in the perineal region. The tumor was excised regionally and the pathological examination with immunohistochemical staining revealed that the tumor was proximal-type epithelioid sarcoma. The patient is free of recurrence and metastasis one year after local excision.

  7. Effect of processing method on the Proximate composition, mineral ...

    African Journals Online (AJOL)

    Effect of processing method on the Proximate composition, mineral content and antinutritional factors of Taro (Colocasia esculenta, L.) growth in Ethiopia. T Adane, A Shimelis, R Negussie, B Tilahun, GD Haki ...

  8. TETRAPOLIS - an exercise in building the complexities of proximity space

    National Research Council Canada - National Science Library

    Cristian Blidariu; Diana Giurea


    ... student’s intuitive ways for understanding these vicinities, their physical and symbolic proximities, through participatory tactics and certain poetic/architectural tools required in the phenomenological build-up of space...

  9. Orthopaedic approaches to proximal humeral fractures following trauma.


    Mafi, R.; Khan, W.; Mafi, P; Hindocha, S.


    Proximal humeral fractures have been a topic of discussion in medical literature dating back as far as 3rd century BC. Today, these fractures are the most common type of humeral fractures and account for about 5-6% of all fractures in adults with the incidence rising rapidly with age. In broad terms the management of proximal humeral fractures can be divided into two categories: conservative versus surgical intervention. The aim of treatment is to stabilize the fracture, aid better union and ...

  10. Conservative Treatment for Bilateral Displaced Proximal Humerus Head Fracture


    Rodriguez-Corlay, Ruy E; Velutini-Becker, Ricardo; Aguilar-Alcal?, Luis D


    Proximal humerus fracture represents five to eight percent of all fractures and is twice as common in women than in men. Most cases of displaced fracture of the proximal humerus are treated surgically; it is probable that more cases are preferred to be treated surgically greater than required. The optimal treatment for these fractures remains controversial, but physicians have a tendency to treat via open reduction and fixation with angular locking plates or glenohumeral arthroplasty.? We pre...

  11. Proximal and distal muscle fatigue differentially affect movement coordination


    Cowley, Jeffrey C.; Gates, Deanna H.


    Muscle fatigue can cause people to change their movement patterns and these changes could contribute to acute or overuse injuries. However, these effects depend on which muscles are fatigued. The purpose of this study was to determine the differential effects of proximal and distal upper extremity muscle fatigue on repetitive movements. Fourteen subjects completed a repetitive ratcheting task before and after a fatigue protocol on separate days. The fatigue protocol either fatigued the proxim...

  12. Developing survey metrics for analysing cross-border proximity

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Williams, Allan


    Cross-border innovation cooperation (CBIC) has been heralded as one of the corner stones of innovation-driven growth opportunities for firms located in cross-border regions (CBRs). The success of this cooperation is affected by varying types of proximities identified in the literature....... The findings indicate that the developed survey metrics are effective in depicting the phenomenon of proximity. The foundational work undertaken in this research note provides a platform, and catalyst, for more extensive investigations of the topic....

  13. Partial proximal trisomy 10q syndrome: a new case. (United States)

    Nucaro, A; Faedda, A; Cao, A; Boccone, L


    We report a case of partial proximal trisomy of the long arm of chromosome 10 confirmed by fluorescence in situ hibridization (FISH) performed with whole chromosome 10 specific painting and specific yac clones. The phenotypic findings, compared to those found in other published cases with the same karyotype, support the recognition of a distinctive partial proximal trisomy 10q syndrome (10q11-->q22).

  14. Proximity functions for electrons up to 10 keV

    Energy Technology Data Exchange (ETDEWEB)

    Chmelevsky, D. (Institut fuer Medizinische Strahlenkunde der Universitaet Wuerzburg, Germany); Kellerer, A.M.; Terrissol, M.; Patau, J.P.


    Proximity functions for electrons up to 10 keV in water are computed from simulated particle tracks. Numerical results are given for the differential functions t(x) and the integral functions T(x). Basic characteristics of these functions and their connections to other microdosimetric quantities are considered. As an example of the applicability of the proximity functions, the quantity y/sub D/ for spheres is derived from t(x).

  15. Inexact proximal Newton methods for self-concordant functions

    DEFF Research Database (Denmark)

    Li, Jinchao; Andersen, Martin Skovgaard; Vandenberghe, Lieven


    We analyze the proximal Newton method for minimizing a sum of a self-concordant function and a convex function with an inexpensive proximal operator. We present new results on the global and local convergence of the method when inexact search directions are used. The method is illustrated...... matrices with chordal sparsity patterns are used to evaluate gradients and matrix-vector products with the Hessian of the smooth component of the objective....

  16. Critical Proximity as a Methodological Move in Techno-Anthropology


    Birkbak, Andreas; Petersen, Morten Krogh; Elgaard Jensen, Torben


    echno-Anthropology is a new field, operating with a broad range of methodologies and approaches. This gives rise to the question: What does it mean for Techno-Anthropological research to be critical? In this paper, we discuss this question by developing and specifying the notion of ‘critical proximity.’ Critical proximity offers an alternative to critical distance, especially with respect to avoiding premature references to abstract panoramas such as democratization and capitalist exploitatio...

  17. Design and Clinical Application of Proximal Humerus Memory Connector (United States)

    Xu, Shuo-Gui; Zhang, Chun-Cai


    Treatment for comminuted proximal humerus fractures and nonunions are a substantial challenge for orthopedic surgeons. Plate and screw fixation does not provide enough stability to allow patients to begin functional exercises early after surgery. Using shape memory material nickel titanium alloy, we designed a new device for treating severe comminuted proximal humerus fractures that accommodates for the anatomical features of the proximal humerus. Twenty-two cases of comminuted fracture, malunion, and nonunion of the proximal humerus were treated with the proximal humeral memory connector (PHMC). No external fixation was needed after the operation and patients began active shoulder exercises an average of 8 days after the operation. Follow-up evaluation (mean 18.5 months) revealed that bone healing with lamellar bone formation occurred an average of 3.6 months after surgery for the fracture cases and 4.5 months after surgery for the nonunion cases. Average shoulder function was 88.5 according to the criteria of Michael Reese. PHMC is an effective new device to treat comminuted proximal humerus fractures and nonunions. The use of this device may reduce the need for shoulder joint arthroplasty.

  18. Optical proximity correction: a first look at manufacturability (United States)

    Liebmann, Lars W.; Grenon, Brian J.; Lavin, Mark A.; Schomody, Stephen; Zell, Thomas


    The feasibility of large scale optical proximity correction with a focus on mask manufacturability is demonstrated on the support and logic gates of a leading edge 64 Mb DRAM chip. Analysis of post reactive ion etch SEM data of the 500 - 600 nm, DUV exposed gates indicates two major contributors to across chip line width variation: first order proximity, that is, the minimum spacing to the nearest neighboring structure, and local area density or pattern loading. Data presented show a very long range (approximately equals 1 mm) impact of pattern density on post reactive ion etch line widths, favoring optical proximity correction approaches that are not based on biasing patterns to compensate for these effects. In this project, pattern density induced effects were alleviated by homogenizing the pattern loading across the chip to approximately 50% instead of biasing the gate structures to compensate for pattern density differences. Proximity induced effects were compensated for with a one- dimensional, single parameter (distance to nearest neighbor), four bucket proximity correction routine with a strong focus on mask manufacturability. Even though the unbiased 64 Mb DRAM gate level challenges mask makers with 480 MB of MEBES data, the optical proximity corrected mask posed no substantial post-processing, writing, or inspection problems in IBM's Burlington, Vermont maskhouse. A very significant 80% reduction in post reactive ion etch across chip line width variation was achieved with this corrected mask.

  19. Lactate oxidation by three segments of the rabbit proximal tubule

    Energy Technology Data Exchange (ETDEWEB)

    Brand, P.H.; Taylor, B.B.


    Oxidation of (U/sup 14/C)lactate to /sup 14/CO/sub 2/ was measured in vitro, in nonperfused anatomically defined segments of rabbit proximal tubule (S1, proximal convoluted, and S2 and S3, proximal straight tubules). The rate of lactate oxidation was similar in S2 and S3 segments, and within the range of lactate oxidation rates measured in vivo. In contrast, the oxidation rate of S1 segments was significantly lower than that of S2 or S3. In proximal straight tubules, lactate oxidation was inhibited by incubation at 0/sup 0/C, or by application of 1 mM ouabain. To determine if the rate of transepithelial transport affected the rate of lactate oxidation, lactate oxidation was measured in proximal straight tubules after the lumen had been opened by perfusion with Ringer's containing 10 mM polyethylene glycol. No difference in lactate oxidation rate was observed between tubules with patent lumina and nonperfused tubules. These results suggest that the various segments of the renal proximal tubule have difference metabolic characteristics, and that the rate of substrate oxidation is related to the activity of the Na/sup +/, K/sup +/-ATPase.

  20. Psychological responses to the proximity of climate change (United States)

    Brügger, Adrian; Dessai, Suraje; Devine-Wright, Patrick; Morton, Thomas A.; Pidgeon, Nicholas F.


    A frequent suggestion to increase individuals' willingness to take action on climate change and to support relevant policies is to highlight its proximal consequences, that is, those that are close in space and time. But previous studies that have tested this proximizing approach have not revealed the expected positive effects on individual action and support for addressing climate change. We present three lines of psychological reasoning that provide compelling arguments as to why highlighting proximal impacts of climate change might not be as effective a way to increase individual mitigation and adaptation efforts as is often assumed. Our contextualization of the proximizing approach within established psychological research suggests that, depending on the particular theoretical perspective one takes on this issue, and on specific individual characteristics suggested by these perspectives, proximizing can bring about the intended positive effects, can have no (visible) effect or can even backfire. Thus, the effects of proximizing are much more complex than is commonly assumed. Revealing this complexity contributes to a refined theoretical understanding of the role that psychological distance plays in the context of climate change and opens up further avenues for future research and for interventions.

  1. The validity of proximal caries detection using magnifying visual aids. (United States)

    Haak, Rainer; Wicht, Michael J; Hellmich, Martin; Gossmann, Andrea; Noack, Michael J


    The purpose of this study was to determine the validity of proximal caries detection supported by a prism loupe and a surgical microscope used by examiners having different professional experience. One hundred and sixty extracted premolars and molars with varying degrees of proximal caries or sound surfaces were embedded in 10 pairs of models with proximal tooth contacts and a simulated gingiva mask. The proximal surfaces were visually evaluated by 14 observers (7 students, 7 dentists) according to a 5-point caries rating scale using a head-worn prism loupe (x4.5), a surgical microscope (x 14) and without any magnifying device (control). The validity of observations was expressed as ROC curves calculated for two gold standard thresholds: (a) the presence of caries and (b) macroscopic cavitation. Repeated measures analysis of variance was used to determine the effects of 'observer group' and 'diagnostic modality'. An influence of the observer group could not be demonstrated (p > 0.72), whereas significant differences were revealed between the diagnostic modalities (p caries detection with magnifying aids were smaller compared to the control group. It was concluded that the use of a prism loupe or a surgical microscope does not improve the validity of proximal caries detection if the operators, irrespective of being dental students or clinical instructors, are inexperienced in its utilisation. In general only moderate validity was achieved with visual inspection of proximal sites. Copyright 2002 S. Karger AG, Basel

  2. High glucose augments angiotensinogen in human renal proximal tubular cells through hepatocyte nuclear factor-5.

    Directory of Open Access Journals (Sweden)

    Juan Wang

    Full Text Available High glucose has been demonstrated to induce angiotensinogen (AGT synthesis in the renal proximal tubular cells (RPTCs of rats, which may further activate the intrarenal renin-angiotensin system (RAS and contribute to diabetic nephropathy. This study aimed to investigate the effects of high glucose on AGT in the RPTCs of human origin and identify the glucose-responsive transcriptional factor(s that bind(s to the DNA sequences of AGT promoter in human RPTCs. Human kidney (HK-2 cells were treated with normal glucose (5.5 mM and high glucose (15.0 mM, respectively. Levels of AGT mRNA and AGT secretion of HK-2 cells were measured by real-time polymerase chain reaction (PCR and enzyme-linked immunosorbent assay (ELISA, respectively. Consecutive 5'-end deletion mutant constructs and different site-directed mutagenesis products of human AGT promoter sequences were respectively transfected into HK-2 cells, followed by AGT promoter activity measurement through dual luciferase assay. High glucose significantly augmented the levels of AGT mRNA and AGT secretion of HK-2 cells, compared with normal glucose treatment. High glucose also significantly augmented AGT promoter activity in HK-2 cells transfected with the constructs of human AGT promoter sequences, compared with normal glucose treatment. Hepatocyte nuclear factor (HNF-5 was found to be one of the glucose-responsive transcriptional factors of AGT in human RPTCs, since the mutation of its binding sites within AGT promoter sequences abolished the above effects of high glucose on AGT promoter activity as well as levels of AGT mRNA and its secretion. The present study has demonstrated, for the first time, that high glucose augments AGT in human RPTCs through HNF-5, which provides a potential therapeutic target for diabetic nephropathy.

  3. Proximity strategies in outsourcing relations: the role of geographical, cultural and relational proximity in the European automotive industry


    Schmitt, Alexander; Van Biesebroeck, Jo


    Several trends that affect the manufacturing of sophisticated goods - increasing international fragmentation of production, and lean and modular process technologies - have increased the importance of proximity in the supply chain. We use the case of the European automotive industry to simultaneously evaluate the relative importance of three dimensions: geographical, cultural, and relational proximity. Using a rich and novel data set, we find that carmakers value some aspects of each dimensio...

  4. Promoting employee health by integrating health protection, health promotion, and continuous improvement: a longitudinal quasi-experimental intervention study. (United States)

    von Thiele Schwarz, Ulrica; Augustsson, Hanna; Hasson, Henna; Stenfors-Hayes, Terese


    To test the effects of integrating health protection and health promotion with a continuous improvement system (Kaizen) on proximal employee outcomes (health promotion, integration, and Kaizen) and distal outcomes (workability, productivity, self-rated health and self-rated sickness absence). Twelve units in a county hospital in Sweden were randomized to control or intervention groups using a quasiexperimental study design. All staff (approximately 500) provided self-ratings in questionnaires at baseline, and a 12- and 24-month follow-up (response rate, 79% to 87.5%). There was a significant increase in the proximal outcomes over time in the intervention group compared with the control group, and a trend toward improvement in the distal outcomes workability and productivity. Integration seems to promote staff engagement in health protection and promotion, as well as to improve their understanding of the link between work and health.

  5. Minimally invasive plate osteosynthesis for proximal humeral fractures. (United States)

    Koljonen, Paul Aarne; Fang, Christian; Lau, Tak Wing; Leung, Frankie; Cheung, Nigel W K


    To report the outcome after minimally invasive plate osteosynthesis (MIPO) through the deltoid-splitting approach for proximal humeral fractures. 10 men and 30 women aged 37 to 88 years underwent MIPO through the deltoid-splitting approach using the Proximal Humerus Internal Locking System or the Locking Proximal Humerus Plate for 2-part (n=18), 3-part (n=20), and 4-part (n=2) proximal humeral fractures. The rehabilitation protocol was standardised. All 40 patients were followed up at 3 months, 34 (85%) at 6 months, 30 (75%) at one year, and 13 (33%) at 2 years. Two patients had malunion. No patient had avascular necrosis, infection, nerve palsy, or nonunion. The mean Constant score at one year and 2 years was 75 and 87.5, respectively. The Constant score at 6 months correlated to that at one year (r=0.926, pfracture grade, or hand dominance. MIPO for fixation of proximal humeral fractures using a locking plate is safe and effective in enabling an early return of shoulder function.

