Prognostic relevance and performance characteristics of serum IGFBP-2 and PAPP-A in women with breast cancer: a long-term Danish cohort study

DEFF Research Database (Denmark)

Espelund, Ulrick; Renehan, Andrew G; Cold, Søren

2018-01-01

-I, IGF-II, pro-IGF-II, IGF bioactivity, IGFBP-2, -3, and pregnancy-associated plasma protein A (PAPP-A), an IGFBP regulator, in baseline samples of 301 women with breast cancer treated on four protocols (Odense, Denmark: 1993-1998). We evaluated performance characteristics (expressed as area under...... noncancer individuals to assess multidimensional relationships (MDR), and evaluated additional prognostic models using survival artificial neural network (SANN) and survival support vector machines (SSVM), as these enhance capture of MDRs. For RFS, increasing concentrations of circulating IGFBP-2 and PAPP-A...... were independently prognostic [HRbiomarker doubling : 1.474 (95% CIs: 1.160, 1.875, P = 0.002) and 1.952 (95% CIs: 1.364, 2.792, P PAPP-A. Derived AUCRFS using SANN...

First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system.

Science.gov (United States)

Cowans, Nicholas J; Spencer, Kevin

2007-03-01

PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group. Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and development by breaking down IGF binding proteins and

Effect of pregnancy-associated plasma protein-A (PAPP-A) single-nucleotide polymorphisms on the level and activity of PAPP-A and the hormone profile in fluid from normal human small antral follicles

DEFF Research Database (Denmark)

Bøtkjær, Jane Alrø; Borgbo, Tanni; Kløverpris, Søren

2016-01-01

Objective: To reveal a possible relationship between two single nucleotide polymorphisms (SNPs) in PAPP-A—1224 (rs7020782) and 327 (rs12375498)—and the level and activity of PAPP-A in follicular fluid (FF) of human small antral follicles, and to analyze the intrafollicular hormone levels. Design:...

Skp2B overexpression alters a prohibitin-p53 axis and the transcription of PAPP-A, the protease of insulin-like growth factor binding protein 4.

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Harish Chander

Full Text Available We previously reported that the degradation of prohibitin by the SCF(Skp2B ubiquitin ligase results in a defect in the activity of p53. We also reported that MMTV-Skp2B transgenic mice develop mammary gland tumors that are characterized by an increased proteolytic cleavage of the insulin-like growth factor binding protein 4 (IGFBP-4, an inhibitor of IGF signaling. However, whether a link exists between a defect in p53 activity and proteolysis of IGFBP-4 was not established.We analyzed the levels of pregnancy-associated plasma protein A (PAPP-A, the protease of IGFBP-4, in MMTV-Skp2B transgenic mice and found that PAPP-A levels are elevated. Further, we found a p53 binding site in intron 1 of the PAPP-A gene and that both wild type and mutant p53 bind to this site. However, binding of wild type p53 results in the transcriptional repression of PAPP-A, while binding of mutant p53 results in the transcriptional activation of PAPP-A. Since MMTV-Skp2B mice express wild type p53 and yet show elevated levels of PAPP-A, at first, these observations appeared contradictory. However, further analysis revealed that the defect in p53 activity in Skp2B overexpressing cells does not only abolish the activity of wild type of p53 but actually mimics that of mutant p53. Our results suggest that in absence of prohibitin, the half-life of p53 is increased and like mutant p53, the conformation of p53 is denatured.These observations revealed a novel function of prohibitin as a chaperone of p53. Further, they suggest that binding of denatured p53 in intron 1 causes an enhancer effect and increases the transcription of PAPP-A. Therefore, these findings indicate that the defect in p53 function and the increased proteolysis of IGFBP-4, we had observed, represent two components of the same pathway, which contributes to the oncogenic function of Skp2B.

Association of serum PAPP-A levels in first trimester with small for gestational age and adverse pregnancy outcomes: systematic review and meta-analysis.

Science.gov (United States)

Morris, R Katie; Bilagi, Ashwini; Devani, Pooja; Kilby, Mark D

2017-03-01

To determine association, and predictive ability, of first trimester maternal serum pregnancy associated plasma protein A (PAPP-A) with adverse pregnancy outcomes. Searches of Medline, Embase and CINAHL (inception September 2015) for studies including pregnant women with first trimester PAPP-A and assessment of pregnancy outcomes. Study characteristics, quality and results extracted. Meta-analysis of odds ratios (ORs), and likelihood ratios (LRs) and 95% confidence intervals (CI). Thirty-two studies including 175 240 pregnancies. PAPP-A <5th centile had a moderate association with: birth weight <10th centile OR 2.08 (95% CI 1.89-2.29), <5th centile OR 2.83 (95% CI 2.52-3.18); pre-eclampsia OR 1.94 (95% CI 1.63-2.30), preterm birth <37 weeks OR 2.09 (95% CI 1.87-2.33), and composite adverse outcome OR 3.31 (95% CI 1.80-5.11). The predictive ability was poor: Birth weight <10th centile LR + ve 1.96 (95% CI 1.58-2.43), LR-ve 0.93 (95% CI 0.89-0.98); birth weight <5th centile LR + ve 2.65 (95% CI 2.35-2.99), LR-ve 0.85 (95% CI 0.74-0.98); PTB <37 weeks LR + ve 1.84 (95% CI 1.41-2.39), LR-ve 0.92 (95% CI 0.87-0.98). First trimester low maternal serum PAPP-A is associated with adverse pregnancy outcome, but predictive values are poor. Further work should address PAPP-A as a continuous variable in combination with other prognostic markers as a prediction model. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

Comparison of two immunoassay systems for hCGβ and PAPP-A in prenatal screening for trisomy 21, 18, and 13 in the first trimester

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Anna Elise Engell

2017-12-01

Full Text Available Objectives: The biochemical serum markers free β-human chorionic gonadotropin (hCGβ and pregnancy associated plasma protein A (PAPP-A, used in screening for trisomy 21 (T21, trisomy 18 (T18, and trisomy 13 (T13 during the first trimester, can be measured on different laboratory instruments e.g. Kryptor (Brahms and Cobas (Roche. We compared the performance of these two analytical instruments when used for first trimester combined testing. Design and methods: Serum samples from 944 singleton pregnant women attending for first trimester combined testing were routinely assayed for hCGβ and PAPP-A on Kryptor, and re-analyzed on Cobas. In addition, serum samples from 70 pregnant women carrying a fetus affected by T21, T18 or T13, were re-assayed on Cobas. Results: For the screening population, the hCGβ and PAPP-A results in multiples of the median (MoM from Kryptor and Cobas were significantly lower on Cobas when compared to Kryptor. The number of pregnant women with a risk above 1:300 for T21 was 48 for both Cobas and Kryptor, although a few patients only had a high risk with one of the methods. Overall, the screen positive rate was 5.1% for both instruments. In the trisomy groups the calculated risks for T21, T18, and T13 agreed well between Cobas and Kryptor. Conclusions: The screen positive rate for T21 (5.1% did not differ between the two analytical platforms in our screening population, although PAPP-A measurements form Cobas were significantly lower than those from Kryptor. The calculated risks for the pregnancies affected by trisomies using hCGβ MoM and PAPP-A MoM from Kryptor agreed well with those from Cobas. Keywords: Aneuploidy, Combined first trimester screening, First trimester risk assessment, Free β-human chorionic gonadotropin (hCGβ, Pregnancy associated plasma protein-A (PAPP-A, Trisomy screening

The role of maternal serumbeta-HCG and PAPP-A levels at gestational weeks 10 to 14 in the prediction of pre-eclampsia

Science.gov (United States)

Ozdamar, Ozkan; Gun, Ismet; Keskin, Ugur; Kocak, Necmettin; Mungen, Ercument

2014-01-01

Objective: We aimed to detect whether maternal serum free β-hCG and PAPP-A levels and NT measurements vary between normal pregnancies and those that subsequently develop pre-eclampsia and to evaluate the role of these screening serum analytes in the prediction of pre-eclampsia. Methods: Using a case-control study design, we identified all women who had been screened by double test within 11+0 and 13+6 weeks of gestation and who had developed pre-eclampsia during the subsequent pregnancy course, over a 6-year period between January 2006 and December 2012 at two tertiary referral hospital. All women who had undergone a double test during that time, without a diagnosis of pre-eclampsia and who had not had any adverse obstetric outcomes, were also identified, and three women among them were randomly selected as controls for each case. Maternal and neonatal data were abstracted from the medical records and PAPP-A, β-hCG, NT and CRL MoM values were compared between the two groups. Results: Although β-hCG values show no statistically significant difference (p=0.882), PAPP-A levels were significantly reduced in the pre-eclampsia group compared to the control group (p<0.001). NT and CRL values showed no significant difference between the two groups (p=0.674 and p=0.558, respectively). Conclusion: Measuring PAPP-A in the first trimester may be useful in the prediction of pre-eclampsia. PMID:24948981

Expression of recombinant murine pregnancy-associated plasma protein-A (PAPP-A) and a novel variant (PAPP-Ai) with differential proteolytic activity

DEFF Research Database (Denmark)

Søe, Rikke; Overgaard, Michael Toft; Thomsen, Anni R

2002-01-01

Murine pregnancy-associated plasma protein-A (PAPP-A) cDNA encoding a 1545 amino-acid protein has been cloned. We have also identified and cloned cDNA that encodes a novel variant of PAPP-A, PAPP-Ai, carrying a 29-residue highly basic insert. The point of insertion corresponds to a junction between...... with the proform of eosinophil major basic protein (proMBP). ProMBP functions as a proteinase inhibitor in the PAPP-A-proMBP complex, but whether any mechanistic parallel on regulation of proteolytic activity can be drawn between the insert of PAPP-Ai and the linkage to proMBP is not known. Importantly, these data...

Pappas' scheme of correlating R6 and R4 co-ordinate transformations

International Nuclear Information System (INIS)

Teli, M.T.

1984-01-01

Pappas has suggested that R 4 co-ordinates can be connected with those in the R 6 by taking t'sub(x)=t'sub(y)=t'sub(z)=t'. Such connection is here obtained by introducing the scaling of space-time co-ordinates xsub(i), tsub(i) in all the frames by the corresponding factor c/c'sub(i) and have shown that taking of t'sub(x)=t'sub(y)=t'sub(z)=t' for this purpose is not necessary. The scaling factors get ignored after the connection

Prospective evaluation of first trimester combined screening for trisomy 21 using a double set of the maternal serum markers PAPP-A and free β-hCG

DEFF Research Database (Denmark)

Ekelund, Charlotte Kvist; Wright, Dave; Ball, Susan

with an early blood sample taken prior to the NT scan, and another blood sample taken at the time of the NT scan. PAPP-A and free β-hCG were measured on both the early and the late samples, and Multiples of the Median (MoM) values were calculated in addition to the corresponding trisomy 21 risk. Using...... taken between gestational week 8+0 to 13+6, and the late samples were taken between week 11+3 and 14+6. The median interval between the samples was 17 days (range 1-40 days). The best performance of the combined screening was obtained using PAPP-A from the early sample and free β-hCG from the late...... sample, with a 95% DR for a 2.5 % FPR at a cut off 1:100. Conclusion: Using repeated biochemical sampling in the first trimester with early PAPP-A and late free β-hCG can optimize the screening performance of combined screening for trisomy 21....

Longer time-to-pregnancy in spontaneously conceived pregnancies is associated with lower PAPP-A and free β-hCG in first trimester screening for Down syndrome

DEFF Research Database (Denmark)

Kirkegaard, I; Uldbjerg, N; Tabor, A

2014-01-01

OBJECTIVE: The aim of this study was to investigate whether subfertility, measured as longer time-to-pregnancy (TTP) in spontaneously conceived pregnancies, affects the first trimester levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin (β-hCG) and......OBJECTIVE: The aim of this study was to investigate whether subfertility, measured as longer time-to-pregnancy (TTP) in spontaneously conceived pregnancies, affects the first trimester levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin (β...

PAPP-A and IGFBP-4 fragment levels in patients with ST-elevation myocardial infarction treated with heparin and PCI

DEFF Research Database (Denmark)

Hjortebjerg, Rikke; Lindberg, Søren; Hoffmann, Søren

2015-01-01

-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). Prior to PCI, patients were injected with 10,000IU of unfractionated heparin (UFH). Blood samples were collected immediately before PCI, but after UFH-injection, immediately after PCI and on day 1 and day 2....... Plasma IGFBP-4, CT-IGFBP-4 and NT-IGFBP-4 levels were determined by specific, novel immunoassays, and PAPP-A and IGF-I by commercial immunoassays. RESULTS: Plasma PAPP-A was strongly elevated upon STEMI, UFH-administration and PCI with mean concentrations (95%-confidence interval) pre-PCI, post-PCI, day...... 1, and day 2 of 13.0 (11.2;15.2), 14.8 (13.1;16.8), 1.03 (0.90;1.18), and 1.08 (0.92;1.28) μg/L, respectively (pPCI concentrations of IGFBP-4, CT-IGFBP-4 and NT-IGFBP-4 were 154 (142;166), 53 (47;60) and 136 (122;150) μg/L, and levels were unaltered post-PCI. Concentrations increased...

Plasma MIC-1 and PAPP-a levels are decreased among women presenting to an early pregnancy assessment unit, have fetal viability confirmed but later miscarry.

Directory of Open Access Journals (Sweden)

Tu'uhevaha J Kaitu'u-Lino

Full Text Available We have recently shown first trimester Macrophage inhibitory cytokine-1 (MIC-1 and Pregnancy Associated Plasma Protein-A (PAPP-A serum concentrations are depressed among asymptomatic women destined to miscarry. Here we examined whether plasma levels of MIC-1 and PAPP-A are depressed among women presenting to an Early Pregnancy Assessment Unit (EPAU, noted to have a confirmed viable fetus, but subsequently miscarry.We performed a prospective cohort study, recruiting 462 women in the first trimester presenting to EPAU and had fetal viability confirmed by ultrasound. We obtained plasma samples on the same day and measured MIC-1, PAPP-A and human chorionic gonadotrophin (hCG, grouping the cohort according to whether they later miscarried or not. To correct for changes in analyte levels across gestation, we expressed the data as Multiples of the normal Median (MoMs.We recruited 462 participants presenting to EPAU at 5-12 weeks gestation. Most (80% presented with symptoms of threatened miscarriage (e.g. abdominal pain, vaginal bleeding. 34 (7.4% subsequently miscarried. Median plasma MIC-1 levels among those who miscarried were 50% of those with ongoing pregnancies (Miscarriage cohort MoM 0.50 (25(th-75(th centiles: 0.29-1.33 vs ongoing pregnancies MoM 1.00 (0.65-1.38; p=0.0025. Median plasma PAPP-A MoMs among those who miscarried was 0.57 (0.00-1.12, significantly lower than those with ongoing pregnancies (MoMs 1.00 (0.59-1.59; p=0.036. Plasma hCG levels were also significantly depressed among those who miscarried compared to those with ongoing pregnancies. However, the performance of MIC-1 as a diagnostic marker to predict miscarriage in this cohort was modest, and not improved with the addition of hCG.MIC-1 and PAPP-A levels are significantly depressed in women presenting to EPAU with ultrasound evidence of fetal viability, but later miscarry. While they are unlikely to be useful as predictive biomarkers in this clinical setting, they probably play

Pregnancy-associated plasma protein-A modulates the anabolic effects of parathyroid hormone in mouse bone.

Science.gov (United States)

Clifton, Kari B; Conover, Cheryl A

2015-12-01

Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and several studies have implicated local insulin-like growth factor (IGF) signaling in mediating this effect. The IGF system is complex and includes ligands and receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by osteoblasts in vitro that has been shown to enhance local IGF action through cleavage of inhibitory IGFBP-4. This study was set up to test two specific hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I, IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80 μg/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly increased in response to PTH treatment. PTH treatment of WT mice, but not PAPP-A KO mice, significantly increased expression of an IGF-responsive gene. Bone mineral density (BMD), as measured by DEXA, was significantly decreased in femurs of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured by pQCT, was significantly decreased in femoral midshaft (primarily cortical bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to WT mice with PTH treatment. These data suggest that stimulation of PAPP-A expression by intermittent PTH treatment contributes to PTH bone anabolism in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

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Wang, Ruoxing [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States); Guo, Yan-Lin, E-mail: yanlin.guo@usm.edu [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States)

2012-10-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: Black-Right-Pointing-Pointer Inhibition of Cdks slows down mESCs proliferation. Black-Right-Pointing-Pointer mESCs display remarkable recovery capacity from short-term cell cycle interruption. Black-Right-Pointing-Pointer Short-term cell cycle interruption does not compromise mESC self-renewal. Black

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

International Nuclear Information System (INIS)

Wang, Ruoxing; Guo, Yan-Lin

2012-01-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: ► Inhibition of Cdks slows down mESCs proliferation. ► mESCs display remarkable recovery capacity from short-term cell cycle interruption. ► Short-term cell cycle interruption does not compromise mESC self-renewal. ► Oct4 and Nanog are up-regulated via de novo synthesis by cell cycle interruption.

First trimester maternal serum PAPP-A, beta-hCG and ADAM12 in prediction of small-for-gestational-age fetuses

DEFF Research Database (Denmark)

Pihl, Kasper; Larsen, Torben; Krebs, Lone

2008-01-01

OBJECTIVE: To examine the ability of predicting fetuses being small-for-gestational-age (SGA) at delivery with the maternal serum markers pregnancy-associated plasma protein A (PAPP-A), beta-human chorionic gonadotrophin (beta-hCG) and A disintegrin and metalloprotease 12 (ADAM12) in first...... trimester. METHODS: In all,36 cases being SGA (birth weight gestational age...

Prognostic relevance and performance characteristics of serum IGFBP-2 and PAPP-A in women with breast cancer: a long-term Danish cohort study.

Science.gov (United States)

Espelund, Ulrick; Renehan, Andrew G; Cold, Søren; Oxvig, Claus; Lancashire, Lee; Su, Zhenqiang; Flyvbjerg, Allan; Frystyk, Jan

2018-05-03

Measurement of circulating insulin-like growth factors (IGFs), in particular IGF-binding protein (IGFBP)-2, at the time of diagnosis, is independently prognostic in many cancers, but its clinical performance against other routinely determined prognosticators has not been examined. We measured IGF-I, IGF-II, pro-IGF-II, IGF bioactivity, IGFBP-2, -3, and pregnancy-associated plasma protein A (PAPP-A), an IGFBP regulator, in baseline samples of 301 women with breast cancer treated on four protocols (Odense, Denmark: 1993-1998). We evaluated performance characteristics (expressed as area under the curve, AUC) using Cox regression models to derive hazard ratios (HR) with 95% confidence intervals (CIs) for 10-year recurrence-free survival (RFS) and overall survival (OS), and compared those against the clinically used Nottingham Prognostic Index (NPI). We measured the same biomarkers in 531 noncancer individuals to assess multidimensional relationships (MDR), and evaluated additional prognostic models using survival artificial neural network (SANN) and survival support vector machines (SSVM), as these enhance capture of MDRs. For RFS, increasing concentrations of circulating IGFBP-2 and PAPP-A were independently prognostic [HR biomarker doubling : 1.474 (95% CIs: 1.160, 1.875, P = 0.002) and 1.952 (95% CIs: 1.364, 2.792, P < 0.001), respectively]. The AUC RFS for NPI was 0.626 (Cox model), improving to 0.694 (P = 0.012) with the addition of IGFBP-2 plus PAPP-A. Derived AUC RFS using SANN and SSVM did not perform superiorly. Similar patterns were observed for OS. These findings illustrate an important principle in biomarker qualification-measured circulating biomarkers may demonstrate independent prognostication, but this does not necessarily translate into substantial improvement in clinical performance. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity

Science.gov (United States)

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Zhang, Nan; Szweda, Luke I.; Griffin, Timothy M.; Barlic-Dicen, Jana

2014-01-01

The chemokine receptor CXCR4 is expressed on adipocytes and macrophages in adipose tissue, but its role in this tissue remains unknown. We evaluated whether deficiency in either adipocyte or myeloid leukocyte CXCR4 affects body weight (BW) and adiposity in a mouse model of high-fat-diet (HFD)-induced obesity. We found that ablation of adipocyte, but not myeloid leukocyte, CXCR4 exacerbated obesity. The HFD-fed adipocyte-specific CXCR4-knockout (AdCXCR4ko) mice, compared to wild-type C57BL/6 control mice, had increased BW (average: 52.0 g vs. 35.5 g), adiposity (average: 49.3 vs. 21.0% of total BW), and inflammatory leukocyte content in white adipose tissue (WAT), despite comparable food intake. As previously reported, HFD feeding increased uncoupling protein 1 (UCP1) expression (fold increase: 3.5) in brown adipose tissue (BAT) of the C57BL/6 control mice. However, no HFD-induced increase in UCP1 expression was observed in the AdCXCR4ko mice, which were cold sensitive. Thus, our study suggests that adipocyte CXCR4 limits development of obesity by preventing excessive inflammatory cell recruitment into WAT and by supporting thermogenic activity of BAT. Since CXCR4 is conserved between mouse and human, the newfound role of CXCR4 in mouse adipose tissue may parallel the role of this chemokine receptor in human adipose tissue.—Yao, L., Heuser-Baker, J., Herlea-Pana, O., Zhang, N., Szweda, L. I., Griffin, T. M., Barlic-Dicen, J. Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity. PMID:25016030

Compromise and Toleration

DEFF Research Database (Denmark)

Rostbøll, Christian F.

Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature, justifi...... in compromise are more stringent than those for being tolerated. Still, the limits of compromise cannot be drawn to narrowly if it is to remain its value as a form of agreement that respects and embodies the differences of opinion in society.......Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature......, justification, and limits of compromise if we see it merely as a matter of toleration. While toleration is mainly a matter of accepting citizens' equal right to co-existence as subjects to law, political compromise includes the parties in making law – it makes them co-authors of law. Toleration entails...

Lower placental growth factor and higher free β-hCG and PAPP-A levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia.

Science.gov (United States)

Paredes, Verónica; Espinoza-Caicedo, Jasson A; Salazar-Pousada, Danny; Escobar, Gustavo S; Pérez-López, Faustino R; Chedraui, Peter

2017-01-01

An imbalance between anti- and angiogenic factors during early placentation is key for the development of preeclampsia. Nevertheless, the majority of studies addressing this issue relate to maternal blood and not the fetal circulation. To measure placental growth factor (PlGF), free beta human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein-A (PAPP-A) levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia (n = 20), and their controls matched for parity, and maternal and gestational age. Upon delivery, a blood sample was withdrawn from the umbilical artery and vein of each case and its control in order to measure the proposed analytes using direct fluoroimmunoassay. Preeclampsia cases showed significantly lower median PlGF levels in fetal circulation as compared to controls (25.2 versus 36.9 and 23.6 versus 33.9 pg/mL, artery and vein, respectively, p < 0.05). Contrarily, cases displayed higher concentrations of PAPP-A (1024.0 versus 720.9 [median] and 1027.0 ± 298.4 versus 690.3 ± 401.9 mIU/L, artery and vein, respectively, p < 0.05), and free β-hCG (mean: 33.9 ± 4.3 versus 17.2 ± 4.0 and 30.1 ± 5.2 versus 13.7 ± 3.3 ng/mL, artery, and vein respectively, p < 0.05). Lower PlGF and higher PAPP-A and free β-hCG levels were found in the fetal circulation of near-term severe preeclamptic pregnancies. There is a need for more research in this regard.

Motor and memory testing of long-lived pregnancy-associated plasma protein--a knock-out mice.

Science.gov (United States)

Mason, Emily J; Grell, Jacquelyn A; West, Sally A; Conover, Cheryl A

2014-12-01

Mice deficient in pregnancy-associated plasma protein-A (PAPP-A), an IGF binding protein protease, have been shown to be resistant to experimentally induced atherosclerosis and diabetic nephropathy, and, in the laboratory environment, live 30-40% longer than wild-type littermates in association with delayed incidence and occurrence of age-related neoplasms and degenerative diseases. PAPP-A is highly expressed in the cerebellum and hippocampus of the mouse brain. Therefore, the studies presented here were aimed at determining motor behavior, learning and retention in PAPP-A knock-out (KO) mice compared to wild-type (WT) littermates with age. Balance and coordination were assessed using an accelerating rotarod; learning and memory were assessed in a Stone T-maze. Time on the rotarod decreased with age but there was no significant difference between PAPP-A KO and WT mice at any of the testing ages. Latency to reach the goal box and number of errors committed in the Stone T-maze did not change with age and there were no significant differences between PAPP-A KO and WT mice. Lack of PAPP-A in mice did not impact central regulation of coordination, learning or memory. Copyright © 2014 Elsevier Ltd. All rights reserved.

Democratic Respect and Compromise

DEFF Research Database (Denmark)

Rostbøll, Christian F.

2017-01-01

Compromise has attained renewed interest among political theorists writing on pluralism and disagreement. It is controversial, however, whether compromise is a mere pragmatic necessity or if it has non-instrumental value. This article argues that the reasons for compromise are inherent in the dem......Compromise has attained renewed interest among political theorists writing on pluralism and disagreement. It is controversial, however, whether compromise is a mere pragmatic necessity or if it has non-instrumental value. This article argues that the reasons for compromise are inherent...

A prospective study evaluating the performance of first trimester combined screening for trisomy 21 using repeated sampling of the maternal serum markers PAPP-A and free β-hCG

DEFF Research Database (Denmark)

Ekelund, Charlotte Kvist; Wright, Dave; Ball, Susan

2012-01-01

OBJECTIVE: To prospectively evaluate the performance of first-trimester combined screening for trisomy 21 using the biochemical markers pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (free β-hCG) obtained before and at the time of the nuchal translucency...

mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice.

Science.gov (United States)

Dominick, Graham; Bowman, Jacqueline; Li, Xinna; Miller, Richard A; Garcia, Gonzalo G

2017-02-01

Studies of the mTOR pathway have prompted speculation that diminished mTOR complex-1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long-lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy-associated protein-A (PAPPA-KO). The ways in which lower mTOR signals slow aging and age-related diseases are, however, not well characterized. Here, we show that Snell, GHKRO, and PAPPA-KO mice express high levels of two proteins involved in DNA repair, O-6-methylguanine-DNA methyltransferase (MGMT) and N-myc downstream-regulated gene 1 (NDRG1). Furthermore, we report that lowering mTOR enhances MGMT and NDRG1 protein expression via post-transcriptional mechanisms. We show that the CCR4-NOT complex, a post-transcriptional regulator of gene expression, is downstream of the mTORC1 pathway and may be responsible for the upregulation of MGMT and NDRG1 in all three varieties of long-lived mice. Our data thus suggest a novel link between DNA repair and mTOR signaling via post-transcriptional regulation involving specific alteration in the CCR4-NOT complex, whose modulation could control multiple aspects of the aging process. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Take care of your mouse!

CERN Multimedia

IT Department

2011-01-01

“Stop --- Think --- Click" is the basic recommendation for securely browsing the Internet and for securely reading e-mails. Users who have followed this recommendation in the past were less likely to have their computer infected or their computing account compromised. We would like to thank all those who donated their mouse to the CERN Animal Shelter for Computer Mice (http://cern.ch/c-a-s). For those who still use a mouse, please stay vigilant and  alert: do not click on links whose origin you do not trust or which look like gibberish. Do not install untrusted software or plug-ins, since software from untrusted sources may infect or compromise your computer, or violate copyrights. Finally, take particular care with e-mails: Do not open unexpected or suspicious e-mails or attachments. Delete them if they do not concern you or if they appear strange. If in doubt, or if you have questions, please do not hesitate to contact Computer.Security@cern.ch

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells.

Science.gov (United States)

Wang, Ruoxing; Guo, Yan-Lin

2012-10-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. Copyright © 2012 Elsevier Inc. All rights reserved.

β-Cell Ca(2+) dynamics and function are compromised in aging.

Science.gov (United States)

Barker, Christopher J; Li, Luosheng; Köhler, Martin; Berggren, Per-Olof

2015-01-01

Defects in pancreatic β-cell function and survival are key components in type 2 diabetes (T2D). An age-dependent deterioration in β-cell function has also been observed, but little is known about the molecular mechanisms behind this phenomenon. Our previous studies indicate that the regulation of cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) may be critical and that this is dependent on the proper function of the mitochondria. The [Ca(2+)]i dynamics of the pancreatic β-cell are driven by an interplay between glucose-induced influx of extracellular Ca(2+) via voltage-dependent Ca(2+) channels and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-mediated liberation of Ca(2+) from intracellular stores. Our previous work has indicated a direct relationship between disruption of Ins(1,4,5)P3-mediated Ca(2+) regulation and loss of β-cell function, including disturbed [Ca(2+)]i dynamics and compromised insulin secretion. To investigate these processes in aging we used three mouse models, a premature aging mitochondrial mutator mouse, a mature aging phenotype (C57BL/6) and an aging-resistant phenotype (129). Our data suggest that age-dependent impairment in mitochondrial function leads to modest changes in [Ca(2+)]i dynamics in mouse β-cells, particularly in the pattern of [Ca(2+)]i oscillations. These changes are driven by modifications in both PLC/Ins(1,4,5)P3-mediated Ca(2+) mobilization from intracellular stores and decreased β-cell Ca(2+) influx over the plasma membrane. Our findings underscore an important concept, namely that even relatively small, time-dependent changes in β-cell signal-transduction result in compromised insulin release and in a diabetic phenotype. Copyright © 2014 Elsevier Ltd. All rights reserved.

Decerebrate mouse model for studies of the spinal cord circuits

DEFF Research Database (Denmark)

Meehan, Claire Francesca; Mayr, Kyle A; Manuel, Marin

2017-01-01

The adult decerebrate mouse model (a mouse with the cerebrum removed) enables the study of sensory-motor integration and motor output from the spinal cord for several hours without compromising these functions with anesthesia. For example, the decerebrate mouse is ideal for examining locomotor be......, which is ample time to perform most short-term procedures. These protocols can be modified for those interested in cardiovascular or respiratory function in addition to motor function and can be performed by trainees with some previous experience in animal surgery....

"Stakkars pappa" – hva kan far-barn-relasjonen si oss om barnerollen?

Directory of Open Access Journals (Sweden)

Kiil, Hanne

2011-03-01

Full Text Available “Poor daddy”–child's perspective and iconotext in three award-winning picture books. The Western dichotomy between children and adults characterize our opinion both on children and childhood. In this understanding framework the children are seen as something totally different from adults. Can artistic children's literature modify this habitual thinking about such hierarchical levels? The three books to examine closer have all won awards from Ministry of Culture as the best Norwegian picture book that year. Both Svein Nyhus: Pappa [Daddy] (1998, Hans Sande and Gry Moursund: Arkimedes og brødskiva [Archimedes and the Sandwich] (2000 and Stein Erik Lunde and Øyvind Torseter: Eg kan ikkje sove no [I Can't Sleep Now] (2008 are first-person narratives where the main character is a child. In such picture books visual and verbal point of view rarely are the same. The illustrations usually observe the central character from a distance and then allow the reader not only to adopt the narrator's point of view. What kind of ambiguities in the complex relationship between text and images give signals to the readers–and to the understanding of the narrator's position and perspective? What can this perspective and the iconotext in the three books tell us about today's children's role?

Compromises.

Science.gov (United States)

Sizer, Theodore R.

1984-01-01

Taking as examples the issues of improving students'"high order thinking skills" and arriving at more equitable teacher salaries and school budgets, the author discusses the need for compromise solutions to widespread problems. (JBM)

Comparison of two immunoassay systems for hCGβ and PAPP-A in prenatal screening for trisomy 21, 18, and 13 in the first trimester

DEFF Research Database (Denmark)

Engell, Anna Elise; Carlsson, Elin Rebecka; Jørgensen, Finn Stener

2017-01-01

OBJECTIVES: The biochemical serum markers free β-human chorionic gonadotropin (hCGβ) and pregnancy associated plasma protein A (PAPP-A), used in screening for trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) during the first trimester, can be measured on different laboratory instruments e.......g. Kryptor (Brahms) and Cobas (Roche). We compared the performance of these two analytical instruments when used for first trimester combined testing. DESIGN AND METHODS: Serum samples from 944 singleton pregnant women attending for first trimester combined testing were routinely assayed for hCGβ and PAPP...

Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

Directory of Open Access Journals (Sweden)

Balamurugan Periaswamy

Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

Compromise and Disagreement in Comtemporary Political Theory

DEFF Research Database (Denmark)

Rostbøll, Christian F.; Scavenius, Theresa

Compromise and Disagreement in Contemporary Political Theory provides a critical discussion of when and to what extent compromise is the best response to pluralism and disagreement in democratic decision-making and beyond. Organized into four parts, the book begins by discussing the justification...... and limits of compromise. Part II discusses the practice of compromise and considers the ethics required for compromise as well as the institutions that facilitate compromise. Part III focuses on pluralism and connects the topic of compromise to current discussions in political theory on public reason...

Accelerated cardiovascular magnetic resonance of the mouse heart using self-gated parallel imaging strategies does not compromise accuracy of structural and functional measures

Directory of Open Access Journals (Sweden)

Dörries Carola

2010-07-01

spatial resolution at sufficiently high CNR. The accuracy of measurements of both structural and functional parameters of the mouse heart was not compromised by the application of the proposed accelerated data acquisition method.

How moral disagreement may ground principled moral compromise

DEFF Research Database (Denmark)

Kappel, Klemens

2018-01-01

In an influential article, Simon C. May forcefully argued that, properly understood, there can never be principled reasons for moral compromise (May, 2005). While there may be pragmatic reasons for compromising that involve, for instance, concern for political expediency or for stability, there a......In an influential article, Simon C. May forcefully argued that, properly understood, there can never be principled reasons for moral compromise (May, 2005). While there may be pragmatic reasons for compromising that involve, for instance, concern for political expediency or for stability......, there are properly speaking no principled reasons to compromise. My aim in the article is to show how principled moral compromise in the context of moral disagreements over policy options is possible. I argue that when we disagree, principled reasons favoring compromises or compromising can assume a more significant...... part of what makes a position all things considered best, and in this way disagreement can ground moral compromise....

Life history and bioeconomy of the house mouse.

Science.gov (United States)

Berry, R J; Bronson, F H

1992-11-01

1. More is known about the western European house mouse, Mus (musculus) domesticus than any other non-human mammal. If laboratory and field information is combined, an extremely valuable understanding of the species' bioeconomy could be obtained. 2. The seven stages of mouse life-history are surveyed (up to birth, nest life, sex life, social structure, population statics and stability, senescence, and death), and the interactions between the changing phenotype and the environment are described. 3. These interactions can be used to build up a model of the opportunities and compromises which result in the fitness of individual mice. It is not yet possible to quantify such a model, but this should in principle be achievable.

Laboratory mouse housing conditions can be improved using common environmental enrichment without compromising data

DEFF Research Database (Denmark)

André, Viola; Gau, Christine; Scheideler, Angelika

2018-01-01

Animal welfare requires the adequate housing of animals to ensure health and well-being. The application of environmental enrichment is a way to improve the well-being of laboratory animals. However, it is important to know whether these enrichment items can be incorporated in experimental mouse...... material and shelters may be used to improve animal welfare without impairment of experimental outcome or loss of comparability to previous data collected under barren housing conditions....

Energy policy - compromise or change?

International Nuclear Information System (INIS)

Lewitz, J.C.

1998-01-01

Is there a contrast between compromise and change? In the author's opinion, there is not. Society changes. Sometimes, change is brought about more easily on the basis of a compromise. A pluralistic society needs compromises in order to participate in change with convictions of its own. To reach a compromise including a large part of one's conviction, the public must be convinced. This is achieved most easily by somebody who is well informed, educated, and trained. In this respect, not only specialized knowledge counts, but also the ability to handle the language and to know how to speak, and the behavior in public. Expert knowledge is acquired at the university, in the execution of one's profession, and in advanced training. Knowledge may be enhanced, for instance, by dealing with the arguments used by the other side. This will help in arguing one's own point more effectively. Individual talks, and events at which information and knowledge are disseminated, enable persons to assume an opinion based on their comprehension. Many uniform opinions create a majority opinion. (orig.) [de

6 CFR 13.46 - Compromise or settlement.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Compromise or settlement. 13.46 Section 13.46 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.46 Compromise or settlement. (a) Parties may Make offers of compromise or settlement at any time...

