Aggregate wage flexibility in selected new EU member states

Czech Academy of Sciences Publication Activity Database

Babetskii, Ian

-, č. 1 (2006), s. 1-41 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : Exchange Rate Mechanism-II * euro adoption * labor market Subject RIV: AH - Economics http://www.cnb.cz/m2export/sites/www.cnb.cz/en/research/research_publications/cnb_wp/download/cnbwp_2006_01.pdf

CT-guided core needle biopsy of pleural lesions: Evaluating diagnostic yield and associated complications

International Nuclear Information System (INIS)

Niu, Xiang Ke; Bhetuwal, Anup; Yang, Han Feng

2015-01-01

The purpose of this study was to retrospectively evaluate the diagnostic accuracy and complications of CT-guided core needle biopsy (CT-guided CNB) of pleural lesion and the possible effects of influencing factors. From September 2007 to June 2013, 88 consecutive patients (60 men and 28 women; mean [+/- standard deviation] age, 51.1 +/- 14.4 years; range, 19-78 years) underwent CT-guided CNB, which was performed by two experienced chest radiologists in our medical center. Out of 88 cases, 56 (63%) were diagnosed as malignant, 28 (31%) as benign and 4 (5%) as indeterminate for CNB of pleural lesions. The final diagnosis was confirmed by either histopathological diagnosis or clinical follow-up. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and complication rates were statistically evaluated. Influencing factors (patient age, sex, lesion size, pleural-puncture angle, patient position, pleural effusion, and number of pleural punctures) were assessed for their effect on accuracy of CT-guided CNB using univariate and subsequent multivariate analysis. Diagnostic accuracy, sensitivity, specificity, PPV, and NPV were 89.2%, 86.1%, 100%, 100%, and 67.8%, respectively. The influencing factors had no significant effect in altering diagnostic accuracy. As far as complications were concerned, occurrence of pneumothorax was observed in 14 (16%) out of 88 patients. Multivariate analysis revealed lesion size/pleural thickening as a significant risk factor (odds ratio [OR]: 8.744, p = 0.005) for occurrence of pneumothorax. Moreover, presence of pleural effusion was noted as a significant protective factor (OR: 0.171, p = 0.037) for pneumothorax. CT-guided CNB of pleural lesion is a safe procedure with high diagnostic yield and low risk of significant complications.

CT-guided core needle biopsy of pleural lesions: Evaluating diagnostic yield and associated complications

Energy Technology Data Exchange (ETDEWEB)

Niu, Xiang Ke [Dept. of Radiology, Affiliated Hospital of Chengdu University, Chengdu (China); Bhetuwal, Anup; Yang, Han Feng [Dept. of Radiology, Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong (China)

2015-02-15

The purpose of this study was to retrospectively evaluate the diagnostic accuracy and complications of CT-guided core needle biopsy (CT-guided CNB) of pleural lesion and the possible effects of influencing factors. From September 2007 to June 2013, 88 consecutive patients (60 men and 28 women; mean [+/- standard deviation] age, 51.1 +/- 14.4 years; range, 19-78 years) underwent CT-guided CNB, which was performed by two experienced chest radiologists in our medical center. Out of 88 cases, 56 (63%) were diagnosed as malignant, 28 (31%) as benign and 4 (5%) as indeterminate for CNB of pleural lesions. The final diagnosis was confirmed by either histopathological diagnosis or clinical follow-up. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and complication rates were statistically evaluated. Influencing factors (patient age, sex, lesion size, pleural-puncture angle, patient position, pleural effusion, and number of pleural punctures) were assessed for their effect on accuracy of CT-guided CNB using univariate and subsequent multivariate analysis. Diagnostic accuracy, sensitivity, specificity, PPV, and NPV were 89.2%, 86.1%, 100%, 100%, and 67.8%, respectively. The influencing factors had no significant effect in altering diagnostic accuracy. As far as complications were concerned, occurrence of pneumothorax was observed in 14 (16%) out of 88 patients. Multivariate analysis revealed lesion size/pleural thickening as a significant risk factor (odds ratio [OR]: 8.744, p = 0.005) for occurrence of pneumothorax. Moreover, presence of pleural effusion was noted as a significant protective factor (OR: 0.171, p = 0.037) for pneumothorax. CT-guided CNB of pleural lesion is a safe procedure with high diagnostic yield and low risk of significant complications.

Supply-side performance and structure in the Czech Republic (1995-2005)

Czech Academy of Sciences Publication Activity Database

Dybczak, K.; Flek, V.; Hájková, Dana; Hurník, J.

-, č. 4 (2006), s. 1-30 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : capital services * factor allocation * growth accounting Subject RIV: AH - Economics http://www.cnb.cz/www.cnb.cz/en/research/research_publications/cnb_wp/index.html

A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domains.

Directory of Open Access Journals (Sweden)

Alexandr P Kornev

2008-04-01

Full Text Available Cyclic nucleotides (cAMP and cGMP regulate multiple intracellular processes and are thus of a great general interest for molecular and structural biologists. To study the allosteric mechanism of different cyclic nucleotide binding (CNB domains, we compared cAMP-bound and cAMP-free structures (PKA, Epac, and two ionic channels using a new bioinformatics method: local spatial pattern alignment. Our analysis highlights four major conserved structural motifs: 1 the phosphate binding cassette (PBC, which binds the cAMP ribose-phosphate, 2 the "hinge," a flexible helix, which contacts the PBC, 3 the beta(2,3 loop, which provides precise positioning of an invariant arginine from the PBC, and 4 a conserved structural element consisting of an N-terminal helix, an eight residue loop and the A-helix (N3A-motif. The PBC and the hinge were included in the previously reported allosteric model, whereas the definition of the beta(2,3 loop and the N3A-motif as conserved elements is novel. The N3A-motif is found in all cis-regulated CNB domains, and we present a model for an allosteric mechanism in these domains. Catabolite gene activator protein (CAP represents a trans-regulated CNB domain family: it does not contain the N3A-motif, and its long range allosteric interactions are substantially different from the cis-regulated CNB domains.

Welfare-based optimal monetary policy in a two-sector small open economy

Czech Academy of Sciences Publication Activity Database

Rychalovska, Yuliya

-, č. 16 (2007), s. 1-46 ISSN 1803-2397 Institutional research plan: CEZ:AV0Z70850503 Keywords : DSGE models * optimal monetary policy * non-traded goods Subject RIV: AH - Economics http://www.cnb.cz/m2export/sites/www.cnb.cz/en/research/research_publications/cnb_wp/download/cnbwp_2007_16.pdf

The measurement of capital services in the Czech Republic

Czech Academy of Sciences Publication Activity Database

Hájková, Dana

-, č. 11 (2008), s. 1-24 ISSN 1803-2397 Institutional research plan: CEZ:AV0Z70850503 Keywords : capital services * growth accounting * production function * total factor productivity Subject RIV: AH - Economics http://www.cnb.cz/m2export/sites/www.cnb.cz/en/research/research_publications/cnb_wp/download/cnbwp_2008_11.pdf

The effects of anticipated future change in monetary policy regime

Czech Academy of Sciences Publication Activity Database

Antal, J.; Brázdik, František

-, č. 15 (2007), s. 1-53 ISSN 1803-2397 Institutional research plan: CEZ:AV0Z70850503 Keywords : macroeconomics * new Keynesian DSGE models * small open economy Subject RIV: AH - Economics http://www.cnb.cz/m2export/sites/www.cnb.cz/en/research/research_publications/cnb_wp/download/cnbwp_2007_15.pdf

Inflation persistence in new EU member states: is it different than in the euro area members?

Czech Academy of Sciences Publication Activity Database

Franta, Michal; Saxa, Branislav; Šmídková, Kateřina

-, č. 10 (2007), s. 1-37 ISSN 1803-2397 Institutional research plan: CEZ:AV0Z70850503 Keywords : inflation persistence * new hybrid Phillips curve * new EU member states Subject RIV: AH - Economics http://www.cnb.cz/m2export/sites/www.cnb.cz/en/research/research_publications/cnb_wp/download/cnbwp_2007_10.pdf

UV Light-Assisted Synthesis of Highly Efficient Pd-Based Catalyst over NiO for Hydrogenation of o-Chloronitrobenzene.

Science.gov (United States)

Jiang, Weidong; Xu, Bin; Fan, Guangyin; Zhang, Kaiming; Xiang, Zhen; Liu, Xiaoqiang

2018-04-14

Supported Pd-based catalyst over active nickel oxide (NiO) was repared using the impregnation method companying with UV-light irradiation. Moreover, the catalytic performance of the obtained Pd-based catalysts was evaluated towards the hydrogenation of o -chloronitrobenzene ( o -CNB). Observations indicate that the as-prepared UV-irradiated Pd/NiO catalyst with a mole fraction 0.2% (0.2%Pd/NiO) has higher activity and selectivity in the o -CNB hydrogenation. Especially, UV-light irradiation played a positive role in the improvement of catalytic activity of 0.2%Pd/NiO catalyst, exhibiting an excess 11-fold activity superiority in contrast with non-UV-irradiated 0.2%Pd/NiO catalyst. In addition, it was investigated that effects of varied factors (i.e., reaction time, temperature, o -CNB/Pd ratio, Pd loading, hydrogen pressure) on the selective hydrogenation of ο -CNB catalyzed by UV-irradiated 0.2%Pd/NiO catalyst. Under the reaction conditions of 60 °C, 0.5 h, 1 MPa H₂ pressure, 100% conversion of o -CNB, and 81.1% o -CAN selectivity were obtained, even at high molar ratio (8000:1) of o -CNB to Pd.

Facile synthesis and enhanced visible-light photocatalysis of graphitic carbon nitride composite semiconductors.

Science.gov (United States)

Li, Huiquan; Liu, Yuxing; Gao, Xing; Fu, Cong; Wang, Xinchen

2015-04-13

The semiconductor heterojunction has been an effective architecture to enhance photocatalytic activity by promoting photogenerated charge separation. Here, graphitic carbon nitride (CN) and B-modified graphitic carbon nitride (CNB) composite semiconductors were fabricated by a facile calcination process using cheap, sustainable, and easily available sodium tetraphenylboron and urea as precursors. The synthetic CN-CNB-25 semiconductor with a suitable CNB content showed the highest visible-light activity. Its degradation ratio for methyl orange and phenol was more than twice that of CN and CNB and its H2 evolution rate was ∼3.4 and ∼1.8 times higher than that of CN and CNB, respectively. It also displayed excellent stability and reusability. The enhanced activity of CN-CNB-25 was attributed predominantly to the efficient separation of photoinduced electrons and holes. This paper describes a visible-light-responsive CN composite semiconductor with great potential in environmental and energy applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comparison of diagnostic performance of vacuum-assisted biopsy and core needle biopsy for breast microcalcification: a systematic review and meta-analysis.

Science.gov (United States)

Huang, Xu Chen; Hu, Xu Hua; Wang, Xiao Ran; Zhou, Chao Xi; Wang, Fei Fei; Yang, Shan; Wang, Gui Ying

2018-03-16

Core needle biopsy (CNB) and vacuum-assisted biopsy (VAB) are both popularly used breast percutaneous biopsies. Both of them have become reliable alternatives to open surgical biopsy (OSB) for breast microcalcification (BM). It is controversial that which biopsy method is more accurate and safer for BM. Hence, we conducted this meta-analysis to compare the diagnostic performance between CNB and VAB for BM, aiming to find out the better method. Articles according with including and excluding criteria were collected from the databases, PubMed, Embase, and the Cochrane Library. Preset outcomes were abstracted and pooled to find out the potential advantages in CNB or VAB. Seven studies were identified and entered final meta-analysis from initially found 138 studies. The rate of ductal carcinoma in situ (DCIS) underestimation was significantly lower in VAB than CNB group [risk ratio (RR) = 1.83, 95% confidence interval (CI) 1.40 to 2.40, p < 0.001]. The microcalcification retrieval rate was significantly higher in VAB than CNB group (RR = 0.89, 95% CI 0.81 to 0.98, p = 0.02), while CNB owned a significantly lower complication rate than VAB (RR = 0.18, 95% CI 0.03 to 0.93, p = 0.04). The atypical ductal hyperplasia (ADH) underestimation rates were not compared for the limited number of studies reporting this outcome. Compared with CNB, VAB shows better diagnostic performance in DCIS underestimation rate and microcalcification retrieval rate. However, CNB shows a significantly lower complication rate. More studies are needed to verify these findings.

Design of a compact high-speed optical modulator based on a hybrid plasmonic nanobeam cavity

Science.gov (United States)

Javid, Mohammad Reza; Miri, Mehdi; Zarifkar, Abbas

2018-03-01

A hybrid plasmonic electro-optic modulator based on a polymer-filled one dimensional photonic crystal nanobeam (1D PhCNB) cavity is proposed here. In the proposed structure the optical intensity modulation is realized by shifting the resonant wavelength of the cavity through electrically tuning the refractive index of the electro-optic polymer in the hybrid plasmonic waveguide. As a result of the subwavelength light confinement in the hybrid plasmonic waveguide and the compact footprint of the 1D PhCNB cavity, the designed modulator has the small overall footprint of 3 . 6 μm2 and the required wavelength shift can be achieved by applying very small actuating power. Three dimensional finite-difference time-domain (3D-FDTD) simulations show that the modulation depth of 10.9 dB, and insertion loss of 1.14 dB, along with very high modulation speed of 224 GHz can be achieved in the proposed modulator with very low modulation energy of 0.75 fJ/bit. A comparison between the performance parameters of the proposed modulator and those of previously reported PhCNB based modulators reveals the superior performance of the proposed structure in terms of modulation speed, energy consumption and overall footprint.

Isl1 is required for multiple aspects of motor neuron development.

Science.gov (United States)

Liang, Xingqun; Song, Mi-Ryoung; Xu, ZengGuang; Lanuza, Guillermo M; Liu, Yali; Zhuang, Tao; Chen, Yihan; Pfaff, Samuel L; Evans, Sylvia M; Sun, Yunfu

2011-07-01

The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in multiple organs and plays essential roles during embryogenesis. Isl1 is required for the survival and specification of spinal cord motor neurons. Due to early embryonic lethality and loss of motor neurons, the role of Isl1 in other aspects of motor neuron development remains unclear. In this study, we generated Isl1 mutant mouse lines expressing graded doses of Isl1. Our study has revealed essential roles of Isl1 in multiple aspects of motor neuron development, including motor neuron cell body localization, motor column formation and axon growth. In addition, Isl1 is required for survival of cranial ganglia neurons. Copyright © 2011 Elsevier Inc. All rights reserved.

Metabolomics of Breast Cancer Using High-Resolution Magic Angle Spinning Magnetic Resonance Spectroscopy: Correlations with 18F-FDG Positron Emission Tomography-Computed Tomography, Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging MRI.

Science.gov (United States)

Yoon, Haesung; Yoon, Dahye; Yun, Mijin; Choi, Ji Soo; Park, Vivian Youngjean; Kim, Eun-Kyung; Jeong, Joon; Koo, Ja Seung; Yoon, Jung Hyun; Moon, Hee Jung; Kim, Suhkmann; Kim, Min Jung

2016-01-01

Our goal in this study was to find correlations between breast cancer metabolites and conventional quantitative imaging parameters using high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) and to find breast cancer subgroups that show high correlations between metabolites and imaging parameters. Between August 2010 and December 2013, we included 53 female patients (mean age 49.6 years; age range 32-75 years) with a total of 53 breast lesions assessed by the Breast Imaging Reporting and Data System. They were enrolled under the following criteria: breast lesions larger than 1 cm in diameter which 1) were suspicious for malignancy on mammography or ultrasound (US), 2) were pathologically confirmed to be breast cancer with US-guided core-needle biopsy (CNB) 3) underwent 3 Tesla MRI with dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) and positron emission tomography-computed tomography (PET-CT), and 4) had an attainable immunohistochemistry profile from CNB. We acquired spectral data by HR-MAS MRS with CNB specimens and expressed the data as relative metabolite concentrations. We compared the metabolites with the signal enhancement ratio (SER), maximum standardized FDG uptake value (SUV max), apparent diffusion coefficient (ADC), and histopathologic prognostic factors for correlation. We calculated Spearman correlations and performed a partial least squares-discriminant analysis (PLS-DA) to further classify patient groups into subgroups to find correlation differences between HR-MAS spectroscopic values and conventional imaging parameters. In a multivariate analysis, the PLS-DA models built with HR-MAS MRS metabolic profiles showed visible discrimination between high and low SER, SUV, and ADC. In luminal subtype breast cancer, compared to all cases, high SER, ADV, and SUV were more closely clustered by visual assessment. Multiple metabolites were correlated with SER and SUV in all cases. Multiple metabolites showed

Metabolomics of Breast Cancer Using High-Resolution Magic Angle Spinning Magnetic Resonance Spectroscopy: Correlations with 18F-FDG Positron Emission Tomography-Computed Tomography, Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging MRI.

Directory of Open Access Journals (Sweden)

Haesung Yoon

Full Text Available Our goal in this study was to find correlations between breast cancer metabolites and conventional quantitative imaging parameters using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS and to find breast cancer subgroups that show high correlations between metabolites and imaging parameters.Between August 2010 and December 2013, we included 53 female patients (mean age 49.6 years; age range 32-75 years with a total of 53 breast lesions assessed by the Breast Imaging Reporting and Data System. They were enrolled under the following criteria: breast lesions larger than 1 cm in diameter which 1 were suspicious for malignancy on mammography or ultrasound (US, 2 were pathologically confirmed to be breast cancer with US-guided core-needle biopsy (CNB 3 underwent 3 Tesla MRI with dynamic contrast-enhanced (DCE and diffusion-weighted imaging (DWI and positron emission tomography-computed tomography (PET-CT, and 4 had an attainable immunohistochemistry profile from CNB. We acquired spectral data by HR-MAS MRS with CNB specimens and expressed the data as relative metabolite concentrations. We compared the metabolites with the signal enhancement ratio (SER, maximum standardized FDG uptake value (SUV max, apparent diffusion coefficient (ADC, and histopathologic prognostic factors for correlation. We calculated Spearman correlations and performed a partial least squares-discriminant analysis (PLS-DA to further classify patient groups into subgroups to find correlation differences between HR-MAS spectroscopic values and conventional imaging parameters.In a multivariate analysis, the PLS-DA models built with HR-MAS MRS metabolic profiles showed visible discrimination between high and low SER, SUV, and ADC. In luminal subtype breast cancer, compared to all cases, high SER, ADV, and SUV were more closely clustered by visual assessment. Multiple metabolites were correlated with SER and SUV in all cases. Multiple metabolites

Changes in quality of goat meat after alterations in animal Handling - doi:10.5020/18061230.2007.p33

Directory of Open Access Journals (Sweden)

Frederico José Beserra

2012-01-01

Full Text Available This study aimed at evaluating the effect of animal handling, consisting in castration and cashew nut diet supplementation, on the cholesterol content and percentage composition of the muscles that constitute the leg meat cut from crossbred goats, grown in Ceará State. A case experimental design was applied with twenty male-animals with 5-6 months age and mean weight of 12 Kg, randomly divided in two groups of castrated (10 and intact (10 animals. In individual bays, they received during 5 months, two food regimen based on dried elephant grass (Pennisetum purpureum and a standard isoproteic ration (corn and soy oil, one of them with the addition of 13% cashew nut bran (CNB, forming four sub-groups: A1 (intact with no CNB supplemented diet; A2 (intact with CNB supplemented diet; B1 (castrated with no CNB supplemented diet and B2 (castrated with CNB supplemented diet. The castration associated with the CNB supplementation increased the meat’s fat yield from 1.16% to 3.57% and the cholesterol content from 36.47 mg/100g to 62.30 mg/100g. The ash yield decreased from 1.14% to 1.04%. The castration isolated only reduced moisture yield from 75.98% on sub-group A2 to 74.19% on sub-group B2. In intact animals that fed diet supplemented with CNB the protein decreased from 20.58% to 18.85% (P < 0.05 (sub-groups A1 and A2. The increased cholesterol content was highly correlated with the increase of the fat (93% In conclusion, these results showed that the combined use of castration and cashew nut bran (13% diet negatively influenced the dietetic and nutritional quality of goat leg meat.

A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis

DEFF Research Database (Denmark)

Jagodic, Maja; Colacios, Celine; Nohra, Rita

2009-01-01

Multiple sclerosis, the most common cause of progressive neurological disability in young adults, is a chronic inflammatory disease. There is solid evidence for a genetic influence in multiple sclerosis, and deciphering the causative genes could reveal key pathways influencing the disease. A genome...... region on rat chromosome 9 regulates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Using interval-specific congenic rat lines and association of single-nucleotide polymorphisms with inflammatory phenotypes, we localized the gene of influence to Vav1, which codes for a signal......-transducing protein in leukocytes. Analysis of seven human cohorts (12,735 individuals) demonstrated an association of rs2546133-rs2617822 haplotypes in the first VAV1 intron with multiple sclerosis (CA: odds ratio, 1.18; CG: odds ratio, 0.86; TG: odds ratio, 0.90). The risk CA haplotype also predisposed for higher...

Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism

International Nuclear Information System (INIS)

Umezu, K.; Sugawara, N.; Chen, C.; Haber, J.E.; Kolodner, R.D.

1998-01-01

Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10 4 to 10 5 times increased sensitivity to these agents. Some of the UV- and MMSsensitive mutants were killed by an HO-induced double-strand break atMAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages. (author)

JDet: interactive calculation and visualization of function-related conservation patterns in multiple sequence alignments and structures.

Science.gov (United States)

Muth, Thilo; García-Martín, Juan A; Rausell, Antonio; Juan, David; Valencia, Alfonso; Pazos, Florencio

2012-02-15

We have implemented in a single package all the features required for extracting, visualizing and manipulating fully conserved positions as well as those with a family-dependent conservation pattern in multiple sequence alignments. The program allows, among other things, to run different methods for extracting these positions, combine the results and visualize them in protein 3D structures and sequence spaces. JDet is a multiplatform application written in Java. It is freely available, including the source code, at http://csbg.cnb.csic.es/JDet. The package includes two of our recently developed programs for detecting functional positions in protein alignments (Xdet and S3Det), and support for other methods can be added as plug-ins. A help file and a guided tutorial for JDet are also available.

Ultrasonography-guided core needle biopsy for the thyroid nodule: does the procedure hold any benefit for the diagnosis when fine-needle aspiration cytology analysis shows inconclusive results?

Science.gov (United States)

Hahn, S Y; Han, B-K; Ko, E Y; Ko, E S

2013-01-01

Objective: We evaluated the diagnostic role of ultrasonography-guided core needle biopsy (CNB) according to ultrasonography features of thyroid nodules that had inconclusive ultrasonography-guided fine-needle aspiration (FNA) results. Methods: A total of 88 thyroid nodules in 88 patients who underwent ultrasonography-guided CNB because of previous inconclusive FNA results were evaluated. The patients were classified into three groups based on ultrasonography findings: Group A, which was suspicious for papillary thyroid carcinoma (PTC); Group B, which was suspicious for follicular (Hurthle cell) neoplasm; and Group C, which was suspicious for lymphoma. The final diagnoses of the thyroid nodules were determined by surgical confirmation or follow-up after ultrasonography-guided CNB. Results: Of the 88 nodules, the malignant rate was 49.1% in Group A, 12.0% in Group B and 90.0% in Group C. The rates of conclusive ultrasonography-guided CNB results after previous incomplete ultrasonography-guided FNA results were 96.2% in Group A, 64.0% in Group B and 90.0% in Group C (p=0.001). 12 cases with inconclusive ultrasonography-guided CNB results were finally diagnosed as 8 benign lesions, 3 PTCs and 1 lymphoma. The number of previous ultrasonography-guided FNA biopsies was not significantly different between the conclusive and the inconclusive result groups of ultrasonography-guided CNB (p=0.205). Conclusion: Ultrasonography-guided CNB has benefit for the diagnosis of thyroid nodules with inconclusive ultrasonography-guided FNA results. However, it is still not helpful for the differential diagnosis in 36% of nodules that are suspicious for follicular neoplasm seen on ultrasonography. Advances in knowledge: This study shows the diagnostic contribution of ultrasonography-guided CNB as an alternative to repeat ultrasonography-guided FNA or surgery. PMID:23564885

Margins of trade: Czech firms before, during and after the crisis

Czech Academy of Sciences Publication Activity Database

Galuščák, K.; Sutóris, Ivan

2017-01-01

Roč. 15, č. 1 (2017), s. 2-5 ISSN 1803-7089 Institutional support: Progres-Q24 Keywords : Czech firms * crisis Subject RIV: AH - Economics http://www.cnb.cz/miranda2/export/sites/www.cnb.cz/en/research/research_publications/erb/download/ERB_No1_2017.pdf

Thyroid nodules with isolated macrocalcification: Malignancy and diagnostic efficacy of fine-needle aspiration and core needle biopsy

Energy Technology Data Exchange (ETDEWEB)

Na, Dong Gyu; Kim, Dae Sik; Kim, Soo Jin [Dept. of Radiology, Human Medical Imaging and Intervention Center, Seoul (Korea, Republic of); Ryoo, Jae Wook [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Jung, So Lyung [Dept. of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

2016-07-15

This study was performed to determine the malignancy risk of thyroid nodules with isolated macrocalcification and to evaluate the diagnostic efficacy of fine-needle aspiration (FNA) and core needle biopsy (CNB). From May 2008 to December 2014, a total of 44 patients with isolated macrocalcifications were enrolled from 4,081 consecutive patients who underwent FNA or CNB at a single institution. We assessed the malignancy risk of nodules with isolated macrocalcification. We compared the diagnostic results between FNA and CNB, and the diagnostic efficacy of each procedure was evaluated by the rate of inconclusive results. We compared the diagnostic performance for malignancy between FNA and CNB with a criterion of malignant or atypia/follicular lesion of undetermined significance (indeterminate) diagnostic results. We investigated whether the ultrasonographic feature of isolated macrocalcification was predictive of malignancy. The malignancy risk of nodules with isolated macrocalcification was 16.1% in 31 nodules with final diagnoses and 11.4% in all nodules. CNB demonstrated a significantly lower rate of nondiagnostic and inconclusive results than FNA (7.7% vs. 53.8%, P=0.002 and 15.4% vs. 57.7%, P=0.003, respectively) in 26 nodules that underwent both FNA and CNB. CNB showed a marginally higher diagnostic performance for identifying malignancy than FNA (P=0.067). The ultrasonographic features of the anterior margin of isolated macrocalcification were not predictive of malignancy (P>0.999). Thyroid nodules with isolated macrocalcification had a low to intermediate malignancy risk and should not be considered benign nodules. CNB showed a higher diagnostic efficacy than FNA in these nodules.

Thyroid nodules with isolated macrocalcification: Malignancy and diagnostic efficacy of fine-needle aspiration and core needle biopsy

International Nuclear Information System (INIS)

Na, Dong Gyu; Kim, Dae Sik; Kim, Soo Jin; Ryoo, Jae Wook; Jung, So Lyung

2016-01-01

This study was performed to determine the malignancy risk of thyroid nodules with isolated macrocalcification and to evaluate the diagnostic efficacy of fine-needle aspiration (FNA) and core needle biopsy (CNB). From May 2008 to December 2014, a total of 44 patients with isolated macrocalcifications were enrolled from 4,081 consecutive patients who underwent FNA or CNB at a single institution. We assessed the malignancy risk of nodules with isolated macrocalcification. We compared the diagnostic results between FNA and CNB, and the diagnostic efficacy of each procedure was evaluated by the rate of inconclusive results. We compared the diagnostic performance for malignancy between FNA and CNB with a criterion of malignant or atypia/follicular lesion of undetermined significance (indeterminate) diagnostic results. We investigated whether the ultrasonographic feature of isolated macrocalcification was predictive of malignancy. The malignancy risk of nodules with isolated macrocalcification was 16.1% in 31 nodules with final diagnoses and 11.4% in all nodules. CNB demonstrated a significantly lower rate of nondiagnostic and inconclusive results than FNA (7.7% vs. 53.8%, P=0.002 and 15.4% vs. 57.7%, P=0.003, respectively) in 26 nodules that underwent both FNA and CNB. CNB showed a marginally higher diagnostic performance for identifying malignancy than FNA (P=0.067). The ultrasonographic features of the anterior margin of isolated macrocalcification were not predictive of malignancy (P>0.999). Thyroid nodules with isolated macrocalcification had a low to intermediate malignancy risk and should not be considered benign nodules. CNB showed a higher diagnostic efficacy than FNA in these nodules

[Exome sequencing revealed Allan-Herndon-Dudley syndrome underlying multiple disabilities].

Science.gov (United States)

Arvio, Maria; Philips, Anju K; Ahvenainen, Minna; Somer, Mirja; Kalscheuer, Vera; Järvelä, Irma

2014-01-01

Normal function of the thyroid gland is the cornerstone of a child's mental development and physical growth. We describe a Finnish family, in which the diagnosis of three brothers became clear after investigations that lasted for more than 30 years. Two of the sons have already died. DNA analysis of the third one, a 16-year-old boy, revealed in exome sequencing of the complete X chromosome a mutation in the SLC16A2 gene, i.e. MCT8, coding for a thyroid hormone transport protein. Allan-Herndon-Dudley syndrome was thus shown to be the cause of multiple disabilities.

Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

Science.gov (United States)

Liu, Shuyuan; Yue, Longtao; Gu, Wenrui; Li, Xiuyun; Zhang, Liuping; Sun, Shujuan

2016-01-01

Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers), amlodipine (AML), nifedipine (NIF), benidipine (BEN) and flunarizine (FNZ) with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1) expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI) <0.5, but no interaction against sensitive strains (FICI = 0.56 ~ 2). The mechanism studies revealed that fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin) and YVC1 (encoding calcium channel protein in vacuole membrane).

Fibroadenoma versus phyllodes tumor: distinguishing factors in patients diagnosed with fibroepithelial lesions after a core needle biopsy

Science.gov (United States)

Wiratkapun, Cholatip; Piyapan, Pawat; Lertsithichai, Panuwat; Larbcharoensub, Noppadol

2014-01-01

PURPOSE We aimed to identify factors that might help differentiate phyllodes tumors from fibroadenomas among cases in which a fibroepithelial breast lesion was diagnosed from core needle biopsy (CNB) under imaging guidance. MATERIALS AND METHODS A retrospective review was performed on 213 lesions in 200 patients who had undergone both CNB and excisional biopsy during a four-year period between 2008 and 2011. The final pathology revealed 173 fibroadenomas and 40 phyllodes tumors. The data, including patient characteristics, clinical presentation, and mammography, ultrasonography (US), and pathology findings were analyzed. RESULTS Upon univariable analysis, the factors that significantly helped to identify phyllodes tumors consisted of the presenting symptoms (palpable mass or breast pain), increased size on clinical examination, hyperdense mass on mammogram, and the following three US features: heterogeneous echo, presence of round cysts within the mass, and presence of clefts within the mass. The pathologist’s suggestion of a phyllodes tumor was also helpful. The factors that remained statistically significant upon multivariable analysis consisted of symptoms of breast pain, the presence of clefts on US, the presence of round cysts on US and the pathologist’s favoring of phyllodes tumors from a CNB specimen. CONCLUSION A multidisciplinary approach was needed to distinguish phyllodes tumors from fibroadenomas in patients who had undergone CNB. US findings (clefts and round cysts), suggestive pathological diagnoses, and clinical symptoms were all useful for the decision to surgically remove the fibroepithelial lesions diagnosed from CNB. PMID:24356293

Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

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Xiaoke Ma

2015-06-01

Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

Exchange rate dynamics and its effect on macroeconomic volatility in selected CEE countries

Czech Academy of Sciences Publication Activity Database

Audzei, Volha; Brázdik, F.

2017-01-01

Roč. 15, č. 1 (2017), s. 15-19 ISSN 1803-7089 Institutional support: Progres-Q24 Keywords : exchange rate dynamics * macroeconomic volatility Subject RIV: AH - Economic s http://www.cnb.cz/miranda2/export/sites/www.cnb.cz/en/research/research_publications/erb/download/ERB_No1_2017.pdf

The fate of a nitrobenzene-degrading bacterium in pharmaceutical wastewater treatment sludge.

Science.gov (United States)

Ren, Yuan; Yang, Juan; Chen, Shaoyi

2015-12-01

This paper describes the fate of a nitrobenzene-degrading bacterium, Klebsiella oxytoca NBA-1, which was isolated from a pharmaceutical wastewater treatment facility. The 90-day survivability of strain NBA-1 after exposure to sludge under anaerobic and aerobic conditions was investigated. The bacterium was inoculated into sludge amended with glucose and p-chloronitrobenzene (p-CNB) to compare the bacterial community variations between the modified sludge and nitrobenzene amendment. The results showed that glucose had no obvious effect on nitrobenzene biodegradation in the co-metabolism process, regardless of the presence/absence of oxygen. When p-CNB was added under anaerobic conditions, the biodegradation rate of nitrobenzene remained unchanged although p-CNB inhibited the production of aniline. The diversity of the microbial community increased and NBA-1 continued to be one of the dominant strains. Under aerobic conditions, the degradation rate of both nitrobenzene and p-CNB was only 20% of that under anaerobic conditions. p-CNB had a toxic effect on the microorganisms in the sludge so that most of the DGGE (denaturing gradient gel electrophoresis) bands, including that of NBA-1, began to disappear under aerobic conditions after 90days of exposure. These data show that the bacterial community was stable under anaerobic conditions and the microorganisms, including NBA-1, were more resistant to the adverse environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

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Schwend Tyler

2009-11-01

Full Text Available Abstract Background The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC. Genetic studies in zebrafish and mice have established that the Hedgehog (Hh-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE, which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia 12. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1 for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1. Results con/disp1 mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primorida occurs normally in con/disp1 mutants, however disp1 is necessary for post-migratory CNCC patterning and differentiation. We show that disp1 is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, sox9a and dlx2a, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to

Somatic mutations, allele loss, and DNA methylation of the Cub and Sushi Multiple Domains 1 (CSMD1 gene reveals association with early age of diagnosis in colorectal cancer patients.

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Austin Y Shull

Full Text Available The Cub and Sushi Multiple Domains 1 (CSMD1 gene, located on the short arm of chromosome 8, codes for a type I transmembrane protein whose function is currently unknown. CSMD1 expression is frequently lost in many epithelial cancers. Our goal was to characterize the relationships between CSMD1 somatic mutations, allele imbalance, DNA methylation, and the clinical characteristics in colorectal cancer patients.We sequenced the CSMD1 coding regions in 54 colorectal tumors using the 454FLX pyrosequencing platform to interrogate 72 amplicons covering the entire coding sequence. We used heterozygous SNP allele ratios at multiple CSMD1 loci to determine allelic balance and infer loss of heterozygosity. Finally, we performed methylation-specific PCR on 76 colorectal tumors to determine DNA methylation status for CSMD1 and known methylation targets ALX4, RUNX3, NEUROG1, and CDKN2A.Using 454FLX sequencing and confirming with Sanger sequencing, 16 CSMD1 somatic mutations were identified in 6 of the 54 colorectal tumors (11%. The nonsynonymous to synonymous mutation ratio of the 16 somatic mutations was 15:1, a ratio significantly higher than the expected 2:1 ratio (p = 0.014. This ratio indicates a presence of positive selection for mutations in the CSMD1 protein sequence. CSMD1 allelic imbalance was present in 19 of 37 informative cases (56%. Patients with allelic imbalance and CSMD1 mutations were significantly younger (average age, 41 years than those without somatic mutations (average age, 68 years. The majority of tumors were methylated at one or more CpG loci within the CSMD1 coding sequence, and CSMD1 methylation significantly correlated with two known methylation targets ALX4 and RUNX3. C:G>T:A substitutions were significantly overrepresented (47%, suggesting extensive cytosine methylation predisposing to somatic mutations.Deep amplicon sequencing and methylation-specific PCR reveal that CSMD1 alterations can correlate with earlier clinical

Simultaneous oxidation and adsorption of As(III) from water by cerium modified chitosan ultrafine nanobiosorbent

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Zhang, Lingfan [School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237 (China); Research Center of Analysis and Test, East China University of Science and Technology, Shanghai 200237 (China); Zhu, Tianyi [School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237 (China); Liu, Xin, E-mail: liuxin@ecust.edu.cn [School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237 (China); Zhang, Wenqing, E-mail: zhwqing@ecust.edu.cn [School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237 (China)

2016-05-05

Highlights: • A novel ultrafine nanobiosorbent of cerium modified chitosan (Ce-CNB) was prepared. • The Ce-CNB possessed properties for simultaneous oxidation and adsorption As(III). • Adsorption of As(III) by Ce-CNB was in high efficiency. • Mechanisms for As(III) adsorption on Ce-CNB were elucidated. - Abstract: Since most existing arsenic removal adsorbents are difficult to effectively remove arsenite (As(III)), an urgent need is to develop an efficient adsorbent for removing As(III) from contaminated water. In this study, a novel ultrafine nanobiosorbent of cerium modified chitosan (Ce-CNB) with simultaneous oxidation and adsorption As(III) performance has been successfully developed. The resulting Ce-CNB with or without As(III) adsorption was characterized by FTIR, XRD, SEM, EDS, TEM, EMI and XPS analysis. Batch of adsorption experiments were performed to investigate the effects of various conditions on the As(III) adsorption. The adsorption behaviors were well described by the Langmuir isotherm and the pseudo-second-order kinetic model, with the maximum adsorption capacities of 57.5 mg g{sup −1}. The adsorption mechanisms for As(III) were (i) formed monodentate and bidentate complexes between hydroxyl groups and arsenite; and (ii) partial As(III) oxidized to As(V) followed by simultaneously adsorbed on the surface of Ce-CNB. This novel nanocomposite can be reused while maintaining a high removal efficiency and can be applied to treat 5.8 L of As(III)-polluted water with the effluent concentration lower than the World Health Organization standard, which suggests its great potential to remove As(III) from contaminated water.

Bioaugmentation of a 4-chloronitrobenzene contaminated soil with Pseudomonas putida ZWL73

Energy Technology Data Exchange (ETDEWEB)

Guilan, Niu [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Graduate School, Chinese Academy of Sciences, Beijing 100049 (China); Junjie, Zhang [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Shuo, Zhao [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Graduate School, Chinese Academy of Sciences, Beijing 100049 (China); Hong, Liu [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Boon, Nico [Laboratory of Microbial Ecology and Technology (LabMET), Ghent University, Coupure Links 653, B-9000 Gent (Belgium); Zhou Ningyi [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)], E-mail: n.zhou@pentium.whiov.ac.cn

2009-03-15

The strain Pseudomonas putida ZWL73, which metabolizes 4-chloronitrobenzene (4CNB) by a partial-reductive pathway, was inoculated into lab-scale 4CNB-contaminated soil for bioaugmentation purposes in this study. The degradation of 4CNB was clearly stimulated, as indicated with the gradual accumulation of ammonium and chloride. Simultaneously, the diversity and quantity of cultivable heterotrophic bacteria decreased due to 4CNB contamination, while the quantity of 4CNB-resistant bacteria increased. During the bioaugmentation, denaturing gradient gel electrophoresis analysis showed the changes of diversity in dominant populations of intrinsic soil microbiota. The results showed that Alphaproteobacteria and Betaproteobacteria were not distinctly affected, but Actinobacteria were apparently stimulated. In addition, an interesting dynamic within Acidobacteria was observed, as well as an influence on ammonia-oxidizing bacteria population. These combined findings demonstrate that the removal of 4CNB in soils by inoculating strain ZWL73 is feasible, and that specific populations in soils rapidly changed in response to 4CNB contamination and subsequent bioaugmentation. - Pseudomonas putida ZWL73 can accelerate 4CNB removal in lab-scale soils, causing dynamic changes within intrinsic Actinobacteria and Acidobacteria.

Bioaugmentation of a 4-chloronitrobenzene contaminated soil with Pseudomonas putida ZWL73

International Nuclear Information System (INIS)

Niu Guilan; Zhang Junjie; Zhao Shuo; Liu Hong; Boon, Nico; Zhou Ningyi

2009-01-01

The strain Pseudomonas putida ZWL73, which metabolizes 4-chloronitrobenzene (4CNB) by a partial-reductive pathway, was inoculated into lab-scale 4CNB-contaminated soil for bioaugmentation purposes in this study. The degradation of 4CNB was clearly stimulated, as indicated with the gradual accumulation of ammonium and chloride. Simultaneously, the diversity and quantity of cultivable heterotrophic bacteria decreased due to 4CNB contamination, while the quantity of 4CNB-resistant bacteria increased. During the bioaugmentation, denaturing gradient gel electrophoresis analysis showed the changes of diversity in dominant populations of intrinsic soil microbiota. The results showed that Alphaproteobacteria and Betaproteobacteria were not distinctly affected, but Actinobacteria were apparently stimulated. In addition, an interesting dynamic within Acidobacteria was observed, as well as an influence on ammonia-oxidizing bacteria population. These combined findings demonstrate that the removal of 4CNB in soils by inoculating strain ZWL73 is feasible, and that specific populations in soils rapidly changed in response to 4CNB contamination and subsequent bioaugmentation. - Pseudomonas putida ZWL73 can accelerate 4CNB removal in lab-scale soils, causing dynamic changes within intrinsic Actinobacteria and Acidobacteria

Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

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Shuyuan Liu

Full Text Available Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers, amlodipine (AML, nifedipine (NIF, benidipine (BEN and flunarizine (FNZ with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1 expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI <0.5, but no interaction against sensitive strains (FICI = 0.56 ~ 2. The mechanism studies revealed that fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin and YVC1 (encoding calcium channel protein in vacuole membrane.

A randomised pilot study comparing 13 G vacuum-assisted biopsy and conventional 14 G core needle biopsy of axillary lymph nodes in women with breast cancer

International Nuclear Information System (INIS)

Maxwell, A.J.; Bundred, N.J.; Harvey, J.; Hunt, R.; Morris, J.; Lim, Y.Y.

2016-01-01

Aim: To compare the acceptability, safety, and feasibility of vacuum-assisted biopsy (VAB) and core needle biopsy (CNB) of axillary lymph nodes in women with breast cancer. Materials and methods: This parallel, non-blinded, randomised study was approved by the National Research Ethics Service. Following written informed consent, women with abnormal appearing axillary lymph nodes and radiologically malignant breast masses were randomised 1:1 to lymph node sampling under local anaesthetic with either 14 G CNB or 13 G VAB in a single UK centre. Primary outcomes were study uptake rate and patient willingness to undergo a repeat procedure if necessary. Procedure duration, immediate and post-procedure pain scores, diagnostic yield, complications, and surgical histopathology were recorded. Results: Ninety-five women were approached; 81 (85.3%) consented and were randomised. Forty underwent CNB; 40 underwent VAB; one was excluded. Median age was 57 years. The median procedure time was 2 minutes for both techniques. The median number of samples obtained was three for CNB and four for VAB. Median pain scores for the procedure and first 3 days were 1/10 and 1/10 for CNB and 1/10 and 2/10 for VAB (p=0.11 and 0.04). More women were prepared to undergo repeat CNB compared to VAB, but the difference was not significant (38/39 versus 33/39; p=0.11). Two patients developed a haematoma after VAB. One CNB and six VABs failed to yield adequate tissue (p=0.11), but the sensitivity was similar at 79% and 78%. Conclusion: Study uptake was high. Acceptability of the two procedures was similar, but VAB was associated with more post-procedure pain. The sensitivity appears to be similar. - Highlights: • Vacuum biopsy of axillary lymph nodes can be performed rapidly. • Post-procedure pain was slightly higher in women who underwent vacuum biopsy. • The inadequate yield rate of vacuum biopsy may be higher than that for core biopsy. • Sensitivity of 13-gauge vacuum biopsy and 14-gauge

Phylogenetic studies reveal existence of multiple lineages of a single genotype of DENV-1 (genotype III in India during 1956–2007

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Bhattacharya D

2009-01-01

Full Text Available Abstract Background Dengue virus type 1 (DENV-1 have been mostly circulating silently with dominant serotypes DENV-2 and DENV-3 in India. However recent times have marked an increase in DENV-1 circulation in yearly outbreaks. Many studies have not been carried out on this virus type, leaving a lacunae pertaining to the circulating genotypes, since its earliest report in India. In the present study, we sequenced CprM gene junction of 13 DENV-1 isolated from Delhi and Gwalior (North India between 2001–2007 and one 1956 Vellore isolate as reference. For comparison, we retrieved 11 other Indian and 70 global reference sequences from NCBI database, making sure that Indian and global isolates from all decades are available for comparative analysis. Results The region was found to be AT rich with no insertion or deletion. Majority of the nucleotide substitutions were silent, except 3 non-conservative amino acid changes (I → T, A → T and L → S at amino acid positions 59,114 and 155 respectively in the Indian DENV-1 sequences, sequenced in this study. Except two 1997–98 Delhi isolates, which group in genotype I; all other Indian isolates group in genotype III. All Indian genotype III DENV-1 exhibited diversity among them, giving rise to at least 4 distinct lineages (India 1–4 showing proximity to isolates from diverse geographic locations. Conclusion The extensive phylogenetic analysis revealed consistent existence of multiple lineages of DENV-1 genotype III during the last 5 decades in India.

Multiple skeletal muscle metastases revealing a cardiac intimal sarcoma

Energy Technology Data Exchange (ETDEWEB)

Crombe, Amandine [Institut Bergonie, Department of Radiology, Bordeaux (France); Lintingre, Pierre-Francois; Dallaudiere, Benjamin [Clinique du Sport de Bordeaux-Merignac, Department of Musculoskeletal Radiology, Merignac (France); Le Loarer, Francois [Institut Bergonie, Department of Pathology, Bordeaux (France); Lachatre, Denis [Dupuytren University Hospital, Department of Radiology, Limoges (France)

2018-01-15

We report the case of a 59-year-old female with progressive bilateral painful swelling of the thighs. MRI revealed multiple intramuscular necrotic masses with similar morphologic patterns. Whole-body CT and 18-FDG PET-CT scans demonstrated additional hypermetabolic muscular masses and a lobulated lesion within the left atrial cavity. As biopsy of a muscular mass was compatible with a poorly differentiated sarcoma with MDM2 oncogene amplification, two diagnoses were discussed: a dedifferentiated liposarcoma with muscle and heart metastases or a primary cardiac sarcoma, mainly a cardiac intimal sarcoma, with muscular metastases, which was finally confirmed by array-comparative genomic hybridization (aCGH) in a sarcoma reference center. This case emphasizes the potential for intimal sarcoma to disseminate in skeletal muscle prior to any other organ and the need for a genomic approach in addition to classical radiopathologic analyses to distinguish primary from secondary locations facing simultaneous tumors of the heart and skeletal muscles with MDM2 amplification. (orig.)

Major complications of central neuraxial block: report on the Third National Audit Project of the Royal College of Anaesthetists.

Science.gov (United States)

Cook, T M; Counsell, D; Wildsmith, J A W

2009-02-01

Serious complications of central neuraxial block (CNB) are rare. Limited information on their incidence and impact impedes clinical decision-making and patient consent. The Royal College of Anaesthetists Third National Audit Project was designed to inform this situation. A 2 week national census estimated the number of CNB procedures performed annually in the UK National Health Service. All major complications of CNBs performed over 1 yr (vertebral canal abscess or haematoma, meningitis, nerve injury, spinal cord ischaemia, fatal cardiovascular collapse, and wrong route errors) were reported. Each case was reviewed by an expert panel to assess causation, severity, and outcome. 'Permanent' injury was defined as symptoms persisting for more than 6 months. Efforts were made to validate denominator (procedures performed) and numerator (complications) data through national databases. The census phase produced a denominator of 707,455 CNB. Eighty-four major complications were reported, of which 52 met the inclusion criteria at the time they were reported. Data were interpreted 'pessimistically' and 'optimistically'. 'Pessimistically' there were 30 permanent injuries and 'optimistically' 14. The incidence of permanent injury due to CNB (expressed per 100,000 cases) was 'pessimistically' 4.2 (95% confidence interval 2.9-6.1) and 'optimistically' 2.0 (1.1-3.3). 'Pessimistically' there were 13 deaths or paraplegias, 'optimistically' five. The incidence of paraplegia or death was 'pessimistically' 1.8 per 100,000 (1.0-3.1) and 'optimistically' 0.7 (0-1.6). Two-thirds of initially disabling injuries resolved fully. The data are reassuring and suggest that CNB has a low incidence of major complications, many of which resolve within 6 months.

Cutting needle biopsy combined with immunohistochemical study of myeloperoxidase for the diagnosis of histiocytic necrotizing lymphadenitis.

Science.gov (United States)

Hanakawa, Hiroyuki; Orita, Yorihisa; Sato, Yasuharu; Takeuchi, Mai; Ohno, Kyotaro; Iwaki, Noriko; Ito, Toshihiro; Nishizaki, Kazunori; Yoshino, Tadashi

2013-12-01

Cutting needle biopsy (CNB) combined with immunohistochemical study of myeloperoxidase (MPO) is a useful minimally invasive diagnostic procedure for histiocytic necrotizing lymphadenitis (HNL). HNL is mainly diagnosed by pathological findings of open surgical biopsy (OSB) specimens. Recently the appearance of anti-MPO positive histiocytes has been reported as a highly specific pathological diagnosis for HNL. Considering the cosmetic impact and burden on the patients, we performed CNB combined with immunohistochemical study of MPO for the diagnosis of HNL. Few studies have reported the utility of this method in the diagnosis of HNL. A retrospective study was conducted using clinical data from 20 HNL patients. CNB was performed in 8 patients and OSB in 13 (OSB after CNB in 1). MPO-positive histiocytes were observed in all of the 20 cases. The accuracy of the diagnoses was finally confirmed by the clinical courses in all cases.

Significant Histological Features Differentiating Cellular Fibroadenoma from Phyllodes Tumor on Core Needle Biopsies

Science.gov (United States)

Yasir, Saba; Gamez, Roberto; Jenkins, Sarah; Visscher, Daniel W.; Nassar, Aziza

2015-01-01

Objectives Cellular fibroepithelial lesions (CFEL) are a heterogeneous group of tumors encompassing cellular fibroadenoma (CFA) and phyllodes tumor (PT). Distinction between the two is challenging on core needle biopsy (CNB). The objective of this study was to evaluate histological features that can help distinguish PT from CFA on CNB. Methods Records of all patients diagnosed with CFEL on CNB with follow-up excision between 2002 and 2012 were retrieved. Histopathological stromal features were evaluated on CNB including mitoses per 10 HPF, overgrowth, increased cellularity, fragmentation, adipose tissue infiltration, heterogeneity, subepithelial condensation, and nuclear pleomorphism. Results Twenty-seven of 64 (42.2%) were diagnosed as PT (24 BPT, 3 borderline PT) and 37 (57.8%) as CFA on excision. All features except for increased stromal cellularity were statistically significant. The average number of histologic features seen in PT and CFA was 3.9 and 1.4, respectively (OR 7.27; 95% CI: 2.44, 21.69; p= 0.0004). The average mitoses per 10 HPF was 3.0 for PT as compared to 0.8 for CFA (OR 2.14; 95% CI: 1.18, 3.86; p= 0.01). Conclusions The presence of mitosis (3 or more) and/or total histologic features of 3 or more on CNB were most helpful features in predicting PT on excision. PMID:25125627

Practical guidelines for ultrasound-guided core needle biopsy of soft-tissue lesions: Transformation from beginner to specialist

Energy Technology Data Exchange (ETDEWEB)

Kim, Sang Yoon; Chung, Hye Won; Oh, Tack Sun; Lee, Jong Seok [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

2017-04-15

Ultrasound-guided core needle biopsy (US-CNB) is an important step in the diagnosis of musculoskeletal soft-tissue lesions. To maximize efficacy and minimize the complications of US-CNB, it is critical to collaborate with a multidisciplinary team and to understand the particular considerations of US-CNB for these lesions. The purpose of this article is to provide a systematic review and step-by-step tips for using US-CNB to diagnose musculoskeletal soft-tissue lesions.