  6. The Applications of Finite Element Analysis in Proximal Humeral Fractures (United States)

    Ye, Yongyu; You, Wei; Zhu, Weimin; Cui, Jiaming; Chen, Kang


    Proximal humeral fractures are common and most challenging, due to the complexity of the glenohumeral joint, especially in the geriatric population with impacted fractures, that the development of implants continues because currently the problems with their fixation are not solved. Pre-, intra-, and postoperative assessments are crucial in management of those patients. Finite element analysis, as one of the valuable tools, has been implemented as an effective and noninvasive method to analyze proximal humeral fractures, providing solid evidence for management of troublesome patients. However, no review article about the applications and effects of finite element analysis in assessing proximal humeral fractures has been reported yet. This review article summarized the applications, contribution, and clinical significance of finite element analysis in assessing proximal humeral fractures. Furthermore, the limitations of finite element analysis, the difficulties of more realistic simulation, and the validation and also the creation of validated FE models were discussed. We concluded that although some advancements in proximal humeral fractures researches have been made by using finite element analysis, utility of this powerful tool for routine clinical management and adequate simulation requires more state-of-the-art studies to provide evidence and bases. PMID:29081829

  7. The Applications of Finite Element Analysis in Proximal Humeral Fractures

    Directory of Open Access Journals (Sweden)

    Yongyu Ye


    Full Text Available Proximal humeral fractures are common and most challenging, due to the complexity of the glenohumeral joint, especially in the geriatric population with impacted fractures, that the development of implants continues because currently the problems with their fixation are not solved. Pre-, intra-, and postoperative assessments are crucial in management of those patients. Finite element analysis, as one of the valuable tools, has been implemented as an effective and noninvasive method to analyze proximal humeral fractures, providing solid evidence for management of troublesome patients. However, no review article about the applications and effects of finite element analysis in assessing proximal humeral fractures has been reported yet. This review article summarized the applications, contribution, and clinical significance of finite element analysis in assessing proximal humeral fractures. Furthermore, the limitations of finite element analysis, the difficulties of more realistic simulation, and the validation and also the creation of validated FE models were discussed. We concluded that although some advancements in proximal humeral fractures researches have been made by using finite element analysis, utility of this powerful tool for routine clinical management and adequate simulation requires more state-of-the-art studies to provide evidence and bases.

  8. Intramedullary Nailing for Pathological Fractures of the Proximal Humerus. (United States)

    Choi, Eun-Seok; Han, Ilkyu; Cho, Hwan Seong; Park, In Woong; Park, Jong Woong; Kim, Han-Soo


    Endoprosthetic reconstruction is widely applied for pathological fractures of the proximal humerus; however, functional impairment is usually unsatisfactory. The aims of the current study are to evaluate the reliability of interlocking intramedullary (IM) nailing with cement augmentation as a fixation method in proximal humeral lesions and to assess functional outcomes. We reviewed 32 patients with pathological fractures of the proximal humerus who underwent interlocking IM nailing and cement augmentation. Functional scores and pain relief were assessed as outcomes. The mean follow-up period was 14.2 months. The mean Musculoskeletal Tumor Society functional score and Karnofsky performance status scale score were 27.7 and 75.6, respectively. Improvement of pain assessed using the visual analogue scale was 6.2 on average. Thirty-one patients (97%) experienced no pain after surgery. The mean ranges of forward flexion and abduction were 115° and 112.6°, respectively. All patients achieved stability and had no local recurrence without failure of fixation until the last follow-up. Proximal interlocking IM nailing with cement augmentation appears to be a reliable treatment option for pathological or impending fractures of the proximal humerus in selected patients with metastatic tumors, even with extensive bone destruction.


    Directory of Open Access Journals (Sweden)

    Ch. Venkateswarlu


    Full Text Available INTRODUCTION Treating a proximal humerus fracture remained a challenging problem until proximal humeral internal locking system has been developed. Our study aims at evaluating the functional outcome of 30 consecutive patients with proximal humeral fracture treated by Philos plate fixation; 30 patients with proximal humeral fractures who attended our hospital between December 2013 and December 2015 were included in the study; 18 women and 12 men with a mean age of 47.5years (30-60 years are included. Data was collected prospectively and outcomes were assessed using constant shoulder score. The mean follow-up period was 12 months (6-18 months. Mean union time of all the fractures was 11.4 weeks (8-20 weeks. The mean constant shoulder score at final review was 70.5 (52-92. Philos plate provides stable fracture fixation for proximal humerus fracture in both young and elderly patients, which enables for early mobilisation and achieves acceptable functional results.

  10. Topology of digital images visual pattern discovery in proximity spaces

    CERN Document Server

    Peters, James F


    This book carries forward recent work on visual patterns and structures in digital images and introduces a near set-based a topology of digital images. Visual patterns arise naturally in digital images viewed as sets of non-abstract points endowed with some form of proximity (nearness) relation. Proximity relations make it possible to construct uniform topolo- gies on the sets of points that constitute a digital image. In keeping with an interest in gaining an understanding of digital images themselves as a rich source of patterns, this book introduces the basics of digital images from a computer vision perspective. In parallel with a computer vision perspective on digital images, this book also introduces the basics of prox- imity spaces. Not only the traditional view of spatial proximity relations but also the more recent descriptive proximity relations are considered. The beauty of the descriptive proximity approach is that it is possible to discover visual set patterns among sets that are non-overlapping ...

  11. Results of the proximal humerus endoprosthetic reconstruction after tumour resection

    Directory of Open Access Journals (Sweden)

    I. M. Mikailov


    Full Text Available The purpose of the study was to evaluate the results of surgical reconstructions of the proximal humerus after transarticular tumour resection, compare the functional results with the results of shoulder arthroplasty in patients with extensive damage of the proximal humerus of non-neoplastic origin. Material and methods. Between 2001 and 2013 38 proximal humeral reconstructions were performed in our clinic: using monopolar endoprostheses - 26 (68% and modular systems with reversible head -12 (32%. The control group included 46 patients with extensive lesions of the proximal humerus of non-neoplastic origin, operated in our clinic in the period from 2006 to 2012. Term follow-up of patients ranged from 7 months to 9 years. Assessment of functional results was carried out in a period from six months to one year. Results. The seven-year survival according the Kaplan - Meier method for patients with primary malignant tumors of the proximal humerus (25 patients was 77%. In the study group the average value of functional outcome MSTS score was 77.7%. Unipolar prosthesis showed a bad result, both in the control (61,3% MSTS, 60,7 Neer and in the main (67,7% MSTS, 61,1 Neer study groups. Conclusion. Currently the method of choice which doesn’t impair the oncologic component of treatment patients with shoulder neoplastic lesions is its replacement with modular reversible systems in combination with additional soft tissue fixation.

  12. Clinical applicability of resin infiltration for proximal caries. (United States)

    Altarabulsi, Mohammad Basel; Alkilzy, Mohammad; Splieth, Christian H


    Resin infiltration is a new microinvasive treatment to arrest the progress of proximal initial caries lesions. This study evaluated the clinical applicability of proximal caries infiltration. In the study population of 50 children, adolescents, and young adults (mean age, 17.3 ± 6.4 years), 10 dentists at the University of Greifswald, Greifswald, Germany, applied the infiltration material Icon on noncavitated proximal lesions in permanent and primary teeth as described by the manufacturer. The applicability was evaluated using two questionnaires filled out by clinicians and patients assessing the comfort, complexity, time, and difficulties of the application in comparison to a filling. The results showed good patient satisfaction with the procedure. The mean time for infiltration (24.3 ± 7.4 minutes), which included rubber dam application (7.7 ± 4 minutes) and the effort were perceived to be comparable to or even easier than a composite filling by clinicians. In three patients (6%), it was not possible to gain sufficient proximal space for the application of an infiltration. The location of the infiltrated tooth, separation problems, and the routine of clinicians with the infiltration technique had an effect on the duration of the infiltration. A clear learning curve with a reduction of treatment time for subsequent treatments was observed (P proximal lesion showed good clinical applicability for clinicians and very high acceptance by patients.

  13. Colorectal Cancer "Methylator Phenotype": Fact or Artifact?

    Directory of Open Access Journals (Sweden)

    Charles Anacleto


    Full Text Available It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a "CpG island methylated phenotype (CIMP," characterized by preferential proximal location in the colon, but otherwise poorly defined. There is considerable overlap between this putative methylator phenotype and the well-known mutator phenotype associated with microsatellite instability (MSI. We have examined hypermethylation of the promoter region of five genes (DAPK, MGMT, hMLH1, p16INK4a, and p14ARF in 106 primary colorectal cancers. A graph depicting the frequency of methylated loci in the series of tumors showed a continuous, monotonically decreasing distribution quite different from the previously claimed discontinuity. We observed a significant association between the presence of three or more methylated loci and the proximal location of the tumors. However, if we remove from analysis the tumors with hMLH1 methylation or those with MSI, the significance vanishes, suggesting that the association between multiple methylations and proximal location was indirect due to the correlation with MSI. Thus, our data do not support the independent existence of the so-called methylator phenotype and suggest that it rather may represent a statistical artifact caused by confounding of associations.

  14. The Proximity Cryogenic System for the ATLAS Toroidal Magnets

    CERN Document Server

    Baynham, D Elwyn; Brown, G; Cragg, D; Crook, M; Haug, F; Mayri, C; Orlowska, A H; Passardi, Giorgio; Pengo, R; ten Kate, H H J; Rochford, J; Sole, D


    ATLAS is a very high-energy detector for the Large Hadron Collider (LHC) at CERN. The superconducting magnet used to provide the required magnetic field consists of four sub-systems: a central solenoid and a very large toroidal magnet comprising two end-cap magnets and the barrel toroid magnet. The associated cryogenic system, currently in the final specification and procurement phase has been sub-divided into three parts: internal, proximity and external. The internal cryogenics minimizes and extracts the heat loads to/from the 4.5 K cold mass and its thermal shields, while the proximity cryogenics takes the cooling capacity generated by the external common system and distributes it to the four magnets according to the various operating scenarios. Two independent proximity cryogenic systems have been designed taking into account the difference in cooling principle of the solenoid and the three toroids, respectively.

  15. The proximity cryogenic system for the ATLAS toroidal magnets (United States)

    Haug, F.; Passardi, G.; Pengo, R.; ten Kate, H.; Baynham, E.; Bradshaw, T.; Brown, G.; Cragg, D.; Crook, M.; Orlowska, A. H.; Rochford, J.; Sole, D.; Mayri, C.


    ATLAS is a very high-energy detector for the Large Hadron Collider (LHC) at CERN. The superconducting magnet used to provide the required magnetic field consists of four sub-systems: a central solenoid and a very large toroidal magnet comprising two end-cap magnets and the barrel toroid magnet. The associated cryogenic system, currently in the final specification and procurement phase has been sub-divided into three parts: internal, proximity and external. The internal cryogenics minimizes and extracts the heat loads to/from the 4.5 K cold mass and its thermal shields, while the proximity cryogenics takes the cooling capacity generated by the external common system and distributes it to the four magnets according to the various operating scenarios. Two independent proximity cryogenic systems have been designed taking into account the difference in cooling principle of the solenoid and the three toroids, respectively.

  16. How to improve outcome in surgery for Proximal Hypospadias? (United States)

    Qureshi, Abdul Hafeez; Zaidi, Syed Zafar


    To evaluate the role of subdartos fascial tissue as watertight layer in improving outcome for 2-stage proximal hypospadias surgery. The experimental study was conducted at the Department of Urology, Indus Hospital, Karachi, and comprised an audit of patients with proximal hypospadias who underwent surgery from July 1, 2007, to December 31, 2011. The initial two-stage repair of proximal hypospadias led to a high rate of urethrocutanous fistula formation (Group A), and, thus, a modification was introduced and subdartos facial double layer was applied over the urethral suture line (Group B). The results were compared regarding age, type of hypospadias, graft failure and urethrocutanous fistula in these patients. There were 27 patients in Group A and 16(59.3%) of them ended up having urethrocutanous fistula. Group B had 25 patients and only 2(8%) had fistula formation. The application of dartos facial flap waterproofing layer reduced fistula rate.

  17. Specifics of proximal caries and their diagnostics in posterior teeth

    Directory of Open Access Journals (Sweden)

    Wojcik-Checinska Ilona


    Full Text Available Proximal surfaces are the second in turn after the occlusal surfaces, as being the most exposed places to the carious process. The specificity of changes and location makes the diagnostic of approximal cavities difficult. The aim of the study was to collect information on possibilities of detection, monitoring and assessment of carious lesions located on proximal surfaces, starting from the early stage. On the base of current literature, chosen methods of diagnosis, from conventional, to advanced technologies were presented. Current literature also suggests that none of the diagnostic methods exclude the possibility of misdiagnosis of proximal caries. Therefore, during the diagnosing of doubtful cases, it is advisable to employ several methods of assessment, with simultaneous individual appraisal of caries risk factors, such as oral hygiene, frequency of eating sweets or the number of active caries foci.

  18. Cilastatin attenuates cisplatin-induced proximal tubular cell damage. (United States)

    Camano, Sonia; Lazaro, Alberto; Moreno-Gordaliza, Estefania; Torres, Ana M; de Lucas, Carmen; Humanes, Blanca; Lazaro, Jose A; Milagros Gomez-Gomez, M; Bosca, Lisardo; Tejedor, Alberto


    A major area in cancer therapy is the search for protective strategies against cisplatin-induced nephrotoxicity. We investigated the protective effect of cilastatin on cisplatin-induced injury to renal proximal tubular cells. Cilastatin is a specific inhibitor of renal dehydrodipeptidase I (DHP-I), which prevents hydrolysis of imipenem and its accumulation in the proximal tubule. Primary cultures of proximal cells were treated with cisplatin (1-30 microM) in the presence or absence of cilastatin (200 microg/ml). Apoptosis and mitochondrial injury were assessed by different techniques. Cisplatin uptake and DNA binding were measured by inductively coupled plasma spectrometry. HeLa cells were used to control the effect of cilastatin on the tumoricidal activity of cisplatin. Cisplatin increased cell death, apoptotic-like morphology, caspase activation, and mitochondrial injury in proximal tubular cells in a dose- and time-dependent way. Concomitant treatment with cilastatin reduced cisplatin-induced changes. Cilastatin also reduced the DNA-bound platinum but did not modify cisplatin-dependent up-regulation of death receptors (Fas) or ligands (tumor necrosis factor alpha, Fas ligand). In contrast, cilastatin did not show any effects on cisplatin-treated HeLa cells. Renal DHP-I was virtually absent in HeLa cells. Cilastatin attenuates cisplatin-induced cell death in proximal tubular cells without reducing the cytotoxic activity of cisplatin in tumor cells. Our findings suggest that the affinity of cilastatin for renal dipeptidase makes this effect specific for proximal tubular cells and may be related to a reduction in intracellular drug accumulation. Therefore, cilastatin administration might represent a novel strategy in the prevention of cisplatin-induced acute renal injury.

  19. One-stage surgical correction of proximal hypospadias. (United States)

    Joseph, V T


    Proximal hypospadias poses major problems in surgical correction owing to the complexity and severity of the abnormalities, leading to the use of staged repairs to correct this condition. However, with precise definition of the components of this deformity a single-stage operation can be developed and applied successfully for surgical correction of this condition. Twenty-six patients with severe proximal hypospadias were subjected to a one-stage repair. Excision of proximal fibrotic dartos tissue and removal of dysplastic urethral plate tissue corrected chordee completely. Urethral reconstruction was then performed by tubularising a flap of dorso-lateral preputial skin which was then anastomosed to the proximal urethra. The glandular part of the urethra was reconstructed using the distal part of the flap as an onlay graft over the meatal groove. The suture lines were covered with a layer of dartos tissue and skin closure was completed by transposing dorsal skin to surface the ventral penile shaft. A urethral catheter was left in for 10 days. All patients have been followed up after surgery from 1 to 5 years with a median period of 2 years. There were no fistulas. Two patients had mild stenosis at the meatus which responded to dilatation. One patient developed a stricture at the proximal anastomosis which required secondary correction. All other patients achieved satisfactory correction, both in terms of voiding and in the cosmetic appearance of the genitalia. Single-stage repair of hypospadias can be successfully applied in the correction of severe proximal hypospadias. It requires meticulous dissection and careful design of reconstructive techniques. The end results are comparable to staged procedures and morbidity is significantly lower.

  20. Fixação interna de fratura de epífise proximal de tíbia em potro Internal fixation of the tibial proximal epiphyses fracture in a foal

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Maciel Brunner


    Full Text Available A fratura Salter Harris tipo II ocorre comumente na epífise proximal de tíbia em potros e tem reparação difícil mas com o advento das técnicas de fixação interna, o prognóstico tem melhorado. No caso descrito, em um potro da raça árabe de 26 dias de idade, com fratura proximal de tíbia direita tipo Salter Harris II, foram utilizadas as placas de compressão para garantirem estabilização e aproximação dos fragmentos fraturados, porém com risco de ocasionar distúrbios no desenvolvimento esquelético. No caso relatado, através do controle radiológico, não foi evidenciada diminuição da radioluscência na região correspondente à cartilagem de conjugação proximal da tíbia. O artigo tem como objetivo discutir o tratamento empregado que se mostrou como alternativa viável pelo resultado favorável com bons resultados.The most frequent fracture is tibia’s proximal epiphysis in foals is Salter Harris type II although its difficult to repair. The development of the inner fixation technique has been made the prognosis better. The dynamic compression bone plate allow guaranteed reduction and stabilization of the bone’s fragments, but it can promote development disturbs. In this case, by the radiological control, it has not shown less radiolucency in the proximal tibia’s growth plate. The treatment used showed itself as a feasible alternative because of the favourable good results.