Laboratory mouse housing conditions can be improved using common environmental enrichment without compromising data

Science.gov (United States)

Gau, Christine; Scheideler, Angelika; Aguilar-Pimentel, Juan A.; Amarie, Oana V.; Becker, Lore; Garrett, Lillian; Hans, Wolfgang; Hölter, Sabine M.; Janik, Dirk; Moreth, Kristin; Neff, Frauke; Östereicher, Manuela; Racz, Ildiko; Rathkolb, Birgit; Rozman, Jan; Bekeredjian, Raffi; Graw, Jochen; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Schmidt-Weber, Carsten; Wolf, Eckhard; Wurst, Wolfgang; Gailus-Durner, Valérie; Brielmeier, Markus; Fuchs, Helmut; Hrabé de Angelis, Martin

2018-01-01

Animal welfare requires the adequate housing of animals to ensure health and well-being. The application of environmental enrichment is a way to improve the well-being of laboratory animals. However, it is important to know whether these enrichment items can be incorporated in experimental mouse husbandry without creating a divide between past and future experimental results. Previous small-scale studies have been inconsistent throughout the literature, and it is not yet completely understood whether and how enrichment might endanger comparability of results of scientific experiments. Here, we measured the effect on means and variability of 164 physiological parameters in 3 conditions: with nesting material with or without a shelter, comparing these 2 conditions to a “barren” regime without any enrichments. We studied a total of 360 mice from each of 2 mouse strains (C57BL/6NTac and DBA/2NCrl) and both sexes for each of the 3 conditions. Our study indicates that enrichment affects the mean values of some of the 164 parameters with no consistent effects on variability. However, the influence of enrichment appears negligible compared to the effects of other influencing factors. Therefore, nesting material and shelters may be used to improve animal welfare without impairment of experimental outcome or loss of comparability to previous data collected under barren housing conditions. PMID:29659570

Laboratory mouse housing conditions can be improved using common environmental enrichment without compromising data.

Directory of Open Access Journals (Sweden)

Viola André

2018-04-01

Full Text Available Animal welfare requires the adequate housing of animals to ensure health and well-being. The application of environmental enrichment is a way to improve the well-being of laboratory animals. However, it is important to know whether these enrichment items can be incorporated in experimental mouse husbandry without creating a divide between past and future experimental results. Previous small-scale studies have been inconsistent throughout the literature, and it is not yet completely understood whether and how enrichment might endanger comparability of results of scientific experiments. Here, we measured the effect on means and variability of 164 physiological parameters in 3 conditions: with nesting material with or without a shelter, comparing these 2 conditions to a "barren" regime without any enrichments. We studied a total of 360 mice from each of 2 mouse strains (C57BL/6NTac and DBA/2NCrl and both sexes for each of the 3 conditions. Our study indicates that enrichment affects the mean values of some of the 164 parameters with no consistent effects on variability. However, the influence of enrichment appears negligible compared to the effects of other influencing factors. Therefore, nesting material and shelters may be used to improve animal welfare without impairment of experimental outcome or loss of comparability to previous data collected under barren housing conditions.

Career Compromises: Framings and Their Implications.

Science.gov (United States)

Gati, Itamar; Houminer, Daphna; Aviram, Tamar

1998-01-01

Career compromise was investigated in three framings (alternatives, aspect importance, within-aspect preference). Young adults and school counselors rated hypothetical stories. Results of four studies with different designs (Average N=106) supported the hypothesis. The alternatives framing was associated with greater compromise and decision…

Suboptimal T-cell receptor signaling compromises protein translation, ribosome biogenesis, and proliferation of mouse CD8 T cells.

Science.gov (United States)

Tan, Thomas C J; Knight, John; Sbarrato, Thomas; Dudek, Kate; Willis, Anne E; Zamoyska, Rose

2017-07-25

Global transcriptomic and proteomic analyses of T cells have been rich sources of unbiased data for understanding T-cell activation. Lack of full concordance of these datasets has illustrated that important facets of T-cell activation are controlled at the level of translation. We undertook translatome analysis of CD8 T-cell activation, combining polysome profiling and microarray analysis. We revealed that altering T-cell receptor stimulation influenced recruitment of mRNAs to heavy polysomes and translation of subsets of genes. A major pathway that was compromised, when TCR signaling was suboptimal, was linked to ribosome biogenesis, a rate-limiting factor in both cell growth and proliferation. Defective TCR signaling affected transcription and processing of ribosomal RNA precursors, as well as the translation of specific ribosomal proteins and translation factors. Mechanistically, IL-2 production was compromised in weakly stimulated T cells, affecting the abundance of Myc protein, a known regulator of ribosome biogenesis. Consequently, weakly activated T cells showed impaired production of ribosomes and a failure to maintain proliferative capacity after stimulation. We demonstrate that primary T cells respond to various environmental cues by regulating ribosome biogenesis and mRNA translation at multiple levels to sustain proliferation and differentiation.

Dental management of medically compromised patients

Directory of Open Access Journals (Sweden)

Sherly Horax

2016-06-01

Full Text Available These days, treatment in dentistry is no longer for patient without complication, but also for patient with bad medical record. With correct treatment management in handling medical condition of patient, not only for dental treatment but also their systematic disease, all the dental staff also can improve for the better quality of life of the patient. Patient with medical compromised start to realize that  keeping good oral hygiene is so important for their lives, therefore dental staff need to improve their science and technology and also for facing patient with medical compromised. This article will discuss and suggest various treatment consideration and protocol for the patient of with medical compromised.

Dopamine D2 receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouse

OpenAIRE

Oien, Derek B.; Ortiz, Andrea N.; Rittel, Alexander G.; Dobrowsky, Rick T.; Johnson, Michael A.; Levant, Beth; Fowler, Stephen C.; Moskovitz, Jackob

2010-01-01

Previous research suggests that brain oxidative stress and altered rodent locomotor behavior are linked. We observed bio-behavioral changes in methionine sulfoxide reductase A knockout mice associated with abnormal dopamine signaling. Compromised ability of these knockout mice to reduce methionine sulfoxide enhances accumulation of sulfoxides in proteins. We examined the dopamine D2-receptor function and expression, which has an atypical arrangement and quantity of methionine residues. Indeed...

Compromise in cooperative game and the VIKOR method

Directory of Open Access Journals (Sweden)

Opricović Serafim

2009-01-01

Full Text Available Five approaches in conflict resolution are distinguished, based on cooperativeness and aggressiveness in resolving conflict. Compromise based on cooperativeness is emphasized here as a solution in conflict resolution. Cooperative game theory oriented towards aiding the conflict resolution is considered and the compromise value for TU(transferable utility-game is presented. The method VIKOR could be applied to determine compromise solution of a multicriteria decision making problem with noncommensurable and conflicting criteria. Compromise is considered as an intermediate state between conflicting objectives or criteria reached by mutual concession. The applicability of the cooperative game theory and the VIKOR method for conflict resolution is illustrated.

22 CFR 213.25 - Standards for compromise.

Science.gov (United States)

2010-04-01

... proceedings. In evaluating the acceptability of the offer, the CFO may consider, among other factors, the... applicable exemptions available to the debtor under State and Federal law in determining the Government's ability to enforce collection. (b) USAID may compromise a claim, or recommend acceptance of a compromise...

Kyphoplasty for osteoporotic fractures with spinal canal compromise

International Nuclear Information System (INIS)

Gan Minfeng; Yang Huilin; Zou Jun; Wang Genlin; Mei Xin; Zhou Feng; Chen Liang; Jiang Weimin

2010-01-01

Objective: To explore the feasibility and clinical outcome of kyphoplasty in the treatment of osteoporotic fractures with canal compromise. Methods: A total of 16 patients with osteoporotic fractures with canal compromise without neurological deficit were attempted to be treated by kyphoplasty. During kyphoplasty, modified techniques including staged bone cement injection and dynamic fluoroscopic monitoring were used. Pain was measured using the self-reporting Visual Analogue pain Scale (VAS) preoperatively, postoperatively and in the final follow-up. Disability was measured using the Oswestry Disability questionnaire (ODI) preoperatively, postoperatively and in the final follow-up. The height of the compromised vertebral body, the kyphotic angle and the spinal canal compromise were measured preoperatively, postoperatively and in the final follow-up. Results: Operations were completed smoothly, with the exception of one patient with less cement leakage but without clinical symptom occurred. Relief of pain was achieved after kyphoplasty. The mean VAS score of these patients decreased from 8.1 ± 1.2 pre-operatively to 2.7 ± 0.6 post-operatively (P 0.05). In the final follow-up, the spinal canal compromise was (14.4 ± 3.1)%. Conclusion: Kyphoplasty is a relatively safe and effective method for the treatment of osteoporotic fractures with canal compromise without neurological deficit. (authors)

20 CFR 255.18 - Compromise of overpayments.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Compromise of overpayments. 255.18 Section 255.18 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... standards which the Board applies in exercising its authority under 31 U.S.C. 3711 to compromise an...

16 CFR 1.96 - Compromise of penalty.

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Compromise of penalty. 1.96 Section 1.96 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE GENERAL... may compromise any penalty or proposed penalty at any time, with leave of court when necessary, taking...

Strained Compromises?

DEFF Research Database (Denmark)

Ibsen, Christian Lyhne

The Danish version of flexicurity is not only about a balance between labour market flexibility and social security. Arguably, it is also series of more or less stable underlying compromises between social partners about the main mechanisms and aims of labour market regulation which – supposedly...... – should be focused on employment rather than jobs and competition on quality rather than on labour costs. However, most studies on Danish flexicurity have been carried out under favourable economic conditions with social partners almost naturally agreeing to the merits of the model – at least in principle...

Compromised data from social media to big data

CERN Document Server

Redden, Joanna; Langlois, Ganaele

2015-01-01

There has been a data rush in the past decade brought about by online communication and, in particular, social media (Facebook, Twitter, Youtube, among others), which promises a new age of digital enlightenment. But social data is compromised: it is being seized by specific economic interests, it leads to a fundamental shift in the relationship between research and the public good, and it fosters new forms of control and surveillance. Compromised Data: From Social Media to Big Data explores how we perform critical research within a compromised social data framework. The expert, international l

Flow-based Compromise Detection

NARCIS (Netherlands)

Hofstede, R.J.

2016-01-01

Brute-force attacks are omnipresent and manyfold on the Internet, and aim at compromising user accounts by issuing large numbers of authentication attempts on applications and daemons. Widespread targets of such attacks are Secure SHell (SSH) and Web applications, for example. The impact of

Impending Airway Compromise due to Cystic Hygroma

Directory of Open Access Journals (Sweden)

Itai Shavit

2011-05-01

Full Text Available We report on a 3-month-old infant, who arrived in the pediatric emergency department (ED with a cervical cystic hygroma causing an impending compromise of the airway. We recognize that such a lesion can rapidly progress, and the judicious use of imaging in the ED may help to avoid airway compromise and possibly fatal complications. [West J Emerg Med. 2011;12(4:368–369.

41 CFR 105-55.019 - Compromise of claims.

Science.gov (United States)

2010-07-01

... and a recommendation for the acceptance of the compromise offer. Justice Department approval is not... exercise the authorities in this section. (b) Unless otherwise provided by law, when the principal balance... Department of Justice. GSA will evaluate the compromise offer, using the factors set forth in § 105-55.020...

Temporal course of pregnancy-associated plasma protein-A in angioplasty-treated ST-elevation myocardial infarction patients and potential significance of concomitant heparin administration

DEFF Research Database (Denmark)

Terkelsen, Christian J; Oxvig, Claus; Nørgaard, Bjarne L

2009-01-01

Pregnancy-associated plasma protein-A (PAPP-A) is a putative plaque instability marker. In acute coronary syndromes, the disrupted culprit plaque contains abundant PAPP-A, and circulating PAPP-A levels predict clinical outcomes. Determinants of circulating PAPP-A levels, however, are not fully...

The role of postoperative hematoma on free flap compromise.

Science.gov (United States)

Ahmad, Faisal I; Gerecci, Deniz; Gonzalez, Javier D; Peck, Jessica J; Wax, Mark K

2015-08-01

Hematomas may develop in the postoperative setting after free tissue transfer. When hematomas occur, they can exert pressure on surrounding tissues. Their effect on the vascular pedicle of a free flap is unknown. We describe our incidence of hematoma in free flaps and outcomes when the flap is compromised. Retrospective chart review of 1,883 free flaps performed between July 1998 and June 2014 at a tertiary referral center. Patients with free flap compromise due to hematoma were identified. Etiology, demographic data, and outcomes were evaluated. Eighty-eight (4.7%) patients developed hematomas. Twenty (22.7%) of those had flap compromise. Twelve compromises (60%) showed evidence of pedicle thrombosis. The salvage rate was 75% versus 54% in 79 flaps with compromise from other causes (P = .12). Mean time to detection of the hematoma was 35.3 hours in salvaged flaps compared to 91.6 hours in unsalvageable flaps (P = .057). Time to operating room (OR) from detection was 2.8 hours in salvageable flaps compared to 12.4 hours in nonsalvageable flaps (P = .053). The salvage rate for flaps that returned to the OR in hematomas developed rarely. When they did, 23% went on to develop flap compromise. Prompt recognition and re-exploration allowed for a high salvage rate. Vessel thrombosis predicted inability to salvage the flap. 4 © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Interspecies chimera between primate embryonic stem cells and mouse embryos: monkey ESCs engraft into mouse embryos, but not post-implantation fetuses.

Science.gov (United States)

Simerly, Calvin; McFarland, Dave; Castro, Carlos; Lin, Chih-Cheng; Redinger, Carrie; Jacoby, Ethan; Mich-Basso, Jocelyn; Orwig, Kyle; Mills, Parker; Ahrens, Eric; Navara, Chris; Schatten, Gerald

2011-07-01

Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor. Copyright © 2011 Elsevier B.V. All rights reserved.

Combating QR-Code-Based Compromised Accounts in Mobile Social Networks.

Science.gov (United States)

Guo, Dong; Cao, Jian; Wang, Xiaoqi; Fu, Qiang; Li, Qiang

2016-09-20

Cyber Physical Social Sensing makes mobile social networks (MSNs) popular with users. However, such attacks are rampant as malicious URLs are spread covertly through quick response (QR) codes to control compromised accounts in MSNs to propagate malicious messages. Currently, there are generally two types of methods to identify compromised accounts in MSNs: one type is to analyze the potential threats on wireless access points and the potential threats on handheld devices' operation systems so as to stop compromised accounts from spreading malicious messages; the other type is to apply the method of detecting compromised accounts in online social networks to MSNs. The above types of methods above focus neither on the problems of MSNs themselves nor on the interaction of sensors' messages, which leads to the restrictiveness of platforms and the simplification of methods. In order to stop the spreading of compromised accounts in MSNs effectively, the attacks have to be traced to their sources first. Through sensors, users exchange information in MSNs and acquire information by scanning QR codes. Therefore, analyzing the traces of sensor-related information helps to identify the compromised accounts in MSNs. This paper analyzes the diversity of information sending modes of compromised accounts and normal accounts, analyzes the regularity of GPS (Global Positioning System)-based location information, and introduces the concepts of entropy and conditional entropy so as to construct an entropy-based model based on machine learning strategies. To achieve the goal, about 500,000 accounts of Sina Weibo and about 100 million corresponding messages are collected. Through the validation, the accuracy rate of the model is proved to be as high as 87.6%, and the false positive rate is only 3.7%. Meanwhile, the comparative experiments of the feature sets prove that sensor-based location information can be applied to detect the compromised accounts in MSNs.

Combating QR-Code-Based Compromised Accounts in Mobile Social Networks

Directory of Open Access Journals (Sweden)

Dong Guo

2016-09-01

Full Text Available Cyber Physical Social Sensing makes mobile social networks (MSNs popular with users. However, such attacks are rampant as malicious URLs are spread covertly through quick response (QR codes to control compromised accounts in MSNs to propagate malicious messages. Currently, there are generally two types of methods to identify compromised accounts in MSNs: one type is to analyze the potential threats on wireless access points and the potential threats on handheld devices’ operation systems so as to stop compromised accounts from spreading malicious messages; the other type is to apply the method of detecting compromised accounts in online social networks to MSNs. The above types of methods above focus neither on the problems of MSNs themselves nor on the interaction of sensors’ messages, which leads to the restrictiveness of platforms and the simplification of methods. In order to stop the spreading of compromised accounts in MSNs effectively, the attacks have to be traced to their sources first. Through sensors, users exchange information in MSNs and acquire information by scanning QR codes. Therefore, analyzing the traces of sensor-related information helps to identify the compromised accounts in MSNs. This paper analyzes the diversity of information sending modes of compromised accounts and normal accounts, analyzes the regularity of GPS (Global Positioning System-based location information, and introduces the concepts of entropy and conditional entropy so as to construct an entropy-based model based on machine learning strategies. To achieve the goal, about 500,000 accounts of Sina Weibo and about 100 million corresponding messages are collected. Through the validation, the accuracy rate of the model is proved to be as high as 87.6%, and the false positive rate is only 3.7%. Meanwhile, the comparative experiments of the feature sets prove that sensor-based location information can be applied to detect the compromised accounts in MSNs.

Myocardial and Peripheral Ischemia Causes an Increase in Circulating Pregnancy-Associated Plasma Protein-A in Non-atherosclerotic, Non-heparinized Pigs.

Science.gov (United States)

Steffensen, Lasse Bach; Poulsen, Christian Bo; Shim, Jeong; Bek, Marie; Jacobsen, Kevin; Conover, Cheryl A; Bentzon, Jacob Fog; Oxvig, Claus

2015-12-01

The usefulness of circulating pregnancy-associated plasma protein-A (PAPP-A) as a biomarker for acute coronary syndrome (ACS) is widely debated. We used the pig as a model to assess PAPP-A dynamics in the setting of myocardial ischemia. Induction of myocardial ischemia by ligation of the left anterior descending (LAD) coronary artery caused a systemic rise in PAPP-A. However, the ischemic myocardium was excluded as the source of PAPP-A. Interestingly, induction of ischemia in peripheral tissues by ligation of the left femoral artery caused a systemic rise in PAPP-A originating from the left hind limb. This is the first study to demonstrate PAPP-A elevations in the absence of atherosclerosis or heparin during myocardial ischemia. Our findings thus add to the current discussion of the usefulness of PAPP-A as a biomarker for ACS.

32 CFR 310.50 - Lost, stolen, or compromised information.

Science.gov (United States)

2010-07-01

... Official for Privacy within 24 hours of discovering that a breach of personally identifiable information... Privacy Office of the breach within 48 hours upon being notified that a loss, theft, or compromise has... (CONTINUED) PRIVACY PROGRAM DOD PRIVACY PROGRAM Privacy Act Violations § 310.50 Lost, stolen, or compromised...

Physically Compromised and Physically Talented Children in Northeastern Slovenia

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Planinšec Jurij

2012-12-01

Full Text Available The aim of our research was to determine the share of physically compromised and physically talented children in northeastern Slovenia. The sample comprised 621 children aged nine to eleven years, among which there were 316 girls (M=10; SD=0.8 and 305 boys (M=10; SD=0.81. In order to assess their motor skills, seven different tests were used, mostly from Eurofit test battery, which covered explosive power, repetitive power balance, eye–hand coordination, speed of simple movements, whole body coordination, and endurance. The assessment was made for each physical fitness test separately. The cut-off points for determination of physically compromised and physically talented children were set at -1SD and +1SD, respectively. The results of all physical fitness tests showed that the share of physically compromised children exceeded ten percent for both genders. The largest number of boys and girls were physically compromised with regard to endurance and balance, respectively. On the other hand, boys proved to be most physically talented with regard to endurance, and girls with regard to explosive power. Gender differences were most obvious with regard to general endurance, as 21 per cent of the boys were physically compromised as opposed to 13 per cent of the girls. As for physical talent, we observed less gender-related differences. The results indicate increasing differences in physical fitness among children from northeastern Slovenia. The implementation of curricular and extracurricular sports activities should aim at reducing the number of physically compromised children. On the other hand, it would make sense to encourage physically talented children to get involved in organized forms of exercise.

Successful sanitation of an EDIM-infected mouse colony by breeding cessation.

Science.gov (United States)

Held, N; Hedrich, H J; Bleich, A

2011-10-01

Despite decreasing prevalence, rotavirus infections still rank among the most important viral infections in colonies of laboratory mice. Although the disease is characterized by low mortality and a relatively short and mild clinical period, the infection has the potential to alter the outcome of experiments substantially. For animal facilities, it is therefore essential to eradicate the virus. Here we report a successful sanitation of a rotavirus-infected mouse colony in an animal facility. Despite a high ratio of transgenic and partially immunodeficient strains, a permanent eradication of the virus was achieved by euthanasia of highly susceptible mice, a prolonged breeding cessation in areas containing immunocompromised mice and a strict hygienic management. The management of a rotavirus infection reported here is a feasible and inexpensive opportunity for sanitation that benefits from maintaining most of the animal population, even in today's mouse colonies comprising mainly transgenic mice with unknown or compromised immune status.

The proteolytic activity of pregnancy-associated plasma protein-A is potentially regulated by stanniocalcin-1 and -2 during human ovarian follicle development

DEFF Research Database (Denmark)

Jepsen, Malene R.; Kløverpris, Søren; Bøtkjær, Jane A.

2016-01-01

STUDY QUESTION: Is the proteolytic activity of pregnancy-associated plasma protein-A (PAPP-A) regulated by the stanniocalcins (STC1 and STC2) during human follicle maturation? SUMMARY ANSWER: The STCs and PAPP-A show similar expression by immunohistochemistry in developing follicles, and regulation...... of PAPP-A proteolytic activity is suggested by the identification of inhibited protein complexes between PAPP-A and STC1 or STC2 in human follicular fluid (FF). WHAT IS KNOWN ALREADY: The insulin-like growth factor (IGF)-regulating proteinase PAPP-A is secreted by the granulosa cells of estrogen...

Biological variation of free β chorionic gonadotropin and pregnancy-associated plasma protein A in first trimester pregnancies

DEFF Research Database (Denmark)

Sennels, Henriette P; Jørgensen, Finn Stener; Sørensen, Steen

2011-01-01

protein A (PAPP-A). However, little knowledge exists regarding the biological variation of hCGβ and PAPP-A when the time interval between sampling increases. Methods: We estimated these variations from double mea-surements of hCGβ and PAPP-A in first trimester pregnancies in 167 women. Data were divided...... into three groups based on the number of days between sampling. The correlation coefficients and biological variation were estimated for each group. Results: The correlation coefficient between the first and second samples was 0.841 for hCGβ, and 0.706 for PAPP-A. The ranges for biological variation were 11.......9%-48.5% for hCGβ and 31.6%-63.3% for PAPP-A, increasing with time between sampling. The average overall biological variation for hCGβ was 29%, and 49.7% for PAPP-A. Conclusions: We found high biological variation for plasma concentrations of hCGβ and PAPP-A, increasing with longer time intervals between...

Biological variation of free β chorionic gonadotropin and pregnancy-associated plasma protein A in first trimester pregnancies

DEFF Research Database (Denmark)

Sennels, Henriette P; Jørgensen, Finn Stener; Sørensen, Steen

2011-01-01

protein A (PAPP-A). However, little knowledge exists regarding the biological variation of hCGß and PAPP-A when the time interval between sampling increases. Methods: We estimated these variations from double mea-surements of hCGß and PAPP-A in first trimester pregnancies in 167 women. Data were divided...... into three groups based on the number of days between sampling. The correlation coefficients and biological variation were estimated for each group. Results: The correlation coefficient between the first and second samples was 0.841 for hCGß, and 0.706 for PAPP-A. The ranges for biological variation were 11.......9%-48.5% for hCGß and 31.6%-63.3% for PAPP-A, increasing with time between sampling. The average overall biological variation for hCGß was 29%, and 49.7% for PAPP-A. Conclusions: We found high biological variation for plasma concentrations of hCGß and PAPP-A, increasing with longer time intervals between...

Compromised Agency: The Case of BabyLegs

Directory of Open Access Journals (Sweden)

Max Liboiron

2017-09-01

Full Text Available The concept of agency is ubiquitous in STS, particularly regarding cases of alternative ways of knowing and doing science such as civic, citizen, and feminist sciences, among others. Yet the focus on agency often glosses over the constraints placed on agents, particularly within asymmetrical power relations. This article follows the case of BabyLegs, a do-it-yourself monitoring tool for marine microplastic pollution, and the attempt to keep the technology open source within an intellectual property (IP system set up to privatize it. The tactics used to design BabyLegs as a feminine, silly, doll-tool to discredit the device in the eyes of an IP system that valued traditional gender roles lead to the eventual success of keeping the device open source. Yet, those same tactics also reinforced and reproduced the structures of power and essentialism they were designed to resist. I characterize this technological ambivalence as compromise, and argue that all agency exercised within asymmetrical power relations is compromised. This is not to say resistance is futile, but that agency is never pure, and this recognition lets us be more intentional in how we might compromise as practitioners of diverse scientific knowledges.

Compromise decision support problems for hierarchical design involving uncertainty

Science.gov (United States)

Vadde, S.; Allen, J. K.; Mistree, F.

1994-08-01

In this paper an extension to the traditional compromise Decision Support Problem (DSP) formulation is presented. Bayesian statistics is used in the formulation to model uncertainties associated with the information being used. In an earlier paper a compromise DSP that accounts for uncertainty using fuzzy set theory was introduced. The Bayesian Decision Support Problem is described in this paper. The method for hierarchical design is demonstrated by using this formulation to design a portal frame. The results are discussed and comparisons are made with those obtained using the fuzzy DSP. Finally, the efficacy of incorporating Bayesian statistics into the traditional compromise DSP formulation is discussed and some pending research issues are described. Our emphasis in this paper is on the method rather than the results per se.

Near-infrared spectroscopy for detection of vascular compromise in paediatric supracondylar fractures

International Nuclear Information System (INIS)

Skowno, Justin J; De Lima, Jonathan; Quick, Tom J; Carpenter, Eleanor C; Gibbons, Paul J; Little, David G

2014-01-01

Children suffering supracondylar fractures of the humerus are at risk of vascular compromise, which is currently assessed clinically, although other modalities such as angiography, pulse oximetry, Doppler ultrasound and magnetic resonance angiography have been used. We sought to ascertain whether tissue haemoglobin oxygenation (StO 2 ) measurement could distinguish between patients with and without clinical vascular compromise following supracondylar fractures of the humerus. We prospectively observed StO 2  using near-infrared spectroscopy in 29 paediatric patients with supracondylar fractures requiring operative manipulation. The injured and uninjured volar forearm compartments were monitored immediately before and after fracture reduction. The relationship between StO 2  in the injured and uninjured limb, and the presence of pre-operative vascular compromise was assessed. Seven out of 29 children presented with vascular compromise. Patients with clinical vascular compromise had significantly lower pre-reduction StO 2  (63.5% ± 15%, mean ± standard deviation), compared to those without compromise (80.9% ± 10%). StO 2  normalized following surgery in all children with vascular compromise. These improvements in muscle StO 2  were associated, in all patients, with the clinical return of pulses and resolution of neurological symptoms if present. StO 2  monitoring can identify patients with clinical vascular compromise, can identify the return of adequate perfusion following operative correction of supracondylar fractures, and may be a useful adjunct to clinical assessment. (paper)

Development of Mouse Models of Ovarian Cancer for Studying Tumor Biology and Testing Novel Molecularly Targeted Therapeutic Strategies

Science.gov (United States)

2011-09-01

obtained from the response of cancer cells in culture or implanted (xenografted) into immuno- compromised mice. Although there are many new drugs and...validation of constructs in vitro (completed, year 1 - Rehemtulla laboratory) Task 3: Plasmid DNA purification for injection, microinjection of mouse...ApoptosisLSL-Luc and Rosa26LSL-Luc reporters, Rehemtulla and Cho laboratories) Task 5: Determine transgene copy number, verify expression of tomato by

When data representation compromise data security

DEFF Research Database (Denmark)

Simonsen, Eivind Ortind; Dahl, Mads Ronald

WHEN DATA REPRESENTATION COMPROMISE DATA SECURITY The workflow of transforming data into informative representations makes extensive usage of computers and software. Scientists have a conventional tradition for producing publications that include tables and graphs as data representations....... These representations can be used for multiple purposes such as publications in journals, teaching and conference material. But when created, stored and distributed in a digital form there is a risk of compromising data security. Data beyond the once used specifically to create the representation can be included...... on the internet over many years? A new legislation proposed in 2012 by the European Commission on protection of personal data will be implemented from 2015. The new law will impose sanction options ranging from a warning to a fine up to 100.000.000 EUR. We argue that this new law will lead to especially...

Tax Administration: IRS Should Evaluate the Changes to Its Offer in Compromise Program

National Research Council Canada - National Science Library

2002-01-01

...) Offer in Compromise (OIC) Program. An offer in compromise is an agreement between a taxpayer and the IRS to settle or compromise the taxpayer's tax liability for less than the full amount owed...

Objections to the Libertarian Stem Cell Compromise

Directory of Open Access Journals (Sweden)

Walter E. Block

2010-11-01

Full Text Available In Block (2010 I offered a compromise between the pro choice position that fervently supports stem cell research, and the pro life philosophy which bitterly opposes it. The compromise was a contest: allow would be researchers to create as many fertilized eggs as they wished. But, also, these should be offered up to would be parents to adopt all of these “children” as they wanted. If and only if there were any unadopted fetuses remaining in the laboratories of the nation would it be licit, on libertarian grounds, for research on them to take place. In the present paper I respond to several objections to this “modest proposal.”

7 CFR 1956.68 - Compromise or adjustment without debtor's signature.

Science.gov (United States)

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Compromise or adjustment without debtor's signature... Loan Programs and Multi-Family Housing § 1956.68 Compromise or adjustment without debtor's signature... made to obtain the debtor's signature and the date(s) of such effort. (c) The specific reasons why it...

32 CFR 842.99 - Compromise, termination, and suspension of collection.

Science.gov (United States)

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Compromise, termination, and suspension of collection. 842.99 Section 842.99 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR... States (31 U.S.C. 3701, 3711-3719) § 842.99 Compromise, termination, and suspension of collection. This...

Genome Transfer Prevents Fragmentation and Restores Developmental Potential of Developmentally Compromised Postovulatory Aged Mouse Oocytes

Directory of Open Access Journals (Sweden)

Mitsutoshi Yamada

2017-03-01

Full Text Available Changes in oocyte quality can have great impact on the developmental potential of early embryos. Here we test whether nuclear genome transfer from a developmentally incompetent to a developmentally competent oocyte can restore developmental potential. Using in vitro oocyte aging as a model system we performed nuclear transfer in mouse oocytes at metaphase II or at the first interphase, and observed that development to the blastocyst stage and to term was as efficient as in control embryos. The increased developmental potential is explained primarily by correction of abnormal cytokinesis at anaphase of meiosis and mitosis, by a reduction in chromosome segregation errors, and by normalization of the localization of chromosome passenger complex components survivin and cyclin B1. These observations demonstrate that developmental decline is primarily due to abnormal function of cytoplasmic factors involved in cytokinesis, while the genome remains developmentally fully competent.

Serum pregnancy-associated plasma protein A levels in the first, second and third trimester of pregnancy: relation to newborn anthropometric parameters and maternal tobacco smoking.

Science.gov (United States)

Chełchowska, Magdalena; Gajewska, Joanna; Mazur, Joanna; Ambroszkiewicz, Jadwiga; Maciejewski, Tomasz M; Leibschang, Jerzy

2016-12-01

The purpose of this study was to evaluate the associations of the first, second and third trimester serum pregnancy-associated plasma protein A (PAPP-A) concentrations with neonatal anthropometric parameters. The effect of tobacco smoking during pregnancy on PAPP-A level was also studied. One hundred and fifty healthy pregnant women were divided into smoking and tobacco-abstinent groups. Serum PAPP-A level was measured with the KRYPTOR rapid random-access immunoassay analyzer. The relationship between PAPP-A and newborn related outcome as well as markers of estimated intensity of cigarette smoking was evaluated by univariate and multivariate linear regression. Pregnancy-associated plasma protein A concentration was positively correlated with birth weight in the first (β = 31.6; p < 0.001), second (β = 10.6; p < 0.05), and third (β = 4.6; p < 0.001) trimester of gestation. A significant association between PAPP-A and birth body length and head circumference in the second (β = 0.02; p < 0.05) and third trimester (β = 0.01; p < 0.01) was also found. The serum PAPP-A levels were significantly lower in the smoking than in the tobacco-abstinent group in each trimester of pregnancy ( p < 0.001). The largest impact of the number of cigarettes smoked per day on PAPP-A level was found in the second (β = -1.2; p = 0.004) and third trimester (β = -2.6; p = 0.001). Maternal serum PAPP-A levels during gestation might be significant predictors for birth weight. Increased PAPP-A concentrations in the second and third trimester appeared to also be predictive for newborn body length and head circumference. Smoking alters maternal PAPP-A levels in all trimesters, with the greatest impact related to the number of cigarettes smoked per day.

10 CFR 15.41 - When a claim may be compromised.

Science.gov (United States)

2010-01-01

... it has not been referred to DOJ for litigation. (b) Unless otherwise provided by law, when the... with the DOJ. The NRC will evaluate the compromise offer, using the factors set forth in this part. If an offer to compromise any debt in excess of $100,000 is acceptable to the NRC, the NRC shall refer...

Strained Compromises? Danish Flexicurity During Crisis

DEFF Research Database (Denmark)

Ibsen, Christian Lyhne

2011-01-01

The Danish concept of flexicurity in a ‘Golden Triangle’ of low job protection, high income security and high employment security is not only about a balance between labor market flexibility and social security. Arguably, it is also a series of more or less stable underlying compromises between...

Regulation of IGF binding protein proteolysis by pregnancy-associated plasma protein-ARegulation of IGF binding protein proteolysis by pregnancy-associated plasma protein-A

DEFF Research Database (Denmark)

Gaidamauskas, Ervinas

During his PhD studies, Ervinas Gaidamauskas researched the proteins pregnancy-associated plasma protein-A (PAPP-A) and its homologue PAPP-A2 in vitro. As suggested by its name, PAPP-A plays an important role in pregnancy and fetal development. Additionally, recent studies indicate a newly...

Securing Single Points of Compromise (SPoC)

Energy Technology Data Exchange (ETDEWEB)

Belangia, David Warren [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2015-06-25

Securing the Single Points of Compromise that provide central services to the institution’s environment is paramount to success when trying to protect the business. (Fisk, 2014) Time Based Security mandates protection (erecting and ensuring effective controls) that last longer than the time to detect and react to a compromise. When enterprise protections fail, providing additional layered controls for these central services provides more time to detect and react. While guidance is readily available for securing the individual critical asset, protecting these assets as a group is not often discussed. Using best business practices to protect these resources as individual assets while leveraging holistic defenses for the group increases the opportunity to maximize protection time, allowing detection and reaction time for the SPoCs that is commensurate with the inherent risk of these centralized services.

Chemical clearing and dehydration of GFP expressing mouse brains.

Science.gov (United States)

Becker, Klaus; Jährling, Nina; Saghafi, Saiedeh; Weiler, Reto; Dodt, Hans-Ulrich

2012-01-01

Generally, chemical tissue clearing is performed by a solution consisting of two parts benzyl benzoate and one part benzyl alcohol. However, prolonged exposure to this mixture markedly reduces the fluorescence of GFP expressing specimens, so that one has to compromise between clearing quality and fluorescence preservation. This can be a severe drawback when working with specimens exhibiting low GFP expression rates. Thus, we screened for a substitute and found that dibenzyl ether (phenylmethoxymethylbenzene, CAS 103-50-4) can be applied as a more GFP-friendly clearing medium. Clearing with dibenzyl ether provides improved tissue transparency and strikingly improved fluorescence intensity in GFP expressing mouse brains and other samples as mouse spinal cords, or embryos. Chemical clearing, staining, and embedding of biological samples mostly requires careful foregoing tissue dehydration. The commonly applied tissue dehydration medium is ethanol, which also can markedly impair GFP fluorescence. Screening for a substitute also for ethanol we found that tetrahydrofuran (CAS 109-99-9) is a more GFP-friendly dehydration medium than ethanol, providing better tissue transparency obtained by successive clearing. Combined, tetrahydrofuran and dibenzyl ether allow dehydration and chemical clearing of even delicate samples for UM, confocal microscopy, and other microscopy techniques.

Transgenic overexpression of pregnancy-associated plasma protein-A in murine arterial smooth muscle accelerates atherosclerotic lesion development

DEFF Research Database (Denmark)

Conover, Cheryl A.; Mason, Megan A.; Bale, Laurie K.

2010-01-01

Pregnancy-associated plasma protein-A (PAPP-A) increases local IGF-I bioavailability through cleavage of inhibitory IGF binding protein (IGFBP)-4 in a variety of systems, including the cardiovascular system. To test the hypothesis that expression of PAPP-A promotes the development of atherosclero......Pregnancy-associated plasma protein-A (PAPP-A) increases local IGF-I bioavailability through cleavage of inhibitory IGF binding protein (IGFBP)-4 in a variety of systems, including the cardiovascular system. To test the hypothesis that expression of PAPP-A promotes the development...

Alchemy or Science? Compromising Archaeology in the Deep Sea

Science.gov (United States)

Adams, Jonathan

2007-06-01

In the torrid debate between archaeology and treasure hunting, compromise is often suggested as the pragmatic solution, especially for archaeology carried out either in deep water or beyond the constraints that commonly regulate such activities in territorial seas. Both the wisdom and the need for such compromise have even been advocated by some archaeologists, particularly in forums such as the internet and conferences. This paper argues that such a compromise is impossible, not in order to fuel confrontation but simply because of the nature of any academic discipline. We can define what archaeology is in terms of its aims, theories, methods and ethics, so combining it with an activity founded on opposing principles must transform it into something else. The way forward for archaeology in the deep sea does not lie in a contradictory realignment of archaeology’s goals but in collaborative research designed to mesh with emerging national and regional research and management plans.