Computed tomography-guided needle aspiration and biopsy of pulmonary lesions - A single-center experience in 1000 patients

Energy Technology Data Exchange (ETDEWEB)

Poulou, Loukia S.; Tsagouli, Paraskevi; Thanos, Loukas [Dept. of Medical Imaging and Interventional Radiology, General Hospital of Chest Diseases ' Sotiria' , Athens (Greece)], e-mail: ploukia@hotmail.com; Ziakas, Panayiotis D. [Program of Outcomes Research, Div. of Infectious Diseases, Warren Alpert Medical School, Brown Univ., RI, and Div. of Infectious Diseases, Rhode Island Hospital, Rhode Island (United States); Politi, Dimitra [Dept. of Cythopathology, General Hospital of Chest Diseases ' Sotiria' Athens (Greece); Trigidou, Rodoula [Dept. of Pathology, General Hospital of Chest Diseases ' Sotiria' Athens (Greece)

2013-07-15

Background: Computed tomography (CT)-guided fine needle aspiration (FNA) and biopsies are well-established, minimally invasive diagnostic tools for pulmonary lesions. Purpose: To analyze retrospectively the results of 1000 consecutive lung CT-guided FNA and/or core needle biopsies (CNB), the main outcome measures being diagnostic yield, and complication rates. Material and Methods: Patients considered eligible were those referred to our department for lung lesions. The choice of FNA, CNB, or both was based upon the radiologist's judgment. Diagnostic yield was defined as the probability of having a definite result by cytology/histology. Results: The study included 733 male patients and 267 female patients, with a mean (SD) age of 66.4 (11.4) years. The mean (SD) lesion size was 3.7 (2.4) cm in maximal diameter. Six hundred and forty-one (64%) patients underwent an FNA procedure, 245 (25%) a CNB, and 114 (11%) had been subjected to both. The diagnostic yield was 960/994 (96.6%); this decreased significantly with the use of CNB only (odds ratio [OR] 0.32; 95% CI 0.12 - 0.88; P = 0.03), while it increased with lesion size (OR 1.35; 95% CI 1.03 - 1.79; P = 0.03 per cm increase). In 506 patients (52.7%), a malignant process was diagnosed by cytopathology/histology. The complication rate reached 97/1000 (9.7%); complications included: hemorrhage, 62 (6.2%); pneumothorax, 28 (2.8%); hemorrhage and pneumothorax, 5 (0.5%); and hemoptysis, 2 (0.2%). It was not significantly affected by the type of procedure or localization of the lesion. The overall risk for complications was three times higher for lesions <4 cm (OR 3.26; 95% CI 1.96 - 5.42; P < 0.001). Conclusion: CT-guided lung biopsy has a high diagnostic yield using FNA, CNB, or both. The CNB procedure alone will not suffice. Complication rates were acceptable and correlated inversely with lesion size, not localization or type of procedure.

Compact-Nanobox Engineering of Transition Metal Oxides with Enhanced Initial Coulombic Efficiency for Lithium-Ion Battery Anodes.

Science.gov (United States)

Zhu, Yanfei; Hu, Aiping; Tang, Qunli; Zhang, Shiying; Deng, Weina; Li, Yanhua; Liu, Zheng; Fan, Binbin; Xiao, Kuikui; Liu, Jilei; Chen, Xiaohua

2018-03-14

A novel strategy is proposed to construct a compact-nanobox (CNB) structure composed of irregular nanograins (average diameter ≈ 10 nm), aiming to confine the electrode-electrolyte contact area and enhance initial Coulombic efficiency (ICE) of transition metal oxide (TMO) anodes. To demonstrate the validity of this attempt, CoO-CNB is taken as an example which is synthesized via a carbothermic reduction method. Benefiting from the compact configuration, electrolyte can only contact the outer surface of the nanobox, keeping the inner CoO nanograins untouched. Therefore, the solid electrolyte interphase (SEI) formation is reduced. Furthermore, the internal cavity leaves enough room for volume variation upon lithiation and delithiation, resulting in superior mechanical stability of the CNB structure and less generation of fresh SEI. Consequently, the SEI remains stable and spatially confined without degradation, and hence, the CoO-CNB electrode delivers an enhanced ICE of 82.2%, which is among the highest values reported for TMO-based anodes in lithium-ion batteries. In addition, the CoO-CNB electrode also demonstrates excellent cyclability with a reversible capacity of 811.6 mA h g -1 (90.4% capacity retention after 100 cycles). These findings open up a new way to design high-ICE electrodes and boost the practical application of TMO anodes.

Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

Directory of Open Access Journals (Sweden)

Maria Liguori

Full Text Available The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF proteomic profiles of Multiple Sclerosis (MS patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS, 16 Relapsing Remitting (RR MS, 11 Progressive (Pr MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da. Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05, whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04. Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013. Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

Core needle biopsy of the thyroid: 2016 consensus statement and recommendations from Korea society of thyroid radiology

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Na, Dong Gyu [Dept. of Radiology, Human Medical Imaging and Intervention Center, Seoul (Korea, Republic of); Baek, Jung Hwan; Lee, Jeong Hyun [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); and others

2017-01-15

Core needle biopsy (CNB) has been suggested as a complementary diagnostic method to fine-needle aspiration in patients with thyroid nodules. Many recent CNB studies have suggested a more advanced role for CNB, but there are still no guidelines on its use. Therefore, the Task Force Committee of the Korean Society of Thyroid Radiology has developed the present consensus statement and recommendations for the role of CNB in the diagnosis of thyroid nodules. These recommendations are based on evidence from the current literature and expert consensus.

Significant histologic features differentiating cellular fibroadenoma from phyllodes tumor on core needle biopsy specimens.

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Yasir, Saba; Gamez, Roberto; Jenkins, Sarah; Visscher, Daniel W; Nassar, Aziza

2014-09-01

Cellular fibroepithelial lesions (CFELs) are a heterogeneous group of tumors encompassing cellular fibroadenoma (CFA) and phyllodes tumor (PT). Distinction between the two is challenging on core needle biopsy (CNB) specimens. The objective of this study was to evaluate histologic features that can help distinguish PT from CFA on CNB specimens. Records of all patients diagnosed with CFELs on CNB specimens with follow-up excision between January 2002 and December 2012 were retrieved. Histopathologic stromal features were evaluated on CNB specimens, including mitoses per 10 high-power fields (hpf), overgrowth, increased cellularity, fragmentation, adipose tissue infiltration, heterogeneity, subepithelial condensation, and nuclear pleomorphism. Twenty-seven (42.2%) of 64 were diagnosed as PT (24 benign PTs and three borderline PTs) and 37 (57.8%) as CFA on excision. All features except for increased stromal cellularity were statistically significant. The average number of histologic features seen in PT and CFA was 3.9 and 1.4, respectively (odds ratio [OR], 7.27; 95% confidence interval [CI], 2.44-21.69; P = .0004). The average number of mitoses per 10 hpf was 3.0 for PT compared with 0.8 for CFA (OR, 2.14; 95% CI, 1.18-3.86; P = .01). The presence of mitoses (three or more) and/or total histologic features of three or more on CNB specimens were the most helpful features in predicting PT on excision. Copyright© by the American Society for Clinical Pathology.

The L1TD1 Protein Interactome Reveals the Importance of Post-transcriptional Regulation in Human Pluripotency

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Maheswara Reddy Emani

2015-03-01

Full Text Available The RNA-binding protein L1TD1 is one of the most specific and abundant proteins in pluripotent stem cells and is essential for the maintenance of pluripotency in human cells. Here, we identify the protein interaction network of L1TD1 in human embryonic stem cells (hESCs and provide insights into the interactome network constructed in human pluripotent cells. Our data reveal that L1TD1 has an important role in RNA splicing, translation, protein traffic, and degradation. L1TD1 interacts with multiple stem-cell-specific proteins, many of which are still uncharacterized in the context of development. Further, we show that L1TD1 is a part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency.

Management of a patient with thermal burns and para-chloronitrobenzene poisoning

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Yuanhai Zhang

2014-10-01

Full Text Available Para-chloronitrobenzene (p-CNB, a hazardous and toxic substance, is widely used as an intermediary in chemical industries. p-CNB can cause methaemoglobinaemia due to electron-withdrawing properties of the nitro and chlorine groups. We present a case of a 23-year-old man suffering from thermal burns and p-CNB poisoning. In this case, severe methaemoglobinaemia was caused by the absorption of p-CNB through the burn wounds. Despite active treatment, such as the antidote of methylene blue, the patient’s methaemoglobinaemia progressed, with slowly increasing methaemoglobin (MetHb level. This case highlights the complexity and difficulty of managing this type of injury. To our knowledge, this case can be the first case report describing methaemoglobinaemia induced by p-CNB in a patient with thermal burns.

Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.

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Chinen, Yoshiaki; Kuroda, Junya; Shimura, Yuji; Nagoshi, Hisao; Kiyota, Miki; Yamamoto-Sugitani, Mio; Mizutani, Shinsuke; Sakamoto, Natsumi; Ri, Masaki; Kawata, Eri; Kobayashi, Tsutomu; Matsumoto, Yosuke; Horiike, Shigeo; Iida, Shinsuke; Taniwaki, Masafumi

2014-12-15

Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells. In the clinical setting, PDPK1 was active in myeloma cells of approximately 90% of symptomatic patients at diagnosis, and the smaller population of patients with multiple myeloma exhibiting myeloma cells without active PDPK1 showed a significantly less frequent proportion of the disease stage III by the International Staging System and a significantly more favorable prognosis, including the longer overall survival period and the longer progression-free survival period by bortezomib treatment, than patients with active PDPK1, suggesting that PDPK1 activation accelerates the disease progression and the resistance to treatment in multiple myeloma. Our study demonstrates that PDPK1 is a potent and a universally targetable signaling mediator in multiple myeloma regardless of the types of cytogenetic/molecular profiles. ©2014 American Association for Cancer Research.

HER2 testing on core needle biopsy specimens from primary breast cancers: interobserver reproducibility and concordance with surgically resected specimens

International Nuclear Information System (INIS)

Tsuda, Hitoshi; Kurosumi, Masafumi; Umemura, Shinobu; Yamamoto, Sohei; Kobayashi, Takayuki; Osamura, Robert Yoshiyuki

2010-01-01

Accurate evaluation of human epidermal growth factor receptor type-2 (HER2) status based on core needle biopsy (CNB) specimens is mandatory for identification of patients with primary breast cancer who will benefit from primary systemic therapy with trastuzumab. The aim of the present study was to validate the application of HER2 testing with CNB specimens from primary breast cancers in terms of interobserver reproducibility and comparison with surgically resected specimens. A total of 100 pairs of archival formalin-fixed paraffin-embedded CNB and surgically resected specimens of invasive breast carcinomas were cut into sections. All 100 paired sections were subjected to HER2 testing by immunohistochemistry (IHC) and 27 paired sections were subjected to that by fluorescence in situ hybridization (FISH), the results being evaluated by three and two observers, respectively. Interobserver agreement levels in terms of judgment and the concordance of consensus scores between CNB samples and the corresponding surgically resected specimens were estimated as the percentage agreement and κ statistic. In CNB specimens, the percentage interobserver agreement of HER2 scoring by IHC was 76% (κ = 0.71) for 3 × 3 categories (0-1+ versus 2+ versus 3+) and 90% (κ = 0.80) for 2 × 2 categories (0-2+ versus 3+). These levels were close to the corresponding ones for the surgically resected specimens: 80% (κ = 0.77) for 3 × 3 categories and 92% (κ = 0.88) for 2 × 2 categories. Concordance of consensus for HER2 scores determined by IHC between CNB and the corresponding surgical specimens was 87% (κ = 0.77) for 3 × 3 categories, and 94% (κ = 0.83) for 2 × 2 categories. Among the 13 tumors showing discordance in the mean IHC scores between the CNB and surgical specimens, the results of consensus for FISH results were concordant in 11. The rate of successful FISH analysis and the FISH positivity rate in cases with a HER2 IHC score of 2+ differed among specimens processed at

HER2 testing on core needle biopsy specimens from primary breast cancers: interobserver reproducibility and concordance with surgically resected specimens

Directory of Open Access Journals (Sweden)

Yamamoto Sohei

2010-10-01

Full Text Available Abstract Background Accurate evaluation of human epidermal growth factor receptor type-2 (HER2 status based on core needle biopsy (CNB specimens is mandatory for identification of patients with primary breast cancer who will benefit from primary systemic therapy with trastuzumab. The aim of the present study was to validate the application of HER2 testing with CNB specimens from primary breast cancers in terms of interobserver reproducibility and comparison with surgically resected specimens. Methods A total of 100 pairs of archival formalin-fixed paraffin-embedded CNB and surgically resected specimens of invasive breast carcinomas were cut into sections. All 100 paired sections were subjected to HER2 testing by immunohistochemistry (IHC and 27 paired sections were subjected to that by fluorescence in situ hybridization (FISH, the results being evaluated by three and two observers, respectively. Interobserver agreement levels in terms of judgment and the concordance of consensus scores between CNB samples and the corresponding surgically resected specimens were estimated as the percentage agreement and κ statistic. Results In CNB specimens, the percentage interobserver agreement of HER2 scoring by IHC was 76% (κ = 0.71 for 3 × 3 categories (0-1+ versus 2+ versus 3+ and 90% (κ = 0.80 for 2 × 2 categories (0-2+ versus 3+. These levels were close to the corresponding ones for the surgically resected specimens: 80% (κ = 0.77 for 3 × 3 categories and 92% (κ = 0.88 for 2 × 2 categories. Concordance of consensus for HER2 scores determined by IHC between CNB and the corresponding surgical specimens was 87% (κ = 0.77 for 3 × 3 categories, and 94% (κ = 0.83 for 2 × 2 categories. Among the 13 tumors showing discordance in the mean IHC scores between the CNB and surgical specimens, the results of consensus for FISH results were concordant in 11. The rate of successful FISH analysis and the FISH positivity rate in cases with a HER2 IHC score of

Multiple frequency ECH (MFECH) in SM-1 and STM-1

International Nuclear Information System (INIS)

Lazar, N.; Barter, J.; Dandl, R.; DiVergilio, W.; Quon, B.; Wuerker, R.

1982-01-01

Plasma properties were studied in a simple mirror (SM-1) and a five-cell axisymmetric tandem mirror (STM-1) using multiple frequency ECH. The cold plasma properties depend predominantly on total power but the efficiency for producing the diamagnetic ring plasma depends critically on heating with multiple frequencies. The effects of frequency separation of the heating sources will be demonstrated. Noise fluctuations in the axial current are suppressed with increasing ring-β, but the observed frequency spectrum are not well understood. Annulus β in the multiple mirror is also dependent on MFECH. Plans for and experiments in the new facility will be described

Mycobacterium malmesburyense sp. nov., a non-tuberculous species of the genus Mycobacterium revealed by multiple gene sequence characterization

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Gcebe, N

2017-04-01

Full Text Available Journal of Systematic and Evolutionary Microbiology: DOI 10.1099/ijsem.0.001678 Mycobacterium malmesburyense sp. nov., a non-tuberculous species of the genus Mycobacterium revealed by multiple gene sequence characterization Gcebe N Rutten V Gey...

Multiple surveys employing a new sample-processing protocol reveal the genetic diversity of placozoans in Japan.

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Miyazawa, Hideyuki; Nakano, Hiroaki

2018-03-01

Placozoans, flat free-living marine invertebrates, possess an extremely simple bauplan lacking neurons and muscle cells and represent one of the earliest-branching metazoan phyla. They are widely distributed from temperate to tropical oceans. Based on mitochondrial 16S rRNA sequences, 19 haplotypes forming seven distinct clades have been reported in placozoans to date. In Japan, placozoans have been found at nine locations, but 16S genotyping has been performed at only two of these locations. Here, we propose a new processing protocol, "ethanol-treated substrate sampling," for collecting placozoans from natural environments. We also report the collection of placozoans from three new locations, the islands of Shikine-jima, Chichi-jima, and Haha-jima, and we present the distribution of the 16S haplotypes of placozoans in Japan. Multiple surveys conducted at multiple locations yielded five haplotypes that were not reported previously, revealing high genetic diversity in Japan, especially at Shimoda and Shikine-jima Island. The observed geographic distribution patterns were different among haplotypes; some were widely distributed, while others were sampled only from a single location. However, samplings conducted on different dates at the same sites yielded different haplotypes, suggesting that placozoans of a given haplotype do not inhabit the same site constantly throughout the year. Continued sampling efforts conducted during all seasons at multiple locations worldwide and the development of molecular markers within the haplotypes are needed to reveal the geographic distribution pattern and dispersal history of placozoans in greater detail.

Characteristics of the Danish families with multiple endocrine neoplasia type 1

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Jäger, Anne Charlotte; Friis-Hansen, Lennart; Hansen, Thomas v.O.

2006-01-01

Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier...... reported mutation. The mutations were predominantly found in exons 9 and 10 encoding the C-terminal part of menin. Seven of the mutations were missense mutations, changing conserved residues. Furthermore screening of 93 out of 153 consecutive patients with primary hyperparathyroidism (pHPT) identified five...... mutation carriers. Two of these belonged to known MEN1 families, whereas the only MEN1-related disease in the other three was pHPT. Screening of 96 consecutive patients with fore-/midgut endocrine tumours revealed five mutation carries out of 28 patients with sporadic gastrinomas, whereas no mutations were...

Laparoscopic and Percutaneous Core Needle Biopsy Plays a Central Role for the Diagnosis of Autoimmune Pancreatitis in a Single-Center Study from Denmark

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Detlefsen, Sönke; Mortensen, Michael Bau; Kjærulf Pless, Torsten

2015-01-01

organ involvement was observed in 40% of type 1 and 13% of type 2, but inflammatory bowel disease only in type 2 (P = 0.001). One patient had IgG4-related chronic perisplenitis as a hitherto undescribed manifestation of IgG4-related disease. Nineteen (91%) of 21 biopsied patients had diagnostic CNB...... Hospital from 2007 to 2013 were included (n = 30; mean follow-up, 26.2 months). Data from laparoscopic or percutaneous ultrasound-guided core needle biopsy (CNB), resection specimens, endoscopic ultrasound (EUS), EUS-guided CNB, computed tomography, serum immunoglobulin G4 (IgG4), and pancreatography were...... retrospectively analyzed according to ICDC. RESULTS: Twenty patients were diagnosed with type 1, 8 with type 2, and 2 with not otherwise specified AIP. Twenty-eight patients (93%) could correctly be classified when ICDC were retrospectively applied. Serum IgG4 was elevated in 44% of type 1 and 0% of type 2. Other...

Utility of core biopsy with concurrent ROSE FNA in the diagnosis of pancreatic tumor-does the biopsy add any diagnostic benefit?

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Yan, Lei; Ikemura, Kenji; Park, Ji-Weon

2018-02-01

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided core-needle biopsy (EUS-CNB) are widely used for diagnosis of pancreatic tumors. The aim of our study was to compare the diagnostic performance of ROSE EUS-FNA and EUS-CNB for diagnosis of pancreatic malignancy during the same EUS. Patients who underwent both FNA and CNB during the same EUS for pancreatic solid lesion were reviewed retrospectively. Sample adequacy, diagnostic yield (defined as percentage of definitive diagnosis), sensitivity and specificity for malignancy were compared between FNA and CNB. A total of 48 patients with solid pancreatic lesions were evaluated. The proportions of adequate samples were 48/48 (100%) for FNA and 45/48 (93.7%) for core biopsy (P = .24). The diagnostic yield was 42/48 (87.5%) and 33/48 (68.7%) for FNA and CNB respectively (P = .046). The incremental increase in diagnostic yield by combining both methods was 2/48 (4%). The diagnostic yield for malignancy was 30/32 (93.7%) for FNA and 23/32 (71.8%) for CNB (P = .043). The sensitivity for the diagnosis of malignancy for FNA and CNB were 90.6% and 69%, respectively (P = .045). The specificity was 100% for both methods. The sensitivity for diagnosing malignancy increased to 93.8% when the two methods were combined. The difference in diagnostic yield was not associated with lesion size or location. EUS-guided FNA is a superior method of assessing solid pancreatic lesion and pancreatic malignancy with better diagnostic yield and higher sensitivity than EUS-CNB. © 2017 Wiley Periodicals, Inc.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

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David Judah

Full Text Available Integrin-linked kinase (ILK is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

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Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Can concurrent core biopsy and fine needle aspiration biopsy improve the false negative rate of sonographically detectable breast lesions?

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Chang Tsai-Wang

2010-07-01

Full Text Available Abstract Background The aims of this study were to determine the accuracy of concurrent core needle biopsy (CNB and fine needle aspiration biopsy (FNAB for breast lesions and to estimate the false-negative rate using the two methods combined. Methods Over a seven-year period, 2053 patients with sonographically detectable breast lesions underwent concurrent ultrasound-guided CNB and FNAB. The sonographic and histopathological findings were classified into four categories: benign, indeterminate, suspicious, and malignant. The histopathological findings were compared with the definitive excision pathology results. Patients with benign core biopsies underwent a detailed review to determine the false-negative rate. The correlations between the ultrasonography, FNAB, and CNB were determined. Results Eight hundred eighty patients were diagnosed with malignant disease, and of these, 23 (2.5% diagnoses were found to be false-negative after core biopsy. After an intensive review of discordant FNAB results, the final false-negative rate was reduced to 1.1% (p-value = 0.025. The kappa coefficients for correlations between methods were 0.304 (p-value p-value p-value Conclusions Concurrent CNB and FNAB under ultrasound guidance can provide accurate preoperative diagnosis of breast lesions and provide important information for appropriate treatment. Identification of discordant results using careful radiological-histopathological correlation can reduce the false-negative rate.

Central Neuraxial Blockade-Assisted External Cephalic Version in Reducing Caesarean Section Rate: Systematic Review and Meta-Analysis

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Bolaji, Ibrahim; Alabi-Isama, Lillian

2009-01-01

We review the medical literature on the success, safety and economic value of central neuraxial blockade-assisted (CNB) external cephalic version from randomized controlled studies identified from 1951 to 2009. The result showed that more women had successful ECV with regional anaesthesia with corresponding reduction in caesarean section rate. They were 1.5 times more likely than women not receiving anaesthesia to have a successful ECV. The number to treat is six women needed to receive anaesthesia for 1 baby to be turned from breech to cephalic presentation. Feto-maternal morbidity was not increased in the CNB-aided group consisting of only transient bradycardia. Although the appropriate amount of force for safe version has not been quantified, there was no report of uterine rupture despite removal of these patients from “excessive force-pain biofeedback loop” induced through motor nerve blockade. We can attribute 30% of cost savings amounting to £42,150.00 directly to CNB using the most up to date Health Resource Group Code (HRG4). The initial results are encouraging but until the benefits and safety of CNB-aided ECV are substantiated by large randomized, blinded controlled trials, this practice cannot be universally recommended. PMID:20069044

Central Neuraxial Blockade-Assisted External Cephalic Version in Reducing Caesarean Section Rate: Systematic Review and Meta-Analysis

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Ibrahim Bolaji

2009-01-01

Full Text Available We review the medical literature on the success, safety and economic value of central neuraxial blockade-assisted (CNB external cephalic version from randomized controlled studies identified from 1951 to 2009. The result showed that more women had successful ECV with regional anaesthesia with corresponding reduction in caesarean section rate. They were 1.5 times more likely than women not receiving anaesthesia to have a successful ECV. The number to treat is six women needed to receive anaesthesia for 1 baby to be turned from breech to cephalic presentation. Feto-maternal morbidity was not increased in the CNB-aided group consisting of only transient bradycardia. Although the appropriate amount of force for safe version has not been quantified, there was no report of uterine rupture despite removal of these patients from “excessive force-pain biofeedback loop” induced through motor nerve blockade. We can attribute 30% of cost savings amounting to £42,150.00 directly to CNB using the most up to date Health Resource Group Code (HRG4. The initial results are encouraging but until the benefits and safety of CNB-aided ECV are substantiated by large randomized, blinded controlled trials, this practice cannot be universally recommended.

IS IT NECESSARY TO EXCISE ALL BREAST LESIONS? EXPERIENCE FROM A UNIVERSITY-BASED BREAST UNIT

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YIP CH

2009-01-01

Full Text Available Background: Breast cancer is becoming more important in Asia since it affect the younger age group. Question arises whether it is safe for breast lesions to be left in-situ if all the elements in triple assessment are benign. The aim of this study is to audit all the excision biopsies of breast lumps done in the University Malaya Medical Centre (UMMC, to review the association of age with the type of pathological finding and to evaluate the rate of carcinoma in these biopsies. Methods: We conducted a retrospective study of all women who had excision biopsy of a breast lump in the University Malaya Medical Centre from January 2005 to December 2006. All patients with malignant preoperative biopsies were excluded. Results: Of 717 lesions in 664 patients, 459 (64% were fibroadenoma, 114 (15.9% were fibrocystic disease, 20 (2.8% were phylloides tumour, 27 (3.8% were papilloma, 59 (8.2% were malignant and 38 (5.3% were of other pathology. Of the 717 open biopsies, 449 (62.6% had fine-needle aspiration cytology (FNAC, 31 (4.3% had core needle biopsy (CNB, while 14 (2.0% had both FNAC and CNB done prior to excision biopsy. 251 (35% had neither FNAC nor CNB. The incidence of fibroadenoma decreased with increasing age and the incidence of fibrocystic changes and papilloma increased with increasing age. There was no association of age with phylloides tumour. The incidence of unexpected malignancy increased with increasing age. The incidence rates were 0.3%, 4.5%, 19.4%, 29.7% and 29.6% for the age group below 30, 30-39, 40-49, 50-59 and above 60 years of age respectively. Of the 59 malignant lesions, FNAC was performed on 47 (79.7% and CNB on 16 (27.1%. 9 had both FNAC and CNB and 3 had neither FNAC nor CNB. Out of the 56 lesions where FNAC/CNB were done, 23 (41.1% were reported as benign, 20 (35.7% as suspicious, 4 (7.1% as atypical, 5 (8.9% as inadequate, 2 (3.6% as equivocal and 2 (3.6% as lymphoid lesions. Out of the 23 prior biopsies reported as

Proteotyping of laboratory-scale biogas plants reveals multiple steady-states in community composition.

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Kohrs, F; Heyer, R; Bissinger, T; Kottler, R; Schallert, K; Püttker, S; Behne, A; Rapp, E; Benndorf, D; Reichl, U

2017-08-01

Complex microbial communities are the functional core of anaerobic digestion processes taking place in biogas plants (BGP). So far, however, a comprehensive characterization of the microbiomes involved in methane formation is technically challenging. As an alternative, enriched communities from laboratory-scale experiments can be investigated that have a reduced number of organisms and are easier to characterize by state of the art mass spectrometric-based (MS) metaproteomic workflows. Six parallel laboratory digesters were inoculated with sludge from a full-scale BGP to study the development of enriched microbial communities under defined conditions. During the first three month of cultivation, all reactors (R1-R6) were functionally comparable regarding biogas productions (375-625 NL L reactor volume -1 d -1 ), methane yields (50-60%), pH values (7.1-7.3), and volatile fatty acids (VFA, 1 gNH 3 L -1 ) showed an increase to pH 7.5-8.0, accumulation of acetate (>10 mM), and decreasing biogas production (<125 NL L reactor volume -1 d -1 ). Tandem MS (MS/MS)-based proteotyping allowed the identification of taxonomic abundances and biological processes. Although all reactors showed similar performances, proteotyping and terminal restriction fragment length polymorphisms (T-RFLP) fingerprinting revealed significant differences in the composition of individual microbial communities, indicating multiple steady-states. Furthermore, cellulolytic enzymes and cellulosomal proteins of Clostridium thermocellum were identified to be specific markers for the thermophilic reactors (R3, R4). Metaproteins found in R3 indicated hydrogenothrophic methanogenesis, whereas metaproteins of acetoclastic methanogenesis were identified in R4. This suggests not only an individual evolution of microbial communities even for the case that BGPs are started at the same initial conditions under well controlled environmental conditions, but also a high compositional variance of microbiomes under

Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase

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Duan, Hongying; Takagi, Akira [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Kayano, Hidekazu [Department of Pathology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Koyama, Isamu [Department of Digestive and General Surgery, Saitama International Medical Center, Faculty of Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298 (Japan); Morisseau, Christophe; Hammock, Bruce D. [Department of Entomology and Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616-8584 (United States); Akatsuka, Toshitaka, E-mail: akatsuka@saitama-med.ac.jp [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan)

2012-04-01

In a previous study, we developed five kinds of monoclonal antibodies against different portions of human mEH: three, anti-N-terminal; one, anti-C-terminal; one, anti-conformational epitope. Using them, we stained the intact and the permeabilized human cells of various kinds and performed flow cytometric analysis. Primary hepatocytes and peripheral blood mononuclear cells (PBMC) showed remarkable differences. On the surface, hepatocytes exhibited 4 out of 5 epitopes whereas PBMC did not show any of the epitopes. mEH was detected inside both cell types, but the most prominent expression was observed for the conformational epitope in the hepatocytes and the two N-terminal epitopes in PBMC. These differences were also observed between hepatocyte-derived cell lines and mononuclear cell-derived cell lines. In addition, among each group, there were several differences which may be related to the cultivation, the degree of differentiation, or the original cell subsets. We also noted that two glioblastoma cell lines reveal marked expression of the conformational epitope on the surface which seemed to correlate with the brain tumor-associated antigen reported elsewhere. Several cell lines also underwent selective permeabilization before flow cytometric analysis, and we noticed that the topological orientation of mEH on the ER membrane in those cells was in accordance with the previous report. However, the orientation on the cell surface was inconsistent with the report and had a great variation between the cells. These findings show the multiple mode of expression of mEH which may be possibly related to the multiple roles that mEH plays in different cells. -- Highlights: ► We examine expression of five mEH epitopes in human cells. ► Remarkable differences exist between hepatocytes and PBMC. ► mEH expression in cell lines differs depending on several factors. ► Some glioblastoma cell lines reveal marked surface expression of mEH. ► Topology of mEH on the cell

Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides.

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Lee, Soo Chan; Li, Alicia; Calo, Silvia; Heitman, Joseph

2013-01-01

Many pathogenic fungi are dimorphic and switch between yeast and filamentous states. This switch alters host-microbe interactions and is critical for pathogenicity. However, in zygomycetes, whether dimorphism contributes to virulence is a central unanswered question. The pathogenic zygomycete Mucor circinelloides exhibits hyphal growth in aerobic conditions but switches to multi-budded yeast growth under anaerobic/high CO₂ conditions. We found that in the presence of the calcineurin inhibitor FK506, Mucor exhibits exclusively multi-budded yeast growth. We also found that M. circinelloides encodes three calcineurin catalytic A subunits (CnaA, CnaB, and CnaC) and one calcineurin regulatory B subunit (CnbR). Mutations in the latch region of CnbR and in the FKBP12-FK506 binding domain of CnaA result in hyphal growth of Mucor in the presence of FK506. Disruption of the cnbR gene encoding the sole calcineurin B subunit necessary for calcineurin activity yielded mutants locked in permanent yeast phase growth. These findings reveal that the calcineurin pathway plays key roles in the dimorphic transition from yeast to hyphae. The cnbR yeast-locked mutants are less virulent than the wild-type strain in a heterologous host system, providing evidence that hyphae or the yeast-hyphal transition are linked to virulence. Protein kinase A activity (PKA) is elevated during yeast growth under anaerobic conditions, in the presence of FK506, or in the yeast-locked cnbR mutants, suggesting a novel connection between PKA and calcineurin. cnaA mutants lacking the CnaA catalytic subunit are hypersensitive to calcineurin inhibitors, display a hyphal polarity defect, and produce a mixture of yeast and hyphae in aerobic culture. The cnaA mutants also produce spores that are larger than wild-type, and spore size is correlated with virulence potential. Our results demonstrate that the calcineurin pathway orchestrates the yeast-hyphal and spore size dimorphic transitions that contribute to

Type 1 diabetes and multiple sclerosis

DEFF Research Database (Denmark)

Nielsen, N.M.; Westergaard, T.; Frisch, M.

2006-01-01

BACKGROUND: Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported...... Multiple Sclerosis Register were used to identify patients with T1D, defined as patients in whom diabetes was diagnosed before age 20 years (N = 6078), and patients with MS (N = 11 862). First-degree relatives (N = 14,771) of patients with MS were identified from family information in the Danish Civil....... OBJECTIVE: To assess the co-occurrence of T1D and MS by estimating the risk for MS in patients with T1D and the risk for T1D in first-degree relatives of patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Two population-based disease registers, the Danish Hospital Discharge Register and the Danish...

MULTIPLICITY OF THE PROTOSTAR SERPENS SMM 1 REVEALED BY MILLIMETER IMAGING

International Nuclear Information System (INIS)

Choi, Minho

2009-01-01

The Serpens SMM 1 region was observed in the 6.9 mm continuum with an angular resolution of about 0.''6. Two sources were found to have steep positive spectra suggesting emission from dust. The stronger one, SMM 1a, is the driving source of the bipolar jet previously known, and the mass of the dense molecular gas traced by the millimeter continuum is about 8 M sun . The newly found source, SMM 1b, positionally coincides with the brightest mid-IR source in this region, which implies that SMM 1b is yet another young stellar object. SMM 1b seems to be less deeply embedded than SMM 1a. SMM 1 is probably a protobinary system with a projected separation of 500 AU.

Effector stage CC chemokine receptor-1 selective antagonism reduces multiple sclerosis-like rat disease.

Science.gov (United States)

Eltayeb, Sana; Sunnemark, Dan; Berg, Anna-Lena; Nordvall, Gunnar; Malmberg, Asa; Lassmann, Hans; Wallström, Erik; Olsson, Tomas; Ericsson-Dahlstrand, Anders

2003-09-01

We have studied the role of the chemokine receptor CCR1 during the effector stage of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in DA rats. In situ hybridization histochemistry revealed local production of the CCR1 ligands CCL3 (MIP-1 alpha) and CCL5 (RANTES), as well as large numbers of CCR1 and CCR5 expressing cells within inflammatory brain lesions. A low-molecular weight CCR1 selective antagonist potently abrogated both clinical and histopathological disease signs during a 5-day treatment period, without signs of peripheral immune compromise. Thus, we demonstrate therapeutic targeting of CCR1-dependent leukocyte recruitment to the central nervous system in a multiple sclerosis (MS)-like rat model.

T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

Science.gov (United States)

van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

2018-05-01

-) expressed the highest very late antigen-4 levels and selectively accumulated in natalizumab-treated patients who remained free of clinical relapses. This was not found in patients who experienced relapses during natalizumab treatment. The enhanced potential of Th17.1 cells to infiltrate the central nervous system was supported by their predominance in cerebrospinal fluid of early multiple sclerosis patients and their preferential transmigration across human brain endothelial layers. These findings reveal a dominant contribution of Th1-like Th17 subpopulations, in particular Th17.1 cells, to clinical disease activity and provide a strong rationale for more specific and earlier use of T cell-targeted therapy in multiple sclerosis.

Fracture toughness versus micro-tensile bond strength testing of adhesive-dentin interfaces.

Science.gov (United States)

De Munck, Jan; Luehrs, Anne-Katrin; Poitevin, André; Van Ende, Annelies; Van Meerbeek, Bart

2013-06-01

To assess interfacial fracture toughness of different adhesive approaches and compare to a standard micro-tensile bond-strength (μTBS) test. Chevron-notched beam fracture toughness (CNB) was measured following a modified ISO 24370 standard. Composite bars with dimensions of 3.0×4.0×25 mm were prepared, with the adhesive-dentin interface in the middle. At the adhesive-dentin interface, a chevron notch was prepared using a 0.15 mm thin diamond blade mounted in a water-cooled diamond saw. Each specimen was loaded until failure in a 4-point bend test setup and the fracture toughness was calculated according to the ISO specifications. Similarly, adhesive-dentin micro-specimens (1.0×1.0×8-10 mm) were stressed in tensile until failure to determine the μTBS. A positive correlation (r(2)=0.64) was observed between CNB and μTBS, which however was only nearly statistically significant, mainly due to the dissimilar outcome of Scotchbond Universal (3M ESPE). While few μTBS specimens failed at the adhesive-dentin interface, almost all CNB specimens failed interfacially at the notch tip. Weibull moduli for interfacial fracture toughness were much higher than for μTBS (3.8-11.5 versus 2.7-4.8, respectively), especially relevant with regard to early failures. Although the ranking of the adhesives on their bonding effectiveness tested using CNB and μTBS corresponded well, the outcome of CNB appeared more reliable and less variable. Fracture toughness measurement is however more laborious and requires specific equipment. The μTBS nevertheless appeared to remain a valid method to assess bonding effectiveness in a versatile way. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Multiplicity of the Protostar Serpens SMM 1 Revealed by Millimeter Imaging

OpenAIRE

Choi, Minho

2009-01-01

The Serpens SMM 1 region was observed in the 6.9 mm continuum with an angular resolution of about 0.6 arcsec. Two sources were found to have steep positive spectra suggesting emission from dust. The stronger one, SMM 1a, is the driving source of the bipolar jet known previously, and the mass of the dense molecular gas traced by the millimeter continuum is about 8 solar mass. The newly found source, SMM 1b, positionally coincides with the brightest mid-IR source in this region, which implies t...

Nuclear Receptors and Multiple Endocrine Neoplasia type 1 (MEN1)

NARCIS (Netherlands)

Dreijerink, K.M.A.

2009-01-01

Multiple Endocrine Neoplasia type 1 (MEN1) is an inherited syndrome that is characterized by the occurrence of tumours of the parathyroid glands, gastroenteropancreatic tumours, pitui-tary gland adenomas, as well as adrenal adenomas and neuro-endocrine tumours, often at a young age. MEN1 tumours can

Core-needle biopsy of breast cancer is associated with a higher rate of distant metastases 5 to 15 years after diagnosis than FNA biopsy.

Science.gov (United States)

Sennerstam, Roland B; Franzén, Bo S H; Wiksell, Hans O T; Auer, Gert U

2017-10-01

The literature offers discordant results regarding whether diagnostic biopsy is associated with the dissemination of cancer cells, resulting in local and/or distant metastasis. The long-term outcomes of patients with breast cancer were compared between those who were diagnosed using either fine-needle aspiration biopsy (FNAB) or core-needle biopsy (CNB) during 2 decades: the 1970s and 1990s. In the 1970s, the only diagnostic needle biopsy method used for breast cancer in Sweden was FNAB. CNB was introduced 1989 and became established in Stockholm Gotland County in the early 1990s. The authors compared the clinical outcomes of patients diagnosed using FNAB from 1971 to 1976 (n = 354) versus those of patients diagnosed using CNB from 1991 to 1995 (n = 1729). Adjusting for differences in various treatment modalities, mammography screening, tumor size, DNA ploidy, and patient age between the 2 decades, 2 strictly matched samples representing FNAB (n = 181) and CNB (n = 203) were selected for a 15-year follow-up study. In a comparison of the rates of distant metastasis in the strictly matched patient groups from the FNAB and CNB cohorts, significantly higher rates of late-appearing (5-15 years after diagnosis) distant metastasis were observed among the patients who were diagnosed on CNB compared with those who were diagnosed on FNAB. No significant difference in local metastasis was observed between the 2 groups. At 5 to 15 years after diagnosis of the primary tumor, CNB-diagnosed patients had significantly higher rates of distant metastases than FNAB-diagnosed patients. Cancer Cytopathol 2017;125:748-56. © 2017 American Cancer Society. © 2017 American Cancer Society.

26 CFR 26.2653-1 - Taxation of multiple skips.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Taxation of multiple skips. 26.2653-1 Section 26.2653-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE...-1 Taxation of multiple skips. (a) General rule. If property is held in trust immediately after a GST...

Mathematical Modeling of Loop Heat Pipes with Multiple Capillary Pumps and Multiple Condensers. Part 1; Stead State Stimulations

Science.gov (United States)

Hoang, Triem T.; OConnell, Tamara; Ku, Jentung

2004-01-01

Loop Heat Pipes (LHPs) have proven themselves as reliable and robust heat transport devices for spacecraft thermal control systems. So far, the LHPs in earth-orbit satellites perform very well as expected. Conventional LHPs usually consist of a single capillary pump for heat acquisition and a single condenser for heat rejection. Multiple pump/multiple condenser LHPs have shown to function very well in ground testing. Nevertheless, the test results of a dual pump/condenser LHP also revealed that the dual LHP behaved in a complicated manner due to the interaction between the pumps and condensers. Thus it is redundant to say that more research is needed before they are ready for 0-g deployment. One research area that perhaps compels immediate attention is the analytical modeling of LHPs, particularly the transient phenomena. Modeling a single pump/single condenser LHP is difficult enough. Only a handful of computer codes are available for both steady state and transient simulations of conventional LHPs. No previous effort was made to develop an analytical model (or even a complete theory) to predict the operational behavior of the multiple pump/multiple condenser LHP systems. The current research project offered a basic theory of the multiple pump/multiple condenser LHP operation. From it, a computer code was developed to predict the LHP saturation temperature in accordance with the system operating and environmental conditions.

The pituitary tumor transforming gene 1 (PTTG-1: An immunological target for multiple myeloma

Directory of Open Access Journals (Sweden)

Gagliano Nicoletta

2008-04-01

Full Text Available Abstract Background Multiple Myeloma is a cancer of B plasma cells, which produce non-specific antibodies and proliferate uncontrolled. Due to the potential relapse and non-specificity of current treatments, immunotherapy promises to be more specific and may induce long-term immunity in patients. The pituitary tumor transforming gene 1 (PTTG-1 has been shown to be a novel oncogene, expressed in the testis, thymus, colon, lung and placenta (undetectable in most other tissues. Furthermore, it is over expressed in many tumors such as the pituitary adenoma, breast, gastrointestinal cancers, leukemia, lymphoma, and lung cancer and it seems to be associated with tumorigenesis, angiogenesis and cancer progression. The purpose was to investigate the presence/rate of expression of PTTG-1 in multiple myeloma patients. Methods We analyzed the PTTG-1 expression at the transcriptional and the protein level, by PCR, immunocytochemical methods, Dot-blot and ELISA performed on patient's sera in 19 multiple myeloma patients, 6 different multiple myeloma cell lines and in normal human tissue. Results We did not find PTTG-1 presence in the normal human tissue panel, but PTTG-1 mRNA was detectable in 12 of the 19 patients, giving evidence of a 63% rate of expression (data confirmed by ELISA. Four of the 6 investigated cell lines (66.6% were positive for PTTG-1. Investigations of protein expression gave evidence of 26.3% cytoplasmic expression and 16% surface expression in the plasma cells of multiple myeloma patients. Protein presence was also confirmed by Dot-blot in both cell lines and patients. Conclusion We established PTTG-1's presence at both the transcriptional and protein levels. These data suggest that PTTG-1 is aberrantly expressed in multiple myeloma plasma cells, is highly immunogenic and is a suitable target for immunotherapy of multiple myeloma.

Proteomic analysis reveals the enhancement of human serum apolipoprotein A-1(APO A-1) in individuals infected with multiple dengue virus serotypes.

Science.gov (United States)

Manchala, Nageswar Reddy; Dungdung, Ranjeet; Pilankatta, Rajendra

2017-10-01

Human serum protein profiling of the individual infected with multiple dengue virus serotypes for identifying the potential biomarkers and to investigate the cause for the severity of dengue virus infection. Dengue virus NS1-positive serum samples were pooled into two groups (S2 and S3) based on the molecular serotyping and number of heterotypic infections. The pooled serum samples were subjected to two-dimensional gel electrophoresis (2DGE) to identify the differentially expressed proteins. The peptide masses of upregulated protein were detected by matrix-assisted laser desorption-ionisation time-of-flight MALDI-TOF mass spectrometry and analysed by MASCOT search engine. The results were compared with the control group (S1). The commonly upregulated protein was validated by quantitative ELISA and compared with control as well as single serotypic infected samples. Based on 2DGE, total thirteen proteins were differentially upregulated in S2 and S3 groups as compared to control. Some of the upregulated proteins were involved in mediating the complement activation of immune response. The apolipoprotein A-1 (APO A-1) was upregulated in S2 and S3 groups. Upon validation, APO A-1 levels were increased in line with the number of heterotypic infection of dengue viruses. Heterotypic infection of dengue viruses upregulate the serum proteins involved in the complement pathway in the early phase of infection. There was a significant increase in the level of APO A-1 in three different serotypic infections of dengue virus as compared to control. Further, the role of APO-A1 can be explored in elucidating the mechanism of dengue pathogenesis. © 2017 John Wiley & Sons Ltd.

Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

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Marcel Cerqueira Cesar Machado

Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

Directory of Open Access Journals (Sweden)

Ji Soo Choi

Full Text Available The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB samples using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA. Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

Preoperative core needle biopsy is accurate in determining molecular subtypes in invasive breast cancer

International Nuclear Information System (INIS)

Chen, Xiaosong; Yuan, Ying; Fei, Xiaochun; Jin, Xiaolong; Shen, Kunwei; Sun, Long; Mao, Yan; Zhu, Siji; Wu, Jiayi; Huang, Ou; Li, Yafen; Chen, Weiguo; Wang, Jianhua

2013-01-01

Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 have been increasingly evaluated by core needle biopsy (CNB) and are recommended for classifying breast cancer into molecular subtypes. However, the concordance rate between CNB and open excision biopsy (OEB) has not been well documented. Patients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive. There were 298 invasive breast cancer patients analyzed. Concordance rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67 expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P = 0.046). Good agreement (κ = 0.658) was demonstrated in evaluating molecular subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%. However, using a cut-point of Ki67 either 14% or 20% for both specimens, there will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and Luminal B on OEB. CNB was accurate in determining ER, PgR, and HER2 status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67 should be retested on OEB samples in HR+/HER2- patients to accurately distinguish Luminal A from B tumors

Myotonic Dystrophy Type 1 RNA Crystal Structures Reveal Heterogeneous 1 × 1 Nucleotide UU Internal Loop Conformations

Energy Technology Data Exchange (ETDEWEB)

Kumar, Amit; Park, HaJeung; Fang, Pengfei; Parkesh, Raman; Guo, Min; Nettles, Kendall W.; Disney, Matthew D. (Scripps)

2012-03-27

RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures of a model DM1 triplet repeating construct, 5'r[{und UU}GGGC(C{und U}G){sub 3}GUCC]{sub 2}, refined to 2.20 and 1.52 {angstrom} resolution are disclosed. Here, differences in the orientation of the 5' dangling UU end between the two structures induce changes in the backbone groove width, which reveals that noncanonical 1 x 1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 {angstrom} structure, CUGa, the 5' UU forms a one hydrogen-bonded pair with a 5' UU of a neighboring helix in the unit cell to form a pseudoinfinite helix. The central 1 x 1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1 x 1 nucleotide UU internal loops each form a one-hydrogen bond pair. In the 1.52 {angstrom} structure, CUGb, the 5' UU dangling end is tucked into the major groove of the duplex. While the canonically paired bases show no change in base pairing, in CUGb the terminal 1 x 1 nucleotide UU internal loops now form two hydrogen-bonded pairs. Thus, the shift in the major groove induced by the 5' UU dangling end alters noncanonical base patterns. Collectively, these structures indicate that 1 x 1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands.

Multiple myeloma

International Nuclear Information System (INIS)

Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

1994-01-01

Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

Genetic Analysis of Multiple Endocrine Neoplasia Type 1 ( Leads to Misdiagnosis of an Extremely Rare Presentation of Intrasellar Cavernous Hemangioma as MEN1

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Dong Min Lee

2014-06-01

Full Text Available BackgroundMultiple endocrine neoplasia type 1 (MEN1 is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands. MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above.MethodsA 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1.ResultsGenomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion.ConclusionThere is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma

Assessing the Multiple Benefits of Clean Energy Chapter 1: Introduction

Science.gov (United States)

Chapter 1 of “Assessing the Multiple Benefits of Clean Energy” provides an introduction to the document. /meta name=DC.title content=Assessing the Multiple Benefits of Clean Energy Chapter 1: Introduction

Formulation and characterization of a multiple emulsion containing 1 ...

African Journals Online (AJOL)

The purpose of the study was to prepare a stable multiple emulsion containing a skin anti-aging agent and using paraffin oil. Vitamin C, was incorporated into the inner aqueous phase of water-in-oil-in-water (w/o/w) multiple emulsion at a concentration of 1%. Multiple emulsion was prepared by two step method. Stability ...

CT-guided core biopsy of malignant lung lesions: how many needle passes are needed?

International Nuclear Information System (INIS)

Lim, Chaehun; Han, Dae Hee; Lee, Kyo Young; Kim, Young Kyoon; Ko, Jeong Min

2013-01-01

The study aims to determine the number of needle pass in the CT-guided core needle biopsy (CNB) in making a diagnosis of pulmonary malignancy. A total of 434 CNB records were retrospectively reviewed. The specimen obtained from each needle pass was put in a formalin container and then labelled for separate histopathological reporting. The patients were divided into five groups according to the total number of needle passes (n=1, n=2, n=3, n=4 and n≥5). In each of the groups 2–4, it was analysed how many needle passes are required before a plateau in diagnostic yield is achieved. CNB produced 283 true-positive and 23 false-negative diagnosis of malignancy. Cumulative sensitivity significantly (P<0.05) increased between the first and second as well as the second and the third (if done) needle passes, but not between the third and fourth ones. Three coaxial needle passes might be optimal in the diagnosis of lung malignancy.

Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

Science.gov (United States)

2015-10-01

AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

Reconfigurable Flight Control System for a STOL (Short Take-Off and Landing) Aircraft Using Quantitative Feedback Theory.

Science.gov (United States)

1984-12-01

XD2, XD3, XD4, XD5, XD6, XD7, XDS, 7M1, MA, MH, M0,MU, MDl,MD2, MD3, MD4, M5, MOS, MD7, MDS REAL CNB, CYB, CL, L, N DIMENSION AMAT(4,4), BMAT (4,S...NO, MU, ND1, MD2, ND3, MD4,ND5, MD6, ND7, NO REAL CNB, CYB, CL, L, N DIMENSION AMAT(4,4), BMAT (4,S)V DIMENSION DIRMAT(5, 5) ,DIRBMAT(5, SJ CHARACTER*3...INPUT MATRIX 8 C BMAT (l,1) - XO1 BMAT (1,2) - X02 BMAT (1,3) = XD3 BMAT (1,4) -XO4 SMAT(1,5) -XD5 BMAT (1,&) - XDG BMQT(1,7) = XD7 EMAT(I,8) - XDB BMAT (,1

Multiple requirements of PLK1 during mouse oocyte maturation.

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Petr Solc

Full Text Available Polo-like kinase 1 (PLK1 orchestrates multiple events of cell division. Although PLK1 function has been intensively studied in centriole-containing and rapidly cycling somatic cells, much less is known about its function in the meiotic divisions of mammalian oocytes, which arrest for a long period of time in prophase before meiotic resumption and lack centrioles for spindle assembly. Here, using specific small molecule inhibition combined with live mouse oocyte imaging, we comprehensively characterize meiotic PLK1's functions. We show that PLK1 becomes activated at meiotic resumption on microtubule organizing centers (MTOCs and later at kinetochores. PLK1 is required for efficient meiotic resumption by promoting nuclear envelope breakdown. PLK1 is also needed to recruit centrosomal proteins to acentriolar MTOCs to promote normal spindle formation, as well as for stable kinetochore-microtubule attachment. Consequently, PLK1 inhibition leads to metaphase I arrest with misaligned chromosomes activating the spindle assembly checkpoint (SAC. Unlike in mitosis, the metaphase I arrest is not bypassed by the inactivation of the SAC. We show that PLK1 is required for the full activation of the anaphase promoting complex/cyclosome (APC/C by promoting the degradation of the APC/C inhibitor EMI1 and is therefore essential for entry into anaphase I. Moreover, our data suggest that PLK1 is required for proper chromosome segregation and the maintenance of chromosome condensation during the meiosis I-II transition, independently of the APC/C. Thus, our results define the meiotic roles of PLK1 in oocytes and reveal interesting differential requirements of PLK1 between mitosis and oocyte meiosis in mammals.