  1. Evolution of treatment of of the proximal humerus fractures (review

    Directory of Open Access Journals (Sweden)

    P. G. Kogan


    Full Text Available The article in generalized form acquaints with the publications devoted to the bases of proximal humeral fractures treatment. A brief digression on anatomy and biomechanics of the humeral joint allows to consider the main morphological features of it. The most commonly used classification of proximal humeral fractures concisely classify many types of damage. According to the clinical and anatomical characteristics of fractures tracked the historical aspect, the development and the current state of the most common methods of treatment. In his review collected works authors share their experience in the application of methods. It allows to further the perspective directions.

  2. Critical Proximity as a Methodological Move in Techno-Anthropology

    DEFF Research Database (Denmark)

    Birkbak, Andreas; Petersen, Morten Krogh; Elgaard Jensen, Torben


    echno-Anthropology is a new field, operating with a broad range of methodologies and approaches. This gives rise to the question: What does it mean for Techno-Anthropological research to be critical? In this paper, we discuss this question by developing and specifying the notion of ‘critical...... work through two cases—one on the involvement of users in innovation projects and another on commercial web technologies for tracing issues—to show how critical proximity may be practiced. We sum up the lessons derived in four methodological guidelines for doing research with critical proximity....

  3. Improving outcomes for patients with proximal femoral fractures. (United States)

    Shah, Dipal; Dhillon, Amritpaul; Mulvaney, Emily; Robinson, Margaret; Weerasuriya, Namal


    A peri-operative bay was created to treat all patients with proximal femoral fractures admitted to one trauma ward at the Queen's Medical Centre, Nottingham. All patients had urinary catheterisation and their fluid intake and output was recorded; patients had daily blood tests and were cared for on pressure-relieving mattresses. In addition, a study day was provided for all nursing staff on the management of patients with proximal femoral fractures. These measures resulted in a significant decrease in the incidence of acute kidney injury, reduced the length of hospital stay for patients on this ward and reduced the numbers of falls and pressure-related injuries for these patients.

  4. Bizarre parosteal osteochondromatous proliferation of the proximal humerus: case report

    Energy Technology Data Exchange (ETDEWEB)

    Bush, J.B.; Meyer, Mark S. [Ochsner Clinic Foundation, Department of Orthopedics, New Orleans, LA (United States); Reith, John D. [University of Florida College of Medicine, Departments of Pathology, Immunology and Laboratory Medicine and Orthopaedics and Rehabilitation, Gainesville, Florida (United States)


    Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is a rare lesion of bone occurring predominantly in the long bones of the hands and feet. It exists as a puzzling clinical entity of uncertain origins and high recurrence rates after surgical resection. To our knowledge, this clinical entity has not been reported in the proximal aspect of the humerus. An interesting report of a lesion occurring in the proximal humerus, which initially was misinterpreted as a parosteal osteosarcoma, is discussed outlining the clinical, radiographic and pathologic features of the BPOP lesion. (orig.)

  5. Proximal antecedents to violent events in adolescent dating relationships. (United States)

    Stephenson, Pamela S; Martsolf, Donna S; Draucker, Claire Burke


    Dating violence affects 25-60% of adolescents. This study developed a typology of proximal antecedents to violent events in adolescent dating relationships. Descriptions of 307 dating violence events were extracted from transcribed interviews with 87 young adults who experienced dating violence as adolescents. Verbatim text preceding the description of each violent event was identified as a proximal antecedent. Cross-case analysis was used to develop a typology of five antecedent categories: "pulling away,"  "demanding obedience," "discovering involvement with a rival," "defining the relationship," "demonstrating disrespect." Practitioners can use this typology to engage teens in discussions of factors that precede dating violence events.

  6. Modelling and Analysis of Proximity Effect in IGBT Fuses

    DEFF Research Database (Denmark)

    Iov, Florin; Blaabjerg, Frede; Rasmussen, Henrik


    . Even with an active protection, a high power IGBT still has a risk of exhibiting a violent rupture in the case of a fault if e.g. IGBT fuses are not protecting it. By introducing fuses into voltage source converters a better protection of IGBT's can be achieved. However, skin and proximity effects...... affect the current distribution in a fuse due to the high frequency currents and thus a need for de-rating the fuse. This paper shows an analytical model for studying the proximity effect into a fuse. The results obtained using this model are compared with experiments....

  7. Efficient Indoor Proximity and Separation Detection for Location Fingerprinting

    DEFF Research Database (Denmark)

    Kjærgaard, Mikkel Baun; Treu, Georg; Ruppel, Peter


    Detecting proximity and separation among mobile targets is a basic mechanism for many location-based services (LBSs) and requires continuous positioning and tracking. However, realizing both mechanisms for indoor usage is still a major challenge. Positioning methods like GPS cannot be applied there......, and for distance calculations the particular building topology has to be taken into account. To address these challenges, this paper presents a novel approach for indoor proximity and separation detection, which uses location fingerprinting for indoor positioning of targets and walking distances for modeling...

  8. Arthroscopic-assisted removal of proximal tibia locking plates

    Directory of Open Access Journals (Sweden)

    Gille Justus


    Full Text Available Abstract We present a new technique to remove plates from the proximal tibia arthroscopic-assisted with all advantages of the minimally invasive surgery and the possibility to treat concomitant intraarticular pathologies. The initial results (n = 7 are promising with an increase of the Lysholm score in all cases studied [preop. median 78 (range 32–100, postop. median 89 (range 60–100]. In conclusion, arthroscopic-assisted hardware removal at the proximal tibia is feasible and may provide patients with all the benefits of minimal-invasive hardware removal. The described technique can be recommended for all surgeons familiar with arthroscopic surgery.

  9. Longitudinal spin Seebeck effect free from the proximity Nernst effect. (United States)

    Kikkawa, T; Uchida, K; Shiomi, Y; Qiu, Z; Hou, D; Tian, D; Nakayama, H; Jin, X-F; Saitoh, E


    This Letter provides evidence for intrinsic longitudinal spin Seebeck effects (LSSEs) that are free from the anomalous Nernst effect (ANE) caused by an extrinsic proximity effect. We report the observation of LSSEs in Au/Y(3)Fe(5)O(12) (YIG) and Pt/Cu/YIG systems, showing that the LSSE appears even when the mechanism of the proximity ANE is clearly removed. In the conventional Pt/YIG structure, furthermore, we separate the LSSE from the ANE by comparing the voltages in different magnetization and temperature-gradient configurations; the ANE contamination was found to be negligibly small even in the Pt/YIG structure.

  10. Proximal focal humeral deficiency in a large breed dog. (United States)

    Kalff, S; Gemmill, T


    A 26-week-old female Boerboel was referred for evaluation of progressive left thoracic limb lameness. Computed tomography and radiographic evaluation revealed radiolucency of the caudal region of the proximal humeral metaphysis, absence of the humeral head, and gross distortion of the glenoid. Given the severe glenohumeral deformation, arthrodesis of the left shoulder was performed using orthogonal locking bone plates, lag screw fixation, and bone grafting. Despite late implant failure, arthrodesis was successful in this case, and satisfactory limb function was restored. To the author's knowledge, this is the first report of a case of a focal developmental deficiency of the proximal humerus reported in a dog.

  11. Proximity Operations Nano-Satellite Flight Demonstration (PONSFD) Rendezvous Proximity Operations Design and Trade Studies (United States)

    Griesbach, J.; Westphal, J. J.; Roscoe, C.; Hawes, D. R.; Carrico, J. P.


    The Proximity Operations Nano-Satellite Flight Demonstration (PONSFD) program is to demonstrate rendezvous proximity operations (RPO), formation flying, and docking with a pair of 3U CubeSats. The program is sponsored by NASA Ames via the Office of the Chief Technologist (OCT) in support of its Small Spacecraft Technology Program (SSTP). The goal of the mission is to demonstrate complex RPO and docking operations with a pair of low-cost 3U CubeSat satellites using passive navigation sensors. The program encompasses the entire system evolution including system design, acquisition, satellite construction, launch, mission operations, and final disposal. The satellite is scheduled for launch in Fall 2015 with a 1-year mission lifetime. This paper provides a brief mission overview but will then focus on the current design and driving trade study results for the RPO mission specific processor and relevant ground software. The current design involves multiple on-board processors, each specifically tasked with providing mission critical capabilities. These capabilities range from attitude determination and control to image processing. The RPO system processor is responsible for absolute and relative navigation, maneuver planning, attitude commanding, and abort monitoring for mission safety. A low power processor running a Linux operating system has been selected for implementation. Navigation is one of the RPO processor's key tasks. This entails processing data obtained from the on-board GPS unit as well as the on-board imaging sensors. To do this, Kalman filters will be hosted on the processor to ingest and process measurements for maintenance of position and velocity estimates with associated uncertainties. While each satellite carries a GPS unit, it will be used sparsely to conserve power. As such, absolute navigation will mainly consist of propagating past known states, and relative navigation will be considered to be of greater importance. For relative observations

  12. Engineering Promoter Architecture in Oleaginous Yeast Yarrowia lipolytica. (United States)

    Shabbir Hussain, Murtaza; Gambill, Lauren; Smith, Spencer; Blenner, Mark A


    Eukaryotic promoters have a complex architecture to control both the strength and timing of gene transcription spanning up to thousands of bases from the initiation site. This complexity makes rational fine-tuning of promoters in fungi difficult to predict; however, this very same complexity enables multiple possible strategies for engineering promoter strength. Here, we studied promoter architecture in the oleaginous yeast, Yarrowia lipolytica. While recent studies have focused on upstream activating sequences, we systematically examined various components common in fungal promoters. Here, we examine several promoter components including upstream activating sequences, proximal promoter sequences, core promoters, and the TATA box in autonomously replicating expression plasmids and integrated into the genome. Our findings show that promoter strength can be fine-tuned through the engineering of the TATA box sequence, core promoter, and upstream activating sequences. Additionally, we identified a previously unreported oleic acid responsive transcription enhancement in the XPR2 upstream activating sequences, which illustrates the complexity of fungal promoters. The promoters engineered here provide new genetic tools for metabolic engineering in Y. lipolytica and provide promoter engineering strategies that may be useful in engineering other non-model fungal systems.

  13. Longitudinal effects of contextual and proximal factors on mother-infant interactions among Brazilian adolescent mothers. (United States)

    Diniz, Eva; DeSousa, Diogo; Koller, Silvia H; Volling, Brenda L


    Adolescent mothers often come from vulnerable backgrounds which might impact the quality of both maternal and infant behavior. Despite the negative impact of adolescent motherhood for maternal and infant behavior, social support may decrease the risks and promote maternal behavior toward the infant. The aim of this study was to investigate longitudinally the effects of proximal (maternal behavior) and distal (mother's perceived social support) variables on infant development in a sample of Brazilian adolescent mothers and their infants. Thirty-nine adolescent mothers (Mage=17.26years; SD=1.71) were observed interacting with their infants at 3 and 6 months postpartum and reported on social support. Results revealed that maternal and infant behavior were associated within and across times. Mothers' perceived social support at 3 months had an indirect effect on infant behavior at 6 months, totally mediated by maternal behavior at 6 months. Our findings revealed the mutual influence between maternal and infant behavior, revealing a proximal process. The results also underscored the importance of the passage of time in the interplay between mother-infant interactions and their developmental context. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Adaptive memory: determining the proximate mechanisms responsible for the memorial advantages of survival processing. (United States)

    Burns, Daniel J; Burns, Sarah A; Hwang, Ana J


    J. S. Nairne, S. R. Thompson, and J. N. S. Pandeirada (2007) suggested that our memory systems may have evolved to help us remember fitness-relevant information and showed that retention of words rated for their relevance to survival is superior to that of words encoded under other deep processing conditions. The authors present 4 experiments that uncover the proximate mechanisms likely responsible. The authors obtained a recall advantage for survival processing compared with conditions that promoted only item-specific processing or only relational processing. This effect was eliminated when control conditions encouraged both item-specific and relational processing. Data from separate measures of item-specific and relational processing generally were consistent with the view that the memorial advantage for survival processing results from the encoding of both types of processing. Although the present study suggests the proximate mechanisms for the effect, the authors argue that survival processing may be fundamentally different from other memory phenomena for which item-specific and relational processing differences have been implicated. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  15. On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry. (United States)

    Long, Marcus J C; Poganik, Jesse R; Aye, Yimon


    Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is "tethering"-a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein-protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: "multifunctional scaffolding" versus "on-demand targeting". By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms.

  16. The theoretical simulation on electrostatic distribution of 1st proximity region in proximity focusing low-light-level image intensifier (United States)

    Zhang, Liandong; Bai, Xiaofeng; Song, De; Fu, Shencheng; Li, Ye; Duanmu, Qingduo


    Low-light-level night vision technology is magnifying low light level signal large enough to be seen by naked eye, which uses the photons - photoelectron as information carrier. Until the micro-channel plate was invented, it has been possibility for the realization of high performance and miniaturization of low-light-level night vision device. The device is double-proximity focusing low-light-level image intensifier which places a micro-channel plate close to photocathode and phosphor screen. The advantages of proximity focusing low-light-level night vision are small size, light weight, small power consumption, no distortion, fast response speed, wide dynamic range and so on. It is placed parallel to each other for Micro-channel plate (both sides of it with metal electrode), the photocathode and the phosphor screen are placed parallel to each other. The voltage is applied between photocathode and the input of micro-channel plate when image intensifier works. The emission electron excited by photo on the photocathode move towards to micro-channel plate under the electric field in 1st proximity focusing region, and then it is multiplied through the micro-channel. The movement locus of emission electrons can be calculated and simulated when the distributions of electrostatic field equipotential lines are determined in the 1st proximity focusing region. Furthermore the resolution of image tube can be determined. However the distributions of electrostatic fields and equipotential lines are complex due to a lot of micro-channel existing in the micro channel plate. This paper simulates electrostatic distribution of 1st proximity region in double-proximity focusing low-light-level image intensifier with the finite element simulation analysis software Ansoft maxwell 3D. The electrostatic field distributions of 1st proximity region are compared when the micro-channel plates' pore size, spacing and inclination angle ranged. We believe that the electron beam movement

  17. In vitro footprinting of promoter regions within supercoiled plasmid DNA. (United States)

    Sun, Daekyu


    Polypurine/polypyrimidine (pPu/pPy) tracts, which exist in the promoter regions of many growth-related genes, have been proposed to be very dynamic in their conformation. In this chapter, we describe a detailed protocol for DNase I and S1 nuclease footprinting experiments with supercoiled plasmid DNA containing the promoter regions to probe whether there are conformational transitions to B-type DNA, melted DNA, and G-quadruplex structures within this tract. This is demonstrated with the proximal promoter region of the human vascular endothelial growth factor (VEGF) gene, which also contains multiple binding sites for Sp1 and Egr-1 transcription factors.

  18. Depressionary Effect of Proximity of Residential Properties to Waste ...

    African Journals Online (AJOL)

    Depressionary Effect of Proximity of Residential Properties to Waste Disposal Sites in Nigeria. ... a helpful Frequently Asked Questions about PDFs. Alternatively, you can download the PDF file directly to your computer, from where it can be opened using a PDF reader. To download the PDF, click the Download link above.