A novel approach for amplification and purification of mouse oligodendrocyte progenitor cells

Directory of Open Access Journals (Sweden)

Junlin Yang

2016-08-01

Full Text Available Although transgenic and knockout mice are widely used to study the specification and differentiation of oligodendrocyte precursor cells (OPCs, mouse primary OPCs are difficult to be purified and maintained, and many in vitro studies have to resort to rat OPCs as substitutes. In this study, we reported that mouse O4 negative early-stage OPCs can be obtained by culturing cortical tissue blocks, and the simultaneous treatment of OPCs with PDGFaa, bFGF and EGF is the key for the propagation of mouse OPCs in culture. Epidermal growth factor (EGF was found to be a potent mitogen for OPCs and cooperate with Platelet Derived Growth Factor-AA (PDGFaa to extend cell division and inhibit their differentiation. EGF also collaborates with PDGFaa and basic fibroblast growth factor (bFGF to convert bipolar or tripolar OPCs to more vital fibroblast-like OPCs without compromising their oligodendrocyte differentiation potential. In addition, EGF promoted the survival and proliferation of glial progenitor cells (GPCs derived from primary OPC cultures, and a mixture of GPCs and OPCs can be obtained and propagated in the presence of EGF, bFGF and PDGFaa. Once EGF is withdrawn, GPC population decreased sharply and fibroblast-like OPCs changed into typical OPCs morphology, then homogeneous OPCs were obtained subsequently.

Strained Compromises? Danish Flexicurity During Crisis

Directory of Open Access Journals (Sweden)

Christian Lyhne Ibsen

2011-01-01

Full Text Available The Danish concept of flexicurity in a `Golden Triangle´ of low job protection, high income security and high employment security is not only about a balance between labor market flexibility and social security. Arguably, it is also a series of more or less stable underlying compromises between social partners about the main mechanisms and aims of labor market regulation which - supposedly - should be focused on employment rather than jobs, and competition on quality rather than on labor costs. However, the `Golden Triangle´ - this article argues - seems in need of complementary concepts. The article therefore introduces, `centralized decentralization´ - a concept that directs our attention to forms of flexibility and security primarily for people in work. Most studies on Danish flexicurity have been carried out under favorable economic conditions. In light of the economic slump hitting Denmark in 2008, this article investigates if and how the recession challenged these compromises by comparing two rounds of case-based interviews in three metalworking companies in 2007 and 2009. It is shown that practice has indeed changed - albeit modestly - due to worsened economic circumstances. For example the case studies show that the hypothesized preference for external numerical flexibility is perhaps too crude as employers use different ways to restructure employment. Especially the examples of de facto concessionary bargaining to save jobs are important here - although the extent of concessions is modest. The evidence thus suggests that the `Golden Triangle´ flexicurity compromises are indeed strained by the economic cycle and that responses to impetus for restructuring are far more nuanced than sometimes portrayed. It is argues that more company studies across national labor markets and industrial relations institutions will enhance our understanding of the dynamics during times of restructuring.

Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels

DEFF Research Database (Denmark)

Bøtkjær, Jane Alrø; Jeppesen, Janni Vikkelsø; Wissing, Marie Louise

2015-01-01

To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological...... activity of PAPP-A in FF was evaluated....

Increase in serum pregnancy-associated plasma protein-A is correlated with increase in cardiovascular risk factors in adult patients with growth hormone deficiency.

Science.gov (United States)

Li, Linman; Ren, Wei; Li, Jinchao; Liu, Jingjing; Wang, Lingli; Zheng, Xiaoya; Liu, Dezhen; Li, Sufang; Souvenir, Rhonda; Tang, Jiping

2012-10-01

Adult Growth Hormone Deficiency (AGHD) is correlated to many adverse effects on metabolism and increased cardiovascular risk. Pregnancy-associated plasma protein-A (PAPP-A) is a protease that promotes IGF-I availability in vascular tissues in recent study, and PAPP-A levels have been proposed as an early predictor of cardiac events. The aim of our study was to compare PAPP-A levels in AGHD patients with that of healthy adult subjects to determine if there is a relationship between serum PAPP-A and glucose and lipid metabolism. Twenty AGHD patients and 20 healthy, age-matched and weight-matched persons were chosen for the study. Their weight, height, blood pressure, body mass index (BMI), body fat percentage, waist and hip circumference, and waist-hips ratio were assessed. An oral glucose tolerance test was performed and venous blood was collected from the each patient's cubital vein for biochemical analysis. Serum PAPP-A level in AGHD patients was significantly higher than that of the control group [(7.62 ± 1.62 vs. 6.54 ± 1.31) p < 0.05], and PAPP-A was positively correlated to age, BMI, waist circumference and so on. After adjusting for the waist circumference, waist-hip ratio, 2 h postprandial blood glucose, triglycerides, the serum PAPP-A in AGHD patients was positively correlated to the BMI (r = 0.728, p < 0.05) and fasting insulin (r = 0.433, p < 0.05). In a multiple step-wise regression analysis, BMI, 2 h postprandial glucose, fasting insulin, HOMA-IR were independently associated with serum PAPP-A in AGHD patients. The increase in serum PAPP-A levels is associated with abnormal glucose metabolism and increased risk of atherosclerosis in AGHD patients.

Does low self-esteem predict health compromising behaviours among adolescents?

Science.gov (United States)

Mcgee, R; Williams, S

2000-10-01

It is often believed that low self-esteem is associated with such health-compromising behaviours in adolescence as substance use, early sexual activity, eating problems and suicidal ideation. Surprisingly, there is little longitudinal research addressing this issue. This longitudinal study examines the predictive association between both global and academic self-esteem from ages 9 to 13 years, and a variety of health compromising behaviours at age 15, in a large sample of young New Zealanders. Levels of global self-esteem significantly predicted adolescent report of problem eating, suicidal ideation, and multiple health compromising behaviours. Earlier levels of self-esteem were unrelated to later substance use and early sexual activity. The findings are discussed in terms of their implications for efforts to raise self-esteem among young people. Copyright 2000 The Association for Professionals in Services for Adolescents.

COMPROMISE EFFECT ON CONSUMERS’ BEHAVIOR

Directory of Open Access Journals (Sweden)

Markus Surkamta Eric Santosa

2016-09-01

Full Text Available The way consumers think about the products they will buy determines their buying behavior. The decision to buy a particular product is obviously in accordance with the buyer’s attitude. The buyers will also feel more comfortable if their behavior meets with the approval and expectations of the people close to them. While the development of a certain attitude has no effect on subjective judgment, the effect of compromise is likely to make a contribution to its development. Since it is still unclear, this study’s main purposed is to clarify this. In addition, while an attitude is theorized as being a predictor of behavior, through behavioral intention, the study’s secondary purpose is to boost the earlier findings. Likewise, in accordance with the theory of planned behavior, the study will also examine the other predictors of behavioral intention, in relation to the behavioral intention itself. A sample consisting of a 100 respondents was compiled by using the convenience and judgment technique. The data were analyzed using Amos 16.0 and SPSS 16.0. As expected, the compromise effect had a significant influence on whether the customers’ attitude or the subjective norm was the main determinant. Likewise, the customers’ attitude, the subjective norm and perceived behavioral control were confirmed as good predictors of customers’ behavioral intentions.

MUTUAL CONCESSIONS - SPECIFIC ELEMENT OF THE COMPROMISE/TRANSACTION CONTRACT

Directory of Open Access Journals (Sweden)

Georgeta-Bianca Spîrchez

2012-11-01

Full Text Available Given the usefulness and practical importance of the compromise contract conclusion and of the amicably dispute resolution, within the business world, we aim to analyze, in what follows, the concrete means by which these kind of settlement are achieved. Two questions become legitimate in the context of concerns about mutual concessions which the parties make in a compromise contract. These questions are the following: “What are the mutual concessions? Do mutual concessions mean equivalent concessions?” and “How mutual concessions are required to complete a valid settlement? Is the requirement of mutual concessions grounded?”

Knowledge is power: averting safety-compromising events in the OR.

Science.gov (United States)

Catalano, Kathleen

2008-12-01

Surgical procedures can be unpredictable, and safety-compromising events can jeopardize patient safety. Perioperative nurses should be watchful for factors that can contribute to safety-compromising events, as well as the errors that can follow, and know how to avert them if possible. Knowledge is power and increased awareness of patient safety issues and the resources that are available to both health care practitioners and consumers can help perioperative nurses ward off patient safety problems before they occur.

Vatican is lone opponent of world conference's compromises on abortion.

Science.gov (United States)

1994-09-07

Three years in the making, the draft program of action of the 1994 International Conference on Population and Development sets nonbinding policy guidelines to contain the world's population at 7.27 billion in 2015. Although the Vatican was pleased to see Pakistan put forward a compromise formula developed to appease Catholic and Muslim objectors of abortion, the Church was unprepared to accept the compromise immediately and requested further discussion. The Vatican's rejection drew a strong chorus of vocal disapproval from other conference delegates. Even Iran accepted the draft as a "perfect text," while Sweden grudgingly accepted it as a "rock-bottom compromise." With no Catholic countries objecting to the compromise, the Vatican stood alone in its refusal to compromise with the rest of the world's leaders and peoples. Germany, speaking for the European Union, warned that enough concessions had already been made. The rationale for Vatican opposition was unclear since the section explicitly rejects abortion as a means of family planning and urges countries to minimize both the incidence of unsafe abortion and abortion overall by improving family planning. Prevention of unwanted pregnancies must be given highest priority and women should have ready access to compassionate counselling, with abortion never promoted as a means of family planning. Moreover, there is no longer a reference to sexual health education, a plea to governments to review their laws and policies on abortion, and a call to consider women's health rather than relying upon criminal codes and punitive measures. Participants said the Vatican objected to a phrase stating that abortions, where legal, should be safe, while the Church representative argued that any suggestion that abortion is safe contradicts church doctrine on the sanctity of life.

Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

OpenAIRE

Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W.; Boyd, Steven K.

2012-01-01

Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostruc...

Adolescent Health-Compromising Behaviors: Motivating School Counselors.

Science.gov (United States)

Nagel, Liza; Scherer, David G.; Lee, William

2000-01-01

Investigated middle and high school counselors' perceptions of adolescent health-compromising behaviors and motivations to intervene. Data from a survey based on protection motivation theory showed differences in counselors' perceptions of the severity of risk-taking behaviors. Perceptions were highly correlated with intentions to seek out…

Predicting intrapartum fetal compromise using the fetal cerebro-umbilical ratio.

Science.gov (United States)

Sabdia, S; Greer, R M; Prior, T; Kumar, S

2015-05-01

The aim of this study was to explore the association between the cerebro-umbilical ratio measured at 35-37 weeks and intrapartum fetal compromise. This retrospective cross sectional study was conducted at the Mater Mothers' Hospital in Brisbane, Australia. Maternal demographics and fetal Doppler indices at 35-37 weeks gestation for 1381 women were correlated with intrapartum and neonatal outcomes. Babies born by caesarean section or instrumental delivery for fetal compromise had the lowest median cerebro-umbilical ratio 1.60 (IQR 1.22-2.08) compared to all other delivery groups (vaginal delivery, emergency delivery for failure to progress, emergency caesarean section for other reasons or elective caesarean section). The percentage of infants with a cerebro-umbilical ratio cerebro-umbilical ratio between the 10th-90th centile and 9.6% of infants with a cerebro-umbilical ratio > 90th centile required delivery for the same indication (p cerebro-umbilical ratio was associated with an increased risk of emergency delivery for fetal compromise, OR 2.03 (95% CI 1.41-2.92), p cerebro-umbilical ratio measured at 35-37 weeks is associated with a greater risk of intrapartum compromise. This is a relatively simple technique which could be used to risk stratify women in diverse healthcare settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

The medically compromised patient: Are dental implants a feasible option?

Science.gov (United States)

Vissink, A; Spijkervet, Fkl; Raghoebar, G M

2018-03-01

In healthy subjects, dental implants have evolved to be a common therapy to solve problems related to stability and retention of dentures as well as to replace failing teeth. Although dental implants are applied in medically compromised patients, it is often not well known whether this therapy is also feasible in these patients, whether the risk of implant failure and developing peri-implantitis is increased, and what specific preventive measures, if any, have to be taken when applying dental implants in these patients. Generally speaking, as was the conclusion by the leading review of Diz, Scully, and Sanz on placement of dental implants in medically compromised patients (J Dent, 41, 2013, 195), in a few disorders implant survival may be lower, and the risk of a compromised peri-implant health and its related complications be greater, but the degree of systemic disease control outweighs the nature of the disorder rather than the risk accompanying dental implant treatment. So, as dental implant treatment is accompanied by significant functional benefits and improved oral health-related quality of life, dental implant therapy is a feasible treatment in almost any medically compromised patient when the required preventive measures are taken and follow-up care is at a high level. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

14 CFR 1261.414 - Compromise of claims.

Science.gov (United States)

2010-01-01

... potential income; (3) Inheritance prospects; (4) The possibility that assets have been concealed or... compromised. The practical benefits of vigorous collection of a small claim may include a demonstration to... requiring a waiver of the tax-loss-carry-back rights of the debtor. (i) Joint and several liability. When...

31 CFR 902.2 - Bases for compromise.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Bases for compromise. 902.2 Section 902.2 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FEDERAL CLAIMS... necessary to further an enforcement principle, such as the Government's willingness to pursue aggressively...

Chemical clearing and dehydration of GFP expressing mouse brains.

Directory of Open Access Journals (Sweden)

Klaus Becker

Full Text Available Generally, chemical tissue clearing is performed by a solution consisting of two parts benzyl benzoate and one part benzyl alcohol. However, prolonged exposure to this mixture markedly reduces the fluorescence of GFP expressing specimens, so that one has to compromise between clearing quality and fluorescence preservation. This can be a severe drawback when working with specimens exhibiting low GFP expression rates. Thus, we screened for a substitute and found that dibenzyl ether (phenylmethoxymethylbenzene, CAS 103-50-4 can be applied as a more GFP-friendly clearing medium. Clearing with dibenzyl ether provides improved tissue transparency and strikingly improved fluorescence intensity in GFP expressing mouse brains and other samples as mouse spinal cords, or embryos. Chemical clearing, staining, and embedding of biological samples mostly requires careful foregoing tissue dehydration. The commonly applied tissue dehydration medium is ethanol, which also can markedly impair GFP fluorescence. Screening for a substitute also for ethanol we found that tetrahydrofuran (CAS 109-99-9 is a more GFP-friendly dehydration medium than ethanol, providing better tissue transparency obtained by successive clearing. Combined, tetrahydrofuran and dibenzyl ether allow dehydration and chemical clearing of even delicate samples for UM, confocal microscopy, and other microscopy techniques.

Factors influencing treatment decision-making for maintaining or extracting compromised teeth.

Science.gov (United States)

Lang-Hua, Bich Hue; McGrath, Colman P J; Lo, Edward C M; Lang, Niklaus P

2014-01-01

To evaluate treatment decision-making with respect to maintaining periodontally compromised teeth among dentists with or without postgraduate qualifications in implant dentistry. A series of patient scenarios with varying degrees of periodontal disease levels was presented to dental practitioners. Practitioners' decision-making outcome was determined, and intention to retain the compromised teeth was analyzed in bivariate and regression analyses (accounting for postgraduate implant training, gender, years in dental practice, and implant placement experience). This study involved 30 dental practitioners with postgraduate implant qualifications (GDPP), 33 dental practitioners without postgraduate implant qualifications (GDP), and 27 practitioners undergoing training for postgraduate implant qualifications (GDPT). Variations in treatment decision-making were evident between the three groups. Differences in treatment approaches to retaining compromised teeth were apparent. Furthermore, variations in rehabilitation of extracted scenarios existed in terms of use of implant and number of implants need for rehabilitation. Accounting for dentist and practice factors in regression analyses, GDPP/GDPT were three times as likely to retain periodontally compromised upper molar, with or without pain, compared to GDP (without pain OR 3.10, 95%CI 1.04, 10.62 P = 0.04; with pain OR 3.08, 95%CI 1.09, 8.14 P = 0.03). Variations in treatment decision-making with respect to retaining periodontally compromised teeth exist between dental practitioners with and those without postgraduate training in implant dentistry. Furthermore differences in management approaches in how they would retain the teeth or rehabilitate the dental arch were apparent. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Fuzzy compromise: An effective way to solve hierarchical design problems

Science.gov (United States)

Allen, J. K.; Krishnamachari, R. S.; Masetta, J.; Pearce, D.; Rigby, D.; Mistree, F.

1990-01-01

In this paper, we present a method for modeling design problems using a compromise decision support problem (DSP) incorporating the principles embodied in fuzzy set theory. Specifically, the fuzzy compromise decision support problem is used to study hierarchical design problems. This approach has the advantage that although the system modeled has an element of uncertainty associated with it, the solution obtained is crisp and precise. The efficacy of incorporating fuzzy sets into the solution process is discussed in the context of results obtained for a portal frame.

Stanniocalcin-1 Potently Inhibits the Proteolytic Activity of the Metalloproteinase Pregnancy-associated Plasma Protein-A

DEFF Research Database (Denmark)

Kløverpris, Søren; Mikkelsen, Jakob Hauge; Pedersen, Josefine Hvidkjær

2015-01-01

regulation in these species. Several physiological functions of STC1 have been reported, although many molecular details are still lacking. We here demonstrate that STC1 is an inhibitor of the metzincin metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A), which modulates insulin-like growth...... that the homologous STC2 inhibits PAPP-A proteolytic activity, and that this depends on the formation of a covalent complex between the inhibitor and the proteinase, mediated by Cys-120 of STC2. We find that STC1 is unable to bind covalently to PAPP-A, in agreement with the absence of a corresponding cysteine residue....... It rather binds to PAPP-A with high affinity (KD = 75 pm). We further demonstrate that both STC1 and STC2 show inhibitory activity toward PAPP-A2, but not selected serine proteinases and metalloproteinases. We therefore conclude that the STCs are proteinase inhibitors, probably restricted in specificity...

Obstetric Outcome in Pregnant Patients with Low Level of Pregnancy-Associated Plasma Protein A in First Trimester

Directory of Open Access Journals (Sweden)

Vesna Livrinova

2018-06-01

CONCLUSION: There is a significant difference in unfavourable outcome in the cases with PAPP-A under 0.4 Mom, particular in the group, with a PAPP-A value under 0.2 MoM. The patients delivered with SC with the main indications in utero hypoxia, growth restriction and elevated blood pressure had PAPP-A between 0.3-0.4 MoM. The patients with intrauterine fetal death and placental abruption in the most of the cases have PAPP-A value under 0.2 MoM. There is a need to be aware in these pregnancies to achieve the preventions of adverse outcome, to decrease perinatal morbidity and mortality.

45 CFR 1177.12 - Compromise, suspension and termination.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Compromise, suspension and termination. 1177.12 Section 1177.12 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON...) debts arising from GAO audit exceptions. ...

15 CFR 19.7 - When will Commerce entities compromise a Commerce debt?

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false When will Commerce entities compromise a Commerce debt? 19.7 Section 19.7 Commerce and Foreign Trade Office of the Secretary of Commerce COMMERCE DEBT COLLECTION Procedures To Collect Commerce Debts § 19.7 When will Commerce entities compromise...

Roles of Melatonin in Fetal Programming in Compromised Pregnancies

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Yu-Chieh Chen

2013-03-01

Full Text Available Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms.

Roles of Melatonin in Fetal Programming in Compromised Pregnancies

Science.gov (United States)

Chen, Yu-Chieh; Sheen, Jiunn-Ming; Tiao, Miao-Meng; Tain, You-Lin; Huang, Li-Tung

2013-01-01

Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms. PMID:23466884

The impact of purchase quantity on the compromise effect: The balance heuristic

Directory of Open Access Journals (Sweden)

Yin-Hui Cheng

2012-07-01

Full Text Available Most prior research on the compromise effect has focused on single rather than multiple choices. This research investigates the potential effects of purchase quantity on the compromise effect. We propose that the share of the middle option in a trinary choice set decreases as the purchase quantity increases, because people tend to employ a balance heuristic to distribute their multiple choices among the available options to achieve a balanced state and to satisfy their variety-seeking tendency. Furthermore, we propose that the need for justification and an optimal stimulation level moderate the relationship between the number of purchase items and the compromise effect. These proposed hypotheses are supported by results from three experiments.

47 CFR 1.1915 - Exploration of compromise.

Science.gov (United States)

2010-10-01

... justification of the offer and addressing the bases for compromise at 31 CFR 902.2. Debtors will provide full.... Unless otherwise provided by law, when the principal balance of a debt, exclusive of interest, penalties... evaluate an offer, using the factors set forth in 31 CFR 902.2 and, as appropriate, refer the offer with...

36 CFR 1011.7 - When will the Presidio Trust compromise a debt?

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false When will the Presidio Trust... Procedures To Collect Presidio Trust Debts § 1011.7 When will the Presidio Trust compromise a debt? (a... debt owed to the Presidio Trust that is not recovered as the result of a compromise will be reported to...

Pregnancy-Associated Plasma Protein A Levels in Late First Trimester Pregnancies with Small-for-Gestational Age Neonates: A Prospective Case-Control Study.

Science.gov (United States)

Agarwal, Rachna; Kumari, Radhika; Mehndiratta, Mohit; Radhakrishnan, Gita; Faridi, M M A; Chandra, Nilesh

2017-08-01

We aimed to investigate the association of pregnancy associated plasma protein A (PAPP-A) levels in late first trimester with small for gestational age (SGA) neonates and adverse pregnancy outcomes in a low-income setting. The inclusion criteria were late first trimester (11-13 + 6 weeks) women with singleton and non-anomalous pregnancy. Enrolled participants were sampled for PAPP-A and prospectively followed up for delivery outcome and antenatal complications. A multiple of median (MoM) was calculated and statistically compared between groups. Out of total 284 subjects, 14.54% delivered SGA babies and formed cases (Group A), 66.5% delivered appropriate for gestational age (AGA) neonates with uneventful antenatal period (controls, Group B), and 19.3% were AGA group with adverse pregnancy complications (Group C). The late first trimester median PAPP-A MoM was significantly lower (0.61) in Group A compared to Group B (1.47). Using receiver operating characteristic (ROC) curve for PAPP-A MoM, optimal cutoff value was found at 0.45 MoM, with positive predictive value of 56.2%, specificity of 92.6% and sensitivity of 45%. The median interquartile range (IQR) of PAPP-A MoM value in Group C in comparison with Group B was significantly lower except for abruption. At PAPP-A MoM cutoff value <1, <0.8, <0.6 and <0.4, the odds ratio for adverse pregnancy outcome was 8.30, 7.29, 10.97 and 10.60, respectively, indicating an inverse relationship. With 0.45 MoM cutoff of PAPP-A, the detection rate, specificity and positive predictive value for SGA were 45, 92.6 and 56.2%, respectively. As PAPP-A MoM values decreased, the odds ratio of having adverse pregnancy outcomes increased.

Activation of GSK3β by Sirt2 is required for early lineage commitment of mouse embryonic stem cell.

Directory of Open Access Journals (Sweden)

Xiaoxing Si

Full Text Available Sirt2, a member of the NAD(+-dependent protein deacetylase family, is increasingly recognized as a critical regulator of the cell cycle, cellular necrosis and cytoskeleton organization. However, its role in embryonic stem cells (ESCs remains unclear. Here we demonstrate that Sirt2 is up-regulated during RA (retinoic acid-induced and embryoid body (EB differentiation of mouse ESCs. Using lentivirus-mediated shRNA methods, we found that knockdown of Sirt2 compromises the differentiation of mouse ESCs into ectoderm while promoting mesoderm and endoderm differentiation. Knockdown of Sirt2 expression also leads to the activation of GSK3β through decreased phosphorylation of the serine at position 9 (Ser9 but not tyrosine at position 216 (Tyr216. Moreover, the constitutive activation of GSK3β during EB differentiation mimics the effect of Sirt2 knockdown, while down-regulation of GSK3β rescues the effect of Sirt2 knockdown on differentiation. In contrast to the effect on lineage differentiation, Sirt2 knockdown and GSK3β up-regulation do not change the self-renewal state of mouse ESCs. Overall, our report reveals a new function for Sirt2 in regulating the proper lineage commitment of mouse ESCs.

Pregnancy-associated plasma protein-A in patients on Maintenance Hemodialysis

International Nuclear Information System (INIS)

Abdel-Messeih, Ph.L.

2012-01-01

A high level of serum pregnancy associated plasma protein-A (PAPP-A) has been observed in patients suffering from renal impairment. The aim of the present study is to evaluate the level of PAPP-A and to elucidate its relationship with renal osteodystrophy and renal functions in patients maintained on hemodialysis (HD). Intact parathyroid hormone (i-PTH), calcium (Ca) and phosphorus (P) levels and alkaline phosphatase activity (ALP) were measured in the serum as markers of renal osteodystrophy while the level of blood urea and serum creatinine were evaluated as markers of renal functions. The results obtained showed that for patients maintained on HD, the levels of PAPP-A, i-PTH, P, urea and creatinine, were significantly higher than controls. Significant positive correlations were obtained between PAPP-A and each of i-PTH, ALP and creatinine in the same group. After dialysis session, the level of PAPP-A increased significantly, compared to its pre -dialysis level. According to the results obtained in the current study, it could be concluded that the increase in PAPP-A level in the serum of patients maintained on hemodialysis is probably the result of chronic inflammation and impairment of kidney functions rather than renal osteodystrophy

Is patient confidentiality compromised with the electronic health record?: a position paper.

Science.gov (United States)

Wallace, Ilse M

2015-02-01

In order for electronic health records to fulfill their expected benefits, protection of privacy of patient information is key. Lack of trust in confidentiality can lead to reluctance in disclosing all relevant information, which could have grave consequences. This position paper contemplates whether patient confidentiality is compromised by electronic health records. The position that confidentiality is compromised was supported by the four bioethical principles and argued that despite laws and various safeguards to protect patients' confidentiality, numerous data breaches have occurred. The position that confidentiality is not compromised was supported by virtue ethics and a utilitarian viewpoint and argued that safeguards keep information confidential and the public feels relatively safe with the electronic health record. The article concludes with an ethically superior position that confidentiality is compromised with the electronic health record. Although organizational and governmental ways of enhancing the confidentiality of patient information within the electronic health record facilitate confidentiality, the ultimate responsibility of maintaining confidentiality rests with the individual end-users and their ethical code of conduct. The American Nurses Association Code of Ethics for nurses calls for nurses to be watchful with data security in electronic communications.

Pregnancy-associated plasma protein-a levels in individuals with and without coronary artery disease

International Nuclear Information System (INIS)

Khan, N.U.; Khan, F.A.; Khan, D.A.; Asim, N.

2011-01-01

Objective: To compare pregnancy-associated plasma protein-A (PAPP-A) levels in individuals with and without coronary artery disease (CAD). Study Design: Cross-sectional comparative study. Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, in collaboration with Armed Forces Institute of Cardiology (AFIC), from September 2008 to March 2010. Methodology: One hundred and twenty five (125) individuals both male and female were included in the study. Blood for PAPP-A and lipid profile was collected, just before angiography. On the basis of angiography, the individuals were divided into those with and without CAD. PAPP-A was analyzed by using Diagnostic System Laboratories (DSL) Enzyme Linked Immunosorbent Assay (ELISA) kit and reading was taken by ELISA reader. Lipid profile was determined on automated analyzers Selectra-2 and Vitros 5.1. Results: Amongst the 125 individuals, 41 individuals were without CAD whereas 84 individuals were having CAD. Mean PAPP-A levels were 0.74 +- 0.35 mIU/L in those without CAD whereas mean PAPP-A levels in those with CAD were 1.35 +- 0.57 mIU/L. The difference between the two groups was statistically significant (p < 0.001). A PAPP-A cut off level of 0.85 mIU/L had a sensitivity and specificity of 78% and 70% respectively for diagnosing atherosclerotic CAD. Conclusion: PAPP-A is a potentially relevant marker of the presence and extent of coronary atherosclerosis as its levels are elevated in CAD as compared to individuals without CAD. Pregnancy-associated plasma protein-A. (author)

How to calculate median Pregnancy-Associated Plasma Protein-A values to predict preeclampsia? Do We Need a Newer Formula?

Directory of Open Access Journals (Sweden)

Burçin Karamustafaoğlu Balcı

2016-12-01

Full Text Available Objective: Preeclampsia is one of the major issues in maternal–fetal medicine. Early risk stratification may be beneficial, so is the aim of several researches. Our goal is to investigate whether PAPP-A MoM calculated for first trimester Down's syndrome screening or MoM calculated according to Ong’s formula can be used to predict the risk of preeclampsia or do we need another method to calculate PAPP-A MoM derived from non preeclamptic cases. Study Design: For this retrospective study, data of randomly selected 150 singleton pregnant women who did not develop preeclampsia are used to create a formula to calculate median value of PAPP-A. PAPP-A values of this subgroup are plotted against gestational age and curve fit analysis is done to determine best fitted regression line to get a formula to calculate median value of our cases. PAPP-A MoM values are calculated for each subject according to Ong’s formula and our formula. We already had MoM values derived from first trimester screening. ROC curve and Delong’s pairwise comparison analyses are used to investigate which MoM value is more predictive for preeclampsia. Results: Although the area under curve value of MoM values derived from this study was the highest, DeLong’s pairwise comparison analysis showed no statistically significant difference between the three curves. Conclusion: PAPP-A MoM calculation specific to preeclampsia does not seem to be necessary; PAPP-A MoM obtained from first trimester aneuploidy scan can be used to predict preeclampsia.

Compromised mitochondrial fatty acid synthesis in transgenic mice results in defective protein lipoylation and energy disequilibrium.

Directory of Open Access Journals (Sweden)

Stuart Smith

Full Text Available A mouse model with compromised mitochondrial fatty acid synthesis has been engineered in order to assess the role of this pathway in mitochondrial function and overall health. Reduction in the expression of mitochondrial malonyl CoA-acyl carrier protein transacylase, a key enzyme in the pathway encoded by the nuclear Mcat gene, was achieved to varying extents in all examined tissues employing tamoxifen-inducible Cre-lox technology. Although affected mice consumed more food than control animals, they failed to gain weight, were less physically active, suffered from loss of white adipose tissue, reduced muscle strength, kyphosis, alopecia, hypothermia and shortened lifespan. The Mcat-deficient phenotype is attributed primarily to reduced synthesis, in several tissues, of the octanoyl precursors required for the posttranslational lipoylation of pyruvate and α-ketoglutarate dehydrogenase complexes, resulting in diminished capacity of the citric acid cycle and disruption of energy metabolism. The presence of an alternative lipoylation pathway that utilizes exogenous free lipoate appears restricted to liver and alone is insufficient for preservation of normal energy metabolism. Thus, de novo synthesis of precursors for the protein lipoylation pathway plays a vital role in maintenance of mitochondrial function and overall vigor.

Integer goal programming approach for finding a compromise ...

African Journals Online (AJOL)

In second model the cost and time spent on repairing the components are considered as two different objectives. Selective maintenance operation is used to select the repairable components and a multi-objective goal programming algorithm is proposed to obtain compromise selection of repairable components for the two ...

Robust Public Key Cryptography — A New Cryptosystem Surviving Private Key Compromise

Science.gov (United States)

Shaik, Cheman

A weakness of the present-day public key cryptosystems is that these cryptosystems do not survive private-key compromise attacks resulting from an internal breach of trust. In a competitive business environment, private key compromise is a common incident that voids the strength of public key cryptosystems such as RSA and ECC. Bribing corporate employees to disclose their secret keys and inadvertently disclosing secret information are among a plethora of practical attacks that occur at the implementation level. Once a breach of trust takes place and subsequently the private key is revealed, any public key cryptosystem fails to secure electronic data in Internet communications. The revealed key may be used by an attacker to decipher the intercepted data at an intermediary router. This weakness of public key cryptography calls for an additional security measure that enables encryptions to survive private key compromise attacks.

Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures.

Directory of Open Access Journals (Sweden)

Cara L Sherwood

Full Text Available Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE cell model we found that both micromolar (3.9 μM and submicromolar (0.8 μM arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-. We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway.

Identifying genetic relatives without compromising privacy.

Science.gov (United States)

He, Dan; Furlotte, Nicholas A; Hormozdiari, Farhad; Joo, Jong Wha J; Wadia, Akshay; Ostrovsky, Rafail; Sahai, Amit; Eskin, Eleazar

2014-04-01

The development of high-throughput genomic technologies has impacted many areas of genetic research. While many applications of these technologies focus on the discovery of genes involved in disease from population samples, applications of genomic technologies to an individual's genome or personal genomics have recently gained much interest. One such application is the identification of relatives from genetic data. In this application, genetic information from a set of individuals is collected in a database, and each pair of individuals is compared in order to identify genetic relatives. An inherent issue that arises in the identification of relatives is privacy. In this article, we propose a method for identifying genetic relatives without compromising privacy by taking advantage of novel cryptographic techniques customized for secure and private comparison of genetic information. We demonstrate the utility of these techniques by allowing a pair of individuals to discover whether or not they are related without compromising their genetic information or revealing it to a third party. The idea is that individuals only share enough special-purpose cryptographically protected information with each other to identify whether or not they are relatives, but not enough to expose any information about their genomes. We show in HapMap and 1000 Genomes data that our method can recover first- and second-order genetic relationships and, through simulations, show that our method can identify relationships as distant as third cousins while preserving privacy.

Centralized mouse repositories.

Science.gov (United States)

Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

2012-10-01

Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

Salivary changes in medically compromised patients: A clinical and biochemical study

Directory of Open Access Journals (Sweden)

Yehoshuva R Tummuru

2017-01-01

Full Text Available Introduction: Medically compromised patients require special attention when dental procedures are performed on them. These individuals may require modified or slightly altered techniques. Aims and Objectives: The present study was taken up with two main objectives. The first one being examining and recording various oral manifestations in medically compromised patients, and the second objective was to collect samples of saliva from such patients and to analyze and establish any salivary changes in such medically compromised patients. Materials and Methods: A total of 100 patients were selected for the study. These patients were divided into four groups of 25 patients each: diabetes mellitus group, chronic renal failure group, liver cirrhosis group and control group. All the selected patients were subjected to a detailed general and intra oral examinations and the relevant data was recorded on a specially designed proforma; salivary analysis was done to know the flow rate, pH, total salivary proteins, sodium, potassium, and LDH levels. Results: From the findings, it can be inferred that salivary changes namely changes in salivary pH, salivary flow rates, salivary sodium, salivary potassium, salivary total proteins, and salivary lactate dehydrogenase are significant in medically compromised patients namely uncontrolled diabetes mellitus, chronic renal failure, cirrhosis of liver compared to the control group. Conclusion: pH of saliva was elevated in chronic renal failure patients. Salivary flow rates and sodium were decreased in diabetes mellitus, chronic renal failure, and cirrhosis of liver patients. There was a significant elevation of salivary potassium in chronic renal failure patients. LDH elevation was significant in uncontrolled diabetes mellitus.

Cyber indicators of compromise: a domain ontology for security information and event management

Science.gov (United States)

2017-03-01

heuristics, mapping, and detection. CybOX is aimed at supporting a broad range of important cyber security domains to include [31]: • Digital...REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE CYBER INDICATORS OF COMPROMISE: A DOMAIN ONTOLOGY FOR SECURITY INFORMATION AND...Distribution is unlimited. CYBER INDICATORS OF COMPROMISE: A DOMAIN ONTOLOGY FOR SECURITY INFORMATION AND EVENT MANAGEMENT Marsha D. Rowell

26 CFR 301.6331-3 - Restrictions on levy while offers to compromise are pending.

Science.gov (United States)

2010-04-01

... are pending. 301.6331-3 Section 301.6331-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... for Collection of Taxes § 301.6331-3 Restrictions on levy while offers to compromise are pending. Cross-reference. For provisions relating to the making of levies while an offer to compromise is pending...

CD133+ cells derived from skeletal muscles of Duchenne muscular dystrophy patients have a compromised myogenic and muscle regenerative capability.