Multiple spectroscopic analyses reveal the fate and metabolism of sulfamide herbicide triafamone in agricultural environments

International Nuclear Information System (INIS)

Wang, Mengcen; Qian, Yuan; Liu, Xiaoyu; Wei, Peng; Deng, Man; Wang, Lei; Wu, Huiming; Zhu, Guonian

2017-01-01

Triafamone, a sulfamide herbicide, has been extensively utilized for weed control in rice paddies in Asia. However, its fate and transformation in the environment have not been established. Through a rice paddy microcosm-based simulation trial combined with multiple spectroscopic analyses, we isolated and identified three novel metabolites of triafamone, including hydroxyl triafamone (HTA), hydroxyl triafamone glycoside (HTAG), and oxazolidinedione triafamone (OTA). When triafamone was applied to rice paddies at a concentration of 34.2 g active ingredient/ha, this was predominantly distributed in the paddy soil and water, and then rapidly dissipated in accordance with the first-order rate model, with half-lives of 4.3–11.0 days. As the main transformation pathway, triafamone was assimilated by the rice plants and was detoxified into HTAG, whereas the rest was reduced into HTA with subsequent formation of OTA. At the senescence stage, brown rice had incurred triafamone at a concentration of 0.0016 mg/kg, but the hazard quotient was <1, suggesting that long-term consumption of the triafamone-containing brown rice is relatively safe. The findings of the present study indicate that triafamone is actively metabolized in the agricultural environment, and elucidation of the link between environmental exposure to these triazine or oxazolidinedione moieties that contain metabolites and their potential impacts is warranted. - Highlights: • Multiple spectroscopic analyses were applied to investigate agrochemicals transformation in environment. • Three novel compounds were isolated and identified as triafamone metabolites. • The fate and transformation pathway of triafamone in rice paddy were revealed. • Long-term consumption of the triafamone-containing brown rice is relatively safe. • Elucidation of environmental impacts by exposure to these triazine or oxazolidinedione metabolites is warranted. - Triafamone rapidly dissipates in agricultural environments

Concordant, non-atypical breast papillomas do not require surgical excision: A 10-year multi-institution study and review of the literature.

Science.gov (United States)

Grimm, Lars J; Bookhout, Christine E; Bentley, Rex C; Jordan, Sheryl G; Lawton, Thomas J

2018-05-01

Non-atypical papillomas (NAPs) diagnosed on core needle biopsy (CNB) frequently undergo surgical excision due to highly variable upstaging rates. The purpose of this study is to document our dual-institution upgrade rates of NAPs diagnosed on core needle biopsy and review the upgrade rates reported in the literature. Following IRB approval, CNB results from Duke University (7/1/2004-6/30/2014) and the University of North Carolina Chapel Hill (1/1/04-6/30/2013) were reviewed to identify non-atypical papillomas. All cases with surgical excision or 2 years of imaging follow up were included. In addition, a literature review identified 60 published studies on upgrades of NAPs diagnosed at CNB. Cases in our cohort and the published literature were reviewed for confounding factors: [1] missing radiologic-pathologic concordance and/or discordance, [2] papillomas included with high-risk lesions, [3] high risk lesions counted as upgrades, [4] review by a nonspecialized breast pathologist, and [5] cancer incidentally detected. Of the 388 CNBs in our dual-institution cohort, 136 (35%) patients underwent surgical excision and 252 (65%) patients had imaging follow up. After controlling for confounders, no cancers (0/388) were found at surgical excision or during follow up imaging. The literature review upstaging rate was 4.0% (166/4157) but 1.8% (4/227) after excluding studies with confounders. The combined upstaging rate from the literature and this study was 0.6% (4/615). The upstaging rate for CNB diagnosed NAPs was 0% in our cohort and 0.6% overall after adjusting for confounders. This low rate does not warrant reflexive surgical excision and diagnostic imaging follow up should be discretionary. Copyright © 2018 Elsevier Inc. All rights reserved.

Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

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Trevor P. Fidler

2017-07-01

Full Text Available Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT 1 and GLUT3 (double knockout [DKO] specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased. Thrombosis and platelet activation were decreased through impairment at multiple activation nodes, including Ca2+ signaling, degranulation, and integrin activation. DKO mice developed thrombocytopenia, secondary to impaired pro-platelet formation from megakaryocytes, and increased platelet clearance resulting from cytosolic calcium overload and calpain activation. Systemic treatment with oligomycin, inhibiting mitochondrial metabolism, induced rapid clearance of platelets, with circulating counts dropping to zero in DKO mice, but not wild-type mice, demonstrating an essential role for energy metabolism in platelet viability. Thus, substrate metabolism is essential for platelet production, activation, and survival.

Breast Intraductal Papillomas without Atypia in Radiologic-Pathologic Concordant Core Needle Biopsies: Predictors of Upgrade to Carcinoma at Excision

Science.gov (United States)

Pareja, Fresia; Corben, Adriana; Brennan, Sandra; Murray, Melissa P.; Bowser, Zenica; Jakate, Kiran; Sebastiano, Christopher; Morrow, Monica; Morris, Elizabeth; Brogi, Edi

2016-01-01

Background The surgical management of breast intraductal papilloma without atypia (IDP) identified at core needle biopsy (CNB) is controversial. We assessed the rate of upgrade to carcinoma at surgical excision, and identified parameters predictive of upgrade. Methods We identified women with CNB diagnosis of intraductal papilloma without atypia or carcinoma at our center between 2003 and 2013. Radiologic-pathologic concordance was assessed for all cases, and discordant cases were excluded. We correlated the radiologic and clinicopathologic features of patients with CNB diagnosis of IDP with upgrade to carcinoma at surgical excision. Results Our study population consists of 189 women with 196 IDPs; 166 women (171 IDPs) underwent excision. The upgrade rate was 2.3% (4/171). The upgrade lesions were 2 invasive lobular carcinomas and 2 cases of ductal carcinoma in situ (DCIS). One case of DCIS involved the residual IDP, whereas the other 3 carcinomas were ≥8 mm away. Twenty-four women (25 IDPs) did not undergo excision, and had stable imaging at follow-up (median of 23.5 months). Conclusions The upgrade rate at excision of IDP diagnosed at CNB with radiologic-pathologic concordance is 2.3%. Our findings suggest that observation is appropriate for patients with radiologic-pathologic concordant CNB yielding IDP, regardless of its size. PMID:27315013

How Do Multiple-Star Systems Form? VLA Study Reveals "Smoking Gun"

Science.gov (United States)

2006-12-01

system, all the antennas could provide data for us. In addition, we improved the level of detail by using the Pie Town, NM, antenna of the Very Long Baseline Array, as part of an expanded system," Lim said. The implementation and improvement of the 43 GHz receiving system was a collaborative program among the German Max Planck Institute, the Mexican National Autonomous University, and the U.S. National Radio Astronomy Observatory. Two popular theoretical models for the formation of multiple-star systems are, first, that the two protostars and their surrounding dusty disks fragment from a larger parent disk, and, second, that the protostars form independently and then one captures the other into a mutual orbit. "Our new study shows that the disks of the two main protostars are aligned with each other, and also are aligned with the larger, surrounding disk. In addition, their orbital motion resembles the rotation of the larger disk. This is a 'smoking gun' supporting the fragmentation model," Lim said. However, the new study also revealed a third young star with a dust disk. "The disk of this one is misaligned with those of the other two, so it may be the result of either fragmentation or capture," Takakuwa said. The misalignment of the third disk could have come through gravitational interactions with the other two, larger, protostars, the scientists said. They plan further observations to try to resolve the question. "We have a very firm indication that two of these protostars and their dust disks formed from the same, larger disk-like cloud, then broke out from it in a fragmentation process. That strongly supports one theoretical model for how multiple-star systems are formed. The misalignment of the third protostar and its disk leaves open the possibility that it could have formed elsewhere and been captured, and we'll continue to work on reconstructing the history of this fascinating system," Lim summarized. The National Radio Astronomy Observatory is a facility of

Phosphoproteomics reveals that glycogen synthase kinase-3 phosphorylates multiple splicing factors and is associated with alternative splicing

Science.gov (United States)

Shinde, Mansi Y.; Sidoli, Simone; Kulej, Katarzyna; Mallory, Michael J.; Radens, Caleb M.; Reicherter, Amanda L.; Myers, Rebecca L.; Barash, Yoseph; Lynch, Kristen W.; Garcia, Benjamin A.; Klein, Peter S.

2017-01-01

Glycogen synthase kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif ((pS/pT)XXX(S/T)), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and MS techniques to analyze the repertoire of GSK-3–dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ∼2.4% of (pS/pT)XXX(S/T) sites are phosphorylated in a GSK-3–dependent manner. A comparison of WT and Gsk3a;Gsk3b knock-out (Gsk3 DKO) ESCs revealed prominent GSK-3–dependent phosphorylation of multiple splicing factors and regulators of RNA biosynthesis as well as proteins that regulate transcription, translation, and cell division. Gsk3 DKO reduced phosphorylation of the splicing factors RBM8A, SRSF9, and PSF as well as the nucleolar proteins NPM1 and PHF6, and recombinant GSK-3β phosphorylated these proteins in vitro. RNA-Seq of WT and Gsk3 DKO ESCs identified ∼190 genes that are alternatively spliced in a GSK-3–dependent manner, supporting a broad role for GSK-3 in regulating alternative splicing. The MS data also identified posttranscriptional regulation of protein abundance by GSK-3, with ∼47 proteins (1.4%) whose levels increased and ∼78 (2.4%) whose levels decreased in the absence of GSK-3. This study provides the first unbiased analysis of the GSK-3 phosphoproteome and strong evidence that GSK-3 broadly regulates alternative splicing. PMID:28916722

Mathematics revealed

CERN Document Server

Berman, Elizabeth

1979-01-01

Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

Enucleation and limited pancreatic resection provide long-term cure for insulinoma in multiple endocrine neoplasia type 1.

Science.gov (United States)

Bartsch, Detlef K; Albers, Max; Knoop, Richard; Kann, Peter H; Fendrich, Volker; Waldmann, Jens

2013-01-01

To assess the characteristics and long-term outcome after surgery in patients with multiple endocrine neoplasia type 1 (MEN1)-associated insulinoma. Retrospective analysis of prospectively collected data of MEN1 patients with organic hyperinsulinism at a tertiary referral center. Thirteen (17%) of 74 patients with MEN1 had organic hyperinsulinism. The median age at diagnosis was 27 (range 9-48) years. In 7 patients insulinoma was the first manifestation of the syndrome. All patients had at least one pancreatic neuroendocrine neoplasm (pNEN) upon imaging, including CT, MRI or endoscopic ultrasonography. Seven patients had solitary lesions upon imaging, 4 patients had one dominant tumor with coexisting multiple small pNENs, and 2 patients had multiple lesions without dominance. Eight patients had limited resections (1 segmental resection, 7 enucleations), 4 subtotal distal pancreatectomies, and 1 patient a partial duodenopancreatectomy. There was no postoperative mortality. Six patients experienced complications, including pancreatic fistula in 5 patients. Pathological examination revealed median three (range 1-14) macro-pNENs sized between 6 and 40 mm, and a total of 14 potentially benign insulinomas were detected in the 13 patients. After median follow-up of 156 months, only 1 patient developed recurrent hyperinsulinism after initial enucleation. Twelve patients developed new pNENs in the pancreatic remnant and 4 patients underwent reoperations (3 for metastatic ZES, 1 for recurrent hyperinsulinism). One of 5 patients with an initial extended pancreatic resection developed insulin-dependent diabetes mellitus. Enucleation and limited resection provide long-term cure for MEN1 insulinoma in patients with solitary or dominant tumors. Subtotal distal pancreatectomy should thus be preserved for patients with multiple pNENs without dominance given the risk of exocrine and endocrine pancreas insufficiency in the mostly young patients. © 2013 S. Karger AG, Basel.

Percutaneous CT-Guided Core Needle Biopsy Versus Fine Needle Aspiration in Diagnosing Pneumonia and Mimics of Pneumonia

International Nuclear Information System (INIS)

Thanos, Loukas; Galani, Panagiota; Mylona, Sophia; Pomoni, Maria; Mpatakis, Nikolaos

2004-01-01

The purpose of this study was to determine the diagnostic value of percutaneous core needle biopsy (CNB) relative to fine needle aspiration (FNA) in patients with pneumonia and pneumonia mimics. In this prospective study we present our experience with 48 thoracic FNAs and CNBs carried out on 48 patients with pneumonia and pneumonia mimics. Samples were obtained from all patients using both CNB (with an automated 18-G core biopsy needle and a gun) and FNA (with a 22-G needle). A specific diagnosis was made in 10/48 cases (20.83%) by FNA and in 42/48 (87.5%) by CNB. The main complications encountered were pneumothorax (n = 4) and hemoptysis (n = 2), yielding a total complication rate of 12.5%. We concluded that CNB using an automated biopsy gun results in a higher diagnostic accuracy for pneumonia and pneumonia mimic biopsies than FNA. Complications should be considered and proper patient observation should follow the procedure

The reliability of ultrasound-guided core needle biopsy in the evaluation of non-palpable solid breast lesions using 18-gauge needles

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Lim, Sung Chul; Kim, Young Sook [Chosun University College of Medicine, Gwangju (Korea, Republic of); Sneige, Nour [The University of Texas M.D. Andreson Carcer Canter, Houston (United States)

2003-04-01

Ultrasound-guided core needle biopsy (US CNB) is increasingly used in the histologic evaluation of non-palpable solid breast lesions. We retrospectively investigated the diagnostic accuracy of this technique, using an 18-gauge needle in 422 non-palpable breast lesions. 583 female patients with an average age 56 (range, 22-90) years underwent 590 US CNBs. Between January 1994 and December 1999, using 18-gauge needles, an average of four cores per lesion was obtained. Three hundred and eighty-five lesions were subsequently surgically excised; for 14 of these, the pathologic diagnosis was breast carcinoma metastasis, while 23 with benign diagnoses were clinically followed up for {>=}2.5 years and were considered for analysis. Of the 422 lesions, 340 (80.6%) were malignant [308 invasive, 24 ductal carcinoma in situ (DCIS), 7 DCIS with undetermined invasion and 1 DCIS vs. lobular carcinoma in situ], 67 (15.9%) were benign [30 fibroadenoma (FA) and 37 other diagnoses], and five (1.2%) were fibroepithelial lesions. The remaining ten samples (2,4%) included six cases of atypical ductal hyperplasia (ADH), two of atypical hyperplasia (AH), and two of lobular neoplasia. The sensitivity, specificity, positive predictive value, and negative predictive value of CNBs were 99%, 100%, 100%, and 96%, respectively. Two cases of invasive carcinoma were missed at CNB; there was no false-positive diagnosis. Five of six ADHs and one of two AHs were found to be carcinomas (3 DCIS and 3 infiltrating duct carcinomas). Sixteen of 24 (66.7%) cases of DCIS were found at excision to be invasion carcinomas. Of 31 FAs, two (6.5%) were found to be low-grade phyllodes tumor (PT). The five fibroepithelial lesions were shown at excision to be either PT (n=4) or FA (n=1). US CNB using an 18-gauge needle is a safe and reliable means of diagnosing breast carcinoma. Because of the high prevalence of ductal carcinoma is these lesions; findings of ADH/AH at US CNB indicate that surgical excision is needed

Who borrows and who may not repay?

Czech Academy of Sciences Publication Activity Database

Bičáková, Alena; Prelcová, Zuzana; Pašaličová, R.

2011-01-01

Roč. 9, č. 2 (2011), s. 10-13 ISSN 1803-7089 Institutional research plan: CEZ:MSM0021620846 Keywords : household credit * debt burden * repayment Subject RIV: AH - Economics http://www.cnb.cz/miranda2/export/sites/www.cnb.cz/en/research/research_publications/erb/download/ERB_No2_2011.pdf

Do financial variables help predict the macroeconomic environment?

Czech Academy of Sciences Publication Activity Database

Havránek, T.; Horváth, R.; Matějů, Jakub

2011-01-01

Roč. 9, č. 2 (2011), s. 14-17 ISSN 1803-7089 Institutional research plan: CEZ:MSM0021620846 Keywords : macroeconomic environment * monetary restriction * financial system Subject RIV: AH - Economics http://www.cnb.cz/miranda2/export/sites/www.cnb.cz/en/research/research_publications/erb/download/ERB_No2_2011.pdf

The amplification of 1q21 is an adverse prognostic factor in patients with multiple myeloma in a Chinese population

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Yu W

2016-01-01

Full Text Available Wenjun Yu,1,2,* Rui Guo,1,* Xiaoyan Qu,1 Hairong Qiu,1 Jianyong Li,1 Run Zhang,1 Lijuan Chen1 1Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 2Department of Cadre Health Care, Jiangsu Province Geriatric Institution, Jiangsu Province Official Hospital, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The prognostic heterogeneity of multiple myeloma (MM is largely due to different genetic abnormalities. Cytogenetic analysis has revealed that most of MM harbor chromosome aberrations. Amplification of 1q21 is one of the most common chromosomal aberrations. Interphase fluorescence in situ hybridization was applied to detect the 1q21 amplification in 86 Chinese patients with newly diagnosed MM. Amp(1q21 was found in totally 40 of 86 (46.5% cases, among which 29 with three copies of 1q21 and eleven with at least four copies of 1q21. Further analysis revealed a significant difference of overall survival and progression-free survival among the three arms (P<0.05. Bortezomib could not significantly improve the overall survival for patients with 1q21 amplification (P>0.05. These findings suggest that 1q21 amplification with four copies or more is prognostic factor for adverse outcomes of MM patients. Furthermore, chromosome 1q21 gains predicted a poor overall survival even in those receiving bortezomib-based regimens. Keywords: multiple myeloma, 1q21 amplification, I-FISH, prognosis

Multiple effects of the special AT-rich binding protein 1 (SATB1) in colon carcinoma.

Science.gov (United States)

Frömberg, Anja; Rabe, Michael; Aigner, Achim

2014-12-01

SATB1 (special AT-rich binding protein 1) is a global chromatin organizer regulating the expression of a large number of genes. Overexpression has been found in various solid tumors and positively correlated with prognostic and clinicopathological properties. In colorectal cancer (CRC), SATB1 overexpression and its correlation with poor differentiation, invasive depth, TNM (tumor, nodes, metastases) stage and prognosis have been demonstrated. However, more detailed studies on the SATB1 functions in CRC are warranted. In this article, we comprehensively analyze the cellular and molecular role of SATB1 in CRC cell lines with different SATB1 expression levels by using RNAi-mediated knockdown. Using siRNAs with different knockdown efficacies, we demonstrate antiproliferative, cell cycle-inhibitory and proapoptotic effects of SATB1 knockdown in a SATB1 gene dose-dependent manner. Tumor growth inhibition is confirmed in vivo in a subcutaneous tumor xenograft mouse model using stable knockdown cells. The in-depth analysis of cellular effects reveals increased activities of caspases-3, -7, -8, -9 and other mediators of apoptotic pathways. Similarly, the analysis of E- and N-cadherin, slug, twist, β-catenin and MMP7 indicates SATB1 effects on epithelial-mesenchymal transition (EMT) and matrix breakdown. Our results also establish SATB1 effects on receptor tyrosine kinases and (proto-)oncogenes such as HER receptors and Pim-1. Taken together, this suggests a more complex molecular interplay between tumor-promoting and possible inhibitory effects in CRC by affecting multiple pathways and molecules involved in proliferation, cell cycle, EMT, invasion and cell survival. © 2014 UICC.

Factors influencing diagnostic yield of CT-guided percutaneous core needle biopsy for bone lesions

International Nuclear Information System (INIS)

Li, Y.; Du, Y.; Luo, T.Y.; Yang, H.F.; Yu, J.H.; Xu, X.X.; Zheng, H.J.; Li, B.

2014-01-01

Aim: To evaluate the factors influencing diagnostic yield of computed tomography (CT)-guided percutaneous core needle biopsy (CNB) for bone lesions. Materials and methods: Between September 2005 and July 2011, 162 consecutive CT-guided CNB procedures were performed in 155 patients. The variables analysed were age, sex, lesion location, lesion type, lesion size, specimen size, biopsy needle gauge, and individual radiologist. The factors influencing diagnostic yield of CT-guided percutaneous CNB for bone lesions were determined by multivariate analysis of variables. Results: The diagnostic yield was 81.5%. Diagnostic yield was 89.9% for lytic bone lesions and 48.5% for sclerotic bone lesions (p < 0.001), and 89.2% for lesions ≥3 cm and 73.4% for lesions <3 cm (p = 0.010). The significant factors influencing diagnostic yield of CT-guided percutaneous CNB for bone lesions were lesion type [p < 0.001; odds ratio (OR) for a lytic lesion was approximately 12 times higher than that for a sclerotic lesion; 95% confidence interval (CI): 4.22–34.01], and lesion size (p = 0.012; OR for a lesion size ≥3 cm was about five-times higher than that for a lesion size <3 cm; 95% CI: 1.42–16.71). Conclusion: Lesion type and lesion size are determining factors in diagnostic yield. The higher diagnostic yield is correlated with lytic lesion and lesion size ≥3 cm

Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

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Hyun-Kyoung Kim

Full Text Available BACKGROUND: The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs, which are abundant in solid tumors, can be utilized for identification of rearranged ends. METHOD: As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP microarray method entailing CNB-region refinement by competitor DNA. RESULT: Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9% were identified, and two polymerase chain reaction (PCR-amplifiable rearrangements were obtained in six cases (66.7%. And significantly, TNGS-CNB, with its high positive identification rate (82.6% of PCR-amplifiable rearrangements at candidate sites (19/23, just from filtering of aligned sequences, requires little effort for validation. CONCLUSION: Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

Science.gov (United States)

Kim, Hyun-Kyoung; Park, Won Cheol; Lee, Kwang Man; Hwang, Hai-Li; Park, Seong-Yeol; Sorn, Sungbin; Chandra, Vishal; Kim, Kwang Gi; Yoon, Woong-Bae; Bae, Joon Seol; Shin, Hyoung Doo; Shin, Jong-Yeon; Seoh, Ju-Young; Kim, Jong-Il; Hong, Kyeong-Man

2014-01-01

The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS) for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can be utilized for identification of rearranged ends. As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB) in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region refinement by competitor DNA. Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)-amplifiable rearrangements were obtained in six cases (66.7%). And significantly, TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable rearrangements at candidate sites (19/23), just from filtering of aligned sequences, requires little effort for validation. Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

Breast intraductal papillomas without atypia in radiologic-pathologic concordant core-needle biopsies: Rate of upgrade to carcinoma at excision.

Science.gov (United States)

Pareja, Fresia; Corben, Adriana D; Brennan, Sandra B; Murray, Melissa P; Bowser, Zenica L; Jakate, Kiran; Sebastiano, Christopher; Morrow, Monica; Morris, Elizabeth A; Brogi, Edi

2016-09-15

The surgical management of mammary intraductal papilloma without atypia (IDP) identified at core-needle biopsy (CNB) is controversial. This study assessed the rate of upgrade to carcinoma at surgical excision (EXC). This study identified women with a CNB diagnosis of intraductal papilloma without atypia or carcinoma at a cancer center between 2003 and 2013. Radiologic-pathologic concordance was assessed for all cases, and discordant cases were excluded. The radiologic and clinicopathologic features of patients with a CNB diagnosis of IDP were correlated with an upgrade to carcinoma at EXC. The study population consists of 189 women with 196 IDPs; 166 women (171 IDPs) underwent EXC. The upgrade rate was 2.3% (4 of 171). The upgraded lesions were 2 invasive lobular carcinomas and 2 cases of ductal carcinoma in situ (DCIS). One case of DCIS involved the residual IDP, whereas the other 3 carcinomas were ≥ 8 mm away. Twenty-four women (25 IDPs) did not undergo EXC and had stable imaging on follow-up (median, 23.5 months). The upgrade rate at EXC for IDPs diagnosed at CNB with radiologic-pathologic concordance was 2.3%. These findings suggest that observation is appropriate for patients with radiologic-pathologic concordant CNB yielding IDP, regardless of its size. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2819-2827. © 2016 American Cancer Society. © 2016 American Cancer Society.

Malignant-looking thyroid nodules with size reduction: Core needle biopsy results

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Lee, Ha Young; Baek, Jung Hwan; Ha, Eun Jun; Park, Jee Won; Lee, Jeong Hyun; Song, Dong Eun; Shong, Young Kee [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2016-08-15

The aim of this study was to evaluate whether malignant-looking thyroid nodules with size reduction were malignant or not. From November 2010 to July 2011, we retrospectively enrolled 16 patients with 16 nodules (11 females and five males; mean age, 55 years) who underwent core needle biopsy (CNB), and whose thyroid nodules had malignant ultrasonographic (US) features, although they showed size reduction (>20% decrease in maximum diameter) during the follow-up period (mean, 37±27 months). The histologic findings of the CNB specimen were reviewed and correlated with the US findings. US studies were analyzed for their internal content, shape, margin, echogenicity, the presence of microcalcification and macrocalcification, inner isoechoic rim, and low-echoic halo. All nodules were confirmed as benign by CNB. Pathologic analysis was available for 12 CNB specimens. US imaging showed central hypoechogenicity or marked hypoechogenicity in all cases and a peripheral isoechoic rim in 15 nodules. US-pathologic correlation showed that the central hypoechoic area was primarily composed of fibrosis (12/12) and hemorrhage (8/12) and that the isoechoic rim was composed of follicular cells. In our study, the CNB results of all of the malignant-looking thyroid nodules with size reduction were benign and were primarily composed of internal fibrosis and hemorrhage. Understanding these US and pathologic features could prevent repeated fine-needle aspiration or unnecessary diagnostic surgery.

A comparison of ultrasound guided fine needle aspiration cytology and core needle biopsy in evaluation of palpable breast lesions

International Nuclear Information System (INIS)

Altaf, H.N.; Farooqui, F.

2015-01-01

Objective: To compare ultrasound guided fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB) in patients presenting with palpable breast lumps (PBLs), in terms of sensitivity and specificity, taking final histopathology as gold standard. Methodology: This cross-sectional study was conducted at Holy Family Hospital, Rawalpindi, Pakistan. Ultrasound guided FNAC and CNB were taken of all female patients with PBLs. The results were compared with final histopathology as gold standard. Data analysis was performed using SPSS software and chi-square test. Results: A total of 60 patients were included in the study. The mean age was 33.8 yrs. The sensitivity and specificity of ultrasound guided FNAC were 68.7% and 93.1%, respectively. The sensitivity and specificity of ultrasound guided CNB was 93.7% and 100%. The accuracy of FNAC was 86.2% and that of core needle biopsy was 98.3%. Conclusion: The ultrasound guided core needle biopsy can be used as an initial diagnostic test for the evaluation of all PBLs. Because of high negative predictive value core needle biopsy can replace surgical excision biopsy for benign lesions. (author)

Excitation density dependence of the photoluminescence from CdxHg1-xTe multiple quantum wells

International Nuclear Information System (INIS)

Tonheim, C R; Selvig, E; Nicolas, S; Breivik, M; Haakenaasen, R; Gunnaes, A E

2008-01-01

A study of the photoluminescence from a four-period Cd x Hg 1-x Te multiple quantum well structure at 11 K as a function of excitation density is presented. High-resolution X-ray diffraction and transmission electron microscopy revealed that the quantum well structure is of high quality. This was supported by the narrow photoluminescence peak originating in the ground state electron - heavy hole transition, with a full width at half maximum of only 7.4 meV for an excitation density of 1.3 W/cm 2 . When the excitation density was increased from 1.3 to 23.4 W/cm 2 , the peak position was shifted toward higher energy by 2.6 meV and the full width at half maximum increased from 7.4 to 10.9 meV

The multiple roles of Bub1 in chromosome segregation during mitosis and meiosis

Energy Technology Data Exchange (ETDEWEB)

Marchetti, Francesco; Venkatachalam, Sundaresan

2009-06-19

Aneuploidy, any deviation from an exact multiple of the haploid number of chromosomes, is a common occurrence in cancer and represents the most frequent chromosomal disorder in newborns. Eukaryotes have evolved mechanisms to assure the fidelity of chromosome segregation during cell division that include a multiplicity of checks and controls. One of the main cell division control mechanisms is the spindle assembly checkpoint (SAC) that monitors the proper attachment of chromosomes to spindle fibers and prevents anaphase until all kinetochores are properly attached. The mammalian SAC is composed by at least 14 evolutionary-conserved proteins that work in a coordinated fashion to monitor the establishment of amphitelic attachment of all chromosomes before allowing cell division to occur. Among the SAC proteins, the budding uninhibited by benzimidazole protein 1 (Bub1), is a highly conserved protein of prominent importance for the proper functioning of the SAC. Studies have revealed many roles for Bub1 in both mitosis and meiosis, including the localization of other SAC proteins to the kinetochore, SAC signaling, metaphase congression and the protection of the sister chromatid cohesion. Recent data show striking sex specific differences in the response to alterations in Bub1 activity. Proper Bub1 functioning is particularly important during oogenesis in preventing the generation of aneuploid gametes that can have detrimental effects on the health status of the fetus and the newborn. These data suggest that Bub1 is a master regulator of SAC and chromosomal segregation in both mitosis and meiosis. Elucidating its many essential functions in regulating proper chromosome segregation can have important consequences for preventing tumorigenesis and developmental abnormalities.

Assessing Heterogeneity of Osteolytic Lesions in Multiple Myeloma by 1H HR-MAS NMR Metabolomics

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Laurette Tavel

2016-10-01

Full Text Available Multiple myeloma (MM is a malignancy of plasma cells characterized by multifocal osteolytic bone lesions. Macroscopic and genetic heterogeneity has been documented within MM lesions. Understanding the bases of such heterogeneity may unveil relevant features of MM pathobiology. To this aim, we deployed unbiased 1H high-resolution magic-angle spinning (HR-MAS nuclear magnetic resonance (NMR metabolomics to analyze multiple biopsy specimens of osteolytic lesions from one case of pathological fracture caused by MM. Multivariate analyses on normalized metabolite peak integrals allowed clusterization of samples in accordance with a posteriori histological findings. We investigated the relationship between morphological and NMR features by merging morphological data and metabolite profiling into a single correlation matrix. Data-merging addressed tissue heterogeneity, and greatly facilitated the mapping of lesions and nearby healthy tissues. Our proof-of-principle study reveals integrated metabolomics and histomorphology as a promising approach for the targeted study of osteolytic lesions.

Multiple proviral integration events after virological synapse-mediated HIV-1 spread

International Nuclear Information System (INIS)

Russell, Rebecca A.; Martin, Nicola; Mitar, Ivonne; Jones, Emma; Sattentau, Quentin J.

2013-01-01

HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection. - Highlights: • Cell-to-cell HIV-1 infection delivers multiple vRNA copies to the target cell. • Cell-to-cell infection results in productive infection of the target cell. • Cell-to-cell transmission is more efficient than cell-free HIV-1 infection. • Suggests a mechanism for recombination in cells infected with multiple viral genomes

Supersymmetric U(1)' model with multiple dark matters

International Nuclear Information System (INIS)

Hur, Taeil; Lee, Hye-Sung; Nasri, Salah

2008-01-01

We consider a scenario where a supersymmetric model has multiple dark matter particles. Adding a U(1) ' gauge symmetry is a well-motivated extension of the minimal supersymmetric standard model (MSSM). It can cure the problems of the MSSM such as the μ problem or the proton decay problem with high-dimensional lepton number and baryon number violating operators which R parity allows. An extra parity (U parity) may arise as a residual discrete symmetry after U(1) ' gauge symmetry is spontaneously broken. The lightest U-parity particle (LUP) is stable under the new parity becoming a new dark matter candidate. Up to three massive particles can be stable in the presence of the R parity and the U parity. We numerically illustrate that multiple stable particles in our model can satisfy both constraints from the relic density and the direct detection, thus providing a specific scenario where a supersymmetric model has well-motivated multiple dark matters consistent with experimental constraints. The scenario provides new possibilities in the present and upcoming dark matter searches in the direct detection and collider experiments

An APC/C-Cdh1 Biosensor Reveals the Dynamics of Cdh1 Inactivation at the G1/S Transition.

Science.gov (United States)

Ondracka, Andrej; Robbins, Jonathan A; Cross, Frederick R

2016-01-01

B-type cyclin-dependent kinase activity must be turned off for mitotic exit and G1 stabilization. B-type cyclin degradation is mediated by the anaphase-promoting complex/cyclosome (APC/C); during and after mitotic exit, APC/C is dependent on Cdh1. Cdh1 is in turn phosphorylated and inactivated by cyclin-CDK at the Start transition of the new cell cycle. We developed a biosensor to assess the cell cycle dynamics of APC/C-Cdh1. Nuclear exit of the G1 transcriptional repressor Whi5 is a known marker of Start; APC/C-Cdh1 is inactivated 12 min after Whi5 nuclear exit with little measurable cell-to-cell timing variability. Multiple phosphorylation sites on Cdh1 act in a redundant manner to repress its activity. Reducing the number of phosphorylation sites on Cdh1 can to some extent be tolerated for cell viability, but it increases variability in timing of APC/C-Cdh1 inactivation. Mutants with minimal subsets of phosphorylation sites required for viability exhibit striking stochasticity in multiple responses including budding, nuclear division, and APC/C-Cdh1 activity itself. Multiple cyclin-CDK complexes, as well as the stoichiometric inhibitor Acm1, contribute to APC/C-Cdh1 inactivation; this redundant control is likely to promote rapid and reliable APC/C-Cdh1 inactivation immediately following the Start transition.

The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

Science.gov (United States)

Diccianni, M B; Imagawa, M; Muramatsu, M

1992-10-11

Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

Interobserver variation in the diagnosis of fibroepithelial lesions of the breast: a multicentre audit by digital pathology.

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Dessauvagie, Benjamin F; Lee, Andrew H S; Meehan, Katie; Nijhawan, Anju; Tan, Puay Hoon; Thomas, Jeremy; Tie, Bibiana; Treanor, Darren; Umar, Seemeen; Hanby, Andrew M; Millican-Slater, Rebecca

2018-02-13

Fibroepithelial lesions (FELs) of the breast span a morphological continuum including lesions where distinction between cellular fibroadenoma (FA) and benign phyllodes tumour (PT) is difficult. The distinction is clinically important with FAs managed conservatively while equivocal lesions and PTs are managed with surgery. We sought to audit core biopsy diagnoses of equivocal FELs by digital pathology and to investigate whether digital point counting is useful in clarifying FEL diagnoses. Scanned slide images from cores and subsequent excisions of 69 equivocal FELs were examined in a multicentre audit by eight pathologists to determine the agreement and accuracy of core needle biopsy (CNB) diagnoses and by digital point counting of stromal cellularity and expansion to determine if classification could be improved. Interobserver variation was high on CNB with a unanimous diagnosis from all pathologists in only eight cases of FA, diagnoses of both FA and PT on the same CNB in 15 and a 'weak' mean kappa agreement between pathologists (k=0.36). 'Moderate' agreement was observed on CNBs among breast specialists (k=0.44) and on excision samples (k=0.49). Up to 23% of lesions confidently diagnosed as FA on CNB were PT on excision and up to 30% of lesions confidently diagnosed as PT on CNB were FA on excision. Digital point counting did not aid in the classification of FELs. Accurate and reproducible diagnosis of equivocal FELs is difficult, particularly on CNB, resulting in poor interobserver agreement and suboptimal accuracy. Given the diagnostic difficulty, and surgical implications, equivocal FELs should be reported in consultation with experienced breast pathologists as a small number of benign FAs can be selected out from equivocal lesions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of axillary ultrasound and core needle biopsy on the utility of intraoperative frozen section analysis and treatment decision making in women with invasive breast cancer.

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Caretta-Weyer, Holly; Sisney, Gale A; Beckman, Catherine; Burnside, Elizabeth S; Salkowsi, Lonie R; Strigel, Roberta M; Wilke, Lee G; Neuman, Heather B

2012-09-01

Our objective was to evaluate the impact of preoperative axillary ultrasound and core needle biopsy (CNB) on breast cancer treatment decision making. A secondary aim was to evaluate the impact on the utility of intraoperative sentinel lymph node (SLN) frozen section. A review of 84 patients with clinically negative axilla who underwent axillary ultrasound was performed. Sensitivity, specificity, and positive/negative predictive value for axillary ultrasound with CNB was calculated. Thirty-one (37%) had suspicious nodes. Of 27 amenable to CNB, 12 (14%) were malignant, changing treatment plans. The sensitivity of ultrasound and CNB was 54% and specificity 100%; the positive and negative predictive values were 100% and 80%, respectively. In 41 patients with normal ultrasounds who underwent SLN frozen section, 10 (24%) were positive. Preoperative axillary ultrasound impacts treatment decision making in 14%. With a sensitivity of 54%, it is a useful adjunct to, but not replacement for, SLN biopsy. Frozen section remains of utility even after a negative axillary ultrasound. Copyright © 2012 Elsevier Inc. All rights reserved.

An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

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Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

2014-01-01

The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

Directory of Open Access Journals (Sweden)

Cecil M Benitez

2014-10-01

Full Text Available The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

REDOR NMR Reveals Multiple Conformers for a Protein Kinase C Ligand in a Membrane Environment

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Hao Yang

2018-01-01

Full Text Available Bryostatin 1 (henceforth bryostatin is in clinical trials for the treatment of Alzheimer’s disease and for HIV/AIDS eradication. It is also a preclinical lead for cancer immunotherapy and other therapeutic indications. Yet nothing is known about the conformation of bryostatin bound to its protein kinase C (PKC target in a membrane microenvironment. As a result, efforts to design more efficacious, better tolerated, or more synthetically accessible ligands have been limited to structures that do not include PKC or membrane effects known to influence PKC–ligand binding. This problem extends more generally to many membrane-associated proteins in the human proteome. Here, we use rotational-echo double-resonance (REDOR solid-state NMR to determine the conformations of PKC modulators bound to the PKCδ-C1b domain in the presence of phospholipid vesicles. The conformationally limited PKC modulator phorbol diacetate (PDAc is used as an initial test substrate. While unanticipated partitioning of PDAc between an immobilized protein-bound state and a mobile state in the phospholipid assembly was observed, a single conformation in the bound state was identified. In striking contrast, a bryostatin analogue (bryolog was found to exist exclusively in a protein-bound state, but adopts a distribution of conformations as defined by three independent distance measurements. The detection of multiple PKCδ-C1b-bound bryolog conformers in a functionally relevant phospholipid complex reveals the inherent dynamic nature of cellular systems that is not captured with single-conformation static structures. These results indicate that binding, selectivity, and function of PKC modulators, as well as the design of new modulators, are best addressed using a dynamic multistate model, an analysis potentially applicable to other membrane-associated proteins.

Systematic analysis of fly models with multiple drivers reveals different effects of ataxin-1 and huntingtin in neuron subtype-specific expression.

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Risa Shiraishi

Full Text Available The fruit fly, Drosophila melanogaster, is a commonly used model organism for neurodegenerative diseases. Its major advantages include a short lifespan and its susceptibility to manipulation using sophisticated genetic techniques. Here, we report the systematic comparison of fly models of two polyglutamine (polyQ diseases. We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers. We systematically analyzed their effects based on multiple phenotypes: eclosion rate, lifespan, motor performance, and circadian rhythms of spontaneous activity. This systematic assay system enabled us to quantitatively evaluate and compare the functional disabilities of different genotypes. The results suggest different effects of Ataxin-1 and Huntingtin on specific types of neural cells during development and in adulthood. In addition, we confirmed the therapeutic effects of LiCl and butyrate using representative models. These results support the usefulness of this assay system for screening candidate chemical compounds that modify the pathologies of polyQ diseases.

Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis

DEFF Research Database (Denmark)

Knudsen, S; Jennum, P J; Korsholm, K

2008-01-01

There is emerging evidence that multiple sclerosis (MS), the hypothalamic sleep-wake regulating neuropeptide hypocretin-1 (hcrt-1) and the sleep disorder narcolepsy may be connected. Thus, the major pathophysiological component of narcolepsy is lack of hcrt-1. Dysfunction of the hypocretin system....../ml). No statistically significant differences were found between attack and remission. MRI scans revealed no hypothalamic lesions. The results show that the hypocretin system is intact and sleepiness is not typical in RRMS and MON without hypothalamic lesions on MRI....

Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia

NARCIS (Netherlands)

Georgitsi, Marianthi; Raitila, Anniina; Karhu, Auli; van der Luijt, Rob B.; Aalfs, Cora M.; Sane, Timo; Vierimaa, Outi; Mäkinen, Markus J.; Tuppurainen, Karoliina; Paschke, Ralph; Gimm, Oliver; Koch, Christian A.; Gündogdu, Sadi; Lucassen, Anneke; Tischkowitz, Marc; Izatt, Louise; Aylwin, Simon; Bano, Gul; Hodgson, Shirley; de Menis, Ernesto; Launonen, Virpi; Vahteristo, Pia; Aaltonen, Lauri A.

2007-01-01

Germline mutations in the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome, but in up to 20-25% of clinical MEN1 cases, no MEN1 mutations can be found. Recently, a germline mutation in the CDKN1B gene, encoding p27(Kip1), was reported in one suspected MEN1 family with two

Multifractal fluctuations in joint angles during infant spontaneous kicking reveal multiplicativity-driven coordination

International Nuclear Information System (INIS)

Stephen, Damian G.; Hsu, Wen-Hao; Young, Diana; Saltzman, Elliot L.; Holt, Kenneth G.; Newman, Dava J.; Weinberg, Marc; Wood, Robert J.; Nagpal, Radhika; Goldfield, Eugene C.

2012-01-01

Previous research has considered infant spontaneous kicking as a form of exploration. According to this view, spontaneous kicking provides information about motor degrees of freedom and may shape multijoint coordinations for more complex movement patterns such as gait. Recent work has demonstrated that multifractal, multiplicative fluctuations in exploratory movements index energy flows underlying perceptual-motor information. If infant spontaneous kicking is exploratory and occasions an upstream flow of information from the motor periphery, we expected not only that multiplicativity of fluctuations at the hip should promote multiplicativity of fluctuations at more distal joints (i.e., reflecting downstream effects of neural control) but also that multiplicativity at more distal joints should promote multiplicativity at the hip. Multifractal analysis demonstrated that infant spontaneous kicking in four typically developing infants for evidence of multiplicative fluctuations in multiple joint angles along the leg (i.e., hip, knee, and ankle) exhibited multiplicativity. Vector autoregressive modeling demonstrated that only one leg exhibited downstream effects but that both legs exhibited upstream effects. These results confirm the exploratory aspect of infant spontaneous kicking and suggest chaotic dynamics in motor coordination. They also resonate with existing models of chaos-controlled robotics and noise-based interventions for rehabilitating motor coordination in atypically developing patients.

Whole-genome sequencing of Bacillus subtilis XF-1 reveals mechanisms for biological control and multiple beneficial properties in plants.

Science.gov (United States)

Guo, Shengye; Li, Xingyu; He, Pengfei; Ho, Honhing; Wu, Yixin; He, Yueqiu

2015-06-01

Bacillus subtilis XF-1 is a gram-positive, plant-associated bacterium that stimulates plant growth and produces secondary metabolites that suppress soil-borne plant pathogens. In particular, it is especially highly efficient at controlling the clubroot disease of cruciferous crops. Its 4,061,186-bp genome contains an estimated 3853 protein-coding sequences and the 1155 genes of XF-1 are present in most genome-sequenced Bacillus strains: 3757 genes in B. subtilis 168, and 1164 in B. amyloliquefaciens FZB42. Analysis using the Cluster of Orthologous Groups database of proteins shows that 60 genes control bacterial mobility, 221 genes are related to cell wall and membrane biosynthesis, and more than 112 are genes associated with secondary metabolites. In addition, the genes contributed to the strain's plant colonization, bio-control and stimulation of plant growth. Sequencing of the genome is a fundamental step for developing a desired strain to serve as an efficient biological control agent and plant growth stimulator. Similar to other members of the taxon, XF-1 has a genome that contains giant gene clusters for the non-ribosomal synthesis of antifungal lipopeptides (surfactin and fengycin), the polyketides (macrolactin and bacillaene), the siderophore bacillibactin, and the dipeptide bacilysin. There are two synthesis pathways for volatile growth-promoting compounds. The expression of biosynthesized antibiotic peptides in XF-1 was revealed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

The accuracy of frozen section analysis in ultrasound- guided core needle biopsy of breast lesions

International Nuclear Information System (INIS)

Brunner, Andreas H; Sagmeister, Thomas; Kremer, Jolanta; Riss, Paul; Brustmann, Hermann

2009-01-01

Limited data are available to evaluate the accuracy of frozen section analysis and ultrasound- guided core needle biopsy of the breast. In a retrospective analysis data of 120 consecutive handheldultrasound- guided 14- gauge automated core needle biopsies (CNB) in 109 consecutive patients with breast lesions between 2006 and 2007 were evaluated. In our outpatient clinic120 CNB were performed. In 59/120 (49.2%) cases we compared histological diagnosis on frozen sections with those on paraffin sections of CNB and finally with the result of open biopsy. Of the cases 42/59 (71.2%) were proved to be malignant and 17/59 (28.8%) to be benign in the definitive histology. 2/59 (3.3%) biopsies had a false negative frozen section result. No false positive results of the intraoperative frozen section analysis were obtained, resulting in a sensitivity, specificity and positive predicting value (PPV) and negative predicting value (NPV) of 95%, 100%, 100% and 90%, respectively. Histological and morphobiological parameters did not show up relevance for correct frozen section analysis. In cases of malignancy time between diagnosis and definitive treatment could not be reduced due to frozen section analysis. The frozen section analysis of suspect breast lesions performed by CNB displays good sensitivity/specificity characteristics. Immediate investigations of CNB is an accurate diagnostic tool and an important step in reducing psychological strain by minimizing the period of uncertainty in patients with breast tumor

Serum galectin-1 in patients with multiple myeloma

DEFF Research Database (Denmark)

Andersen, Morten Nørgaard; Ludvigsen, Maja; Abildgaard, Niels

2017-01-01

with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma...

NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

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Joshua M. Baughman

2016-07-01

Full Text Available We introduce neutron-encoded (NeuCode amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver-specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology.

Use of percutaneous image-guided coaxial core-needle biopsy for diagnosis of intraabdominal lymphoma

International Nuclear Information System (INIS)

Shimizu, Ikuo; Okazaki, Yoichi; Takeda, Wataru; Kirihara, Takehiko; Sato, Keijiro; Fujikawa, Yuko; Ueki, Toshimitsu; Hiroshima, Yuki; Sumi, Masahiko; Ueno, Mayumi; Ichikawa, Naoaki; Kobayashi, Hikaru

2014-01-01

Although pathological diagnosis is essential for managing malignant lymphoma, intraabdominal lesions are generally difficult to approach due to the invasiveness of abdominal surgery. Here, we report the use of percutaneous image-guided coaxial core-needle biopsy (CNB) to obtain intraabdominal specimens for diagnosing intraabdominal lymphomas, which typically requires histopathological and immunohistochemical evaluation. We retrospectively reviewed consecutive cases involving computed tomography (CT)- or ultrasonography (US)-guided CNB to obtain pathological specimens for intraabdominal lesions from 1999 to 2011. Liver, spleen, kidney, and inguinal node biopsies were excluded. We compared CNBs with laparotomic biopsies. A total of 66 CNBs were performed for 59 patients (32 males, 27 females; median age, 63.5), including second or third repeat procedures. Overall diagnostic rate was 88.5%. None of the patients required additional surgical biopsies. Notably, the median interval between recognition of an intraabdominal mass and biopsy was only 1 day. Forty-five procedures were performed for hematological malignancies. Adequate specimens were obtained for histopathological diagnosis in 86% of cases. Flow cytometry detected lymphoma cells in 79.5% of cases. Twelve patients (nine males, three females; median age, 60) were eligible for surgical biopsy. While every postoperative course was satisfactory, median duration from lesion recognition to therapy initiation for lymphoma cases was significantly shorter for CNB than for surgical biopsy (14 vs. 35 days). While one-fourth of the patients were not eligible for the procedures, CNB is safe and highly effective for diagnosis of intraabdominal lymphomas. This method significantly improves sampling and potentially helps attain immunohistological distinction, allowing for more timely therapy initiation

Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

International Nuclear Information System (INIS)

Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

2012-01-01

We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present

Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism

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S Birla

2016-01-01

Full Text Available Background and Objectives: Primary hyperparathyroidism (PHPT can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1 is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein “menin.” We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. Materials and Methods: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. Results: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. Conclusions: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation.

A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development.

Science.gov (United States)

Covassin, L D; Siekmann, A F; Kacergis, M C; Laver, E; Moore, J C; Villefranc, J A; Weinstein, B M; Lawson, N D

2009-05-15

In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development.

XRCC1 and PCNA are loading platforms with distinct kinetic properties and different capacities to respond to multiple DNA lesions

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Leonhardt Heinrich

2007-09-01

Full Text Available Abstract Background Genome integrity is constantly challenged and requires the coordinated recruitment of multiple enzyme activities to ensure efficient repair of DNA lesions. We investigated the dynamics of XRCC1 and PCNA that act as molecular loading platforms and play a central role in this coordination. Results Local DNA damage was introduced by laser microirradation and the recruitment of fluorescent XRCC1 and PCNA fusion proteins was monitored by live cell microscopy. We found an immediate and fast recruitment of XRCC1 preceding the slow and continuous recruitment of PCNA. Fluorescence bleaching experiments (FRAP and FLIP revealed a stable association of PCNA with DNA repair sites, contrasting the high turnover of XRCC1. When cells were repeatedly challenged with multiple DNA lesions we observed a gradual depletion of the nuclear pool of PCNA, while XRCC1 dynamically redistributed even to lesions inflicted last. Conclusion These results show that PCNA and XRCC1 have distinct kinetic properties with functional consequences for their capacity to respond to successive DNA damage events.

XRCC1 and PCNA are loading platforms with distinct kinetic properties and different capacities to respond to multiple DNA lesions

Science.gov (United States)

Mortusewicz, Oliver; Leonhardt, Heinrich

2007-01-01

Background Genome integrity is constantly challenged and requires the coordinated recruitment of multiple enzyme activities to ensure efficient repair of DNA lesions. We investigated the dynamics of XRCC1 and PCNA that act as molecular loading platforms and play a central role in this coordination. Results Local DNA damage was introduced by laser microirradation and the recruitment of fluorescent XRCC1 and PCNA fusion proteins was monitored by live cell microscopy. We found an immediate and fast recruitment of XRCC1 preceding the slow and continuous recruitment of PCNA. Fluorescence bleaching experiments (FRAP and FLIP) revealed a stable association of PCNA with DNA repair sites, contrasting the high turnover of XRCC1. When cells were repeatedly challenged with multiple DNA lesions we observed a gradual depletion of the nuclear pool of PCNA, while XRCC1 dynamically redistributed even to lesions inflicted last. Conclusion These results show that PCNA and XRCC1 have distinct kinetic properties with functional consequences for their capacity to respond to successive DNA damage events. PMID:17880707

Loss of Centrobin Enables Daughter Centrioles to Form Sensory Cilia in Drosophila.