    Directory of Open Access Journals (Sweden)



    Full Text Available 17 Year Old student, Pavan presents with swelling since 8 months. Swelling was diffuse over forearm. Tenderness was present. No local rise of temperature. Range of m ovement at elbow was restricted and painful terminally. No distal neurovascular deficits. X - ray reveale d it to be an a neurysmal bone cyst of proximal right radius. FNAC showed Aneurysmal bone cyst for which curettage and bone grafting was done. Post 6 months tumour recurred with a swelling around upper third of right fo rearm. FNAC and J - needle biopsy showed it to be a neurysmal bone cyst. MRI showed ABC of proximal radius without soft tissue involvement. Excision of proximal third of radius with reconstruction by 3 rd metatarsal and augmented with fib ular graft and stabili zed with dynamic c ompression plate and screws . Tumour specimen was sent for h istopathology a t 2 weeks p ost operatively patient had good range of movements. At present patient has full range of flexion , extension , supination & pronation . He is able to carry out his ADL. In the literature proximal radius reconstruction has been tried in traumatic communited radial head fractures. Here it done for r ecurrent benign tumour like aneurysmal bone cyst, as the base of 3rd metatarsal anatomically coincides with radial head and hence a better radio - capital articulation

  20. outcome of plate osteosynthesis in the management of proximal

    African Journals Online (AJOL)

    through decreased bone mineral density, disruption of bone micro-architecture and reduction in non- collagenous proteins. Proximal humerus fractures are difficult to manage, particularly in the osteoporotic bone, where the fracture is usually .... is followed by pendulum shoulder exercises which gradually graduate to active ...

  1. Proximate analysis and total lycopene content of some tomato ...

    African Journals Online (AJOL)

    Standard analytical techniques were employed to determine the proximate composition and lycopene content of three tomato cultivars namely: Roma VF, Ronita and UTC grown in six local government areas of Kano state, Nigeria. Results indicated mean values of 0.15±0.03, 0.16±0.01, 0.15±0.01% titratable acidity; ...

  2. Case report of LCP pediatric hip osteosynthesis of a proximal ...

    African Journals Online (AJOL)

    We present a case report demonstrating the experience of the department of pediatric orthopaedics of the University Orthopedic Hospital at Sofia Medical University in the treatment of an intertrochanteric proximal femoral fracture in a child with osteopetrosis. We performed open fracture reduction with stable 120° LCP ...

  3. Quality Assessment and Proximate Analysis of Amaranthus hybridus ...

    African Journals Online (AJOL)


    ABSTRACT: The aim of this research is to determine the quality and proximate composition of. Amaranthus hybridus, Celosia argentea, and Talinum triangulare obtained from open .... Vegetable microbiota is very diverse and vegetable quality and safety depend on many factors, including soil, fertilizer, irrigation water, ...

  4. Noncycling mappings and best proximity pair results in Hilbert and ...

    African Journals Online (AJOL)

    A new class of noncyclic mappings, called generalized noncyclic relatively nonexpansive, is introduced and used to study the existence of best proximity pairs in the setting of uniformly convex Banach spaces. We also obtain a weak convergence theorem for noncyclic relatively nonexpansive mappings in the setting of ...

  5. Two Stages repair of proximal hypospadias: Review of 33 cases

    African Journals Online (AJOL)


    It decreases the rate of fistula formation; disruption; stenosis and gives a satisfactory cosmetic appearance. Index Word: proximal hypospadias, two stages repair. ... Second procedure: a) formation of the neo-urethra, b) skin closure, c) dressing. Complete degloving of the penile shaft was performed till its base. Then artificial ...

  6. Fractures of the proximal humerus in children and adolescents

    Directory of Open Access Journals (Sweden)

    Ruban Raj Joshi, Dr


    Full Text Available Background: In most children proximal humeral fractures are treated non-operatively with generally good results. The aim of the study was to evaluate the clinical outcome of closed/open reduction in children with severely displaced proximal humeral fractures. Materials and Methods: The charts of 15 patients (8 girls and 7 boys; mean age: 9.4 years with proximal humeral fractures who were managed at our institution were reviewed from October 2011 to December 2013. Results: There were 7 metaphyseal fractures and 8 physeal injuries which were angulated according to Neer-Horowitz score as grade II (n=2, grade III(n=4 and grade IV(n=9. Associated lesions comprised open fracture with head trauma in a 2 year old female child which was operated on primarily and the 14 others by secondary intention. All patients were treated surgically with either closed (n = 5 or open (n=10 reduction and internal fixation with Kirschner wire or titanium elastic nails (TENs. They were assessed for clinical and radiological healing at a mean follow up of 1.25 years ranging from 0.5 to 2.0 years. Conclusion: Surgical option is indicated for severely displaced and unstable fractures in older children and adolescents. In addition to the periosteum , long head of the biceps, deltoid muscle, and bone fragments in combination can prevent fracture reduction. Key words: Proximal humerus fracture, Children, Open reduction, Operative.

  7. Proximate composition and amino acid profile of rice husk ...

    African Journals Online (AJOL)

    Native rice husk (NRH) was fermented with Pleurotus ostreatus for 7, 14 and 21 days to improve the nutritional values. The proximate composition and amino acid profiles were determined. The results showed that crude fibre (CF), nitrogen free extract (NFE), acid detergent fibre (ADF), and neutral detergent fibre (NDF) were ...

  8. Proximate composition of traditional local sorghum beer “dolo ...

    African Journals Online (AJOL)

    Dolo is a local beer manufactured from malted sorghum grains. It is the most commonly consumed alcoholic beverage in Burkina Faso (60% of population). Thirty (30) samples of dolo were collected from local markets in Ouagadougou and analyzed with respect to their proximate compositions and pH values using ...

  9. Effect of cooking method on proximate and mineral composition of ...

    African Journals Online (AJOL)

    This study investigated effect(s) of cooking fresh fish (Lake Malawi tilapia) by boiling, roasting, pan frying and, using a locally made fireless cooker) on its proximate (protein, fat, ash and moisture) and mineral (calcium, magnesium, zinc, iron and phosphorus) composition. Highest and lowest values for crude protein were ...

  10. Proximate composition of some agricultural wastes in Nigeria and ...

    African Journals Online (AJOL)

    The proximate composition of five agricultural wastes were determined and latter subjected to low temperature conversion process in the presence of nitrogen atmosphere.These agricultural wastes are Cocos nucifera husk,Theobroma cacao pod, Kola nitida pods and Plantago major peels(ripe and unripe peels). All the ...

  11. Proximal focal femoral deficiency in Ibadan a developing country's ...

    African Journals Online (AJOL)

    Prof Ezechukwu


    Jun 9, 2011 ... The major problems are limb length inequality and variable inadequacy of the proximal femoral musculature and hip joint. Treatment is indicated and ranges from amputation and prosthetic rehabilitation to limb salvage, lengthening, and hip re- construction. Until the early 1960s, treatment for PFFD at the St.

  12. Using an index of habitat patch proximity for landscape design (United States)

    Eric J. Gustafson; George R. Parker


    A proximity index (PX) inspired by island biogeography theory is described which quantifies the spatial context of a habitat patch in relation to its neighbors. The index distinguishes sparse distributions of small habitat patches from clusters of large patches. An evaluation of the relationship between PX and variation in the spatial characteristics of clusters of...

  13. Proximate and mineral composition of Tamarindus indica linn 1753 ...

    African Journals Online (AJOL)

    Science World Journal ... Physical parameters and nutrient contents of the whole seeds and seed nuts of Tamarindus indica L. 1753 were determined. ... were found to be potential sources of mineral elements while the whole seeds were richer in other proximate components with the exception of moisture and ash contents.

  14. Private and Flexible Proximity Detection in Mobile Social Networks

    DEFF Research Database (Denmark)

    Siksnys, Laurynas; Thomsen, Jeppe Rishede; Saltenis, Simonas


    A privacy-aware proximity detection service determines if two mobile users are close to each other without requiring them to disclose their exact locations. Existing proposals for such services provide weak privacy, give low accuracy guarantees, incur high communication costs, or lack flexibility...

  15. Comparative physico-chemical and proximate analysis of oils of ...

    African Journals Online (AJOL)

    In rural areas of developing countries like Burkina Faso, nutritive elements are mainly composed of vegetable source. Shea nut, seeds of Sesamum indicum, Cucumis melo and Cucurbita pepo, four species widely consumed were studied. The proximate parameters: moisture, proteins and fat were analysed. Saponification ...

  16. Oscillations in the proximal intratubular pressure: a mathematical model

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Leyssac, P P


    This study presents a dynamic continuous time model of the regulation of the renal proximal intratubular pressure in the rat. The model integrates a functional model of the glomerulus, a tubular model, a feedback model, and an afferent arteriolar model. The model has one equilibrium solution for ...

  17. Levels and proximate determinants of fertility in Butajira District ...

    African Journals Online (AJOL)


    and child health services in Ethiopia were one of the main aims of the health extension program. The impediment of ... Objectives: This study aimed at measuring levels and fertility inhibition effects of proximate determinants in Butajira district. Methods: A ... its link to the success of reproductive health programs and policies ...

  18. Proximate analysis on four edible mushrooms | Adedayo | Journal of ...

    African Journals Online (AJOL)

    Proximate study was conducted on four edible mushrooms commonly found in farmlands in West Yagba Local Government Areas of Kogi state of Nigeria to ... The high fibre content make them a good source of roughages while their low acidity and alkalinity confirms their edibility and the fact that they are not likely to ...

  19. Seasonal variations in the proximate compositions of five ...

    African Journals Online (AJOL)

    Proximate compositions of five economically-important fish species from Lake Victoria and Lake Tanganyika, Tanzania were determined using standard methods and procedures of the Association of the Analytical Chemists. Samples of Lates niloticus, Oreochromis niloticus, Rastrineobola argentea, Limnothrissa miodon ...

  20. Two stages repair of proximal hypospadias: Review of 700 cases

    Directory of Open Access Journals (Sweden)

    Arvind Kumar Shukla


    Conclusion: Two stages procedure using the principles of Byar's technique is a versatile operation that can be used for 2 two-stage procedures the proximal hypospadias. It decreases the rate of fistula formation, disruption, and stenosis and gives a satisfactory cosmetic appearance.

  1. Proximate analysis of Sweet Potato Toasted Granules | Meludu ...

    African Journals Online (AJOL)

    Sweet potato is an important root crop in the food system of many African countries. The yield, nutrition and economic potential of sweet potato have been identified as very high. In this study, sweet potato was processed and toasted into granules. The proximate analysis performed on the toasted granules showed protein, ...

  2. Impact of Relational Proximity on Distress from Infidelity

    NARCIS (Netherlands)

    Fisher, Maryanne; Geher, Glenn; Cox, Anthony; Tran, Ulrich S.; Hoben, Ashley; Arrabaca, Andrew; Chaize, Corinna; Dietrich, Robert; Voracek, Martin


    Men are generally more distressed by a partner's sexual infidelity whereas women are generally more distressed by a partner's emotional infidelity. The importance of the identity of the interloper, however, has been neglected. We explored the influence of relational proximity (i.e., the degree of

  3. User's proximity effects for talk mode in mobile phones

    DEFF Research Database (Denmark)

    Pelosi, Mauro; B. Knudsen, Mikael; Pedersen, Gert Frølund

    Thanks to a recent grip study, 3D CAD model of the human hand have been generated, investigating user's proximity effects for talk mode in mobile phones. The simulation results show that the human hand exhibits a major contribution in determining the total loss when compared to the phantom head...

  4. Proximate composition of Mystus bleekeri in relation to body size ...

    African Journals Online (AJOL)

    Proximate composition of small catfish, Mystus bleekeri, from Nala Daik, Sialkot, Pakistan was investigated and fluctuation in relation to body size and condition factor was carried out. Mean percentages for water, fat, protein and ash contents in the whole wet body weight of wild M. bleekeri were 77.87, 3.26, 15.01 and ...


    African Journals Online (AJOL)

    Dr. Tilahun


    Apr 2, 2013 ... Although taro is widely grown in Ethiopia, it is an underutilized crop and little is known about its proximate and micro-element composition and the antinutritional factors of the raw, boiled and fermented products. Boiling and fermentation processing techniques are widely used in the country, especially ...

  6. Heavy metal and proximate composition associated with the ...

    African Journals Online (AJOL)



    May 8, 2014 ... Changes in the heavy metal content and proximate composition during the 28 day composting of cassava peels used in the cultivation of the oyster mushrooms Pleurotus ostreatus strain EM-1 was studied. Significant dry weight variations of cellulose, hemicellulose and fat contents were observed from day ...

  7. Proximal femoral nail: a minimally invasive treatment for ...

    African Journals Online (AJOL)

    Materials and Methods: In our study patients who presented to department of orthopaedics, Katuri Medical College between January 2013 and December 2014, with intertrochanteric fractures were included and treated with Proximal Femoral Nail. Total of 82 patients were included in the study. Medically unfit patients and ...

  8. Comparative analysis of the Proximate composition and Sensory ...

    African Journals Online (AJOL)

    Comparative analysis of the Proximate composition and Sensory properties of dokuwa produced in Niger State Metropolis. ... Sensory evaluation of the samples on the basis of colour, texture, aroma, taste and overall acceptability showed that significant difference (p<0.05) existed between the samples. The sample from ...

  9. Do Proximate Micro-Swimmers Synchronize their Gait?

    CERN Document Server

    Yuan, Jinzhou; Raizen, David M; Bau, Haim H


    In this fluid dynamics video, we show that low Reynolds number swimmers, such as Caenorhabditis (C.) elegans, synchronize their gait when swimming in close proximity to maximize utilization of space. Synchronization most likely results from steric hindrance and enhances the propulsive speed only marginally.

  10. Proximity to coast is linked to climate change belief. (United States)

    Milfont, Taciano L; Evans, Laurel; Sibley, Chris G; Ries, Jan; Cunningham, Andrew


    Psychologists have examined the many psychological barriers to both climate change belief and concern. One barrier is the belief that climate change is too uncertain, and likely to happen in distant places and times, to people unlike oneself. Related to this perceived psychological distance of climate change, studies have shown that direct experience of the effects of climate change increases climate change concern. The present study examined the relationship between physical proximity to the coastline and climate change belief, as proximity may be related to experiencing or anticipating the effects of climate change such as sea-level rise. We show, in a national probability sample of 5,815 New Zealanders, that people living in closer proximity to the shoreline expressed greater belief that climate change is real and greater support for government regulation of carbon emissions. This proximity effect held when adjusting for height above sea level and regional poverty. The model also included individual differences in respondents' sex, age, education, political orientation, and wealth. The results indicate that physical place plays a role in the psychological acceptance of climate change, perhaps because the effects of climate change become more concrete and local.

  11. Effect of Soaking Time on Proximate and Mineral Compositions and ...

    African Journals Online (AJOL)

    Effect of soaking time on some composition of yellow maize was investigated. Yellow maize seeds (Zea mays) were soaked in deionized water for 12, 24, 36 and 48 hours respectively followed by draining, drying and milling. The unsoaked seeds were milled and served as the control. Proximate and mineral compositions ...

  12. Phytochemical, proximate and anti-nutrient compositions of four ...

    African Journals Online (AJOL)

    Chemical constituents of plants are influenced by environmental factors and fluctuations just as many other polygenic traits. Four different green leafy vegetables commonly used in the diets of South Eastern Nigeria were analyzed with a view to determine the phytochemicals, proximate and anti-nutrient compositions of ...

  13. Studies on the proximate composition, functional properties and ...

    African Journals Online (AJOL)

    The present study produced full fat and defatted flours from matured ackee apple arils and evaluated the proximate composition and the effect of pH and salt concentrations on some of the functional properties of the full fat flour and the defatted flour. Matured ackee apple arils were oven-dried at 60 oC and milled to obtain ...

  14. Proximate and elemental composition of Bauhinia rufescens Lam ...

    African Journals Online (AJOL)

    This study is aimed at investigating the proximate contents, concentrations of some micro/macroelements and anions of the stem bark and leaves of B. rufescens with the view of validating its used as forage and medicinally by man in the treatment of diarrhoea, dysentery and in wound healing. The stem bark and leaves of ...

  15. Bridging Pedagogies: Drama, Multiliteracies, and the Zone of Proximal Development (United States)

    Macy, Leonora


    This article examines how one educator embraced Vygotsky's concept of the zone of proximal development (ZPD) while using drama to scaffold learning about Dr. Seuss's "The Lorax" for first-grade students. This learning event is interpreted with reference to the ZPD and the New London Group's pedagogy of multiliteracies. The author asserts…

  16. Proximate analyses and mineral compositions of the pulp and seeds ...

    African Journals Online (AJOL)

    Proximate analyses and mineral compositions of the pulp and seeds of Adansonia digitata (Baobab fruit) ... It was concluded that the pulp of Adansonia digitata is an important source of vitamin C, while the seed is a potential source of edible oil, potassium, sodium, calcium and magnesium. Keywords: Baobab, Adansonia ...