Science.gov (United States)

Meng, Jinhong; Muntoni, Francesco; Morgan, Jennifer

2018-05-12

Cell-mediated gene therapy is a possible means to treat muscular dystrophies like Duchenne muscular dystrophy. Autologous patient stem cells can be genetically-corrected and transplanted back into the patient, without causing immunorejection problems. Regenerated muscle fibres derived from these cells will express the missing dystrophin protein, thus improving muscle function. CD133+ cells derived from normal human skeletal muscle contribute to regenerated muscle fibres and form muscle stem cells after their intra-muscular transplantation into an immunodeficient mouse model. But it is not known whether CD133+ cells derived from DMD patient muscles have compromised muscle regenerative function. To test this, we compared CD133+ cells derived from DMD and normal human muscles. DMD CD133+ cells had a reduced capacity to undergo myogenic differentiation in vitro compared with CD133+ cells derived from normal muscle. In contrast to CD133+ cells derived from normal human muscle, those derived from DMD muscle formed no satellite cells and gave rise to significantly fewer muscle fibres of donor origin, after their intra-muscular transplantation into an immunodeficient, non-dystrophic, mouse muscle. DMD CD133+ cells gave rise to more clones of smaller size and more clones that were less myogenic than did CD133+ cells derived from normal muscle. The heterogeneity of the progeny of CD133+ cells, combined with the reduced proliferation and myogenicity of DMD compared to normal CD133+ cells, may explain the reduced regenerative capacity of DMD CD133+ cells. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Requirement of B-Raf, C-Raf, and A-Raf for the growth and survival of mouse embryonic stem cells

International Nuclear Information System (INIS)

Guo, Wenjing; Hao, Baixia; Wang, Qian; Lu, Yingying; Yue, Jianbo

2013-01-01

Extracellular signal-regulated kinases (ERKs) have been implicated to be dispensable for self-renewal of mouse embryonic stem (ES) cells, and simultaneous inhibition of both ERK signaling and glycogen synthase kinase 3 (GSK3) not only allows mouse ES cells to self-renew independent of extracellular stimuli but also enables more efficient derivation of naïve ES cells from mouse and rat strains. Interestingly, some ERKs stay active in mouse ES cells which are maintained in regular medium containing leukemia inhibitory factor (LIF) and bone morphogenetic protein (BMP). Yet, the upstream signaling for ERK activation and their roles in mouse ES cells, other than promoting or priming differentiation, have not been determined. Here we found that mouse ES cells express three forms of Raf kinases, A-Raf, B-Raf, and C-Raf. Knocking-down each single Raf member failed to affect the sustained ERK activity, neither did A-Raf and B-Raf double knockdown or B-Raf and C-Raf double knockdown change it in ES cells. Interestingly, B-Raf and C-Raf double knockdown, not A-Raf and B-Raf knockdown, inhibited the maximal ERK activation induced by LIF, concomitant with the slower growth of ES cells. On the other hand, A-Raf, B-Raf, and C-Raf triple knockdown markedly inhibited both the maximal and sustained ERK activity in ES cells. Moreover, Raf triple knockdown, similar to the treatment of U-0126, an MEK inhibitor, significantly inhibited the survival and proliferation of ES cells, thereby compromising the colony propagation of mouse ES cells. In summary, our data demonstrate that all three Raf members are required for ERK activation in mouse ES cells and are involved in growth and survival of mouse ES cells. - Highlights: ●Mouse ES (mES) cells express all three Raf members, A-Raf, B-Raf, and C-Raf. ●Leukemia inhibitory factor (LIF) temporally activates ERKs in mES cells. ●B-Raf and C-Raf are required for LIF-induced maximal ERKs activity in mES cells. ●All Raf members are

Requirement of B-Raf, C-Raf, and A-Raf for the growth and survival of mouse embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Guo, Wenjing; Hao, Baixia; Wang, Qian; Lu, Yingying; Yue, Jianbo, E-mail: jbyue@me.com

2013-11-01

Extracellular signal-regulated kinases (ERKs) have been implicated to be dispensable for self-renewal of mouse embryonic stem (ES) cells, and simultaneous inhibition of both ERK signaling and glycogen synthase kinase 3 (GSK3) not only allows mouse ES cells to self-renew independent of extracellular stimuli but also enables more efficient derivation of naïve ES cells from mouse and rat strains. Interestingly, some ERKs stay active in mouse ES cells which are maintained in regular medium containing leukemia inhibitory factor (LIF) and bone morphogenetic protein (BMP). Yet, the upstream signaling for ERK activation and their roles in mouse ES cells, other than promoting or priming differentiation, have not been determined. Here we found that mouse ES cells express three forms of Raf kinases, A-Raf, B-Raf, and C-Raf. Knocking-down each single Raf member failed to affect the sustained ERK activity, neither did A-Raf and B-Raf double knockdown or B-Raf and C-Raf double knockdown change it in ES cells. Interestingly, B-Raf and C-Raf double knockdown, not A-Raf and B-Raf knockdown, inhibited the maximal ERK activation induced by LIF, concomitant with the slower growth of ES cells. On the other hand, A-Raf, B-Raf, and C-Raf triple knockdown markedly inhibited both the maximal and sustained ERK activity in ES cells. Moreover, Raf triple knockdown, similar to the treatment of U-0126, an MEK inhibitor, significantly inhibited the survival and proliferation of ES cells, thereby compromising the colony propagation of mouse ES cells. In summary, our data demonstrate that all three Raf members are required for ERK activation in mouse ES cells and are involved in growth and survival of mouse ES cells. - Highlights: ●Mouse ES (mES) cells express all three Raf members, A-Raf, B-Raf, and C-Raf. ●Leukemia inhibitory factor (LIF) temporally activates ERKs in mES cells. ●B-Raf and C-Raf are required for LIF-induced maximal ERKs activity in mES cells. ●All Raf members are

Levels of pregnancy-associated plasma protein-A in patients with coronary heart diseases and clinic significance

International Nuclear Information System (INIS)

Wang Lingyan; Cai Gaojun; Zhang Wenwei; Wang Wenzhi; Sun Wenwei; Yan Weiqun

2006-01-01

Objective: To explore the relationship between pregnancy-associated plasma protein-A (PAPP-A) and occurance, development of cardiovascular diseases, and lipids. Methods: 75 patients with coronary disease were divided into acute myocardial infarction (n=32), unstable angina pectoris (n=22) and stable angina pectoris (n=21) groups, and 60 subjects without coronary diseases were used as controls. The serum PAPP-A, IL-6, IL-10, lipids were measured in all patients and controls by different methods of enzymatically amplified two-step sandwith- type immunoassay, double antibody radio-immunoassay, ABC-HRP, auto biochemistic analytist. Results: (1) The level of PAPP-A in acute coronary syndrome (ACS, including acute myocardial infarction and unstable angina pectoris) patients was significantly higher than that in stable angina pectoris patients and controls (P<0.05). (2) There were significantly associations between PAPP-A and serum totle cholesterol, ApoA1/ApoB (r=0.348, 0.420, P<0.05). (3) The levels of IL-6 and IL-10 in coronary heart disease patients were significantly higher than those in controls (P<0.05), and the variations among acute myocardial infarction, unstable angina pectoris, stable angina pectoris patients were significantly (P<0.05). There were significantly associations between PAPP-A, IL-6 and IL-10 (Spearman r 0.446, 0.523, P<0.05). Conclusion: PAPP-A is significantly associated with occurance and development of coronary heart disease, probablely as a marker of unstable plaque in coronary heart disease. (authors)

Sustainable Development Compromise[d] in the Planning of Metro Vancouver’s Agricultural Lands—the Jackson Farm Case

Directory of Open Access Journals (Sweden)

Meg Holden

2013-11-01

Full Text Available This research provides analysis of the case of the Jackson Farm development application, embedded within the particular dynamics of the municipal, regional, and provincial sustainability land use policy culture of the Metro Vancouver region, in Canada. Within a culture of appreciation of the increasing need for sustainability in land use policy, including the protection of agricultural lands at the provincial level through the Agricultural Land Reserve (ALR, to urban intensification and protection of the green zone at the regional scale, lies a political conflict that comes into focus in individual land use decisions, within municipalities struggling for autonomy. This case is neither driven strictly by “the politics of the highest bidder” nor by policy failure; the case of the Jackson Farm is instead a case of the challenges of implementing inter-governmental coordination and collaborative governance in a context of both significant sustainability policy and urban growth. The process can be seen to follow an ecological modernization agenda, seeking “win–win” alternatives rather than recognizing that typical compromises, over time, may tip the direction of development away from sustainability policy goals. Understanding the twists, turns, and eventual compromise reached in the case of the Jackson Farm brings to light the implications of the shift in the regional planning culture which may necessitate a less flexible, more structured prioritization of competing goals within plans and policies in order to meet sustainability goals. We highlight this, and present an alternative implementation process within the existing policy regime with potential to aid the specific goal of agricultural land protection.

Development of a radioimmunoassay for pregnancy-associated plasma protein A and establishment of normal levels in the first trimester of pregnancy

Energy Technology Data Exchange (ETDEWEB)

Anthony, F; Masson, G M; Wood, P J [Southampton Univ. (UK)

1983-01-01

An accelerated double antibody method has been developed for the radioimmunoassay of pregnancy-associated plasma protein A (PAPP-A) in serum. The workable range for the assay was 0.04-1.8 mg/l of serum. PAPP-A levels were determined in single serum samples from 110 women with prospective normal pregnancies of between 7 and 14 weeks' gestation. The level of pregnancy specific ..beta../sub 1/ glycoprotein (SP/sub 1/) was also measured in these samples and normal ranges for PAPP-A and SP/sub 1/ were constructed from the results obtained.

Effect of passive smoking on the levels of pregnancy associated plasma protein-A in normal rats

International Nuclear Information System (INIS)

Naveed, A.K.; Rahim, A.; Malik, M.S.

2010-01-01

To measure the levels of pregnancy associated plasma protein- A (PAPPA-A) in normal rats exposed to cigarette smoke. Sixty albino rats of Sprague- Dawley strain weighing 200-250 gm, divided into two groups. Both the groups were kept in identical chambers. One group of 30 rats was further exposed to passive cigarette smoke for 4 weeks. No increase was observed in the levels of serum PAPP-A of both the groups: Passive smokers and not exposed to passive smoking i.e. P > 0.05. Smoking does not increase the levels of PAPP-A. (author)

Sterile diets for the immuno-compromised: Is there a need?

Science.gov (United States)

Butterweck, Joseph S.

1995-02-01

There is a general misunderstanding in the radiation processing industry about the use of sterile diets in the medical profession. Sterile diets are used on a limited basis in hospitals that specialize in cancer treatment and organ transplants. These patients are severely immuno-compromised. There are many other patients that are immuno-compromised that do not require sterile diets. These patients may require a diet that is pathogen-free and are aslo "low-microbial diets". Nosocomial infections have become a major issue in US hospitals. The "infection control committee" is the focus group responsible to assure nosocomial infections incidence are below the hospital goals. Application of ionizing radiation to sterilize diets has not been chosen because the product is not available at a reasonable total cost. This paper will discuss the hospitals views.

Mouse allergen exposure and immunologic responses: IgE-mediated mouse sensitization and mouse specific IgG and IgG4 levels

NARCIS (Netherlands)

Matsui, Elizabeth C.; Krop, Esmeralda J. M.; Diette, Gregory B.; Aalberse, Rob C.; Smith, Abigail L.; Eggleston, Peyton A.

2004-01-01

Although there is evidence that contact with mice is associated with IgE-mediated mouse sensitization and mouse specific antibody responses, the exposure-response relationships remain unclear. To determine whether IgE-mediated mouse sensitization and mouse specific IgG (mIgG) and mIgG4 levels

Association of first-trimester pregnancy-associated plasma protein A levels and idiopathic preterm delivery: A population-based screening study

Directory of Open Access Journals (Sweden)

Piyathida Pummara

2016-02-01

Conclusion: A PAPP-A level of ≤10th percentile was significantly associated with an increased risk for idiopathic preterm birth. Therefore, pregnant women with low PAPP-A levels in the first trimester should be considered at a high risk of preterm delivery.

Pregnancy-associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy-a prospective follow--up study

DEFF Research Database (Denmark)

Astrup, A S; Tarnow, L; Christiansen, M

2007-01-01

AIM: Pregnancy-associated plasma protein A (PAPP-A) has been implicated in the aetiology of acute coronary syndromes and carotid and peripheral artherosclerosis. Diabetic nephropathy is characterized by increased cardiovascular risk. We investigated the prognostic value of PAPP-A in a large cohor...

A Compromise Programming Model for Highway Maintenance Resources Allocation Problem

Directory of Open Access Journals (Sweden)

Hui Xiong

2012-01-01

Full Text Available This paper formulates a bilevel compromise programming model for allocating resources between pavement and bridge deck maintenances. The first level of the model aims to solve the resource allocation problems for pavement management and bridge deck maintenance, without considering resource sharing between them. At the second level, the model uses the results from the first step as an input and generates the final solution to the resource-sharing problem. To solve the model, the paper applies genetic algorithms to search for the optimal solution. We use a combination of two digits to represent different maintenance types. Results of numerical examples show that the conditions of both pavements and bridge decks are improved significantly by applying compromise programming, rather than conventional methods. Resources are also utilized more efficiently when the proposed method is applied.

Ultrasonographic Characterization of the db/db Mouse: An Animal Model of Metabolic Abnormalities

Directory of Open Access Journals (Sweden)

Francesco Faita

2018-01-01

Full Text Available The availability of an animal model able to reliably mirror organ damage occurring in metabolic diseases is an urgent need. These models, mostly rodents, have not been fully characterized in terms of cardiovascular, renal, and hepatic ultrasound parameters, and only sparse values can be found in literature. Aim of this paper is to provide a detailed, noninvasive description of the heart, vessels, liver, and kidneys of the db/db mouse by ultrasound imaging. Sixteen wild type and thirty-four db/db male mice (11-week-old were studied. State-of-the-art ultrasound technology was used to acquire images of cardiovascular, renal, and hepatic districts. A set of parameters describing function of the selected organs was evaluated. db/db mice are characterized by systolic and diastolic dysfunction, confirmed by strain analysis. Abdominal aortic and carotid stiffness do not seem to be increased in diabetic rodents; furthermore, they are characterized by a smaller mean diameter for both vessels. Renal microcirculation is significantly compromised, while liver steatosis is only slightly higher in db/db mice than in controls. We offer here for the first time an in vivo detailed ultrasonographic characterization of the db/db mouse, providing a useful tool for a thoughtful choice of the right rodent model for any experimental design.

The compromised gut in the neonate : Diagnostic and clinical aspects

NARCIS (Netherlands)

Schurink, Maarten

2016-01-01

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease predominantly occurring in preterm infants, causing significant patient morbidity and mortality. It is characterized by loss of bowel wall integrity due to ischemia (lack of oxygen due to a compromised blood flow) and

Release patterns of pregnancy-associated plasma protein A in patients with acute coronary syndromes assessed by an optimized monoclonal antibody assay

DEFF Research Database (Denmark)

Schoos, Mikkel; Iversen, Kasper; Teisner, Ane

2008-01-01

Objective. Pregnancy-associated plasma protein A (PAPP-A) is expressed in eroded and ruptured atheromatous plaques, and circulating levels are elevated in acute coronary syndromes (ACS). Our objective was to investigate release patterns of PAPP-A in ACS and whether they differ among different typ...

Pregnancy associated plasma protein-A as a marker for myocardial infarction and death in patients with stable coronary artery disease: A prognostic study within the CLARICOR Trial

DEFF Research Database (Denmark)

Iversen, Kasper K; Teisner, Børge; Winkel, Per

2011-01-01

OBJECTIVE: Pregnancy associated plasma protein-A (PAPP-A) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease (CAD) in patients undergoing coronary angiography. Here we address the prognostic value of serum PAPP-A in unselected stable...

Whatever It Takes: Health Compromising Behaviors in Female Athletes

Science.gov (United States)

Waldron, Jennifer J.; Krane, Vikki

2005-01-01

The power and performance model of sport stresses a sport ethic of doing "whatever it takes" to win (Coakley, 2004). Uncritical acceptance of this model may lead to various health-compromising behaviors. Employing achievement goal theory, we examine why female athletes may adopt the power and performance approach. An ego motivational climate and a…

Mouse adhalin

DEFF Research Database (Denmark)

Liu, L; Vachon, P H; Kuang, W

1997-01-01

. To analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin...... was specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation...

48 CFR 239.7102-2 - Compromising emanations-TEMPEST or other standard.

Science.gov (United States)

2010-10-01

... INFORMATION TECHNOLOGY Security and Privacy for Computer Systems 239.7102-2 Compromising emanations—TEMPEST or... requiring activity is responsible for providing to the contracting officer— (a) The required protections, i...

A novel lung slice system with compromised antioxidant defenses

Energy Technology Data Exchange (ETDEWEB)

Hardwick, S.J.; Adam, A.; Cohen, G.M. (Univ. of London (England)); Smith, L.L. (Imperial Chemical Industries PLC, Cheshire (England))

1990-04-01

In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 {mu}M) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP{sup +}, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of {sup 14}CO{sub 2} from D-({sup 14}C(U))-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.

A novel lung slice system with compromised antioxidant defenses

International Nuclear Information System (INIS)

Hardwick, S.J.; Adam, A.; Cohen, G.M.; Smith, L.L.

1990-01-01

In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 μM) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP + , and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of 14 CO 2 from D-[ 14 C(U)]-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone

A libertarian perspective on the stem cell debate: compromising the uncompromisible.

Science.gov (United States)

Block, Walter

2010-08-01

The present paper attempts to forge a compromise between those who maintain that stem cell research is out-and-out murder of young helpless human beings and those who favor this practice. The compromise is predicated upon the libertarian theory of private property rights. Starting out with the premise that not only the fetus but even the fertilized egg is a human being, with all rights thereto, it offers a competition between those who fertilize eggs for research and those who wish to adopt them. If and only if the former win this competition will they be allowed to use these very young human beings for the purposes they have constructed them. This is justified on grounds of avoiding child abuse.

Anthropogenic noise compromises antipredator behaviour in European eels.

Science.gov (United States)

Simpson, Stephen D; Purser, Julia; Radford, Andrew N

2015-02-01

Increases in noise-generating human activities since the Industrial Revolution have changed the acoustic landscape of many terrestrial and aquatic ecosystems. Anthropogenic noise is now recognized as a major pollutant of international concern, and recent studies have demonstrated impacts on, for instance, hearing thresholds, communication, movement and foraging in a range of species. However, consequences for survival and reproductive success are difficult to ascertain. Using a series of laboratory-based experiments and an open-water test with the same methodology, we show that acoustic disturbance can compromise antipredator behaviour--which directly affects survival likelihood--and explore potential underlying mechanisms. Juvenile European eels (Anguilla anguilla) exposed to additional noise (playback of recordings of ships passing through harbours), rather than control conditions (playback of recordings from the same harbours without ships), performed less well in two simulated predation paradigms. Eels were 50% less likely and 25% slower to startle to an 'ambush predator' and were caught more than twice as quickly by a 'pursuit predator'. Furthermore, eels experiencing additional noise had diminished spatial performance and elevated ventilation and metabolic rates (indicators of stress) compared with control individuals. Our results suggest that acoustic disturbance could have important physiological and behavioural impacts on animals, compromising life-or-death responses. © 2014 John Wiley & Sons Ltd.

Creating clones, kids & chimera: liberal democratic compromise at the crossroads.

Science.gov (United States)

Adams, Nathan A

2004-01-01

The objective of this article is to find middle ground between the supporters and opponents of biotechnology by perpetuating the existing legal compromise pertaining to the complete range of health and welfare doctrines relevant to the biotechnological industry. The author aspires neither to add to nor detract from this liberal democratic consensus, but to preserve its constitutive balance between positivism and natural law and over-regulation and under-regulation in the hopes of stabilizing new political fault lines developing around the few biotechnological innovations already grabbing headlines. The most feasible solution is to extend the existing liberal democratic compromise with respect to equal protection, reproductive rights, the First Amendment, human subject experimentation, patent law, and parental rights. This includes banning or monopolizing certain biotechnologies and extending substantive special respect to the ex vivo living human embryo. Biotechnology must not be left to regulate itself.

No-compromise reptation quantum Monte Carlo

International Nuclear Information System (INIS)

Yuen, W K; Farrar, Thomas J; Rothstein, Stuart M

2007-01-01

Since its publication, the reptation quantum Monte Carlo algorithm of Baroni and Moroni (1999 Phys. Rev. Lett. 82 4745) has been applied to several important problems in physics, but its mathematical foundations are not well understood. We show that their algorithm is not of typical Metropolis-Hastings type, and we specify conditions required for the generated Markov chain to be stationary and to converge to the intended distribution. The time-step bias may add up, and in many applications it is only the middle of a reptile that is the most important. Therefore, we propose an alternative, 'no-compromise reptation quantum Monte Carlo' to stabilize the middle of the reptile. (fast track communication)

Pulmonary, neurological and hepatic compromise in paragonimiasis: case report

International Nuclear Information System (INIS)

Uriza Carrasco, Alfonso Jose; Cuervo Valencia, Catalina; Valencia M, Andres Mauricio; Echeverri Toro, Lina Maria

2011-01-01

Paragonimiasis is a parasitic infectious disease, frequently with pulmonary abnormalities, although erratic parasite migration can compromise other organs. this disease is endemic in areas of southeast Asia, but it has been described in other tropical and subtropical regions. In this article, we report a case of indigenous patient with pulmonary abnormalities by Paragonimiasis, neurologic and hepatic abnormalities too.

Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development.

Science.gov (United States)

Fung, Camille M; White, Jessica R; Brown, Ashley S; Gong, Huiyu; Weitkamp, Jörn-Hendrik; Frey, Mark R; McElroy, Steven J

2016-01-01

Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A2-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent "first hit", rendering IUGR intestine susceptible to further injury, infection, or inflammation.

Pregnancy-associated plasma protein-A and the vulnerable plaque

DEFF Research Database (Denmark)

Jespersen, Camilla H B; Vestergaard, Kirstine R; Schou, Morten

2014-01-01

For more than a decade, pregnancy-associated plasma protein-A (PAPP-A) has been examined for its relation to acute coronary syndrome (ACS) and the vulnerable plaque. This review summarizes the current knowledge of plasma PAPP-A in relation to nonpregnant individuals focusing on patients with ACS...

Would Enforcing Competition Law Compromise Industry Policy Objectives?

OpenAIRE

Evenett, Simon J.

2005-01-01

One recurring concern in the debate over the efficacy of enacting competition laws in developing countries is that its enforcement may compromise important industrial policy goals. This concern has been raised in regional fora and in multilateral organizations such as the World Trade Organization, where officials have considered the pros and cons of including competition provisions in international trade agreements. However, the concern is broader and often national debates over the merits of...

Transplantation of adult mouse iPS cell-derived photoreceptor precursors restores retinal structure and function in degenerative mice.

Directory of Open Access Journals (Sweden)

Budd A Tucker

2011-04-01

Full Text Available This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs, could be used to produce retinal precursors and subsequently photoreceptor cells for retinal transplantation to restore retinal function in degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse ES cells, adult dsRed iPSCs expressed the pluripotency genes SSEA1, Oct4, Sox2, KLF4, c-Myc and Nanog. Following transplantation into the eye of immune-compromised retinal degenerative mice these cells proceeded to form teratomas containing tissue comprising all three germ layers. At 33 days post-differentiation a large proportion of the cells expressed the retinal progenitor cell marker Pax6 and went on to express the photoreceptor markers, CRX, recoverin, and rhodopsin. When tested using calcium imaging these cells were shown to exhibit characteristics of normal retinal physiology, responding to delivery of neurotransmitters. Following subretinal transplantation into degenerative hosts differentiated iPSCs took up residence in the retinal outer nuclear layer and gave rise to increased electro retinal function as determined by ERG and functional anatomy. As such, adult fibroblast-derived iPSCs provide a viable source for the production of retinal precursors to be used for transplantation and treatment of retinal degenerative disease.

Principles of treatment planning for compromised first permanent molars in mixed dentition period: A review article

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Behrad Tanbakuchi

2017-02-01

Full Text Available Background and Aims: The first permanent molar is susceptible to caries, endodontic complications and developmental anomalies. Compromised teeth with poor prognosis could cause the clinician to face dilemmas. The aim of this review article was to assess recent guidelines on the treatment planning of compromised first permanent molars in mixed dentition period. Materials and Methods: The design of the study was based on review of literature by searching the MEDLINE, Web of science and Google scholar. Key words (permanent first molar, extraction, treatment plan were used. This search was limited to the English articles published after the year 2000. Conclusion: A number of factors influenced decision-making process regarding compromised first permanent molars including the restorative status of the tooth, dental age of the patient, degree of crowding and occlusal relationships were assessed. The ideal time for removal of these teeth was 8-9 years of age. However, the current evidence for managing compromised first permanent molars demands clinical trials.

Pregnancy-associated plasma protein A in non-cardiac conditions

DEFF Research Database (Denmark)

Iversen, K.K.; Teisner, A.S.; Teisner, B.

2008-01-01

OBJECTIVE: PAPP-A is a promising new marker in coronary heart disease. It is important to investigate its specificity in order to establish its clinical utility as a marker of coronary heart disease. DESIGN AND METHODS: PAPP-A was measured within 24 h following hospital admission in 1448 consecut...

[Tuberculosis in compromised hosts].

Science.gov (United States)

2003-11-01

Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

Secretion of salivary statherin is compromised in uncontrolled diabetic patients

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Masahiro Izumi

2015-06-01

Conclusions and general significance: The results show that synthesis and secretion of statherin is reduced in diabetics and this reduction is salivary gland specific. As compromised salivary statherin secretion leads to increased oral health risk, this study indicates that routine oral health assessment of these patients is warranted.

Influence of political opposition and compromise on conservation outcomes in the Tongass National Forest, Alaska.

Science.gov (United States)

Beier, Colin M

2008-12-01

To understand how a highly contentious policy process influenced a major conservation effort, I examined the origins, compromises, and outcomes of the Alaska National Interest Lands Conservation Act of 1980 (ANILCA) for the Tongass National Forest. Tongass wilderness designation was among the most controversial issues in the ANILCA debate, and it faced strong opposition from influential lawmakers, land managers, and Alaska residents. To investigate the influence of this opposition on Tongass conservation outcomes, I conducted a gap analysis of Tongass reserves and a policy analysis of the ANILCA debate and traced the influence of specific interests through the amendments, negotiations, and resulting compromises needed to enact ANILCA. Overall, I found that Tongass reserves comprise a broadly representative cross-section of ecosystems and species habitats in southeastern Alaska. Redrawn reserve boundaries, industry subsidies, and special access regulations reflected compromises to minimize the impact of wilderness conservation on mining, timber, and local stakeholder interests, respectively. Fragmentation of the Admiralty Island National Monument-the most ecologically valuable and politically controversial reserve-resulted from compromises with Alaskan Native (indigenous peoples of Alaska) corporations and timber interests. Despite language to accommodate "reasonable access" to wilderness reserves, ongoing access limitations highlight the concerns of Alaska residents that opposed ANILCA several decades ago. More broadly, the Tongass case suggests that early and ambitious conservation action may offset strong political opposition; compromises needed to establish key reserves often exacerbate development impacts in unprotected areas; and efforts to minimize social conflicts are needed to safeguard the long-term viability of conservation measures.

Diagnosis of hemodynamic compromise in patients with chronic cerebral ischemia

International Nuclear Information System (INIS)

Kuroda, Satoshi; Sakuragi, Mitsugi; Motomiya, Mineo; Nakagawa, Tango; Mitsumori, Kenji; Tsuru, Mitsuo; Takigawa, Shugo; Kamiyama, Hiroyasu; Abe, Hiroshi.

1990-01-01

To evaluate the efficacy of tests for selecting patients with hemodynamic compromise, measurement of cerebral blood volume (CBV) with 99m Tc-RBC single photon emission computed tomography (SPECT) was performed in thirteen patients with occlusive cerebrovascular disease, and was compared with results obtained by 133 Xe SPECT and acetazolamide (Diamox) test. All patients in our study suffered TIA, RIND, or minor completed stroke. Cerebral angiography demonstrated severe stenosis or occlusion in the ipsilateral internal carotid artery or middle cerebral artery, although plain CT scan or MRI revealed no or, if any, only localized infarcted lesions. Regional cerebral blood volume (rCBV) was measured with 99m Tc-RBC SPECT and regional cerebral blood flow (rCBF) was measured with 133 Xe SPECT before and after intravenous injection of 10 - 12 mg/kg acetazolamide (Diamox). Our results suggest that the ipsilateral rCBV/rCBF (mean transit time) is a more sensitive index of the cerebral perfusion reserve than the use of only rCBV or rCBF of the ipsilateral hemisphere. Also, the ipsilateral rCBV/rCBF is significantly correlated (r= -0.72) with the Diamox reactivity of rCBF, which is considered to represent the cerebral vasodilatory capacity in patients with chronic cerebral ischemia. Postoperative SPECT study revealed remarkable improvement of ipsilateral rCBV/rCBF and Diamox reactivity in four patients who underwent EC/IC bypass surgery to improve the hemodynamic compromise. In conclusion, our results suggest that the measurement of rCBV/rCBF with 133 Xe SPECT and 99m Tc-RBC SPECT is useful for detecting the hemodynamic compromise in patients with occlusive cerebrovascular disease. (author)

Pregnancy-associated plasma protein-A, a marker for outcome in patients suspected for acute coronary syndrome

DEFF Research Database (Denmark)

Iversen, Kasper K; Dalsgaard, Morten; Teisner, Ane S

2010-01-01

To examine if pregnancy-associated plasma protein-A (PAPP-A) in patients with chest pain, could identify patients at risk for death or myocardial infarction.......To examine if pregnancy-associated plasma protein-A (PAPP-A) in patients with chest pain, could identify patients at risk for death or myocardial infarction....

Autobiographical memory compromise in Alzheimer's disease: a cognitive and clinical overview.

Science.gov (United States)

El Haj, Mohamad; Roche, Jean; Gallouj, Karim; Gandolphe, Marie-Charlotte

2017-12-01

Autobiographical memory refers to memory for personal information. The compromise of autobiographical memory in Alzheimer's disease (AD) results in a loss of knowledge about events and facts that defined the patients' life, and consequently, degradation of their self-knowledge and sense of identity. The compromise of autobiographical memory in AD can be attributed to a diminished subjective experience of memory and a diminished sense of the self. Our review provides a comprehensive overview of cognitive and clinical processes that may be involved in difficulties to retrieve autobiographical memories in Alzheimer's disease. Our review also proposes a theoretical model according to which, the diminished ability to retrieve contextual information and the overgenerality of recall result in a diminished subjective experience of past and future thinking. Besides its theoretical contribution, our review proposes clinical applicability for evaluation and rehabilitation of autobiographical memory in AD.

Orthodontic space closure using simple mechanics in compromised first molar extraction spaces: Case series

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Prashant M Dhole

2018-01-01

Full Text Available Orthodontic treatments involving missing or compromised first permanent molars are often challenging cases to treat considering the loss of potential anchor tooth. The case series presents orthodontic treatment in three patients with mutilated/absent first permanent molars. The treatment goals were to be accomplished by extraction of compromised teeth and retention of healthy dentition. The diagnosis and problem list needed extractions to accomplish the treatment goals. The possibility of extracting compromised first permanent molars instead of other healthy teeth was considered. A setup was done to determine the final occlusion in asymmetric extraction cases. Fixed appliances were used with simple mechanics without any additional anchorage devices. Case-based retention protocols were followed. All the three patients achieved the predetermined treatment objectives of improved esthetics and healthy and stable functional occlusion. The simple and efficient mechanics and finishing techniques for comprehensive orthodontic treatment with first molar extractions presented in the report should help clinicians when treating similar patients.

Iran. Nuclear crisis: the continuous compromise?

International Nuclear Information System (INIS)

Cherief, Hamza

2016-01-01

The author comments and discusses the content and implications of the Joint Comprehensive Plan of Action which has been adopted in July 2015 by the Republic of Iran and the members of the E3/EU+3 group. According to this text, a flexible normative and institutional framework is defined, according to which negotiation must prevail on the reinstatement of economic sanctions. While significantly lowering objectives related to non proliferation, this plan aims (through various arrangements which are discussed by the author) at maintaining Iran under the threshold of nuclear power. The author also comments various aspects related to the implementation of this Plan of Action, and outlines that they rely on the search for a continuous compromise: negotiations and involvement of international bodies are foreseen before application of sanctions

A method for identifying compromised clients based on DNS traffic analysis

DEFF Research Database (Denmark)

Stevanovic, Matija; Pedersen, Jens Myrup; D’Alconzo, Alessandro

2017-01-01

DNS is widely abused by Internet criminals in order to provide reliable communication within malicious network infrastructure as well as flexible and resilient hosting of malicious content. This paper presents a novel detection method that can be used for identifying potentially compromised clien...

Impact of type 1 diabetes and glycemic control on fetal aneuploidy biochemical markers

DEFF Research Database (Denmark)

Madsen, Helen Nordahl; Ekelund, Charlotte Kvist; Tørring, Niels

2012-01-01

Objective: To determine the influence of type 1 diabetes mellitus (T1DM) on the first trimester serum markers of fetal aneuploidy; pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) and to evaluate the influence of glycemic control...... on these parameters in the pregnant diabetic women. Design: Retrospective study. Setting: Data were extracted from electronic obstetric and laboratory databases at two Danish University Hospitals. Population: Based on 36,415 pregnancies without T1DM (non-T1DM) and 331 pregnancies with T1DM; β-hCG and PAPP-A were...... across the T1DM and non-T1DM groups, respectively. Additionally, the relation between PAPP-A MoM and HgbA1C was examined in 348 T1DM pregnancies by Spearman’s rank correlation. Main outcome measure: Difference in biochemical marker levels between T1DM and non-T1DM. Results: PAPP-A was 0.86 MoM in T1DM...

Early Biochemical Screening for Fetal Aneuploidy in the First Trimester

DEFF Research Database (Denmark)

Tørring, Niels

2013-01-01

Background Screening for fetal trisomy 21 in the first trimester includes analysis of the serological markers pregnancy-associated plasma protein A (PAPP-A) and free beta human choriogonadotropin (free βhCG). With the recent launch of the PAPP-A free βhCG and assays on the Roche Cobas and Elecsys...... assays showed slopes of 0.94 and 0.95 and Pearson’s correlation of r = 0.981 and r = 0.987 respectively. Similar comparison to AutoDELFIA PerkinElmer Perkin gave slopes of 0,83 (free βhCG) and 1.20 (PAPP-A). With a cut off at 1:300 the overall sensitivity of the first trimester screening including nuchal...

Acute gastrointestinal compromise in neonates with congenital diaphragmatic hernia prior to repair.

Science.gov (United States)

Fox, Catherine; Stewart, Michael; King, Sebastian K; Patel, Neil

2016-12-01

Congenital diaphragmatic hernia (CDH) affects 1 in 3000 live births. Modern management strategies include delayed repair of the diaphragm to permit pre-operative optimization of cardiorespiratory status. We describe a cohort of neonates in whom early emergency operative intervention was required for potentially fatal intestinal compromise. A retrospective review was performed of all neonatal CDH patients managed at a tertiary center in an 8-year period (2005-2012). A total of 126 CDH patients were managed during the 8-year period. Five neonates (male - 1; gestation 37+4-39+7; birth weight 2.9-3.7kg; left CDH - 5) required emergency operative intervention for presumed gastrointestinal compromise. All five neonates demonstrated systemic hypotension despite inotropic support, raised serum lactate (>2mmol/L), and abnormal radiographic findings. Operative intervention occurred within 3days of birth (1-3days). Findings included gastric volvulus, jejunal volvulus, and perforated caecum. All patients underwent primary diaphragmatic repair without a patch. Temporary ileostomy was required in 1 patient. All patients remain alive. Gastrointestinal compromise is a rare, but potentially catastrophic, complication of CDH. Emergency operative intervention may be required in a select cohort of patients. Early deterioration following birth should alert clinicians to the possibility of significant intestinal pathology. Level IV case series with no comparison group. Copyright © 2016 Elsevier Inc. All rights reserved.

Parental care compromises feeding in the pumpkinseed ( Lepomis gibbosus)

Science.gov (United States)

Zięba, G.; Dukowska, M.; Przybylski, M.; Fox, M. G.; Smith, C.

2018-04-01

Providing parental care is potentially costly. Costs can arise through elevated energy expenditure or from an increased risk of mortality. A cost of parental care can also occur because a parent is compromised in their ability to forage. We used pumpkinseed Lepomis gibbosus, a fish with an alternative male mating strategy, to test whether parental males differed in their feeding in comparison with females and cuckolder males. To address this question, we examined the stomach contents of female, cuckolder male, and parental male pumpkinseed during the breeding season over an entire diel cycle. We showed that parental males had a lower total weight of food in their stomachs in comparison with females, while cuckolder males did not. Parental males also had a lower weight and number of chironomids in their stomachs. The temporal pattern of feeding of parental males diverged from that of females, and they had a lower probability of pupal chironomids in their stomachs, which implies spatial segregation in foraging. Parental males had a greater probability of conspecific eggs in their stomachs than females, while the probability of egg cannibalism did not differ between cuckolder males and females. Overall, these finding meet predictions in accordance with an assumption that parental care and territoriality can compromise feeding.

7 CFR 4290.1710 - Secretary's authority to collect or compromise claims.

Science.gov (United States)

2010-01-01

... BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Miscellaneous § 4290.1710... consideration as he or she deems reasonable, collect or compromise all claims relating to obligations he or she...

Planar cell polarity enables posterior localization of nodal cilia and left-right axis determination during mouse and Xenopus embryogenesis.