Science.gov (United States)

Gottardo, Marco; Pollarolo, Giulia; Llamazares, Salud; Reina, Jose; Riparbelli, Maria G; Callaini, Giuliano; Gonzalez, Cayetano

2015-08-31

Sensory cilia are organelles that convey information to the cell from the extracellular environment. In vertebrates, ciliary dysfunction results in ciliopathies that in humans comprise a wide spectrum of developmental disorders. In Drosophila, sensory cilia are found only in the neurons of type I sensory organs, but ciliary dysfunction also has dramatic consequences in this organism because it impairs the mechanosensory properties of bristles and chaetae and leads to uncoordination, a crippling condition that causes lethality shortly after eclosion. The cilium is defined by the ciliary membrane, a protrusion of the cell membrane that envelops the core structure known as the axoneme, a microtubule array that extends along the cilium from the basal body. In vertebrates, basal body function requires centriolar distal and subdistal appendages and satellites. Because these structures are acquired through centriole maturation, only mother centrioles can serve as basal bodies. Here, we show that although centriole maturity traits are lacking in Drosophila, basal body fate is reserved to mother centrioles in Drosophila type I neurons. Moreover, we show that depletion of the daughter-centriole-specific protein Centrobin (CNB) enables daughter centrioles to dock on the cell membrane and to template an ectopic axoneme that, although structurally defective, protrudes out of the cell and is enveloped by a ciliary membrane. Conversely, basal body capability is inhibited in mother centrioles modified to carry CNB. These results reveal the crucial role of CNB in regulating basal body function in Drosophila ciliated sensory organs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Expression of hybrid fusion protein (Cry1Ac::ASAL) in transgenic rice plants imparts resistance against multiple insect pests.

Science.gov (United States)

Boddupally, Dayakar; Tamirisa, Srinath; Gundra, Sivakrishna Rao; Vudem, Dashavantha Reddy; Khareedu, Venkateswara Rao

2018-05-31

To evolve rice varieties resistant to different groups of insect pests a fusion gene, comprising DI and DII domains of Bt Cry1Ac and carbohydrate binding domain of garlic lectin (ASAL), was constructed. Transgenic rice lines were generated and evaluated to assess the efficacy of Cry1Ac::ASAL fusion protein against three major pests, viz., yellow stem borer (YSB), leaf folder (LF) and brown planthopper (BPH). Molecular analyses of transgenic plants revealed stable integration and expression of the fusion gene. In planta insect bioassays on transgenics disclosed enhanced levels of resistance compared to the control plants. High insect mortality of YSB, LF and BPH was observed on transgenics compared to that of control plants. Furthermore, honeydew assays revealed significant decreases in the feeding ability of BPH on transgenic plants as compared to the controls. Ligand blot analysis, using BPH insects fed on cry1Ac::asal transgenic rice plants, revealed a modified receptor protein-binding pattern owing to its ability to bind to additional receptors in insects. The overall results authenticate that Cry1Ac::ASAL protein is endowed with remarkable entomotoxic effects against major lepidopteran and hemipteran insects. As such, the fusion gene appears promising and can be introduced into various other crops to control multiple insect pests.

High-resolution deep sequencing reveals biodiversity, population structure, and persistence of HIV-1 quasispecies within host ecosystems

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Yin Li

2012-12-01

Full Text Available Abstract Background Deep sequencing provides the basis for analysis of biodiversity of taxonomically similar organisms in an environment. While extensively applied to microbiome studies, population genetics studies of viruses are limited. To define the scope of HIV-1 population biodiversity within infected individuals, a suite of phylogenetic and population genetic algorithms was applied to HIV-1 envelope hypervariable domain 3 (Env V3 within peripheral blood mononuclear cells from a group of perinatally HIV-1 subtype B infected, therapy-naïve children. Results Biodiversity of HIV-1 Env V3 quasispecies ranged from about 70 to 270 unique sequence clusters across individuals. Viral population structure was organized into a limited number of clusters that included the dominant variants combined with multiple clusters of low frequency variants. Next generation viral quasispecies evolved from low frequency variants at earlier time points through multiple non-synonymous changes in lineages within the evolutionary landscape. Minor V3 variants detected as long as four years after infection co-localized in phylogenetic reconstructions with early transmitting viruses or with subsequent plasma virus circulating two years later. Conclusions Deep sequencing defines HIV-1 population complexity and structure, reveals the ebb and flow of dominant and rare viral variants in the host ecosystem, and identifies an evolutionary record of low-frequency cell-associated viral V3 variants that persist for years. Bioinformatics pipeline developed for HIV-1 can be applied for biodiversity studies of virome populations in human, animal, or plant ecosystems.

The analysis of correlation between IL-1B gene expression and genotyping in multiple sclerosis patients.

Science.gov (United States)

Heidary, Masoumeh; Rakhshi, Nahid; Pahlevan Kakhki, Majid; Behmanesh, Mehrdad; Sanati, Mohammad Hossein; Sanadgol, Nima; Kamaladini, Hossein; Nikravesh, Abbas

2014-08-15

IL-1B is released by monocytes, astrocytes and brain endothelial cells and seems to be involved in inflammatory reactions of the central nervous system (CNS) in multiple sclerosis (MS). This study aims to evaluate the expression level of IL-1B mRNA in peripheral blood mononuclear cells (PBMCs), genotype the rs16944 SNP and find out the role of this SNP on the expression level of IL-1B in MS patients. We found that the expression level of IL-1B in MS patients increased 3.336 times more than controls in PBMCs but the rs16944 SNP in the promoter region of IL-1B did not affect the expression level of this gene and there was not association of this SNP with MS in the examined population. Also, our data did not reveal any correlation between normalized expressions of IL-1B gene with age of participants, age of onset, and disease duration. Copyright © 2014 Elsevier B.V. All rights reserved.

Genome sequencing reveals complex secondary metabolome in themarine actinomycete Salinispora tropica

Energy Technology Data Exchange (ETDEWEB)

Udwary, Daniel W.; Zeigler, Lisa; Asolkar, Ratnakar; Singan,Vasanth; Lapidus, Alla; Fenical, William; Jensen, Paul R.; Moore, BradleyS.

2007-05-01

Recent fermentation studies have identified actinomycetes ofthe marine-dwelling genus Salinispora as prolific natural productproducers. To further evaluate their biosynthetic potential, we analyzedall identifiable secondary natural product gene clusters from therecently sequenced 5,184,724 bp S. tropica CNB-440 circular genome. Ouranalysis shows that biosynthetic potential meets or exceeds that shown byprevious Streptomyces genome sequences as well as other naturalproduct-producing actinomycetes. The S. tropica genome features ninepolyketide synthase systems of every known formally classified family,non-ribosomal peptide synthetases and several hybrid clusters. While afew clusters appear to encode molecules previously identified inStreptomyces species,the majority of the 15 biosynthetic loci are novel.Specific chemical information about putative and observed natural productmolecules is presented and discussed. In addition, our bioinformaticanalysis was critical for the structure elucidation of the novelpolyenemacrolactam salinilactam A. This study demonstrates the potentialfor genomic analysis to complement and strengthen traditional naturalproduct isolation studies and firmly establishes the genus Salinispora asa rich source of novel drug-like molecules.

Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes

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Elvezia Maria Paraboschi

2015-09-01

Full Text Available Abnormalities in RNA metabolism and alternative splicing (AS are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls, followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p = 0.0015 by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.

Effect of Needle Size in Ultrasound-guided Core Needle Breast Biopsy: Comparison of 14-, 16-, and 18-Gauge Needles.

Science.gov (United States)

Giuliani, Michela; Rinaldi, Pierluigi; Rella, Rossella; Fabrizi, Gina; Petta, Federica; Carlino, Giorgio; Di Leone, Alba; Mulè, Antonino; Bufi, Enida; Romani, Maurizio; Belli, Paolo; Bonomo, Lorenzo

2017-11-01

The aim of the present study was to assess the diagnostic accuracy of ultrasound-guided core needle biopsy (US-CNB) of breast lesions, comparing smaller needles (16- and 18-gauge) with the 14-gauge needle, and to analyze the lesion characteristics influencing US-CNB diagnostic performance. All the patients provided informed consent before the biopsy procedure. The data from breast lesions that had undergone US-CNB in our institution from January 2011 to January 2015 were retrospectively reviewed. The inclusion criterion was the surgical histopathologic examination findings of the entire lesion or radiologic follow-up data for ≥ 24 months. The exclusion criterion was the use of preoperative neoadjuvant therapy. The US-CNB results were compared with the surgical pathologic results or with the follow-up findings in the 3 needle size groups (14-, 16-, and 18-gauge). The needle size- and lesion characteristic-specific diagnostic accuracy parameters were evaluated. Statistical analysis was performed using a dedicated software program, and P ≤ .01 was considered significant. A total of 1118 US-CNB cases (1042 patients) were included. Of the 1118 cases, 630 (56.3%) were in the 14-gauge group, 136 (12.2%) in the 16-gauge, and 352 (31.5%) in the 18-gauge needle group. Surgery was performed on 800 lesions (71.6%). Of these, 619 were malignant, 77 were high risk, and 104 were benign. The remaining 318 lesions (28.4%) underwent follow-up imaging studies. All the lesions were stable and, therefore, were considered benign. No differences were observed in the diagnostic accuracy parameters among the 3 needle size groups (P > .01). The false-negative rate was greater for lesions  .01). US-CNB performed with small needles (16 and 18 gauge) had the same diagnostic accuracy as that performed with 14-gauge needles, regardless of the lesion characteristics. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of clinical state of patients with acute leukemia, multiple myeloma and malignant lymphoma by means of in vitro T1 and T2 measurements in serum

International Nuclear Information System (INIS)

Kuliszkiewicz-Janus, M.; Urbaniak-Kujda, D.; Burczak, K.

1995-01-01

A dynamic relaxation times T1 and T2 in vitro study has been performed in the human sera of patients with haematological malignant diseases to monitor their clinical state. Two hundred studies were performed in 20 healthy volunteers and in 180 patients with different malignancies, mostly: acute leukemia, Hodgkin's disease, non-Hodgkin's lymphomas, multiple myeloma. Determinations were performed in active phase of disease and in remission. Measurements were carried out on spectrometer Minispect PC 20B (Bruker; 20 MHz) in 27 C. Additionally, serum proteins of all patients were examined, including total protein content, serum electrophoresis and measurement of Ig classes. Remarkable increase of T1 values in active phase of the disease was found (compared to healthy volunteers) in all malignancies, except multiple myeloma. It was associated with the severeness of the illness, not with diagnose. During remission T1 values did not differ significantly from those of healthy persons. All sera of patients with multiple myeloma in active phase of the disease showed strongly reduced values of T1, associated with the high level of pathological proteins. In 45 patients the measurements were repeated up to 4 times before and during chemotherapy. During treatment resulting in remission, mean T1 values progressively decreased (from 1560 ms to 1394 ms) except of those patients with multiple myeloma. In persons non-responding to therapy these mean values were prolonged (from 1474 ms to 1620 ms) during therapy. In patients with multiple myeloma we noted the reverse changes of mean T1 values in comparison with other malignancies: those responding to the treatment revealed prolonged T1 (from 1165 to 1303 ms) while in those non-responding were decreased (from 1184 ms to 1158 ms). Statistically significant negative correlation was observed between the T1 and total protein content, percentage of gamma-globulin, especially of IgG class. Moreover, a remarkable positive correlation of T1

Expression of Mucin-1 in multiple myeloma and its precursors

DEFF Research Database (Denmark)

Andrulis, Mindaugas; Ellert, Elena; Mandel, Ulla

2014-01-01

AIMS: Recent reports suggest a possible role for extracellular (MUC1N) and transmembrane (MUC1C) subunits of Mucin 1 (MUC1) in the pathogenesis of multiple myeloma (MM). Nuclear translocation of MUC1C is involved in activation of various oncogenic signalling pathways and both MUC1 subunits...

Prospects for cosmic neutrino detection in tritium experiments in the case of hierarchical neutrino masses

International Nuclear Information System (INIS)

Blennow, Mattias

2008-01-01

We discuss the effects of neutrino mixing and the neutrino mass hierarchy when considering the capture of the cosmic neutrino background (CNB) on radioactive nuclei. The implications of mixing and hierarchy at future generations of tritium decay experiments are considered. We find that the CNB should be detectable at these experiments provided that the resolution for the kinetic energy of the outgoing electron can be pushed to a few 0.01 eV for the scenario with inverted neutrino mass hierarchy, about an order of magnitude better than that of the upcoming KATRIN experiment. Another order of magnitude improvement is needed in the case of normal neutrino mass hierarchy. We also note that mixing effects generally make the prospects for CNB detection worse due to an increased maximum energy of the normal beta decay background

In-Situ Liquid Hydrogenation of m-Chloronitrobenzene over Fe-Modified Pt/Carbon Nanotubes Catalysts

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Feng Li

2018-02-01

Full Text Available In-situ liquid-phase hydrogenation of m-chloronitrobenzene (m-CNB based on aqueous-phase reforming (APR of ethanol and catalytic hydrogenation was carried out over Fe-modified Pt/carbon nanotubes (CNTs catalysts. The effects of Pt loading over CNTs and Fe modification on the catalytic performance of Pt/CNTs catalysts were studied. In-tube loading of Pt particles, compared with out-tube loading, considerably improved the catalytic activity. With in-tube loading, Fe-modified Pt/CNTs catalysts further improved the m-CNB in-situ hydrogenation performance. After Fe modification, Pt–Fe/CNTs catalysts formed, inside CNTs, a Pt–Fe alloy and iron oxides, which both improved catalytic hydrogenation performance and significantly enhanced ethanol APR hydrogen producing performance, thereby increasing the m-CNB in-situ hydrogenation reactivity.

Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

Energy Technology Data Exchange (ETDEWEB)

Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

2004-05-18

Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

Mcph1-deficient mice reveal a role for MCPH1 in otitis media.

Directory of Open Access Journals (Sweden)

Jing Chen

Full Text Available Otitis media is a common reason for hearing loss, especially in children. Otitis media is a multifactorial disease and environmental factors, anatomic dysmorphology and genetic predisposition can all contribute to its pathogenesis. However, the reasons for the variable susceptibility to otitis media are elusive. MCPH1 mutations cause primary microcephaly in humans. So far, no hearing impairment has been reported either in the MCPH1 patients or mouse models with Mcph1 deficiency. In this study, Mcph1-deficient (Mcph1(tm1a (/tm1a mice were produced using embryonic stem cells with a targeted mutation by the Sanger Institute's Mouse Genetics Project. Auditory brainstem response measurements revealed that Mcph1(tm1a (/tm1a mice had mild to moderate hearing impairment with around 70% penetrance. We found otitis media with effusion in the hearing-impaired Mcph1(tm1a (/tm1a mice by anatomic and histological examinations. Expression of Mcph1 in the epithelial cells of middle ear cavities supported its involvement in the development of otitis media. Other defects of Mcph1(tm1a (/tm1a mice included small skull sizes, increased micronuclei in red blood cells, increased B cells and ocular abnormalities. These findings not only recapitulated the defects found in other Mcph1-deficient mice or MCPH1 patients, but also revealed an unexpected phenotype, otitis media with hearing impairment, which suggests Mcph1 is a new gene underlying genetic predisposition to otitis media.

Human mast cell tryptase: Multiple cDNAs and genes reveal a multigene serine protease family

International Nuclear Information System (INIS)

Vanderslice, P.; Ballinger, S.M.; Tam, E.K.; Goldstein, S.M.; Craik, C.S.; Caughey, G.H.

1990-01-01

Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned and sequenced in their entirety. The deduced amino acid sequences reveal a 30-amino acid prepropeptide followed by a 245-amino acid catalytic domain. The C-terminal undecapeptide of the human preprosequence is identical in dog tryptase and appears to be part of a prosequence unique among serine proteases. The differences among the three human tryptase catalytic domains include the loss of a consensus N-glycosylation site in one cDNA, which may explain some of the heterogeneity in size and susceptibility to deglycosylation seen in tryptase preparations. All three tryptase cDNAs are distinct from a recently reported cDNA obtained from a human lung mast cell library. A skin tryptase cDNA was used to isolate a human tryptase gene, the exons of which match one of the skin-derived cDNAs. The organization of the ∼1.8-kilobase-pair tryptase gene is unique and is not closely related to that of any other mast cell or leukocyte serine protease. The 5' regulatory regions of the gene share features with those of other serine proteases, including mast cell chymase, but are unusual in being separated from the protein-coding sequence by an intron. High-stringency hybridization of a human genomic DNA blot with a fragment of the tryptase gene confirms the presence of multiple tryptase genes. These findings provide genetic evidence that human mast cell tryptases are the products of a multigene family

ENU mutagenesis reveals that Notchless homolog 1 (Drosophila affects Cdkn1a and several members of the Wnt pathway during murine pre-implantation development

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Lossie Amy C

2012-12-01

Full Text Available Abstract Background Our interests lie in determining the genes and genetic pathways that are important for establishing and maintaining maternal-fetal interactions during pregnancy. Mutation analysis targeted to a 34 Mb domain flanked by Trp53 and Wnt3 demonstrates that this region of mouse chromosome 11 contains a large number of essential genes. Two mutant alleles (l11Jus1 and l11Jus4, which fall into the same complementation group, survive through implantation but fail prior to gastrulation. Results Through a positional cloning strategy, we discovered that these homozygous mutant alleles contain non-conservative missense mutations in the Notchless homolog 1 (Drosophila (Nle1 gene. NLE1 is a member of the large WD40-repeat protein family, and is thought to signal via the canonical NOTCH pathway in vertebrates. However, the phenotype of the Nle1 mutant mice is much more severe than single Notch receptor mutations or even in animals in which NOTCH signaling is blocked. To test the hypothesis that NLE1 functions in multiple signaling pathways during pre-implantation development, we examined expression of multiple Notch downstream target genes, as well as select members of the Wnt pathway in wild-type and mutant embryos. We did not detect altered expression of any primary members of the Notch pathway or in Notch downstream target genes. However, our data reveal that Cdkn1a, a NOTCH target, was upregulated in Nle1 mutants, while several members of the Wnt pathway are downregulated. In addition, we found that Nle1 mutant embryos undergo caspase-mediated apoptosis as hatched blastocysts, but not as morulae or blastocysts. Conclusions Taken together, these results uncover potential novel functions for NLE1 in the WNT and CDKN1A pathways during embryonic development in mammals.

Intraosseous Atypical Chondroid Tumor or Chondrosarcoma Grade 1 in Patients with Multiple Osteochondromas

NARCIS (Netherlands)

Goud, Annemarie L.; Wuyts, Wim; Bessems, Johannes; Bramer, Jos; van der Woude, Henk Jan; Ham, John

2015-01-01

Background: The autosomal dominant condition multiple osteochondromas, formerly called multiple hereditary exostoses, is associated with a risk of malignant progression of osteochondroma into secondary peripheral chondrosarcoma. Most patients with multiple osteochondromas have exostosin-1 or

Can Breast Cancer Biopsy Influence Sentinel Lymph Node Status?

Science.gov (United States)

Giuliani, Michela; Patrolecco, Federica; Rella, Rossella; Di Giovanni, Silvia Eleonora; Infante, Amato; Rinaldi, Pierluigi; Romani, Maurizio; Mulè, Antonino; Arciuolo, Damiano; Belli, Paolo; Bonomo, Lorenzo

2016-12-01

We evaluated whether the needle size could influence metastasis occurrence in the axillary sentinel lymph node (SLN) in ultrasound-guided core needle biopsy (US-CNB) of breast cancer (BC). The data from all patients with breast lesions who had undergone US-CNB at our institution from January 2011 to January 2015 were retrospectively reviewed. A total of 377 BC cases were included using the following criteria: (1) percutaneous biopsy-proven invasive BC; and (2) SLN dissection with histopathologic examination. The patients were divided into 2 groups according to the needle size used: 14 gauge versus 16 or 18 gauge. SLN metastasis classification followed the 7th American Joint Committee on Cancer (2010) TNM pathologic staging factors: macrometastases, micrometastases, isolated tumor cells, or negative. Only macrometastases and micrometastases were considered positive, and the positive and negative rates were calculated for the overall population and for both needle size groups. Of the 377 BC cases, 268 US-CNB procedures were performed using a 14-gauge needle and 109 with a 16- or 18-gauge needle, respectively. The negative rate was significantly related statistically with the needle size, with a greater prevalence in the 14-gauge group on both extemporaneous analysis (P = .019) and definitive analysis (P = .002). The macrometastasis rate was 17% (63 of 377) for the 14-gauge and 3% (12 of 377) for the 16- and 18-gauge needles, respectively. Our preliminary results have suggested that use of a large needle size in CNB does not influence SLN status; thus, preoperative breast biopsy can be considered a safe procedure in the diagnosis of malignant breast lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

The mitochondrial ND1 m.3337G>A mutation associated to multiple mitochondrial DNA deletions in a patient with Wolfram syndrome and cardiomyopathy

Energy Technology Data Exchange (ETDEWEB)

Mezghani, Najla [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Mnif, Mouna [Service d' endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Mkaouar-Rebai, Emna, E-mail: emna_mkaouar@mail2world.com [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Kallel, Nozha [Service d' endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Salem, Ikhlass Haj [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Charfi, Nadia; Abid, Mohamed [Service d' endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Fakhfakh, Faiza [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)

2011-07-29

Highlights: {yields} We reported a patient with Wolfram syndrome and dilated cardiomyopathy. {yields} We detected the ND1 mitochondrial m.3337G>A mutation in 3 tested tissues (blood leukocytes, buccal mucosa and skeletal muscle). {yields} Long-range PCR amplification revealed the presence of multiple mitochondrial deletions in the skeletal muscle. {yields} The deletions remove several tRNA and protein-coding genes. -- Abstract: Wolfram syndrome (WFS) is a rare hereditary disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is a heterogeneous disease and full characterization of all clinical and biological features of this disorder is difficult. The wide spectrum of clinical expression, affecting several organs and tissues, and the similarity in phenotype between patients with Wolfram syndrome and those with certain types of respiratory chain diseases suggests mitochondrial DNA (mtDNA) involvement in Wolfram syndrome patients. We report a Tunisian patient with clinical features of moderate Wolfram syndrome including diabetes, dilated cardiomyopathy and neurological complications. The results showed the presence of the mitochondrial ND1 m.3337G>A mutation in almost homoplasmic form in 3 tested tissues of the proband (blood leukocytes, buccal mucosa and skeletal muscle). In addition, the long-range PCR amplifications revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient's skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of moderate Wolfram syndrome associated with cardiomyopathy, in whom we detected the ND1 m.3337G>A mutation with mitochondrial multiple deletions.

The mitochondrial ND1 m.3337G>A mutation associated to multiple mitochondrial DNA deletions in a patient with Wolfram syndrome and cardiomyopathy

International Nuclear Information System (INIS)

Mezghani, Najla; Mnif, Mouna; Mkaouar-Rebai, Emna; Kallel, Nozha; Salem, Ikhlass Haj; Charfi, Nadia; Abid, Mohamed; Fakhfakh, Faiza

2011-01-01

Highlights: → We reported a patient with Wolfram syndrome and dilated cardiomyopathy. → We detected the ND1 mitochondrial m.3337G>A mutation in 3 tested tissues (blood leukocytes, buccal mucosa and skeletal muscle). → Long-range PCR amplification revealed the presence of multiple mitochondrial deletions in the skeletal muscle. → The deletions remove several tRNA and protein-coding genes. -- Abstract: Wolfram syndrome (WFS) is a rare hereditary disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is a heterogeneous disease and full characterization of all clinical and biological features of this disorder is difficult. The wide spectrum of clinical expression, affecting several organs and tissues, and the similarity in phenotype between patients with Wolfram syndrome and those with certain types of respiratory chain diseases suggests mitochondrial DNA (mtDNA) involvement in Wolfram syndrome patients. We report a Tunisian patient with clinical features of moderate Wolfram syndrome including diabetes, dilated cardiomyopathy and neurological complications. The results showed the presence of the mitochondrial ND1 m.3337G>A mutation in almost homoplasmic form in 3 tested tissues of the proband (blood leukocytes, buccal mucosa and skeletal muscle). In addition, the long-range PCR amplifications revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient's skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of moderate Wolfram syndrome associated with cardiomyopathy, in whom we detected the ND1 m.3337G>A mutation with mitochondrial multiple deletions.

Neurofibromatosis type 1 and multiple sclerosis: Genetically related ...

African Journals Online (AJOL)

Neurofibromatosis type I (NF1) is an autosomal dominant disorder with involvement of both the cutaneous and nervous systems. Patients are susceptible to neurological complication in the form of tumors of the brain and spinal cord. Multiple sclerosis (MS) is a chronic autoimmune disease that affects the myelinated axons ...

Multiple parton interactions in photoproduction at HERA/H1

Energy Technology Data Exchange (ETDEWEB)

Magro, Lluis Marti

2009-02-15

Photoproduction data of HERA-I are analysed by requiring dijets with transverse momenta of at least 5 GeV. The two jets define in azimuth a towards region (leading jet), an away region (usually the 2nd jet) and transverse regions between them. The charged particle and jet with low transverse momentum multiplicity, so called minijets, are measured in these regions as a function of the variables x{sup obs}{sub {gamma}} and P{sup Jet{sub 1T}} (leading jet). The measurement is compared to predictions including parton showers and matrix elements at leading order in {alpha}{sub s}. Some predictions include contributions from multiple parton interactions and use different parton evolution equations. It was found that existing MC programs do not fully describe the measurements but the description can be improved by including multiple parton interactions. (orig.)

The Management Strategy of Benign Solitary Intraductal Papilloma on Breast Core Biopsy.

Science.gov (United States)

Ko, Dayoung; Kang, Eunyoung; Park, So Yeon; Kim, Sun Mi; Jang, Mijung; Yun, Bo La; Chae, Sumin; Jang, Yerang; Kim, Hye Jin; Kim, Sung-Won; Kim, Eun-Kyu

2017-08-01

Intraductal papilloma (IDP) is well-known as one of the common benign breast lesions requiring excision. However, treatment of IDP without atypia is controversial. The aim of our study was to determine the proper management of solitary IDP by core needle biopsy (CNB). We retrospectively reviewed patients with solitary IDP confirmed by CNB from March 2003 to March 2015. We collected data about final pathology after excision, as well as clinical, histologic, and radiologic findings at initial diagnosis. The final pathology was categorized as benign or malignant. We evaluated the rate of upgrade to malignancy and factors associated with malignancy. We identified 405 patients who presented benign solitary IDP by CNB. The mean age was 46.1 years (range, 15-86 years). In total, 135 patients underwent surgical excision, and 211 underwent vacuum-assisted excision. Of 346 patients, malignant lesions were found in 8 patients (2.3%): 7 underwent surgical excision, and 1 underwent vacuum-assisted excision. Only the size of IDP was significantly associated with cancer upgrade (P = .003). Our study shows that overall malignancy upgrade rate of benign solitary IDP after excision is very low (2.3%). Even when the size of IDP was less than 1 cm, the upgrade rate to cancer was only 0.9%. Therefore, for patients with small solitary IDP, we recommend close follow-up with ultrasound instead of excision. Copyright © 2017 Elsevier Inc. All rights reserved.

Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

International Nuclear Information System (INIS)

Erdas, Enrico; Mariotti, Stefano; Pomata, Mariano; Aste, Nicola; Pilloni, Luca; Nicolosi, Angelo; Licheri, Sergio; Cappai, Antonello; Mastinu, Marco; Cetani, Filomena; Pardi, Elena

2012-01-01

Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99m Tc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence. Despite

Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple sclerosis.

Directory of Open Access Journals (Sweden)

Polona Lavtar

Full Text Available Prevalence of multiple sclerosis varies with geographic latitude. We hypothesized that this fact might be partially associated with the influence of latitude on circadian rhythm and consequently that genetic variability of key circadian rhythm regulators, ARNTL and CLOCK genes, might contribute to the risk for multiple sclerosis. Our aim was to analyse selected polymorphisms of ARNTL and CLOCK, and their association with multiple sclerosis. A total of 900 Caucasian patients and 1024 healthy controls were compared for genetic signature at 8 SNPs, 4 for each of both genes. We found a statistically significant difference in genotype (ARNTL rs3789327, P = 7.5·10-5; CLOCK rs6811520 P = 0.02 distributions in patients and controls. The ARNTL rs3789327 CC genotype was associated with higher risk for multiple sclerosis at an OR of 1.67 (95% CI 1.35-2.07, P = 0.0001 and the CLOCK rs6811520 genotype CC at an OR of 1.40 (95% CI 1.13-1.73, P = 0.002. The results of this study suggest that genetic variability in the ARNTL and CLOCK genes might be associated with risk for multiple sclerosis.

Imaging Finding of Multiple Endocrine Neoplasia Type 1: Case Report

International Nuclear Information System (INIS)

Yum, Tae Jun; Cho, Hee Woo

2012-01-01

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited syndrome with characteristic clinical and radiological manifestations. Many reports on MEN1 have been published; however, no cases of radiologically diagnosed MEN1 have been reported. Therefore, we report on a radiologically diagnosed case of MEN1 with clinical symptoms of gastroduodenal ulcer.

Multiple sclerosis

International Nuclear Information System (INIS)

Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

1986-01-01

Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

Lesion stiffness measured by shear-wave elastography: Preoperative predictor of the histologic underestimation of US-guided core needle breast biopsy.

Science.gov (United States)

Park, Ah Young; Son, Eun Ju; Kim, Jeong-Ah; Han, Kyunghwa; Youk, Ji Hyun

2015-12-01

To determine whether lesion stiffness measured by shear-wave elastography (SWE) can be used to predict the histologic underestimation of ultrasound (US)-guided 14-gauge core needle biopsy (CNB) for breast masses. This retrospective study enrolled 99 breast masses from 93 patients, including 40 high-risk lesions and 59 ductal carcinoma in situ (DCIS), which were diagnosed by US-guided 14-gauge CNB. SWE was performed for all breast masses to measure quantitative elasticity values before US-guided CNB. To identify the preoperative factors associated with histologic underestimation, patients' age, symptoms, lesion size, B-mode US findings, and quantitative SWE parameters were compared according to the histologic upgrade after surgery using the chi-square test, Fisher's exact test, or independent t-test. The independent factors for predicting histologic upgrade were evaluated using multivariate logistic regression analysis. The underestimation rate was 28.3% (28/99) in total, 25.0% (10/40) in high-risk lesions, and 30.5% (18/59) in DCIS. All elasticity values of the upgrade group were significantly higher than those of the non-upgrade group (PBreast lesion stiffness quantitatively measured by SWE could be helpful to predict the underestimation of malignancy in US-guided 14-gauge CNB. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Psychiatric disorders revealing multiple sclerosis after 20 years of evolvement

Directory of Open Access Journals (Sweden)

Aicha Slassi Sennou

2014-01-01

Full Text Available Previous research indicates that the onset of psychiatric disorders is sometimes associated with multiple sclerosis (MS evolving several years later. However, information on why this might occur, and on the outcomes of such patients, is still lacking. We aim to discuss these limitations with the current paper. We describe a 51-year-old female who demonstrated severe anxiety disorder and depression years before developing MS neurological symptoms. The patient was treated for these psychiatric disorders over 20 years. In the last 3 years of her treatment, the patient demonstrated a choreic-type of movement disorder in all her limbs. This disorder is consistent with relapsing-remitting MS. Clinical and magnetic resonance imaging (MRI examinations demonstrated aspects of MS, without MS being diagnosed conclusively. The visual evoked potential indicated a diagnosis of conduction abnormalities. The established diagnosis was slow relapsing MS. The patient underwent methylprednisolone bolus (1 g/day. This case-study suggests that health professionals should conduct a full neurological assessment when they find atypical psychiatric symptoms in a patient. This would make sure that patients receive a better standard of care, and thus experience a better quality of life.

Detection of Extramedullary Multiple Myeloma in Liver by FDG-PET/CT

International Nuclear Information System (INIS)

Kim, Daeweung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Choi, Keum Ha; Kim, Chang Guhn

2014-01-01

We present the case of a 42-year-old man with a painful mass lesion in the right shoulder that was detected by contrast-enhanced computed tomography (CT) and 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT. Excisional biopsy revealed infiltration of plasma cells with anaplastic features, consistent with solitary plasmacytoma (PC). Serum analysis showed elevation of serum free lambda light chain levels (27.78 mg/l), with an abnormally high kappa:lambda ratio (2.33) and high total proteins (10.4 g/dl). Serum protein electrophoresis revealed an M spike in the gamma-globulin region (56.1 %=5.8 g/dl). Subsequently, 18 F-FDG PET/CT revealed another hypermetabolic mass in the right lobe of the liver. CT-guided biopsy of the liver lesion revealed plasma cell myeloma, consistent with multiple myeloma. Multiple myeloma presenting as nodular liver masses is very rare in clinical practice. In a retrospective review of more than 2,000 patients, Talamo et al. reported only nine cases where there was nodular involvement of the liver by multiple myeloma. The organ most commonly involved was the liver, followed by pancreas, stomach, peritoneum with malignant ascites, colon, rectum, duodenum and ileum. Therefore, the literature published thus far has been limited to a few reports and case series. Among these reports, some had demonstrated the PET or PET/CT findings of nodular liver involvement of multiple myeloma. About 10 % of the solitary myelomas appeared as extramedullary PC or solitary PC of bone. In spite of the advances in therapy, the treatment of multiple myeloma is still palliative. However, solitary PC could be cured by resection or radiation therapy. Thus, differentiation between PC and multiple myeloma is essential in making a decision for the appropriate therapeutic regimen. 18 F-FDG PET/CT has the unique ability to detect and characterize malignant lesions in one single examination. Schirrmeister et al. reported that 18 F-FDG PET revealed

Caveolin-1 influences human influenza A virus (H1N1 multiplication in cell culture

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Hemgård Gun-Viol

2010-05-01

Full Text Available Abstract Background The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets. The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication. Results Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1 as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1 strains of swine origin circulating from spring 2009 on. The influence of Cav-1 on human influenza A/PR/8/34 (H1N1 virus replication was determined in inhibition and competition experiments. RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK, a cell line commonly used in basic influenza research as well as in virus vaccine production. To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search. Pull-down assays and co-immunoprecipitation experiments showed that caveolin-1 binds to M2. The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction. Conclusion As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents.

Resistance of the Extreme Halophile Halobacterium sp. NRC-1 to Multiple Stresses

International Nuclear Information System (INIS)

Gygli, Patrick E.; Prajapati, Surendra; DeVeaux, Linda C.; DasSarma, Shiladitya; DasSarma, Priya; Mestari, Mohammed Amine; Wells, Douglas P.

2009-01-01

The model Archaeon Halobacterium sp. NRC-1 is an extreme halophile known for its resistance to multiple stressors, including electron-beam and ultraviolet radiation. It is a well-developed system with a completely sequenced genome and extensive post-genomic tools for the study of a variety of biological processes. To further understand the mechanisms of Halobacterium's, radiation resistance, we previously reported the selection for multiple independent highly resistant mutants using repeated exposure to high doses of 18-20 MeV electrons using a medical S-band Linac. Molecular analysis of the transcriptional profile of several of these mutants revealed a single common change: upregulation of the rfa3 operon. These genes encode proteins homologous to the subunits of eukaryotic Replication Protein A (RPA), a DNA binding protein with major roles in DNA replication, recombination, and repair. This operon has also been implicated in a somewhat lesser role in resistance of wild type Halobacterium to ultraviolet radiation, suggesting common mechanisms for resistance. To further understand the mechanism of radiation resistance in the mutant strains, we measured the survival after exposure to both electron-beam and ultraviolet radiation, UV-A, B, and C All mutant strains showed increased resistance to electrons when compared with the parent. However, the mutant strains do not display increased UV resistance, and in one case is more sensitive than the parent strain. Thus, the protective role of increased RPA expression within a cell may be specific to the DNA damage caused by the different physical effects induced by high energy electron-beam radiation.

Monocyte chemoattractant protein-1 promoter -2518 polymorphism and susceptibility to vasculitis, rheumatoid arthritis, and multiple sclerosis: A meta-analysis.

Science.gov (United States)

Lee, Y H; Bae, S-C

2016-03-20

The purpose of this study was to examine whether the monocyte chemoattractant protein-1 (MCP-1) promoter -2518 A/G polymorphism (rs1024611) is associated with susceptibility to vasculitis, rheumatoid arthritis (RA), or multiple sclerosis (MS). A meta-analysis was conducted on the association between the MCP-1 -2518 A/G polymorphism and vasculitis, RA, and MS. Fourteen studies from 13 articles, including six on vasculitis, five on RA, and three on MS, consisting of 3,038 patients and 3,545 controls were available for the meta-analysis. The meta-analysis revealed no association between the MCP-1 -2518 G allele and vasculitis (odds ratio [OR] = 0.990, 95% confidence interval [CI] = 0.749-1.309, p = 0.943). Stratification by ethnicity indicated no association between the G allele of the MCP-1 -2518 A/G polymorphism and vasculitis in Asians and Caucasians. Meta-analysis by vasculitis type revealed an association between the GG+GA genotype of the MCP-1 -2518 A/G polymorphism and Behçet's disease (BD; OR = 1.349, 95% CI = 1.013-1.796, p = 0.040). However, sensitivity analysis showed that the association was not statistically significant after removing a study that was conducted in China (OR = 1.030, 95% CI = 0.667-1.590, p = 0.895), which indicated that the association was not statistically robust. The meta-analysis revealed no association between the MCP-1 -2518 G allele and RA (OR = 0.986, 95% CI = 0.890-1.093, p = 0.793) or MS (OR = 1.281, 95% CI = 0.802-2.046, p = 0.301). Our meta-analysis demonstrates that the MCP-1 -2518 A/G polymorphism is not associated with susceptibility to vasculitis, RA, or MS.

Logic programming reveals alteration of key transcription factors in multiple myeloma.

Science.gov (United States)

Miannay, Bertrand; Minvielle, Stéphane; Roux, Olivier; Drouin, Pierre; Avet-Loiseau, Hervé; Guérin-Charbonnel, Catherine; Gouraud, Wilfried; Attal, Michel; Facon, Thierry; Munshi, Nikhil C; Moreau, Philippe; Campion, Loïc; Magrangeas, Florence; Guziolowski, Carito

2017-08-23

Innovative approaches combining regulatory networks (RN) and genomic data are needed to extract biological information for a better understanding of diseases, such as cancer, by improving the identification of entities and thereby leading to potential new therapeutic avenues. In this study, we confronted an automatically generated RN with gene expression profiles (GEP) from a cohort of multiple myeloma (MM) patients and normal individuals using global reasoning on the RN causality to identify key-nodes. We modeled each patient by his or her GEP, the RN and the possible automatically detected repairs needed to establish a coherent flow of the information that explains the logic of the GEP. These repairs could represent cancer mutations leading to GEP variability. With this reasoning, unmeasured protein states can be inferred, and we can simulate the impact of a protein perturbation on the RN behavior to identify therapeutic targets. We showed that JUN/FOS and FOXM1 activities are altered in almost all MM patients and identified two survival markers for MM patients. Our results suggest that JUN/FOS-activation has a strong impact on the RN in view of the whole GEP, whereas FOXM1-activation could be an interesting way to perturb an MM subgroup identified by our method.

Gene array analysis of PD-1H overexpressing monocytes reveals a pro-inflammatory profile

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Preeti Bharaj

2018-02-01

Full Text Available We have previously reported that overexpression of Programmed Death -1 Homolog (PD-1H in human monocytes leads to activation and spontaneous secretion of multiple pro inflammatory cytokines. Here we evaluate changes in monocytes gene expression after enforced PD-1H expression by gene array. The results show that there are significant alterations in 51 potential candidate genes that relate to immune response, cell adhesion and metabolism. Genes corresponding to pro-inflammatory cytokines showed the highest upregulation, 7, 3.2, 3.0, 5.8, 4.4 and 3.1 fold upregulation of TNF-α, IL-1 β, IFN-α, γ, λ and IL-27 relative to vector control. The data are in agreement with cytometric bead array analysis showing induction of proinflammatory cytokines, IL-6, IL-1β and TNF-α by PD-1H. Other genes related to inflammation, include transglutaminase 2 (TG2, NF-κB (p65 and p50 and toll like receptors (TLR 3 and 4 were upregulated 5, 4.5 and 2.5 fold, respectively. Gene set enrichment analysis (GSEA also revealed that signaling pathways related to inflammatory response, such as NFκB, AT1R, PYK2, MAPK, RELA, TNFR1, MTOR and proteasomal degradation, were significantly upregulated in response to PD-1H overexpression. We validated the results utilizing a standard inflammatory sepsis model in humanized BLT mice, finding that PD-1H expression was highly correlated with proinflammatory cytokine production. We therefore conclude that PD-1H functions to enhance monocyte activation and the induction of a pro-inflammatory gene expression profile.

Multiple Object Permanence Tracking: Maintenance, Retrieval and Transformation of Dynamic Object Representations

OpenAIRE

Saiki, Jun

2008-01-01

Multiple object permanence tracking (MOPT) task revealed that our ability of maintaining and transforming multiple representations of complex feature-bound objects is limited to handle only 1-2 objects. Often reported capacity of 3-5 objects likely reflects memory for partial representations of objects and simple cases such as just color and their locations. Also, performance in multiple object tracking (MOT) task is likely mediated by spatiotemporal indices, not by feature-bound object repre...

Syndrome disintegration: Exome sequencing reveals that Fitzsimmons syndrome is a co-occurrence of multiple events.

Science.gov (United States)

Armour, Christine M; Smith, Amanda; Hartley, Taila; Chardon, Jodi Warman; Sawyer, Sarah; Schwartzentruber, Jeremy; Hennekam, Raoul; Majewski, Jacek; Bulman, Dennis E; Suri, Mohnish; Boycott, Kym M

2016-07-01

In 1987 Fitzsimmons and Guilbert described identical male twins with progressive spastic paraplegia, brachydactyly with cone shaped epiphyses, short stature, dysarthria, and "low-normal" intelligence. In subsequent years, four other patients, including one set of female identical twins, a single female child, and a single male individual were described with the same features, and the eponym Fitzsimmons syndrome was adopted (OMIM #270710). We performed exome analysis of the patient described in 2009, and one of the original twins from 1987, the only patients available from the literature. No single genetic etiology exists that explains Fitzsimmons syndrome; however, multiple different genetic causes were identified. Specifically, the twins described by Fitzsimmons had heterozygous mutations in the SACS gene, the gene responsible for autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS), as well as a heterozygous mutation in the TRPS1, the gene responsible in Trichorhinophalangeal syndrome type 1 (TRPS1 type 1) which includes brachydactyly as a feature. A TBL1XR1 mutation was identified in the patient described in 2009 as contributing to his cognitive impairment and autistic features with no genetic cause identified for his spasticity or brachydactyly. The findings show that these individuals have multiple different etiologies giving rise to a similar phenotype, and that "Fitzsimmons syndrome" is in fact not one single syndrome. Over time, we anticipate that continued careful phenotyping with concomitant genome-wide analysis will continue to identify the causes of many rare syndromes, but it will also highlight that previously delineated clinical entities are, in fact, not syndromes at all. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multiple social identifications and adolescents' self-esteem.

Science.gov (United States)

Benish-Weisman, Maya; Daniel, Ella; Schiefer, David; Möllering, Anna; Knafo-Noam, Ariel

2015-10-01

The research examined the relationship between multiple social identifications and self-esteem. Early adolescents (M = 11.4, SD = .95) and mid-adolescents (M = 15.9, SD = 1.18) from Germany and Israel (n = 2337) were studied. Respondents described their social identification as students, family members, and as members of the majority national group and reported self-esteem. A longitudinal, cross-sectional and cross-cultural design revealed, as predicted, multiple social identifications related positively to self-esteem concurrently; they also related positively to self-esteem longitudinally over the course of a year. Moreover, multiple social identifications were found to be antecedent to self-esteem, not vice versa. Finally, multiple social identifications were found to decrease over time. The article discusses the contribution of multiple social identifications to self-esteem at different ages and in various contexts. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

Science.gov (United States)

Pei, Xin-Yan; Dai, Yun; Felthousen, Jessica; Chen, Shuang; Takabatake, Yukie; Zhou, Liang; Youssefian, Leena E; Sanderson, Michael W; Bodie, Wesley W; Kramer, Lora B; Orlowski, Robert Z; Grant, Steven

2014-01-01

The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

Directory of Open Access Journals (Sweden)

Xin-Yan Pei

Full Text Available The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

Corrected multiple upsets and bit reversals for improved 1-s resolution measurements

International Nuclear Information System (INIS)

Brucker, G.J.; Stassinopoulos, E.G.; Stauffer, C.A.

1994-01-01

Previous work has studied the generation of single and multiple errors in control and irradiated static RAM samples (Harris 6504RH) which were exposed to heavy ions for relatively long intervals of time (minute), and read out only after the beam was shut off. The present investigation involved storing 4k x 1 bit maps every second during 1 min ion exposures at low flux rates of 10 3 ions/cm 2 -s in order to reduce the chance of two sequential ions upsetting adjacent bits. The data were analyzed for the presence of adjacent upset bit locations in the physical memory plane, which were previously defined to constitute multiple upsets. Improvement in the time resolution of these measurements has provided more accurate estimates of multiple upsets. The results indicate that the percentage of multiples decreased from a high of 17% in the previous experiment to less than 1% for this new experimental technique. Consecutive double and triple upsets (reversals of bits) were detected. These were caused by sequential ions hitting the same bit, with one or two reversals of state occurring in a 1-min run. In addition to these results, a status review for these same parts covering 3.5 years of imprint damage recovery is also presented

MULTIPLE PROJECTIONS SYSTEM (MPS) - USER'S MANUAL VERSION 1.0

Science.gov (United States)

The report is a user's manual for version 1.0 of the Multiple Projections Systems (MPS), a computer system that can perform "what if" scenario analysis and report the final results (i.e., Rate of Further Progress - ROP - inventories) to EPA (i.e., the Aerometric Information Retri...

Excitation density dependence of the photoluminescence from Cd{sub x}Hg{sub 1-x}Te multiple quantum wells

Energy Technology Data Exchange (ETDEWEB)

Tonheim, C R; Selvig, E; Nicolas, S; Breivik, M; Haakenaasen, R [Norwegian Defence Research Establishment, PO Box 25, N-2027 Kjeller (Norway); Gunnaes, A E [Department of Physics, University of Oslo, Boks 1048 Blindern, N-0316 Oslo (Norway)], E-mail: celin.tonheim@ffi.no

2008-03-15

A study of the photoluminescence from a four-period Cd{sub x}Hg{sub 1-x}Te multiple quantum well structure at 11 K as a function of excitation density is presented. High-resolution X-ray diffraction and transmission electron microscopy revealed that the quantum well structure is of high quality. This was supported by the narrow photoluminescence peak originating in the ground state electron - heavy hole transition, with a full width at half maximum of only 7.4 meV for an excitation density of 1.3 W/cm{sup 2}. When the excitation density was increased from 1.3 to 23.4 W/cm{sup 2}, the peak position was shifted toward higher energy by 2.6 meV and the full width at half maximum increased from 7.4 to 10.9 meV.

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Knudsen, L; Jensen, K

1994-01-01

In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

Directory of Open Access Journals (Sweden)

Erdas Enrico

2012-12-01

Full Text Available Abstract Background Diagnosis of multiple endocrine neoplasia type 1 (MEN1 is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. Case presentation The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21. The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well

Transmission of single and multiple viral variants in primary HIV-1 subtype C infection.

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Vladimir Novitsky

2011-02-01

Full Text Available To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity of transmitted HIV's, recently developed approaches for analysis of viral evolution in acute HIV-1 infection [1,2] were applied. Specifically, phylogenetic reconstruction, inter- and intra-patient distribution of maximum and mean genetic distances, analysis of Poisson fitness, shape of highlighter plots, recombination analysis, and estimation of time to the most recent common ancestor (tMRCA were utilized for resolving multiplicity of HIV-1 transmission in a set of viral quasispecies collected within 50 days post-seroconversion (p/s in 25 HIV-infected individuals with estimated time of seroconversion. The decision on multiplicity of HIV infection was made based on the model's fit with, or failure to explain, the observed extent of viral sequence heterogeneity. The initial analysis was based on phylogeny, inter-patient distribution of maximum and mean distances, and Poisson fitness, and was able to resolve multiplicity of HIV transmission in 20 of 25 (80% cases. Additional analysis involved distribution of individual viral distances, highlighter plots, recombination analysis, and estimation of tMRCA, and resolved 4 of the 5 remaining cases. Overall, transmission of a single viral variant was identified in 16 of 25 (64% cases, and transmission of multiple variants was evident in 8 of 25 (32% cases. In one case multiplicity of HIV-1 transmission could not be determined. In primary HIV-1 subtype C infection, samples collected within 50 days p/s and analyzed by a single-genome amplification/sequencing technique can provide reliable identification of transmission multiplicity in 24 of 25 (96% cases. Observed transmission frequency of a single viral variant and multiple viral variants were within the ranges of 64% to 68%, and 32% to 36%, respectively.

Revealing the uncultivated majority: combining DNA stable-isotope probing, multiple displacement amplification and metagenomic analyses of uncultivated Methylocystis in acidic peatlands.

Science.gov (United States)

Chen, Yin; Dumont, Marc G; Neufeld, Josh D; Bodrossy, Levente; Stralis-Pavese, Nancy; McNamara, Niall P; Ostle, Nick; Briones, Maria J I; Murrell, J Colin

2008-10-01

Peatlands represent an enormous carbon reservoir and have a potential impact on the global climate because of the active methanogenesis and methanotrophy in these soils. Uncultivated methanotrophs from seven European peatlands were studied using a combination of molecular methods. Screening for methanotroph diversity using a particulate methane monooxygenase-based diagnostic gene array revealed that Methylocystis-related species were dominant in six of the seven peatlands studied. The abundance and methane oxidation activity of Methylocystis spp. were further confirmed by DNA stable-isotope probing analysis of a sample taken from the Moor House peatland (England). After ultracentrifugation, (13)C-labelled DNA, containing genomic DNA of these Methylocystis spp., was separated from (12)C DNA and subjected to multiple displacement amplification (MDA) to generate sufficient DNA for the preparation of a fosmid metagenomic library. Potential bias of MDA was detected by fingerprint analysis of 16S rRNA using denaturing gradient gel electrophoresis for low-template amplification (0.01 ng template). Sufficient template (1-5 ng) was used in MDA to circumvent this bias and chimeric artefacts were minimized by using an enzymatic treatment of MDA-generated DNA with S1 nuclease and DNA polymerase I. Screening of the metagenomic library revealed one fosmid containing methanol dehydrogenase and two fosmids containing 16S rRNA genes from these Methylocystis-related species as well as one fosmid containing a 16S rRNA gene related to that of Methylocella/Methylocapsa. Sequencing of the 14 kb methanol dehydrogenase-containing fosmid allowed the assembly of a gene cluster encoding polypeptides involved in bacterial methanol utilization (mxaFJGIRSAC). This combination of DNA stable-isotope probing, MDA and metagenomics provided access to genomic information of a relatively large DNA fragment of these thus far uncultivated, predominant and active methanotrophs in peatland soil.