  17. Effect Of Processing On The Proximate, Mineral, And Pasting ...

    African Journals Online (AJOL)

    Effect Of Processing On The Proximate, Mineral, And Pasting Properties Of Whole Flour Made From Some New Plantain And Banana Hybrids Pulp And Peel ... Whole plantain and banana flour may constitute an important feeding stuff for livestock, which may eventually provide protein in human diet from consumption of ...

  18. Proximate and mineral composition of six commercially important ...

    African Journals Online (AJOL)

    This study was conducted from May 2015 to April 2016 on the proximate and mineral composition of six species of fish from Obueyinomo River in Edo State, Nigeria. The six (6) species are M. electricus, C. gariepinus, T. zilli, A. monkei, P. obscura, P. africana. Biochemical assay of moisture, ash, crude protein, crude fiber, ...

  19. Rate of water absorption and proximate analysis of different varieties ...

    African Journals Online (AJOL)

    Water absorption and proximate composition of four varieties of maize; sweet corn, pop corn, white corn and yellow corn soaked at different temperatures and time duration were determined. Absorption increased with increase in temperatures and time but generally low at 45°C. The total average rate of hydration at different ...

  20. Correction of Misclassifications Using a Proximity-Based Estimation Method

    Directory of Open Access Journals (Sweden)

    Shmulevich Ilya


    Full Text Available An estimation method for correcting misclassifications in signal and image processing is presented. The method is based on the use of context-based (temporal or spatial information in a sliding-window fashion. The classes can be purely nominal, that is, an ordering of the classes is not required. The method employs nonlinear operations based on class proximities defined by a proximity matrix. Two case studies are presented. In the first, the proposed method is applied to one-dimensional signals for processing data that are obtained by a musical key-finding algorithm. In the second, the estimation method is applied to two-dimensional signals for correction of misclassifications in images. In the first case study, the proximity matrix employed by the estimation method follows directly from music perception studies, whereas in the second case study, the optimal proximity matrix is obtained with genetic algorithms as the learning rule in a training-based optimization framework. Simulation results are presented in both case studies and the degree of improvement in classification accuracy that is obtained by the proposed method is assessed statistically using Kappa analysis.

  1. The Grammaticalization of the Proximative in Tok Pisin. (United States)

    Romaine, Suzanne


    Discusses grammaticalization of "laik" in Tok Pisin, meaning "want/like/desire" (from English "like") and "klostu," meaning "near" (from English "close to") as markers of proximative. Shows although "klostu" was more generally a feature of Pacific Pidgin English and began to…

  2. Phytochemical, Proximate and Mineral contents of Leaves and Back ...

    African Journals Online (AJOL)

    The phytochemical, proximate and mineral contents of Ficus capensis (leaves & bark) were analyzed, using Trease and Evans and Harboure procedure, the Association of Official Analytical Chemist (AOAC) method and Atomic Absorption Spectrophotometry and Flame Photometry respectively. This study is aimed at ...

  3. Nutritive Value Assessment of Four Crop Residues by Proximate ...

    African Journals Online (AJOL)

    Dr Grace Tona

    and well-being of the populace. There is regular supply of different kinds of animal protein sources. The keeping of sheep and goats in rural communities is an age long practice in Nigeria. The West ... the amount of methane produced as reported by Fievezet al. (2005). .... negatively to global warming. Table 2: Proximate ...

  4. Local Perception and Proximate Analysis of some Edible Forest ...

    African Journals Online (AJOL)

    Local perception and proximate analysis of some edible forest plants around the University of Agriculture Makurdi Wildlife Park were investigated. The selected plants were Anona senegalensis, Cissus populnea, Tacca leontopetaloides and Vitex doniana. The Focus Group Discussion (FGD) technique was employed to ...

  5. 75 FR 5009 - Proximity Detection Systems for Underground Mines (United States)


    ..., feeders, loaders/muckers, track equipment, trucks, roof bolting machines, and mobile bridge conveyors... which you rely. Include experiences, data, models, calculations, studies and articles, and standard... outreach and/or training in the area of proximity detection (e.g., red zone warning materials). How often...

  6. Dislocation of the proximal tibiofibular joint, do not miss it

    NARCIS (Netherlands)

    van Wulfften Palthe, A.F.Y.; Musters, L.; Sonnega, R.J.A.; van der Sluijs, J.A.


    We present a case of a 45-year-old woman with a right proximal tibiofibular dislocation she sustained after a fall during roller skating. Anteroposterior and lateral radiographs confirmed the diagnosis; there were no other injuries. The dislocation was reduced by direct manipulation after

  7. Proximate and Amino Acid Composition of Celosia argentea Leaves ...

    African Journals Online (AJOL)

    The proximate, trace metals and amino acids composition of Celosia argentea were determined. The crude fat, fibre and protein contents were moderate with 1.10, 3.53 and 5.17% respectively while high in the ash content (22.43%). Results of the amino acid analysis revealed high contents of the essential amino acids with ...

  8. Proximate, phytochemical and mineral compositions of seeds of ...

    African Journals Online (AJOL)

    The envelopes were put into an oven set at 60°C for 6 h. Seeds of each plant species were milled ... This research work recommends that little quantities of these seeds should be taken periodically to minimize the adverse effects arising from consuming large quantities of the seeds. Key words: Proximate, oil, Poga oleosa, ...

  9. Performance, proximate and mineral analyses of African giant land ...

    African Journals Online (AJOL)

    Performance, proximate and mineral analyses of African giant land snail ( Archachatina marginata ) fed different nitrogen sources. ... Analysis of the Hemolymph mineral composition revealed that snails fed Diet I had the highest value for Ca2+, Mg2+ and Fe2+ while the highest value in Na+ and Zn2+ was recorded in snails ...

  10. Proximate and Anti-Nutritional Constituents of Forage Legumes at ...

    African Journals Online (AJOL)

    Five non-conventional forage legumes used as alternative plant protein sources in livestock nutrition in Nigeria were assayed for proximate and anti-nutritional compositions. The forages, Cajanus cajan, Vigna radiata, Mucuna ghana, Mucuna conchinchinensis and Mucuna rajada were harvested at emergence, 4 and 8 ...

  11. Proximate composition and functional properties of raw and ...

    African Journals Online (AJOL)

    Water binding capacity was affected in the order boiled > roasted > steeped > control. No significant change was observed for oil absorption capacity of the processed samples when compared with increase observed in water binding capacity. Key Words: Plantain, proximate composition, functional properties and ...

  12. Proximity effect in normal metal-multiband superconductor hybrid structures

    NARCIS (Netherlands)

    Brinkman, Alexander; Golubov, Alexandre Avraamovitch; Kupriyanov, M. Yu


    A theory of the proximity effect in normal metal¿multiband superconductor hybrid structures is formulated within the quasiclassical Green's function formalism. The quasiclassical boundary conditions for multiband hybrid structures are derived in the dirty limit. It is shown that the existence of

  13. local perception and proximate analysis of some edible forest plants ...

    African Journals Online (AJOL)


    2. S.A. Shomkegh and. 3. Mbakwe, R. 1. Department of Forest Production and Products, University of Agriculture Makurdi, Benue State. ... Key words: Local Perception, Proximate Analysis, Edible Forest Plants, Focused Group. Discussions. INTRODUCTION ..... Deciduous Forests of India: An Explorative. Study Towards Non ...

  14. Proximate composition and sensory properties of freeze-dried ...

    African Journals Online (AJOL)

    Two Nigerian soups (Egusi soup and bitter leaf soup) were prepared and freeze - dried to produce instant soups. These instant soups and the freshly prepared portions were subjected to proximate and sensory analysis using standard methods. The results of the analysis showed that instant egusi soup contained 10.89 ...

  15. Microbiological, proximate analysis and sensory evaluation of baked ...

    African Journals Online (AJOL)

    The possibility of making bread of good nutritional, microbiological and sensory qualities from blends of wheat-breadfruit flours was examined. Blends of wheat flour (WF) with percentages of 0, 5, 10, 15, 20 and 25 of breadfruits flour (BF) were used in the production process. The proximate analysis, sensory evaluation and ...

  16. Depressionary Effect of Proximity of Residential Properties to Waste ...

    African Journals Online (AJOL)

    It is important to know if and to which extent proximity to waste disposal sites or treatment plants depresses residential property values for many reasons. Whether as a measure of the impact of the sites on health and general welfare of the resident, or to ascertain the degree of monetary depression that would be suffered by ...

  17. Proximal tibiofibular dislocation: a case report and review of literature

    NARCIS (Netherlands)

    Nieuwe Weme, R. A.; Somford, M. P.; Schepers, T.


    An isolated dislocation of the proximal tibiofibular joint is uncommon. The mechanism of this injury is usually sports related. We present a case where initial X-rays did not show the tibiofibular joint dislocation conclusively. It was diagnosed after comparative bilateral AP X-rays of the knees

  18. Unilateral proximal focal femoral deficiency, fibular aplasia, tibial ...

    African Journals Online (AJOL)

    Rabah M. Shawky


    Apr 30, 2014 ... Unilateral proximal focal femoral deficiency, fibular aplasia, tibial campomelia and oligosyndactyly in an Egyptian child – Probable. FFU syndrome. Rabah M. ... Our patient is an Egyptian male child, fifteen months old, the third in order of .... 4th and 5th metatarsal bones are absent), absent middle phalanx.

  19. Proximate Compositions and physical properties of selected maize ...

    African Journals Online (AJOL)

    Proximate compositions and physical properties of five different maize grain varieties, Oba Supa, DMR, Popcorn, local Tiv and SWAM 1 were determined in accordance with established methods. Significant differences (P≤ 0.05) were found in the moisture, ash, crude fibre, carbohydrate and fat contents among the varieties.

  20. Effect of Processing Methods on the Proximate and Energy ...

    African Journals Online (AJOL)

    Four methods of processing were assessed to investigate the effect of processing methods on the digestibility, proximate and energy composition of Lablab purpureus (Rongai) beans. The processing methods were boiling (in water), fermentation, toasting and fermentation plus toasting. Some of The beans were boiled for 0, ...

  1. Irreducible Proximal Interphalangeal Joint Dislocation of the Fourth ...

    African Journals Online (AJOL)

    Dislocation of the interphalangeal joint of the toe is a very rare injury and there are only few published reports. Most of the cases reported are those of the hallucal interphalangeal joint. There are only very few reports of complex dislocations of the proximal interphalangeal joint of the fourth toe in the world literature. Nigerian ...

  2. Worlds largest particle physics laboratory selects Proxim Wireless Mesh

    CERN Multimedia


    "Proxim Wireless has announced that the European Organization for Nuclear Research (CERN), the world's largest particle physics laboratory and the birthplace of the World Wide Web, is using it's ORiNOCO AP-4000 mesh access points to extend the range of the laboratory's Wi-Fi network and to provide continuous monitoring of the lab's calorimeters" (1/2 page)

  3. Outcome of plate osteosynthesis in the management of proximal ...

    African Journals Online (AJOL)

    Background: This paper reports the aetiology, presentation and management of proximal humeral fractures (PHF) in our setup. Objective: To ... Five of thirty two operated cases (15%) developed significant shoulder joint stiffness. ... There is need for arthroplasty in those with severe injury, particularly those with osteoporosis.

  4. Two Stages repair of proximal hypospadias: Review of 33 cases ...

    African Journals Online (AJOL)

    Materials & Methods: During the period from June 2002 to December 2009, I performed 33 cases with proximal hypospadias, at Demerdash hospital; Ain Shams University; department of paediatric surgery. Data were collected retrospectively and included patient's age at operation, degree of the hypospadias, degree of ...

  5. Reflections on the Ecolab and the Zone of Proximal Development (United States)

    Luckin, Rosemary; du Boulay, Benedict


    In 1999 we reported a study that explored the way that Vygotsky's Zone of Proximal Development could be used to inform the design of an Interactive Learning Environment called the Ecolab. Two aspects of this work have subsequently been used for further research. Firstly, there is the interpretation of the ZPD and its associated theory that was…

  6. Biomechanical superiority of plate fixation for proximal tibial osteotomy. (United States)

    Hartford, James M; Hester, Peter; Watt, Phil M; Hamilton, Doris; Rohmiller, Michael; Pienkowski, David


    Proximal tibial osteotomies require secure and durable fixation to allow early range of motion; however, biomechanical data comparing commonly used fixation methods are lacking. The current study was done to quantify the dynamic biomechanical performance of blade staple fixation and plate fixation of simulated proximal tibial osteotomies. A 15 degrees proximal tibial osteotomy was done on each of 18 synthetic adult composite tibias. Blade staples were used as the means of fixation in nine tibias; plate fixation was used in the remaining nine tibias. The specimens were stressed cyclically in sinusoidal loading whose peak compression and tension loads imitate those measured during normal gait. Device performance was quantified by measuring displacement at the osteotomy site and the number of cycles to failure. Plate fixation had a greater fatigue life than staples (eight plates surviving past 200,000 cycles versus one blade staple) and showed a trend toward less displacement (0.69 mm versus 0.97 mm). Plate fixation of proximal tibial osteotomies offers better fixation and dynamic mechanical performance than blade staples.

  7. Unilateral proximal focal femoral deficiency, fibular aplasia, tibial ...

    African Journals Online (AJOL)

    ... dominant mutation with possible gonadal mosaicism and with variable expression in the family, as limb anomaly in one child and cyanotic congenital heart disease in another child. Keywords: Short femur; Limb anomaly; FFU syndrome; Proximal focal femoral deficiency; Fibular aplasia; Tibial campomelia; Oligosyndactyly ...

  8. Proximity effects of high voltage electric power transmission lines on ...

    African Journals Online (AJOL)


    Zeki Demir. Department of Landscape Architecture, Faculty of Forestry, Düzce University. Konuralp, 81620 Düzce, Turkey. E-mail: Tel: +90-380-5421136. Fax: +90-380-5421136. Accepted 18 August, 2010. The proximity effects of high voltage electric power transmission lines on Leyland Cypress.

  9. Effect of Graded Bambara Nut Flour on Proximate Composition and ...

    African Journals Online (AJOL)

    Proximate composition and some physico-chemical properties were determined using the parameters of protein, fat, fibre, ash, moisture, carbohydrate, swelling capacity, foam capacity, foam stability, loose and packed bulk density, water absorption capacity, pH and TTA. The protein content of the samples ranged between ...

  10. Proximity Effect at Graphene - High Tc Superconductor Junctions (United States)

    Wang, Da; Shih, En-Min; Arefe, Ghidewon; Kim, Youngduck; Edelberg, Drew; Andrade, Erick; Wang, Dennis; Hone, James; Dean, Cory; Pasupathy, Abhay; Department of Physics, Columbia University, New York, NY 10027, USA Collaboration

    The proximity effect is a well-known mesoscopic phenomenon where Cooper pairs from a superconductor (S) enter into a normal metal (N) that is well coupled to it. Since graphene was discovered a decade ago, the proximity effect at superconductor-graphene junctions has been extensively studied and interesting phenomena such as specular Andreev reflection and ballistic transport at graphene Josephson junctions have been observed. However, superconductors used in these experiments to date are of conventional low Tc, such as aluminum(Tc=1.2K), NbSe2(Tc=7K), and MoRe(Tc=8K). Understanding how the proximity effect works between high-Tc superconductors (pnictides and cuprates) and the Dirac Fermions of graphene remains largely unexplored. The chief technical challenge here is to create high-quality junctions between high-Tc superconductors and graphene. In this work, we will introduce a home-made setup that allows us to exfoliate, transfer and encapsulate superconductor-graphene junctions in a well controlled inert atmosphere. Transport measurements of the proximity effect at graphene-iron pnictide(FeSe, FeTeSe) and graphene-cuprate(BSCCO) junctions will be described.

  11. Effects of Planting Locations on the Proximate Compositions of ...

    African Journals Online (AJOL)

    ADOWIE PERE Keywords: locations, moringa, LGA, proximate composition, soil factors. Moringa leaves contain more vitamin A than carrots, more calcium than milk, more iron than spinach, more potassium than bananas, and more vitamin C than oranges. The leaves are considered to offer great.

  12. Proximate analysis of some dry season vegetables in Anyigba, Kogi ...

    African Journals Online (AJOL)



    May 16, 2008 ... the exotic vegetables cultivated in Nigeria are cabbage, lettuce, cauli-flower and turnip leafy as well as stems such as Carrot (Aliyu, 2006). ... at 550°C for 48 h, proximate chemical composition of each vegetable sample was carried out to determine the moisture, ash, fat, crude fibre, protein and carbohydrate ...