Directory of Open Access Journals (Sweden)

Dragana Antic

2010-02-01

Full Text Available Left-right asymmetry in vertebrates is initiated in an early embryonic structure called the ventral node in human and mouse, and the gastrocoel roof plate (GRP in the frog. Within these structures, each epithelial cell bears a single motile cilium, and the concerted beating of these cilia produces a leftward fluid flow that is required to initiate left-right asymmetric gene expression. The leftward fluid flow is thought to result from the posterior tilt of the cilia, which protrude from near the posterior portion of each cell's apical surface. The cells, therefore, display a morphological planar polarization. Planar cell polarity (PCP is manifested as the coordinated, polarized orientation of cells within epithelial sheets, or as directional cell migration and intercalation during convergent extension. A set of evolutionarily conserved proteins regulates PCP. Here, we provide evidence that vertebrate PCP proteins regulate planar polarity in the mouse ventral node and in the Xenopus gastrocoel roof plate. Asymmetric anterior localization of VANGL1 and PRICKLE2 (PK2 in mouse ventral node cells indicates that these cells are planar polarized by a conserved molecular mechanism. A weakly penetrant Vangl1 mutant phenotype suggests that compromised Vangl1 function may be associated with left-right laterality defects. Stronger functional evidence comes from the Xenopus GRP, where we show that perturbation of VANGL2 protein function disrupts the posterior localization of motile cilia that is required for leftward fluid flow, and causes aberrant expression of the left side-specific gene Nodal. The observation of anterior-posterior PCP in the mouse and in Xenopus embryonic organizers reflects a strong evolutionary conservation of this mechanism that is important for body plan determination.

CLINICAL CASE OF TREATMENT WITH RIBOSOMAL COMPLEX IN CHILD WITH COMPROMISED IMMUNITY

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A.A. Alekseeva

2011-01-01

Full Text Available The leading pathology in children is acute respiratory infections (ARI according to the expert data of WHO. The incidence of prolonged and recurrent types of ARI increases during recent years. Patients with these diseases subsequently form the group of children with compromised immunity. Immunogens and immunomodulators are the drugs of nonspecific prophylaxis which are used for the prevention of ARI. The group of bacterial immunomodulators is big but most well-studied systemic drug from this group is Ribomunyl. Ribosomal complex is effective and safe in pediatric practice. The article presents the clinical case of treatment with ribosomal complex in immunocompronised child with allergic pathology.Key words: children with compromised immunity, allergy, acute respiratory infections, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 211–215

Caffeine alleviates the deterioration of Ca2+ release mechanisms and fragmentation of in vitro aged mouse eggs

Science.gov (United States)

Zhang, Nan; Wakai, Takuya; Fissore, Rafael. A.

2011-01-01

The developmental competence of mammalian eggs is compromised by postovulatory aging. We and others found that in these eggs the intracellular calcium ([Ca2+]i) responses required for egg activation and initiation of development are altered. Nevertheless, the mechanism(s) underlying this defective Ca2+ release is not well known. Here, we investigated if the function of IP3R1, the major Ca2+ release channel at fertilization, was undermined in in vitro aged mouse eggs. We found that in aged eggs IP3R1 displayed reduced function, as many of the changes acquired during maturation that enhance IP3R1 Ca2+ conductivity such as phosphorylation, receptor reorganization and increased Ca2+ store content ([Ca2+]ER) were lost with increasing postovulatory time. IP3R1 fragmentation, possibly associated with the activation of caspase-3, was also observed in these eggs. Many of these changes were prevented when the postovulatory aging of eggs was carried out in the presence of caffeine, which minimized the decline in IP3R1 function and maintained [Ca2+]ER content. Caffeine also maintained mitochondrial membrane potential as measured by JC-1 fluorescence. We therefore conclude that [Ca2+]i responses in aged eggs are undermined by reduced IP3R1 sensitivity, decreased [Ca2+]ER and compromised mitochondrial function, and that addition of caffeine ameliorates most of these aging-associated changes. Understanding the molecular basis of the protective effects of caffeine will be useful in elucidating, and possibly reversing, the signaling pathway(s) compromised by in vitro culture of eggs. PMID:22095868

The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

Science.gov (United States)

Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

2015-01-01

The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Optimization of the virtual mouse HeadMouse to foster its classroom use by children with physical disabilities

Directory of Open Access Journals (Sweden)

Merce TEIXIDO

2014-03-01

Full Text Available This paper presents the optimization of a virtual mouse called HeadMouse in order to foster its classroom use by children with physical disabilities. HeadMouse is an absolute virtual mouse that converts head movements in cursor displacement and facial gestures in click actions. The virtual mouse combines different image processing algorithms: face detection, pattern matching and optical flow in order to emulate the behaviour of a conventional computer mouse. The original implementation of HeadMouse requires large computational power and this paper proposes specific optimizations in order to enable its use by children with disabilities in standard low cost classroom computers.

Quantitative imaging of lipids in live mouse oocytes and early embryos using CARS microscopy

Science.gov (United States)

Bradley, Josephine; Pope, Iestyn; Masia, Francesco; Sanusi, Randa; Langbein, Wolfgang; Borri, Paola

2016-01-01

Mammalian oocytes contain lipid droplets that are a store of fatty acids, whose metabolism plays a substantial role in pre-implantation development. Fluorescent staining has previously been used to image lipid droplets in mammalian oocytes and embryos, but this method is not quantitative and often incompatible with live cell imaging and subsequent development. Here we have applied chemically specific, label-free coherent anti-Stokes Raman scattering (CARS) microscopy to mouse oocytes and pre-implantation embryos. We show that CARS imaging can quantify the size, number and spatial distribution of lipid droplets in living mouse oocytes and embryos up to the blastocyst stage. Notably, it can be used in a way that does not compromise oocyte maturation or embryo development. We have also correlated CARS with two-photon fluorescence microscopy simultaneously acquired using fluorescent lipid probes on fixed samples, and found only a partial degree of correlation, depending on the lipid probe, clearly exemplifying the limitation of lipid labelling. In addition, we show that differences in the chemical composition of lipid droplets in living oocytes matured in media supplemented with different saturated and unsaturated fatty acids can be detected using CARS hyperspectral imaging. These results demonstrate that CARS microscopy provides a novel non-invasive method of quantifying lipid content, type and spatial distribution with sub-micron resolution in living mammalian oocytes and embryos. PMID:27151947

17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients

NARCIS (Netherlands)

Wieten, R. W.; Goorhuis, A.; Jonker, E. F. F.; de Bree, G. J.; de Visser, A. W.; van Genderen, P. J. J.; Remmerswaal, E. B. M.; ten Berge, I. J. M.; Visser, L. G.; Grobusch, M. P.; van Leeuwen, E. M. M.

2016-01-01

The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen

Evaluation of instant cup noodle, irradiated for immuno-compromised patients

International Nuclear Information System (INIS)

Lee, Ji-Hye; Kim, Jae-Kyung; Park, Jae-Nam; Yoon, Young-Min; Sung, Nak-Yun; Kim, Jae-Hun; Song, Beom-Seok; Yook, Hong-Sun; Kim, Byeong-Keun; Lee, Ju-Woon

2012-01-01

In the present study, initial microbial load of instant cup noodle (ICN) was investigated and gamma irradiation applied to develop immuno-compromised patients food for their safe consumption. The initial microbial population of dried vegetable and meat, and noodle was below the detection limit (1 log CFU/g); however, that of seasoning powder was just above 4 log CFU/g. Moreover, rehydrated-ICN with water at 100 °C still show above 3 log CFU/g of microbial load, which indicates the need for an additional process to control microbial safety of the seasoning powder. The total aerobic bacteria in seasoning powder and rehydrated-ICN could be controlled with 17 kGy gamma irradiation. This result referred 17 kGy gamma irradiation could reach ‘practical sterility’ of ICN. The overall difference in sensory properties between the non-irradiated and irradiated ICN was insignificant. Thus, gamma irradiation could improve the microbial quality of ICN, and reduce the risk of infection posed by the seasoning powder, without any adverse effects on their sensory quality. These results suggest that gamma-irradiated ICN can be used as a snack food for immuno-compromised patients.

Evaluation of instant cup noodle, irradiated for immuno-compromised patients

Science.gov (United States)

Lee, Ji-Hye; Kim, Jae-Kyung; Park, Jae-Nam; Yoon, Young-Min; Sung, Nak-Yun; Kim, Jae-Hun; Song, Beom-Seok; Yook, Hong-Sun; Kim, Byeong-Keun; Lee, Ju-Woon

2012-08-01

In the present study, initial microbial load of instant cup noodle (ICN) was investigated and gamma irradiation applied to develop immuno-compromised patients food for their safe consumption. The initial microbial population of dried vegetable and meat, and noodle was below the detection limit (1 log CFU/g); however, that of seasoning powder was just above 4 log CFU/g. Moreover, rehydrated-ICN with water at 100 °C still show above 3 log CFU/g of microbial load, which indicates the need for an additional process to control microbial safety of the seasoning powder. The total aerobic bacteria in seasoning powder and rehydrated-ICN could be controlled with 17 kGy gamma irradiation. This result referred 17 kGy gamma irradiation could reach 'practical sterility' of ICN. The overall difference in sensory properties between the non-irradiated and irradiated ICN was insignificant. Thus, gamma irradiation could improve the microbial quality of ICN, and reduce the risk of infection posed by the seasoning powder, without any adverse effects on their sensory quality. These results suggest that gamma-irradiated ICN can be used as a snack food for immuno-compromised patients.

Differential diagnosis of the signal-compromised lunate in MRI

International Nuclear Information System (INIS)

Schmitt, R.; Christopoulos, G.; Coblenz, G.; Froehner, S.; Brunner, H.; Kalb, K.; Krimmer, H.; Lanz, U.

2005-01-01

Purpose: To define both the underlying pathology and diagnostic criteria in lunates presenting with conspicuous signal pattern in MRI. Materials and Methods: The retrospective evaluation of 2940 MRI examinations revealed 203 patients with signal alterations of the lunate. All MRI examinations were performed on 1.5-Tesla platforms using dedicated surface coils and an intravenous contrast agent. To establish a definitive diagnosis, a total of 252 MRI examinations (49 follow-ups), 22 CT examinations and 4 arthroscopic studies were obtained in addition to the obligatory conventional radiographs. Results: Incorporating all clinical data, radiographs and MRI examinations succeeded in assigning a diagnosis in 136 signal-compromised lunates (67.0%), whereas additional diagnostic procedures or follow-up examinations were required for the definitive diagnosis in 57 cases (33.0%). The most frequent entities were 51 cases of Kienboeck's disease (25.1%), 47 cases of ulnolunate-(triquetral) impaction syndromes (23.2%) and 44 cases of intra-osseous ganglion cysts (21.7%). Other pathologies included 23 degenerative, 19 traumatic and 10 inflammatory changes as well as 9 congenital conditions. For MRI assessment of the altered lunate, the most important parameters were location and morphology as well as involvement of the articular and osseous structures of the carpus. Conclusion: The lunate may be affected by different pathological states of the wrist. In total, only one quarter of the signal-compromised lunate represented Kienboeck's disease. (orig.)

Development of mPMab-1, a Mouse-Rat Chimeric Antibody Against Mouse Podoplanin.

Science.gov (United States)

Yamada, Shinji; Kaneko, Mika K; Nakamura, Takuro; Ichii, Osamu; Konnai, Satoru; Kato, Yukinari

2017-04-01

Podoplanin (PDPN), the ligand of C-type lectin-like receptor-2, is used as a lymphatic endothelial marker. We previously established clone PMab-1 of rat IgG 2a as a specific monoclonal antibody (mAb) against mouse PDPN. PMab-1 is also very sensitive in immunohistochemical analysis; however, rat mAbs seem to be unfavorable for pathologists because anti-mouse IgG and anti-rabbit IgG are usually used as secondary antibodies in commercially available kits for immunohistochemical analysis. In this study, we develop a mouse-rat chimeric antibody, mPMab-1 of mouse IgG 2a , which was derived from rat PMab-1 mAb. Immunohistochemical analysis shows that mPMab-1 detects podocytes of the kidney, lymphatic endothelial cells of the colon, and type I alveolar cells of the lung. Importantly, mPMab-1 is more sensitive than PMab-1. This conversion strategy from rat mAb to mouse mAb could be applicable to other mAbs.

Gaze beats mouse

DEFF Research Database (Denmark)

Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin

2008-01-01

Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze...

Relationship between first trimester aneuploidy screening test serum analytes and placenta accreta.

Science.gov (United States)

Büke, Barış; Akkaya, Hatice; Demir, Sibel; Sağol, Sermet; Şimşek, Deniz; Başol, Güneş; Barutçuoğlu, Burcu

2018-01-01

The aim of this study is to determine whether there is a relationship between first trimester serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) MoM values and placenta accreta in women who had placenta previa. A total of 88 patients with placenta previa who had first trimester aneuploidy screening test results were enrolled in the study. Nineteen of these patients were also diagnosed with placenta accreta. As probable markers of excessive placental invasion, serum PAPP-A and fβhCG MoM values were compared in two groups with and without placenta accreta. Patients with placenta accreta had higher statistically significant serum PAPP-A (1.20 versus 0.865, respectively, p = 0.045) and fβhCG MoM (1.42 versus 0.93, respectively, p = 0.042) values than patients without accreta. Higher first trimester serum PAPP-A and fβhCG MoM values seem to be associated with placenta accreta in women with placenta previa. Further studies are needed to use these promising additional tools for early detection of placenta accreta.

Happenstance and compromise: a gendered analysis of students' computing degree course selection

Science.gov (United States)

Lang, Catherine

2010-12-01

The number of students choosing to study computing at university continues to decline this century, with an even sharper decline in female students. This article presents the results of a series of interviews with university students studying computing courses in Australia that uncovered the influence of happenstance and compromise on course choice. This investigation provides an insight into the contributing factors into the continued downturn of student diversity in computing bachelor degree courses. Many females interviewed made decisions based on happenstance, many males interviewed had chosen computing as a compromise course, and family helped in the decision-making to a large degree in both genders. The major implication from this investigation is the finding that students of both genders appear to be socialised away from this discipline, which is perceived as a support or insurance skill, not a career in itself, in all but the most technical-oriented (usually male) student.

Is ridge preservation/augmentation at periodontally compromised extraction sockets safe? A retrospective study.

Science.gov (United States)

Kim, Jung-Ju; Ben Amara, Heithem; Schwarz, Frank; Kim, Hae-Young; Lee, Jung-Won; Wikesjö, Ulf M E; Koo, Ki-Tae

2017-10-01

This study aimed to evaluate the safety of ridge preservation/augmentation procedures when performed at compromised extraction sockets. Patients subject to ridge preservation/augmentation at periodontally compromised sockets at Seoul National University Dental Hospital (SNUDH) were evaluated in a chart review. Tooth extractions due to acute infection were not included in our study as chronically formed lesions are the only lesions that can be detected from radiographic images. If inflammatory symptoms persisted following ridge preservation/augmentation and antimicrobial and anti-inflammatory therapy, the patient was categorized as a re-infection case and implanted biomaterial removed. Of 10,060 patients subject to tooth extractions at SNUDH, 2011 through 2015, 297 cases meeting inclusion criteria were reviewed. The severity and type of lesions were not specific because extracting data was only done by radiographic images and chart records. The review identified eight patients exhibiting inflammatory symptoms that required additional antimicrobial and anti-inflammatory therapy. Within this group, re-infection occurred in two patients requiring biomaterials removal. The final safety rate for the ridge preservation/augmentation was 99.3%. None of the demographic factors, systemic conditions or choice of biomaterial affected the safety of ridge preservation/augmentation. Alveolar ridge preservation/augmentation at periodontally compromised sockets appears safe following thorough removal of infectious source. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Outcomes of Soft Tissue Reconstruction for Traumatic Lower Extremity Fractures with Compromised Vascularity.

Science.gov (United States)

Badash, Ido; Burtt, Karen E; Leland, Hyuma A; Gould, Daniel J; Rounds, Alexis D; Azadgoli, Beina; Patel, Ketan M; Carey, Joseph N

2017-10-01

Traumatic lower extremity fractures with compromised arterial flow are limb-threatening injuries. A retrospective review of 158 lower extremities with traumatic fractures, including 26 extremities with arterial injuries, was performed to determine the effects of vascular compromise on flap survival, successful limb salvage and complication rates. Patients with arterial injuries had a larger average flap surface area (255.1 vs 144.6 cm2, P = 0.02) and a greater number of operations (4.7 vs 3.8, P = 0.01) than patients without vascular compromise. Patients presenting with vascular injury were also more likely to require fasciotomy [odds ratio (OR): 6.5, confidence interval (CI): 2.3-18.2] and to have a nerve deficit (OR: 16.6, CI: 3.9-70.0), fracture of the distal third of the leg (OR: 2.9, CI: 1.15-7.1) and intracranial hemorrhage (OR: 3.84, CI: 1.1-12.9). After soft tissue reconstruction, patients with arterial injuries had a higher rate of amputation (OR: 8.5, CI: 1.3-53.6) and flap failure requiring a return to the operating room (OR: 4.5, CI: 1.5-13.2). Arterial injury did not correlate with infection or overall complication rate. In conclusion, arterial injuries resulted in significant complications for patients with lower extremity fractures requiring flap coverage, although limb salvage was still effective in most cases.

Corporate corruption of the environment: sustainability as a process of compromise.

Science.gov (United States)

Nyberg, Daniel; Wright, Christopher

2013-09-01

A key response to environmental degradation, climate change and declining biodiversity has been the growing adoption of market principles in an effort to better value the social good of nature. Through concepts such as 'natural capitalism' and 'corporate environmentalism', nature is increasingly viewed as a domain of capitalist endeavour. In this article, we use convention theory and a pluralist understanding of social goods to investigate how the social good of the environment is usurped by the alternate social good of the market. Through analysis of interviews with sustainability managers and corporate documentation, we highlight how organizational actors employ compromise to temporally settle disputes between competing claims about environmental activities. Our findings contribute to an understanding of the processes of empirically grounded critique and the under-theorized concept of compromise between social goods. Rather than protecting the environment, the corporate promotion of sustainability facilitates the corruption of the social good of the environment and its conversion into a market commodity. © London School of Economics and Political Science 2013.

Assessment of plasminogen synthesis in vitro by mouse tumor cells using a competition radioimmunoassay for mouse plasminogen

International Nuclear Information System (INIS)

Roblin, R.O.; Bell, T.E.; Young, P.L.

1978-01-01

A sensitive, specific competition radioimmunoassay for mouse plasmin(ogen) has been developed in order to determine whether mouse tumor cells can synthesize plasminogen in vitro. The rabbit anti-BALB/c mouse plasminogen antibodies used in the assay react with the plasminogen present in serum from BALB/c, C3H, AKR and C57BL/6 mice, and also recognized mouse plasmin. The competition radiommunoassay can detect as little as 50 ng of mouse plasminogen. No competition was observed with preparations of fetal calf, human and rabbit plasminogens. A variety of virus-transformed and mouse tumor cell lines were all found to contain less than 100 ng mouse plasminogen/mg of cell extract protein. Thus, if the plasminogen activator/plasmin system is important in the growth or movement of this group of tumor cells, the cells will be dependent upon the circulatory system of the host for their plasminogen supply. (Auth.)

Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies.

Science.gov (United States)

Giorgetti, C; Vanden Meerschaut, F; De Roo, C; Saunier, O; Quarello, E; Hairion, D; Penaranda, G; Chabert-Orsini, V; De Sutter, P

2013-10-01

Can independent predictors of pregnancy-associated plasma protein-A (PAPP-A) levels be identified in a group of women who conceived following IVF/ICSI? The significantly decreased PAPP-A level in IVF and ICSI pregnancies compared with non-IVF/ICSI pregnancies was correlated strongly with the serum estradiol (E2) level at ovulation triggering. The first trimester prenatal combined screening test for fetal aneuploidies in pregnancies conceived following assisted reproduction techniques (ART) is complicated by an alteration of the maternal biomarkers free β-hCG and PAPP-A, causing a higher false-positive rate compared with pregnancies which are conceived naturally. The use of controlled ovarian stimulation prior to IVF/ICSI is suggested to be the principle reason for these alterations of biomarkers in ART pregnancies. Between January 2010 and December 2011, 1474 women who conceived naturally and 374 women who conceived following IVF (n = 89), ICSI (n = 204) or intrauterine insemination (IUI, n = 81) were included in this retrospective study. Only singleton pregnancies were eligible for this study. For all women, serum analysis was performed in the same clinical laboratory. Measurement of nuchal translucency (NT) thickness was performed by four physicians belonging to the same infertility centre. First-trimester combined screening test of aneuploidy parameters (maternal age, PAPP-A and free β-hCG, NT thickness) were compared between non-ART and ART (IVF, ICSI and IUI) singleton pregnancies. Next, a minimal threshold E2 level at ovulation triggering was suggested for IVF/ICSI pregnancies above which the PAPP-A levels were significantly decreased compared with non-ART pregnancies. Finally, a multivariate analysis was performed to reveal independent predictors of PAPP-A level in IVF/ICSI pregnancies. We showed a decrease of the multiple of the median (MoM) PAPP-A level in IVF and ICSI singleton pregnancies compared with non-ART singleton pregnancies (P IVF and ICSI

The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

Science.gov (United States)

Krupke, Debra M; Begley, Dale A; Sundberg, John P; Richardson, Joel E; Neuhauser, Steven B; Bult, Carol J

2017-11-01

Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR . ©2017 American Association for Cancer Research.

Towards a legitimate compromise?: An exploration of Integrated Reporting in the Netherlands

NARCIS (Netherlands)

van Bommel, K.

2014-01-01

Purpose – The purpose of this paper is to examine the multiplicity of views on integrated reporting and to consider the possibility of, and impediments to, reconciling these multiple rationales (“orders of worth”) and thus gain legitimacy through a compromise. This sheds light on the understanding

Safety and Efficacy of Alginate Adhesion Barrier Gel in Compromised Intestinal Anastomosis

NARCIS (Netherlands)

Chaturvedi, A.; Yauw, S.T.K.; Lomme, R.M.L.M.; Hendriks, T.; Goor, H. van

2017-01-01

BACKGROUND: For any anti-adhesive barrier developed for abdominal surgery, the use under conditions in which anastomotic healing is compromised needs to be investigated. The current study evaluates the effect of a new ultrapure alginate gel on early healing of high-risk anastomoses in the ileum and

Fibre reinforcement in a structurally compromised endodontically treated molar: a case report

Directory of Open Access Journals (Sweden)

Renita Soares

2016-05-01

Full Text Available The reconstruction of structurally compromised posterior teeth is a rather challenging procedure. The tendency of endodontically treated teeth (ETT to fracture is considerably higher than vital teeth. Although posts and core build-ups followed by conventional crowns have been generally employed for the purpose of reconstruction, this procedure entails sacrificing a considerable amount of residual sound enamel and dentin. This has drawn the attention of researchers to fibre reinforcement. Fibre-reinforced composite (FRC, designed to replace dentin, enables the biomimetic restoration of teeth. Besides improving the strength of the restoration, the incorporation of glass fibres into composite resins leads to favorable fracture patterns because the fibre layer acts as a stress breaker and stops crack propagation. The following case report presents a technique for reinforcing a badly broken-down ETT with biomimetic materials and FRC. The proper utilization of FRC in structurally compromised teeth can be considered to be an economical and practical measure that may obviate the use of extensive prosthetic treatment.

Striking a Balance between Program Requirements and GT Principles: Writing a compromised GT proposal

Directory of Open Access Journals (Sweden)

Sherry L. Xie, Ph.D. Candidate

2009-06-01

Full Text Available Glaser’s term “compromised GT proposal” (2001, p.114 refers to the type of Grounded Theory (GT proposal that is written in order to conform to the requirements of a standardized qualitative research proposal. A GT proposal needs only to supply information on the area of interest, the data source and a statement of method to the effect that the researcher begin to collect, code and analyse the data and let the theory emerge. Thus, the proposal may only occupy “a page or two” (Glaser, 2001, p. 111. Whilst being consistent with the methodology, a GT proposal sometimes has to give way to the format specified by a PhD program or committee even though the format was not defined for a GT proposal and in some areas, conflicts with GT principles; for example, the format may require a literature review. This short paper reports on my experience of writing a compromised GT proposal as a first-time GT researcher. It describes how both Glaser’s advice on writing compromised GT research proposals and the characteristics of the substantive area of the proposed research were used to satisfy program requirements while still maintaining GT fundamentals.

Resveratrol protects mouse embryonic stem cells from ionizing radiation by accelerating recovery from DNA strand breakage.

Science.gov (United States)

Denissova, Natalia G; Nasello, Cara M; Yeung, Percy L; Tischfield, Jay A; Brenneman, Mark A

2012-01-01

Resveratrol has elicited many provocative anticancer effects in laboratory animals and cultured cells, including reduced levels of oxidative DNA damage, inhibition of tumor initiation and progression and induction of apoptosis in tumor cells. Use of resveratrol as a cancer-preventive agent in humans will require that its anticancer effects not be accompanied by damage to normal tissue stem or progenitor cells. In mouse embryonic stem cells (mESC) or early mouse embryos exposed to ethanol, resveratrol has been shown to suppress apoptosis and promote survival. However, in cells exposed to genotoxic stress, survival may come at the expense of genome stability. To learn whether resveratrol can protect stem cells from DNA damage and to study its effects on genomic integrity, we exposed mESC pretreated with resveratrol to ionizing radiation (IR). Forty-eight hours pretreatment with a comparatively low concentration of resveratrol (10 μM) improved survival of mESC >2-fold after exposure to 5 Gy of X-rays. Cells pretreated with resveratrol sustained the same levels of reactive oxygen species and DNA strand breakage after IR as mock-treated controls, but repaired DNA damage more rapidly and resumed cell division sooner. Frequencies of IR-induced mutation at a chromosomal reporter locus were not increased in cells pretreated with resveratrol as compared with controls, indicating that resveratrol can improve viability in mESC after DNA damage without compromising genomic integrity.

The Mouse That Soared

Science.gov (United States)

2004-09-01

Astronomers have used an X-ray image to make the first detailed study of the behavior of high-energy particles around a fast moving pulsar. The image, from NASA's Chandra X-ray Observatory, shows the shock wave created as a pulsar plows supersonically through interstellar space. These results will provide insight into theories for the production of powerful winds of matter and antimatter by pulsars. Chandra's image of the glowing cloud, known as the Mouse, shows a stubby bright column of high-energy particles, about four light years in length, swept back by the pulsar's interaction with interstellar gas. The intense source at the head of the X-ray column is the pulsar, estimated to be moving through space at about 1.3 million miles per hour. VLA Radio Image of the Mouse, Full Field VLA Radio Image of the Mouse, Full Field A cone-shaped cloud of radio-wave-emitting particles envelopes the X-ray column. The Mouse, a.k.a. G359.23-0.82, was discovered in 1987 by radio astronomers using the National Science Foundation's Very Large Array in New Mexico. It gets its name from its appearance in radio images that show a compact snout, a bulbous body, and a remarkable long, narrow, tail that extends for about 55 light years. "A few dozen pulsar wind nebulae are known, including the spectacular Crab Nebula, but none have the Mouse's combination of relatively young age and incredibly rapid motion through interstellar space," said Bryan Gaensler of the Harvard-Smithsonian Center for Astrophysics and lead author of a paper on the Mouse that will appear in an upcoming issue of The Astrophysical Journal. "We effectively are seeing a supersonic cosmic wind tunnel, in which we can study the effects of a pulsar's motion on its pulsar wind nebula, and test current theories." Illustration of the Mouse System Illustration of the Mouse System Pulsars are known to be rapidly spinning, highly magnetized neutron stars -- objects so dense that a mass equal to that of the Sun is packed into a

ZO-1 and ZO-2 are required for extra-embryonic endoderm integrity, primitive ectoderm survival and normal cavitation in embryoid bodies derived from mouse embryonic stem cells.

Directory of Open Access Journals (Sweden)

Dominic C Y Phua

Full Text Available The Zonula Occludens proteins ZO-1 and ZO-2 are cell-cell junction-associated adaptor proteins that are essential for the structural and regulatory functions of tight junctions in epithelial cells and their absence leads to early embryonic lethality in mouse models. Here, we use the embryoid body, an in vitro peri-implantation mouse embryogenesis model, to elucidate and dissect the roles ZO-1 and ZO-2 play in epithelial morphogenesis and de novo tight junction assembly. Through the generation of individual or combined ZO-1 and ZO-2 null embryoid bodies, we show that their dual deletion prevents tight junction formation, resulting in the disorganization and compromised barrier function of embryoid body epithelial layers. The disorganization is associated with poor microvilli development, fragmented basement membrane deposition and impaired cavity formation, all of which are key epithelial tissue morphogenetic processes. Expression of Podocalyxin, which positively regulates the formation of microvilli and the apical membrane, is repressed in embryoid bodies lacking both ZO-1 and ZO-2 and this correlates with an aberrant submembranous localization of Ezrin. The null embryoid bodies thus give an insight into how the two ZO proteins influence early mouse embryogenesis and possible mechanisms underlying the embryonic lethal phenotype.

Burn mouse models

DEFF Research Database (Denmark)

Calum, Henrik; Høiby, Niels; Moser, Claus

2014-01-01

Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third...... with infected burn wound compared with the burn wound only group. The burn mouse model resembles the clinical situation and provides an opportunity to examine or develop new strategies like new antibiotics and immune therapy, in handling burn wound victims much....

32 CFR 310.14 - Notification when information is lost, stolen, or compromised.

Science.gov (United States)

2010-07-01

... THE SECRETARY OF DEFENSE (CONTINUED) PRIVACY PROGRAM DOD PRIVACY PROGRAM Systems of Records § 310.14... the individual of any loss, theft, or compromise (See also, § 310.50 for reporting of the breach to Senior Component Official for Privacy and the Defense Privacy Office). (1) The notification shall be made...

A Transgenic Tri-Modality Reporter Mouse

OpenAIRE

Yan, Xinrui; Ray, Pritha; Paulmurugan, Ramasamy; Tong, Ricky; Gong, Yongquan; Sathirachinda, Ataya; Wu, Joseph C.; Gambhir, Sanjiv S.

2013-01-01

Transgenic mouse with a stably integrated reporter gene(s) can be a valuable resource for obtaining uniformly labeled stem cells, tissues, and organs for various applications. We have generated a transgenic mouse model that ubiquitously expresses a tri-fusion reporter gene (fluc2-tdTomato-ttk) driven by a constitutive chicken β-actin promoter. This "Tri-Modality Reporter Mouse" system allows one to isolate most cells from this donor mouse and image them for bioluminescent (fluc2), fluorescent...

Osseous pseudo-myelomatose compromise, in leukemia chronic lymphoid

International Nuclear Information System (INIS)

Martinez Betancur, Octavio; Lopez de Goenaga, Maria Ines

2000-01-01

It was described a case of chronic lymphocytic leukemia in a 75 year old man, with pseudomyelomatosis osteolytic lesions in the skull, excluding other potential causes of osteolytic lesions in the clinical context of malignant lymphoproliferative neoplasm. The real frequency of osseous compromise in chronic lymphocytic leukemia is 10%. Lesions are defined as generalized osteoporosis and osteolysis with lacunar aspect, similar to myeloma lesions. Because histopathology in lymphoproliferative neoplasms may be similar, it might be difficult to diagnose chronic lymphocytic leukemia certainly, if the clinical manifestations are not considered. Differential diagnosis with other lymphoproliferative neoplasm is based basically in absolute lymphocytosis greater than 10 X 109/L, with lymphocytes with mature appearance

The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma.

Directory of Open Access Journals (Sweden)

Travis McMurphy

Full Text Available Environmental and genetic activation of a brain-adipocyte axis inhibits cancer progression. Leptin is the primary peripheral mediator of this anticancer effect in a mouse model of melanoma. In this study we assessed the effect of a leptin receptor antagonist on melanoma progression. Local administration of a neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor decreased tumor mass with no effects on body weight or food intake. In contrast, systemic administration of the nanobody failed to suppress tumor growth. Daily intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia, increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects mimicking leptin deficiency. The blockade of central actions of leptin by systemic delivery of nanobody may compromise its anticancer effect, underscoring the need to develop peripherally acting leptin antagonists coupled with efficient cancer-targeting delivery.

The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma.

Science.gov (United States)

McMurphy, Travis; Xiao, Run; Magee, Daniel; Slater, Andrew; Zabeau, Lennart; Tavernier, Jan; Cao, Lei

2014-01-01

Environmental and genetic activation of a brain-adipocyte axis inhibits cancer progression. Leptin is the primary peripheral mediator of this anticancer effect in a mouse model of melanoma. In this study we assessed the effect of a leptin receptor antagonist on melanoma progression. Local administration of a neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor decreased tumor mass with no effects on body weight or food intake. In contrast, systemic administration of the nanobody failed to suppress tumor growth. Daily intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia, increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects mimicking leptin deficiency. The blockade of central actions of leptin by systemic delivery of nanobody may compromise its anticancer effect, underscoring the need to develop peripherally acting leptin antagonists coupled with efficient cancer-targeting delivery.

Comment on "Compromised birth outcomes and infant mortality among racial and ethnic groups"

NARCIS (Netherlands)

Van der Veen, WJ

Frisbie, Forbes, and Pullum (1996) show that it is meaningful to account for low birth weight, preterm delivery, and intrauterine growth-retardation when analyzing differences in compromised birth outcomes and infant mortality among racial and ethnic groups. I compare their findings for the 1987

Morgellons: contested illness, diagnostic compromise and medicalisation.

Science.gov (United States)

Fair, Brian

2010-05-01

The case of Morgellons illustrates how the emergence of a new medically contested illness intersected with and impacted on the diagnostic processes of an existing uncontested psychiatric condition, Delusional Parasitosis (DP). More specifically, the sociopolitical processes at play in the contested illness, Morgellons, dubiously reflect patient empowerment, as well the resilience and power of medical jurisdiction. This research offers insights into the contested illness and medicalisation literatures, and aims to bridge these two approaches towards the relationship between patient empowerment and medical authority, which I do through the notion of doctor-patient compromise. The data for this research come from a comprehensive qualitative analysis of Morgellons discourse through four key sources: the pro-Morgellons website Morgellons.org; the anti-Morgellons website Morgellonswatch.com; the popular media's portrayal of Morgellons; and the DP and Morgellons articles published in peer-reviewed medical journals, as made available on PubMed.

Addressing diversity in schools through dialogue and compromise

DEFF Research Database (Denmark)

Olsen, Tore Vincents

2018-01-01

This article evaluates a decentralized Danish model for dealing with cultural and religious diversity at individual schools. This evaluation is based upon normative theories of toleration, recognition and domination and examines whether the model implies compromise with the (liberal) educational...... values stipulated in the national legislation. The model, reconstructed from government publications, is based on reaching accommodation through dialogue between school staff and parents/students, with the pragmatic aim of facilitating the participation of students in everyday school activities....... The model is noteworthy because it appears to break with the widespread ‘retreat from multiculturalism’ predicated on the defence of liberal values, and because properly dealing with diversity at schools is important for ensuring students’ well-being and academic success....

Management and design of hospital pens relative to behavior of the compromised dairy cow: A questionnaire survey of Iowa dairy farms

DEFF Research Database (Denmark)

Fogsgaard, Katrine Kop; Herskin, Mette S.; Gorden, Patrick J.

2016-01-01

on best prac-tices for housing and management of compromised cows. The purpose of this study was to providedescriptive information about management and husbandry practices of compromised cows on dairyfarms in Iowa. A questionnaire-based survey was designed to examine demographic information, designand...

Effect of reinforcement with resin composite on fracture strength of structurally compromised roots.

Science.gov (United States)

Fukui, Yuji; Komada, Wataru; Yoshida, Keiichi; Otake, Shiho; Okada, Daizo; Miura, Hiroyuki

2009-09-01

This study was aimed at evaluating the fracture resistance of structurally compromised roots restored with four different post and core systems. Thirty-two bovine roots were uniformly shaped to simulate human mandibular premolar roots. The roots were divided into four groups based on the type of restoration: cemented cast post and core (Group MC), resin composite build-up (Group CR), resin composite and prefabricated glass fiber post build-up (Group FRC), and thick-layer dual-cured resin composite-reinforced small-diameter tapered cast post and core (Group CRM). After a static loading test, the failure mode and fracture resistance were recorded. Group CRM (719.38+/-196.73 N) exhibited a significantly high fracture resistance compared with the other groups (Group MC: 429.56+/-82.43 N; Group CR: 349.56+/-66.21 N; Group FRC: 398.94+/-112.71 N; pCRM exhibited better mechanical properties for structurally compromised roots with no ferrules, although all types of restorations showed non-restorable fracture modes.

Relationship between Lower Tendency to Deceive in Aging and Inhibitory Compromise.