Detection of Extramedullary Multiple Myeloma in Liver by FDG-PET/CT

Energy Technology Data Exchange (ETDEWEB)

Kim, Daeweung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Choi, Keum Ha; Kim, Chang Guhn [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

2014-06-15

We present the case of a 42-year-old man with a painful mass lesion in the right shoulder that was detected by contrast-enhanced computed tomography (CT) and {sup 18}F-fluoro-2-deoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/CT. Excisional biopsy revealed infiltration of plasma cells with anaplastic features, consistent with solitary plasmacytoma (PC). Serum analysis showed elevation of serum free lambda light chain levels (27.78 mg/l), with an abnormally high kappa:lambda ratio (2.33) and high total proteins (10.4 g/dl). Serum protein electrophoresis revealed an M spike in the gamma-globulin region (56.1 %=5.8 g/dl). Subsequently, {sup 18}F-FDG PET/CT revealed another hypermetabolic mass in the right lobe of the liver. CT-guided biopsy of the liver lesion revealed plasma cell myeloma, consistent with multiple myeloma. Multiple myeloma presenting as nodular liver masses is very rare in clinical practice. In a retrospective review of more than 2,000 patients, Talamo et al. reported only nine cases where there was nodular involvement of the liver by multiple myeloma. The organ most commonly involved was the liver, followed by pancreas, stomach, peritoneum with malignant ascites, colon, rectum, duodenum and ileum. Therefore, the literature published thus far has been limited to a few reports and case series. Among these reports, some had demonstrated the PET or PET/CT findings of nodular liver involvement of multiple myeloma. About 10 % of the solitary myelomas appeared as extramedullary PC or solitary PC of bone. In spite of the advances in therapy, the treatment of multiple myeloma is still palliative. However, solitary PC could be cured by resection or radiation therapy. Thus, differentiation between PC and multiple myeloma is essential in making a decision for the appropriate therapeutic regimen. {sup 18}F-FDG PET/CT has the unique ability to detect and characterize malignant lesions in one single examination. Schirrmeister et al. reported that

A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization.

Science.gov (United States)

Jao, Li-En; Appel, Bruce; Wente, Susan R

2012-04-01

In humans, GLE1 is mutated in lethal congenital contracture syndrome 1 (LCCS1) leading to prenatal death of all affected fetuses. Although the molecular roles of Gle1 in nuclear mRNA export and translation have been documented, no animal models for this disease have been reported. To elucidate the function of Gle1 in vertebrate development, we used the zebrafish (Danio rerio) model system. gle1 mRNA is maternally deposited and widely expressed. Altering Gle1 using an insertional mutant or antisense morpholinos results in multiple defects, including immobility, small eyes, diminished pharyngeal arches, curved body axis, edema, underdeveloped intestine and cell death in the central nervous system. These phenotypes parallel those observed in LCCS1 human fetuses. Gle1 depletion also results in reduction of motoneurons and aberrant arborization of motor axons. Unexpectedly, the motoneuron deficiency results from apoptosis of neural precursors, not of differentiated motoneurons. Mosaic analyses further indicate that Gle1 activity is required extrinsically in the environment for normal motor axon arborization. Importantly, the zebrafish phenotypes caused by Gle1 deficiency are only rescued by expressing wild-type human GLE1 and not by the disease-linked Fin(Major) mutant form of GLE1. Together, our studies provide the first functional characterization of Gle1 in vertebrate development and reveal its essential role in actively dividing cells. We propose that defective GLE1 function in human LCCS1 results in both neurogenic and non-neurogenic defects linked to the apoptosis of proliferative organ precursors.

Cytologic diagnosis of primary peritoneal high grade serous carcinoma in a man.

Science.gov (United States)

Umphress, Brandon; Philip, John; Zhang, Yaxia; Lin, Xiaoqi

2018-04-16

Primary peritoneal serous carcinoma (PPSC) is a rare neoplasm histologically indistinguishable from ovarian serous carcinoma primarily occurring in the female population. To date, extremely rare cases of PPSC have been reported in men; however, diagnosis by cytology has yet to be described. Here we present the clinical, radiographic, cytomorphologic, histologic and immunohistochemical (IHC) findings of a high-grade (HG) PPSC in a 70-year-old man with a history of prostatic adenocarcinoma. Core needle biopsy (CNB) touch preparation smears showed pleomorphic, round, columnar and polygonal epithelioid cells present singly or arranged in loosely cohesive three-dimensional clusters. The tumor cells are characterized by enlarged nuclei containing prominent nucleoli, and variable scant to moderate, slightly dense cytoplasm. Scattered cells contained cytoplasmic vacuoles. Examination of CNB revealed an infiltrating tumor in sheets with focal papillary configuration. Tumor cells were morphologically consistent with HG carcinoma. IHC studies demonstrated diffuse positivity for CK7, PAX-8, ER, WT1, p53, p16 and BerEP4 with focal/weak staining for calretinin and CK5/6, which supporting the diagnosis of HG PPSC. The patient was treated with 6 cycles of carboplatin and paclitaxel with near resolution of the mass at 10 month follow-up. To the best of our knowledge, this is the first reported case in the literature of PPSC in a man diagnosed by cytology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Pleurobemini (Bivalvia: Unionida) revisited: Molecular species delineation using a mitochondrial DNA gene reveals multiple conspecifics and undescribed species

Science.gov (United States)

Inoue, Kentaro; Hayes, David M.; Harris, John L.; Johnson, Nathan A.; Morrison, Cheryl L.; Eackles, Michael S.; King, Tim; Jones, Jess W.; Hallerman, Eric M.; Christian, Alan D.; Randklev, Charles R.

2018-01-01

The Pleurobemini (Bivalvia: Unionida) represent approximately one-third of freshwater mussel diversity in North America. Species identification within this group is challenging due to morphological convergence and phenotypic plasticity. Accurate species identification, including characterization of currently unrecognized taxa, is required to develop effective conservation strategies because many species in the group are imperiled. We examined 573 cox1 sequences from 110 currently recognized species (including 13 Fusconaia and 21 Pleurobema species) to understand phylogenetic relationships among pleurobemine species (mainly Fusconaia and Pleurobema) and to delineate species boundaries. The results of phylogenetic analyses showed no geographic structure within widespread species and illustrated a close relationship between Elliptio lanceolata and Parvaspina collina. Constraint tests supported monophyly of the genera Fusconaia and Pleurobema, including the subgenus P. (Sintoxia). Furthermore, results revealed multiple conspecifics, including P. hanleyianum and P. troschelianum, P. chattanoogaense and P. decisum, P. clava and P. oviforme, P. rubrum and P. sintoxia, F. askewi and F. lananensis, and F. cerina and F. flava. Species delimitation analyses identified three currently unrecognized taxa (two in Fusconaia and one in Pleurobema). Further investigation using additional genetic markers and other lines of evidence (e.g., morphology, life history, ecology) are necessary before any taxonomic changes are formalized.

Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum.

Science.gov (United States)

Kidwell, Chelsea U; Su, Chen-Ying; Hibi, Masahiko; Moens, Cecilia B

2018-06-01

A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons. Surprisingly, the two genes are expressed in non-overlapping granule cell progenitor populations, indicating that fish use duplicate atoh1 genes to generate granule cell diversity that is not detected in mammals. Finally, live imaging of granule cell migration in wildtype and atoh1c mutant embryos reveals that while atoh1c is not required for granule cell specification per se, it is required for granule cells to delaminate and migrate away from the rhombic lip. Copyright © 2018 Elsevier Inc. All rights reserved.

Ethics committees in Italy--a time for change?

Science.gov (United States)

Wray, E

2000-01-01

The Comitato Nazionale per la Bioetica (CNB) in Italy has recently produced an unprecedented discussion document on the state of ethics committees in Italy, with an invitation to interested parties to comment on proposed changes to their fundamental structure. After this consultation, and taking note of relevant official publications and the most recent national and international literature on the subject, the CNB proposes to produce a final, definitive document that will consider options for the future development of such committees.

Immobilization of biogenic Pd(0) in anaerobic granular sludge for the biotransformation of recalcitrant halogenated pollutants in UASB reactors.

Science.gov (United States)

Pat-Espadas, Aurora M; Razo-Flores, Elías; Rangel-Mendez, J Rene; Ascacio-Valdes, Juan A; Aguilar, Cristobal N; Cervantes, Francisco J

2015-10-19

The capacity of anaerobic granular sludge to reduce Pd(II), using ethanol as electron donor, in an upflow anaerobic sludge blanket (UASB) reactor was demonstrated. Results confirmed complete reduction of Pd(II) and immobilization as Pd(0) in the granular sludge. The Pd-enriched sludge was further evaluated regarding biotransformation of two recalcitrant halogenated pollutants: 3-chloro-nitrobenzene (3-CNB) and iopromide (IOP) in batch and continuous operation in UASB reactors. The superior removal capacity of the Pd-enriched biomass when compared with the control (not exposed to Pd) was demonstrated in both cases. Results revealed 80 % of IOP removal efficiency after 100 h of incubation in batch experiments performed with Pd-enriched biomass whereas only 28 % of removal efficiency was achieved in incubations with biomass lacking Pd. The UASB reactor operated with the Pd-enriched biomass achieved 81 ± 9.5 % removal efficiency of IOP and only 61 ± 8.3 % occurred in the control reactor lacking Pd. Regarding 3-CNB, it was demonstrated that biogenic Pd(0) promoted both nitro-reduction and dehalogenation resulting in the complete conversion of 3-CNB to aniline while in the control experiment only nitro-reduction was documented. The complete biotransformation pathway of both contaminants was proposed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis evidencing a higher degree of nitro-reduction and dehalogenation of both contaminants in the experiments with Pd-enriched anaerobic sludge as compared with the control. A biotechnological process is proposed to recover Pd(II) from industrial streams and to immobilize it in anaerobic granular sludge. The Pd-enriched biomass is also proposed as a biocatalyst to achieve the biotransformation of recalcitrant compounds in UASB reactors.

Cell-Specific PEAR1 Methylation Studies Reveal a Locus that Coordinates Expression of Multiple Genes

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Benedetta Izzi

2018-04-01

Full Text Available Chromosomal interactions connect distant enhancers and promoters on the same chromosome, activating or repressing gene expression. PEAR1 encodes the Platelet-Endothelial Aggregation Receptor 1, a contact receptor involved in platelet function and megakaryocyte and endothelial cell proliferation. PEAR1 expression during megakaryocyte differentiation is controlled by DNA methylation at its first CpG island. We identified a PEAR1 cell-specific methylation sensitive region in endothelial cells and megakaryocytes that showed strong chromosomal interactions with ISGL20L2, RRNAD1, MRLP24, HDGF and PRCC, using available promoter capture Hi-C datasets. These genes are involved in ribosome processing, protein synthesis, cell cycle and cell proliferation. We next studied the methylation and expression profile of these five genes in Human Umbilical Vein Endothelial Cells (HUVECs and megakaryocyte precursors. While cell-specific PEAR1 methylation corresponded to variability in expression for four out of five genes, no methylation change was observed in their promoter regions across cell types. Our data suggest that PEAR1 cell-type specific methylation changes may control long distance interactions with other genes. Further studies are needed to show whether such interaction data might be relevant for the genome-wide association data that showed a role for non-coding PEAR1 variants in the same region and platelet function, platelet count and cardiovascular risk.

Neurocutaneous spectrum of multiple endocrine neoplasia-1

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Shireen Furtado

2012-01-01

Full Text Available Multiple endocrine neoplasia type I or Wermer syndrome is characterized by primary hyperparathyroidism, enteropancreatic endocrine tumor, and a pituitary pathology. A 35-year-old male presented with visual field defects, hyperprolactinemia, and hypogonadism. He also had multiple infraumbilical skin-colored nodules. A syndromal association of Wermer syndrome was derived using the dermal, pituitary, parathyroid, and gastrointestinal hormonal manifestations of the tumor. The radiological and histological findings of lesion which underwent biopsy are discussed. The presence of collagenomas, lipomas, and hypopigmented macules in a patient with neuroendocrine symptoms should raise the suspicion of an underlying multiple endocrine neoplasia.

Meningioma growth and interferon beta-1b treated multiple sclerosis: coincidence or relationship?

International Nuclear Information System (INIS)

Drevelegas, A.; Xinou, E.; Karacostas, D.; Parissis, D.; Milonas, I.; Karkavelas, G.

2005-01-01

Although the coincidence of multiple sclerosis (MS) and central nervous system (CNS) tumors has been reported in over 30 cases in English literature, meningioma growth was associated with interferon-beta (INF-b) treated MS only in two of them. We report the case of a 19-year-old woman with clinically possible, laboratory supported MS, and a concomitant right intraventricular tumor with magnetic resonance imaging (MRI) characteristics consistent with meningioma (similar signal with grey matter on T1 and T2-weighted images and homogenous, intense enhancement). Two years after initiation of INF-b treatment, follow-up brain MRI revealed enlargement of the intraventricular mass and relative increase in the number of white matter lesions without significant clinical deterioration. She underwent almost total resection of the mass and histology confirmed the diagnosis of papillary meningioma. Based on the immunohistochemistry results, we speculate that INF-b resulted in meningioma growth by enhancing platelet derived growth factor (PDGF) receptors or/and down-regulating transforming growth factor receptors on the tumor itself. (orig.)

Meningioma growth and interferon beta-1b treated multiple sclerosis: coincidence or relationship?

Energy Technology Data Exchange (ETDEWEB)

Drevelegas, A.; Xinou, E. [AHEPA University Hospital, Aristotele University School of Medicine, Department of Radiology, Thessaloniki (Greece); Karacostas, D.; Parissis, D.; Milonas, I. [AHEPA University Hospital, Aristotele University School of Medicine, B' Department of Neurology, Thessaloniki (Greece); Karkavelas, G. [AHEPA University Hospital, Aristotele University School of Medicine, Laboratory of Pathology, Thessaloniki (Greece)

2005-07-01

Although the coincidence of multiple sclerosis (MS) and central nervous system (CNS) tumors has been reported in over 30 cases in English literature, meningioma growth was associated with interferon-beta (INF-b) treated MS only in two of them. We report the case of a 19-year-old woman with clinically possible, laboratory supported MS, and a concomitant right intraventricular tumor with magnetic resonance imaging (MRI) characteristics consistent with meningioma (similar signal with grey matter on T1 and T2-weighted images and homogenous, intense enhancement). Two years after initiation of INF-b treatment, follow-up brain MRI revealed enlargement of the intraventricular mass and relative increase in the number of white matter lesions without significant clinical deterioration. She underwent almost total resection of the mass and histology confirmed the diagnosis of papillary meningioma. Based on the immunohistochemistry results, we speculate that INF-b resulted in meningioma growth by enhancing platelet derived growth factor (PDGF) receptors or/and down-regulating transforming growth factor receptors on the tumor itself. (orig.)

Contrast-Enhanced Ultrasound Improves the Pathological Outcomes of US-Guided Core Needle Biopsy That Targets the Viable Area of Anterior Mediastinal Masses

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Jian-hua Zhou

2018-01-01

Full Text Available Based on the option that ultrasound-guided core needle biopsy (US-CNB of the enhanced portion of anterior mediastinal masses (AMMs identified by contrast-enhanced ultrasound (CEUS would harvest viable tissue and benefit the histological diagnoses, a retrospective study was performed to elucidate the correlation between the prebiopsy CEUS and diagnostic yield of AMMs and found that CEUS potentially improved the diagnostic yield of AMMs compared with conventional US with a significant increase in the cellularity of samples. Furthermore, the marginal blood flow signals and absence of necrosis can predict the diagnostic yield of AMM. It was concluded that US-CNB of the viable part of AMMs, as verified by CEUS, was able to harvest sufficient tissue with more cellularity that could be used for ancillary studies and improve the diagnostic yield. And CEUS was recommended to those patients with AMMs undergoing repeated US-CNB, with the absence of marginal blood signals or presence of necrosis.

Critical parameters for the molecular beam epitaxial growth of 1.55 μm (Ga,In)(N,As) multiple quantum wells

International Nuclear Information System (INIS)

Ishikawa, Fumitaro; Luna, Esperanza; Trampert, Achim; Ploog, Klaus H.

2006-01-01

The authors discuss the effect of substrate temperature and As beam equivalent pressure (BEP) on the molecular beam epitaxial growth of (Ga,In)(N,As) multiple quantum wells (MQWs). Transmission electron microscopy studies reveal that a low substrate temperature essentially prevents composition modulations. Secondary ion mass spectrometry results indicate that a low As BEP reduces the incorporation competition of group V elements. The low substrate temperature and low As BEP growth condition leads to (Ga,In)(N,As) MQWs containing more than 4% N preserving good structural and optical properties, and hence demonstrating 1.55 μm photoluminescence emission at room temperature

Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

International Nuclear Information System (INIS)

Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

1986-01-01

Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [ 3 H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause

Finding Multiple Peaks Signal in Fast Beam Conditions Monitor (BCM1F)

CERN Document Server

Bin Ab Maalek, Abu Ubaidah Amir; CERN. Geneva. EP Department

2017-01-01

Fast Beam Conditions Monitor (BCM1F) is diamond and silicon sensors based luminometer of CMS detector. The methods of finding multiple peaks signal in BCM1F is shown. Multiple peaks signal found at signal with width between 60 ns - 300 ns. Double peaks are counted as single hit in the constant threshold analysis and leads to underestimation in the luminosity. Therefore it should be estimated for different filling schemes and sensor types. The percentage of long width pulse in different sensor for different fill are calculated. About 30 \\% long width pulse found in sCVD sensor, 12 \\% in pCVD and no more than 1 \\% for silicon sensor.

Biosensor reveals multiple sources for mitochondrial NAD⁺.

Science.gov (United States)

Cambronne, Xiaolu A; Stewart, Melissa L; Kim, DongHo; Jones-Brunette, Amber M; Morgan, Rory K; Farrens, David L; Cohen, Michael S; Goodman, Richard H

2016-06-17

Nicotinamide adenine dinucleotide (NAD(+)) is an essential substrate for sirtuins and poly(adenosine diphosphate-ribose) polymerases (PARPs), which are NAD(+)-consuming enzymes localized in the nucleus, cytosol, and mitochondria. Fluctuations in NAD(+) concentrations within these subcellular compartments are thought to regulate the activity of NAD(+)-consuming enzymes; however, the challenge in measuring compartmentalized NAD(+) in cells has precluded direct evidence for this type of regulation. We describe the development of a genetically encoded fluorescent biosensor for directly monitoring free NAD(+) concentrations in subcellular compartments. We found that the concentrations of free NAD(+) in the nucleus, cytoplasm, and mitochondria approximate the Michaelis constants for sirtuins and PARPs in their respective compartments. Systematic depletion of enzymes that catalyze the final step of NAD(+) biosynthesis revealed cell-specific mechanisms for maintaining mitochondrial NAD(+) concentrations. Copyright © 2016, American Association for the Advancement of Science.

Primary bone lymphoma with multiple vertebral involvement

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Showkat Hussain Dar

2013-01-01

Full Text Available A 20-year-old student presented with 2 months history of fever and night sweats, 15 days history of low backache, progressive weakness of both limbs of 7 days duration, and urinary retention for last 24 h. Examination revealed a sensory level at D 10 dermatome and grade two power in both the lower limbs with absent reflexes. Examination of spine revealed a knuckle at T8 level, which was tender on palpation. MRI spine showed erosion of D11-12 and L1 in vertebral bodies with destruction of left pedicles, transverse processes and lamina, and a prominent psoas abscess. Post gadolinium study revealed ring-enhancing lesions in the D11-12 and L1 vertebrae as well as the dural sac. Fine needle aspiration cytology (FNAC and bone biopsy demonstrated a non-Hodgkin′s lymphoma (NHL, large cell high-grade of the spine (primary, which as per age is the youngest case of NHL ever reported in literature with multiple vertebral involvement.

47 CFR 1.735 - Copies; service; separate filings against multiple defendants.

Science.gov (United States)

2010-10-01

... overnight delivery service such as, or comparable to, the US Postal Service Express Mail, United Parcel... 47 Telecommunication 1 2010-10-01 2010-10-01 false Copies; service; separate filings against... Complaints § 1.735 Copies; service; separate filings against multiple defendants. (a) Complaints may...

Nodular fasciitis of the face diagnosed by US-guided core needle biopsy: a case report

International Nuclear Information System (INIS)

Lee, Sang Kwon; Kwon, Sun Young

2006-01-01

We report here on a case of nodular fasciitis (NF) that was diagnosed by ultrasonography (US)-guided core needle biopsy in a 31-year-old man, and we include the US and computed tomographic (CT) findings and the histopathologic findings at US-guided core needle biopsy (CNB). We suggest that high-resolution US is useful for the detailed evaluation of NF in the superficial regions, such as the face, and US-guided CNB is useful for the definitive histologic diagnosis of NF without causing scarring

EХPERIENCE IN INTERFERON β-1A USE FOR TREATMENT OF MULTIPLE SCLEROSIS IN CHILDREN

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L. M. Kuzenkova

2013-01-01

Full Text Available Aim: to evaluate the impact of subcutaneous interferon β-1a on matrix metalloproteinases 3, 8, 9 (MMP, cytokines (tumor necrosis factor α — TNF α, and transforming growth factor β1 — TGF β1 levels in serum of children with relapsing-remitting multiple sclerosis. Patients and methods: the results of treatment of 32 patients with relapsing-remitting multiple sclerosis aged 12–18 years (22 girls and 10 boys were analyzed. Treatment efficacy was assessed by the number of relapsing-remitting multiple sclerosis exacerbations during 12 months, MRI data, MMP and cytokines dynamics in serum. Results: statistical evidence acquired for MMPs, their tissue inhibitor and cytokines levels decrease (p < 0,005 in patients receiving therapy with subcutaneous INF β-1a. Conclusions: subcutaneous interferon β-1а is highly efficient in treatment of relapsing-remitting multiple sclerosis in children and adolescents.

Crystallization and preliminary X-ray crystallographic characterization of a cyclic nucleotide-binding homology domain from the mouse EAG potassium channel

International Nuclear Information System (INIS)

Marques-Carvalho, Maria João; Morais-Cabral, João Henrique

2012-01-01

The crystallization conditions and preliminary crystal characterization of the cytoplasmic cyclic nucleotide-binding homology domain from the mouse EAG potassium channel are reported. The members of the family of voltage-gated KCNH potassium channels play important roles in cardiac and neuronal repolarization, tumour proliferation and hormone secretion. These channels have a C-terminal cytoplasmic domain which is homologous to cyclic nucleotide-binding domains (CNB-homology domains), but it has been demonstrated that channel function is not affected by cyclic nucleotides and that the domain does not bind nucleotides in vitro. Here, the crystallization and preliminary crystallographic analysis of a CNB-homology domain from a member of the KCNH family, the mouse EAG channel, is reported. X-ray diffraction data were collected to 2.2 Å resolution and the crystal belonged to the hexagonal space group P3 1 21

EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

International Nuclear Information System (INIS)

Huang, Er-Wen; Xue, Sheng-Jiang; Li, Xiao-Yan; Xu, Suo-Wen; Cheng, Jian-Ding; Zheng, Jin-Xiang; Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong; Li, Jie; Liu, Chao

2014-01-01

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

Energy Technology Data Exchange (ETDEWEB)

Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

2014-05-02

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

(1)H NMR-based metabonomics revealed protective effect of Naodesheng bioactive extract on ischemic stroke rats.

Science.gov (United States)

Luo, Lan; Zhen, Lifeng; Xu, Yatao; Yang, Yongxia; Feng, Suxiang; Wang, Shumei; Liang, Shengwang

2016-06-20

Stroke is a leading cause of death and disability in the world. However, current therapies are limited. Naodesheng, a widely used traditional Chinese medicine prescription, has shown a good clinical curative effect on ischemic stroke. Also, Naodesheng has been suggested to have neuroprotective effect on focal cerebral ischemia rats, but the underlying molecular mechanism remains unclear. The present study was designed to evaluate the effect of Naodesheng bioactive extract on the metabolic changes in brain tissue, plasma and urine induced by cerebral ischemia perfusion injury, and explore the possible metabolic mechanisms by using a (1)H NMR-based metabonomics approach. A middle cerebral artery occlusion rat model was established and confirmed by the experiments of neurobehavioral abnormality evaluation, brain tissue TTC staining and pathological examination. The metabolic changes in brain tissue, plasma and urine were then assessed by a (1)H NMR technique combined with multivariate statistical analysis method. These NMR data showed that cerebral ischemia reperfusion induced great metabolic disorders in brain tissue, plasma and urine metabolisms. However, Naodesheng bioactive extract could reverse most of the imbalanced metabolites. Meanwhile, it was found that both the medium and high dosages of Naodesheng bioactive extract were more effective on the metabolic changes than the low dosage, consistent with histopathological assessments. These results revealed that Naodesheng had protective effect on ischemic stroke rats and the underlying mechanisms involved multiple metabolic pathways, including energy metabolism, amino acid metabolism, oxidative stress and inflammatory injury. The present study could provide evidence that metabonomics revealed its capacity to evaluate the holistic efficacy of traditional Chinese medicine and explore the underlying mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Crystal structure of human importin-α1 (Rch1, revealing a potential autoinhibition mode involving homodimerization.

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Hideyuki Miyatake

Full Text Available In this study, we determined the crystal structure of N-terminal importin-β-binding domain (IBB-truncated human importin-α1 (ΔIBB-h-importin-α1 at 2.63 Å resolution. The crystal structure of ΔIBB-h-importin-α1 reveals a novel closed homodimer. The homodimer exists in an autoinhibited state in which both the major and minor nuclear localization signal (NLS binding sites are completely buried in the homodimerization interface, an arrangement that restricts NLS binding. Analytical ultracentrifugation studies revealed that ΔIBB-h-importin-α1 is in equilibrium between monomers and dimers and that NLS peptides shifted the equilibrium toward the monomer side. This finding suggests that the NLS binding sites are also involved in the dimer interface in solution. These results show that when the IBB domain dissociates from the internal NLS binding sites, e.g., by binding to importin-β, homodimerization possibly occurs as an autoinhibition state.

TEACHING MULTIPLICATION OF NUMBERS FROM 1 TO 10 TO STKIP SURYA STUDENTS USING MATEMATIKA GASING

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Josephine Kusuma

2014-01-01

Full Text Available Multiplication of numbers from 1 to 10 is very important as it provides the basis for learning multiplication of other larger numbers as well as other related mathematical operations. How do students learn multiplication? Usually students just memorize the results of multiplication. This is often performed without a complete comprehension of the concept of multiplication. This study aimed to discuss how to teach multiplication of numbers from 1 to 10 to STKIP Surya students using Matematika GASING. GASING stands for Gampang, ASyIk dan menyenaNGkan which is translated as easy, fun and enjoyable. The materials are taught according to its unique way of teaching mathematics which follows three stages: concrete, abstract and mental calculation. The first stage (concrete encourages students to explore using concrete objects. This is done prior to the second stage called the abstract stage. Students are then able to move on to the third stage where they can do mathematical calculation mentally and instantly. By following these stages in this order, students can understand mathematics more easily and clearly. The research method used in this study was design research. It consists of three phases; they are preliminary design, teaching experiment and retrospective analysis.The sample was fourteen first-year undergraduate students (matriculation level at STKIP Surya (Surya College of Education, Tangerang, Banten. The instruments used were both oral and written tests. They were used to measure the ability of performing mental computation as well as the ability to teach this material. This study showed that Matematika GASING helpedthese students to understand and be able to teach multiplication of numbers from 1 to 10 better.Keywords: multiplication of numbers from 1 to 10, Matematika GASING, design research DOI: http://dx.doi.org/10.22342/jme.5.1.1450.66-84

A Dual-Band Multiple Input Multiple Output Frequency Agile Antenna for GPSL1/Wi-Fi/WLAN2400/LTE Applications

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Sajid Aqeel

2016-01-01

Full Text Available A novel dual-band, single element multiple input multiple output (MIMO dielectric resonator antenna (DRA with a modest frequency tuning ability is presented in this communication. The proposed antenna operates at GPS L1/Bluetooth/Wi-Fi/LTE2500/WLAN2400 frequency bands. A single dielectric resonator element is fed by two coaxial probes to excite the orthogonal modes. A couple of slots are introduced on the ground plane to improve the isolation between antenna ports. The slots also serve the purpose of reconfiguration in the lower band on placement of switches at optimized locations. The measured impedance bandwidth is 5.16% (1.41–1.49 GHz in the lower band and 26% (2.2–2.85 GHz in the higher band. The lower band reconfigures with an impedance bandwidth of 6.5% (1.55–1.65 GHz when PIN diodes are switched ON. The gain, efficiency, correlation coefficient, and diversity gain of the MIMO DRA are presented with a close agreement between simulated and measured results.

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

NARCIS (Netherlands)

Rudick, R.A.; Stuart, W.H.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Radue, E.W.; Lublin, F.D.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

2006-01-01

BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.

Modified Core Wash Cytology: A reliable same day biopsy result for breast clinics.

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Bulte, J P; Wauters, C A P; Duijm, L E M; de Wilt, J H W; Strobbe, L J A

2016-12-01

Fine Needle Aspiration Biopsy (FNAB), Core Needle biopsy (CNB) and hybrid techniques including Core Wash Cytology (CWC) are available for same-day diagnosis in breast lesions. In CWC a washing of the biopsy core is processed for a provisional cytological diagnosis, after which the core is processed like a regular CNB. This study focuses on the reliability of CWC in daily practice. All consecutive CWC procedures performed in a referral breast centre between May 2009 and May 2012 were reviewed, correlating CWC results with the CNB result, definitive diagnosis after surgical resection and/or follow-up. Symptomatic as well as screen-detected lesions, undergoing CNB were included. 1253 CWC procedures were performed. Definitive histology showed 849 (68%) malignant and 404 (32%) benign lesions. 80% of CWC procedures yielded a conclusive diagnosis: this percentage was higher amongst malignant lesions and lower for benign lesions: 89% and 62% respectively. Sensitivity and specificity of a conclusive CWC result were respectively 98.3% and 90.4%. The eventual incidence of malignancy in the cytological 'atypical' group (5%) was similar to the cytological 'benign' group (6%). CWC can be used to make a reliable provisional diagnosis of breast lesions within the hour. The high probability of conclusive results in malignant lesions makes CWC well suited for high risk populations. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Metastatic renal cell carcinoma in the thyroid gland: ultrasonographic features and the diagnostic role of core needle biopsy

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Song, Ok Kyu; Koo, Ja Seung; Kwak, Jin Young; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Eun Kyung [Severance Hospital, Yonsei University College of Medicine, Seoul(Korea, Republic of)

2017-07-15

The aims of this study were to present the ultrasonographic (US) features of metastatic renal cell carcinoma (RCC) in the thyroid gland and to evaluate the diagnostic utility of fine needle aspiration (FNA) and core needle biopsy (CNB). Eight patients with nine metastatic RCC nodules in the thyroid glands who were treated from January 2002 to March 2015 in a single tertiary hospital were consecutively selected and retrospectively reviewed. US features and clinical history were obtained from the institution’s medical database. FNA was performed nine times on eight nodules and CNB was performed six times on six nodules. The diagnostic utility of FNA and CNB was evaluated. All nine nodules showed mass formation without diffuse thyroid involvement. On ultrasonography, metastatic RCC nodules were solid (100%), hypoechoic (100%), and ovalshaped nodules with a well-defined smooth margin (88.9%) and increased vascularity (100%, with 55% showing extensive vascularity). No calcifications were noted in any nodules. Lymph node metastasis and direct extension to nearby structures beyond the thyroid gland were not found. One FNA (11%) was able to confirm metastatic RCC, whereas all six CNBs confirmed metastatic RCC. Metastatic RCC appears as oval-shaped hypoechoic solid nodules with well-defined smooth margins, no calcifications, and increased vascularity on ultrasonography. Characteristic US features along with a previous history of RCC should raise clinical suspicion, and CNB should be performed to make an accurate diagnosis.

Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland

OpenAIRE

Vierimaa, O. (Outi)

2008-01-01

Abstract Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome characterized by parathyroid, gastroenteropancreatic and pituitary neuroendocrine tumours. In Northern Finland, two founder mutations of the MEN1 gene (1466del12, 1657insC) accounting for the majority of the MEN1 cases, have common ancestors born in the 18th and 19th centuries, respectively. Three small clusters of familial pituitary adenoma have also been detected, two of which could be linked by genealogy to a ...

The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients.

Science.gov (United States)

Sosenko, Jay M; Skyler, Jay S; Palmer, Jerry P; Krischer, Jeffrey P; Yu, Liping; Mahon, Jeffrey; Beam, Craig A; Boulware, David C; Rafkin, Lisa; Schatz, Desmond; Eisenbarth, George

2013-09-01

We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity. The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23-3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons). These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.

IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D)

Science.gov (United States)

Alcina, Antonio; Fedetz, María; Ndagire, Dorothy; Fernández, Oscar; Leyva, Laura; Guerrero, Miguel; Abad-Grau, María M.; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Matesanz, Fuencisla

2009-01-01

Background IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. Methods and Results Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. Conclusions These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases. PMID:19125193

Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.

Science.gov (United States)

Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

2016-11-01

Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Effect of multiple austenitizing treatments on HT-9 steels

International Nuclear Information System (INIS)

Emigh, R.A.

1985-12-01

The effect of multiple austenitizing treatments on the toughness of an Fe-12Cr-1.0Mo-0.5W-0.3V (HT-9) steel was studied. The resulting microstructures were characterized by their mechanical properties, precipitated carbide distribution, and fracture surface appearance. It was proposed that multiple transformations would refine the martensite structure and improve toughness. Optical and scanning electron microscopic observations revealed that the martensite packet structure was somewhat refined by a second austenite transformation. Transmission electron microscopy studies of carbon extraction replicas showed that this multiple step treatment had eliminated grain boundary carbide films seen in single treated specimens on prior austenite grain boundaries. The 0.2% yield strength, tensile strength, and elongation were relatively unchanged, but the toughness measured by fatigue pre-cracked Charpy impact tests increased for the multiple step specimens

Coexistence of GH-Producing Pituitary Macroadenoma and Meningioma in a Patient with Multiple Endocrine Neoplasia Type 1 with Hyperglycemia and Ketosis as First Clinical Sign

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A. Herrero-Ruiz

2017-01-01

Full Text Available We present the clinical case of a patient who was admitted with an onset of diabetes mellitus (DM with associated ketosis and whose clinical, hormonal, and radiological evolution revealed the presence of primary hyperparathyroidism, pancreatic neuroendocrine tumor, and GH-producing pituitary macroadenoma in the context of multiple endocrine neoplasia type 1 (MEN1. DM is relatively common in cases of acromegaly, but it is not generally associated with ketosis. Simultaneously, the patient presented a meningioma, which is associated with pituitary macroadenoma only in extremely rare cases.

The effect of S1P receptor signaling pathway on the survival and drug resistance in multiple myeloma cells.

Science.gov (United States)

Fu, Di; Li, Yingchun; Li, Jia; Shi, Xiaoyan; Yang, Ronghui; Zhong, Yuan; Wang, Huihan; Liao, Aijun

2017-01-01

Multiple myeloma (MM) remains incurable by conventional chemotherapy. Sphingosine-1-phosphate (S1P) receptor-mediated signaling has been recently demonstrated to have critical roles in cell survival and drug resistance in a number of hematological malignancies. To dissect the roles of S1P receptor pathway in MM, we systematically examined cell viability and protein expression associated with cell survival and drug resistance in MM cell lines upon treatment with either pathway activator (S1P) or inhibitor (FTY720). Our results reveal that FTY720 inhibits cell proliferation by downregulating expression of target genes, while S1P has an opposite effect. Knocking down of S1P receptor S1P5R results in a reduction of cell survival-related gene expression; however, it does not have impacts on expression of drug resistance genes. These results suggest that S1P signaling plays a role in cell proliferation and drug resistance in MM, and targeting this pathway will provide a new therapeutic direction for MM management.

Methods of fast, multiple-point in vivo T1 determination

International Nuclear Information System (INIS)

Zhang, Y.; Spigarelli, M.; Fencil, L.E.; Yeung, H.N.

1989-01-01

Two methods of rapid, multiple-point determination of T1 in vivo have been evaluated with a phantom consisting of vials of gel in different Mn + + concentrations. The first method was an inversion-recovery- on-the-fly technique, and the second method used a variable- tip-angle (α) progressive saturation with two sub- sequences of different repetition times. In the first method, 1/T1 was evaluated by an exponential fit. In the second method, 1/T1 was obtained iteratively with a linear fit and then readjusted together with α to a model equation until self-consistency was reached

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

International Nuclear Information System (INIS)

Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I.; Barranger, J.A.

1988-01-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is ∼80% informative in all Gaucher patients studied

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

Energy Technology Data Exchange (ETDEWEB)

Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I. (National Institute of Mental Health, Bethesda, MD (USA)); Barranger, J.A. (Childrens Hospital of Los Angeles, CA (USA))

1988-04-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is {approx}80% informative in all Gaucher patients studied.

[Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

Science.gov (United States)

Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

2016-01-01

To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

ß-cell specific overexpression of suppressor of cytokine signalling-3 does not protect against multiple low dose streptozotocin induced type 1 diabetes in mice

DEFF Research Database (Denmark)

Börjesson, A; Rønn, S G; Karlsen, A E

2011-01-01

We investigated the impact of ß-cell specific overexpression of suppressor of cytokine signalling-3 (SOCS-3) on the development of multiple low dose streptozotocin (MLDSTZ) induced Type 1 diabetes and the possible mechanisms involved. MLDSTZ treatment was administered to RIP-SOCS-3 transgenic......RNA in islet cells and secretion of IL-1Ra into culture medium. MLDSTZ treatment caused gradual hyperglycemia both in the wt mice and in the transgenic mice with the latter tending to be more sensitive. In vitro experiments on wt and transgenic islets did not reveal any differences in sensitivity to damaging...

Multiple Sclerosis Risk Variant HLA-DRB1*1501 Associates with High Expression of DRB1 Gene in Different Human Populations

Science.gov (United States)

Abad-Grau, María del Mar; Fedetz, María; Izquierdo, Guillermo; Lucas, Miguel; Fernández, Óscar; Ndagire, Dorothy; Catalá-Rabasa, Antonio; Ruiz, Agustín; Gayán, Javier; Delgado, Concepción; Arnal, Carmen

2012-01-01

The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone. PMID:22253788

The Drosophila nerfin-1 mRNA requires multiple microRNAs to regulate its spatial and temporal translation dynamics in the developing nervous system.

Science.gov (United States)

Kuzin, Alexander; Kundu, Mukta; Brody, Thomas; Odenwald, Ward F

2007-10-01

The mRNA encoding the Drosophila Zn-finger transcription factor Nerfin-1, required for CNS axon pathfinding events, is subject to post-transcriptional silencing. Although nerfin-1 mRNA is expressed in many neural precursor cells including all early delaminating CNS neuroblasts, the encoded Nerfin-1 protein is detected only in the nuclei of neural precursors that divide just once to generate neurons and then only transiently in nascent neurons. Using a nerfin-1 promoter-controlled reporter transgene, replacement of the nerfin-1 3' UTR with the viral SV-40 3' UTR releases the neuroblast translational block and prolongs reporter protein expression in neurons. Comparative genomics analysis reveals that the nerfin-1 mRNA 3' UTR contains multiple highly conserved sequence blocks that either harbor and/or overlap 21 predicted binding sites for 18 different microRNAs. To determine the functional significance of these microRNA-binding sites and less conserved microRNA target sites, we have studied their ability to block or limit the expression of reporter protein in nerfin-1-expressing cells during embryonic development. Our results indicate that no single microRNA is sufficient to fully inhibit protein expression but rather multiple microRNAs that target different binding sites are required to block ectopic protein expression in neural precursor cells and temporally restrict expression in neurons. Taken together, these results suggest that multiple microRNAs play a cooperative role in the post-transcriptional regulation of nerfin-1 mRNA, and the high degree of microRNA-binding site evolutionary conservation indicates that all members of the Drosophila genus employ a similar strategy to regulate the onset and extinction dynamics of Nerfin-1 expression.

Baicklund transformation and multiple soliton solutions for the (3+1)-dimensional Jimbo-Miwa equation

Institute of Scientific and Technical Information of China (English)

张解放; 吴锋民

2002-01-01

We study an approach to constructing multiple soliton solutions of the (3+1)-dimensional nonlinear evolution equation. We take the (3+1)-dimensional Jimbo-Miwa (JM) equation as an example. Using the extended homogeneous balance method, one can find a Backlund transformation to decompose the (3+1)-dimensional JM equation into a linear partial differential equation and two bilinear partial differential equations. Starting from these linear and bilinear partial differential equations, some multiple soliton solutions for the (3+1)-dimensional JM equation are obtained by introducing a class of formal solutions.

CT-guided percutaneous core needle biopsy for small (≤20 mm) pulmonary lesions

International Nuclear Information System (INIS)

Li, Y.; Du, Y.; Yang, H.F.; Yu, J.H.; Xu, X.X.

2013-01-01

Aim: To assess the accuracy and risk factors for complications of computed tomography (CT)-guided percutaneous core needle biopsy (CNB) for small (≤20 mm) pulmonary lesions. Materials and methods: A retrospective study was undertaken comprising 169 patients who underwent CT-guided CNB for small (≤20 mm) pulmonary lesions. To assess the accuracy of the procedure, the diagnosis at biopsy was compared with the diagnosis after definitive surgery or clinical follow-up. The risk factors for pneumothorax and bleeding were determined by multivariate analysis of variables. Results: The overall diagnostic accuracy was 93.5%. The sensitivity for malignancy and specificity for benign lesions were 90.4% and 100%, respectively. Positive and negative predictive values were 100% and 83.3%, respectively. Twenty-five patients (14.8%) had pneumothorax after CT percutaneous CNB of the lung. The significant risk factors affecting the incidence of pneumothorax were lesion–pleural distance (p = 0.008) and needle–pleural angle (p = 0.012). The highest rate of pneumothorax correlated with a lesion–pleural distance ≥21 mm (OR = 18.46; 95%CI: 2.27–149.95) and a needle–pleural angle ≥51° (OR = 8.22; 95%CI: 2.14–31.49). Bleeding occurred in 30 patients (17.8%). The only significant risk factor affecting the incidence of bleeding was lesion–pleural distance (p = 0.011). The highest bleeding rate correlated with a lesion–pleural distance ≥21 mm (OR = 7.93; 95%CI: 1.73–36.43). Conclusion: CT-guided percutaneous CNB of small (≤20 mm) pulmonary lesions provides high diagnostic accuracy with acceptable complications. A lesion–pleural distance of ≥21 mm and needle–pleural angle of ≥51° are identified as the risk factors for highest pneumothorax rate. In addition, the needle–pleural angle is a novel predictor of pneumothorax. A lesion–pleural distance of ≥21 mm is also identified as a risk factor for the highest bleeding rate.

Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues

Directory of Open Access Journals (Sweden)

Ahmed Al-Jazzar

2016-12-01

Full Text Available Mice harbouring a dentin matrix protein 1 (Dmp1 promoter-driven human diphtheria toxin (DT receptor (HDTR transgene (Tg have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2, was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.

Single-copy nuclear genes place haustorial Hydnoraceae within piperales and reveal a cretaceous origin of multiple parasitic angiosperm lineages.

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Julia Naumann

Full Text Available Extreme haustorial parasites have long captured the interest of naturalists and scientists with their greatly reduced and highly specialized morphology. Along with the reduction or loss of photosynthesis, the plastid genome often decays as photosynthetic genes are released from selective constraint. This makes it challenging to use traditional plastid genes for parasitic plant phylogenetics, and has driven the search for alternative phylogenetic and molecular evolutionary markers. Thus, evolutionary studies, such as molecular clock-based age estimates, are not yet available for all parasitic lineages. In the present study, we extracted 14 nuclear single copy genes (nSCG from Illumina transcriptome data from one of the "strangest plants in the world", Hydnora visseri (Hydnoraceae. A ~15,000 character molecular dataset, based on all three genomic compartments, shows the utility of nSCG for reconstructing phylogenetic relationships in parasitic lineages. A relaxed molecular clock approach with the same multi-locus dataset, revealed an ancient age of ~91 MYA for Hydnoraceae. We then estimated the stem ages of all independently originated parasitic angiosperm lineages using a published dataset, which also revealed a Cretaceous origin for Balanophoraceae, Cynomoriaceae and Apodanthaceae. With the exception of Santalales, older parasite lineages tend to be more specialized with respect to trophic level and have lower species diversity. We thus propose the "temporal specialization hypothesis" (TSH implementing multiple independent specialization processes over time during parasitic angiosperm evolution.

Sarcoidosis and multiple myeloma: Concurrent presentation of an unusual association

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Vidya Nair

2016-01-01

Full Text Available Literature on concurrent association of sarcoidosis with lymphoproliferative malignancies other than lymphoma e.g. multiple myeloma is meager. The rarity of the situation prompted us to report this patient who was a 51-year-old woman with a 2-years history of breathlessness, cough with expectoration, chest pain and backache. Initial evaluation revealed mild anemia, increased alkaline phosphatase with chest skiagram showing both lower zone non homogenous opacities with calcified hilar lymph nodes. CECT chest showed mediastinal with bilateral hilar lymphadenopathy, parenchymal fibrosis, traction bronchiectasis, ground glass opacities, septal and peribronchovascular thickening affecting mid and lower lung zones bilaterally. MRI Dorsolumbar spine was suggestive of marrow infiltrative disorder. EBUS FNA of intrathoracic nodes, EBB and TBLB confirmed sarcoidosis. PET CT revealed hyper metabolic activity in lung, multiple lymph nodes and lytic bone lesions. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin IgG kappa type. Bone marrow biopsy revealed an increase in plasma cells (15%, but no granulomas. Diagnosis of Indolent or multiple myeloma with sarcoidosis was established. 12 cases of sarcoidosis and multiple myeloma have been reported in literature, and mostly preceding the onset of multiple myeloma by many years, in our case both were diagnosed concurrently.

Anisotropies in the cosmic neutrino background after Wilkinson Microwave Anisotropy Probe five-year data

International Nuclear Information System (INIS)

De Bernardis, Francesco; Pagano, Luca; Melchiorri, Alessandro; Serra, Paolo; Cooray, Asantha

2008-01-01

We search for the presence of cosmological neutrino background (CNB) anisotropies in recent Wilkinson Microwave Anisotropy Probe (WMAP) five-year data using their signature imprinted on modifications to the cosmic microwave background (CMB) anisotropy power spectrum. By parameterizing the neutrino background anisotropies with the speed viscosity parameter c vis , we find that the WMAP five-year data alone provide only a weak indication for CNB anisotropies with c vis 2 >0.06 at the 95% confidence level. When we combine CMB anisotropy data with measurements of galaxy clustering, the SN-Ia Hubble diagram, and other cosmological information, the detection increases to c vis 2 >0.16 at the same 95% confidence level. Future data from Planck, combined with a weak lensing survey such as the one expected with DUNE from space, will be able to measure the CNB anisotropy parameter at about 10% accuracy. We discuss the degeneracy between neutrino background anisotropies and other cosmological parameters such as the number of effective neutrinos species and the dark energy equation of state

Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth

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Charalampos Rallis

2014-01-01

Target of rapamycin complex 1 (TORC1, which controls growth in response to nutrients, promotes ageing in multiple organisms. The fission yeast Schizosaccharomyces pombe emerges as a valuable genetic model system to study TORC1 function and cellular ageing. Here we exploited the combinatorial action of rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent manner. We screened a deletion library, comprising ∼84% of all non-essential fission yeast genes, for drug-resistant mutants. This screen identified 33 genes encoding functions such as transcription, kinases, mitochondrial respiration, biosynthesis, intra-cellular trafficking, and stress response. Among the corresponding mutants, 5 showed shortened and 21 showed increased maximal chronological lifespans; 15 of the latter mutants showed no further lifespan increase with rapamycin and might thus represent key targets downstream of TORC1. We pursued the long-lived sck2 mutant with additional functional analyses, revealing that the Sck2p kinase functions within the TORC1 network and is required for normal cell growth, global protein translation, and ribosomal S6 protein phosphorylation in a nutrient-dependent manner. Notably, slow cell growth was associated with all long-lived mutants while oxidative-stress resistance was not.

Multiple Spectral Ratio Analyses Reveal Earthquake Source Spectra of Small Earthquakes and Moment Magnitudes of Microearthquakes

Science.gov (United States)

Uchide, T.; Imanishi, K.

2016-12-01

Spectral studies for macroscopic earthquake source parameters are helpful for characterizing earthquake rupture process and hence understanding earthquake source physics and fault properties. Those studies require us mute wave propagation path and site effects in spectra of seismograms to accentuate source effect. We have recently developed the multiple spectral ratio method [Uchide and Imanishi, BSSA, 2016] employing many empirical Green's function (EGF) events to reduce errors from the choice of EGF events. This method helps us estimate source spectra more accurately as well as moment ratios among reference and EGF events, which are useful to constrain the seismic moment of microearthquakes. First, we focus on earthquake source spectra. The source spectra have generally been thought to obey the omega-square model with single corner-frequency. However recent studies imply the existence of another corner frequency for some earthquakes. We analyzed small shallow inland earthquakes (3.5 multiple spectral ratio analyses. For 20000 microearthquakes in Fukushima Hamadori and northern Ibaraki prefecture area, we found that the JMA magnitudes (Mj) based on displacement or velocity amplitude are systematically below Mw. The slope of the Mj-Mw relation is 0.5 for Mj 5. We propose a fitting curve for the obtained relationship as Mw = (1/2)Mj + (1/2)(Mjγ + Mcorγ)1/γ+ c, where Mcor is a corner magnitude, γ determines the sharpness of the corner, and c denotes an offset. We obtained Mcor = 4.1, γ = 5.6, and c = -0.47 to fit the observation. The parameters are useful for characterizing the Mj-Mw relationship. This non-linear relationship affects the b-value of the Gutenberg-Richter law. Quantitative discussions on b-values are affected by the definition of magnitude to use.

Operation of a 1.3 GHz, 10 MW Multiple Beam Klystron

CERN Document Server

Bohlen, H P; Cattelino, M; Cox, L; Cusick, M; Forrest, S; Friedlander, F; Staprans, A; Wright, E; Zitelli, L

2004-01-01

Results will be reported for a 1.3 GHz, 10 MW multiple beam klystron that is being developed for the TESLA linear accelerator facility. The design parameters for the device are 10 MW peak RF output power with 150 kW average power, 1.5 ms pulse length, 65% efficiency, 50 dB gain, and 2.0 A/cm2

Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis.

Science.gov (United States)

Iparraguirre, Leire; Muñoz-Culla, Maider; Prada-Luengo, Iñigo; Castillo-Triviño, Tamara; Olascoaga, Javier; Otaegui, David

2017-09-15

Multiple sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g. microRNAs). Indeed, some of these have been suggested as biomarkers for multiple sclerosis even though few biomarkers have reached the clinical practice. Recently, a novel family of non-coding RNAs, circular RNAs, has emerged as a new player in the complex network of gene-expression regulation. MicroRNA regulation function through a 'sponge system' and a RNA splicing regulation function have been proposed for the circular RNAs. This regulating role together with their high stability in biofluids makes them seemingly good candidates as biomarkers. Given the dysregulation of both protein-coding and non-coding transcriptome that have been reported in multiple sclerosis patients, we hypothesised that circular RNA expression may also be altered. Therefore, we carried out expression profiling of 13.617 circular RNAs in peripheral blood leucocytes from multiple sclerosis patients and healthy controls finding 406 differentially expressed (P-value  1.5) and demonstrate after validation that, circ_0005402 and circ_0035560 are underexpressed in multiple sclerosis patients and could be used as biomarkers of the disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Light chain deposition disease in multiple myeloma: MR imaging features correlated with histopathological findings

International Nuclear Information System (INIS)

Baur, A.; Staebler, A.; Reiser, M.; Lamerz, R.; Bartl, R.