  13. Comparison of proximate and fatty acid compositions of wild brown ...

    African Journals Online (AJOL)

    The purpose of this study was to compare the fatty acid and proximate composition of two commercially exploited trout species (wild brown trout (WBT) and farmed rainbow trout (FRT)). The mean crude lipid content in FRT (4.3%) was significantly higher than that in WBT (2.7%). Total saturated fatty acid concentration ...

  14. Proximate and chemical composition of three species of snails in ...

    African Journals Online (AJOL)

    This trial was conducted to determine the proximate and chemical composition of three common species of snails in Nigeria. The species were Archachatina marginata (T1), Achatina achatina (T2), and Achatina fulica (T3). The three species constituted the three treatments and thirty-six adult snails were used for this trial ...

  15. Proximate, Physical And Sensory Properties Of Soy-Sweet Potato ...

    African Journals Online (AJOL)

    Flour mixtures consisting of full-fat soy flour and sweet potato flour at 25-75% levels were used in cookie production. Proximate, physical and sensory properties of the cookies were determined. Physical and sensory properties investigated included thickness, diameter, spread factor, spread ratio, fragility, appearance, ...

  16. Proximate and Cholesterol Composition of Selected Fast Foods ...

    African Journals Online (AJOL)

    Fast foods consumption has been on the increase in Nigeria raising concerns about the nutritional and health implications. This study was carried out to determine the proximate composition and cholesterol contents of four commonly consumed fast foods (doughnut, chicken pie, roasted chicken, and Jollof rice) sold in ...

  17. Proximate composition and basic phytochemical assessment of two ...

    African Journals Online (AJOL)


    The nut of the yellow variety had terpenoids and steroids present in it while the nut of the red variety had alkaloids present. Statistical analyses carried out showed that there were no significant differences (p≤0.05) between the two varieties based on their proximate composition. INTRODUCTION. Terminalia catappa is ...

  18. Fertility decline in Malawi: An analysis of the proximate determinants ...

    African Journals Online (AJOL)

    The paper examines trends in the proximate determinants of fertility (nuptiality or marriage, contraception and post-partum infecundability) in Malawi during the twelve-year period 1992-2004, with a view to explaining the factors responsible for fertility decline in the country. The study uses the Malawi Demographic and ...

  19. Levels and proximate determinants of fertility in Butajira District ...

    African Journals Online (AJOL)

    The impediment of early marriage was revised in the national family code which claims assessment of fertility situations. Objectives: This study aimed at measuring levels and fertility inhibition effects of proximate determinants in Butajira district. Methods: A cross-sectional study was conducted on resident women of ...

  20. Proximity effect of electron beam lithography on single-electron ...

    Indian Academy of Sciences (India)

    monly used technique in this field, and many researchers have been investigating its application to make nanopatterns. In electron beam lithography, the well-known proximity effect refers to .... electrodes are grounded. The charging effect, which blocks the injection/ejection of a single charge into/from a quantum dot, ...

  1. Proximate and Vitamin Content of Four Nigerian Pterocarpus Species

    African Journals Online (AJOL)

    Determination of the proximate and vitamin contents of four Nigerian Pterocarpus species; Pterocarpus osun, P. soyauxii, P. santalinoides and P. mildbraedii was carried out. Freshly expanded and mature leaves of the plants were used for the analysis. The investigation revealed that on the average the plants contained ...

  2. Proximity focusing RICH detector based on multilayer silica aerogel radiator

    CERN Document Server

    De Leo, R; Bellunato, T; Calvi, M; Cisbani, E; Cusanno, F; Garibaldi, F; Lagamba, L; Marra, M; Marrone, S; Matteuzzi, C; Musico, P; Nappi, E; Perego, D L; Torrioli, S; Vilardi, I


    The performance of a proximity focusing Ring Imaging Cherenkov detector equipped with a radiator of silica aerogel is presented. The aerogel tile used is a monolith with variable index of refraction. Cherenkov photons are detected with high granularity by eight Hamamatsu H9500 flat panel multi anode phototubes.

  3. Proximate, Vitamins and Mineral Composition of Vitex doniana ...

    African Journals Online (AJOL)

    Keywords: Vitex doniana, micronutrients, proximate, vitamins and mineral composition, Fruit. ... Vitamin B2 and Spectrophotometric method for. Vitamin B6, while titremetric method was used for Vitamin C. Mineral content: Mineral analysis was carried out after sample .... to calcium for bone, teeth and muscles growth.

  4. Effect of drought/irrigation on proximate composition and ...

    African Journals Online (AJOL)

    Enset [Ensete ventricosum (Welw.) Cheesman] is an important root crop serving as a carbohydrate rich food source in Ethiopia. Perennial crops, like enset, are often exposed to recurrent dry periods which could greatly affect their growth, physiology and yield. The effect of induced drought/irrigation on the proximate ...

  5. Heavy metal and proximate composition associated with the ...

    African Journals Online (AJOL)

    Changes in the heavy metal content and proximate composition during the 28 day composting of cassava peels used in the cultivation of the oyster mushrooms Pleurotus ostreatus strain EM-1 was studied. Significant dry weight variations of cellulose, hemicellulose and fat contents were observed from day 0 to 12.

  6. Proximate and mineral analysis of some wild edible mushrooms ...

    African Journals Online (AJOL)

    Proximate and mineral analysis of five species of mushroom, Lentinus squarrosulus, Volvariella volvacea, Coprinus micaceus, Lepiota procera, and Auricularia auricula were examined in this study to determine their nutritional value. These mushrooms were found to contain on the average, 3.24 to 8.70% of crude fibre; 4.12 ...

  7. Proximal femoral periprosthetic fracture fixation with a hooked ...

    African Journals Online (AJOL)

    Proximal femoral periprosthetic fracture fixation with a hooked locking plate: a Kenyan experience. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more information about how to print, save, and ...

  8. Proximate, mineral and vitamin C composition of vegetable Gbolo ...

    African Journals Online (AJOL)

    Gbolo (Crassocephalum crepidioides and Crassocephalum rubens) is a traditional leafy vegetable highly consumed in southern and central Benin, as well as in some part of northern Benin. The nutritional potential of the two species of Gbolo were evaluated through their proximate composition, mineral and vitamin C ...

  9. Effect of drying temperatures on the proximate composition and ...

    African Journals Online (AJOL)

    A study was conducted to dry chicken eggs in order to determine the effect of drying temperatures on the proximate composition and sensory attributes of dried eggs. The albumen, yolk and whole egg were dried separately at temperatures of 50, 55 and 60oC. The drying time for the samples ranged from 7hrs20mins to ...

  10. Long‑Term Outcome of Endoprosthetic Replacement for Proximal ...

    African Journals Online (AJOL)

    Giant cell tumor (GCT) represents 5% of neoplasms of bone. It is a benign locally aggressive tumor usually involving the distal end of the femur, proximal tibia and distal radius in young adults.[1-3] The main variables to be considered for planning treatment include the site of involvement and Campanacci stage of the tumor.

  11. Children's Attentional Processing of Mother and Proximity Seeking.

    Directory of Open Access Journals (Sweden)

    Guy Bosmans

    Full Text Available Attachment expectations regarding the availability of mother as a source for support are supposed to influence distressed children's support seeking behavior. Because research is needed to better understand the mechanisms related to support seeking behavior, this study tested the hypothesis that the cognitive processing of mother-related information is linked to proximity and support seeking behavior. Uncertainty in maternal support has been shown to be characterized by a biased attentional encoding of mother, reducing the breadth of children's attentional field around her. We investigated whether this attentional bias is related to how long distressed children wait before seeking their mother's proximity. Thirty-three children (9-11 years participated in this study that consisted of experimental tasks to measure attentional breadth and to observe proximity seeking behavior and of questionnaires to measure confidence in maternal support and experienced distress. Results suggested that distressed children with a more narrow attentional field around their mother wait longer to seek her proximity. Key Message: These findings provide a first support for the hypothesis that the attentional processing of mother is related to children's attachment behavior.

  12. Effect of thermal processing methods on the proximate composition ...

    African Journals Online (AJOL)

    The nutritive value of raw and thermal processed castor oil seed (Ricinus communis) was investigated using the following parameters; proximate composition, gross energy, mineral constituents and ricin content. Three thermal processing methods; toasting, boiling and soaking-and-boiling were used in the processing of the ...

  13. Proximity effects of high voltage electric power transmission lines on ...

    African Journals Online (AJOL)

    The proximity effects of high voltage electric power transmission lines on Leyland Cypress (xCupressocyparis leylandii (Dallim. and A.B. Jacks.) Dallim) and Japanese Privet (Ligustrum japonicum Thunb.) growth were examined in a private nursery located in Sakarya, Turkey. Five transect were randomly chosen in both ...

  14. 37 Nigerian Journal of Chemical Research Vol. 19, 2014 Proximate ...

    African Journals Online (AJOL)


    Nigerian Journal of Chemical Research. Vol. 19, 2014. Proximate, Mineral and Anti-nutritional Composition of Cucurbita Maxima Fruits Parts. Mohaammed S. S. 1 ., Paiko Y. B. 2 ., Mann A. 2 ., Ndamitso M. M. 3 ., Mathew J. T. 2 . and Maaji, S. 1 . 1. Deparment of Biochemistry, Federal University of Technology, P.M. B. 65, ...

  15. Observing Complex Systems Thinking in the Zone of Proximal Development (United States)

    Danish, Joshua; Saleh, Asmalina; Andrade, Alejandro; Bryan, Branden


    Our paper builds on the construct of the zone of proximal development (ZPD) (Vygotsky in Mind in society: the development of higher psychological processes, Harvard University Press, Cambridge, 1978) to analyze the relationship between students' answers and the help they receive as they construct them. We report on a secondary analysis of…

  16. Visualizing cellular interactions with a generalized proximity reporter. (United States)

    Sellmyer, Mark A; Bronsart, Laura; Imoto, Hiroshi; Contag, Christopher H; Wandless, Thomas J; Prescher, Jennifer A


    Interactions among neighboring cells underpin many physiological processes ranging from early development to immune responses. When these interactions do not function properly, numerous pathologies, including infection and cancer, can result. Molecular imaging technologies, especially optical imaging, are uniquely suited to illuminate complex cellular interactions within the context of living tissues in the body. However, no tools yet exist that allow the detection of microscopic events, such as two cells coming into close proximity, on a global, whole-animal scale. We report here a broadly applicable, longitudinal strategy for probing interactions among cells in living subjects. This approach relies on the generation of bioluminescent light when two distinct cell populations come into close proximity, with the intensity of the optical signal correlating with relative cellular location. We demonstrate the ability of this reporter strategy to gauge cell-cell proximity in culture models in vitro and then evaluate this approach for imaging tumor-immune cell interactions using a murine breast cancer model. In these studies, our imaging strategy enabled the facile visualization of features that are otherwise difficult to observe with conventional imaging techniques, including detection of micrometastatic lesions and potential sites of tumor immunosurveillance. This proximity reporter will facilitate probing of numerous types of cell-cell interactions and will stimulate the development of similar techniques to detect rare events and pathological processes in live animals.

  17. Proximate composition and the functional properties of defatted ...

    African Journals Online (AJOL)

    The proximate composition of the Kargo seeds and the physico-chemical properties of the seed oil have been determined. Matured dried seeds were collected. They were then dehusked and pulverized into a fine powder and kept in air tight sample bottle for further analysis. Functional properties of the defatted sample and ...

  18. Proximate and nutrient analysis of selected vegetable species: A ...

    African Journals Online (AJOL)



    Jun 17, 2009 ... ascorbic acid and palpable concentration of trace minerals (Prakash and Pal, ... vegetables plays a crucial role in assessing their nutri- tional significance .... Table 4. Correlation matrix of the various parameters studied for the proximate analysis of selected plant species. Moisture. (wet). Moistures. (dry). Ash.

  19. Determination of Proximate Composition and Amino Acid Profile of ...

    African Journals Online (AJOL)


    livestock nutrition. Keywords: Sesamum indicum; Proximate composition; Amino acid profile; Nutrient value. Correspondence: Introduction. Sesame ... presence of oxygen in the air to CO2 at a temperature of 600 0C (dry ashing). The % ash content was ..... Effect of Heat Treatment and Defatting.

  20. Proximity to coast is linked to climate change belief.

    Directory of Open Access Journals (Sweden)

    Taciano L Milfont

    Full Text Available Psychologists have examined the many psychological barriers to both climate change belief and concern. One barrier is the belief that climate change is too uncertain, and likely to happen in distant places and times, to people unlike oneself. Related to this perceived psychological distance of climate change, studies have shown that direct experience of the effects of climate change increases climate change concern. The present study examined the relationship between physical proximity to the coastline and climate change belief, as proximity may be related to experiencing or anticipating the effects of climate change such as sea-level rise. We show, in a national probability sample of 5,815 New Zealanders, that people living in closer proximity to the shoreline expressed greater belief that climate change is real and greater support for government regulation of carbon emissions. This proximity effect held when adjusting for height above sea level and regional poverty. The model also included individual differences in respondents' sex, age, education, political orientation, and wealth. The results indicate that physical place plays a role in the psychological acceptance of climate change, perhaps because the effects of climate change become more concrete and local.

  1. Some Proximate Analysis of African Pear ( Dacryodes Edulis ...

    African Journals Online (AJOL)

    0.05) were observed between the samples for all the parameters measured. Fruit density showed a negative correlation (r = -0.86) with the pulp/seed ratio. Significant differences were also observed in the proximate composition of the African pear pulp. The major components of the pulp were moisture (36.5% to 53.82%), ...

  2. Proximate composition and mineral content in different, types of ...

    African Journals Online (AJOL)

    Proximate composition and mineral content in different, types of traditional TOGWA used in Tanzania as a weaning food. ... Crude fibre was also higher in traditional and simulated togwa than in the main ingredients, while carbohydrate percent of DM and energy contents were lower than in the ingredients. Ash contents in ...

  3. Proximate analysis of selected sorghum cultivars | Jimoh | Bayero ...

    African Journals Online (AJOL)

    The proximate analysis revealed that sorghum samples contains appreciable nutrient contents. Also from the result, it has shown that the values of the improved varieties from the Institute for Agricultural research (IAR) Zaria is higher in the parameters analysed as compared to the local samples. The mineral composition of ...

  4. Extraoral imaging for proximal caries detection: Bitewings vs scanogram. (United States)

    Khan, Emad A; Tyndall, Donald A; Caplan, Daniel


    The objective of this study was to compare the diagnostic accuracy of 3 extraoral imaging modalities with an intraoral bitewing radiograph for proximal caries detection. Three modalities of Cranex TOME scanograms, x-ray film and DenOptix photostimulable phosphor plates with and without digital enhancement, were compared with Insight intraoral radiographs for proximal caries detection. Nine observers evaluated images of the proximal surfaces of 45 extracted posterior teeth. The presence or absence of caries was scored using a 5-point confidence scale. The ground truth was determined from histological sections. Responses were evaluated by repeated measures analysis of variance (ANOVA) for areas under receiver operating characteristic (ROC) curves (A z ). Repeated measures ANOVA (at alpha = 0.05) demonstrated significant differences among modalities ( P = .041). Paired t tests with Bonferroni correction demonstrated that Insight was superior to only unenhanced digital scanograms ( P = .003). Mean A z scores (+/-SD) were 0.73 (+/-0.08) for Insight, 0.65 (+/-0.06) for screen/film scanogram, 0.64 (+/-0.04) for unenhanced digital scanogram, and 0.66 (+/-0.07) for enhanced digital scanogram. The performances of film-based and enhanced digital scanograms were not statistically different from Insight film for proximal caries detection. Unenhanced digital scanograms exhibited a statistically significant lower diagnostic accuracy than Insight film.

  5. Sharpening a Tool for Teaching: The Zone of Proximal Development (United States)

    Wass, Rob; Golding, Clinton


    Vygotsky's Zone of Proximal Development (ZPD) provides an important understanding of learning, but its implications for teachers are often unclear or limited and could be further explored. We use conceptual analysis to sharpen the ZPD as a teaching tool, illustrated with examples from teaching critical thinking in zoology. Our conclusions are…

  6. Scaffolding Critical Thinking in the Zone of Proximal Development (United States)

    Wass, Rob; Harland, Tony; Mercer, Alison


    This paper explores student experiences of learning to think critically. Twenty-six zoology undergraduates took part in the study for three years of their degree at the University of Otago, New Zealand. Vygotsky's developmental model of the Zone of Proximal Development (ZPD) provided a framework as we examined how critical thinking was developed.…

  7. Effect of Different Soaking Time and Boiling on the Proximate ...

    African Journals Online (AJOL)

    The effect of soaking time on the proximate composition and functional properties of sprouted sesame seed flour were investigated. Sesame seed samples were cleaned and pretreated by soaking in clean water for 8, 10, 12, 14 and 16 h. One batch was sprouted for 36 h and another portion was sprouted and then boiled ...