Science.gov (United States)

El Haj, Mohamad; Antoine, Pascal

2018-01-01

Deception can be associated with a heterogeneous network of concepts such as exaggeration, misleading, white lies, and faking. This paper assesses the tendency to deceive in aging. Our main aim was to assess whether older adults would demonstrate a low tendency to deceive. A total of 42 older adults (mean age 67.64 years, SD 7.87) and 45 younger adults (mean age 21.71 years, SD 2.66) were administered a deception scale including items such as "I sometimes tell lies if I have to" or "I never take things that don't belong to me." Participants were also administered an inhibition task. The results demonstrated a low tendency to deceive and low inhibition in older adults compared with younger ones. The low tendency to deceive in the older adults was significantly correlated with their diminished inhibitory ability. The low tendency to deceive in aging seems to be related to a difficulty in inhibiting an honest response. Since inhibitory compromise has been considered mainly to trigger negative consequences for cognition, the present paper illustrates how this age-related compromise can be associated with positive social outcomes, i.e., a low tendency to deceive. © 2017 S. Karger AG, Basel.

Mouse SNP Miner: an annotated database of mouse functional single nucleotide polymorphisms

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Ramensky Vasily E

2007-01-01

Full Text Available Abstract Background The mapping of quantitative trait loci in rat and mouse has been extremely successful in identifying chromosomal regions associated with human disease-related phenotypes. However, identifying the specific phenotype-causing DNA sequence variations within a quantitative trait locus has been much more difficult. The recent availability of genomic sequence from several mouse inbred strains (including C57BL/6J, 129X1/SvJ, 129S1/SvImJ, A/J, and DBA/2J has made it possible to catalog DNA sequence differences within a quantitative trait locus derived from crosses between these strains. However, even for well-defined quantitative trait loci ( Description To help identify functional DNA sequence variations within quantitative trait loci we have used the Ensembl annotated genome sequence to compile a database of mouse single nucleotide polymorphisms (SNPs that are predicted to cause missense, nonsense, frameshift, or splice site mutations (available at http://bioinfo.embl.it/SnpApplet/. For missense mutations we have used the PolyPhen and PANTHER algorithms to predict whether amino acid changes are likely to disrupt protein function. Conclusion We have developed a database of mouse SNPs predicted to cause missense, nonsense, frameshift, and splice-site mutations. Our analysis revealed that 20% and 14% of missense SNPs are likely to be deleterious according to PolyPhen and PANTHER, respectively, and 6% are considered deleterious by both algorithms. The database also provides gene expression and functional annotations from the Symatlas, Gene Ontology, and OMIM databases to further assess candidate phenotype-causing mutations. To demonstrate its utility, we show that Mouse SNP Miner successfully finds a previously identified candidate SNP in the taste receptor, Tas1r3, that underlies sucrose preference in the C57BL/6J strain. We also use Mouse SNP Miner to derive a list of candidate phenotype-causing mutations within a previously

Political crisіs and compromise as the casual determinants in the process of political decisions making

Directory of Open Access Journals (Sweden)

Shkuro Anton Sergiyovich

2013-12-01

Full Text Available There is a risk of certain ineffective results in the system of political decisions making. That’s why we should pay a special attention to the criteria of political crisis evaluation. Today the problem of national politics lies only in an adequate raising of questions about the way out of the political crisis using the mechanism of compromise achieving. The article is about the fundamental role of the crisis and the compromise and about their influence on the formation of the strategic development of policy.

Characteristics of virtual histology-intravascular unltrasound of infarction-related artery atheromatous plaque and pregnancy-associated plasma protein A level: a correlation study

International Nuclear Information System (INIS)

Chen Shaobo; Jiang Tiemin; Liang Guoqing; Zhao Jihong; Li Yuming

2011-01-01

Objective: To observe the characteristics of virtual histology-intravascular ultrasound (VH-IVUS) in 70 patients with acute ST segment elevated type myocardial infarction (AMI), the findings were compared with that in 70 patients with stable angina (control group), and to analyze the correlation between VH-IVUS characteristics and pregnancy-associated plasma protein A (PAPPA) level. Methods: Seventy patients with ST segment elevated AMI and 70 patients with stable angina, who received percutaneous coronary artery intervention and were encountered from Jan. 2008 to Dec. 2009, were involved in this study. After coronary angiography was completed,the plasma was aspirated from culprit coronary artery with ZEEK catheter. Then, IVUS examination to culprit lesion was carried out and grayscale and VH data were stored. The characteristics of VH-IVUS of culprit atheromatous plaque were observed and its correlation with PAPPA was analyzed. Results: The difference in age,gender, hypertension, smoking, diabetes mellitus and hyperlipidemia between two groups was of no statistical significance, but statistically significant difference in VH-IVUS characteristics of the atheromatous plaque existed between two groups, more fibro-fatty tissue and necrotic tissue with less dense calcium were seen in AMI group. The ratio of necrotic tissue area to calcified tissue area was (3.62±1.46) in AMI group and(7.18±2.53) in control group (P<0.01). PAPPA in AMI group was significantly higher than that in control group (P<0.01). Parameters of VH-IVUS in AMI group were highly correlated with PAPPA (P<0.05 or P<0.01). Conclusion: The characteristics of virtual histology-intravascular ultrasound of infarction-related artery atheromatous plaque include more necrotic tissue, higher ratio of necrotic tissue area to calcified tissue area and a closer correlation with PAPPA. (authors)

Steroid metabolism in the mouse placenta

International Nuclear Information System (INIS)

Okker-Reitsma, G.H.

1976-01-01

The purpose of the study described in this thesis was to investigate the capacity for steroid synthesis of the mouse placenta - especially the production of progesterone, androgens and estrogens - and to determine, if possible, the relation of steroid synthesis to special cell types. In an introductory chapter the androgen production in the mouse placenta is surveyed by means of a histochemical and bioindicator study of different stages of development of the placenta. The metabolism of [ 3 H]-dehydroepiandrosterone and [ 3 H]-progesterone by mouse placental tissue in vitro is studied. The metabolism of [ 3 H]-progesterone by the mouse fetal adrenal in vitro is also studied

Mouse Genome Informatics (MGI) Is the International Resource for Information on the Laboratory Mouse.

Science.gov (United States)

Law, MeiYee; Shaw, David R

2018-01-01

Mouse Genome Informatics (MGI, http://www.informatics.jax.org/ ) web resources provide free access to meticulously curated information about the laboratory mouse. MGI's primary goal is to help researchers investigate the genetic foundations of human diseases by translating information from mouse phenotypes and disease models studies to human systems. MGI provides comprehensive phenotypes for over 50,000 mutant alleles in mice and provides experimental model descriptions for over 1500 human diseases. Curated data from scientific publications are integrated with those from high-throughput phenotyping and gene expression centers. Data are standardized using defined, hierarchical vocabularies such as the Mammalian Phenotype (MP) Ontology, Mouse Developmental Anatomy and the Gene Ontologies (GO). This chapter introduces you to Gene and Allele Detail pages and provides step-by-step instructions for simple searches and those that take advantage of the breadth of MGI data integration.

Pregnancy-associated plasma protein A gene polymorphism in pregnant women with preeclampsia and intrauterine growth restriction

Directory of Open Access Journals (Sweden)

Sultan Ozkan

2015-10-01

Full Text Available Preeclampsia (PE and intrauterine growth restriction (IUGR are still among the most commonly researched titles in perinatology. To shed light on their etiology, new prevention and treatment strategies are the major targets of studies. In this study, we aimed to investigate the relation between gene polymorphism of one of the products of trophoblasts, pregnancy-associated plasma protein A (PAPP-A and PE/IUGR.A total of 147 women (IUGR, n = 61; PE, n = 47; IUGR + PE, n = 37; eclampsia, n = 2 were compared with 103 controls with respect to the sequencing of exon 14 of the PAPP-A gene to detect (rs7020782 polymorphism. Genotypes “AA” and “CC” were given in the event of A or C allele homozygosity and “AC” in A and C allele heterozygosity. Our findings revealed that the rate of AA, CC homozygotes, and AC heterozygotes did not differ between groups. Moreover, there was no difference in the distribution of PAPP-A genotypes among the patients with IUGR, PE, IUGR + PE, or eclampsia. Finally, birth weight, rate of the presence of proteinuria, and total protein excretion on 24-hour urine were similar in the subgroups of AA, AC, and CC genotypes in the study group. Our study demonstrated no association between PAPP-A gene rs7020782 polymorphism and PE/IUGR.

Pregnancy-associated plasma protein A gene polymorphism in pregnant women with preeclampsia and intrauterine growth restriction.

Science.gov (United States)

Ozkan, Sultan; Sanhal, Cem Yasar; Yeniel, Ozgur; Arslan Ates, Esra; Ergenoglu, Mete; Bınbır, Birol; Onay, Huseyin; Ozkınay, Ferda; Sagol, Sermet

2015-10-01

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are still among the most commonly researched titles in perinatology. To shed light on their etiology, new prevention and treatment strategies are the major targets of studies. In this study, we aimed to investigate the relation between gene polymorphism of one of the products of trophoblasts, pregnancy-associated plasma protein A (PAPP-A) and PE/IUGR.A total of 147 women (IUGR, n = 61; PE, n = 47; IUGR + PE, n = 37; eclampsia, n = 2) were compared with 103 controls with respect to the sequencing of exon 14 of the PAPP-A gene to detect (rs7020782) polymorphism. Genotypes "AA" and "CC" were given in the event of A or C allele homozygosity and "AC" in A and C allele heterozygosity. Our findings revealed that the rate of AA, CC homozygotes, and AC heterozygotes did not differ between groups. Moreover, there was no difference in the distribution of PAPP-A genotypes among the patients with IUGR, PE, IUGR + PE, or eclampsia. Finally, birth weight, rate of the presence of proteinuria, and total protein excretion on 24-hour urine were similar in the subgroups of AA, AC, and CC genotypes in the study group. Our study demonstrated no association between PAPP-A gene rs7020782 polymorphism and PE/IUGR. Copyright © 2015. Published by Elsevier Taiwan.

Constraining the brachial plexus does not compromise regional control in oropharyngeal carcinoma

International Nuclear Information System (INIS)

Robert, Mutter W; Wolden, Suzanne L; Lee, Nancy Y; Lok, Benjamin H; Dutta, Pinaki R; Riaz, Nadeem; Setton, Jeremy; Berry, Sean L; Goenka, Anuj; Zhang, Zhigang; Rao, Shyam S

2013-01-01

Accumulating evidence suggests that brachial plexopathy following head and neck cancer radiotherapy may be underreported and that this toxicity is associated with a dose–response. Our purpose was to determine whether the dose to the brachial plexus (BP) can be constrained, without compromising regional control. The radiation plans of 324 patients with oropharyngeal carcinoma (OPC) treated with intensity-modulated radiation therapy (IMRT) were reviewed. We identified 42 patients (13%) with gross nodal disease <1 cm from the BP. Normal tissue constraints included a maximum dose of 66 Gy and a D 05 of 60 Gy for the BP. These criteria took precedence over planning target volume (PTV) coverage of nodal disease near the BP. There was only one regional failure in the vicinity of the BP, salvaged with neck dissection (ND) and regional re-irradiation. There have been no reported episodes of brachial plexopathy to date. In combined-modality therapy, including ND as salvage, regional control did not appear to be compromised by constraining the dose to the BP. This approach may improve the therapeutic ratio by reducing the long-term risk of brachial plexopathy

Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.

Science.gov (United States)

Hook, Paul W; McClymont, Sarah A; Cannon, Gabrielle H; Law, William D; Morton, A Jennifer; Goff, Loyal A; McCallion, Andrew S

2018-03-01

Genetic variation modulating risk of sporadic Parkinson disease (PD) has been primarily explored through genome-wide association studies (GWASs). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal time points. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including genes with known PD associations and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1-null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Copyright © 2018 American Society of Human Genetics. All rights reserved.

The role of dentists on medically compromised children’s oral and dental prophylaxis in Hospital

Directory of Open Access Journals (Sweden)

Roosje Rosita Oewen

2008-12-01

Full Text Available Background: One of dentist’s main roles is to coordinate the management of medically compromised children. The term of medically compromised refers to those children who have medical conditions which affect the dental treatment or manifest as a specific oral and dental problem. Patient’s visit to Special Care for Dentistry Clinic Dr. Hasan Sadikin Hospital Bandung showed a remarkable increase. From under 10 new visit in 2003, now July–December 2008 showed 81 new visit. Purpose: This paper discusses several medical problems (cardiovascular, hematology, respiratory system, and genetic disorder in children and the role of dentist in the treatment of those patients in the hospital. Review: The increase of attention by all level to these medically compromised children in the hospital also increases the dentist’s role in supporting the prognosis of the disease and patient’s quality of life. The most important effort is oral and dental prophylaxis to prevent oral pathology which is caused by the manifestation of disease as well as the side effects of treatment. Conclusion: It is, concluded that role of the dentist in managing these patients is giving preventive efforts and dental treatment that may be improve patient’s quality of life. The preventive effort and dental treatment is customize according to the patients condition. Nevertheless, cooperation from the dentist and other professional is needed in treating these patients.

MouseMine: a new data warehouse for MGI.

Science.gov (United States)

Motenko, H; Neuhauser, S B; O'Keefe, M; Richardson, J E

2015-08-01

MouseMine (www.mousemine.org) is a new data warehouse for accessing mouse data from Mouse Genome Informatics (MGI). Based on the InterMine software framework, MouseMine supports powerful query, reporting, and analysis capabilities, the ability to save and combine results from different queries, easy integration into larger workflows, and a comprehensive Web Services layer. Through MouseMine, users can access a significant portion of MGI data in new and useful ways. Importantly, MouseMine is also a member of a growing community of online data resources based on InterMine, including those established by other model organism databases. Adopting common interfaces and collaborating on data representation standards are critical to fostering cross-species data analysis. This paper presents a general introduction to MouseMine, presents examples of its use, and discusses the potential for further integration into the MGI interface.

Mitigating Reptile Road Mortality: Fence Failures Compromise Ecopassage Effectiveness

Science.gov (United States)

Baxter-Gilbert, James H.; Riley, Julia L.; Lesbarrères, David; Litzgus, Jacqueline D.

2015-01-01

Roadways pose serious threats to animal populations. The installation of roadway mitigation measures is becoming increasingly common, yet studies that rigorously evaluate the effectiveness of these conservation tools remain rare. A highway expansion project in Ontario, Canada included exclusion fencing and ecopassages as mitigation measures designed to offset detrimental effects to one of the most imperial groups of vertebrates, reptiles. Taking a multispecies approach, we used a Before-After-Control-Impact study design to compare reptile abundance on the highway before and after mitigation at an Impact site and a Control site from 1 May to 31 August in 2012 and 2013. During this time, radio telemetry, wildlife cameras, and an automated PIT-tag reading system were used to monitor reptile movements and use of ecopassages. Additionally, a willingness to utilize experiment was conducted to quantify turtle behavioral responses to ecopassages. We found no difference in abundance of turtles on the road between the un-mitigated and mitigated highways, and an increase in the percentage of both snakes and turtles detected dead on the road post-mitigation, suggesting that the fencing was not effective. Although ecopassages were used by reptiles, the number of crossings through ecopassages was lower than road-surface crossings. Furthermore, turtle willingness to use ecopassages was lower than that reported in previous arena studies, suggesting that effectiveness of ecopassages may be compromised when alternative crossing options are available (e.g., through holes in exclusion structures). Our rigorous evaluation of reptile roadway mitigation demonstrated that when exclusion structures fail, the effectiveness of population connectivity structures is compromised. Our project emphasizes the need to design mitigation measures with the biology and behavior of the target species in mind, to implement mitigation designs in a rigorous fashion, and quantitatively evaluate road

Mitigating reptile road mortality: fence failures compromise ecopassage effectiveness.

Directory of Open Access Journals (Sweden)

James H Baxter-Gilbert

Full Text Available Roadways pose serious threats to animal populations. The installation of roadway mitigation measures is becoming increasingly common, yet studies that rigorously evaluate the effectiveness of these conservation tools remain rare. A highway expansion project in Ontario, Canada included exclusion fencing and ecopassages as mitigation measures designed to offset detrimental effects to one of the most imperial groups of vertebrates, reptiles. Taking a multispecies approach, we used a Before-After-Control-Impact study design to compare reptile abundance on the highway before and after mitigation at an Impact site and a Control site from 1 May to 31 August in 2012 and 2013. During this time, radio telemetry, wildlife cameras, and an automated PIT-tag reading system were used to monitor reptile movements and use of ecopassages. Additionally, a willingness to utilize experiment was conducted to quantify turtle behavioral responses to ecopassages. We found no difference in abundance of turtles on the road between the un-mitigated and mitigated highways, and an increase in the percentage of both snakes and turtles detected dead on the road post-mitigation, suggesting that the fencing was not effective. Although ecopassages were used by reptiles, the number of crossings through ecopassages was lower than road-surface crossings. Furthermore, turtle willingness to use ecopassages was lower than that reported in previous arena studies, suggesting that effectiveness of ecopassages may be compromised when alternative crossing options are available (e.g., through holes in exclusion structures. Our rigorous evaluation of reptile roadway mitigation demonstrated that when exclusion structures fail, the effectiveness of population connectivity structures is compromised. Our project emphasizes the need to design mitigation measures with the biology and behavior of the target species in mind, to implement mitigation designs in a rigorous fashion, and quantitatively

Study of flood defense structural measures priorities using Compromise Programming technique

Science.gov (United States)

Lim, D.; Jeong, S.

2017-12-01

Recent climate change of global warming has led to the frequent occurrence of heavy regional rainfalls. As such, inundation vulnerability increases in urban areas with high population density due to the low runoff carrying capacity. This study selects a sample area (Janghang-eup, the Republic of Korea), which is one of the most vulnerable areas to flooding, analyzing the urban flood runoff model (XP-SWMM) and using the MCDM (Multi-Criteria Decision Making) technique to establish flood protection structural measures. To this end, we compare the alternatives and choose the optimal flood defense measure: our model is utilized with three flood prevention structural measures; (i) drainage pipe construction; (ii) water detention; and (iii) flood pumping station. Dividing the target area into three small basins, we propose flood evaluations for an inundation decrease by studying the flooded area, the maximum inundation depth, the damaged residential area, and the construction cost. In addition, Compromise Programming determines the priority of the alternatives. As a consequent, this study suggests flood pumping station for Zone 1 and drainage pipe construction for Zone 2 and Zone 3, respectively, as the optimal flood defense alternative. Keywords : MCDM; Compromise Programming; Urban Flood Prevention; This research was supported by a grant [MPSS-DP-2013-62] through the Disaster and Safety Management Institute funded by Ministry of Public Safety and Security of Korean government.

The Swiss approach to finding compromises in nuclear waste governance

Energy Technology Data Exchange (ETDEWEB)

Kuppler, Sophie; Grunwald, Armin [Karlsruhe Institute of Technology (Germany). Inst. for Technology Assessment and Systems Analysis

2015-07-01

In Switzerland, a new site selection procedure is being implemented since 2008. This procedure, which is laid down in a 'sectoral plan', shows strong elements of public participation and transparency and can be considered a step away from the classical 'decide-announce-defend' approach in decision-making. This procedure tends towards a more governance-oriented approach based on ideas of 'civility' of decision-making. Despite this renewal, the Swiss case clearly shows that any kind of selection process has to be considered as a 'working compromise', which needs to be adapted when new challenges emerge.

The Swiss approach to finding compromises in nuclear waste governance

International Nuclear Information System (INIS)

Kuppler, Sophie; Grunwald, Armin

2015-01-01

In Switzerland, a new site selection procedure is being implemented since 2008. This procedure, which is laid down in a 'sectoral plan', shows strong elements of public participation and transparency and can be considered a step away from the classical 'decide-announce-defend' approach in decision-making. This procedure tends towards a more governance-oriented approach based on ideas of 'civility' of decision-making. Despite this renewal, the Swiss case clearly shows that any kind of selection process has to be considered as a 'working compromise', which needs to be adapted when new challenges emerge.

Host lung immunity is severely compromised during tropical pulmonary eosinophilia: role of lung eosinophils and macrophages.

Science.gov (United States)

Sharma, Pankaj; Sharma, Aditi; Vishwakarma, Achchhe Lal; Agnihotri, Promod Kumar; Sharma, Sharad; Srivastava, Mrigank

2016-04-01

Eosinophils play a central role in the pathogenesis of tropical pulmonary eosinophilia, a rare, but fatal, manifestation of filariasis. However, no exhaustive study has been done to identify the genes and proteins of eosinophils involved in the pathogenesis of tropical pulmonary eosinophilia. In the present study, we established a mouse model of tropical pulmonary eosinophilia that mimicked filarial manifestations of human tropical pulmonary eosinophilia pathogenesis and used flow cytometry-assisted cell sorting and real-time RT-PCR to study the gene expression profile of flow-sorted, lung eosinophils and lung macrophages during tropical pulmonary eosinophilia pathogenesis. Our results show that tropical pulmonary eosinophilia mice exhibited increased levels of IL-4, IL-5, CCL5, and CCL11 in the bronchoalveolar lavage fluid and lung parenchyma along with elevated titers of IgE and IgG subtypes in the serum. Alveolar macrophages from tropical pulmonary eosinophilia mice displayed decreased phagocytosis, attenuated nitric oxide production, and reduced T-cell proliferation capacity, and FACS-sorted lung eosinophils from tropical pulmonary eosinophilia mice upregulated transcript levels of ficolin A and anti-apoptotic gene Bcl2,but proapoptotic genes Bim and Bax were downregulated. Similarly, flow-sorted lung macrophages upregulated transcript levels of TLR-2, TLR-6, arginase-1, Ym-1, and FIZZ-1 but downregulated nitric oxide synthase-2 levels, signifying their alternative activation. Taken together, we show that the pathogenesis of tropical pulmonary eosinophilia is marked by functional impairment of alveolar macrophages, alternative activation of lung macrophages, and upregulation of anti-apoptotic genes by eosinophils. These events combine together to cause severe lung inflammation and compromised lung immunity. Therapeutic interventions that can boost host immune response in the lungs might thus provide relief to patients with tropical pulmonary eosinophilia. �

9 CFR 113.33 - Mouse safety tests.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mouse safety tests. 113.33 Section 113.33 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be...

Understanding Youth's Health-Compromising Behaviors in Germany: An Application of the Risk-Behavior Framework.

Science.gov (United States)

Hazard, Barbara P.; Lee, Che-Fu

1999-01-01

Analyzed the health-compromising behaviors of German youth using responses of 2,330 seventh, eighth, and ninth graders from the German Youth Study. Smoking and drinking are not seen by these students as health-threatening behaviors, but as socially appealing behaviors. Discusses implications for health education. (SLD)

Resale Price Maintenance Under the Hong Kong Competition Ordinance—An Uneasy Compromise

OpenAIRE

Mark Jephcott; Adelaide Luke; Lisa Geary; Molly Herron

2015-01-01

However, the compromise position reached in the Guideline provides relatively little in terms of legal certainty as to the circumstances in which RPM may be acceptable. Mark Jephcott, Adelaide Luke, Lisa Geary, & Molly Herron (Herbert Smith Freehills)

Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites

Directory of Open Access Journals (Sweden)

Guillermo López-Doménech

2016-10-01

Full Text Available Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.

Conflicting perspectives compromising discussions on cardiopulmonary resuscitation.

LENUS (Irish Health Repository)

Groarke, J

2010-09-01

Healthcare professionals, patients and their relatives are expected to discuss resuscitation together. This study aims to identify the differences in the knowledge base and understanding of these parties. Questionnaires examining knowledge and opinion on resuscitation matters were completed during interviews of randomly selected doctors, nurses and the general public. 70% doctors, 24% nurses and 0% of a public group correctly estimated survival to discharge following in-hospital resuscitation attempts. Deficiencies were identified in doctor and nurse knowledge of ethics governing resuscitation decisions. Public opinion often conflicts with ethical guidelines. Public understanding of the nature of cardiopulmonary arrests and resuscitation attempts; and of the implications of a \\'Do Not Attempt Resuscitation (DNAR)\\' order is poor. Television medical dramas are the primary source of resuscitation knowledge. Deficiencies in healthcare professionals\\' knowledge of resuscitation ethics and outcomes may compromise resuscitation decisions. Educational initiatives to address deficiencies are necessary. Parties involved in discussion on resuscitation do not share the same knowledge base reducing the likelihood of meaningful discussion. Public misapprehensions surrounding resuscitation must be identified and corrected during discussion.

Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain.

Science.gov (United States)

Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich

2014-01-01

The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial- lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. http://mouseidgenes.helmholtz-muenchen.de. © The Author(s) 2014. Published by Oxford University Press.

76 FR 17843 - Intent To Compromise Claim Against the District of Columbia Public Schools

Science.gov (United States)

2011-03-31

... District of Columbia Public Schools (DCPS) now pending before the Office of Administrative Law Judges (OALJ... DEPARTMENT OF EDUCATION Intent To Compromise Claim Against the District of Columbia Public Schools... Application for Review of this PDL with the Office of Administrative Law Judges (OALJ) on September 10, 2007...

The Virtual Mouse Brain: A Computational Neuroinformatics Platform to Study Whole Mouse Brain Dynamics.

Science.gov (United States)

Melozzi, Francesca; Woodman, Marmaduke M; Jirsa, Viktor K; Bernard, Christophe

2017-01-01

Connectome-based modeling of large-scale brain network dynamics enables causal in silico interrogation of the brain's structure-function relationship, necessitating the close integration of diverse neuroinformatics fields. Here we extend the open-source simulation software The Virtual Brain (TVB) to whole mouse brain network modeling based on individual diffusion magnetic resonance imaging (dMRI)-based or tracer-based detailed mouse connectomes. We provide practical examples on how to use The Virtual Mouse Brain (TVMB) to simulate brain activity, such as seizure propagation and the switching behavior of the resting state dynamics in health and disease. TVMB enables theoretically driven experimental planning and ways to test predictions in the numerous strains of mice available to study brain function in normal and pathological conditions.

Small intestine epithelial barrier function is compromised in pigs with low feed intake at weaning.

NARCIS (Netherlands)

Spreeuwenberg, M.A.; Verdonk, J.M.; Gaskins, H.R.; Verstegen, M.W.A.

2001-01-01

Compromising alterations in gastrointestinal architecture are common during the weaning transition of pigs. The relation between villous atrophy and epithelial barrier function at weaning is not well understood. This study evaluated in vitro transepithelial transport by Ussing metabolic chambers,

Sarcoidosis with Major Airway, Vascular and Nerve Compromise

Directory of Open Access Journals (Sweden)

Hiroshi Sekiguchi

2013-01-01

Full Text Available The present report describes a 60-year-old Caucasian woman who presented with progressive dyspnea, cough and wheeze. A computed tomography scan of the chest showed innumerable bilateral inflammatory pulmonary nodules with bronchovascular distribution and a mediastinal and hilar infiltrative process with calcified lymphadenopathy leading to narrowing of lobar bronchi and pulmonary arteries. An echocardiogram revealed pulmonary hypertension. Bronchoscopy showed left vocal cord paralysis and significant narrowing of the bilateral bronchi with mucosal thickening and multiple nodules. Transbronchial biopsy was compatible with sarcoidosis. Despite balloon angioplasty of the left lower lobe and pulmonary artery, and medical therapy with oral corticosteroids, her symptoms did not significantly improve. To the authors’ knowledge, the present report describes the first case of pulmonary sarcoidosis resulting in major airway, vascular and nerve compromise due to compressive lymphadenopathy and suspected concurrent granulomatous infiltration. Its presentation mimicked idiopathic mediastinal fibrosis.

Advanced medical life support procedures in vitally compromised children by a helicopter emergency medical service.

NARCIS (Netherlands)

Gerritse, B.M.; Schalkwijk, A.; Pelzer, B.J.; Scheffer, G.J.; Draaisma, J.M.T.

2010-01-01

BACKGROUND: To determine the advanced life support procedures provided by an Emergency Medical Service (EMS) and a Helicopter Emergency Medical Service (HEMS) for vitally compromised children. Incidence and success rate of several procedures were studied, with a distinction made between procedures

Immunostimulatory mouse granuloma protein.

Science.gov (United States)

Fontan, E; Fauve, R M; Hevin, B; Jusforgues, H

1983-10-01

Earlier studies have shown that from subcutaneous talc-induced granuloma in mice, a fraction could be extracted that fully protected mice against Listeria monocytogenes. Using standard biochemical procedures--i.e., ammonium sulfate fractionation, preparative electrophoresis, gel filtration chromatography, isoelectric focusing, and preparative polyacrylamide gel electrophoresis--we have now purified an active factor to homogeneity. A single band was obtained in NaDodSO4/polyacrylamide gel with an apparent Mr of 55,000. It migrated with alpha 1-globulins and the isoelectric point was 5 +/- 0.1. The biological activity was destroyed with Pronase but not with trypsin and a monospecific polyclonal rabbit antiserum was obtained. The intravenous injection of 5 micrograms of this "mouse granuloma protein" fully protects mice against a lethal inoculum of L. monocytogenes. Moreover, after their incubation with 10 nM mouse granuloma protein, mouse peritoneal cells became cytostatic against Lewis carcinoma cells.

28 CFR 0.163 - Approval by Solicitor General of action on compromise offers in certain cases.

Science.gov (United States)

2010-07-01

... advice from the Solicitor General that the principles of law involved do not require appellate review in... JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Authority To Compromise and Close Civil Claims and...

Normative weight-adjusted models for the median levels of first trimester serum biomarkers for trisomy 21 screening in a specific ethnicity.

Directory of Open Access Journals (Sweden)

Ounjai Kor-Anantakul

Full Text Available To establish normative weight-adjusted models for the median levels of first trimester serum biomarkers for trisomy 21 screening in southern Thai women, and to compare these reference levels with Caucasian-specific and northern Thai models.A cross-sectional study was conducted in 1,150 normal singleton pregnancy women to determine serum pregnancy-associated plasma protein-A (PAPP-A and free β-human chorionic gonadotropin (β-hCG concentrations in women from southern Thailand. The predicted median values were compared with published equations for Caucasians and northern Thai women.The best-fitting regression equations for the expected median serum levels of PAPP-A (mIU/L and free β- hCG (ng/mL according to maternal weight (Wt in kg and gestational age (GA in days were: [Formula: see text] and [Formula: see text] Both equations were selected with a statistically significant contribution (p< 0.05. Compared with the Caucasian model, the median values of PAPP-A were higher and the median values of free β-hCG were lower in the southern Thai women. And compared with the northern Thai models, the median values of both biomarkers were lower in southern Thai women.The study has successfully developed maternal-weight- and gestational-age-adjusted median normative models to convert the PAPP-A and free β-hCG levels into their Multiple of Median equivalents in southern Thai women. These models confirmed ethnic differences.

Mouse Resource Browser-a database of mouse databases

NARCIS (Netherlands)

Zouberakis, Michael; Chandras, Christina; Swertz, Morris; Smedley, Damian; Gruenberger, Michael; Bard, Jonathan; Schughart, Klaus; Rosenthal, Nadia; Hancock, John M.; Schofield, Paul N.; Kollias, George; Aidinis, Vassilis

2010-01-01

The laboratory mouse has become the organism of choice for discovering gene function and unravelling pathogenetic mechanisms of human diseases through the application of various functional genomic approaches. The resulting deluge of data has led to the deployment of numerous online resources and the

Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease

Directory of Open Access Journals (Sweden)

Laurent P. Bogdanik

2013-05-01

Charcot-Marie-Tooth disease (CMT is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P. Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease.

Science.gov (United States)

Bogdanik, Laurent P; Sleigh, James N; Tian, Cong; Samuels, Mark E; Bedard, Karen; Seburn, Kevin L; Burgess, Robert W

2013-05-01

Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P). Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

Hepatic S1P deficiency lowers plasma cholesterol levels in apoB-containing lipoproteins when LDLR function is compromised.

Science.gov (United States)

Basu, Debapriya; Huq, Afroza; Iqbal, Jahangir; Hussain, M Mahmood; Jiang, Xian-Cheng; Jin, Weijun

2015-01-01

Site-1 protease (S1P) is the key enzyme required for activation of the sterol regulatory element binding proteins (SREBPs) that govern lipid synthesis. While S1P has been speculated to influence plasma apoB-containing lipoprotein (Blp) metabolism, there has been little investigative work. LDL receptor (LDLR) is the major receptor for clearing plasma LDL cholesterol (LDL-c). Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR. A hepatic-specific knockdown (KD) of S1P was achieved using floxed S1P mouse models (S1P(f/f) and LDLR(-/-)S1P(f/f)) and hepatic expression of Cre recombinase. Lipids were measured in total plasma and size fractionated plasma using colorimetric assays. Realtime polymerase chain reaction, western blotting and ELISA were used to determine hepatic expression of key genes/protein. Plasmid mediated overexpression and siRNA mediated knockdown of genes were performed in mouse primary hepatocytes to determine the mechanistic basis of PCSK9 gene regulation. A hepatic-specific KD of S1P resulted in a 45 % and 38 % reduction in plasma total cholesterol and triglyceride levels, respectively. Hepatic S1P KD had a minimal effect on plasma Blp cholesterol (Blp-c) in S1P(f/f) mice, despite significantly reducing VLDL secretion. Notably, hepatic S1P KD decreased the LDL receptor (LDLR) mRNA expression by 50 %. However, the reduction in LDLR protein levels was less than that of mRNA expression, especially under fed conditions. Further assessment of hepatic S1P deficiency revealed that it increased LDLR protein stability in vivo. Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. This effect was more prominent in the fed condition and sufficient to account for the discordance in LDLR mRNA and protein levels. Furthermore, hepatic S1P was shown to regulate PCSK9

A Pirate too Needs to be Heard: Procedural Compromises in Online Copyright Infringement Cases in the UK

Directory of Open Access Journals (Sweden)

Poorna Mysoor

2014-08-01

Full Text Available Online copyright infringement is one of the toughest challenges the content industry has faced in the twenty first century. Article 8(3 of the Information Society Directive, implemented under section 97A of the UK Copyright, Designs and Patents Act, 1988, provides an injunctive remedy in response to such online infringement. Given the elusive nature of the website operators and the sheer number of their users, rights owners have turned to the Internet Service Providers (ISPs to implement the injunctions granted under section 97A to block websites with infringing content. In their battle to keep pace with online infringers, the UK courts have permitted significant compromises to the procedures while granting these injunctive blocking orders. One of the pioneers in this line of cases in the UK is the Pirate Bay case (TPB case, which ruled as a matter of law that the procedure under Section 97A does not require the alleged infringers to be made parties to those proceedings. TPB case also marks the trend of the ISPs consenting to an order of injunction, and not defending the proceedings. This has resulted in the absence of any adverse party in the proceedings under section 97A. This threatens the basic tenets of procedural fairness and propriety, having adverse consequences on both the substantive and procedural aspects, evident in the cases that followed TPB case. This article examines the aspects of the judgment in TPB case that led to these procedural compromises, whether it had any basis in the pre-existing case law, what the nature of an injunction under section 97A is and how the subsequent line of cases have followed TPB case as a precedent. It further explores the adverse consequences of the procedural compromises and whether any safeguards are available against such compromises.

Hydro-environmental management of groundwater resources: A fuzzy-based multi-objective compromise approach

Science.gov (United States)

Alizadeh, Mohammad Reza; Nikoo, Mohammad Reza; Rakhshandehroo, Gholam Reza

2017-08-01

Sustainable management of water resources necessitates close attention to social, economic and environmental aspects such as water quality and quantity concerns and potential conflicts. This study presents a new fuzzy-based multi-objective compromise methodology to determine the socio-optimal and sustainable policies for hydro-environmental management of groundwater resources, which simultaneously considers the conflicts and negotiation of involved stakeholders, uncertainties in decision makers' preferences, existing uncertainties in the groundwater parameters and groundwater quality and quantity issues. The fuzzy multi-objective simulation-optimization model is developed based on qualitative and quantitative groundwater simulation model (MODFLOW and MT3D), multi-objective optimization model (NSGA-II), Monte Carlo analysis and Fuzzy Transformation Method (FTM). Best compromise solutions (best management policies) on trade-off curves are determined using four different Fuzzy Social Choice (FSC) methods. Finally, a unanimity fallback bargaining method is utilized to suggest the most preferred FSC method. Kavar-Maharloo aquifer system in Fars, Iran, as a typical multi-stakeholder multi-objective real-world problem is considered to verify the proposed methodology. Results showed an effective performance of the framework for determining the most sustainable allocation policy in groundwater resource management.

Contraction-evoked vasodilation and functional hyperaemia are compromised in branching skeletal muscle arterioles of young pre-diabetic mice.