1998-01-01

The clinical, histopathological, and imaging findings on MRI of a 56-year-old woman with light chain deposition disease occurring in multiple myeloma are presented. Light chain deposition disease is a variant of multiple myeloma with distinct clinical and histological characteristics. MRI of this patient also revealed an infiltration pattern in the bone marrow distinct from that of typical multiple myeloma. Multiple small foci of low signal intensity were present on T1- and T2-weighted spin echo and STIR images, corresponding to conglomerates of light chains in bone marrow biopsy. Contrast-enhanced T1-weighted spin echo images show diffuse enhancement of 51% over all vertebral bodies, with a minor enhancement of the focal conglomerates of light chains. Light chain deposition disease in multiple myeloma should be added to the list of those few entities with normal radiographs and discrete low-signal marrow lesions on T1- and T2-weighted spin echo pulse sequences. (orig.)

Cyp1a reporter zebrafish reveals target tissues for dioxin

Energy Technology Data Exchange (ETDEWEB)

Kim, Kun-Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Park, Hye-Jeong [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Jin Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Suhyun [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Williams, Darren R. [New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of); Kim, Myeong-Kyu [Department of Neurology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Jung, Young Do [Department of Biochemistry, Chonnam National University Medical School, Gwangju (Korea, Republic of); Teraoka, Hiroki [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Park, Hae-Chul [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Choy, Hyon E., E-mail: hyonchoy@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Shin, Boo Ahn, E-mail: bashin@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Choi, Seok-Yong, E-mail: zebrafish@chonnam.ac.kr [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); School of Biological Sciences and Technology, Chonnam National University, Gwangju (Korea, Republic of)

2013-06-15

Highlights: •2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic anthropogenic substance ever identified. •Transgenic cyp1a reporter zebrafish reveals target tissues for TCDD. •The retinal bipolar cells, otic vesicle, lateral line, pancreas, cloaca and pectoral fin bud are novel targets in zebrafish for TCDD. •Our findings will further understanding of human health risks by TCDD. -- Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems. Induction of cyp1a1 is used as an indicator of TCDD exposure. We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model. We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering. The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD. Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA. In addition, exposure of the embryos to TCDD at as low as 10 pM for 72 h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression. Furthermore, the reporter embryos responded to other AhR ligands as well. Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD. Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD. In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.

Targeting MUC1-C suppresses polycomb repressive complex 1 in multiple myeloma.

Science.gov (United States)

Tagde, Ashujit; Markert, Tahireh; Rajabi, Hasan; Hiraki, Masayuki; Alam, Maroof; Bouillez, Audrey; Avigan, David; Anderson, Kenneth; Kufe, Donald

2017-09-19

The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2 proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1-C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also necessary for MM cell survival. The present studies show that targeting MUC1-C with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1, RING1 and RING2 expression. The results demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism. MUC1-C thus promotes MYC occupancy on the BMI1 promoter and thereby activates BMI1 expression. We also show that the MUC1-C→MYC pathway induces RING2 expression. Moreover, in contrast to BMI1 and RING2, we found that MUC1-C drives RING1 by an NF-κB p65-dependent mechanism. Targeting MUC1-C and thereby the suppression of these key PRC1 proteins was associated with downregulation of the PRC1 E3 ligase activity as evidenced by decreases in ubiquitylation of histone H2A. Targeting MUC1-C also resulted in activation of the PRC1-repressed tumor suppressor genes, PTEN, CDNK2A and BIM . These findings identify a heretofore unrecognized role for MUC1-C in the epigenetic regulation of MM cells.

Multiple Measures Reveal Antiretroviral Adherence Successes and Challenges in HIV-Infected Ugandan Children

Science.gov (United States)

Haberer, Jessica E.; Kiwanuka, Julius; Nansera, Denis; Ragland, Kathleen; Mellins, Claude; Bangsberg, David R.

2012-01-01

Background Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood. Methodology/Principal Findings To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2–10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of ≥48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = −0.25, p = 0.04). Multivariable regression found the following to be associated with liquid formulation use (AOR 1.4, 95%CI 1.0–2.0; p = 0.04), and caregiver’s alcohol use (AOR 3.1, 95%CI 1.8–5.2; passets (AOR 0.7, 95%CI 0.6–0.9; p = 0.0007) were protective against these interruptions. Conclusions/Significance Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and shame may reflect fear of poor outcomes, functioning as motivation for the child to adhere. Further research is needed to better understand and build on these key influential factors for adherence intervention development. PMID:22590600

The Pleurobemini (Bivalvia: Unionida) revisited: Molecular species delineation using a mitochondrial DNA gene reveals multiple conspecifics and undescribed species

Science.gov (United States)

Inoue, Kentaro; Hayes, David M.; Harris, John L.; Johnson, Nathan A.; Morrison, Cheryl L.; Eackles, Michael S.; King, Tim; Jones, Jess W.; Hallerman, Eric M.; Christian, Alan D.; Randklev, Charles R.

2018-01-01

The Pleurobemini (Bivalvia: Unionida) represent approximately one-third of freshwater mussel diversity in North America. Species identification within this group is challenging due to morphological convergence and phenotypic plasticity. Accurate species identification, including characterisation of currently unrecognised taxa, is required to develop effective conservation strategies because many species in the group are imperiled. We examined 575 cox1 sequences from 110 currently recognised species (including 13 Fusconaia and 21 Pleurobema species) to understand phylogenetic relationships among pleurobemine species (mainly Fusconaia and Pleurobema) and to delineate species boundaries. The results of phylogenetic analyses showed no geographic structure within widespread species and illustrated a close relationship between Elliptio lanceolata and Parvaspina collina. Constraint tests supported monophyly of the genera Fusconaia and Pleurobema, including the subgenus P. (Sintoxia). Furthermore, results revealed multiple conspecifics, including P. hanleyianum and P. troschelianum, P. chattanoogaense and P. decisum, P. clava and P. oviforme, P. rubrum and P. sintoxia, F. askewi and F. lananensis, and F. cerina and F. flava. Species delimitation analyses identified three currently unrecognised taxa (two in Fusconaia and one in Pleurobema). Further investigation using additional genetic markers and other lines of evidence (e.g. morphology, life history, ecology) are necessary before any taxonomic changes are formalised.

Multiplication: From Thales to Lie1

Indian Academy of Sciences (India)

Addition. To describe the geometric constructions of addition, as ..... general, we could apply the implicit function theorem of calculus to solve locally the defining ... and whose multiplication and inverse are analytic maps, is called a Lie group.

Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis

Directory of Open Access Journals (Sweden)

Nichole M Miller

2015-08-01

Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS mediated by T helper (h1 and/or Th17 CD4 T cells that drive inflammatory lesion development along with demyelination and neuronal damage. Defects in immune regulatory mechanisms are thought to play a role in the pathogenesis of MS. While an early clinical trial indicated that IFN-γ administration was detrimental to MS, studies in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE, indicated that IFN-γ exhibits a number of anti-inflammatory properties within the CNS. These mechanisms include inhibition of IL-17 production, induction of regulatory T cells, T cell apoptosis and regulation of chemokine production. Mice deficient in IFN-γ or its receptor were instrumental in deciphering the anti-inflammatory properties of IFN-γ in the CNS. In particular, they revealed that IFN-γ is a major regulator of neutrophil recruitment into the CNS, which by a variety of mechanisms including disruption of the blood-brain-barrier (BBB and production of reactive oxygen species are thought to contribute to the onset and progression of EAE. Neutrophils were also shown to be instrumental in EAE relapses. To date neutrophils have not been appreciated as a driver of MS, but more recently based largely on the strong EAE data this view is being reevaluated by some investigators in the field.

Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.

Directory of Open Access Journals (Sweden)

Antonio Alcina

Full Text Available The human leukocyte antigen (HLA DRB1*1501 has been consistently associated with multiple sclerosis (MS in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS. We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.

Multiple faulting events revealed by trench analysis of the seismogenic structure of the 1976 Ms7.1 Luanxian earthquake, Tangshan Region, China

Science.gov (United States)

Guo, Hui; Jiang, Wali; Xie, Xinsheng

2017-10-01

The Ms7.8 Tangshan earthquake occurred on 28 July 1976 at 03:42 CST. Approximately 15 h later, the Ms7.1 Luanxian earthquake occurred approximately 40 km northeast of the main shock. The two earthquakes formed different surface rupture zones. The surface rupture of the Tangshan earthquake was NNE-trending and more than 47 km long. The surface rupture of the Luanxian earthquake was more than 6 km long and consisted of two sections, forming a protruding arc to the west. The north and south sections were NE- and NW-trending and 2 km and 4 km long, respectively. A trench was excavated in Sanshanyuan Village across the NE-trending rupture of the Luanxian earthquake, at the macroscopic epicenter of the Luanxian earthquake. Analysis of this trench revealed that the surface rupture is connected to the underground active fault. The following major conclusions regarding Late Quaternary fault activity have been reached. (1) The Sanshanyuan trench indicated that its fault planes trend NE30° and dip SE or NW at angles of approximately 69-82°. (2) The fault experienced four faulting events prior to the Luanxian earthquake at 27.98 ka with an average recurrence interval of approximately 7.5 ka. (3) The Ms7.1 Luanxian earthquake resulted from the activity of the Luanxian Western fault and was triggered by the Ms7.8 Tangshan earthquake. The seismogenic faults of the 1976 Ms7.1 Luanxian earthquake and the 1976 Ms7.8 Tangshan earthquake are not the same fault. This example of an M7 earthquake triggered by a nearly M8 earthquake after more than 10 h on a nearby fault is a worthy topic of research for the future prediction of strong earthquakes.

Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.

Science.gov (United States)

Yee, S W; Giacomini, M M; Hsueh, C-H; Weitz, D; Liang, X; Goswami, S; Kinchen, J M; Coelho, A; Zur, A A; Mertsch, K; Brian, W; Kroetz, D L; Giacomini, K M

2016-11-01

Transporter-mediated drug-drug interactions (DDIs) are a major cause of drug toxicities. Using published genome-wide association studies (GWAS) of the human metabolome, we identified 20 metabolites associated with genetic variants in organic anion transporter, OATP1B1 (P acids and fatty acid dicarboxylates were among the metabolites discovered using both GWAS and CSA administration. In vitro studies confirmed tetradecanedioate (TDA) and hexadecanedioate (HDA) were novel substrates of OATP1B1 as well as OAT1 and OAT3. This study highlights the use of multiple datasets for the discovery of endogenous metabolites that represent potential in vivo biomarkers for transporter-mediated DDIs. Future studies are needed to determine whether these metabolites can serve as qualified biomarkers for organic anion transporters. Quantitative relationships between metabolite levels and modulation of transporters should be established. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Studying the co-evolution of protein families with the Mirrortree web server.

Science.gov (United States)

Ochoa, David; Pazos, Florencio

2010-05-15

The Mirrortree server allows to graphically and interactively study the co-evolution of two protein families, and investigate their possible interactions and functional relationships in a taxonomic context. The server includes the possibility of starting from single sequences and hence it can be used by non-expert users. The web server is freely available at http://csbg.cnb.csic.es/mtserver. It was tested in the main web browsers. Adobe Flash Player is required at the client side to perform the interactive assessment of co-evolution. pazos@cnb.csic.es Supplementary data are available at Bioinformatics online.

A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility.

Science.gov (United States)

Bush, W S; McCauley, J L; DeJager, P L; Dudek, S M; Hafler, D A; Gibson, R A; Matthews, P M; Kappos, L; Naegelin, Y; Polman, C H; Hauser, S L; Oksenberg, J; Haines, J L; Ritchie, M D

2011-07-01

Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also increases power to detect weak main effects. We conducted a knowledge-driven interaction analysis of a GWAS of 931 multiple sclerosis (MS) trios to discover gene-gene interactions within established biological contexts. We identify heterogeneous signals, including a gene-gene interaction between CHRM3 (muscarinic cholinergic receptor 3) and MYLK (myosin light-chain kinase) (joint P=0.0002), an interaction between two phospholipase C-β isoforms, PLCβ1 and PLCβ4 (joint P=0.0098), and a modest interaction between ACTN1 (actinin alpha 1) and MYH9 (myosin heavy chain 9) (joint P=0.0326), all localized to calcium-signaled cytoskeletal regulation. Furthermore, we discover a main effect (joint P=5.2E-5) previously unidentified by single-locus analysis within another related gene, SCIN (scinderin), a calcium-binding cytoskeleton regulatory protein. This work illustrates that knowledge-driven interaction analysis of GWAS data is a feasible approach to identify new genetic effects. The results of this study are among the first gene-gene interactions and non-immune susceptibility loci for MS. Further, the implicated genes cluster within inter-related biological mechanisms that suggest a neurodegenerative component to MS.

Opposing effects of the HLA-DRB1*0301-DQB1*0201 haplotype on the risk for multiple sclerosis in diverse Arab populations in Israel.

Science.gov (United States)

Benedek, G; Paperna, T; Avidan, N; Lejbkowicz, I; Oksenberg, J R; Wang, J; Brautbar, C; Israel, S; Miller, A

2010-07-01

Different multiple sclerosis (MS) prevalence rates were reported for Muslim and Christian Arabs in Israel. In this study, we evaluated whether associations of human leukocyte antigen (HLA) genes with MS may contribute to this prevalence difference. DNA samples from Israeli Arab MS patients (n=109) and controls (n=132) were typed for HLA class I (HLA-A, -B and -C) and II (HLA-DRB1 and -DQB1) genes. Global comparisons of HLA allele frequencies revealed significant differences between Christians and Muslims; therefore, case-control analyses were stratified by religious affiliation. Disease characteristics of Muslim and Christian Arab MS patients were similar to those reported for European populations. Opposing association signals with MS were observed for alleles composing the DRB1*0301-DQB1*0201 haplotype: positive association of the HLA-DRB1*0301 allele in Muslims (P(Bonferroni)=0.004, odds ratio (OR)=3.07), and negative association in Christian Arabs (P(Bonferroni)=0.01, OR=0.12), with similar results obtained for HLA-DQB1*0201. HLA-B*52 was negatively associated with MS only in Muslims (P(Bonferroni)=0.01, OR=0.03). The study presents for the first time a high-resolution HLA gene analysis in clinically well-characterized Arab populations with MS, and shows the population-specific contribution of the DRB1*0301-DQB1*0201 haplotype to disease susceptibility.

Cerebral metastases from multiple myeloma

International Nuclear Information System (INIS)

Norum, J.; Wist, E.; Dahl, I.M.; University Hospital, Tromsoe

1991-01-01

The authors report a patient with multiple intracerebral lesions from myeloma. The case also demonstrates that myeloma is a radiosensitive tumour and that radiotherapy is important to keep in mind when intracranial lesions are revealed. (orig.)

VLA Zeeman Observations of the NGC 6334 Complex

Science.gov (United States)

Mayo, E. A.; Sarma, A. P.; Troland, T. H.

2004-05-01

We present OH 1665 and 1667 MHz observations of the NGC 6334 complex taken with the Very Large Array in the BnA configuration. We have combined our data with the lower resolution CnB data of Sarma et al (1999), in order to perform a detailed study of Source A, a compact continuum source in the SW region of the complex. Our observations reveal magnetic fields with peak values of the order of 700μ G toward Source A. Virial estimates presented indicate the significance of the magnetic field in the support of the molecular cloud against gravitational collapse.

Theoretical study of the adsorption of rhodium on a TiO{sub 2}(1 1 0)-1 Multiplication-Sign 1 surface

Energy Technology Data Exchange (ETDEWEB)

Mutombo, P., E-mail: mutombo@fzu.cz [Institute of Physics of Academy of Sciences of the Czech Republic, Cukrovarnicka 10, 16253 Praha 6 (Czech Republic); Balazs, N. [Reaction Kinetics Laboratory, Institute of Nanochemistry and Catalysis, CRC of the Hungarian Academy of Sciences, University of Szeged, P.O. Box 168, H-6701 Szeged (Hungary); Majzik, Z. [Institute of Physics of Academy of Sciences of the Czech Republic, Cukrovarnicka 10, 16253 Praha 6 (Czech Republic); Reaction Kinetics Laboratory, Institute of Nanochemistry and Catalysis, CRC of the Hungarian Academy of Sciences, University of Szeged, P.O. Box 168, H-6701 Szeged (Hungary); Berko, A. [Reaction Kinetics Laboratory, Institute of Nanochemistry and Catalysis, CRC of the Hungarian Academy of Sciences, University of Szeged, P.O. Box 168, H-6701 Szeged (Hungary); Chab, V. [Institute of Physics of Academy of Sciences of the Czech Republic, Cukrovarnicka 10, 16253 Praha 6 (Czech Republic)

2012-03-01

Density functional theory (DFT) calculations were used to study the adsorption of rhodium on a TiO{sub 2}(1 1 0)-1 Multiplication-Sign 1 surface as a function of coverage. It was found that Rh atom prefers the hollow site between a bridging oxygen atom, a threefold oxygen atom and a fivefold coordinated Ti atom, regardless of the coverage used. DFT calculations also suggest that Rh-Rh interaction is attractive along the [0 0 1] direction, implying that the Rh 1D nanostructure should grow preferentially along this direction. Simulated Rh dimer clusters resemble strongly Pd dimers resolved in STM experiments suggesting that both metals occupy the same adsorption site at the TiO{sub 2}(1 1 0) surface.

Cell characteristics of a multiple alloy nano-dots memory structure

International Nuclear Information System (INIS)

Bea, Ji Chel; Lee, Kang-Wook; Tanaka, Tetsu; Koyanagi, Mitsumasa; Song, Yun Heub; Lee, Gae-Hun

2009-01-01

A multiple alloy metal nano-dots memory using FN tunneling was investigated in order to confirm its structural possibility for future flash memory. In this work, a multiple FePt nano-dots device with a high work function (∼5.2 eV) and extremely high dot density (∼1.2 × 10 13 cm −2 ) was fabricated. Its structural effect for multiple layers was evaluated and compared to the one with a single layer in terms of the cell characteristics and reliability. We confirm that MOS capacitor structures with two to four multiple FePt nano-dot layers provide a larger threshold voltage window and better retention characteristics. Furthermore, it was also revealed that several process parameters for block oxide and inter-tunnel oxide between the nano-dot layers are very important to improve the efficiency of electron injection into multiple nano-dots. From these results, it is expected that a multiple FePt nano-dots memory using Fowler–Nordheim (FN) tunneling could be a candidate structure for future flash memory

Evolution of the stellar mass function in multiple-population globular clusters

Science.gov (United States)

Vesperini, Enrico; Hong, Jongsuk; Webb, Jeremy J.; D'Antona, Franca; D'Ercole, Annibale

2018-05-01

We present the results of a survey of N-body simulations aimed at studying the effects of the long-term dynamical evolution on the stellar mass function (MF) of multiple stellar populations in globular clusters. Our simulations show that if first-(1G) and second-generation (2G) stars have the same initial MF (IMF), the global MFs of the two populations are affected similarly by dynamical evolution and no significant differences between the 1G and 2G MFs arise during the cluster's evolution. If the two populations have different IMFs, dynamical effects do not completely erase memory of the initial differences. Should observations find differences between the global 1G and 2G MFs, these would reveal the fingerprints of differences in their IMFs. Irrespective of whether the 1G and 2G populations have the same global IMF or not, dynamical effects can produce differences between the local (measured at various distances from the cluster centre) 1G and 2G MFs; these differences are a manifestation of the process of mass segregation in populations with different initial structural properties. In dynamically old and spatially mixed clusters, however, differences between the local 1G and 2G MFs can reveal differences between the 1G and 2G global MFs. In general, for clusters with any dynamical age, large differences between the local 1G and 2G MFs are more likely to be associated with differences in the global MF. Our study also reveals a dependence of the spatial mixing rate on the stellar mass, another dynamical consequence of the multiscale nature of multiple-population clusters.

A 2:1 MUX Based on Multiple MEMS Resonators

KAUST Repository

Hafiz, Md Abdullah Al

2017-01-09

Micro/nano-electromechanical resonator based mechanical computing has recently attracted significant attention. This paper reports a realization of a 2:1 MUX, a concatenable digital logic element, based on electrothermal frequency tuning of electrically connected multiple arch resonators. Toward this, shallow arch shaped microresonators are electrically connected and their resonance frequencies are tuned based on an electrothermal frequency modulation scheme. This study demonstrates that by reconfiguring the same basic building block, the arch microresonator, complex logic circuits can be realized.

A 2:1 MUX Based on Multiple MEMS Resonators

KAUST Repository

Hafiz, Md Abdullah Al; Kosuru, Lakshmoji; Younis, Mohammad I.; Fariborzi, Hossein

2017-01-01

Micro/nano-electromechanical resonator based mechanical computing has recently attracted significant attention. This paper reports a realization of a 2:1 MUX, a concatenable digital logic element, based on electrothermal frequency tuning of electrically connected multiple arch resonators. Toward this, shallow arch shaped microresonators are electrically connected and their resonance frequencies are tuned based on an electrothermal frequency modulation scheme. This study demonstrates that by reconfiguring the same basic building block, the arch microresonator, complex logic circuits can be realized.

Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.

Directory of Open Access Journals (Sweden)

Alessandro Silvani

Full Text Available Cannabinoid type 1 (CB1 receptors are highly expressed in the brain and play a role in behavior control. Endogenous cannabinoid signaling is modulated by high-fat diet (HFD. We investigated the consequences of congenital lack of CB1 receptors on sleep in mice fed standard diet (SD and HFD. CB1 cannabinoid receptor knock-out (KO and wild-type (WT mice were fed SD or HFD for 4 months (n = 9-10 per group. Mice were instrumented with electroencephalographic (EEG and electromyographic electrodes. Recordings were performed during baseline (48 hours, sleep deprivation (gentle handling, 6 hours, sleep recovery (18 hours, and after cage switch (insomnia model paradigm, 6 hours. We found multiple significant effects of genotype on sleep. In particular, KO spent more time awake and less time in non-rapid-eye-movement sleep (NREMS and rapid-eye-movement sleep (REMS than WT during the dark (active period but not during the light (rest period, enhancing the day-night variation of wake-sleep amounts. KO had slower EEG theta rhythm during REMS. REMS homeostasis after sleep deprivation was less effective in KO than in WT. Finally, KO habituated more rapidly to the arousing effect of the cage-switch test than WT. We did not find any significant effects of diet or of diet x genotype interaction on sleep. The occurrence of multiple sleep alterations in KO indicates important roles of CB1 cannabinoid receptors in limiting arousal during the active period of the day, in sleep regulation, and in sleep EEG in mice.

Evidence of multiple introductions of HIV-1 subtype C in Angola.

Science.gov (United States)

Afonso, Joana Morais; Morgado, Mariza G; Bello, Gonzalo

2012-10-01

HIV-1 subtype C is the most prevalent group M clade in southern Africa and some eastern African countries. Subtype C is also the most frequent subtype in Angola (southwestern Africa), with an estimated prevalence of 10-20%. In order to better understand the origin of the HIV-1 subtype C strains circulating in Angola, 31 subtype C pol sequences of Angolan origin were compared with 1950 subtype C pol sequences sampled in other African countries. Phylogenetic analyses reveal that the Angolan subtype C sequences were distributed in 16 different lineages that were widely dispersed among other African strains. Ten subtype C Angolan lineages were composed by only one sequence, while the remaining six clades contain between two and seven sequences. Bayesian phylogeographic analysis indicates that most Angolan clades probably originated in different southern African countries with the exception of one lineage that most likely originated in Burundi. Evolutionary analysis suggests that those Angolan subtype C clades composed by ≥ 2 sequences were introduced into the country between the late 1970s and the mid 2000s. The median estimated time frame for the origin of those Angolan lineages coincides with periods of positive migration influx in Angola that were preceded by phases of negative migratory outflow. These results demonstrate that the Angolan subtype C epidemic resulted from multiple introductions of subtype C viruses mainly imported from southern African countries over the last 30years, some of which have been locally disseminated establishing several autochthonous transmission networks. This study also suggests that population mobility between Angola and southern African countries during civil war (1974-2002) may have played a key role in the emergence of the Angolan subtype C epidemic. Copyright © 2012 Elsevier B.V. All rights reserved.

Multiple barriers to recombination between divergent HIV-1 variants revealed by a dual-marker recombination assay

DEFF Research Database (Denmark)

Nikolaitchik, Olga A; Galli, Andrea; Moore, Michael D

2011-01-01

Recombination is a major force for generating human immunodeficiency virus type 1 (HIV-1) diversity and produces numerous recombinants circulating in the human population. We previously established a cell-based system using green fluorescent protein gene (gfp) as a reporter to study the mechanisms...... of HIV-1 recombination. We now report an improved system capable of detecting recombination using authentic viral sequences. Frameshift mutations were introduced into the gag gene so that parental viruses do not express full-length Gag; however, recombination can generate a progeny virus that expresses...

Multiplicative properties of quantum channels

Science.gov (United States)

Rahaman, Mizanur

2017-08-01

In this paper, we study the multiplicative behaviour of quantum channels, mathematically described by trace preserving, completely positive maps on matrix algebras. It turns out that the multiplicative domain of a unital quantum channel has a close connection to its spectral properties. A structure theorem (theorem 2.5), which reveals the automorphic property of an arbitrary unital quantum channel on a subalgebra, is presented. Various classes of quantum channels (irreducible, primitive, etc) are then analysed in terms of this stabilising subalgebra. The notion of the multiplicative index of a unital quantum channel is introduced, which measures the number of times a unital channel needs to be composed with itself for the multiplicative algebra to stabilise. We show that the maps that have trivial multiplicative domains are dense in completely bounded norm topology in the set of all unital completely positive maps. Some applications in quantum information theory are discussed.

Analysis of Brassica oleracea early stage abiotic stress responses reveals tolerance in multiple crop types and for multiple sources of stress.

Science.gov (United States)

Beacham, Andrew M; Hand, Paul; Pink, David Ac; Monaghan, James M

2017-12-01

Brassica oleracea includes a number of important crop types such as cabbage, cauliflower, broccoli and kale. Current climate conditions and weather patterns are causing significant losses in these crops, meaning that new cultivars with improved tolerance of one or more abiotic stress types must be sought. In this study, genetically fixed B. oleracea lines belonging to a Diversity Fixed Foundation Set (DFFS) were assayed for their response to seedling stage-imposed drought, flood, salinity, heat and cold stress. Significant (P ≤ 0.05) variation in stress tolerance response was found for each stress, for each of four measured variables (relative fresh weight, relative dry weight, relative leaf number and relative plant height). Lines tolerant to multiple stresses were found to belong to several different crop types. There was no overall correlation between the responses to the different stresses. Abiotic stress tolerance was identified in multiple B. oleracea crop types, with some lines exhibiting resistance to multiple stresses. For each stress, no one crop type appeared significantly more or less tolerant than others. The results are promising for the development of more environmentally robust lines of different B. oleracea crops by identifying tolerant material and highlighting the relationship between responses to different stresses. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Canonical correlation analysis of multiple sensory directed metabolomics data blocks reveals corresponding parts between data blocks.

NARCIS (Netherlands)

Doeswijk, T. G.; Hageman, J.A.; Westerhuis, J.A.; Tikunov, Y.; Bovy, A.; van Eeuwijk, F.A.

2011-01-01

Multiple analytical platforms are frequently used in metabolomics studies. The resulting multiple data blocks contain, in general, similar parts of information which can be disclosed by chemometric methods. The metabolites of interest, however, are usually just a minor part of the complete data

The value of touch imprint cytology of prostate core needle biopsy ...

African Journals Online (AJOL)

S. Hussein

2015-11-10

Nov 10, 2015 ... causes of cancer mortality [1]. ... in 5 African-American men will be diagnosed with prostate cancer ... a 20–40% false negative rate of sextant biopsies [6], and it has .... to CNB in breast cancer cases, TIC has been found to improve ... sampling the tissue at three levels only missed an average of 7%.

Accuracy of 3 T versus 1.5 T breast MRI for pre-operative assessment of extent of disease in newly diagnosed DCIS

Energy Technology Data Exchange (ETDEWEB)

Rahbar, Habib, E-mail: hrahbar@uw.edu; DeMartini, Wendy B.; Lee, Amie Y.; Partridge, Savannah C.; Peacock, Sue; Lehman, Constance D.

2015-04-15

Highlights: •We compared sizes of known ductal carcinoma in situ (DCIS) on pre-operative breast MRI at 3 T and 1.5 T with final pathology sizes. •DCIS sizes on 3 T MRI correlated better with pathologic sizes than 1.5 T MRI. •Imaging features of DCIS, including morphology and kinetics, were similar at 3 T and 1.5 T MRI. -- Abstract: Objectives: While 3 T breast magnetic resonance imaging has increased in use over the past decade, there is little data comparing its use for assessing ductal carcinoma in situ (DCIS) versus 1.5 T. We sought to compare the accuracies of DCIS extent of disease measures on pre-operative 3 T versus 1.5 T MRI. Methods: This institutional review board-approved prospective study included 20 patients with ductal carcinoma in situ diagnosed by core needle biopsy (CNB) who underwent pre-operative breast MRI at both 3 T (resolution = 0.5 mm × 0.5 mm × 1.3 mm) and 1.5 T (0.85 mm × 0.85 mm × 1.6 mm). All patients provided informed consent, and the study was HIPPA compliant. Lesion sizes and imaging characteristics (morphologic and kinetic enhancement) were recorded for the 3 T and 1.5 T examinations. Lesion size measures at both field strengths were correlated to final pathology, and imaging characteristics also were compared. Results: Of the initial cohort of 20 patients with CNB-diagnosed DCIS, 19 underwent definitive surgery. Median DCIS sizes of these 19 patients were 6 mm (range: 0–67 mm) on 3 T, 13 mm (0–60 mm) on 1.5 T, and 6 mm (0–55 mm) on surgical pathology. Size correlation between MRI and pathology was higher for 3 T (Spearman's ρ = 0.66, p = 0.002) than 1.5 T (ρ = 0.36, p = 0.13). In 10 women in which a residual area of suspicious enhancement was identified on both field strengths, there was agreement of morphologic description (NME vs. mass) in nine, and no significant difference in dynamic contrast enhanced kinetics at 3 T compared to 1.5 T. Conclusions: Pre-operative breast MRI at 3 T provided higher

Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cysts

Energy Technology Data Exchange (ETDEWEB)

Koh, Kwang Joon; Park, Ha Na; Kim, Kyoung A [Dept. of Oral and Maxillofacial Radiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju (Korea, Republic of)

2016-12-15

Gardner syndrome is known as a variant of familial adenomatous polyposis. This syndrome is characterized by multiple intestinal polyposes, osteomas, and epidermoid cysts. In addition, dental abnormalities include an increased frequency of multiple odontomas, as well as supernumerary and impacted teeth. The authors report the case of a 7-year-old male patient with Gardner syndrome. Radiographic findings revealed multiple osteomas in both sides of the maxilla, multiple diffuse enostoses in both jaws, and a complex odontoma in the left mandibular body. Two years later, multiple epidermoid cysts on the scalp were found. Since this patient was suspected to have Gardner syndrome, the authors recommended gastrointestinal endoscopy to check for intestinal polyposis. Gastrointestinal endoscopic examination revealed multiple polyposes in the upper gastrointestinal tract and fundus of the stomach. As a result, the final diagnosis was Gardner syndrome.

Transient analysis of an M/M/1 queue with multiple vacations

Directory of Open Access Journals (Sweden)

Kaliappan Kalidass

2014-05-01

Full Text Available In this paper, we have obtained explicit expressions for the time dependent probabilities of the M/M/1  queue with server vacations under a multiple vacation scheme. The corresponding steady state probabilities have been obtained. We also obtain the time dependent performance measures of the systems

Preparation, optical properties and 1 Multiplication-Sign 2 polymeric thermo-optic switch of polyurethane-urea

Energy Technology Data Exchange (ETDEWEB)

Qiu, Fengxian, E-mail: fxqiuchem@163.com [School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013 (China); Cao, Zhijuan [School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013 (China); Cao, Guorong; Guan, Yijun; Shen, Qiang [Department of Physics, Jiangsu University, Zhenjiang 212013 (China); Wang, Qing; Yang, Dongya [School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013 (China)

2012-08-15

A polyurethane-urea (PUU) containing azo chromophore, polyether polyol (NJ-220) and isophorone diisocyanate (IPDI) was prepared. The structure, thermal property and mechanical properties of obtained PUU were characterized and measured by the UV-visible spectroscopy, Fourier transform infrared, Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The refractive index (n) of PUU was determined at different temperature and wavelength (532 nm, 650 nm and 850 nm) using attenuated total reflection (ATR) technique, and the thermo-optic coefficients (dn/dT) were -5.3643 Multiplication-Sign 10{sup -4} Degree-Sign C{sup -1}, -5.2500 Multiplication-Sign 10{sup -4} Degree-Sign C{sup -1} and -4.6071 Multiplication-Sign 10{sup -4} Degree-Sign C{sup -1}, respectively. Using the Charge Coupled Device (CCD) digital imaging devices, transmission loss of PUU was measured and the value was 0.659 dB cm{sup -1}. A 1 Multiplication-Sign 2 polymeric thermo-optic switch based on the thermo-optic effect of PUU film was proposed. With branching angle of 0.143 Degree-Sign and the finite difference beam propagation method (FD-BPM), the polymeric thermo-optic switch was simulated. The result showed that the power consumption of the thermo-optic switch could be only 0.72 mW, and the response time of the switch was about 3.0 ms. The obtained PUU has a significant improvement in reducing the power consumption and response time compared with those of the normal polymeric thermo-optic switches. -- Highlights: Black-Right-Pointing-Pointer Preparation and structural characterization of a novel azo polyurethane-urea (PUU). Black-Right-Pointing-Pointer The mechanical performance and thermal property of PUU film. Black-Right-Pointing-Pointer The thermo-optic property, transmission loss and dispersion property of PUU. Black-Right-Pointing-Pointer Proposed a new 1 Multiplication-Sign 2 polymeric thermo-optic switch.

Recognition of viral and self-antigens by TH1 and TH1/TH17 central memory cells in patients with multiple sclerosis reveals distinct roles in immune surveillance and relapses.

Science.gov (United States)

Paroni, Moira; Maltese, Virginia; De Simone, Marco; Ranzani, Valeria; Larghi, Paola; Fenoglio, Chiara; Pietroboni, Anna M; De Riz, Milena A; Crosti, Maria C; Maglie, Stefano; Moro, Monica; Caprioli, Flavio; Rossi, Riccardo; Rossetti, Grazisa; Galimberti, Daniela; Pagani, Massimiliano; Scarpini, Elio; Abrignani, Sergio; Geginat, Jens

2017-09-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that is caused by autoreactive T cells and associated with viral infections. However, the phenotype of pathogenic T cells in peripheral blood remains to be defined, and how viruses promote MS is debated. We aimed to identify and characterize potentially pathogenic autoreactive T cells, as well as protective antiviral T cells, in patients with MS. We analyzed CD4 + helper T-cell subsets from peripheral blood or cerebrospinal fluid for cytokine production, gene expression, plasticity, homing potentials, and their reactivity to self-antigens and viral antigens in healthy subjects and patients with MS. Moreover, we monitored their frequencies in untreated and fingolimod- or natalizumab-treated patients with MS. T H 1/T H 17 central memory (T H 1/T H 17 CM ) cells were selectively increased in peripheral blood of patients with relapsing-remitting MS with a high disease score. T H 1/T H 17 CM cells were closely related to conventional T H 17 cells but had more pathogenic features. In particular, they could shuttle between lymph nodes and the CNS and produced encephalitogenic cytokines. The cerebrospinal fluid of patients with active MS was enriched for CXCL10 and contained mainly CXCR3-expressing T H 1 and T H 1/T H 17 subsets. However, while T H 1 cells responded consistently to viruses, T H 1/T H 17 CM cells reacted strongly with John Cunningham virus in healthy subjects but responded instead to myelin-derived self-antigens in patients with MS. Fingolimod and natalizumab therapies efficiently targeted autoreactive T H 1/T H 17 CM cells but also blocked virus-specific T H 1 cells. We propose that autoreactive T H 1/T H 17 CM cells expand in patients with MS and promote relapses after bystander recruitment to the CNS, whereas T H 1 cells perform immune surveillance. Thus the selective targeting of T H 1/T H 17 cells could inhibit relapses without causing John

Effects of extinction in multiple contexts on renewal of instrumental responses.

Science.gov (United States)

Bernal-Gamboa, Rodolfo; Nieto, Javier; Uengoer, Metin

2017-09-01

In two experiments with rats, we investigated the effects of using multiple contexts during extinction on renewal of lever-pressing behavior. During the first phase of both experiments, rats were reinforced to press a lever for food in Context A. Then, responses underwent extinction. For half of the animals, extinction sessions were conducted in a single context, whereas the other half received extinction in three different contexts. In Experiment 1, we observed that extinction in multiple contexts eliminated ABC renewal, but had no detectable impact on ABA renewal. Experiment 2 revealed that conducting extended extinction training in multiple contexts attenuated ABA renewal. Theoretical and clinical implications of the present findings are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of Reclassification on Thyroid Nodules with Architectural Atypia: From Non-Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinomas to Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features.

Directory of Open Access Journals (Sweden)

Min Ji Jeon

Full Text Available The follicular variant of papillary thyroid cancer (FVPTC, especially the encapsulated non-invasive subtype, is a controversial entity. Recent study suggested using 'non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP' for these indolent carcinomas. We evaluated the impact of reclassification from non-invasive encapsulated FVPTCs (EFVPTCs to NIFTPs in the diagnosis of thyroid nodules with architectural atypia.We reviewed 1301 thyroid nodules with architectural atypia in core needle biopsy (CNB specimens obtained from March 2012 to February 2013. Nodules were classified into atypia of undetermined significance with architectural atypia (AUS-A, 984, 76% or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, 317, 24%. Among them, diagnostic surgery was performed in 384 nodules (30%.In total, 160 nodules (42% presented final malignant diagnoses including 39 non-invasive encapsulated FVPTCs (10%. The malignancy rate was estimated to be 7-35% in AUS-A nodules and 28-49% in FN/SFN nodules. After reclassification, the malignancy rate was much decreased and estimated to be 5-24% in AUS-A nodules, and 23-39% in FN/SFN nodules. Thyroid nodules with final malignant diagnoses were significantly more likely to have a FN/SFN CNB diagnosis, malignant US features and concomitant nuclear atypia in CNB specimens. However, these factors could not differentiate NIFTPs from other malignancies.After reclassification of non-invasive EFVPTCs to NIFTPs, the malignancy rate of thyroid nodules with architectural atypia in CNB specimens was decreased. However, there were no preoperative factors differentiating other malignancies from NIFTPs. The presence of malignant US features or concomitant nuclear atypia might help clinicians deciding diagnostic surgery but, these features also might indicate NIFTPs.

Interesting images: Multiple coronary artery aneurysms.

Science.gov (United States)

Howard, Jonathon M; Viswanath, Omar; Armas, Alfredo; Santana, Orlando; Rosen, Gerald P

2017-01-01

We present the case of a 65-year-old male who presented with stable angina and dyspnea on exertion. His initial workup yielded a positive treadmill stress test for reversible apical ischemia, and transthoracic echocardiogram demonstrated impaired systolic function. Cardiac catheterization was then performed, revealing severe atherosclerotic disease including multiple coronary artery aneurysms. As a result, the patient was advised to and subsequently underwent a coronary artery bypass graft. This case highlights the presence of multiple coronary artery aneurysms and the ability to appreciate these pathologic findings on multiple imaging modalities, including coronary angiogram, transesophageal echocardiography, and direct visualization through the surgical field.

Multiple Realizability and Biological Laws

NARCIS (Netherlands)

Raerinne, Jani P.; Eronen, Markus I.

2012-01-01

We critically analyze Alexander Rosenberg's argument based on the multiple realizability of biological properties that there are no biological laws. The argument is intuitive and suggestive. Nevertheless, a closer analysis reveals that the argument rests on dubious assumptions about the nature of

Genomic insights into the Acidobacteria reveal strategies for their success in terrestrial environments

Science.gov (United States)

Trojan, Daniela; Roux, Simon; Herbold, Craig; Rattei, Thomas; Woebken, Dagmar

2018-01-01

Summary Members of the phylum Acidobacteria are abundant and ubiquitous across soils. We performed a large‐scale comparative genome analysis spanning subdivisions 1, 3, 4, 6, 8 and 23 (n = 24) with the goal to identify features to help explain their prevalence in soils and understand their ecophysiology. Our analysis revealed that bacteriophage integration events along with transposable and mobile elements influenced the structure and plasticity of these genomes. Low‐ and high‐affinity respiratory oxygen reductases were detected in multiple genomes, suggesting the capacity for growing across different oxygen gradients. Among many genomes, the capacity to use a diverse collection of carbohydrates, as well as inorganic and organic nitrogen sources (such as via extracellular peptidases), was detected – both advantageous traits in environments with fluctuating nutrient environments. We also identified multiple soil acidobacteria with the potential to scavenge atmospheric concentrations of H2, now encompassing mesophilic soil strains within the subdivision 1 and 3, in addition to a previously identified thermophilic strain in subdivision 4. This large‐scale acidobacteria genome analysis reveal traits that provide genomic, physiological and metabolic versatility, presumably allowing flexibility and versatility in the challenging and fluctuating soil environment. PMID:29327410

Suppression of HIV-1 viral load after multiple changes in high active ...

African Journals Online (AJOL)

1-infected patients. However, the virus persists ... chronological changes in HIV viral load and CD4+ T-cell count, and treatment outcomes of multiple combinations of .... Lewin SR, Rouzioux C. HIV cure and eradication: how will we get from the ...

Joint Estimation of Multiple Precision Matrices with Common Structures.

Science.gov (United States)

Lee, Wonyul; Liu, Yufeng

Estimation of inverse covariance matrices, known as precision matrices, is important in various areas of statistical analysis. In this article, we consider estimation of multiple precision matrices sharing some common structures. In this setting, estimating each precision matrix separately can be suboptimal as it ignores potential common structures. This article proposes a new approach to parameterize each precision matrix as a sum of common and unique components and estimate multiple precision matrices in a constrained l 1 minimization framework. We establish both estimation and selection consistency of the proposed estimator in the high dimensional setting. The proposed estimator achieves a faster convergence rate for the common structure in certain cases. Our numerical examples demonstrate that our new estimator can perform better than several existing methods in terms of the entropy loss and Frobenius loss. An application to a glioblastoma cancer data set reveals some interesting gene networks across multiple cancer subtypes.

Concanavalin-A conjugated fine-multiple emulsion loaded with 6-mercaptopurine.

Science.gov (United States)

Khopade, A J; Jain, N K

2000-01-01

Fine-multiple (water-in-oil-in-water) emulsions were prepared by two-step emulsification using sonication. They were coated with concanavalin-A (Con-A) by three methods. The one involving covalent coupling of Con-A to the multiple emulsion incorporated anchor was better compared with lipid derivatized Con-A anchoring or the glutaraldehyde-based cross-linking method, as shown by the faster rate of dextran-induced aggregation. The selected multiple emulsions were characterized by physical properties such as droplet size, encapsulation efficiency, and zeta potential. Stability parameters such as droplet size, creaming, leakage, and aggregation as a function of relative turbidity were monitored over a 1-month period, which revealed good stability of the formulations. The release profile of 6-mercaptopurine followed zero-order kinetics. Pharmacokinetic studies showed an increase in half-life and bioavailability from multiple emulsion formulations administered intravenously. There was prolonged retention of drug in various tissues of rats when treated with Con-A-coated multiple emulsion as compared with uncoated one. Our study demonstrates the suitability of fine-multiple emulsion for intravenous administration and the potential for prolonged retention of drugs and targeting in biological systems.

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men.

Directory of Open Access Journals (Sweden)

Hui Li

2010-05-01

Full Text Available Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM and found that a high proportion (10 of 28; 36% had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38% versus 34 of 175 subjects (19%; Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5' and 3' half genome or env-only sequences from plasma viral RNA (vRNA and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3-6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml. All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1

Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1

Directory of Open Access Journals (Sweden)

Grzegorz Piecha

2010-01-01

Full Text Available Primary hyperparathyroidism may occur as a part of an inherited syndrome in a combination with pancreatic endocrine tumours and/or pituitary adenoma, which is classified as Multiple Endocrine Neoplasia type 1 (MEN-1. This syndrome is caused by a germline mutation in MEN-1 gene encoding a tumour-suppressor protein, menin. Primary hyperparathyroidism is the most frequent clinical presentation of MEN-1, which usually appears in the second decade of life as an asymptomatic hypercalcemia and progresses through the next decades. The most frequent clinical presentation of MEN-1-associated primary hyperparathyroidism is bone demineralisation and recurrent kidney stones rarely followed by chronic kidney disease. The aim of this paper is to present the pathomechanism, screening procedures, diagnosis, and management of primary hyperparathyroidism in the MEN-1 syndrome. It also summarises the recent advances in the pharmacological therapy with a new group of drugs—calcimimetics.

Synthesis and characterization of the cyanobenzene-ethylenedithio-TTF donor

Directory of Open Access Journals (Sweden)

Sandrina Oliveira

2015-06-01

Full Text Available A dissymmetric TTF-type electron donor, cyanobenzene-ethylenedithio-tetrathiafulvalene (CNB-EDT-TTF, was obtained in high yield, by a cross-coupling reaction with triethyl phosphite between 2-thioxobenzo[d][1,3]dithiole-5-carbonitrile and 5,6-dihydro-[1,3]dithiolo[4,5-b][1,4]dithiin-2-one. This new donor was characterized namely by single crystal X-ray diffraction, cyclic voltammetry, NMR, UV-visible and IR spectroscopy.

neutron multiplicity measurements on 220 l waste drums containing Pu in the range 0.1-1 g 240Pueff with the time interval analysis method

International Nuclear Information System (INIS)

Baeten, P.; Bruggeman, M.; Carchon, R.; De Boeck, W.

1998-01-01

Measurement results are presented for the assay of plutonium in 220 l waste drums containing Pu-masses in the range 0.1-1 g 240 Pu eff obtained with the time interval analysis (TIA) method. TIA is a neutron multiplicity method based on the concept of one- and two-dimensional Rossi-alpha distributions. The main source of measurement bias in neutron multiplicity measurements at low count-rates is the impredictable variation of the high-multiplicity neutron background of spallation neutrons induced by cosmic rays. The TIA-method was therefore equipped with a special background filter, which is designed and optimized to reduce the influence of these spallation neutrons by rejecting the high-multiplicity events. The measurement results, obtained with the background correction filter outlined in this paper, prove the repeatability and validity of the TIA-method and show that multiplicity counting with the TIA-technique is applicable for masses as low as 0.1 g 240 Pu eff even at a detection efficiency of 12%. (orig.)

HIV-1 adaptation studies reveal a novel Env-mediated homeostasis mechanism for evading lethal hypermutation by APOBEC3G.

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Terumasa Ikeda

2018-04-01

Full Text Available HIV-1 replication normally requires Vif-mediated neutralization of APOBEC3 antiviral enzymes. Viruses lacking Vif succumb to deamination-dependent and -independent restriction processes. Here, HIV-1 adaptation studies were leveraged to ask whether viruses with an irreparable vif deletion could develop resistance to restrictive levels of APOBEC3G. Several resistant viruses were recovered with multiple amino acid substitutions in Env, and these changes alone are sufficient to protect Vif-null viruses from APOBEC3G-dependent restriction in T cell lines. Env adaptations cause decreased fusogenicity, which results in higher levels of Gag-Pol packaging. Increased concentrations of packaged Pol in turn enable faster virus DNA replication and protection from APOBEC3G-mediated hypermutation of viral replication intermediates. Taken together, these studies reveal that a moderate decrease in one essential viral activity, namely Env-mediated fusogenicity, enables the virus to change other activities, here, Gag-Pol packaging during particle production, and thereby escape restriction by the antiviral factor APOBEC3G. We propose a new paradigm in which alterations in viral homeostasis, through compensatory small changes, constitute a general mechanism used by HIV-1 and other viral pathogens to escape innate antiviral responses and other inhibitions including antiviral drugs.

Directional phonon-assisted cascading of photoexcited carriers in stepped Inx(Al0.17Ga0.83)1-xAs/Al0.17Ga0.83As multiple quantum wells

DEFF Research Database (Denmark)

Machida, S.; Matsuo, M.; Fujiwara, K.

2002-01-01

Perpendicular motion of photoexcited electron and hole pairs assisted by phononscattering is investigated in a novel step-graded staircase heterostructure consisting of strained In-1(Al0.17Ga0.83)(1-x). As multiple quantum wells (QWs) with similar widths but five different x values by cw and time...... amplitude in the inter-mediate temperature range, These variations reveal that the photoexcited carriers directionally move from shallower to deeper QWs via phonon-assisted activation above the barrier hand edge state. The PL dynamics directly indicate the perpendicular flowing of photoexcited carriers...

Boron distribution in silicon after multiple pulse excimer laser annealing

International Nuclear Information System (INIS)

Monakhov, E.V.; Svensson, B.G.; Linnarsson, M.K.; La Magna, A.; Italia, M.; Privitera, V.; Fortunato, G.; Cuscuna, M.; Mariucci, L.

2005-01-01

We have studied B redistribution in Si after excimer laser annealing (ELA) with multiple laser pulses. B was implanted with energies of 1 and 10 keV and doses of 1x10 14 and 1x10 15 cm -2 . ELA with the number of pulses from 1 to 100 was performed at room temperature and 450 deg. C in vacuum. Irrespective of the implantation parameters and the ELA conditions used, a pile-up in the B concentration is observed near the maximum melting depth after ten pulses of ELA. Moreover, a detailed study has revealed that B accumulates at the maximum melt depth gradually with the number of ELA pulses. Besides, an increase in the carrier concentration is observed at the maximum melt depth, suggesting electrical activity of the accumulated B. Formation of Si-B complexes and vacancy accumulation during multiple ELA are discussed as possible mechanisms for the B build-up

Effects of infectious mononucleosis and HLA-DRB1*15 in multiple sclerosis

DEFF Research Database (Denmark)

Nielsen, T.R.; Rostgaard, K.; Askling, J.

2009-01-01

BACKGROUND: Both human leukocyte antigen (HLA)-DRB1*15 and Epstein-Barr virus infection presenting as infectious mononucleosis (IM) are recognized as risk factors for multiple sclerosis (MS). However, their combined effect and possible interaction on MS risk is not known. OBJECTIVE: To assess...

Ductal carcinoma in a multiple fibroadenoma: Diagnostic inaccuracies

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Rao Shalinee

2010-01-01

Full Text Available We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.

Ductal carcinoma in a multiple fibroadenoma: diagnostic inaccuracies.

Science.gov (United States)

Rao, Shalinee; Latha, P Suvarna; Ravi, A; Thanka, J

2010-01-01

We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.

Multiple measures reveal antiretroviral adherence successes and challenges in HIV-infected Ugandan children.

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Jessica E Haberer

Full Text Available Adherence to HIV antiretroviral therapy (ART among children in developing settings is poorly understood.To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2-10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS. Interruptions in MEMS adherence of ≥ 48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = -0.25, p = 0.04. Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6-5.5; p = 0.001, liquid formulation use (AOR 1.4, 95%CI 1.0-2.0; p = 0.04, and caregiver's alcohol use (AOR 3.1, 95%CI 1.8-5.2; p<0.0001. Child's use of co-trimoxazole (AOR 0.5, 95%CI 0.4-0.9; p = 0.009, caregiver's use of ART (AOR 0.6, 95%CI 0.4-0.9; p = 0.03, possible caregiver depression (AOR 0.6, 95%CI 0.4-0.8; p = 0.001, and caregiver feeling ashamed of child's HIV status (AOR 0.5, 95%CI 0.3-0.6; p<0.0001 were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5-11.5; p = 0.009 and caregiver's alcohol use (AOR 5.5, 95%CI 2.8-10.7; p<0.0001 were associated with ≥ 48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95%CI 0.1-0.99; p = 0.049 and increasing assets (AOR 0.7, 95%CI 0.6-0.9; p = 0.0007 were protective against these interruptions.Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and shame may reflect fear of poor outcomes, functioning as motivation for

A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth.