  8. Proximal dup(10q): Case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Barritt, J.A.; Teague, K.E.; Bodurtha, J.N. [Virginia Commonwealth Univ., Richmond, VA (United States)] [and others


    We report a case of a proximal dir dup(10q) in a female with multiple congenital anomalies. During infancy she was noted to gave growth retardation, microcephaly, microphthalmia, coloboma, a long, beaked nose, posteriorly rotated ears with simple helices, full bowed lips, widely-spaced nipples, broad first toes, hypermobile and proximally placed thumbs, a heart murmur, PDA, and coarctation of the aorta. Additional findings at age 13 included a full columella, short philtrum, thin limbs, bilateral blindness, and mental retardation, as well as continued growth retardation. Her medical history included precocious puberty at age 8 and a diagnosis of hyperactivity. Using FISH with multiple probes combined with GTG-banding, the aberrant chromosome was determined to be a dir dup(10)(q21{r_arrow}q22). Parental chromosomes were normal and the family history was unremarkable. The parental origin of the dir dup(10) is being assessed using DNA markers. Five similar cases of proximal dup(10q) have been reported previously. Consistent characteristics include low birth weight, developmental and psychomotor delay, growth retardation, and microcephaly. Also found in most cases were short prominent philtrum, bowed mouth, PDA, thin limbs, coloboma, micropthalmia, deep set eyes, and other ocular anomalies. Our case is unique in that she has a long, beaked nose, precocious puberty, and hyperactivity. Future studies such as this, using molecular cytogenetic techniques to better define the chromatin involved in proximal dup(10q), may lead to its recognition as a distinct clinical phenotype.

  9. Distal and proximal predictors of snacking at work: A daily-survey study. (United States)

    Sonnentag, Sabine; Pundt, Alexander; Venz, Laura


    This study aimed at examining predictors of healthy and unhealthy snacking at work. As proximal predictors we looked at food-choice motives (health motive, affect-regulation motive); as distal predictors we included organizational eating climate, emotional eating, and self-control demands at work. We collected daily survey data from 247 employees, over a period of 2 workweeks. Multilevel structural equation modeling showed that organizational eating climate predicted health as food-choice motive, whereas emotional eating and self-control demands predicted affect regulation as food-choice motive. The health motive, in turn, predicted consuming more fruits and more cereal bars and less sweet snacks; the affect-regulation motive predicted consuming more sweet snacks. Findings highlight the importance of a health-promoting eating climate within the organization and point to the potential harm of high self-control demands at work. (PsycINFO Database Record (c) 2017 APA, all rights reserved).


    Directory of Open Access Journals (Sweden)

    Praveen Sivakumar K


    Full Text Available BACKGROUND Techniques for treating complex proximal humeral fractures vary and include fixations using tension bands, percutaneous pins, bone suture, T-plates, intramedullary nails, double tubular plates, hemiarthroplasty, plant tan humerus fixator plates, Polaris nails and blade plates. Complications of these techniques include cutout or back out of the screws and plates, avascular necrosis, nonunion, malunion, nail migration, rotator cuff impairment and impingement syndromes. Insufficient anchorage from conventional implants may lead to early loosening and failure, especially in osteoporotic bones. In general, nonoperative treatment of displaced three and four-part fractures of the proximal humerus leads to poor outcome due to intraarticular nature of injury and inherent instability of the fragments. Comminuted fractures of the proximal humerus are at risk of fixation failure, screw loosening and fracture displacement. Open reduction and internal fixation with conventional plate and screws has been associated with unacceptably high incidence of screw pull out. PHILOS (the proximal humeral internal locking system plate is an internal fixation system that enables angled stabilisation with multiple interlocking screws for fractures of the proximal humerus. MATERIALS AND METHODS 30 patients with proximal humerus fractures who were admitted in the Department of Orthopaedics, Government General Hospital, Kakinada, during the period November 2014 - November 2016 were taken up for study according to inclusion criteria. All patients were treated with PHILOS plate. These proximal humerus fractures were classified according to Neer’s classification. Patients were followed up at 6 weeks, 12 weeks and 6 months’ interval. Functional outcomes for pain, range of motion and muscle power and function were assessed using the Constant-Murley scoring system. Collected data analysed with independent t-test and ANNOVA test. RESULTS The outcome of the study was 1

  11. Surgical treatment of proximal humerus fractures using PHILOS plate

    Directory of Open Access Journals (Sweden)

    Vijay Sharma


    Full Text Available 【Abstract】Objective: To evaluate functional outcome and complications of open reduction and internal fixation with proximal humeral internal locking system (PHILOS plate for proximal humerus fractures. Methods: We reviewed 51 patients who underwent open reduction and internal fixation with PHILOS plate between the years 2007 to 2012. There were 35 men and 16 women with a mean age of 38 years (range 24-68. There were 41 patients in the age group of <60 years and 10 patients in the age group of >60 years. According to Neer classification system, 8, 15 and 23 patients had 2-part, 3-part, and 4-part fractures, respectively and 5 patients had 4-part fracture dislocation. All surgeries were carried out at our tertiary care trauma centre. Functional evaluation of the shoulder at final follow-up was done using Constant-Murley score. Results: The mean follow-up period was 30 months (range 12-44 months. Two patients were lost to followup. Of the remaining 49 patients, all fractures were united clinically and radiologically. The mean time for radiological union was 12 weeks (range 8-20 weeks. At the final follow-up the mean Constant-Murley score was 79 (range 50-100. The results were excellent in 25 patients, good in 13 patients, fair in 6 atients and poor in 5 patients. During the follow-up, four cases of varus malunion, one case of subacromial impingement, one case of deep infection, one case of intraarticular screw penetration and one case of failure of fi xation were noted. No cases of avascular necrosis, hardware failure, locking screw loosening or nonunion were noted. Conclusion: PHILOS provides stable fixation in proximal humerus fractures. To prevent potential complications like avascular necrosis, meticulous surgical dissection to preserve vascularity of humeral head is necessary. Key words: Proximal humerus fracture; Fracture fixation, internal; Proximal humeral internal locking system

  12. Proximal supination osteotomy of the first metatarsal for hallux valgus. (United States)

    Yasuda, Toshito; Okuda, Ryuzo; Jotoku, Tsuyoshi; Shima, Hiroaki; Hida, Takashi; Neo, Masashi


    Risk factors for hallux valgus recurrence include postoperative round-shaped lateral edge of the first metatarsal head and postoperative incomplete reduction of the sesamoids. To prevent the occurrence of such conditions, we developed a proximal supination osteotomy of the first metatarsal. Our aim was to describe this novel technique and report the outcomes in this report. Sixty-six patients (83 feet) underwent a distal soft tissue procedure combined with a proximal supination osteotomy. After the proximal crescentic osteotomy, the proximal fragment was pushed medially, and the distal fragment was abducted, and then the distal fragment of the first metatarsal was manually supinated. Outcomes were assessed using the American Orthopaedic Foot & Ankle Society (AOFAS) score and radiographic examinations. The average follow-up duration was 34 (range, 25 to 52) months. The mean AOFAS score improved significantly from 58.0 points preoperatively to 93.8 points postoperatively (P hallux valgus and intermetatarsal angle decreased significantly from 38.6 and 18.0 degrees preoperatively to 11.0 and 7.9 degrees postoperatively, respectively (both, P hallux valgus, defined as a hallux valgus angle ≥ 25 degrees. The rates of occurrence of a positive round sign and incomplete reduction of the sesamoids significantly decreased postoperatively, which may have contributed to the low hallux valgus recurrence rates. We conclude that a proximal supination osteotomy was an effective procedure for correction of hallux valgus and can achieve a low rate of hallux valgus recurrence. Level IV, retrospective case series. © The Author(s) 2015.

  13. A randomized, double-blind, placebo-controlled, clinical trial on probiotic soy milk and soy milk: effects on epigenetics and oxidative stress in patients with type II diabetes. (United States)

    Hariri, Mitra; Salehi, Rasoul; Feizi, Awat; Mirlohi, Maryam; Ghiasvand, Reza; Habibi, Nahal


    This clinical trial aimed to discover the effects of probiotic soy milk and soy milk on MLH1 and MSH2 promoter methylation, and oxidative stress among type II diabetic patients. Forty patients with type II diabetes mellitus aged 35-68 years were assigned to two groups in this randomized, double-blind, controlled clinical trial. Patients in the intervention group consumed 200 ml/day of probiotic soy milk containing Lactobacillus plantarum A7, while those in the control group consumed 200 ml/d of conventional soy milk for 8 weeks. Fasting blood samples, anthropometric measurements, and 24-h dietary recalls were collected at the baseline and at the end of the study, respectively. Probiotic soy milk significantly decreased promoter methylation in proximal and distal MLH1 promoter region (P soy milk (P soy milk group compared with baseline value (P  0.05). The consumption of probiotic soy milk improved antioxidant status in type II diabetic patients and may decrease promoter methylation among these patients, indicating that probiotic soy milk is a promising agent for diabetes management.

  14. Perceptions of health promoters about health promotion ...

    African Journals Online (AJOL)


    Feb 11, 2013 ... care level workers such as caregivers to render health promotion and education in the homes and communities. .... Health promotion:defined byO'Donnel as 'the science and art ..... Trinity Hospice and Palliative Care Services.

  15. Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis. (United States)

    Yu, Jian; Ni, Min; Xu, Jian; Zhang, Hongyu; Gao, Baomei; Gu, Jianren; Chen, Jianguo; Zhang, Lisheng; Wu, Mengchao; Zhen, Sushen; Zhu, Jingde


    Hepatocellular carcinoma (HCC) presents one of the major health threats in China today. A better understanding of the molecular genetics underlying malignant transformation of hepatocytes is critical to success in the battle against this disease. The methylation state of C5 of the cytosine in the CpG di-nucleotide that is enriched within or near the promoter region of over 50 % of the polymerase II genes has a drastic effect on transcription of these genes. Changes in the methylation profile of the promoters represent an alternative to genetic lesions as causative factors for the tumor-specific aberrant expression of the genes. We have used the methylation specific PCR method in conjunction with DNA sequencing to assess the methylation state of the promoter CpG islands of twenty genes. Aberrant expression of these genes have been attributed to the abnormal methylation profile of the corresponding promoter CpG islands in human tumors. While the following sixteen genes remained the unmethylated in all tumor and normal tissues: CDH1, APAF1, hMLH1, BRCA1, hTERC, VHL, RARbeta, TIMP3, DAPK1, SURVIVIN, p14ARF, RB1, p15INK4b, APC, RASSF1c and PTEN, varying degrees of tumor specific hypermethylation were associated with the p16INK4a, RASSF1a, CASP8 and CDH13 genes. For instance, the p16INK4a was highly methylated in HCC (17/29, 58.6%) and less significantly methylated in non-cancerous tissue (4/29. 13.79%). The RASSF1a was fully methylated in all tumor tissues (29/29, 100%), and less frequently methylated in corresponding non-cancerous tissue (24/29, 82.75%). Furthermore, co-existence of methylated with unmethylated DNA in some cases suggested that both genetic and epigenetic (CpG methylation) mechanisms may act in concert to inactivate the p16INK4a and RASSF1a in HCC. Finally, we found a significant association of cirrhosis with hypermethylation of the p16INK4a and hypomethylation of the CDH13 genes. For the first time, the survey was carried out on such an extent that it

  16. Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis

    Directory of Open Access Journals (Sweden)

    Zhang Lisheng


    Full Text Available Abstract Background Hepatocellular carcinoma (HCC presents one of the major health threats in China today. A better understanding of the molecular genetics underlying malignant transformation of hepatocytes is critical to success in the battle against this disease. The methylation state of C5 of the cytosine in the CpG di-nucleotide that is enriched within or near the promoter region of over 50 % of the polymerase II genes has a drastic effect on transcription of these genes. Changes in the methylation profile of the promoters represent an alternative to genetic lesions as causative factors for the tumor-specific aberrant expression of the genes. Methods We have used the methylation specific PCR method in conjunction with DNA sequencing to assess the methylation state of the promoter CpG islands of twenty genes. Aberrant expression of these genes have been attributed to the abnormal methylation profile of the corresponding promoter CpG islands in human tumors. Results While the following sixteen genes remained the unmethylated in all tumor and normal tissues: CDH1, APAF1, hMLH1, BRCA1, hTERC, VHL, RARβ, TIMP3, DAPK1, SURVIVIN, p14ARF, RB1, p15INK4b, APC, RASSF1c and PTEN, varying degrees of tumor specific hypermethylation were associated with the p16INK4a , RASSF1a, CASP8 and CDH13 genes. For instance, the p16INK4a was highly methylated in HCC (17/29, 58.6% and less significantly methylated in non-cancerous tissue (4/29. 13.79%. The RASSF1a was fully methylated in all tumor tissues (29/29, 100%, and less frequently methylated in corresponding non-cancerous tissue (24/29, 82.75%. Conclusions Furthermore, co-existence of methylated with unmethylated DNA in some cases suggested that both genetic and epigenetic (CpG methylation mechanisms may act in concert to inactivate the p16INK4a and RASSF1a in HCC. Finally, we found a significant association of cirrhosis with hypermethylation of the p16INK4a and hypomethylation of the CDH13 genes. For the

  17. Open reduction and internal fixation of proximal humeral fractures with use of the locking proximal humerus plate. Surgical technique. (United States)

    Konrad, G; Bayer, J; Hepp, P; Voigt, C; Oestern, H; Kääb, M; Luo, C; Plecko, M; Wendt, K; Köstler, W; Südkamp, N


    The treatment of unstable displaced proximal humeral fractures, especially in the elderly, remains controversial. The objective of the present prospective, multicenter, observational study was to evaluate the functional outcome and the complication rate after open reduction and internal fixation of proximal humeral fractures with use of a locking proximal humeral plate. One hundred and eighty-seven patients (mean age, 62.9 +/- 15.7 years) with an acute proximal humeral fracture were managed with open reduction and internal fixation with a locking proximal humeral plate. At the three-month, six month,and one-year follow-up examinations, 165 (88%), 158 (84%), and 155 (83%) of the 187 patients were assessed with regard to pain, shoulder mobility, and strength. The Constant score was determined at each interval, and the Disabilities of the Arm, Shoulder and Hand (DASH) score was determined for the injured and contralateral extremities at the time of the one-year follow-up. Between three months and one year, the mean range of motion and the mean Constant score for the injured shoulders improved substantially. Twelve months after surgery, the mean Constant score for the injured side was 70.6 +/- 13.7 points, corresponding to 85.1% +/- 14.0% of the score for the contralateral side. The mean DASH score at the time of the one-year follow-up was 15.2 +/- 16.8 points. Sixty-two complications were encountered in fifty-two (34%) of 155 patients at the time of the one-year follow-up. Twenty-five complications (40%) were related to incorrect surgical technique and were present at the end of the operative procedure. The most common complication, noted in twenty-one (14%) of 155 patients, was intraoperative screw perforation of the humeral head. Twenty-nine patients (19%) had an unplanned second operation within twelve months after the fracture. Surgical treatment of displaced proximal humeral fractures with use of the locking proximal humeral plate that was evaluated in the

  18. Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin

    Directory of Open Access Journals (Sweden)

    Smith Jennifer M


    Full Text Available Abstract Background One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. Methods RNA interference (RNAi was used to reduce the transcription-coupled nucleotide excision repair (TC-NER capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. Results These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. Conclusion The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic.

  19. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    NARCIS (Netherlands)

    Luchtenborg, M.; Weijenberg, M.P.; Wark, P.A.; Saritas, A.M.; Roemen, G.M.; Muijen, G.N.P. van; Bruine, A.P. de; Brandt, P.A. van den; Goeij, A.F. de


    BACKGROUND: The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of

  20. Selenium compounds activate ATM-dependent DNA damage responses via the mismatch repair protein hMLH1 in colorectal cancer cells (United States)

    Epidemiological and animal studies indicate that selenium supplementation suppresses risk of colorectal and other cancers. The majority of colorectal cancers are characterized by a defective DNA mismatch repair (MMR) process. Here, we have employed the MMR-deficient HCT 116 colorectal cancer cells ...