Science.gov (United States)

Novielli, N M; Jackson, D N

2014-06-01

To investigate the effects of pre-diabetes on microvascular network function in contracting skeletal muscle. We hypothesized that pre-diabetes compromises contraction-evoked vasodilation of branching second-order (2A), third-order (3A) and fourth-order (4A) arterioles, where distal arterioles would be affected the greatest. Intravital video microscopy was used to measure arteriolar diameter (in 2A, 3A and 4A) and blood flow (in 2A and 3A) changes to electrical field stimulation of the gluteus maximus muscle in pre-diabetic (The Pound Mouse, PD) and control (c57bl6, CTRL) mice. Baseline diameter and blood flow were similar between groups (2A: ~20 μm, 3A: ~14 μm and 4A: ~8 μm; 2A: ~1 nL s(-1) and 3A: ~0.5 nL s(-1) ). Single tetanic contraction (100 Hz; 200, 400, 800 ms duration) evoked rapid-onset vasodilation (ROV) and blood flow responses that were blunted by ~50% and up to 81%, respectively, in PD vs. CTRL (P contraction (2 and 8 Hz, 30 s) evoked vasodilatory and blood flow responses that were also attenuated by ~50% and up to 71%, respectively, in PD vs. CTRL (P contraction was also up to 2.5-fold greater at 4A vs. 2A in CTRL; however spatial differences in vasodilation across arteriolar branch orders was disrupted in PD. Arteriolar dysregulation in pre-diabetes causes deficits in contraction-evoked dilation and blood flow, where greatest deficits occur at distal arterioles. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

EuroPhenome and EMPReSS: online mouse phenotyping resource.

Science.gov (United States)

Mallon, Ann-Marie; Blake, Andrew; Hancock, John M

2008-01-01

EuroPhenome (http://www.europhenome.org) and EMPReSS (http://empress.har.mrc.ac.uk/) form an integrated resource to provide access to data and procedures for mouse phenotyping. EMPReSS describes 96 Standard Operating Procedures for mouse phenotyping. EuroPhenome contains data resulting from carrying out EMPReSS protocols on four inbred laboratory mouse strains. As well as web interfaces, both resources support web services to enable integration with other mouse phenotyping and functional genetics resources, and are committed to initiatives to improve integration of mouse phenotype databases. EuroPhenome will be the repository for a recently initiated effort to carry out large-scale phenotyping on a large number of knockout mouse lines (EUMODIC).

Development of a radioimmunoassay for pregnancy-associated plasma protein A and establishment of normal levels in the first trimester of pregnancy

Energy Technology Data Exchange (ETDEWEB)

Anthony, F; Masson, G M; Wood, P J [Southampton Univ. (UK)

1983-01-01

An accelerated double antibody method has been developed for the radioimmunoassay of pregnancy-associated plasma protein A (PAPP-A) in serum. The workable range for the assay was 0.4-1.8 mg/l of serum. PAPP-A levels were determined in single serum samples from 110 women with prospective normal pregnancies of between 7 and 14 weeks' gestation. The level of pregnancy specific ..beta../sub 1/ glycoprotein (SP/sub 1/) was also measured in these samples and normal ranges for PAPP-P and SP/sub 1/ were constructed from the results obtained.

Development of a radioimmunoassay for pregnancy-associated plasma protein A and establishment of normal levels in the first trimester of pregnancy

International Nuclear Information System (INIS)

Anthony, F.; Masson, G.M.; Wood, P.J.

1983-01-01

An accelerated double antibody method has been developed for the radioimmunoassay of pregnancy-associated plasma protein A (PAPP-A) in serum. The workable range for the assay was 0.4-1.8 mg/l of serum. PAPP-A levels were determined in single serum samples from 110 women with prospective normal pregnancies of between 7 and 14 weeks' gestation. The level of pregnancy specific #betta# 1 glycoprotein (SP 1 ) was also measured in these samples and normal ranges for PAPP-P and SP 1 were constructed from the results obtained. (author)

Methamphetamine compromises gap junctional communication in astrocytes and neurons.

Science.gov (United States)

Castellano, Paul; Nwagbo, Chisom; Martinez, Luis R; Eugenin, Eliseo A

2016-05-01

Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood-brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine. However, little is known about the effects of meth on connexin (Cx) containing channels, such as gap junctions (GJ) and hemichannels (HC). We examined the effects of meth on Cx expression, function, and its role in NeuroAIDS. We found that meth altered Cx expression and localization, decreased GJ communication between neurons and astrocytes, and induced the opening of Cx43/Cx36 HC. Furthermore, we found that these changes in GJ and HC induced by meth treatment were mediated by activation of dopamine receptors, suggesting that dysregulation of dopamine signaling induced by meth is essential for GJ and HC compromise. Meth-induced changes in GJ and HC contributed to amplified CNS toxicity by dysregulating glutamate metabolism and increasing the susceptibility of neurons and astrocytes to bystander apoptosis induced by HIV. Together, our results indicate that connexin containing channels, GJ and HC, are essential in the pathogenesis of meth and increase the sensitivity of the CNS to HIV CNS disease. Methamphetamine (meth) is an extremely addictive central nervous system stimulant. Meth reduced gap junctional (GJ) communication by inducing internalization of connexin-43 (Cx43) in astrocytes and reducing expression of Cx36 in neurons by a mechanism involving activation of dopamine receptors (see cartoon). Meth-induced changes in Cx containing channels increased extracellular levels of glutamate and resulted in higher

Teratology studies in the mouse.

Science.gov (United States)

Marsden, Edward; Leroy, Mariline

2013-01-01

The rat is the routine species of choice as the rodent model for regulatory safety testing of xenobiotics such as medicinal products, food additives, and other chemicals. However, the rat is not always suitable for pharmacological, toxicological, immunogenic, pharmacokinetic, or even practical reasons. Under such circumstances, the mouse offers an alternative for finding a suitable rodent model acceptable to the regulatory authorities. Since all essential routes of administration are possible, the short reproductive cycle and large litter size of the mouse make it a species well adapted for use in teratology studies. Given that good quality animals, including virgin mated females, can be acquired relatively easily and inexpensively, the mouse has been used in reproductive toxicity studies for decades and study protocols are well established.

Circadian oscillators in the mouse brain

DEFF Research Database (Denmark)

Rath, Martin F; Rovsing, Louise; Møller, Morten

2014-01-01

with conditional cell-specific clock gene deletions. This prompted us to analyze the molecular clockwork of the mouse neocortex and cerebellum in detail. Here, by use of in situ hybridization and quantitative RT-PCR, we show that clock genes are expressed in all six layers of the neocortex and the Purkinje...... and granular cell layers of the cerebellar cortex of the mouse brain. Among these, Per1, Per2, Cry1, Arntl, and Nr1d1 exhibit circadian rhythms suggesting that local running circadian oscillators reside within neurons of the mouse neocortex and cerebellar cortex. The temporal expression profiles of clock genes...... are similar in the neocortex and cerebellum, but they are delayed by 5 h as compared to the SCN, suggestively reflecting a master-slave relationship between the SCN and extra-hypothalamic oscillators. Furthermore, ARNTL protein products are detectable in neurons of the mouse neocortex and cerebellum...

Clustering of health-compromising behavior and delinquency in adolescents and adults in the Dutch population

NARCIS (Netherlands)

van Nieuwenhuijzen, Maroesjka; Junger, Marianne; Klein Velderman, Mariska; Wiefferink, Karin H.; Paulussen, Theo W. G. M.; Hox, Joop; Reijneveld, Sijmen A.

Objective. This study investigates the clustering of a broad range of health-compromising and delinquent behaviors. We examine whether these behaviors belong to a single but broad cluster. 'risk-taking behavior', and whether the nature and degree of clustering in adolescents differs from that in

Towards mesoscience the principle of compromise in competition

CERN Document Server

Li, Jinghai

2014-01-01

This brief is devoted to providing a complete outline of meso-science by briefing the relevant contents from the published book and by updating evidences and concepts of meso-science. The importance of meso-science in solving various problems in energy, resource, and the environment is introduced.  The whole evolutionary development of the EMMS principle is reviewed to show how a simple idea on the customized modeling of particle clustering in gas-solid systems was developed, verified, extended, and finally generalized into the common principle of compromise in competition between dominant mechanisms for all mesoscale phenomena in science and engineering, leading to the proposition of meso-science. More importantly, updates on the concept of meso-science and perspectives are presented, along with new insights and findings from after the publication of the original book. In this way, we hope to help readers more easily familiarize themselves with meso-science, and to trigger interest and attention to this int...

Long term influence of regular intake of high dose n-3 fatty acids on CD40-ligand, pregnancy-associated plasma protein A and matrix metalloproteinase-9 following acute myocardial infarction.

Science.gov (United States)

Aarsetøy, Hildegunn; Brügger-Andersen, Trygve; Hetland, Øyvind; Grundt, Heidi; Nilsen, Dennis W T

2006-02-01

Pregnancy-associated plasma protein A (PAPP-A) and matrix metalloproteinase 9 (MMP-9), both zinc-binding endopeptidases, are abundantly expressed in ruptured and eroded plaques in patients with acute coronary syndromes (ACS). The adhesion molecule CD-40 ligand (CD40L), expressed on activated platelets and T-lymphocytes, can activate metalloproteinases and thereby promote plaque-rupture. N-3 fatty acids, through their anti-inflammatory and anti-thrombotic properties, might reduce the levels of these proatherosclerotic markers and thereby the development of ACS. 300 patients were randomized on day 4 to 6 following an acute myocardial infarction (MI) to receive either 4 g of n-3 fatty acids or a similar daily dose of corn oil for at least one year. We compared levels of PAPP-A, MMP-9 and sCD-40 L at baseline and 12 months in each group, and also looked for inter-group changes. In the omega-3 group, the median level of PAPP-A rose from 0.47 mU/l to 0.56 mU/l (p < 0.001). In the same group, sCD-40 L decreased from a mean baseline value of 5.19 ng/ml to 2.45 ng/ml (p < 0.001) and MMP-9 decreased nonsignificantly from 360.50 ng/ml to 308.00 ng/ml. Corresponding values for the corn oil group were 0.54 mU/l to 0.59 mU/l for PAPP-A (p = 0.007), 5.27 ng/ml to 2.84 ng/ml for sCD-40 L (p < 0.001) and 430.00 ng/ml to 324.00 ng/ml for MMP-9 (p = ns), respectively. In conclusion; both interventions resulted in a significant rise in PAPP-A, a significant decrease in sCD40L and a non-significant decrease in MMP-9 after 12 months of treatment in MI survivors. No inter-group differences were noted.

Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors.

Science.gov (United States)

Groner, B; Hynes, N E

1980-01-01

The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. Images PMID:6245257

The mouse-human anatomy ontology mapping project.

Science.gov (United States)

Hayamizu, Terry F; de Coronado, Sherri; Fragoso, Gilberto; Sioutos, Nicholas; Kadin, James A; Ringwald, Martin

2012-01-01

The overall objective of the Mouse-Human Anatomy Project (MHAP) was to facilitate the mapping and harmonization of anatomical terms used for mouse and human models by Mouse Genome Informatics (MGI) and the National Cancer Institute (NCI). The anatomy resources designated for this study were the Adult Mouse Anatomy (MA) ontology and the set of anatomy concepts contained in the NCI Thesaurus (NCIt). Several methods and software tools were identified and evaluated, then used to conduct an in-depth comparative analysis of the anatomy ontologies. Matches between mouse and human anatomy terms were determined and validated, resulting in a highly curated set of mappings between the two ontologies that has been used by other resources. These mappings will enable linking of data from mouse and human. As the anatomy ontologies have been expanded and refined, the mappings have been updated accordingly. Insights are presented into the overall process of comparing and mapping between ontologies, which may prove useful for further comparative analyses and ontology mapping efforts, especially those involving anatomy ontologies. Finally, issues concerning further development of the ontologies, updates to the mapping files, and possible additional applications and significance were considered. DATABASE URL: http://obofoundry.org/cgi-bin/detail.cgi?id=ma2ncit.

mouseTube – a database to collaboratively unravel mouse ultrasonic communication [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Nicolas Torquet

2016-09-01

Full Text Available Ultrasonic vocalisation is a broadly used proxy to evaluate social communication in mouse models of neuropsychiatric disorders. The efficacy and robustness of testing these models suffer from limited knowledge of the structure and functions of these vocalisations as well as of the way to analyse the data. We created mouseTube, an open database with a web interface, to facilitate sharing and comparison of ultrasonic vocalisations data and metadata attached to a recording file. Metadata describe 1 the acquisition procedure, e.g., hardware, software, sampling frequency, bit depth; 2 the biological protocol used to elicit ultrasonic vocalisations; 3 the characteristics of the individual emitting ultrasonic vocalisations (e.g., strain, sex, age. To promote open science and enable reproducibility, data are made freely available. The website provides searching functions to facilitate the retrieval of recording files of interest. It is designed to enable comparisons of ultrasonic vocalisation emission between strains, protocols or laboratories, as well as to test different analysis algorithms and to search for protocols established to elicit mouse ultrasonic vocalisations. Over the long term, users will be able to download and compare different analysis results for each data file. Such application will boost the knowledge on mouse ultrasonic communication and stimulate sharing and comparison of automatic analysis methods to refine phenotyping techniques in mouse models of neuropsychiatric disorders.

Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis

OpenAIRE

Chen, Hung-Chih; Chin, Yu-Feng; Lundy, David J.; Liang, Chung-Tiang; Chi, Ya-Hui; Kuo, Paolin; Hsieh, Patrick C. H.

2017-01-01

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder resulting from mutations in the dystrophin gene. The mdx/utrn ?/? mouse, lacking in both dystrophin and its autosomal homologue utrophin, is commonly used to model the clinical symptoms of DMD. Interestingly, these mice are infertile but the mechanisms underlying this phenomenon remain unclear. Using dystrophin deficient mdx mouse and utrophin haplodeficient mdx/utrn +/? mouse models, we demonstrate the contribution of Dp427 (f...

Mousetrap: An integrated, open-source mouse-tracking package.

Science.gov (United States)

Kieslich, Pascal J; Henninger, Felix

2017-10-01

Mouse-tracking - the analysis of mouse movements in computerized experiments - is becoming increasingly popular in the cognitive sciences. Mouse movements are taken as an indicator of commitment to or conflict between choice options during the decision process. Using mouse-tracking, researchers have gained insight into the temporal development of cognitive processes across a growing number of psychological domains. In the current article, we present software that offers easy and convenient means of recording and analyzing mouse movements in computerized laboratory experiments. In particular, we introduce and demonstrate the mousetrap plugin that adds mouse-tracking to OpenSesame, a popular general-purpose graphical experiment builder. By integrating with this existing experimental software, mousetrap allows for the creation of mouse-tracking studies through a graphical interface, without requiring programming skills. Thus, researchers can benefit from the core features of a validated software package and the many extensions available for it (e.g., the integration with auxiliary hardware such as eye-tracking, or the support of interactive experiments). In addition, the recorded data can be imported directly into the statistical programming language R using the mousetrap package, which greatly facilitates analysis. Mousetrap is cross-platform, open-source and available free of charge from https://github.com/pascalkieslich/mousetrap-os .

'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example.

Science.gov (United States)

Rosewall, Tara; Yan, Jing; Alasti, Hamideh; Cerase, Carla; Bayley, Andrew

2017-04-01

Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2  = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were -0.4 to 1.8 mm (LR), -1.2 to 5.2 mm (SI) and -1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer. © 2016 The Royal Australian and New Zealand College of Radiologists.

National Report presented by the Mexican United States to satisfy the compromises of the Nuclear Safety Convention

International Nuclear Information System (INIS)

1998-01-01

In order to satisfy to the compromises derived of the ratification by part of the Mexican Government for the Nuclear Safety Convention it is presented this National Report which is based on the directives proposed as a result of the preparatory meetings held in the IAEA Headquarters in the city of Vienna, Austria. This National Report represents a document summary and activities realized at present in relation with the only nuclear facility in Mexico: the Nuclear Power Plant in Laguna Verde, Veracruz. This report consists of two parts: In the first one it is described how have been satisfied each one of the compromises. The second one talks about the Laws and Regulations on nuclear activities in the country. (Author)

Compromises produced by the dialectic between self-verification and self-enhancement.

Science.gov (United States)

Morling, B; Epstein, S

1997-12-01

Three studies of people's reactions to evaluative feedback demonstrated that the dialectic between self-enhancement and self-verification results in compromises between these 2 motives, as hypothesized in cognitive-experiential self-theory. The demonstration was facilitated by 2 procedural improvements: Enhancement and verification were established by calibrating evaluative feedback against self appraisals, and degree of enhancement and of verification were varied along a continuum, rather than categorically. There was also support for the hypotheses that processing in an intuitive-experiential mode favors enhancement and processing in an analytical-rational mode favors verification in the kinds of situations investigated.

Impact of type 1 diabetes and glycemic control on fetal aneuploidy biochemical markers

DEFF Research Database (Denmark)

Madsen, Helen Nordahl; Ekelund, Charlotte K; Tørring, Niels

2012-01-01

Objective. To determine the influence of type 1 diabetes mellitus (T1DM) on the first trimester serum markers of fetal aneuploidy; pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) and to evaluate the influence of glycemic control...... on these parameters in the pregnant diabetic women. Design. Retrospective study. Setting. Data were extracted from electronic obstetric and laboratory databases at two Danish University Hospitals. Population. Based on 36 415 pregnancies without T1DM (non-T1DM) and 331 pregnancies with T1DM; β-hCG and PAPP-A were...... across the T1DM and non-T1DM groups, respectively. Additionally, the relationship between PAPP-A MoM and HgbA1C was examined in 348 T1DM pregnancies by Spearman's rank correlation. Main outcome measures. Difference in biochemical marker levels between T1DM and non-T1DM. Results. PAPP-A was 0.86 MoM in T1...

An anthelmintic drug, pyrvinium pamoate, thwarts fibrosis and ameliorates myocardial contractile dysfunction in a mouse model of myocardial infarction.

Directory of Open Access Journals (Sweden)

Motoaki Murakoshi

Full Text Available Metabolic adaptation to limited supplies of oxygen and nutrients plays a pivotal role in health and disease. Heart attack results from insufficient delivery of oxygen and nutrients to the heart, where cardiomyocytes die and cardiac fibroblasts proliferate--the latter causing scar formation, which impedes regeneration and impairs contractility of the heart. We postulated that cardiac fibroblasts survive metabolic stress by adapting their intracellular metabolism to low oxygen and nutrients, and impeding this metabolic adaptation would thwart their survival and facilitate the repair of scarred heart. Herein, we show that an anthelmintic drug, Pyrvinium pamoate, which has been previously shown to compromise cancer cell survival under glucose starvation condition, also disables cardiac fibroblast survival specifically under glucose deficient condition. Furthermore, Pyrvinium pamoate reduces scar formation and improves cardiac contractility in a mouse model of myocardial infarction. As Pyrvinium pamoate is an FDA-approved drug, our results suggest a therapeutic use of this or other related drugs to repair scarred heart and possibly other organs.

Downregulation of the Glial GLT1 Glutamate Transporter and Purkinje Cell Dysfunction in a Mouse Model of Myotonic Dystrophy

Directory of Open Access Journals (Sweden)

Géraldine Sicot

2017-06-01

Full Text Available Brain function is compromised in myotonic dystrophy type 1 (DM1, but the underlying mechanisms are not fully understood. To gain insight into the cellular and molecular pathways primarily affected, we studied a mouse model of DM1 and brains of adult patients. We found pronounced RNA toxicity in the Bergmann glia of the cerebellum, in association with abnormal Purkinje cell firing and fine motor incoordination in DM1 mice. A global proteomics approach revealed downregulation of the GLT1 glutamate transporter in DM1 mice and human patients, which we found to be the result of MBNL1 inactivation. GLT1 downregulation in DM1 astrocytes increases glutamate neurotoxicity and is detrimental to neurons. Finally, we demonstrated that the upregulation of GLT1 corrected Purkinje cell firing and motor incoordination in DM1 mice. Our findings show that glial defects are critical in DM1 brain pathophysiology and open promising therapeutic perspectives through the modulation of glutamate levels.

Life-threatening systemic toxicity and airway compromise from a common European adder bite to the tongue

DEFF Research Database (Denmark)

Hoegberg, L C G; Jessen, C L; Lambertsen, K

2009-01-01

, pharyngeal and facial oedema compromised the airway, leading to respiratory failure, concomitant with circulatory failure related to hypoxaemia and systemic toxic effects. Acute tracheotomy secured the airway, and two doses of antivenom successfully treated the systemic, toxic effects. The reaction...

Thiamine absorption is not compromised in folate-deficient rats

International Nuclear Information System (INIS)

Walzem, R.L.; Clifford, A.J.

1988-01-01

Thiamine absorption and excretion were assessed in rats with severe folate deficiency (FD) by determining the fate of oral 3 H-labeled and intravenous 14 C-labeled thiamine over a 6-h test period. Thiamine status was evaluated in these same rats by measuring transketolase activity levels of blood before (TKA) and after (TPPE) addition of thiamine pyrophosphate to the incubation mixture of the assay procedure. Two additional experiments assessed active transport of thiamine and the effect of dietary succinylsulfathiazole (SST) on TKA and TPPE in rats with moderate FD. Intestinal absorption in general and thiamine absorption in particular and thiamine status were unaltered in rats with severe FD. Inanition associated with severe FD may impair thiamine status. Thiamine absorption by active transport was not compromised in FD, and dietary succinylsulfathiazole did not affect thiamine status

2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells.

Science.gov (United States)

Bauer, Matthias R; Joerger, Andreas C; Fersht, Alan R

2016-09-06

The tumor suppressor p53 has the most frequently mutated gene in human cancers. Many of p53's oncogenic mutants are just destabilized and rapidly aggregate, and are targets for stabilization by drugs. We found certain 2-sulfonylpyrimidines, including one named PK11007, to be mild thiol alkylators with anticancer activity in several cell lines, especially those with mutationally compromised p53. PK11007 acted by two routes: p53 dependent and p53 independent. PK11007 stabilized p53 in vitro via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. Unstable p53 was reactivated by PK11007 in some cancer cell lines, leading to up-regulation of p53 target genes such as p21 and PUMA. More generally, there was cell death that was independent of p53 but dependent on glutathione depletion and associated with highly elevated levels of reactive oxygen species and induction of endoplasmic reticulum (ER) stress, as also found for the anticancer agent PRIMA-1(MET)(APR-246). PK11007 may be a lead for anticancer drugs that target cells with nonfunctional p53 or impaired reactive oxygen species (ROS) detoxification in a wide variety of mutant p53 cells.

Melatonin receptors: latest insights from mouse models

Science.gov (United States)

Tosini, Gianluca; Owino, Sharon; Guillame, Jean-Luc; Jockers, Ralf

2014-01-01

Summary Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications towards type 2 diabetes development, visual functions, sleep disturbances and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models. PMID:24903552

Using Emergence Theory-Based Curriculum to Teach Compromise Skills to Students with Autistic Spectrum Disorders

Science.gov (United States)

Fein, Lance; Jones, Don

2015-01-01

This study addresses the compromise skills that are taught to students diagnosed with autistic spectrum disorders (ASD) and related social and communication deficits. A private school in the southeastern United States implemented an emergence theory-based curriculum to address these skills, yet no formal analysis was conducted to determine its…

Radioprotection by dipyridamole in the aging mouse. Effects on lipid peroxidation in mouse liver, spleen and brain after whole-body X-ray irradiation

International Nuclear Information System (INIS)

Seino, Noritaka

1995-01-01

To investigate the radioprotective effect of dipyridamole in the aging mouse, the lipid peroxide content in aging mouse liver, spleen and brain irradiated by X-ray were measured both before and after injection of dipyridamole. The lipid peroxide content increased with aging from 2 months old to 16 months old in the mouse liver, spleen and brain. The content of lipid peroxide in the liver and spleen of the aging mouse was significantly increased in 7 days after whole-body irradiation with 8 Gy, but was unchanged in the brain. Dipyridamole, given before irradiation, significantly inhibited the increase of lipid peroxide after irradiation. These results suggest that dipyridamole may have radioprotective effects on aging mouse liver and spleen as well as on young mouse, and that inhibition of lipid peroxidation is a possible factor in the radioprotective effect of dipyridamole. (author)

Characterization of 7A7, an anti-mouse EGFR monoclonal antibody proposed to be the mouse equivalent of cetuximab.

Science.gov (United States)

He, Xuzhi; Cruz, Jazmina L; Joseph, Shannon; Pett, Nicola; Chew, Hui Yi; Tuong, Zewen K; Okano, Satomi; Kelly, Gabrielle; Veitch, Margaret; Simpson, Fiona; Wells, James W

2018-02-23

The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer. However, only 15-20% patients benefit from this drug, thus new strategies to improve cetuximab efficiency are required. We aimed to develop a reliable and easy preclinical mouse model to evaluate the efficacy of EGFR-targeted antibodies and examine the immune mechanisms involved in tumour regression. We selected an anti-mouse EGFR mAb, 7A7, which has been reported to be "mouse cetuximab" and to exhibit similar properties to its human counterpart. Unfortunately, we were unable to reproduce previous results obtained with the 7A7 mAb. In our hands, 7A7 failed to recognize mouse EGFR, both in native and reducing conditions. Moreover, in vivo administration of 7A7 in an EGFR-expressing HPV38 tumour model did not have any impact on tumour regression or animal survival. We conclude that 7A7 does not recognize mouse EGFR and therefore cannot be used as the mouse equivalent of cetuximab use in humans. As a number of groups have spent effort and resources with similar issues we feel that publication is a responsible approach.

The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

Science.gov (United States)

Brohus, Malene; Gorbunova, Vera; Faulkes, Chris G; Overgaard, Michael T; Conover, Cheryl A

2015-01-01

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process.

Dioxin induces genomic instability in mouse embryonic fibroblasts.

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Merja Korkalainen

Full Text Available Ionizing radiation and certain other exposures have been shown to induce genomic instability (GI, i.e., delayed genetic damage observed many cell generations later in the progeny of the exposed cells. The aim of this study was to investigate induction of GI by a nongenotoxic carcinogen, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. Mouse embryonic fibroblasts (C3H10T1/2 were exposed to 1, 10 or 100 nM TCDD for 2 days. Micronuclei (MN and expression of selected cancer-related genes were assayed both immediately and at a delayed point in time (8 days. For comparison, similar experiments were done with cadmium, a known genotoxic agent. TCDD treatment induced an elevated frequency of MN at 8 days, but not directly after the exposure. TCDD-induced alterations in gene expression were also mostly delayed, with more changes observed at 8 days than at 2 days. Exposure to cadmium produced an opposite pattern of responses, with pronounced effects immediately after exposure but no increase in MN and few gene expression changes at 8 days. Although all responses to TCDD alone were delayed, menadione-induced DNA damage (measured by the Comet assay, was found to be increased directly after a 2-day TCDD exposure, indicating that the stability of the genome was compromised already at this time point. The results suggested a flat dose-response relationship consistent with dose-response data reported for radiation-induced GI. These findings indicate that TCDD, although not directly genotoxic, induces GI, which is associated with impaired DNA damage response.

Esthetic management of compromised ridge in the anterior maxilla, a modified prosthetic approach

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R Lambodharan

2017-01-01

Full Text Available Replacing a missing tooth with an implant, especially in the esthetic zone has been increasing demand for the patient. Placing dental implants in the esthetic zone, especially in the compromised ridge with thin gingival thin biotype is considered to be the ultimate challenge for many dentists. This case report illustrates the implant placement in the traumatic anterior maxilla with thin gingival biotype (Class IV and a modified approach in prosthetic placement.

A report from the Sixth International Mouse Genome Conference

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Brown, S. [Saint Mary`s Hospital Medical School, London (United Kingdom). Dept. of Biochemistry and Molecular Genetics

1992-12-31

The Sixth Annual Mouse Genome Conference was held in October, 1992 at Buffalo, USA. The mouse is one of the primary model organisms in the Human Genome Project. Through the use of gene targeting studies the mouse has become a powerful biological model for the study of gene function and, in addition, the comparison of the many homologous mutations identified in human and mouse have widened our understanding of the biology of these two organisms. A primary goal in the mouse genome program has been to create a genetic map of STSs of high resolution (<1cM) that would form the basis for the physical mapping of the whole mouse genome. Buffalo saw substantial new progress towards the goal of a very high density genetic map and the beginnings of substantive efforts towards physical mapping in chromosome regions with a high density of genetic markers.

Enhanced casein kinase II activity during mouse embryogenesis. Identification of a 110-kDa phosphoprotein as the major phosphorylation product in mouse embryos and Krebs II mouse ascites tumor cells

DEFF Research Database (Denmark)

Schneider, H R; Reichert, G H; Issinger, O G

1986-01-01

Mouse embryos at various stages of development were used to study the relationship of protein kinase activities with normal embryogenesis. Casein kinase II (CKII) activity in developing mouse embryos shows a 3-4-fold activity increase at day 12 of gestation. Together with the CKII activity...... mouse tumour cells also show an enhanced CKII activity. Here too, a 110-kDa phosphoprotein was the major phosphoryl acceptor. Partial proteolytic digestion shows that both proteins are identical. Other protein kinases tested (cAMP- and cGMP-dependent protein kinases) only show a basal level of enzyme...

The MAGIC Touch: Combining MAGIC-Pointing with a Touch-Sensitive Mouse

Science.gov (United States)

Drewes, Heiko; Schmidt, Albrecht

In this paper, we show how to use the combination of eye-gaze and a touch-sensitive mouse to ease pointing tasks in graphical user interfaces. A touch of the mouse positions the mouse pointer at the current gaze position of the user. Thus, the pointer is always at the position where the user expects it on the screen. This approach changes the user experience in tasks that include frequent switching between keyboard and mouse input (e.g. working with spreadsheets). In a user study, we compared the touch-sensitive mouse with a traditional mouse and observed speed improvements for pointing tasks on complex backgrounds. For pointing task on plain backgrounds, performances with both devices were similar, but users perceived the gaze-sensitive interaction of the touch-sensitive mouse as being faster and more convenient. Our results show that using a touch-sensitive mouse that positions the pointer on the user’s gaze position reduces the need for mouse movements in pointing tasks enormously.

Managing Campus Energy: Compromising between Rapid Needs and Environmental Requirement

Science.gov (United States)

Ambariyanto, Ambariyanto; Utama, Yos J.; Purwanto

2018-02-01

The utilization of energy, especially electricity at Diponegoro University campus continues to increase in line with the development of the university. This increase has a direct impact on the increased costs to be paid by the university. Some of the causes of increased utilization of electrical energy is the construction of new buildings to meet the needs, increased learning activities and education, research activities in the laboratory, and various other activities. On the other hand, the increase of energy utilization is considered not good from the environment point of view, especially the utilization of electrical energy coming from non sustainable resources. Efforts to compromise on both are to develop policies in developing environmentally friendly buildings, efficiency in utilization of electrical energy, and development of sustainable energy sources.

First trimester pregnancy-associated plasma protein A and human chorionic gonadotropin-beta in early and late pre-eclampsia

DEFF Research Database (Denmark)

Karahasanovic, Azra; Sørensen, Steen; Nilas, Lisbeth

2014-01-01

Abstract Background: The aim of this study was to compare pregnancy-associated plasma protein A (PAPP-A) and the β-subunit of human chorionic gonadotropin (hCGβ) measured in maternal plasma at the first trimester screening, in women who later developed early or late pre-eclampsia (PE) to women...... with normal pregnancies. Methods: In the study were included 161 cases with PE and 88 controls with uncomplicated pregnancies. Plasma PAPP-A and hCGβ were measured between gestational age (GA) 8+2 and 14+0, and cases with early and late onset PE were compared with controls. Results: Median of hCGβ (Mo...

Mathematical Footprints Discovering Mathematics Everywhere

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Pappas, Theoni

1999-01-01

MATHEMATICAL FOOTPRINTS takes a creative look at the role mathematics has played since prehistoric times, and will play in the future, and uncovers mathematics where you least expect to find it from its many uses in medicine, the sciences, and its appearance in art to its patterns in nature and its central role in the development of computers. Pappas presents mathematical ideas in a readable non-threatening manner. MATHEMATICAL FOOTPRINTS is another gem by the creator of THE MATHEMATICS CALENDAR and author of THE JOY OF MATHEMATICS. "Pappas's books have been gold mines of mathematical ent

CO2-driven compromises to marine life along the Chilean coast

Science.gov (United States)

Mayol, E.; Ruiz-Halpern, S.; Duarte, C. M.; Castilla, J. C.; Pelegrí, J. L.

2010-12-01

CO2-driven compromises to marine life were examined along the Chilean sector of the Humboldt Current System, a particularly vulnerable hypoxic and upwelling area, applying the Respiration index (RI = log10 pO2) and the pH-dependent aragonite saturation (Ω) to delineate the water masses where aerobic and calcifying organisms are stressed. There was a remarkable negative relationship between oxygen concentration and pH or pCO2 in the studied area, with the subsurface hypoxic Equatorial Subsurface Waters extending from 100 m to about 300 m depth and supporting elevated pCO2 values. The RI reached a minimum at about 200 m depth and decreased towards the Equator. Increased pCO2 in the hypoxic water layer reduced the RI values by as much as 0.59 RI units, with the upper water layer that presents conditions suitable for aerobic life (RI>0.7) declining by half between 42° S and 28° S. The intermediate waters hardly reached those stations closer to the equator so that the increased pCO2 lowered pH and the saturation of aragonite. A significant fraction of the water column along the Chilean sector of the Humboldt Current System suffers from CO2-driven compromises to biota, including waters corrosive to calcifying organisms, stress to aerobic organisms or both. The habitat free of CO2-driven stresses was restricted to the upper mixed layer and to small water parcels at about 1000 m depth. pCO2 acts as a hinge connecting respiratory and calcification challenges expected to increase in the future, resulting in a spread of the challenges to aerobic organisms.

Natural Tooth Pontic: An Instant Esthetic Option for Periodontally Compromised Teeth—A Case Series

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Rishi Raj

2016-01-01

Full Text Available Sudden tooth loss in the esthetic zone of the maxillary or mandibular anterior region can be due to trauma, periodontal disease, or endodontic failure. The treatment options for replacing the missing tooth can vary between removable prosthesis, tooth-supported prosthesis, and implant-supported prosthesis. Irrespective of the final treatment, the first line of management would be to provisionally restore the patient’s esthetic appearance at the earliest, while functionally stabilizing the compromised arch. Using the patient’s own natural tooth as a pontic offers the benefits of being the right size, shape, and color and provides exact repositioning in its original intraoral three-dimensional position. Additionally, using the patient’s platelet concentrate (platelet rich fibrin facilitates early wound healing and preservation of alveolar ridge shape following tooth extraction. The abutment teeth can also be preserved with minimal or no preparation, thus keeping the technique reversible, and can be completed at the chair side thereby avoiding laboratory costs. This helps the patient better tolerate the effect of tooth loss psychologically. The article describes a successful, immediate, and viable technique for rehabilitation of three different patients requiring replacement of a single periodontally compromised tooth in an esthetic region.

Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

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David C Geary

2016-04-01

Full Text Available Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children's and adolescent's physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children's play and cognitive (e.g., language fluency traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments.

Prosthodontic decision-making relating to dentitions with compromised molars: the perspective of Swedish General Dental Practitioners.

Science.gov (United States)

Korduner, E-K; Collin Bagewitz, I; Vult von Steyern, P; Wolf, E

2016-12-01

The aim of this investigation was to study the clinical prosthodontic decision-making process relating to dentitions with compromised molars among Swedish general dental practitioners (GDPs). Eleven Swedish GDPs were purposively selected, and all agreed to participate. Then, in-depth, semi-structured interviews were conducted and covered treatment considerations concerning two authentic patient cases, initially with complete dental arches, and later, a final treatment based on a shortened dental arch (SDA) was discussed. The cases involved patients with compromised teeth situated mainly in the molar regions. One patient suffered from extensive caries and the other from severe periodontal disease. Qualitative content analysis was used to analyse the data. In the systematic analysis, two main categories were identified: holistic and functional approach. Among the interviewed GDPs, focus was put on patients' needs, background history and motivation for treatment as well as the preservation of molar support. Within the limitations of this study, the following can be concluded: keeping a dental arch with molars seems to be important to Swedish general dental practitioners. The SDA concept does not seem to have a substantial impact on the prosthodontic decision-making relating to dentitions with compromised molars. The dentist's experiences, as well as colleagues' or consulting specialist advice together with aetiological factors and the patient's individual situation, influence the decision-making more than the SDA concept. The conflicting results in the prosthetic decision-making process concerning the relevance of age and the need for molar support need further investigation, for example based on decisions made in the dentist's own clinical practice. © 2016 John Wiley & Sons Ltd.

Relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin levels in mouse serum

DEFF Research Database (Denmark)

Lukácová, Slávka; Khalil, Azza Ahmed; Overgaard, Jens

2005-01-01

To investigate the possible relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin (OPN) levels measured in mouse serum. MATERIAL AND METHODS: Experiments were performed in CDF1 mice that were either non-tumour bearing or with different sized tumours implanted...... in the right rear foot. Osteopontin levels in extracted mouse blood serum and tissue from the transplanted tumours were measured using an ELISA assay. The tumour oxygenation status was estimated using the Eppendorf Histograph and the fraction of oxygen partial pressure (pO2) values =5 mm Hg (HF5...

Chronic Lymphocytic Leukemia as an Unusual Cause of Rapid Airway Compromise

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Adrian R. Bersabe

2017-01-01

Full Text Available Chronic Lymphocytic Leukemia (CLL is the most prevalent form of non-Hodgkin’s lymphoma (NHL in Western countries predominantly affecting adults over the age of 65. CLL is commonly indolent in nature but can present locally and aggressively at extranodal sites. Although CLL may commonly present with cervical lymphadenopathy, manifestation in nonlymphoid regions of the head and neck is not well described. CLL causing upper airway obstruction is even more uncommon. We describe a case of a patient with known history of CLL and stable lymphocytosis that developed an enlarging lymphoid base of tongue (BOT mass resulting in rapid airway compromise.