Science.gov (United States)

Viloria, Katrina; Munasinghe, Amanda; Asher, Sharan; Bogyere, Roberto; Jones, Lucy; Hill, Natasha J

2016-11-25

SPARC is a matricellular protein that is involved in both pancreatic cancer and diabetes. It belongs to a wider family of proteins that share structural and functional similarities. Relatively little is known about this extended family, but evidence of regulatory interactions suggests the importance of a holistic approach to their study. We show that Hevin, SPOCKs, and SMOCs are strongly expressed within islets, ducts, and blood vessels, suggesting important roles for these proteins in the normal pancreas, while FSTL-1 expression is localised to the stromal compartment reminiscent of SPARC. In direct contrast to SPARC, however, FSTL-1 expression is reduced in pancreatic cancer. Consistent with this, FSTL-1 inhibited pancreatic cancer cell proliferation. The complexity of SPARC family proteins is further revealed by the detection of multiple cell-type specific isoforms that arise due to a combination of post-translational modification and alternative splicing. Identification of splice variants lacking a signal peptide suggests the existence of novel intracellular isoforms. This study underlines the importance of addressing the complexity of the SPARC family and provides a new framework to explain their controversial and contradictory effects. We also demonstrate for the first time that FSTL-1 suppresses pancreatic cancer cell growth.

Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

Science.gov (United States)

Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

2016-09-01

Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras. Copyright © 2016 Elsevier Inc. All rights reserved.

A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

Science.gov (United States)

Salašová, Alena; Yokota, Chika; Potěšil, David; Zdráhal, Zbyněk; Bryja, Vítězslav; Arenas, Ernest

2017-07-11

Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Our study shows for the first time that LRRK2 activates the WNT

Multiple Ectopic Hepatocellular Carcinomas Arising in the Abdominal Cavity

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Toru Miyake

2012-09-01

Full Text Available Ectopic hepatocellular carcinoma (HCC is a very rare clinical entity that is defined as HCC arising from extrahepatic liver tissue. This report presents a case of ectopic multiple HCC arising in the abdominal cavity. A 42-year-old otherwise healthy male presented with liver dysfunction at a general health checkup. Both HCV antibody and hepatitis B surface antigen were negative. Laboratory examination showed elevations in serum alpha-fetoprotein and PIVKA-II. Ultrasonography and computed tomography revealed multiple nodular lesions in the abdominal cavity with ascites without a possible primary tumor. Exploratory laparoscopy was performed, which revealed bloody ascites and multiple brown nodular tumors measuring approximately 10 mm in size that were disseminated on the perineum and mesentery. A postoperative PET-CT scan was performed but it did not reveal any evidence of a tumor in the liver. The tumors resected from the peritoneum were diagnosed as HCC. The present case of HCC was thought to have possibly developed from ectopic liver on the peritoneum or mesentery.

Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

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Mahe J

2013-08-01

Full Text Available Julien Mahe,1 Aurélie Meurette,2 Anne Moreau,3 Caroline Vercel,2 Pascale Jolliet1,4 1Clinical Pharmacology Department, Institute of Biology, University Hospital, Nantes, France; 2Clinical Nephrology and Immunology Department, University Hospital, Nantes, France; 3Laboratory of Pathology, University Hospital, Nantes, France; 4EA 4275 Biostatistics, Pharmacoepidemiology and Subjective Measures in Health Sciences, University of Nantes, Nantes, France Abstract: Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. Keywords: thrombotic microangiopathy, interferon beta, hemolytic-uremic syndrome, antiangiogenic activity

Abundance of Stress, Anxiety and Depression in Multiple Sclerosis Patients

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A. Dehghan

2013-05-01

Conclusion: The findings of this research revealed high stress, anxiety and depression in Multiple Sclerosis Patients that can jeopardize their health. Hence the providing appropriate education for coping and adapting with the symptoms in Multiple Sclerosis Patients seems to be necessary.

LUT REVEALS AN ALGOL-TYPE ECLIPSING BINARY WITH THREE ADDITIONAL STELLAR COMPANIONS IN A MULTIPLE SYSTEM

Energy Technology Data Exchange (ETDEWEB)

Zhu, L.-Y.; Zhou, X.; Qian, S.-B.; Li, L.-J.; Liao, W.-P.; Tian, X.-M.; Wang, Z.-H. [Yunnan Observatories, Chinese Academy of Sciences (CAS), P.O. Box 110, 650011 Kunming (China); Hu, J.-Y., E-mail: zhuly@ynao.ac.cn [National Astronomical Observatories, Chinese Academy of Sciences, 100012 Beijing (China)

2016-04-15

A complete light curve of the neglected eclipsing binary Algol V548 Cygni in the UV band was obtained with the Lunar-based Ultraviolet Telescope in 2014 May. Photometric solutions are obtained using the Wilson–Devinney method. It is found that solutions with and without third light are quite different. The mass ratio without third light is determined to be q = 0.307, while that derived with third light is q = 0.606. It is shown that V548 Cygni is a semi-detached binary where the secondary component is filling the critical Roche lobe. An analysis of all available eclipse times suggests that there are three cyclic variations in the O–C diagram that are interpreted by the light travel-time effect via the presence of three additional stellar companions. This is in agreement with the presence of a large quantity of third light in the system. The masses of these companions are estimated as m sin i′ ∼ 1.09, 0.20, and 0.52 M{sub ⊙}. They are orbiting the central binary with orbital periods of about 5.5, 23.3, and 69.9 years, i.e., in 1:4:12 resonance orbit. Their orbital separations are about 4.5, 13.2, and 26.4 au, respectively. Our photometric solutions suggest that they contribute about 32.4% to the total light of the multiple system. No obvious long-term changes in the orbital period were found, indicating that the contributions of the mass transfer and the mass loss due to magnetic braking to the period variations are comparable. The detection of three possible additional stellar components orbiting a typical Algol in a multiple system make V548 Cygni a very interesting binary to study in the future.

Structure of the human protein kinase MPSK1 reveals an atypical activation loop architecture.

Science.gov (United States)

Eswaran, Jeyanthy; Bernad, Antonio; Ligos, Jose M; Guinea, Barbara; Debreczeni, Judit E; Sobott, Frank; Parker, Sirlester A; Najmanovich, Rafael; Turk, Benjamin E; Knapp, Stefan

2008-01-01

The activation segment of protein kinases is structurally highly conserved and central to regulation of kinase activation. Here we report an atypical activation segment architecture in human MPSK1 comprising a beta sheet and a large alpha-helical insertion. Sequence comparisons suggested that similar activation segments exist in all members of the MPSK1 family and in MAST kinases. The consequence of this nonclassical activation segment on substrate recognition was studied using peptide library screens that revealed a preferred substrate sequence of X-X-P/V/I-phi-H/Y-T*-N/G-X-X-X (phi is an aliphatic residue). In addition, we identified the GTPase DRG1 as an MPSK1 interaction partner and specific substrate. The interaction domain in DRG1 was mapped to the N terminus, leading to recruitment and phosphorylation at Thr100 within the GTPase domain. The presented data reveal an atypical kinase structural motif and suggest a role of MPSK1 regulating DRG1, a GTPase involved in regulation of cellular growth.

Effect of gelation of inner dispersed phase on stability of (w1/o/w2) multiple emulsions

NARCIS (Netherlands)

Oppermann, A.K.L.; Renssen, M.; Schuch, A.; Stieger, M.A.; Scholten, E.

2015-01-01

The use of water-in-oil-in-water (w1/o/w2) multiple emulsions offers a method for the reduction of oil in foods. In this study we investigated the influence of osmotic pressure tailoring and gelation of the inner dispersed w1 water droplets on the stability and yield of multiple emulsions. Yield is

Streptococcus oralis Neuraminidase Modulates Adherence to Multiple Carbohydrates on Platelets

Science.gov (United States)

Singh, Anirudh K.; Woodiga, Shireen A.; Grau, Margaret A.

2016-01-01

ABSTRACT Adherence to host surfaces is often mediated by bacterial binding to surface carbohydrates. Although it is widely appreciated that some bacterial species express glycosidases, previous studies have not considered whether bacteria bind to multiple carbohydrates within host glycans as they are modified by bacterial glycosidases. Streptococcus oralis is a leading cause of subacute infective endocarditis. Binding to platelets is a critical step in disease; however, the mechanisms utilized by S. oralis remain largely undefined. Studies revealed that S. oralis, like Streptococcus gordonii and Streptococcus sanguinis, binds platelets via terminal sialic acid. However, unlike those organisms, S. oralis produces a neuraminidase, NanA, which cleaves terminal sialic acid. Further studies revealed that following NanA-dependent removal of terminal sialic acid, S. oralis bound exposed β-1,4-linked galactose. Adherence to both these carbohydrates required Fap1, the S. oralis member of the serine-rich repeat protein (SRRP) family of adhesins. Mutation of a conserved residue required for sialic acid binding by other SRRPs significantly reduced platelet binding, supporting the hypothesis that Fap1 binds this carbohydrate. The mechanism by which Fap1 contributes to β-1,4-linked galactose binding remains to be defined; however, binding may occur via additional domains of unknown function within the nonrepeat region, one of which shares some similarity with a carbohydrate binding module. This study is the first demonstration that an SRRP is required to bind β-1,4-linked galactose and the first time that one of these adhesins has been shown to be required for binding of multiple glycan receptors. PMID:27993975

Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines

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Kan Anne A

2012-08-01

Full Text Available Abstract Mesial temporal lobe epilepsy (mTLE is a chronic and often treatment-refractory brain disorder characterized by recurrent seizures originating from the hippocampus. The pathogenic mechanisms underlying mTLE remain largely unknown. Recent clinical and experimental evidence supports a role of various inflammatory mediators in mTLE. Here, we performed protein expression profiling of 40 inflammatory mediators in surgical resection material from mTLE patients with and without hippocampal sclerosis, and autopsy controls using a multiplex bead-based immunoassay. In mTLE patients we identified 21 upregulated inflammatory mediators, including 10 cytokines and 7 chemokines. Many of these upregulated mediators have not previously been implicated in mTLE (for example, CCL22, IL-7 and IL-25. Comparing the three patient groups, two main hippocampal expression patterns could be distinguished, pattern I (for example, IL-10 and IL-25 showing increased expression in mTLE + HS patients compared to mTLE-HS and controls, and pattern II (for example, CCL4 and IL-7 showing increased expression in both mTLE groups compared to controls. Upregulation of a subset of inflammatory mediators (for example, IL-25 and IL-7 could not only be detected in the hippocampus of mTLE patients, but also in the neocortex. Principle component analysis was used to cluster the inflammatory mediators into several components. Follow-up analyses of the identified components revealed that the three patient groups could be discriminated based on their unique expression profiles. Immunocytochemistry showed that IL-25 IR (pattern I and CCL4 IR (pattern II were localized in astrocytes and microglia, whereas IL-25 IR was also detected in neurons. Our data shows co-activation of multiple inflammatory mediators in hippocampus and neocortex of mTLE patients, indicating activation of multiple pro- and anti-epileptogenic immune pathways in this disease.

Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells

International Nuclear Information System (INIS)

Rhee, Yun-Hee; Jeong, Soo-Jin; Lee, Hyo-Jeong; Lee, Hyo-Jung; Koh, Wonil; Jung, Ji Hoon; Kim, Sun-Hee; Sung-Hoon, Kim

2012-01-01

Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells. Despite weak cytotoxicity against U266 cells, EP suppressed phosphorylation, DNA binding activity and nuclear translocalization of signal transducer and activator of transcription 3 (STAT3) in U266 cells at nontoxic concentrations. Also, EP inhibited phosphorylation of the upstream kinases Janus kinase 2 (JAK2) and Src in a time-dependent manner. Furthermore, EP increased the expression of protein tyrosine phosphatase SHP-1 at protein and mRNA levels, and conversely silencing of the SHP-1 gene clearly blocked EP-mediated STAT3 inactivation. In addition, EP significantly decreased vascular endothelial growth factor (VEGF), one of STAT3 target genes at cellular and protein levels as well as disrupted in vitro tube formation assay. Moreover, EP significantly suppressed the growth of U266 cells inoculated in female BALB/c athymic nude mice and immunohistochemistry revealed that EP effectively reduced the expression of STAT3 and CD34 in tumor sections compared to untreated control. These findings suggest that EP can exert antitumor activity in multiple myeloma U266 cells partly with antiangiogenic activity targeting JAK2/STAT3 signaling pathway as a potent cancer preventive agent for treatment of multiple myeloma cells

Surgical approach in patients with hyperparathyroidism in multiple endocrine neoplasia type 1: total versus partial parathyroidectomy

Directory of Open Access Journals (Sweden)

Francesco Tonelli

2012-01-01

Full Text Available Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1 correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2 avoid persistent hypoparathyroidism; and 3 facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1 subtotal parathyroidectomy with removal of at least 3-3 K glands; and 2 total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1 the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2 the surgeon's experience; 3 the timing of surgery; 4 the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay of the curative potential of the surgical procedure; and, 5 the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence.

Predicting Fuel Ignition Quality Using 1H NMR Spectroscopy and Multiple Linear Regression

KAUST Repository

Abdul Jameel, Abdul Gani; Naser, Nimal; Emwas, Abdul-Hamid M.; Dooley, Stephen; Sarathy, Mani

2016-01-01

An improved model for the prediction of ignition quality of hydrocarbon fuels has been developed using 1H nuclear magnetic resonance (NMR) spectroscopy and multiple linear regression (MLR) modeling. Cetane number (CN) and derived cetane number (DCN

Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

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Monika Tschochner

Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

Heterologous expression of mammalian Plk1 in Drosophila reveals divergence from Polo during late mitosis

International Nuclear Information System (INIS)

Pearson, John; Godinho, Susana A.; Tavares, Alvaro; Glover, David M.

2006-01-01

Drosophila Polo kinase is the founder member of a conserved kinase family required for multiple stages of mitosis. We assessed the ability of mouse Polo-like kinase 1 (Plk1) to perform the multiple mitotic functions of Polo kinase, by expressing a Plk1-GFP fusion in Drosophila. Consistent with the previously reported localization of Polo kinase, Plk1-GFP was strongly localized to centrosomes and recruited to the centromeric regions of condensing chromosomes during early mitosis. However, in contrast to a functional Polo-GFP fusion, Plk1-GFP failed to localize to the central spindle midzone in both syncytial embryo mitosis and the conventional mitoses of cellularized embryos and S2 cells. Moreover, unlike endogenous Polo kinase and Polo-GFP, Plk1-GFP failed to associate with the contractile ring. Expression of Plk1-GFP enhanced the lethality of hypomorphic polo mutants and disrupted the organization of the actinomyosin cytoskeleton in a dominant-negative manner. Taken together, our results suggest that endogenous Polo kinase has specific roles in regulating actinomyosin rearrangements during Drosophila mitoses that its mammalian counterpart, Plk1, cannot fulfill. Consistent with this hypothesis, we observed defects in the cortical recruitment of myosin and myosin regulatory light chain in Polo deficient cells

Optimizing antiemetic therapy in multiple-day and multiple cycles of chemotherapy

DEFF Research Database (Denmark)

Ellebaek, E.; Herrstedt, J.

2008-01-01

PURPOSE OF REVIEW: Only a few studies have investigated the effect of antiemetic therapy in patients treated with multiple-day or multiple cycles of chemotherapy. The present review will assess the available data, highlight the current recommendations and draw attention towards the remaining...... of chemotherapy the addition of a NK1-receptor antagonist aprepitant to standard antiemetic therapy has increased the antiemetic effect, and multiple cycle extension studies have demonstrated that this increment in effect is sustained during multiple cycles of chemotherapy. A recent study indicated...... that the dopamine D2-receptor antagonist metopimazine has some additive effect on delayed symptoms induced by multiple-day chemotherapy. SUMMARY: The development of the NK1-receptor antagonist aprepitant has significantly improved the antiemetic control in patients treated with multiple cycles of chemotherapy. Far...

MULTIPLE SHELLS AROUND G79.29+0.46 REVEALED FROM NEAR-IR TO MILLIMETER DATA

International Nuclear Information System (INIS)

Jimenez-Esteban, F. M.; Rizzo, J. R.; Palau, Aina

2010-01-01

Aiming to perform a study of the warm dust and gas in the luminous blue variable star G79.29+0.46 and its associated nebula, we present infrared Spitzer imaging and spectroscopy, and new CO J = 2 → 1 and 4 → 3 maps obtained with the IRAM 30 m radio telescope and the Submillimeter Telescope, respectively. We have analyzed the nebula detecting multiple shells of dust and gas connected to the star. Using Infrared Spectrograph-Spitzer spectra, we have compared the properties of the central object, the nebula, and their surroundings. These spectra show a rich variety of solid-state features (amorphous silicates, polycyclic aromatic hydrocarbons, and CO 2 ices) and narrow emission lines, superimposed on a thermal continuum. We have also analyzed the physical conditions of the nebula, which point to the existence of a photo-dissociation region.

An Investigation of Aging Behaviour in Microalloyed Steel (X70) UOE Pipe

Science.gov (United States)

Wiskel, J. B.; Ma, J.; Ivey, D. G.; Henein, H.

Aging of microalloyed steel pipe can occur at relatively low temperatures associated with the pipe coating process and/or during long term storage or use. The aging phenomenon is primarily attributed to C diffusion to dislocations and subsequent pinning of these dislocations. Important factors in the aging process include time, temperature, chemical composition and plastic deformation (arising from the pipe forming process). The work presented in this paper uses a Box-Behnken experimental design to determine the effect of time, temperature, location in the UOE pipe (90° or 180° to the weld), position through the pipe wall thickness (ID, CL or OD) and the steel's C/Nb ratio (0.60, 1.25 and 1.80) on the change in yield strength of three (uncoated) X70 UOE pipes. Quantitative microstructure analysis is undertaken to determine the grain size and microconstituent fractions of the as-received pipe material. Quadratic equations and response surface(s) correlating the significant aging variables with changes in the longitudinal yield stress of the pipe are developed. Both through thickness position and the C/Nb ratio, followed by aging temperature, had the largest effect on the change in longitudinal yield strength.

CAMKII and calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16.

Science.gov (United States)

Tao, Li; Xie, Qi; Ding, Yue-He; Li, Shang-Tong; Peng, Shengyi; Zhang, Yan-Ping; Tan, Dan; Yuan, Zengqiang; Dong, Meng-Qiu

2013-06-25

The insulin-like signaling pathway maintains a relatively short wild-type lifespan in Caenorhabditis elegans by phosphorylating and inactivating DAF-16, the ortholog of the FOXO transcription factors of mammalian cells. DAF-16 is phosphorylated by the AKT kinases, preventing its nuclear translocation. Calcineurin (PP2B phosphatase) also limits the lifespan of C. elegans, but the mechanism through which it does so is unknown. Herein, we show that TAX-6•CNB-1 and UNC-43, the C. elegans Calcineurin and Ca(2+)/calmodulin-dependent kinase type II (CAMKII) orthologs, respectively, also regulate lifespan through DAF-16. Moreover, UNC-43 regulates DAF-16 in response to various stress conditions, including starvation, heat or oxidative stress, and cooperatively contributes to lifespan regulation by insulin signaling. However, unlike insulin signaling, UNC-43 phosphorylates and activates DAF-16, thus promoting its nuclear localization. The phosphorylation of DAF-16 at S286 by UNC-43 is removed by TAX-6•CNB-1, leading to DAF-16 inactivation. Mammalian FOXO3 is also regulated by CAMKIIA and Calcineurin. DOI:http://dx.doi.org/10.7554/eLife.00518.001.

The complete genome sequence of Bacillus velezensis strain GH1-13 reveals agriculturally beneficial properties and a unique plasmid.

Science.gov (United States)

Kim, Sang Yoon; Song, Hajin; Sang, Mee Kyung; Weon, Hang-Yeon; Song, Jaekyeong

2017-10-10

The bacterial strain Bacillus velezensis GH1-13, isolated from rice paddy soil in Korea, has been shown to promote plant growth and have strong antagonistic activities against pathogens. Here, we report the complete genome sequence of GH1-13, revealing that it possesses a single 4,071,980-bp circular chromosome with 46.2% GC-content. The chromosome encodes 3,930 genes, and we have also identified a unique plasmid in the strain that encodes a further 104 genes (71,628bp and 31.7% GC-content). The genome was found to contain various enzyme-encoding operons, including indole-3-acetic acid (IAA) biosynthesis proteins, 2,3-butanediol dehydrogenase, various non-ribosomal peptide synthetases, and several polyketide synthases. These properties are responsible for the promotion of plant growth and the biosynthesis of secondary metabolites. They therefore have multiple beneficial effects that could be applied to agriculture. Through curing, we found that the unique plasmid of GH1-13 has important roles in the production of phytohormones, such as IAA, and in shaping phenotypic and physiological characteristics. The plasmid therefore likely influences the biological activities of GH1-13. The complete genome sequence of B. velezensis GH1-13 contributes to our understanding of this beneficial strain and will encourage research into its development for agricultural or biotechnological applications, enhancing productivity and crop quality. Copyright © 2017 Elsevier B.V. All rights reserved.

Fibroblast growth factor receptor 3 interacts with and activates TGFβ-activated kinase 1 tyrosine phosphorylation and NFκB signaling in multiple myeloma and bladder cancer.

Directory of Open Access Journals (Sweden)

Lisa Salazar

Full Text Available Cancer is a major public health problem worldwide. In the United States alone, 1 in 4 deaths is due to cancer and for 2013 a total of 1,660,290 new cancer cases and 580,350 cancer-related deaths are projected. Comprehensive profiling of multiple cancer genomes has revealed a highly complex genetic landscape in which a large number of altered genes, varying from tumor to tumor, impact core biological pathways and processes. This has implications for therapeutic targeting of signaling networks in the development of treatments for specific cancers. The NFκB transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFκB activation. A critical mediator of NFκB activity is TGFβ-activated kinase 1 (TAK1. Here, we identify TAK1 as a novel interacting protein and target of fibroblast growth factor receptor 3 (FGFR3 tyrosine kinase activity. We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes that regulate NFκB signaling, and promote both NFκB transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types. Our findings suggest TAK1 as a potential therapeutic target for FGFR3-associated cancers, and other malignancies in which TAK1 contributes to constitutive NFκB activation.

Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3

DEFF Research Database (Denmark)

Hovden, Silje; Jespersen, Marie Louise; Nissen, Peter H

2016-01-01

Familial hypocalciuric hypercalcemia type 3 should be considered as differential diagnosis in patients with suspected primary hyperparathyroidism and/or suspected multiple neoplasia syndrome, as correct diagnosis will spare the patients for going through multiple futile parathyroidectomies...... and for the worry of being diagnosed with a cancer susceptibility syndrome....

The mitochondrial ND1 m.3337G>A mutation associated to multiple mitochondrial DNA deletions in a patient with Wolfram syndrome and cardiomyopathy.

Science.gov (United States)

Mezghani, Najla; Mnif, Mouna; Mkaouar-Rebai, Emna; Kallel, Nozha; Salem, Ikhlass Haj; Charfi, Nadia; Abid, Mohamed; Fakhfakh, Faiza

2011-07-29

Wolfram syndrome (WFS) is a rare hereditary disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is a heterogeneous disease and full characterization of all clinical and biological features of this disorder is difficult. The wide spectrum of clinical expression, affecting several organs and tissues, and the similarity in phenotype between patients with Wolfram syndrome and those with certain types of respiratory chain diseases suggests mitochondrial DNA (mtDNA) involvement in Wolfram syndrome patients. We report a Tunisian patient with clinical features of moderate Wolfram syndrome including diabetes, dilated cardiomyopathy and neurological complications. The results showed the presence of the mitochondrial ND1 m.3337G>A mutation in almost homoplasmic form in 3 tested tissues of the proband (blood leukocytes, buccal mucosa and skeletal muscle). In addition, the long-range PCR amplifications revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient's skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of moderate Wolfram syndrome associated with cardiomyopathy, in whom we detected the ND1 m.3337G>A mutation with mitochondrial multiple deletions. Copyright © 2011 Elsevier Inc. All rights reserved.

Preimplantation genetic diagnosis for a patient with multiple endocrine neoplasia type 1: case report.

Science.gov (United States)

Lima, Aline Dt; Alves, Vanessa R; Rocha, Andressa R; Martinhago, Ana C; Martinhago, Ciro; Donadio, Nilka; Dzik, Artur; Cavagna, Mario; Gebrim, Luiz H

2018-03-01

Preimplantation genetic diagnosis was carried out for embryonic analysis in a patient with multiple endocrine neoplasia type 1 (MEN1). This is a rare autosomal-dominant cancer syndrome and the patients with MEN1 are characterized by the occurrence of tumors in multiple endocrine tissues, associated with germline and somatic inactivating mutations in the MEN1 gene. This case report documents a successful preimplantation genetic diagnosis (PGD) involving a couple at-risk for MEN1 syndrome, with a birth of a healthy infant. The couple underwent a cycle of controlled ovarian stimulation and intracytoplasmic sperm injection (ICSI). Embryos were biopsied at the blastocyst stage and cryopreserved; we used PCR-based DNA analysis for PGD testing. Only one of the five embryos analyzed for MEN1 syndrome was unaffected. This embryo was thawed and transferred following endometrial preparation. After positive βHCG test; clinical pregnancy was confirmed by ultrasound, and a healthy infant was born. PGD for single gene disorders has been an emerging therapeutic tool for couples who are at risk of passing a genetic disease on to their offspring.

Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.

Science.gov (United States)

Zhou, Yebin; Wu, Jianming; Kucik, Dennis F; White, Nathan B; Redden, David T; Szalai, Alexander J; Bullard, Daniel C; Edberg, Jeffrey C

2013-11-01

Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1. Neutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Mac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE

Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.

Science.gov (United States)

Du, QiaoLing; Pan, YouDong; Zhang, YouHua; Zhang, HaiLong; Zheng, YaJuan; Lu, Ling; Wang, JunLei; Duan, Tao; Chen, JianFeng

2014-07-07

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.

Characterization of a ZnxCd1-xSe/Znx'Cdy'Mg1-x'-y'Se multiple quantum well structure for mid-infrared device applications by contactless electroreflectance and Fourier transform infrared spectroscopy

International Nuclear Information System (INIS)

Wu, J D; Lin, J W; Huang, Y S; Charles, W O; Shen, A; Zhang, Q; Tamargo, M C

2009-01-01

Contactless electroreflectance (CER) and Fourier transform infrared (FTIR) spectroscopy were used to study the intersubband transitions of a Zn x Cd 1-x Se/Zn x' Cd y' Mg 1-x'-y' Se multiple quantum well (MQW) structure grown by molecular beam epitaxy for mid-infrared device applications. The CER spectrum revealed a wide range of possible optical transitions in the MQW structure. The ground state transition was assigned by comparison with the photoluminescence emission signal taken from the same structure. A comprehensive analysis of the CER spectrum led to the identification of various interband transitions. The intersubband transitions were estimated and confirmed by FTIR measurements. The results demonstrate the potential of using CER as a complementary technique for the contactless and nondestructive characterization of the wide band gap II-VI MQW structures for mid-IR intersubband device applications.

Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1.

Science.gov (United States)

Seely, Jeffrey S; Kaufman, Matthew T; Ryu, Stephen I; Shenoy, Krishna V; Cunningham, John P; Churchland, Mark M

2016-11-01

Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure-a basic example is the frequency spectrum-and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1) and primary motor cortex (M1). All V1 datasets were 'simplest' (there were relatively few degrees of freedom) along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models.

Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1.

Directory of Open Access Journals (Sweden)

Jeffrey S Seely

2016-11-01

Full Text Available Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure-a basic example is the frequency spectrum-and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1 and primary motor cortex (M1. All V1 datasets were 'simplest' (there were relatively few degrees of freedom along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models.

Formulation and characterization of a multiple emulsion containing 1% L-ascorbic acid

Directory of Open Access Journals (Sweden)

Naveed Akhtar

2010-04-01

Full Text Available The purpose of the study was to prepare a stable multiple emulsion containing a skin anti-aging agent and using paraffin oil. Vitamin C, was incorporated into the inner aqueous phase of water-in-oil-in-water (w/o/w multiple emulsion at a concentration of 1%. Multiple emulsion was prepared by two step method. Stability studies were performed at different accelerated conditions, i.e. 8 oC (in refrigerator, 25 oC (in oven, 40 oC (in oven, and 40 oC at 75% RH (in stability cabin for 28 days to predict the stability of formulations. Different parameters, namely pH, globule size, electrical conductivity and effect of centrifugation (simulating gravity were determined during stability studies. Data obtained was evaluated statistically using ANOVA two way analyses and LSD tests. Multiple emulsion formulated was found to be stable at lower temperatures (i.e. 8 and 25 oC for 28 days. No phase separation was observed in the samples during stability testing. It was found that there was no significant change (p > 0.05 in globule sizes in most of the samples kept at various conditions. Insignificant changes (p > 0.05 in both pH and conductivity values were determined for the samples kept at 8, 40, and 40 oC at 75% RH, throughout the study period. Further studies are needed to formulate more stable emulsions with other emulsifying agents.

Dynamic Response Genes in CD4+ T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Sandra Hellberg

2016-09-01

Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

Electrochemical properties of arc-black and carbon nano-balloon as electrochemical capacitor electrodes

International Nuclear Information System (INIS)

Sato, T; Suda, Y; Uruno, H; Takikawa, H; Tanoue, H; Ue, H; Aoyagi, N; Okawa, T; Shimizu, K

2012-01-01

In this study, we used two types of carbon nanomaterials, arc-black (AcB) which has an amorphous structure and carbon nano-balloon (CNB) which has a graphitic structure as electrochemical capacitor electrodes. We made a coin electrode from these carbon materials and fabricated an electric double-layer capacitor (EDLC) that sandwiches a separator between the coin electrodes. On the other hand, RuO 2 was loaded on these carbon materials, and we fabricated a pseudo-capacitor that has an ion insertion mechanism into RuO 2 . For comparison with these carbon materials, activated carbon (AC) was also used for a capacitor electrode. The electrochemical properties of all the capacitors were evaluated in 1M H 2 SO 4 aqueous solution. As a result of EDLC performance, AcB electrode had a higher specific capacitance than AC electrode at a high scan rate (≥ 100 mV/s). In the evaluation of pseudo-capacitor performance, RuO 2 -loaded CNB electrode showed a high specific capacitance of 734 F/g per RuO 2 weight.

Econometric Analysis of Croatia’s Proclaimed Foreign Exchange Rate

Directory of Open Access Journals (Sweden)

Mance Davor

2015-04-01

Full Text Available The officially proclaimed foreign exchange policy of the Croatian National Bank (CNB is a managed float with a discretionary right of intervention on the Croatian kuna/euro foreign exchange (FX market in order to maintain price stability. This paper examines the validity of three monetary policy hypotheses: the stability of the nominal exchange rate, the stability of exchange rate changes, and the exchange rate to inflation pass-through effect. The CNB claims a direct FX to inflation rate pass-through channel for which we find no evidence, but we find a strong link between FX rate changes and changes in M4, as well as between M4 changes and inflation. Changes in foreign investment Granger cause changes in monetary aggregates that further Granger cause inflation. Changes in FX rate Granger cause a reaction in M4 that indirectly Granger causes a further rise in inflation. Vector Autoregression Impulse Response Functions of changes in FX rate, M1, M4, and CPI confirm the Granger causalities in the established order.

Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody.

Science.gov (United States)

Donahue, Renee N; Lepone, Lauren M; Grenga, Italia; Jochems, Caroline; Fantini, Massimo; Madan, Ravi A; Heery, Christopher R; Gulley, James L; Schlom, Jeffrey

2017-01-01

Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers. This study was designed to investigate the effect on immune cell subsets in the peripheral blood of cancer patients prior to and following multiple administrations of avelumab. One hundred twenty-three distinct immune cell subsets in the peripheral blood of cancer patients ( n  = 28) in a phase I trial were analyzed by flow cytometry prior to and following one, three, and nine cycles of avelumab. Changes in soluble (s) CD27 and sCD40L in plasma were also evaluated. In vitro studies were also performed to determine if avelumab would mediate ADCC of PBMC. No statistically significant changes in any of the 123 immune cell subsets analyzed were observed at any dose level, or number of doses, of avelumab. Increases in the ratio of sCD27:sCD40L were observed, suggesting potential immune activation. Controlled in vitro studies also showed lysis of tumor cells by avelumab versus no lysis of PBMC from five donors. These studies demonstrate the lack of any significant effect on multiple immune cell subsets, even those expressing PD-L1, following multiple cycles of avelumab. These results complement prior studies showing anti-tumor effects of avelumab and comparable levels of adverse events with avelumab versus other anti-PD-1/PD-L1 MAbs. These studies provide the rationale to further exploit the potential ADCC mechanism of action of avelumab as well as other human IgG1 checkpoint

ARCHITECTURE AND DYNAMICS OF KEPLER'S CANDIDATE MULTIPLE TRANSITING PLANET SYSTEMS

Energy Technology Data Exchange (ETDEWEB)

Lissauer, Jack J.; Jenkins, Jon M.; Borucki, William J.; Bryson, Stephen T.; Howell, Steve B. [NASA Ames Research Center, Moffett Field, CA 94035 (United States); Ragozzine, Darin; Holman, Matthew J.; Carter, Joshua A. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Fabrycky, Daniel C.; Fortney, Jonathan J. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Steffen, Jason H. [Fermilab Center for Particle Astrophysics, Batavia, IL 60510 (United States); Ford, Eric B. [211 Bryant Space Science Center, University of Florida, Gainesville, FL 32611 (United States); Shporer, Avi [Las Cumbres Observatory Global Telescope Network, Santa Barbara, CA 93117 (United States); Rowe, Jason F.; Quintana, Elisa V.; Caldwell, Douglas A. [SETI Institute/NASA Ames Research Center, Moffett Field, CA 94035 (United States); Batalha, Natalie M. [Department of Physics and Astronomy, San Jose State University, San Jose, CA 95192 (United States); Ciardi, David [Exoplanet Science Institute/Caltech, Pasadena, CA 91125 (United States); Dunham, Edward W. [Lowell Observatory, Flagstaff, AZ 86001 (United States); Gautier, Thomas N. III, E-mail: Jack.Lissauer@nasa.gov [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); and others

2011-11-01

About one-third of the {approx}1200 transiting planet candidates detected in the first four months of Kepler data are members of multiple candidate systems. There are 115 target stars with two candidate transiting planets, 45 with three, 8 with four, and 1 each with five and six. We characterize the dynamical properties of these candidate multi-planet systems. The distribution of observed period ratios shows that the vast majority of candidate pairs are neither in nor near low-order mean-motion resonances. Nonetheless, there are small but statistically significant excesses of candidate pairs both in resonance and spaced slightly too far apart to be in resonance, particularly near the 2:1 resonance. We find that virtually all candidate systems are stable, as tested by numerical integrations that assume a nominal mass-radius relationship. Several considerations strongly suggest that the vast majority of these multi-candidate systems are true planetary systems. Using the observed multiplicity frequencies, we find that a single population of planetary systems that matches the higher multiplicities underpredicts the number of singly transiting systems. We provide constraints on the true multiplicity and mutual inclination distribution of the multi-candidate systems, revealing a population of systems with multiple super-Earth-size and Neptune-size planets with low to moderate mutual inclinations.

Nuclear topography of the 1q21 genomic region and MCl-1 protein levels associated with pathophysiology of multiple myeloma

Czech Academy of Sciences Publication Activity Database

Legartová, Soňa; Krejčí, Jana; Harničarová, Andrea; Hájek, R.; Kozubek, Stanislav; Bártová, Eva

2009-01-01

Roč. 56, č. 5 (2009), s. 404-413 ISSN 0028-2685 R&D Projects: GA MŠk(CZ) LC06027; GA AV ČR(CZ) 1QS500040508 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : multiple myeloma * 1q21 * DNA-FISH Subject RIV: BO - Biophysics Impact factor: 1.192, year: 2009

Cellular response of pulp fibroblast to single or multiple photobiomodulation applications

Science.gov (United States)

Fernandes, Amanda; Lourenço Neto, Natalino; Teixeira Marques, Nadia Carolina; Lourenço Ribeiro Vitor, Luciana; Tavares Oliveira Prado, Mariel; Cardoso Oliveira, Rodrigo; Moreira Machado, Maria Aparecida Andrade; Marchini Oliveira, Thais

2018-06-01

This study aimed to evaluate in vitro the effects of single or multiple photobiomodulation (PBM) applications on the viability and proliferation of pulp fibroblasts. Pulp fibroblasts from human deciduous teeth were obtained from a biorepository, plated into 96-well plates, and irradiated according to the experimental groups. At 24 h, 48 h, and 72 h after irradiation, cell viability and proliferation were assessed through MTT and Crystal Violet assays, respectively. The intragroup comparison revealed statistically significant differences for 2.5 J cm‑2 (3×) with increasing viability at 72 h over 48 h (p  =  0.027). The intergroup analysis showed a greater viability of the multiple PBM applications 2.5 J cm‑2 (3×) over the single application 7.5 J cm‑2 (1×) at 72 h. The application of 5 J cm‑2 (1×) exhibited greater proliferation than the application of 7.5 J cm‑2 (1×), 2.5 J cm‑2 (2×) and 2.5 J cm‑2 (3×). Single or multiple PBM applications demonstration different stimulatory effects on pulp fibroblast. The results show that the group submitted to multiple irradiation presented significantly higher cell viability than the groups with single irradiation at 72 h. However, the photobiomodulation therapy with single irradiations was more effective on cell proliferation at 24 h.

Multiple ciguatoxins present in Indian Ocean reef fish.

Science.gov (United States)

Hamilton, Brett; Hurbungs, Mira; Jones, Alun; Lewis, Richard J

2002-09-01

Optimised gradient reversed-phase high-performance liquid chromatography electrospray ionisation mass spectrometry (LC/MS) methods, in combination with a [3H]-brevetoxin binding assay (RLB), revealed multiple ciguatoxins in a partially purified extract of a highly toxic Lutjanus sebae (red emperor) from the Indian Ocean. Two major ciguatoxins of 1140.6 Da (I-CTX-1 and -2) and two minor ciguatoxins of 1156.6 Da (I-CTX-3 and -4) were identified. Accurate mass analysis revealed that I-CTX-1 and -2 and Caribbean C-CTX-1 had indistinguishable masses (1140.6316 Da, at 0.44 ppm resolution). Toxicity estimated from LC/MS/RLB responses indicated that I-CTX-1 and -2 were both approximately 60% the potency of Pacific ciguatoxin-1 (P-CTX-1). In contrast to ciguatoxins of the Pacific where the more oxidised ciguatoxins are more potent, I-CTX-3 and -4 were approximately 20% of P-CTX-1 potency. Interconversion in dilute acid or on storage, typical of spiroketal and hemiketal functionality found in P-CTXs and C-CTXs, respectively, was not observed to occur between I-CTX-1 and -2. The ratio of CTX-1 and -2 varied depending on the fish extract being analysed. These results suggest that I-CTX-1 and -2 may arise from separate dinoflagellate precursors that may be oxidatively biotransformed to I-CTX-3 and -4 in fish.

Inhibitory phenotype of HBV-specific CD4+ T-cells is characterized by high PD-1 expression but absent coregulation of multiple inhibitory molecules.

Directory of Open Access Journals (Sweden)

Bijan Raziorrouh

Full Text Available T-cell exhaustion seems to play a critical role in CD8+ T-cell dysfunction during chronic viral infections. However, up to now little is known about the mechanisms underlying CD4+ T-cell dysfunction during chronic hepatitis B virus (CHB infection and the role of inhibitory molecules such as programmed death 1 (PD-1 for CD4+ T-cell failure.The expression of multiple inhibitory molecules such as PD-1, CTLA-4, TIM-3, CD244, KLRG1 and markers defining the grade of T-cell differentiation as CCR7, CD45RA, CD57 and CD127 were analyzed on virus-specific CD4+ T-cells from peripheral blood using a newly established DRB1*01-restricted MHC class II Tetramer. Effects of in vitro PD-L1/2 blockade were defined by investigating changes in CD4+ T-cell proliferation and cytokine production.CD4+ T-cell responses during chronic HBV infection was characterized by reduced Tetramer+CD4+ T-cell frequencies, effector memory phenotype, sustained PD-1 but low levels of CTLA-4, TIM-3, KLRG1 and CD244 expression. PD-1 blockade revealed individualized patterns of in vitro responsiveness with partly increased IFN-γ, IL-2 and TNF-α secretion as well as enhanced CD4+ T-cell expansion almost in treated patients with viral control.HBV-specific CD4+ T-cells are reliably detectable during different courses of HBV infection by MHC class II Tetramer technology. CD4+ T-cell dysfunction during chronic HBV is basically linked to strong PD-1 upregulation but absent coregulation of multiple inhibitory receptors. PD-L1/2 neutralization partly leads to enhanced CD4+ T-cell functionality with heterogeneous patterns of CD4+ T-cell rejunivation.

Prognostic Classification Factors Associated With Development of Multiple Autoantibodies, Dysglycemia, and Type 1 Diabetes?A Recursive Partitioning Analysis

OpenAIRE

Xu, Ping; Krischer, Jeffrey P.

2016-01-01

OBJECTIVE To define prognostic classification factors associated with the progression from single to multiple autoantibodies, multiple autoantibodies to dysglycemia, and dysglycemia to type 1 diabetes onset in relatives of individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS Three distinct cohorts of subjects from the Type 1 Diabetes TrialNet Pathway to Prevention Study were investigated separately. A recursive partitioning analysis (RPA) was used to determine the risk classes. Clini...

Streptococcus oralis Neuraminidase Modulates Adherence to Multiple Carbohydrates on Platelets.

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Singh, Anirudh K; Woodiga, Shireen A; Grau, Margaret A; King, Samantha J

2017-03-01

Adherence to host surfaces is often mediated by bacterial binding to surface carbohydrates. Although it is widely appreciated that some bacterial species express glycosidases, previous studies have not considered whether bacteria bind to multiple carbohydrates within host glycans as they are modified by bacterial glycosidases. Streptococcus oralis is a leading cause of subacute infective endocarditis. Binding to platelets is a critical step in disease; however, the mechanisms utilized by S. oralis remain largely undefined. Studies revealed that S. oralis , like Streptococcus gordonii and Streptococcus sanguinis , binds platelets via terminal sialic acid. However, unlike those organisms, S. oralis produces a neuraminidase, NanA, which cleaves terminal sialic acid. Further studies revealed that following NanA-dependent removal of terminal sialic acid, S. oralis bound exposed β-1,4-linked galactose. Adherence to both these carbohydrates required Fap1, the S. oralis member of the serine-rich repeat protein (SRRP) family of adhesins. Mutation of a conserved residue required for sialic acid binding by other SRRPs significantly reduced platelet binding, supporting the hypothesis that Fap1 binds this carbohydrate. The mechanism by which Fap1 contributes to β-1,4-linked galactose binding remains to be defined; however, binding may occur via additional domains of unknown function within the nonrepeat region, one of which shares some similarity with a carbohydrate binding module. This study is the first demonstration that an SRRP is required to bind β-1,4-linked galactose and the first time that one of these adhesins has been shown to be required for binding of multiple glycan receptors. Copyright © 2017 American Society for Microbiology.

Measuring multiple residual-stress components using the contour method and multiple cuts

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Prime, Michael B [Los Alamos National Laboratory; Swenson, Hunter [Los Alamos National Laboratory; Pagliaro, Pierluigi [U. PALERMO; Zuccarello, Bernardo [U. PALERMO

2009-01-01

The conventional contour method determines one component of stress over the cross section of a part. The part is cut into two, the contour of the exposed surface is measured, and Bueckner's superposition principle is analytically applied to calculate stresses. In this paper, the contour method is extended to the measurement of multiple stress components by making multiple cuts with subsequent applications of superposition. The theory and limitations are described. The theory is experimentally tested on a 316L stainless steel disk with residual stresses induced by plastically indenting the central portion of the disk. The stress results are validated against independent measurements using neutron diffraction. The theory has implications beyond just multiple cuts. The contour method measurements and calculations for the first cut reveal how the residual stresses have changed throughout the part. Subsequent measurements of partially relaxed stresses by other techniques, such as laboratory x-rays, hole drilling, or neutron or synchrotron diffraction, can be superimposed back to the original state of the body.

Multiple spinal nerve enlargement and SOS1 mutation: Further evidence of overlap between neurofibromatosis type 1 and Noonan phenotype.

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Santoro, C; Giugliano, T; Melone, M A B; Cirillo, M; Schettino, C; Bernardo, P; Cirillo, G; Perrotta, S; Piluso, G

2018-01-01

Neurofibromatosis type 1 (NF1) has long been considered a well-defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines (NSML) or RASopathy phenotype. We describe a 15-year-old boy, whose mother previously received clinical diagnosis of NF1 due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of NS. NF1 molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. Next-generation sequencing analysis of all RASopathy genes identified p.Ser548Arg missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal magnetic resonance imaging scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a SOS1 mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in RASopathy genes. Our results highlight the overlap between RASopathies, suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of RASopathy genes should be considered when diagnosis is uncertain. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease.

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Lieber, Daniel S; Vafai, Scott B; Horton, Laura C; Slate, Nancy G; Liu, Shangtao; Borowsky, Mark L; Calvo, Sarah E; Schmahmann, Jeremy D; Mootha, Vamsi K

2012-01-06

Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients.

Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease

Directory of Open Access Journals (Sweden)

Lieber Daniel S

2012-01-01

Full Text Available Abstract Background Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Case Presentation Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. Conclusion This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients.

Guide to using Multiple Regression in Excel (MRCX v.1.1) for Removal of River Stage Effects from Well Water Levels

Energy Technology Data Exchange (ETDEWEB)

Mackley, Rob D.; Spane, Frank A.; Pulsipher, Trenton C.; Allwardt, Craig H.

2010-09-01

A software tool was created in Fiscal Year 2010 (FY11) that enables multiple-regression correction of well water levels for river-stage effects. This task was conducted as part of the Remediation Science and Technology project of CH2MHILL Plateau Remediation Company (CHPRC). This document contains an overview of the correction methodology and a user’s manual for Multiple Regression in Excel (MRCX) v.1.1. It also contains a step-by-step tutorial that shows users how to use MRCX to correct river effects in two different wells. This report is accompanied by an enclosed CD that contains the MRCX installer application and files used in the tutorial exercises.

Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing

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Ikeda H

2015-10-01

Full Text Available Hiroshi Ikeda,1 Kazuya Ishiguro,1 Tetsuyuki Igarashi,1 Yuka Aoki,1 Toshiaki Hayashi,1 Tadao Ishida,1 Yasushi Sasaki,1,2 Takashi Tokino,2 Yasuhisa Shinomura1 1Department of Gastroenterology, Rheumatology and Clinical Immunology, 2Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan Abstract: A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM, Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients. Keywords: multiple myeloma, drug resistance, genome-wide sequencing, semiconductor sequencer, target therapy

Comparing strategies to assess multiple behavior change in behavioral intervention studies.

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Drake, Bettina F; Quintiliani, Lisa M; Sapp, Amy L; Li, Yi; Harley, Amy E; Emmons, Karen M; Sorensen, Glorian

2013-03-01

Alternatives to individual behavior change methods have been proposed, however, little has been done to investigate how these methods compare. To explore four methods that quantify change in multiple risk behaviors targeting four common behaviors. We utilized data from two cluster-randomized, multiple behavior change trials conducted in two settings: small businesses and health centers. Methods used were: (1) summative; (2) z-score; (3) optimal linear combination; and (4) impact score. In the Small Business study, methods 2 and 3 revealed similar outcomes. However, physical activity did not contribute to method 3. In the Health Centers study, similar results were found with each of the methods. Multivitamin intake contributed significantly more to each of the summary measures than other behaviors. Selection of methods to assess multiple behavior change in intervention trials must consider study design, and the targeted population when determining the appropriate method/s to use.

PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update

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Reuss R

2013-05-01

Full Text Available Reinhard ReussDepartment of Neurology, BKH Bayreuth, Bayreuth, GermanyAbstract: Current standard immunomodulatory therapy with interferons (IFNs for relapsing–remitting multiple sclerosis (MS exhibits proven, but limited, efficacy and increased side effects due to the need of frequent application of the drug. Therefore, there is a need for more effective and tolerable drugs. Due to their small size, optimization of therapy with IFNs in MS by PEGylation is feasible. PEGylation of an IFN means that at least one molecule of polyethylene glycol (PEG is covalently added. This modification is a standard procedure to increase the stability, solubility, half-life, and efficacy of a drug, and is applied in several drugs and diseases. Currently, a therapy regimen applying PEG-IFN beta-1a in MS is being developed to achieve an optimized relationship between therapy-related side effects and pharmacokinetic/pharmacodynamic efficacy. Phase I studies demonstrated that subcutaneous PEG-IFN beta-1a at a dose of 125 µg every 2 or 4 weeks might be at least as efficient and safe as the current standard therapy with IFN beta-1a. A global Phase III clinical study is investigating the efficacy of PEG-IFN beta-1a in terms of reduction of the relapse rate in relapsing–remitting MS patients. The latest primary safety and efficacy analysis after 1 year has revealed a favorable risk–benefit profile with no significant difference between dosing regimens. Compared to placebo, the annualized relapse rate was reduced by about one-third and new or newly enlarging T2 brain lesions were reduced by about one-third when dosing every 4 weeks or by two-thirds when dosing every 2 weeks. This presents a significant effect of the dosing interval, favoring administration every 2 weeks. Chronic administration of PEGylated proteins mostly at toxic concentrations causes vacuolation of renal epithelium in animals, which – along with the issue of occurrence of anti-PEG antibodies �

Intact protein analysis of ubiquitin in cerebrospinal fluid by multiple reaction monitoring reveals differences in Alzheimer's disease and frontotemporal lobar degeneration.

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Oeckl, Patrick; Steinacker, Petra; von Arnim, Christine A F; Straub, Sarah; Nagl, Magdalena; Feneberg, Emily; Weishaupt, Jochen H; Ludolph, Albert C; Otto, Markus

2014-11-07

The impairment of the ubiquitin-proteasome system (UPS) is thought to be an early event in neurodegeneration, and monitoring UPS alterations might serve as a disease biomarker. Our aim was to establish an alternate method to antibody-based assays for the selective measurement of free monoubiquitin in cerebrospinal fluid (CSF). Free monoubiquitin was measured with liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MS/MS) in CSF of patients with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), behavioral variant of frontotemporal dementia (bvFTD), Creutzfeldt-Jakob disease (CJD), Parkinson's disease (PD), primary progressive aphasia (PPA), and progressive supranuclear palsy (PSP). The LC-MS/MS method showed excellent intra- and interassay precision (4.4-7.4% and 4.9-10.3%) and accuracy (100-107% and 100-106%). CSF ubiquitin concentration was increased compared with that of controls (33.0 ± 9.7 ng/mL) in AD (47.5 ± 13.1 ng/mL, p < 0.05) and CJD patients (171.5 ± 103.5 ng/mL, p < 0.001) but not in other neurodegenerative diseases. Receiver operating characteristic curve (ROC) analysis of AD vs control patients revealed an area under the curve (AUC) of 0.832, and the specificity and sensitivity were 75 and 75%, respectively. ROC analysis of AD and FTLD patients yielded an AUC of 0.776, and the specificity and sensitivity were 53 and 100%, respectively. In conclusion, our LC-MS/MS method may facilitate ubiquitin determination to a broader community and might help to discriminate AD, CJD, and FTLD patients.

Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

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Viswanathan, S.; Rose, N.; Masita, A.; Dhaliwal, J. S.; Puvanarajah, S. D.; Rafia, M. H.; Muda, S.

2013-01-01

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here. PMID:24455266

Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

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S. Viswanathan

2013-01-01

Full Text Available Background. Multiple sclerosis (MS is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

Validation and genotyping of multiple human polymorphic inversions mediated by inverted repeats reveals a high degree of recurrence.

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Cristina Aguado

2014-03-01

Full Text Available In recent years different types of structural variants (SVs have been discovered in the human genome and their functional impact has become increasingly clear. Inversions, however, are poorly characterized and more difficult to study, especially those mediated by inverted repeats or segmental duplications. Here, we describe the results of a simple and fast inverse PCR (iPCR protocol for high-throughput genotyping of a wide variety of inversions using a small amount of DNA. In particular, we analyzed 22 inversions predicted in humans ranging from 5.1 kb to 226 kb and mediated by inverted repeat sequences of 1.6-24 kb. First, we validated 17 of the 22 inversions in a panel of nine HapMap individuals from different populations, and we genotyped them in 68 additional individuals of European origin, with correct genetic transmission in ∼ 12 mother-father-child trios. Global inversion minor allele frequency varied between 1% and 49% and inversion genotypes were consistent with Hardy-Weinberg equilibrium. By analyzing the nucleotide variation and the haplotypes in these regions, we found that only four inversions have linked tag-SNPs and that in many cases there are multiple shared SNPs between standard and inverted chromosomes, suggesting an unexpected high degree of inversion recurrence during human evolution. iPCR was also used to check 16 of these inversions in four chimpanzees and two gorillas, and 10 showed both orientations either within or between species, providing additional support for their multiple origin. Finally, we have identified several inversions that include genes in the inverted or breakpoint regions, and at least one disrupts a potential coding gene. Thus, these results represent a significant advance in our understanding of inversion polymorphism in human populations and challenge the common view of a single origin of inversions, with important implications for inversion analysis in SNP-based studies.

Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A

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Marshall, Kris S.; Cohen, Michael J.; Fonseca, Greg J.; Todorovic, Biljana; King, Cason R. [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Yousef, Ahmed F. [Department of Chemical and Environmental Engineering, Masdar Institute, Abu Dhabi (United Arab Emirates); Zhang, Zhiying [College of Animal Science and Technologies, Northwest A and F University, Yangling, Shaanxi 712100 (China); Mymryk, Joe S., E-mail: jmymryk@uwo.ca [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Department of Oncology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada)

2014-04-15

The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear localization signal (NLS) located at its C-terminus. We used a genetic assay in the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is present and functional in the E1A proteins of each of the six HAdV species. This assay also detects a previously described non-canonical NLS within conserved region 3 and a novel active NLS within the N-terminal/conserved region 1 portion of HAdV-5 E1A. These activities were also present in the E1A proteins of each of the other five HAdV species. These results demonstrate that, despite substantial differences in primary sequence, HAdV E1A proteins are remarkably consistent in that they contain one canonical and two non-canonical NLSs. By utilizing independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in the infected cell. - Highlights: • HAdV E1A uses multiple mechanisms for nuclear import. • We identified an additional non-canonical NLS in the N-terminal/CR1 portion of E1A. • The new NLS does not contact importin-alpha directly. • All NLSs are functionally conserved in the E1A proteins of all 6 HAdV species.

Magnetic resonance imaging of the spine in multiple myeloma

International Nuclear Information System (INIS)

Tanaka, Masato; Nakahara, Shinnosuke; Koura, Hiroshi; Kai, Nobuo; Asaumi, Koji; Tanaka, Shunsuke; Sezaki, Tatsuo; Fukuda, Shunichi; Sunami, Kazutaka

2000-01-01

The characteristics of diagnostic imaging of the spine in multiple myeloma were examined. Twenty-one patients with stage II-III multiple myeloma (male=12, female=9, mean age=64) underwent MRI of the spine. Other diagnostic imaging modalities used in these patients included, CT bone scintigraphy, and radiography. All images of the spine were assessed and compared with the MRI images. The type of progression was evaluated based on the tumor distribution classification established by Sezaki. T1-weighted images of all 21 patients showed low signals in vertebral bodies, including 14 cases with a focal low signal intensity and 7 cases with diffuse low signal intensity. On the T2-weighted images, 15 of the 21 cases (71%) showed equivalent signals, while T2*-weighted images obtained by the field-echo method yielded high signals in 10 out of 11 cases. It was difficult to differentiate between senile osteoporosis and multiple myeloma by MRI, but CT images clearly distinguished between them. The results suggested that fat-suppressive T1-contrast images and T2*-weighted images are useful in detecting lesions, especially focal low signal intensity lesions. Patients with the multiple-lesion-tumor type of disease were more likely to develop paralysis more than those with the diffuse myeloproliferative type. Thus, the tumor distribution classification established by Sezaki was useful in considering radiotherapy for the treatment of patients at risk of paralysis. Bone scintigraphy revealed accumulation only in spinal lesions caused by compression fractures, while CT appeared to be useful in localizing the diffuse myeloproliferative type of lesions. The problems associated with diagnosis by MRI are differentiation of multiple myeloma from senile osteoporosis and metastatic bone tumors of the spine. There are few specific findings in multiple myeloma. (K.H.)

Essential Genes for In Vitro Growth of the Endophyte Herbaspirillum seropedicae SmR1 as Revealed by Transposon Insertion Site Sequencing.

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Rosconi, Federico; de Vries, Stefan P W; Baig, Abiyad; Fabiano, Elena; Grant, Andrew J

2016-11-15

The interior of plants contains microorganisms (referred to as endophytes) that are distinct from those present at the root surface or in the surrounding soil. Herbaspirillum seropedicae strain SmR1, belonging to the betaproteobacteria, is an endophyte that colonizes crops, including rice, maize, sugarcane, and sorghum. Different approaches have revealed genes and pathways regulated during the interactions of H. seropedicae with its plant hosts. However, functional genomic analysis of transposon (Tn) mutants has been hampered by the lack of genetic tools. Here we successfully employed a combination of in vivo high-density mariner Tn mutagenesis and targeted Tn insertion site sequencing (Tn-seq) in H. seropedicae SmR1. The analysis of multiple gene-saturating Tn libraries revealed that 395 genes are essential for the growth of H. seropedicae SmR1 in tryptone-yeast extract medium. A comparative analysis with the Database of Essential Genes (DEG) showed that 25 genes are uniquely essential in H. seropedicae SmR1. The Tn mutagenesis protocol developed and the gene-saturating Tn libraries generated will facilitate elucidation of the genetic mechanisms of the H. seropedicae endophytic lifestyle. A focal point in the study of endophytes is the development of effective biofertilizers that could help to reduce the input of agrochemicals in croplands. Besides the ability to promote plant growth, a good biofertilizer should be successful in colonizing its host and competing against the native microbiota. By using a systematic Tn-based gene-inactivation strategy and massively parallel sequencing of Tn insertion sites (Tn-seq), it is possible to study the fitness of thousands of Tn mutants in a single experiment. We have applied the combination of these techniques to the plant-growth-promoting endophyte Herbaspirillum seropedicae SmR1. The Tn mutant libraries generated will enable studies into the genetic mechanisms of H. seropedicae-plant interactions. The approach that we

Novel somatic single nucleotide variants within the RNA binding protein hnRNP A1 in multiple sclerosis patients [v1; ref status: indexed, http://f1000r.es/3nv

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Sangmin Lee

2014-06-01

Full Text Available Some somatic single nucleotide variants (SNVs are thought to be pathogenic, leading to neurological disease. We hypothesized that heterogeneous nuclear ribonuclear protein A1 (hnRNP A1, an autoantigen associated with multiple sclerosis (MS would contain SNVs. MS patients develop antibodies to hnRNP A1293-304, an epitope within the M9 domain (AA268-305 of hnRNP A1. M9 is hnRNP A1’s nucleocytoplasmic transport domain, which binds transportin-1 (TPNO-1 and allows for hnRNP A1’s transport into and out of the nucleus. Genomic DNA sequencing of M9 revealed nine novel SNVs that resulted in an amino acid substitution in MS patients that were not present in controls. SNVs occurred within the TPNO-1 binding domain (hnRNP A1268-289 and the MS IgG epitope (hnRNP A1293-304, within M9.  In contrast to the nuclear localization of wild type (WT hnRNP A1, mutant hnRNP A1 mis-localized to the cytoplasm, co-localized with stress granules and caused cellular apoptosis. Whilst WT hnRNP A1 bound TPNO-1, mutant hnRNP A1 showed reduced TPNO-1 binding. These data suggest SNVs in hnRNP A1 might contribute to pathogenesis of MS.

Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

DEFF Research Database (Denmark)

Goudie, David R; D'Alessandro, Mariella; Merriman, Barry

2011-01-01

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving s......-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer....

Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

DEFF Research Database (Denmark)

Goudie, David R; D'Alessandro, Mariella; Merriman, Barry

2011-01-01

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving......-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer....

T1- Thresholds in Black Holes Increase Clinical-Radiological Correlation in Multiple Sclerosis Patients.

Science.gov (United States)

Thaler, Christian; Faizy, Tobias; Sedlacik, Jan; Holst, Brigitte; Stellmann, Jan-Patrick; Young, Kim Lea; Heesen, Christoph; Fiehler, Jens; Siemonsen, Susanne

2015-01-01

Magnetic Resonance Imaging (MRI) is an established tool in diagnosing and evaluating disease activity in Multiple Sclerosis (MS). While clinical-radiological correlations are limited in general, hypointense T1 lesions (also known as Black Holes (BH)) have shown some promising results. The definition of BHs is very heterogeneous and depends on subjective visual evaluation. We aimed to improve clinical-radiological correlations by defining BHs using T1 relaxation time (T1-RT) thresholds to achieve best possible correlation between BH lesion volume and clinical disability. 40 patients with mainly relapsing-remitting MS underwent MRI including 3-dimensional fluid attenuated inversion recovery (FLAIR), magnetization-prepared rapid gradient echo (MPRAGE) before and after Gadolinium (GD) injection and double inversion-contrast magnetization-prepared rapid gradient echo (MP2RAGE) sequences. BHs (BHvis) were marked by two raters on native T1-weighted (T1w)-MPRAGE, contrast-enhancing lesions (CE lesions) on T1w-MPRAGE after GD and FLAIR lesions (total-FLAIR lesions) were detected separately. BHvis and total-FLAIR lesion maps were registered to MP2RAGE images, and the mean T1-RT were calculated for all lesion ROIs. Mean T1 values of the cortex (CTX) were calculated for each patient. Subsequently, Spearman rank correlations between clinical scores (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite) and lesion volume were determined for different T1-RT thresholds. Significant differences in T1-RT were obtained between all different lesion types with highest T1 values in visually marked BHs (BHvis: 1453.3±213.4 ms, total-FLAIR lesions: 1394.33±187.38 ms, CTX: 1305.6±35.8 ms; p1500 ms (Expanded Disability Status Scale vs. lesion volume: rBHvis = 0.442 and rtotal-FLAIR = 0.497, p<0.05; Multiple Sclerosis Functional Composite vs. lesion volume: rBHvis = -0.53 and rtotal-FLAIR = -0.627, p<0.05). Clinical-radiological correlations in MS patients are

Measuring floodplain spatial patterns using continuous surface metrics at multiple scales

Science.gov (United States)

Scown, Murray W.; Thoms, Martin C.; DeJager, Nathan R.

2015-01-01

Interactions between fluvial processes and floodplain ecosystems occur upon a floodplain surface that is often physically complex. Spatial patterns in floodplain topography have only recently been quantified over multiple scales, and discrepancies exist in how floodplain surfaces are perceived to be spatially organised. We measured spatial patterns in floodplain topography for pool 9 of the Upper Mississippi River, USA, using moving window analyses of eight surface metrics applied to a 1 × 1 m2 DEM over multiple scales. The metrics used were Range, SD, Skewness, Kurtosis, CV, SDCURV,Rugosity, and Vol:Area, and window sizes ranged from 10 to 1000 m in radius. Surface metric values were highly variable across the floodplain and revealed a high degree of spatial organisation in floodplain topography. Moran's I correlograms fit to the landscape of each metric at each window size revealed that patchiness existed at nearly all window sizes, but the strength and scale of patchiness changed within window size, suggesting that multiple scales of patchiness and patch structure exist in the topography of this floodplain. Scale thresholds in the spatial patterns were observed, particularly between the 50 and 100 m window sizes for all surface metrics and between the 500 and 750 m window sizes for most metrics. These threshold scales are ~ 15–20% and 150% of the main channel width (1–2% and 10–15% of the floodplain width), respectively. These thresholds may be related to structuring processes operating across distinct scale ranges. By coupling surface metrics, multi-scale analyses, and correlograms, quantifying floodplain topographic complexity is possible in ways that should assist in clarifying how floodplain ecosystems are structured.

Crystal structure of Arabidopsis thaliana Dawdle forkhead-associated domain reveals a conserved phospho-threonine recognition cleft for dicer-like 1 binding.

Science.gov (United States)

Machida, Satoru; Yuan, Y Adam

2013-07-01

Dawdle (DDL) is a microRNA processing protein essential for the development of Arabidopsis. DDL contains a putative nuclear localization signal at its amino-terminus and forkhead-associated (FHA) domain at the carboxyl-terminus. Here, we report the crystal structure of the FHA domain of Arabidopsis Dawdle, determined by multiple-wavelength anomalous dispersion method at 1.7-Å resolution. DDL FHA structure displays a seven-stranded β-sandwich architecture that contains a unique structural motif comprising two long anti-parallel strands. Strikingly, crystal packing of the DDL FHA domain reveals that a glutamate residue from the symmetry-related DDL FHA domain, a structural mimic of the phospho-threonine, is specifically recognized by the structurally conserved phospho-threonine binding cleft. Consistently with the structural observations, co-immuno-precipitation experiments performed in Nicotiana benthamiana show that the DDL FHA domain co-immuno-precipitates with DCL1 fragments containing the predicted pThr+3(Ile/Val/Leu/Asp) motif. Taken together, we count the recognition of the target residue by the canonical binding cleft of the DDL FHA domain as the key molecular event to instate FHA domain-mediated protein-protein interaction in plant miRNA processing.

Financial burden is associated with worse health-related quality of life in adults with multiple endocrine neoplasia type 1.

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Peipert, Benjamin J; Goswami, Sneha; Helenowski, Irene; Yount, Susan E; Sturgeon, Cord

2017-12-01

Health-related quality of life and financial burden among patients with multiple endocrine neoplasia type 1 is poorly described. It is not known how financial burden influences health-related quality of life in this population. We hypothesized that the financial burden attributable to multiple endocrine neoplasia type 1 is associated with worse health-related quality of life. United States adults (≥18 years) with multiple endocrine neoplasia type 1 were recruited from the AMENSupport MEN online support group. Patient demographics, clinical characteristics, and financial burden were assessed via an online survey. The instrument Patient-Reported Outcomes Measurement Information System 29-item profile measure was used to assess health-related quality of life. Multivariable linear regression was used to identify significant variables in each Patient-Reported Outcomes Measurement Information System domain. Out of 1,378 members in AMENSupport, our survey link was accessed 449 times (33%). Of 153 US respondents who completed our survey, 84% reported financial burden attributable to multiple endocrine neoplasia type 1. The degree of financial burden had a linear relationship with worse health-related quality of life across all Patient-Reported Outcomes Measurement Information System domains (r = 0.36-0.55, P financial event(s). Borrowing money from friends/family (30%), unemployment (13%), and spending >$100/month out-of-pocket on prescription medications (46%) were associated consistently with impaired health-related quality of life (ß = 3.75-6.77, P times more likely to be unemployed and declare bankruptcy than the US population, respectively. This study characterizes the financial burden in patients with multiple endocrine neoplasia type 1. Individuals with multiple endocrine neoplasia type 1 report a high degree of financial burden, negative financial events, and unemployment. Each of these factors was associated with worse health-related quality of life

Effectiveness of Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion for Children with Type 1 Diabetes Mellitus in Clinical Practice

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Chun-xiu Gong

2014-01-01

Full Text Available Aims. To determine whether multiple daily injections (MDIs or continuous subcutaneous insulin infusion (CSII contributes to better glucose control in children with different type 1 diabetes duration. Methods. Subjects were grouped according to early (≤1 year after disease onset; 1A or late (1–3 years after onset; 2A MDIs/CSII treatment initiation. Corresponding control groups (1B, 2B received insulin injections twice daily. Results. HbA1c levels were consistently lower in group 1A than in group 1B (6 months (T2: 7.37% versus 8.21%; 12 months (T3: 7.61% versus 8.41%; 24/36 months (T4/T5: 7.61% versus 8.72%; all P<0.05, but were lower in group 2A than in group 2B only at T2 (8.36% versus 9.19%; P=0.04. Levels were lower in group 1A than in group 2A when disease duration was matched (7.61% versus 8.49%; P<0.05. Logistic regression revealed no correlation between HbA1c level and MDIs/CSII therapy. HbA1c levels were only negatively related to insulin dosage. Conclusions. Blood glucose control was better in patients receiving MDIs/CSII than in those receiving conventional treatment. Early MDIs/CSII initiation resulted in prolonged maintenance of low HbA1c levels compared with late initiation. MDIs/CSII therapy should be combined with comprehensive management.

No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

NARCIS (Netherlands)

Nell, Sjoerd; van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Borel Rinkes, Inne H. M.; Vriens, Menno R.; Valk, Gerlof D.

2015-01-01

An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood

No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

NARCIS (Netherlands)

Nell, S.; Leeuwaarde, R.S. van; Pieterman, C.R.; Laat, J.M. de; Hermus, A.R.M.M.; Dekkers, O.M.; Herder, W.W. de; Horst-Schrivers, A.N. van der; Drent, M.L.; Bisschop, P.H.; Havekes, B.; Rinkes, I.H.; Vriens, M.R.; Valk, G.D.

2015-01-01

CONTEXT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

NARCIS (Netherlands)

Nell, Sjoerd; Van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

2015-01-01

Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells

DEFF Research Database (Denmark)

Blomqvist, Maria; Rhost, Sara; Teneberg, Susann

2009-01-01

The glycosphingolipid sulfatide (SO(3)-3Galbeta1Cer) is a demonstrated ligand for a subset of CD1d-restricted NKT cells, which could regulate experimental autoimmune encephalomyelitis, a murine model for multiple sclerosis, as well as tumor immunity and experimental hepatitis. Native sulfatide...

Multiple metachronous cancer of the esophagus

International Nuclear Information System (INIS)

Mamontov, A.S.; Shlakov, S.L.; Bitotskij, P.G.; Volchenko, N.N.

1996-01-01

Treatment of a patient with the most characteristics combination of primary multiple metachronous cancer of esophagus involving the esophagus tumor localization on the one hand and tumors in the head and neck organs, on the other hand is described. Remote radiation therapy has been applied in the area of the primary tumor ( 60 Co radiation - carrying needles) and interstitial cavitary therapy as been undertaken. According to the authors data in 1988-1995 in Moscow oncological institute named after Gertsen multiple metachronous cancer cases, esophagus being one of localizations were revealed in 7% of all the patients with esophagus cancer diagnosis [ru

Phylogenetic analysis reveals multiple introductions of Cynodon species in Australia.

Science.gov (United States)

Jewell, M; Frère, C H; Harris-Shultz, K; Anderson, W F; Godwin, I D; Lambrides, C J

2012-11-01

The distinction between native and introduced flora within isolated land masses presents unique challenges. The geological and colonisation history of Australia, the world's largest island, makes it a valuable system for studying species endemism, introduction, and phylogeny. Using this strategy we investigated Australian cosmopolitan grasses belonging to the genus Cynodon. While it is believed that seven species of Cynodon are present in Australia, no genetic analyses have investigated the origin, diversity and phylogenetic history of Cynodon within Australia. To address this gap, 147 samples (92 from across Australia and 55 representing global distribution) were sequenced for a total of 3336bp of chloroplast DNA spanning six genes. Data showed the presence of at least six putatively introduced Cynodon species (C. transvaalensis, C. incompletus, C. hirsutus, C. radiatus, C. plectostachyus and C. dactylon) in Australia and suggested multiple recent introductions. C. plectostachyus, a species often confused with C. nlemfuensis, was not previously considered to be present in Australia. Most significantly, we identified two common haplotypes that formed a monophyletic clade diverging from previously identified Cynodon species. We hypothesise that these two haplotypes may represent a previously undescribed species of Cynodon. We provide further evidence that two Australian native species, Brachyachne tenella and B. convergens belong in the genus Cynodon and, therefore, argue for the taxonomic revision of the genus Cynodon. Copyright © 2012 Elsevier Inc. All rights reserved.

Premature infants' health at multiple induced pregnancy.

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Chernenkov Yu.V.

2015-09-01

Full Text Available Objective: to define the risk factors adversely influencing prenatal development at premature birth at use of methods of assisted reproductive technology (ART; to estimate premature' infants health from multiple induced pregnancy according to Perinatal Center of Saratov for last 3 years. Material and Methods. Under supervision there were 139 pregnant women with application ART. 202 children (51 twins were born and 5 triplet babies, from them 83 premature infants born from multiple induced pregnancy have been analyzed. Results. The newborns examined by method ART, were distributed as follows: 22-28 weeks — 19 children; 29-32 weeks — 23; 33-36 weeks — 41. Asphyxia at birth was marked at all premature infants. Respiratory insufficiency at birth is revealed in 87,3% of cases. The most frequent pathologies in premature infants are revealed: neurologic infringements and bronchopulmonary pathology occured at all children, developmental anomaly — 33, 8%, retinopathies in premature infants — 26,5%. The mortality causes include: extreme immaturity, cerebral leukomalacia, IVN 3 degrees. Conclusion. The risk factors, premature birth at application of methods ART are revealed: aged primiparas, pharmacological influence, absence of physiological conditions of prenatal development; multifetation. The high percent of birth of children with ELBW and ULBW is revealed. RDCN with further BPD development, retinopathies in premature infants and CNS defeat is more often occured.

[Multiple mandibular radiolucencies in an asymptomatic girl

NARCIS (Netherlands)

Barkhuysen, R.; Merkx, M.A.W.; Berge, S.J.

2007-01-01

Routine dental radiographic examination in a 16-year-old girl revealed the presence of 3 well-defined radiolucent cystlike structures in the mandible. After clinical and radiological examination, a multiple traumatic bone cyst was diagnosed. Surgical exploration confirmed the diagnosis. Curettage of

Analysis of Msx1; Msx2 double mutants reveals multiple roles for Msx genes in limb development.

Science.gov (United States)

Lallemand, Yvan; Nicola, Marie-Anne; Ramos, Casto; Bach, Antoine; Cloment, Cécile Saint; Robert, Benoît

2005-07-01

The homeobox-containing genes Msx1 and Msx2 are highly expressed in the limb field from the earliest stages of limb formation and, subsequently, in both the apical ectodermal ridge and underlying mesenchyme. However, mice homozygous for a null mutation in either Msx1 or Msx2 do not display abnormalities in limb development. By contrast, Msx1; Msx2 double mutants exhibit a severe limb phenotype. Our analysis indicates that these genes play a role in crucial processes during limb morphogenesis along all three axes. Double mutant limbs are shorter and lack anterior skeletal elements (radius/tibia, thumb/hallux). Gene expression analysis confirms that there is no formation of regions with anterior identity. This correlates with the absence of dorsoventral boundary specification in the anterior ectoderm, which precludes apical ectodermal ridge formation anteriorly. As a result, anterior mesenchyme is not maintained, leading to oligodactyly. Paradoxically, polydactyly is also frequent and appears to be associated with extended Fgf activity in the apical ectodermal ridge, which is maintained up to 14.5 dpc. This results in a major outgrowth of the mesenchyme anteriorly, which nevertheless maintains a posterior identity, and leads to formation of extra digits. These defects are interpreted in the context of an impairment of Bmp signalling.

Study on the multiple cancer in A-bomb survivors

International Nuclear Information System (INIS)

Wakabayashi, Toshiro; Yamamoto, Tsutomu.

1984-01-01

Autopsy data from cohort studies performed on A-bomb victims revealed that the incidence rate of multiple cancer was 7.8% (193 of 2,472 cancer A-bomb victims), being higher than that (5.8%) found from the tumor registry in Hiroshima and Nagasaki. Multiple cancer occurred more frequently in women than in men in both Nagasaki and Hiroshima. The incidence of multiple cancer was 1.5 times higher in the victims exposed to more than 100 rad (Vsub(+) group) than in those exposed to less than one rad (V 0 group), suggesting that there might be dose-response relationship, although this was not statistically significant between the exposed groups. According to the organs, relative risk ratio of developing cancer in the Vsub(+) group to that in the V 0 group was high in the colon and rectum, bladder, lungs, and testes in men; in the thyroid gland, lungs, colon and rectum, bladder, and breast in women, although no statistically significant differences were observed between the groups. This was suggestive of cancer that arises frequently in the lungs of men in the Vsub(+) group. Occult cancer of the thyroid gland and testes was also discussed in relation to the incidence of multiple cancer. (Namekawa, K.)

Unfolding of core nucleosomes by PARP-1 revealed by spFRET microscopy

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Daniel Sultanov

2017-01-01

Full Text Available DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose polymerase 1 increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer microscopy. PARP-1 binding to a double-strand break in the vicinity of a nucleosome results in a significant increase of the distance between the adjacent gyres of nucleosomal DNA. This partial uncoiling of the entire nucleosomal DNA occurs without apparent loss of histones and is reversed after poly(ADP-ribosylation of PARP-1. Thus PARP-1-nucleosome interactions result in reversible, partial uncoiling of the entire nucleosomal DNA.

Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways.

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Senthil K Chinnakannan

Full Text Available Morbilliviruses form a closely related group of pathogenic viruses which encode three non-structural proteins V, W and C in their P gene. Previous studies with rinderpest virus (RPV and measles virus (MeV have demonstrated that these non-structural proteins play a crucial role in blocking type I (IFNα/β and type II (IFNγ interferon action, and various mechanisms have been proposed for these effects. We have directly compared four important morbilliviruses, rinderpest (RPV, measles virus (MeV, peste des petits ruminants virus (PPRV and canine distemper virus (CDV. These viruses and their V proteins could all block type I IFN action. However, the viruses and their V proteins had varying abilities to block type II IFN action. The ability to block type II IFN-induced gene transcription correlated with co-precipitation of STAT1 with the respective V protein, but there was no correlation between co-precipitation of either STAT1 or STAT2 and the abilities of the V proteins to block type I IFN-induced gene transcription or the creation of the antiviral state. Further study revealed that the V proteins of RPV, MeV, PPRV and CDV could all interfere with phosphorylation of the interferon-receptor-associated kinase Tyk2, and the V protein of highly virulent RPV could also block the phosphorylation of another such kinase, Jak1. Co-precipitation studies showed that morbillivirus V proteins all form a complex containing Tyk2 and Jak1. This study highlights the ability of morbillivirus V proteins to target multiple components of the IFN signalling pathways to control both type I and type II IFN action.

Germline mutations in lysine specific demethylase 1 (LSD1/KDM1A) confer susceptibility to multiple myeloma.

Science.gov (United States)

Wei, Xiaomu; Calvo-Vidal, M Nieves; Chen, Siwei; Wu, Gang; Revuelta, Maria V; Sun, Jian; Zhang, Jinghui; Walsh, Michael F; Nichols, Kim E; Joseph, Vijai; Snyder, Carrie; Vachon, Celine M; McKay, James D; Wang, Shu-Ping; Jayabalan, David S; Jacobs, Lauren M; Becirovic, Dina; Waller, Rosalie G; Artomov, Mykyta; Viale, Agnes; Patel, Jayeshkumar; Phillip, Jude M; Chen-Kiang, Selina; Curtin, Karen; Salama, Mohamed; Atanackovic, Djordje; Niesvizky, Ruben; Landgren, Ola; Slager, Susan L; Godley, Lucy A; Churpek, Jane; Garber, Judy E; Anderson, Kenneth C; Daly, Mark J; Roeder, Robert G; Dumontet, Charles; Lynch, Henry T; Mullighan, Charles G; Camp, Nicola J; Offit, Kenneth; Klein, Robert J; Yu, Haiyuan; Cerchietti, Leandro; Lipkin, Steven M

2018-03-20

Given the frequent and largely incurable occurrence of multiple myeloma (MM), identification of germline genetic mutations that predispose cells to MM may provide insight into disease etiology and the developmental mechanisms of its cell of origin, the plasma cell. Here we identified familial and early-onset MM kindreds with truncating mutations in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal. Additionally, we found higher rates of germline truncating and predicted deleterious missense KDM1A mutations in MM patients unselected for family history compared to controls. Both monoclonal gammopathy of unknown significance (MGUS) and MM cells have significantly lower KDM1A transcript levels compared with normal plasma cells. Transcriptome analysis of MM cells from KDM1A mutation carriers shows enrichment of pathways and MYC target genes previously associated with myeloma pathogenesis. In mice, antigen challenge followed by pharmacological inhibition of KDM1A promoted plasma cell expansion, enhanced secondary immune response, elicited appearance of serum paraprotein, and mediated upregulation of MYC transcriptional targets. These changes are consistent with the development of MGUS. Collectively, our findings show KDM1A is the first autosomal dominant MM germline predisposition gene, providing new insights into its mechanistic roles as a tumor suppressor during post-germinal center B cell differentiation. Copyright ©2018, American Association for Cancer Research.

Sphingosine 1-Phosphate Receptor 1 as a Useful Target for Treatment of Multiple Sclerosis

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Kunitomo Adachi

2012-05-01

Full Text Available Sphingosine 1-phosphate (S1P, a lysophospholipid mediator, is generated from sphingosine by sphingosine kinases and binds five known cell surface receptors. S1P receptor 1 (S1P₁ plays an essential role in lymphocyte egress from secondary lymphoid organs (SLO, as evinced by the inability of lymphocytes to exit from the SLO in mice lacking lymphocytic S1P₁. Fingolimod hydrochloride (FTY720 is a first-in-class, orally active, S1P receptor modulator with a structure closely related to sphingosine. FTY720 was first synthesized by chemical modification of a natural product, myriocin. FTY720 is effectively converted to an active metabolite, FTY720 phosphate (FTY720-P by sphingosine kinases. FTY720-P shows high affinity to 4 of the S1P receptors (S1P₁, S1P₃, S1P₄, and S1P₅. In particular, FTY720-P strongly induces internalization and degradation of S1P₁, inhibits S1P responsiveness of lymphocytes in the SLO, and acts as a functional antagonist at lymphocytic S1P₁. Consequently, FTY720 inhibits S1P₁-dependent lymphocyte egress from the SLO to decrease circulation of lymphocytes including autoreactive Th17 cells and is highly effective in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Because FTY720 shows a superior efficacy in relapsing remitting MS patients compared to intramuscular interferon-β-1a (Avonex^®, S1P₁ is presumed to be a useful target for the therapy of MS.

Minocycline added to subcutaneous interferon β-1a in multiple sclerosis

DEFF Research Database (Denmark)

Sørensen, P S; Sellebjerg, F; Lycke, J

2016-01-01

BACKGROUND AND PURPOSE: Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. METHODS: This was a double......-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying...... were assessed. RESULTS: One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence...

T1 Shortening in the Globus Pallidus after Multiple Administrations of Gadobutrol: Assessment with a Multidynamic Multiecho Sequence.

Science.gov (United States)

Kang, Koung Mi; Choi, Seung Hong; Hwang, Moonjung; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho

2018-04-01

Purpose To determine the association between the administration of the macrocyclic contrast medium gadobutrol and T1 relaxation time in the brains of patients with normal renal function by using multidynamic multiecho (MDME) magnetic resonance (MR) imaging sequences. Materials and Methods The institutional review board approved this retrospective study, and the need to obtain written informed consent was waived. This study included 46 patients (revealed by an electronic medical record search) who had received one or more gadobutrol injections and a maximum of one MR imaging contrast medium injection other than gadobutrol before MDME sequence acquisition. One radiologist performed quantitative analyses of regions of interest on quantitative T1 maps twice to cover the normal-appearing globus pallidus (GP), frontal white matter, frontal cortex, and thalamus. The number of administrations and the cumulative dose of gadobutrol, age, intervals between administrations, sex, and treatment were investigated. Univariable and multivariable linear regression analyses of the T1 values in four brain regions and the GP-to-thalamus signal intensity (SI) ratio were performed. P values of less than the Bonferroni-corrected value of .01 were considered to indicate significant differences. Results Intraobserver reproducibility was good to excellent (intraclass correlation coefficients, 0.62-0.81). Because of high multicollinearity between the number of gadobutrol administrations and accumulated dose (r = 0.96, P .01). Conclusion Multiple exposures to gadobutrol are associated with T1 shortening in the GP. © RSNA, 2017 Online supplemental material is available for this article.

High surface area niobium oxides as catalysts for improved hydrogen sorption properties of ball milled MgH2

International Nuclear Information System (INIS)

Bhat, V.V.; Rougier, A.; Aymard, L.; Nazri, G.A.; Tarascon, J.-M.

2008-01-01

We report, high surface area (up to 200 m 2 /g) nanocrystalline niobium oxide (so called p-Nb 2 O 5 ) synthesized by 'chimie douce' route and its importance in enhancing the hydrogen sorption properties of MgH 2 . p-Nb 2 O 5 induces faster kinetics than commonly used commercial Nb 2 O 5 (c-Nb 2 O 5 ) when ball milled with MgH 2 (named (MgH 2 ) catalyst ) by reducing the time of desorption from 35 min in (MgH 2 ) c-Nb 2 O 5 to 12 min in (MgH 2 ) p-Nb 2 O 5 at 300 deg. C. The BET surface area of as-prepared Nb 2 O 5 was tuned by heat treatment and its effect on sorption properties was studied. Among them, both p-Nb 2 O 5 and Nb 2 O 5 :350 (p-Nb 2 O 5 heated to 350 deg. C with a BET specific surface area of 46 m 2 /g) desorb 5 wt.% within 12 min, exhibiting the best catalytic activity. Furthermore, thanks to the addition of high surface area Nb 2 O 5 , the desorption temperature was successfully lowered down to 200 deg. C, with a significant amount of desorbed hydrogen (4.5 wt.%). In contrast, the composite (MgH 2 ) c-Nb 2 O 5 shows no desorption at this 'low' temperature

Solid state synthesis, crystal growth and optical properties of urea and p-chloronitrobenzene solid solution

Energy Technology Data Exchange (ETDEWEB)

Rai, R.N., E-mail: rn_rai@yahoo.co.in [Department of Chemistry, Centre of Advanced Study, Banaras Hindu University, Varanasi 221005 (India); Kant, Shiva; Reddi, R.S.B. [Department of Chemistry, Centre of Advanced Study, Banaras Hindu University, Varanasi 221005 (India); Ganesamoorthy, S. [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603102, Tamilnadu (India); Gupta, P.K. [Laser Materials Development & Devices Division, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India)

2016-01-15

Urea is an attractive material for frequency conversion of high power lasers to UV (for wavelength down to 190 nm), but its usage is hindered due to its hygroscopic nature, though there is no alternative organic NLO crystal which could be transparent up to 190 nm. The hygroscopic character of urea has been modified by making the solid solution (UCNB) of urea (U) and p-chloronitrobenzene (CNB). The formation of the solid solution of CNB in U is explained on the basis of phase diagram, powder XRD, FTIR, elemental analysis and single crystal XRD studies. The solubility of U, CNB and UCNB in ethanol solution is evaluated at different temperatures. Transparent single crystals of UCNB are grown from its saturated solution in ethanol. Optical properties e.g., second harmonic generation (SHG), refractive index and the band gap for UCNB crystal were measured and their values were compared with the parent compounds. Besides modification in hygroscopic nature, UCNB has also shown the higher SHG signal and mechanical hardness in comparison to urea crystal. - Highlights: • The hygroscopic character of urea was modified by making the solid solution • Solid solution formation is support by elemental, powder- and single crystal XRD • Crystal of solid solution has higher SHG signal and mechanical stability. • Refractive index and band gap of solid solution crystal have determined.

A comparison of different ways of including baseline counts in negative binomial models for data from falls prevention trials.

Science.gov (United States)

Zheng, Han; Kimber, Alan; Goodwin, Victoria A; Pickering, Ruth M

2018-01-01

A common design for a falls prevention trial is to assess falling at baseline, randomize participants into an intervention or control group, and ask them to record the number of falls they experience during a follow-up period of time. This paper addresses how best to include the baseline count in the analysis of the follow-up count of falls in negative binomial (NB) regression. We examine the performance of various approaches in simulated datasets where both counts are generated from a mixed Poisson distribution with shared random subject effect. Including the baseline count after log-transformation as a regressor in NB regression (NB-logged) or as an offset (NB-offset) resulted in greater power than including the untransformed baseline count (NB-unlogged). Cook and Wei's conditional negative binomial (CNB) model replicates the underlying process generating the data. In our motivating dataset, a statistically significant intervention effect resulted from the NB-logged, NB-offset, and CNB models, but not from NB-unlogged, and large, outlying baseline counts were overly influential in NB-unlogged but not in NB-logged. We conclude that there is little to lose by including the log-transformed baseline count in standard NB regression compared to CNB for moderate to larger sized datasets. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.

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Schnorr, J D; Holdcraft, R; Chevalier, B; Berg, C A

2001-10-01

Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype.

Multiple antibiotic susceptibility of polyphosphate kinase mutants (ppk1 and ppk2 from Pseudomonas aeruginosa PAO1 as revealed by global phenotypic analysis

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Javiera Ortiz-Severín

2015-01-01

Full Text Available BACKGROUND: Pseudomonas aeruginosa is known to be a multidrug resistant opportunistic pathogen. Particularly, P. aeruginosa PAO1 polyphosphate kinase mutant (ppk1 is deficient in motility, quorum sensing, biofilm formation and virulence FINDINGS: By using Phenotypic Microarrays (PM we analyzed near 2000 phenotypes of P. aeruginosa PAO1 polyP kinase mutants (ppk1 and ppk2. We found that both ppk mutants shared most of the phenotypic changes and interestingly many of them related to susceptibility toward numerous and different type of antibiotics such as Ciprofloxacin, Chloramphenicol and Rifampicin CONCLUSIONS: Combining the fact that ppk1 mutants have reduced virulence and are more susceptible to antibiotics, polyP synthesis and particularly PPK1, is a good target for the design of molecules with anti-virulence and anti-persistence properties.

Multiple adenomatoid tumours in the Epididymis and Tunica vaginalis: Case report

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Ahmed Abroaf

2014-03-01

Full Text Available We describe the case of a 65 year-old male presenting with a tender right testicular mass, confirmed to be a tumour on ultrasound. The patient underwent a radical inguinal orchidectomy and histology revealed multiple adenomatoid tumours in epididymis and tunica vaginalis. This is an infrequent benign tumour of mesothelial origin that has rarely been reported as multiple lesions in the literature. Immunohistochemistry demonstrates that adenomatoid tumour and mesotheliomas share the expression of podoplanin (D2-40 which is helpful to differentiate them from carcinomas. On the other hand adenomatoid tumour is differentiated from mesothelioma on morphological grounds since the former does not exhibit cellular atypia, mitotic activity or bland focal tumour necrosis. Although testis preserving surgery can be an option for benign adenomatoid tumours, most patients (as in our case proceed to orchidectomy as diagnosing them confidently can be difficult.---------------------------Cite this article as: Abroaf A, Veeratterapillay R, Vasdev N, Majo J, Sherif AE, Paez E. Multiple adenomatoid tumours in the Epididymis and Tunica vaginalis : Case Report. Int J Cancer Ther Oncol 2014; 2(1:02021.DOI: http://dx.doi.org/10.14319/ijcto.0202.1

Mixed multiplicities for arbitrary ideals and generalized Buchsbaum-Rim multiplicities

International Nuclear Information System (INIS)

Callejas-Bedregal, R.; Jorge Perez, V.H.

2005-12-01

We introduce first the notion of mixed multiplicities for arbitrary ideals in a local d-dimensional noetherian ring (A, m) which, in some sense, generalizes the concept of mixed multiplicities for m-primary ideals. We also generalize Teissier's Product Formula for a set of arbitrary ideals. We also extend the notion of the Buchsbaum-Rim multiplicity (in short, we write BR-multiplicity) of a submodule of a free module to the case where the submodule no longer has finite colength. For a submodule M of A p we introduce a sequence e BR k (M), k = 0,...,d + p - 1 which in the ideal case coincides with the multiplicity sequence c 0 (I, A),...,c d (I, A) defined for an arbitrary ideal I of A by Achilles and Manaresi in [AM]. In case that M has finite colength in A p and it is totally decomposable we prove that our BR-multiplicity sequence essentially falls into the standard BR-multiplicity of M. (author)

Neoclassical transport in a multiple-helicity torsatron in the low-collisionality (1/#betta#) regime

International Nuclear Information System (INIS)

Shaing, K.C.; Hokin, S.A.

1983-02-01

For a sufficiently high number of field periods (m/iota > l), the magnetic field of a multiple helicity torsatron can be reduced to a simple form such that the second adiabatic invariant J can be calculated. It is found that the particle and the heat fluxes for a multiple helicity torsatron in the low collisionality (1/#betta#) regime have the same geometric dependences. An optimization of both quantities is carried out for a given equilibrium constraint. It is shown that the transport fluxes can be smaller than those of the conventional stellarator by an order of magnitude. The effect of finite plasma beta on the neoclassical fluxes is also studied

Multiple Scattering Analysis of Cu - K EXAFS in Bi2Sr1.5 Cu2O8+δ

International Nuclear Information System (INIS)

Roehler, J.; Cruesemann, R.

1995-01-01

We have analyzed the Cu K-EXAFS of Bi 2 Sr 1.5 Ca 1.5 Cu 2 O 8+δ using a full multiple scattering analysis in a cluster with diameter d∼ 7.6 A. The layered structure has numerous quasi one-dimensional structural elements which give rise to significant multiple scattering contributions in the EXAFS. We confirm the Sr/Ca ratio of the sample is 1:1, and one Ca atom is located close to a nominal Sr-site. At 40 K the dimpling angle in the CuO 2 -plane is found to be ≤ 3.5 . (author)

Multiple routes and milestones in the folding of HIV-1 protease monomer.

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Massimiliano Bonomi

Full Text Available Proteins fold on a time scale incompatible with a mechanism of random search in conformational space thus indicating that somehow they are guided to the native state through a funneled energetic landscape. At the same time the heterogeneous kinetics suggests the existence of several different folding routes. Here we propose a scenario for the folding mechanism of the monomer of HIV-1 protease in which multiple pathways and milestone events coexist. A variety of computational approaches supports this picture. These include very long all-atom molecular dynamics simulations in explicit solvent, an analysis of the network of clusters found in multiple high-temperature unfolding simulations and a complete characterization of free-energy surfaces carried out using a structure-based potential at atomistic resolution and a combination of metadynamics and parallel tempering. Our results confirm that the monomer in solution is stable toward unfolding and show that at least two unfolding pathways exist. In our scenario, the formation of a hydrophobic core is a milestone in the folding process which must occur along all the routes that lead this protein towards its native state. Furthermore, the ensemble of folding pathways proposed here substantiates a rational drug design strategy based on inhibiting the folding of HIV-1 protease.

Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

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Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

2011-06-01

Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

Nanocolloidal Ru/MgF2 Catalyst for Hydrogenation of Chloronitrobenzene and Toluene

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Pietrowski Mariusz

2014-06-01

Full Text Available The use of magnesium fluoride support for ruthenium active phase allowed obtaining new catalysts of high activities in the hydrogenation of toluene and ortho-chloronitrobenzene. Ruthenium colloid catalysts (1 wt.% of Ru were prepared by impregnation of the support with the earlier produced polyvinylpyrrolidone (PVP-stabilized ruthenium colloids. The performances of the colloidal catalysts and those obtained by traditional impregnation were tested in the reactions of toluene hydrogenation to methylcyclohexane and selective hydrogenation of ortho-chloronitrobenzene (o-CNB to ortho-chloroaniline (o-CAN. It was shown that the use of chemical reduction method allows obtaining highly monodisperse ruthenium nanoparticles of 1.6–2.6 nm in size. After reduction in hydrogen at 400oC, the colloidal ruthenium nanoparticles were found to strongly interact with MgF2 surface (SMSI, which decreased the catalyst ability to hydrogen chemisorption, but despite this, the colloid catalysts showed higher activity in o-CNB hydrogenation and higher selectivity to o-CAN than the traditional ones. It is supposed that their higher activity can be a result of high dispersion of Ru in colloid catalysts and the higher selectivity can be a consequence of the lower availability of hydrogen on the surface.

A case of multiple metastatic malignant melanoma with the largest lesion in the ileum and no skin lesion

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Shuji Suzuki

2012-12-01

Full Text Available We report the case of a 72-year-old woman with malignant melanoma and multiple metastases; the largest tumor was in the ileum. The patient experienced general fatigue and bloody feces for 1 month before consulting a nearby clinic. Blood tests revealed anemia, and fecal occult blood was positive, but no abnormalities were detected using gastrointestinal endoscopy and colonoscopy or the skin of the entire body. Computed tomography images of the chest, abdomen, and pelvic region, and positron emission tomography–computed tomography images of the entire body revealed multiple nodules in the ileum, left mammary gland, left thyroid, right inguinal lymph node, and on the fascia of the right thoracic area and right buttocks. The tumor in the left mammary gland was excised and immunohistochemical analysis revealed that the excised tissue was positive for HMB45, melan-A, and MITF, but negative for S-100 protein. Diagnosed with melanoma with multiple metastases, the patient underwent four cycles of dacarbazine, nimustine hydrochloride, and vincristine (DAV plus interferon beta chemotherapy and one cycle of dacarbazine, nimustine hydrochloride, cisplatin, and tamoxifen (DAC-Tam chemotherapy. Two series of embolizations of the artery feeding the ileum tumors, as well as a series of plasma and red blood cell transfusions, were performed for ileum tumor hemorrhage. The patient was hospitalized eight times, for a total of 204 days during the 1-year survival period before her death from respiratory failure.

Endocarditis due to Gemella haemolysans in a newly diagnosed multiple myeloma patient

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Dongyan Liu

2016-09-01

Full Text Available An 87-year-old Caucasian woman with hypertension, diabetes mellitus type 2, and COPD was admitted with 1-week duration of back pain and weight gain. The physical examination revealed jugular venous distention, rales in the left lower lung field, and severe pitting edema over lower extremities. As workup for leukocytosis, blood cultures grew Gemella haemolysans. Subsequently, a transthoracic echocardiogram revealed vegetation on the non-coronary aortic leaflet and mild aortic stenosis. She was treated with ampicillin and gentamicin. After further investigation, the patient was diagnosed with plasma cell myeloma, the monoclonal lambda type. This is the first reported case of G. haemolysans endocarditis in a multiple myeloma patient.

The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

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Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

2015-12-01

Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of

The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells

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Andrew Parker

2015-12-01

Full Text Available Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182 in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss.

A novel serine protease, Sep1, from Bacillus firmus DS-1 has nematicidal activity and degrades multiple intestinal-associated nematode proteins.

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Geng, Ce; Nie, Xiangtao; Tang, Zhichao; Zhang, Yuyang; Lin, Jian; Sun, Ming; Peng, Donghai

2016-04-27

Plant-parasitic nematodes (PPNs) cause serious harm to agricultural production. Bacillus firmus shows excellent control of PPNs and has been produced as a commercial nematicide. However, its nematicidal factors and mechanisms are still unknown. In this study, we showed that B. firmus strain DS-1 has high toxicity against Meloidogyne incognita and soybean cyst nematode. We sequenced the whole genome of DS-1 and identified multiple potential virulence factors. We then focused on a peptidase S8 superfamily protein called Sep1 and demonstrated that it had toxicity against the nematodes Caenorhabditis elegans and M. incognita. The Sep1 protein exhibited serine protease activity and degraded the intestinal tissues of nematodes. Thus, the Sep1 protease of B. firmus is a novel biocontrol factor with activity against a root-knot nematode. We then used C. elegans as a model to elucidate the nematicidal mechanism of Sep1, and the results showed that Sep1 could degrade multiple intestinal and cuticle-associated proteins and destroyed host physical barriers. The knowledge gained in our study will lead to a better understanding of the mechanisms of B. firmus against PPNs and will aid in the development of novel bio-agents with increased efficacy for controlling PPNs.

The MAPKK FgMkk1 of Fusarium graminearum regulates vegetative differentiation, multiple stress response, and virulence via the cell wall integrity and high-osmolarity glycerol signaling pathways.

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Yun, Yingzi; Liu, Zunyong; Zhang, Jingze; Shim, Won-Bo; Chen, Yun; Ma, Zhonghua

2014-07-01

Mitogen-activated protein (MAP) kinases play crucial roles in regulating fungal development, growth and pathogenicity, and in responses to the environment. In this study, we characterized a MAP kinase kinase FgMkk1 in Fusarium graminearum, the causal agent of wheat head blight. Phenotypic analyses of the FgMKK1 mutant (ΔFgMKK1) showed that FgMkk1 is involved in the regulation of hyphal growth, pigmentation, conidiation, deoxynivalenol biosynthesis and virulence of F. graminearum. ΔFgMKK1 also showed increased sensitivity to cell wall-damaging agents, and to osmotic and oxidative stresses, but exhibited decreased sensitivity to the fungicides iprodione and fludioxonil. In addition, the mutant revealed increased sensitivity to a biocontrol agent, Trichoderma atroviride. Western blot assays revealed that FgMkk1 positively regulates phosphorylation of the MAP kinases Mgv1 and FgOs-2, the key component in the cell wall integrity (CWI) and high-osmolarity glycerol (HOG) signalling pathway respectively. Yeast two-hybrid assay indicated that Mgv1 interacts with a transcription factor FgRlm1. The FgRLM1 mutant (ΔFgRLM1) showed increased sensitivity to cell wall-damaging agents and exhibited decreased virulence. Taken together, our data indicated that FgMkk1 is an upstream component of Mgv1, and regulates vegetative differentiation, multiple stress response and virulence via the CWI and HOG signalling pathways. FgRlm1 may be a downstream component of Mgv1 in the CWI pathway in F. graminearum. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

A Rich Assessment Task as a Window into Students' Multiplicative Reasoning

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Downton, Ann; Wright, Vince

2016-01-01

This study explored the potential of a rich assessment task to reveal students' multiplicative thinking in respect to a hypothetical learning trajectory. Thirty pairs of students in grades 5 and 6 attempted the task. Twenty-two pairs applied multiplicative structure to find the number of items in arrays. However counting and computational errors…

HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment

Energy Technology Data Exchange (ETDEWEB)

Borsi, Enrica, E-mail: enrica.borsi2@unibo.it [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy); Perrone, Giulia [Fondazione IRCCS Istituto Nazionale dei Tumori, Hematology Department, Via Venezian 1, 20133 Milano (Italy); Terragna, Carolina; Martello, Marina; Zamagni, Elena; Tacchetti, Paola; Pantani, Lucia; Brioli, Annamaria; Dico, Angela Flores; Zannetti, Beatrice Anna; Rocchi, Serena; Cavo, Michele [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy)

2014-11-01

Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma. - Highlights: • HIF-1α inhibition induces a mild apoptotic cell death. • Down-modulation of cytokine-induced signaling cascades upon HIF-1α inhibition. • Reduced interaction between MM cells and BMSCs upon HIF-1α down-modulation. • Reduced PCs adhesion to the extracellular matrix protein induced by EZN-2968. • HIF-1α inhibition may be an attractive therapeutic strategy for Multiple Myeloma.