  1. Microsatellite instability and expression of hMLH-1 and hMSH-2 in sebaceous gland carcinomas as markers for Muir-Torre syndrome

    NARCIS (Netherlands)

    Entius, M. M.; Keller, J. J.; Drillenburg, P.; Kuypers, K. C.; Giardiello, F. M.; Offerhaus, G. J.


    Sebaceous gland carcinomas (SGCs) are rare malignant skin tumors occurring sporadically or as a phenotypic feature of the Muir-Torre syndrome (MTS). A subset of patients with MTS have a variant of the hereditary nonpolyposis colorectal cancer syndrome caused by mutations in mismatch repair (MMR)

  2. Identification of Factors Interacting with hMSH2 and hMLH1 in the Fetal Liver and Investigations of how Mitochondrial Dysfunction Creates a Mutator Phenotype

    DEFF Research Database (Denmark)

    Rasmussen, Anne Karin

    demonstrated that hMSH2 interacts with a human 5’ → 3’ exonuclease 1 (hEXO1). Data presented in this thesis also support the conclusion that mitochondrial dysfunction leads to spontaneous nuclear DNA damage. We employed the yeast Saccharomyces cerevisiae as a model system to investigate a potential link...... between mitochondrial activity and genomic instability. Mitochondrial dysfunction and genetic instability are characteristic features of cancer cells. Furthermore, mitochondrial dysfunction is a key feature of aging due to accumulation of mutations in mtDNA. Our studies in a yeast model system suggest...

  3. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva


    hybridization (CGH) platform of 60mer oligonucleotides. The 4 x 44 K array format provides high-resolution coverage (200-300 bp) of 400-700 kb genomic regions surrounding six cancer susceptibility genes. We evaluate its performance to accurately detect and precisely map earlier described or novel large germline...... of primers for sequence determination of the breakpoints. The array platform can be streamlined for a particular application, e.g., focusing on breast cancer susceptibility genes, with increased capacity using multiformat design, and represents a valuable new tool and complement for genetic screening...

  4. Radiographic and Computed Tomographic Configuration of Incomplete Proximal Fractures of the Proximal Phalanx in Horses Not Used for Racing. (United States)

    Brünisholz, Hervé P; Hagen, Regine; Fürst, Anton E; Kuemmerle, Jan M


    To characterize the configuration of incomplete proximal fractures of the proximal phalanx (P1) in horses not used for racing and compare radiographic with computed tomography (CT) findings. Historical cohort. Twenty-four horses with incomplete fractures of P1. Medical records of horses not used for racing diagnosed with an incomplete proximal fracture of P1 based on clinical and radiographic examination and confirmed by CT between 2008 and 2013 were retrieved. Radiographs and CT studies of these horses were analyzed using a subjective grading system and by measuring variables that characterized fracture configuration. Twenty-four horses were included (20 Warmbloods) with a mean age of 9.5 years and mean body weight of 574 kg. Fourteen forelimbs and 10 hind limbs were affected. Mean duration of lameness was 8.7 weeks. Computed tomography was superior to radiography in both identifying the fracture and determining fracture size and location. On CT, 92% of fractures were located in the mid-sagittal plane. Mean proximodistal length of the fracture was 13 mm. Fractures were frequently not bicortical. Fractures in forelimbs were located significantly more dorsally than fractures in hind limbs. A distinct fracture pattern with 2 subchondral lines running parallel in close proximity to each other was identified in 54% of cases. Incomplete proximal fractures of P1 have significant variation in their configurations, especially their dorsopalmar/-plantar location. Computed tomography examination allowed clear identification of the fracture configurations and was superior to radiography. © Copyright 2015 by The American College of Veterinary Surgeons.

  5. Extrapolating demography with climate, proximity and phylogeny: approach with caution. (United States)

    Coutts, Shaun R; Salguero-Gómez, Roberto; Csergő, Anna M; Buckley, Yvonne M


    Plant population responses are key to understanding the effects of threats such as climate change and invasions. However, we lack demographic data for most species, and the data we have are often geographically aggregated. We determined to what extent existing data can be extrapolated to predict population performance across larger sets of species and spatial areas. We used 550 matrix models, across 210 species, sourced from the COMPADRE Plant Matrix Database, to model how climate, geographic proximity and phylogeny predicted population performance. Models including only geographic proximity and phylogeny explained 5-40% of the variation in four key metrics of population performance. However, there was poor extrapolation between species and extrapolation was limited to geographic scales smaller than those at which landscape scale threats typically occur. Thus, demographic information should only be extrapolated with caution. Capturing demography at scales relevant to landscape level threats will require more geographically extensive sampling. © 2016 John Wiley & Sons Ltd/CNRS.

  6. Proximal Limb Weakness Reverting After CSF Diversion In Intracranial Hypertension

    Directory of Open Access Journals (Sweden)

    Sinha S


    Full Text Available We report about two young girls who developed progressive visual failure secondary to increased intracranial pressure and had significant proximal muscle weakness of limbs. Patients with elevated intracranial pressure (ICP may present with "false localizing signs", besides having headache, vomiting and papilledema. Radicular pain as a manifestation of raised ICP is rare and motor weakness attributable to polyradiculopathy is exceptional. Two patients with increased intracranial pressure without lateralizing signs′ had singnificant muscle weakness. Clinical evaluation and laboratory tests did not disclose any other cause for weakness. Following theco-peritoneal shunt, in both patients, there was variable recovery of vision but the proximal weakness and symptoms of elevated ICP improved rapidly. Recognition of this uncommon manifestation of raised ICP may obviate the need for unnecessary investigation and reduce morbidity due to weakness by CSF diversion procedure.

  7. STRaND-2: Visual inspection, proximity operations & nanosatellite docking (United States)

    Bridges, C. P.; Taylor, B.; Horri, N.; Underwood, C. I.; Kenyon, S.; Barrera-Ars, J.; Pryce, L.; Bird, R.

    The Surrey Training Research and Nanosatellite Demonstrator (STRaND) programme has been success in identifying and creating a leading low-cost nanosatellite programme with advanced attitude and orbit control system (AOCS) and experimental computing platforms based on smart-phone technologies. The next demonstration capabilities, that provide a challenging mission to the existing STRaND platform, is to perform visual inspection, proximity operations and nanosatellite docking. Visual inspection is to be performed using a COTS LIDAR system to estimate range and pose under 100 m. Proximity operations are controlled using a comprehensive guidance, navigation and control (GNC) loop in a polar form of the Hills Clohessy Wiltshire (HCW) frame including J2 perturbations. And finally, nanosatellite docking is performed at under 30 cm using a series of tuned magnetic coils. This paper will document the initial experiments and calculations used to qualify LIDAR components, size the mission thrust and tank requirements, and air cushion table demonstrations of the docking mechanism.

  8. Proximate composition analysis posterior to the cryopreservation of Chaetoceros calcitrans

    Directory of Open Access Journals (Sweden)

    Joan Salas-Leiva


    Full Text Available Objective. The effect of cryopreservation on the proximate composition of microalgae Chaetoceros calcitrans was evaluated. Materials and methods. C. calcitrans was cultured and cryopreserved using 5% (v/v dimethylsulfoxide as cryoprotectant. The freezing was controlled at a rate of 3°C/min, up to -60°C and then the microalgae were immersed in liquid nitrogen (-196°C. After storage in liquid nitrogen, microalgae were rapidly thawed out and subcultured. The percentage of proteins, lipids and carbohydrates was analyzed using absorption spectrophotometry and the organic matter was studied by gravimetric analysis. Results. There was no significant variation between the proximate composition of C. calcitrans cryopreserved and the controls (p>0.05. Conclusion. Our results show that, despite low cell recovery after the preservation of this organism at low temperatures, there is no apparent loss of nutritional characteristics caused by the storing process at low temperatures.

  9. Impact of Relational Proximity on Distress from Infidelity

    Directory of Open Access Journals (Sweden)

    Maryanne Fisher


    Full Text Available Men are generally more distressed by a partner's sexual infidelity whereas women are generally more distressed by a partner's emotional infidelity. The importance of the identity of the interloper, however, has been neglected. We explored the influence of relational proximity (i.e., the degree of genetic relatedness on distress about infidelity. In Study 1, participants were most distressed when the imagined infidelity occurred between their current mate and close kin. In Study 2, relational proximity mattered more than the type of sexual behavior, the likelihood of contracting a sexually transmitted disease, and the likelihood of the infidelity leading to a damaged reputation. Together, the results indicate that identity matters, especially if the interloper is someone with whom we have familial bonds.

  10. Automated space vehicle control for rendezvous proximity operations (United States)

    Lea, Robert N.


    Rendezvous during the unmanned space exploration missions, such as a Mars Rover/Sample Return will require a completely automatic system from liftoff to docking. A conceptual design of an automated rendezvous, proximity operations, and docking system is being implemented and validated at the Johnson Space Center (JSC). The emphasis is on the progress of the development and testing of a prototype system for control of the rendezvous vehicle during proximity operations that is currently being developed at JSC. Fuzzy sets are used to model the human capability of common sense reasoning in decision making tasks and such models are integrated with the expert systems and engineering control system technology to create a system that performs comparably to a manned system.

  11. Proximal hamstring lengthening in the sitting cerebral palsy patient. (United States)

    Elmer, E B; Wenger, D R; Mubarak, S J; Sutherland, D H


    We retrospectively studied 62 nonambulatory children with spastic quadriplegic cerebral palsy who underwent proximal hamstring lengthening to improve hip and spine positioning. Preoperatively, all had hamstring contracture, with difficulty sitting due to hip extensor thrust and increased kyphosis. Thirty-five patients with follow-up greater than or equal to 2 years were studied using a modified Reimer scale to assess sitting ability. Sitting ability improved significantly (p less than 0.01) postoperatively, along with popliteal angle (p less than 0.001) and straight leg raising (p less than 0.001). Proximal hamstring lengthening is effective in treating severe hamstring contractures in the wheelchair-bound child with cerebral palsy.

  12. Affordable dual-sensing proximity sensor for touchless interactive systems

    KAUST Repository

    Nassar, Joanna M.


    We report an ultra-low cost flexible proximity sensor using only off-the-shelf recyclable materials such as aluminum foil, napkin and double-sided tape. Unlike previous reports, our device structure exhibits two sensing capabilities in one platform, with outstanding long detection range of 20 cm and pressure sensitivity of 0.05 kPa. This is the first ever demonstration of a low-cost, accessible, and batch manufacturing process for pressure and proximity sensing on a singular platform. The mechanical flexibility of the sensor makes it possible to mount on various irregular platforms, which is vital in many areas, such as robotics, machine automation, vehicular technology and inspection tools.

  13. Alternating proximal gradient method for nonnegative matrix factorization

    CERN Document Server

    Xu, Yangyang


    Nonnegative matrix factorization has been widely applied in face recognition, text mining, as well as spectral analysis. This paper proposes an alternating proximal gradient method for solving this problem. With a uniformly positive lower bound assumption on the iterates, any limit point can be proved to satisfy the first-order optimality conditions. A Nesterov-type extrapolation technique is then applied to accelerate the algorithm. Though this technique is at first used for convex program, it turns out to work very well for the non-convex nonnegative matrix factorization problem. Extensive numerical experiments illustrate the efficiency of the alternating proximal gradient method and the accleration technique. Especially for real data tests, the accelerated method reveals high superiority to state-of-the-art algorithms in speed with comparable solution qualities.

  14. Longitudinal Proximity Effects in Superconducting Transition-Edge Sensors

    Energy Technology Data Exchange (ETDEWEB)

    Sadleir, John E.; Smith, Stephen J.; Bandler, Simon R.; Chervenak, James A.; Clem, John R.


    We have found experimentally that the critical current of a square thin-film superconducting transition-edge sensor (TES) depends exponentially upon the side length L and the square root of the temperature T, a behavior that has a natural theoretical explanation in terms of longitudinal proximity effects if the TES is regarded as a weak link between superconducting leads. As a consequence, the effective transition temperature T{sub c} of the TES is current dependent and at fixed current scales as 1/L{sup 2}. We have also found that the critical current can show clear Fraunhofer-like oscillations in an applied magnetic field, similar to those found in Josephson junctions. We have observed the longitudinal proximity effect in these devices over extraordinarily long lengths up to 290 {micro}m, 1450 times the mean-free path.

  15. Indications for computed tomography (CT-) diagnostics in proximal humeral fractures

    DEFF Research Database (Denmark)

    Bahrs, Christian; Rolauffs, Bernd; Südkamp, Norbert P


    diagnostics depending on the fractured parts. METHODS: In a prospective diagnostic study in two level 1 trauma centers, 44 patients with proximal humeral fractures were diagnosed with conventional X-rays (22 AP + axillary views, 22 AP + scapular Y-views) and CT (multi-planar reconstruction (MPR) and maximum...... a significantly better assessment of the relevant structures than conventional diagnostics (p X-rays with AP view and a high-quality axillary view are useful for primary diagnostics of the fracture......--independently of the number of fractured parts--when the proximal humerus and the shoulder joint are not presented with sufficient X-ray-quality to establish a treatment plan....

  16. Copper in silicon: Quantitative analysis of internal and proximity gettering

    Energy Technology Data Exchange (ETDEWEB)

    McHugo, S.A. [Lawrence Berkeley National Lab., CA (United States); Flink, C.; Weber, E.R. [Univ. of California, Berkeley, CA (United States)] [and others


    The behavior of copper in the presence of a proximity gettering mechanism and a standard internal gettering mechanism in silicon was studied. He implantation-induced cavities in the near surface region were used as a proximity gettering mechanism and oxygen precipitates in the bulk of the material provided internal gettering sites. Moderate levels of copper contamination were introduced by ion implantation such that the copper was not supersaturated during the anneals, thus providing realistic copper contamination/gettering conditions. Copper concentrations at cavities and internal gettering sites were quantitatively measured after the annealings. In this manner, the gettering effectiveness of cavities was measured when in direct competition with internal gettering sites. The cavities were found to be the dominant gettering mechanism with only a small amount of copper gettered at the internal gettering sites. These results reveal the benefits of a segregation-type gettering mechanism for typical contamination conditions.

  17. Synostosis of proximal phalangeal bases for loss of distal metacarpal

    Directory of Open Access Journals (Sweden)

    Pankaj Jindal


    Full Text Available A finger rendered unstable due to loss of metacarpal head can be stabilized by creating a synostosis at the base of the proximal phalanx of the affected finger with the adjacent normal finger. A cortico cancellous graft bridges the two adjacent proximal phalanges at their bases which are temporarily stabilized with an external fixator. The procedure can be done for, recurrence of giant cell tumor of metacarpal and for traumatic metacarpal loss. The procedure and long term follow up of one patient is presented who had giant cell tumor. This option should be considered before offering ray amputation. There is no micro vascular surgery involved, nor is there any donor site morbidity. The graft heals well without any absorption. The affected finger shows excellent function in the long term followup.

  18. Proximate Composition, Macro and Trace Mineral Compositions of ...

    African Journals Online (AJOL)

    The proximate composition of the whole portion was significantly (P<0.05) higher in levels of moisture and carbohydrates (9.10± 0.33 % and 62.66± 0.54%), crude protein in the flesh (41.94± 0.69% and 4.36± 0.14%) whereas fat, ash and crude fibre content (2.20± 0.05% and 0.56± 0.02%) were higher in the exoskeleton.

  19. The Applications of Finite Element Analysis in Proximal Humeral Fractures


    Yongyu Ye; Wei You; Weimin Zhu; Jiaming Cui; Kang Chen; Daping Wang


    Proximal humeral fractures are common and most challenging, due to the complexity of the glenohumeral joint, especially in the geriatric population with impacted fractures, that the development of implants continues because currently the problems with their fixation are not solved. Pre-, intra-, and postoperative assessments are crucial in management of those patients. Finite element analysis, as one of the valuable tools, has been implemented as an effective and noninvasive method to analyze...

  20. Pseudoarthrosis following proximal humeral fractures: A possible mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Rooney, P.J.; Cockshott, W.P.


    A small series of four patients with pseudarthrosis of the proximal humeral shaft is reported. These patients all had restricted movement of the shoulder joint prior to the trauma, three as a result of rheumatoid arthritis and one due a surgical fusion of the glenohumeral joint. It is suggested that pseudarthrosis is more likely under these circumstances and that pursuit of union of the fracture in such patients may not always be necessary.