Management of compromised anterior maxillary edentulous arch with symphyseal bone graft

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Sunil Kumar Mishra

2018-01-01

Full Text Available Achieving optimal aesthetics, function and phonetics with implant-supported restorations depends largely on the amount of bone present at the site where implant has to be placed. Sometimes, patient reports with compromised conditions which makes the implant placement difficult. Today, reconstruction procedures such as autogenous bone graft and guided bone regeneration make the implant placement possible in different ridge deficient cases. This case report describes step-by-step procedure of restoring the missing maxillary right central incisor with implant-supported prostheses. In missing left central incisor region, the alveolar bony defect was corrected by autogenous bone graft obtained from symphysis region, for restoration with implant prostheses.

Hypoxia-response plasmid vector producing bcl-2 shRNA enhances the apoptotic cell death of mouse rectum carcinoma.

Science.gov (United States)

Fujioka, Takashi; Matsunaga, Naoya; Okazaki, Hiroyuki; Koyanagi, Satoru; Ohdo, Shigehiro

2010-01-01

Hypoxia-induced gene expression frequently occurs in malignant solid tumors because they often have hypoxic areas in which circulation is compromised due to structurally disorganized blood vessels. Hypoxia-response elements (HREs) are responsible for activating gene transcription in response to hypoxia. In this study, we constructed a hypoxia-response plasmid vector producing short hairpin RNA (shRNA) against B-cell leukemia/lymphoma-2 (bcl-2), an anti-apoptotic factor. The hypoxia-response promoter was made by inserting tandem repeats of HREs upstream of cytomegalovirus (CMV) promoter (HRE-CMV). HRE-CMV shbcl-2 vector consisted of bcl-2 shRNA under the control of HRE-CMV promoter. In hypoxic mouse rectum carcinoma cells (colon-26), the production of bcl-2 shRNA driven by HRE-CMV promoter was approximately 2-fold greater than that driven by CMV promoter. A single intratumoral (i.t.) injection of 40 microg HRE-CMV shbcl-2 to colon-26 tumor-bearing mice caused apoptotic cell death, and repetitive treatment with HRE-CMV shbcl-2 (40 microg/mouse, i.t.) also significantly suppressed the growth of colon-26 tumor cells implanted in mice. Apoptotic and anti-tumor effects were not observed in tumor-bearing mice treated with CMV shbcl-2. These results reveal the ability of HRE-CMV shbcl-2 vector to suppress the expression of bcl-2 in hypoxic tumor cells and suggest the usefulness of our constructed hypoxia-response plasmid vector to treat malignant tumors. [Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.10054FP].

The European directive on renewable electricity: conflicts and compromises

International Nuclear Information System (INIS)

Rowlands, I.H.

2005-01-01

As part of its efforts to increase the use of renewable energy in Europe, a Directive regarding renewable electricity was agreed by the European Union in 2001. The purpose of this article is to examine this Directive, examining how the discussions surrounding its content unfolded. The investigation focuses upon three contentious issues that were debated during the Directive's development: the definition of 'renewable', the national targets for renewable electricity (their levels, as well as whether they should be 'binding' or 'indicative') and the questions associated with harmonisation (whether one Union-wide 'support scheme' for renewable electricity should be in place, and, if so, what it should be). During the 5 years that the Directive was negotiated, many intra-Union conflicts were eventually resolved, at least temporarily, by compromises. Nevertheless, some difficult decisions regarding the promotion of renewable electricity in the European Union still have to be taken

Enhanced susceptibility to predation in corals of compromised condition.

Science.gov (United States)

Bright, Allan J; Cameron, Caitlin M; Miller, Margaret W

2015-01-01

The marine gastropod, Coralliophila abbreviata, is an obligate corallivore that causes substantial mortality in Caribbean Acropora spp. Considering the imperiled status of Acropora cervicornis and A. palmata, a better understanding of ecological interactions resulting in tissue loss may enable more effective conservation strategies. We examined differences in susceptibility of A. cervicornis to C. abbreviata predation based on coral tissue condition. Coral tissue condition was a strong determinant of snail prey choice, with snails preferring A. cervicornis fragments that were diseased or mechanically damaged over healthy fragments. In addition, snails always chose fragments undergoing active predation by another snail, while showing no preference for a non-feeding snail when compared with an undisturbed prey fragment. These results indicate that the condition of A. cervicornis prey influenced foraging behavior of C. abbreviata, creating a potential feedback that may exacerbate damage from predation in coral populations compromised by other types of disturbance.

Sequence and chromosomal localization of the mouse brevican gene

DEFF Research Database (Denmark)

Rauch, U; Meyer, H; Brakebusch, C

1997-01-01

Brevican is a brain-specific proteoglycan belonging to the aggrecan family. Phage clones containing the complete mouse brevican open reading frame of 2649 bp and the complete 3'-untranslated region of 341 bp were isolated from a mouse brain cDNA library, and cosmid clones containing the mouse...

The wobbler mouse, an ALS animal model

DEFF Research Database (Denmark)

Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

2013-01-01

This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...

Chemical Aspects of Lesser Mouse Deer Meat

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Djalal Rosyidi

2012-02-01

Full Text Available An experiment aiming for studying chemical aspects of lesser mouse deer meat (Tragulus javanicus. This research explored the chemical aspects of lesser mouse deer meat (Tragulus javanicus. Eight lesser mouse deer (four female and four male were used in chemical aspects of lesser mouse deer meat. The parameters observed included proximate analysis, amino acid, fatty acid, cholesterol and EPA-DHA of the meat. The results showed that average meat chemical composition were content of water, protein, fat, ash and cholesterol were 76.33 %, 21.42 %, 0.51 %, 1.20% and 50.00 mg/100 g, respectively. Fatty acid consist of lauric acid, miristate, palmitate, stearic, oleic, linoleic, and linolenic were 1.04 % 3.09%, 30.97, 0.77%., 59.41%, 3.22% and 1.12%, respectively. The total EPA and DHA was 0.13% and 0.05%,   Keywords: amino acid, fatty acid, cholesterol and EPA-DHA

A catalog of the mouse gut metagenome

DEFF Research Database (Denmark)

Xiao, Liang; Feng, Qiang; Liang, Suisha

2015-01-01

laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human......We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing...... counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies....

Video-Assisted versus Open Lobectomy in Patients with Compromised Lung Function: A Literature Review and Meta-Analysis.

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Ruoyu Zhang

Full Text Available It has been suggested that video-assisted (VATS lobectomy is safer than open lobectomy in patients with compromised lung function, but data regarding this are limited. We assessed acute outcomes of VATS compared to open lobectomy in these high-risk patients using a systematic literature review and meta-analysis of data.The databases PubMed and Scopus were searched for studies published between 2000 and 2013 that reported mortality and morbidity of VATS in high-risk lung cancer patients defined as having compromised pulmonary or cardiopulmonary function. Study selection, data collection and critical assessment of the included studies were performed according to the recommendations of the Cochrane Collaboration.Three case-control studies and three case series that included 330 VATS and 257 open patients were identified for inclusion. Operative mortality, overall morbidity and pulmonary morbidity were 2.5%, 39.3%, 26.2% in VATS patients and 7.8%, 57.5%, 45.5% in open lobectomy group, respectively. VATS lobectomy patients experienced significantly lower pulmonary morbidity (RR = 0.45; 95% CI, 0.30 to 0.67; p = 0.0001, somewhat reduced operative mortality (RR = 0.51; 95% CI, 0.24 to 1.06; p = 0.07, but no significant difference in overall morbidity (RR = 0.68; 95% CI, 0.41 to 1.14; p = 0.14.The existing data suggest that VATS lobectomy is associated with lower risk for pulmonary morbidity compared with open lobectomy in lung cancer patients with compromised lung function.

Orientation of handle for successful prosthetic treatment in patients with an anatomic compromise after a maxillectomy.

Science.gov (United States)

Sumita, Yuka I; Hattori, Mariko; Elbashti, Mahmoud E; Taniguchi, Hisashi

2017-05-01

This clinical technique provides a key procedure for successful prosthetic treatment in patients with an anatomical compromise after a maxillectomy. When making a preliminary impression, the clinician must keep the handle of the stock tray parallel to the patient's interpupillary line extraorally to maintain the correct position of the tray and to make a record of the inclination of the occlusal plane. This simple consideration during this first step of making a preliminary impression can be an important guide for both dentists and dental technicians. Information about the correct positioning of the tray and the inclination of the occlusal plane obtained by using a stock tray handle will greatly reduce the stress experienced by dentists, dental technicians, and patients during the fabrication of the prosthesis and will ultimately lead to successful prosthetic treatment in patients with anatomic compromise resulting from a maxillectomy. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

10. international mouse genome conference

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Meisler, M.H.

1996-12-31

Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.

Mouse Models of Gastric Cancer

Science.gov (United States)

Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

2013-01-01

Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

Mouse models of Fanconi anemia

International Nuclear Information System (INIS)

Parmar, Kalindi; D'Andrea, Alan; Niedernhofer, Laura J.

2009-01-01

Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

Mouse models of Fanconi anemia

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Parmar, Kalindi; D' Andrea, Alan [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Niedernhofer, Laura J., E-mail: niedernhoferl@upmc.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine and Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center, Research Pavilion 2.6, Pittsburgh, PA 15213-1863 (United States)

2009-07-31

Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

Navigating safety necessary compromises and trade-offs : theory and practice

CERN Document Server

Amalberti, René

2013-01-01

Managing safety in a professional environment requires constant negotiation with other competitive dimensions of risk management (finances, market and political drivers, manpower and social crisis). This is obvious, although generally not said in safety manuals. The book provides a unique vision of how to best find these compromises, starting with lessons learnt from natural risk management by individuals, then applying them to the craftsman industry, complex industrial systems (civil aviation, nuclear energy) and public services (like transportation and medicine). It offers a unique, illustrated, easy to read and scientifically based set of original concepts and pragmatic methods to revisit safety management and adopt a successful system vision. As such, and with illustrations coming from many various fields (aviation, fishing, nuclear, oil, medicine), it potentially covers a broad readership.

Tract-Specific Analyses of Diffusion Tensor Imaging Show Widespread White Matter Compromise in Autism Spectrum Disorder

Science.gov (United States)

Shukla, Dinesh K.; Keehn, Brandon; Muller, Ralph-Axel

2011-01-01

Background: Previous diffusion tensor imaging (DTI) studies have shown white matter compromise in children and adults with autism spectrum disorder (ASD), which may relate to reduced connectivity and impaired function of distributed networks. However, tract-specific evidence remains limited in ASD. We applied tract-based spatial statistics (TBSS)…

Left Ventricular Gene Expression Profile of Healthy and Cardiovascular Compromised Rat Models Used in Air Pollution Studies

Science.gov (United States)

The link between pollutant exposure and cardiovascular disease (CVD) has prompted mechanistic research with animal models of CVD. We hypothesized that the cardiac gene expression patterns of healthy and genetically compromised, CVD-prone rat models, with or without metabolic impa...

Results of endoscopic surgery and intralesional steroid therapy for airway compromise due to tracheobronchial Wegener's granulomatosis

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S. A. R. Nouraei

2008-04-01

Full Text Available Background: Upper airway compromise due to tracheobronchial stenosis commonly occurs in patients with Wegener's Granulomatosis (WG. There is at present no consensus on the optimal management of this life-threatening condition. Objective: To assess the results of laryngo-tracheo-bronchoscopy, intralesional steroid therapy, laser surgery, and dilatation in managing obstructive tracheobronchial WG. Methods: Records of eighteen previously-untreated stridulous patients with obstructive tracheobronchial WG, treated between 2004 and 2006 were prospectively recorded on an airway database and retrospectively reviewed. Information about patient and lesion characteristics and treatment details were recorded. Treatment progress was illustrated using a timeline plot, and intervention-free intervals were calculated with actuarial analysis. Results: There were nine males and the average age at presentation was 40 (16 years [range 13–74]. There were thirteen patients with tracheal, and five patients with tracheal and bronchial lesions. The average tracheal lesion height was 8 (3 mm, located 23 (9 mm below the glottis. There were 1, 10 and 7 Myer-Cotton grade I, II and III lesions respectively. Mean intervention-free interval following minimally-invasive treatment was 26 (2.8 months. Following endobronchial therapy the median intervention-free interval was 22 months (p>0.8 vs. tracheal lesions. No patient required a tracheostomy or endoluminal stenting. Conclusions: Intralesional steroid therapy and conservative endoluminal surgery is an effective strategy for treating airway compromise due to active tracheal and bronchial WG, obviating the need for airway bypass or stenting. We recommend the combination of endotracheal dilatation, conservative laser surgery and steroid therapy as the standard of care for treating airway compromise due to obstructive tracheobronchial WG.

Commonly Employed African Neonatal Skin Care Products Compromise Epidermal Function in Mice.

Science.gov (United States)

Man, Mao-Qiang; Sun, Richard; Man, George; Lee, Dale; Hill, Zelee; Elias, Peter M

2016-09-01

Neonatal mortality is much higher in the developing world than in developed countries. Infections are a major cause of neonatal death, particularly in preterm infants, in whom defective epidermal permeability barrier function facilitates transcutaneous pathogen invasion. The objective was to determine whether neonatal skin care products commonly used in Africa benefit or compromise epidermal functions in murine skin. After twice-daily treatment of 6- to 8-week-old hairless mice with each skin care product for 3 days, epidermal permeability barrier function, skin surface pH, stratum corneum hydration, and barrier recovery were measured using a multiprobe adapter system physiology monitor. For products showing some benefits in these initial tests, the epidermal permeability barrier homeostasis was assessed 1 and 5 hours after a single application to acutely disrupted skin. All of the skin care products compromised basal permeability barrier function and barrier repair kinetics. Moreover, after 3 days of treatment, most of the products also reduced stratum corneum hydration while elevating skin surface pH to abnormal levels. Some neonatal skin care products that are widely used in Africa perturb important epidermal functions, including permeability barrier homeostasis in mice. Should these products have similar effects on newborn human skin, they could cause a defective epidermal permeability barrier, which can increase body fluid loss, impair thermoregulation, and contribute to the high rates of neonatal morbidity and mortality seen in Africa. Accordingly, alternative products that enhance permeability barrier function should be identified, particularly for use in preterm infants. © 2016 Wiley Periodicals, Inc.

Consequences of early extraction of compromised first permanent molar: a systematic review.

Science.gov (United States)

Saber, Afnan M; Altoukhi, Doua H; Horaib, Mariam F; El-Housseiny, Azza A; Alamoudi, Najlaa M; Sabbagh, Heba J

2018-04-05

The aim of this study was to systematically review the literature to determine the sequelae of early extraction of compromised first permanent molars (FPMs) with regard to the skeletal and dental development of 5- to 15-year-old children. Meta-analysis was conducted when applicable. Our research protocol included a search strategy, inclusion/exclusion criteria, and a data extraction plan. The search engines used were PubMed, Scopus, and Science Direct. Study selection was performed independently by three reviewers. Articles published from 1960 to 2017 were reviewed based on inclusion and exclusion criteria. Meta-analysis was performed to compare space closure between upper and lower arches. Eleven studies fulfilled the inclusion criteria. The consequences were decrease in post extraction space, accelerated development and eruption of second permanents molars (SPMs) and third molars, a decrease in caries and/or fillings on the proximal surfaces of adjacent teeth, lingual tipping and retrusion of incisors, and counter clockwise rotation of the occlusal plane. There were several consequences of early extraction of FPMs, which were related to skeletal and dental development. Our systematic review suggests that comprehensive evaluation of the compromised FPMs should be performed before planning an extraction. The ideal time for FPM extraction is when the SPM is at the early bifurcation stage in order to achieve complete closure of the extraction space by the SPM. Benefits should be weighed over the risks to decrease the risk of unfavorable outcomes as much as possible. However, due to the limited evidence on the outcomes and variables that influence them, high-quality prospective studies are needed.

Compromised Global and Regional Cerebral Blood Flow in Congestive Heart Failure

Energy Technology Data Exchange (ETDEWEB)

Kim, J. S.; Kim, J. J.; Im, K. C.; Moon, D. H. [College of Medicine, Univ. of Ulsan, Seoul (Korea, Republic of)

2003-07-01

It has been known that cerebral perfusion is maintained in patients with congestive heart failure (CHF) by a complex series of compensatory mechanisms. However cognitive impairment is a common problem experienced by patients with CHF and may result from deranged cerebral perfusion. We prospectively investigated the global and regional CBF of patients with CHF and compared the results with that of normal controls. Thirty two patients (M/F: 22/10, 4211 yr) with CHF (LVEF=218.1%) and 10 healthy controls (M/F: 6/4, 398 yr) were prospectively studied. No patients had cerebrovascular disease or other disease affecting cognitive function. All patients and normal controls underwent radionuclide angiography including cerebral hemispheres and aortic arch, and brain perfusion SPECT using Tc-99m ECD. Global CBF was measured non-invasively by the application of Patlak plot graphical analysis. Quantitative rCBF images were obtained from SPECT image using global CBF values, regional/global count ratios, and Lassen's linearization correction algorithm. Difference of regional CBF between CHF and normal control were assessed using a SPM99 without global count normalization (uncorrected p<0.0001, extent threshold>100 voxels). Global CBF (41.54.7 ml/min/100g) of the patients with CHF were significantly lower than those (49.15.7 ml/min/100g) of controls (p<0.001). Regional CBF was significantly decreased in frontal, temporal and parietal neocortex of both cerebral hemispheres compared to normal controls. Regional rCBF of basal ganglia, thalamus, and brain stem were preserved, even though global CBF was variably compromised. Our study show that global CBF is significantly decreased in CHF and regional CBF of frontal, parietal and temporal neocortex is compromised preferentially. Further studies would be needed to investigate the relationship of rCBF change and cognitive impairment in patients with CHF.

Enhanced susceptibility to predation in corals of compromised condition

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Allan J. Bright

2015-09-01

Full Text Available The marine gastropod, Coralliophila abbreviata, is an obligate corallivore that causes substantial mortality in Caribbean Acropora spp. Considering the imperiled status of Acropora cervicornis and A. palmata, a better understanding of ecological interactions resulting in tissue loss may enable more effective conservation strategies. We examined differences in susceptibility of A. cervicornis to C. abbreviata predation based on coral tissue condition. Coral tissue condition was a strong determinant of snail prey choice, with snails preferring A. cervicornis fragments that were diseased or mechanically damaged over healthy fragments. In addition, snails always chose fragments undergoing active predation by another snail, while showing no preference for a non-feeding snail when compared with an undisturbed prey fragment. These results indicate that the condition of A. cervicornis prey influenced foraging behavior of C. abbreviata, creating a potential feedback that may exacerbate damage from predation in coral populations compromised by other types of disturbance.

Mouse myocardial first-pass perfusion MR imaging

NARCIS (Netherlands)

Coolen, Bram F.; Moonen, Rik P. M.; Paulis, Leonie E. M.; Geelen, Tessa; Nicolay, Klaas; Strijkers, Gustav J.

2010-01-01

A first-pass myocardial perfusion sequence for mouse cardiac MRI is presented. A segmented ECG-triggered acquisition combined with parallel imaging acceleration was used to capture the first pass of a Gd-DTPA bolus through the mouse heart with a temporal resolution of 300-400 msec. The method was

Mouse adenovirus type 1 infection of macrophages

NARCIS (Netherlands)

Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.

2009-01-01

Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

Compromised epidermal barrier stimulates Harderian gland activity and hypertrophy in ACBP-/- mice

DEFF Research Database (Denmark)

Sørensen, Signe Bek; Neess, Ditte; Dixen, Karen

2015-01-01

of the eye lid. We show that disruption of the Acbp gene leads to a significant enlargement of this gland with hypertrophy of the acinar cells and increased de novo synthesis of monoalkyl diacylglycerol, the main lipid species produced by the gland. Mice with conditional targeting of the Acbp gene......Acyl-CoA binding protein (ACBP) is a small, ubiquitously expressed intracellular protein that binds C14-C22 acyl-CoA esters with very high affinity and specificity. We have recently shown that targeted disruption of the Acbp gene leads to a compromised epidermal barrier and that this causes delayed...

The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

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Malene Brohus

Full Text Available Naked mole-rats (Heterocephalus glaber (NMRs are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs, and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A, shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process.

Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.

Science.gov (United States)

Bale, Laurie K; West, Sally A; Conover, Cheryl A

2017-08-01

Pregnancy-associated plasma protein-A (PAPP-A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild-type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP-A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)-inducible Cre recombinase-mediated excision of the floxed PAPP-A (fPAPP-A) gene in mice at 5 months of age. fPAPP-A mice, which were either positive (pos) or negative (neg) for Tam-Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP-A/neg and fPAPP-A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP-A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP-A/pos compared to fPAPP-A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP-A/pos mice were lower than fPAPP-A/neg mice at young adult ages (P = 0.002 for 601-800 days) and higher than fPAPP-A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age-specific mortality indicate that female mice with knockdown of PAPP-A gene expression as adults have an extended healthy life span. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example

International Nuclear Information System (INIS)

Rosewall, Tara; Alasti, Hamideh; Bayley, Andrew; Yan, Jing

2017-01-01

Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2 = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were −0.4 to 1.8 mm (LR), −1.2 to 5.2 mm (SI) and −1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer.

Managing forest and marginal agricultural land for multiple tradeoffs : compromising on economic, carbon and structural biodiversity objectives

NARCIS (Netherlands)

Krcmar, E.; Kooten, van G.C.; Vertinsky, I.

2005-01-01

In this paper, we use compromise programming to solve a multiple-objective land use and forest management planning model. Long- and short- (`fast¿) term carbon uptake, maintenance of structural diversity, and economic (net returns to forestry and agriculture) objectives are simultaneously achieved

Orthodontic management of a periodontally compromised dentition

Directory of Open Access Journals (Sweden)

Prashant K Zaveri

2016-01-01

Full Text Available Malocclusion superimposed with severe periodontitis may present a great challenge to clinicians while providing orthodontic treatment due the episodic and site-specific nature of the disease with risk of rapid tissue breakdown. However, orthodontic treatment in such situation may contribute significantly to the overall rehabilitation both functionally and esthetically. In this article, a case report outlines a combined periodontic-orthodontic management of compromised dentition. A 37-year-old female patient with significant medical history was treated for Class II Division 1 type of malocclusion associated with spaced upper and lower anterior teeth, deep overbite, and increased overjet, superimposed with chronic generalized periodontitis and bone loss. Treatment was completed using temporary anchorage devices assisted strategically applied force and modified tandem retraction biomechanics amidst management of acute inflammatory episodes during and mucogingival complication after treatment. Affected areas healed very well after post-orthodontic periodontal treatment with minimal pocket depth, and bleeding on probing, and a healthy zone of attached gingiva at the follow up visits. The orthodontic results lead to improvement in patient's facial profile, lip posture, and correction of protrusion which addressed her main concern. One year follow-up shows good orthodontic and periodontic stability. The report highlights the importance of identifying “at risk” individuals and continuous monitoring of disease status during treatment. Despite all precautionary measures, a flare-up during the treatment can be anticipated.

Which Statistic Should Be Used to Detect Item Preknowledge When the Set of Compromised Items Is Known?

Science.gov (United States)

Sinharay, Sandip

2017-09-01

Benefiting from item preknowledge is a major type of fraudulent behavior during educational assessments. Belov suggested the posterior shift statistic for detection of item preknowledge and showed its performance to be better on average than that of seven other statistics for detection of item preknowledge for a known set of compromised items. Sinharay suggested a statistic based on the likelihood ratio test for detection of item preknowledge; the advantage of the statistic is that its null distribution is known. Results from simulated and real data and adaptive and nonadaptive tests are used to demonstrate that the Type I error rate and power of the statistic based on the likelihood ratio test are very similar to those of the posterior shift statistic. Thus, the statistic based on the likelihood ratio test appears promising in detecting item preknowledge when the set of compromised items is known.

Mouse myocardial first-pass perfusion MR imaging

NARCIS (Netherlands)

Coolen, B.F.; Moonen, R.P.M.; Paulis, L.E.M.; Geelen, T.; Nicolay, K.; Strijkers, G.J.

2010-01-01

A first-pass myocardial perfusion sequence for mouse cardiac MRI is presented. A segmented ECG-triggered acquisition combined with parallel imaging acceleration was used to capture the first pass of a Gd-DTPA bolus through the mouse heart with a temporal resolution of 300–400 msec. The method was

Immunologic analyses of mouse cystathionase in normal and leukemic cells

International Nuclear Information System (INIS)

Bikel, I.; Faibes, D.; Uren, J.R.; Livingston, D.M.

1978-01-01

Rabbit antisera have been raised against mouse liver cystathionase and shown to possess enzyme neutralizing activity. Agar gel double immunodiffusion analyses demonstrated that both mouse liver cystathionase and rat liver cystathionase react with the antisera, the latter enzyme being completely cross-reactive with the former. Following radioiodination of the purified rat liver enzyme, a double antibody radioimmunoassay was developed in which greater than 90% of the labeled protein could be specifically precipitated with the anti-mouse cystathionase antibodies. In this test the purified rat liver and mouse liver enzymes were virtually indistinguishable, generating superimposable competition displacement curves on a protein mass basis. These results indicate that both enzymes are immunologically identical, thus validating the use of the rat in lieu of the murine liver enzyme as radiolabeled tracer in an assay for mouse cystathionase. In addition, competition radioimmunoassays demonstrated that the immunological reactivities of both the purified rat liver and mouse liver enzymes were equally heat sensitive. The sensitivity of the assay was determined to be 1 ng of enzyme protein/0.22 mL of assay mixture, and the assay could be used to detect the presence of enzyme protein in tissue homogenates of single mouse organs. Mouse or rat cross-reactivity with human liver cystathionase was incomplete; but, with the exception of heart and spleen, parallel radioimmunoassay competition displacement curves were obtained for cystathionase from different mouse organs including thymus. Extracts of 7-, 9-, and 10-month-old spontaneous AKR mouse thymomas were tested in the radioimmunoassay along with extracts of age-matched thymuses which were grossly tumor free. A reaction of nonidentity was observed for all of the tumor extracts while a reaction identical with that of the pure liver enzyme was found with all of the normal thymus extracts

CYP1A1 and CYP1A2 expression: Comparing 'humanized' mouse lines and wild-type mice; comparing human and mouse hepatoma-derived cell lines

International Nuclear Information System (INIS)

Uno, Shigeyuki; Endo, Kaori; Ishida, Yuji; Tateno, Chise; Makishima, Makoto; Yoshizato, Katsutoshi; Nebert, Daniel W.

2009-01-01

Human and rodent cytochrome P450 (CYP) enzymes sometimes exhibit striking species-specific differences in substrate preference and rate of metabolism. Human risk assessment of CYP substrates might therefore best be evaluated in the intact mouse by replacing mouse Cyp genes with human CYP orthologs; however, how 'human-like' can human gene expression be expected in mouse tissues? Previously a bacterial-artificial-chromosome-transgenic mouse, carrying the human CYP1A1 C YP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible CYP1A2 (mRNAs, proteins, enzyme activities) in each of nine mouse tissues examined. Chimeric mice carrying humanized liver have also been generated, by transplanting human hepatocytes into a urokinase-type plasminogen activator(+/+) s evere-combined-immunodeficiency (uPA/SCID) line with most of its mouse hepatocytes ablated. Herein we compare basal and dioxin-induced CYP1A mRNA copy numbers, protein levels, and four enzymes (benzo[a]pyrene hydroxylase, ethoxyresorufin O-deethylase, acetanilide 4-hydroxylase, methoxyresorufin O-demethylase) in liver of these two humanized mouse lines versus wild-type mice; we also compare these same parameters in mouse Hepa-1c1c7 and human HepG2 hepatoma-derived established cell lines. Most strikingly, mouse liver CYP1A1-specific enzyme activities are between 38- and 170-fold higher than human CYP1A1-specific enzyme activities (per unit of mRNA), whereas mouse versus human CYP1A2 enzyme activities (per unit of mRNA) are within 2.5-fold of one another. Moreover, both the mouse and human hepatoma cell lines exhibit striking differences in CYP1A mRNA levels and enzyme activities. These findings are relevant to risk assessment involving human CYP1A1 and CYP1A2 substrates, when administered to mice as environmental toxicants or drugs.

The electromagnetic impulse pendulum and momentum conservation

International Nuclear Information System (INIS)

Graneau, P.; Graneau, P.N.

1986-01-01

Largely quantitative experiments by Pappas have indicated that the momentum imparted to an electrodynamic impulse pendulum was not balanced by an equal and opposite momentum change of field energy as required by the special theory of relativity. The authors repeated Pappas' experiment using discharge currents from a capacitor bank which contained a known amount of stored energy. It turned out that, for momentum conservation, the magnetic-field energy required would have been 1000 to 2000 times as large as the energy that was actually stored in the capacitors. In the second part of the paper the pendulum experiments are interpreted in terms of Ampere's force law

Math Stuff

CERN Document Server

Pappas, Theoni

2002-01-01

Whether it's stuff in your kitchen or garden, stuff that powers your car or your body, stuff that helps you work, communicate or play, or stuff that you've never heard of you can bet that mathematics is there. MATH STUFF brings it all in the open in the Pappas style. Not many people think of mathematics as fascinating, exciting and invaluable. Yet Pappas writes about math ideas in such a way that conveys its often overlooked fascination, excitement, and worth. MATH STUFF deals with 38 topics in an non-threatening way that piques our curiosities. Open the book at random, and learn about such to

Effect of Duplicate Genes on Mouse Genetic Robustness: An Update

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Zhixi Su

2014-01-01

Full Text Available In contrast to S. cerevisiae and C. elegans, analyses based on the current knockout (KO mouse phenotypes led to the conclusion that duplicate genes had almost no role in mouse genetic robustness. It has been suggested that the bias of mouse KO database toward ancient duplicates may possibly cause this knockout duplicate puzzle, that is, a very similar proportion of essential genes (PE between duplicate genes and singletons. In this paper, we conducted an extensive and careful analysis for the mouse KO phenotype data and corroborated a strong effect of duplicate genes on mouse genetics robustness. Moreover, the effect of duplicate genes on mouse genetic robustness is duplication-age dependent, which holds after ruling out the potential confounding effect from coding-sequence conservation, protein-protein connectivity, functional bias, or the bias of duplicates generated by whole genome duplication (WGD. Our findings suggest that two factors, the sampling bias toward ancient duplicates and very ancient duplicates with a proportion of essential genes higher than that of singletons, have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic buffering may be correlated with sequence conservation as well as protein-protein interactivity.

Neglecting legumes has compromised human health and sustainable food production.

Science.gov (United States)

Foyer, Christine H; Lam, Hon-Ming; Nguyen, Henry T; Siddique, Kadambot H M; Varshney, Rajeev K; Colmer, Timothy D; Cowling, Wallace; Bramley, Helen; Mori, Trevor A; Hodgson, Jonathan M; Cooper, James W; Miller, Anthony J; Kunert, Karl; Vorster, Juan; Cullis, Christopher; Ozga, Jocelyn A; Wahlqvist, Mark L; Liang, Yan; Shou, Huixia; Shi, Kai; Yu, Jingquan; Fodor, Nandor; Kaiser, Brent N; Wong, Fuk-Ling; Valliyodan, Babu; Considine, Michael J

2016-08-02

The United Nations declared 2016 as the International Year of Pulses (grain legumes) under the banner 'nutritious seeds for a sustainable future'. A second green revolution is required to ensure food and nutritional security in the face of global climate change. Grain legumes provide an unparalleled solution to this problem because of their inherent capacity for symbiotic atmospheric nitrogen fixation, which provides economically sustainable advantages for farming. In addition, a legume-rich diet has health benefits for humans and livestock alike. However, grain legumes form only a minor part of most current human diets, and legume crops are greatly under-used. Food security and soil fertility could be significantly improved by greater grain legume usage and increased improvement of a range of grain legumes. The current lack of coordinated focus on grain legumes has compromised human health, nutritional security and sustainable food production.

Hyperactivation of PARP triggers nonhomologous end-joining in repair-deficient mouse fibroblasts.

Directory of Open Access Journals (Sweden)

Natalie R Gassman

Full Text Available Regulation of poly(ADP-ribose (PAR synthesis and turnover is critical to determining cell fate after genotoxic stress. Hyperactivation of PAR synthesis by poly(ADP-ribose polymerase-1 (PARP-1 occurs when cells deficient in DNA repair are exposed to genotoxic agents; however, the function of this hyperactivation has not been adequately explained. Here, we examine PAR synthesis in mouse fibroblasts deficient in the base excision repair enzyme DNA polymerase β (pol β. The extent and duration of PARP-1 activation was measured after exposure to either the DNA alkylating agent, methyl methanesulfonate (MMS, or to low energy laser-induced DNA damage. There was strong DNA damage-induced hyperactivation of PARP-1 in pol β nullcells, but not in wild-type cells. In the case of MMS treatment, PAR synthesis did not lead to cell death in the pol β null cells, but instead resulted in increased PARylation of the nonhomologous end-joining (NHEJ protein Ku70 and increased association of Ku70 with PARP-1. Inhibition of the NHEJ factor DNA-PK, under conditions of MMS-induced PARP-1 hyperactivation, enhanced necrotic cell death. These data suggest that PARP-1 hyperactivation is a protective mechanism triggering the classical-NHEJ DNA repair pathway when the primary alkylated base damage repair pathway is compromised.

Cultures of preimplantation mouse embryos

International Nuclear Information System (INIS)

Streffer, C.; Molls, M.

1987-01-01

In the preimplantation mouse embryos the chromosomal damage develops through several postradiation cell cycles and mitoses. New chromosome aberrations are seen during the second and third postradiation mitoses. Also, more micronuclei appear during later postradiation interphases. This is in agreement with the assumption that unrepaired chromosomal radiation damage develops during the cell generation cycle to such a form (i.e. double-strand breaks in DNA) that chromosomal breaks occur. This proposition is strengthened by the observation that radiation-induced damage is more rapidly expressed after neutron exposure (first or second postradiation mitosis) than after exposure to X rays at the one- or two-cell stage. The preimplantation mouse embryo culture is an inviting system for additional studies at the molecular level, especially now that within the last few years more sensitive methods have been developed for study of DNA and protein structure, regulation, and synthesis. The results from these studies of cultures of preimplantation mouse embryos present a favorable case for the study of complex biological systems under very defined conditions in vitro for extrapolation to effects in vivo

Sterilization of freeze dried manila clam (Ruditapea philippinarum) porridge for immuno-compromised patients

Energy Technology Data Exchange (ETDEWEB)

Song, Beom Seok; Park, Jae Nam [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

2017-02-15

This study was conducted to evaluate the combined effect of gamma irradiation and different conditions (vacuum packaging, antioxidant and freezing) on the microbiological and sensory characteristics of freeze dried Manila clam porridge (MCP) for immuno-compromised patient food. McP can be sterilized at 1 kGy to 10 kGy. the initial counts of total aerobic bacteria and yeast molds in the non-irradiated MCP were 2.4±0.5 and 1.2±0.3 log CFU g{sup -}'1, respectively, but gamma irradiation significantly decreased the total aerobic bacteria to below the detection limit (1 log CFU g{sup -1}) (5 kGy). Moreover, gamma irradiation effectively eliminated yeasts/molds at dose below than 1 kGy. However, gamma irradiation accelerated the increase of lipid oxidation and therefore, decreased the sensory characteristics of MCP as irradiation dose increased. to improve the sensory qualities of gamma irradiated MCP, combination treatment (vacuum packaging, 0.1% vitamin c) were applied. there was no significant difference in the overall acceptance scores between the combined-treatment sample (5.6 points) and the non-irradiated samples (6.0). the results indicate that combination treatment (vacuum packaging, 0.1% vitamin c) may help to maintain the quality of MCP. therefore, it considered that irradiation of MCP with combined treatment and this is an effective method for the consumption as a special purpose food such as for space travel or immuno-compromised patients.

Sterilization of freeze dried manila clam (Ruditapea philippinarum) porridge for immuno-compromised patients

International Nuclear Information System (INIS)

Song, Beom Seok; Park, Jae Nam

2017-01-01

This study was conducted to evaluate the combined effect of gamma irradiation and different conditions (vacuum packaging, antioxidant and freezing) on the microbiological and sensory characteristics of freeze dried Manila clam porridge (MCP) for immuno-compromised patient food. McP can be sterilized at 1 kGy to 10 kGy. the initial counts of total aerobic bacteria and yeast molds in the non-irradiated MCP were 2.4±0.5 and 1.2±0.3 log CFU g"-'1, respectively, but gamma irradiation significantly decreased the total aerobic bacteria to below the detection limit (1 log CFU g"-"1) (5 kGy). Moreover, gamma irradiation effectively eliminated yeasts/molds at dose below than 1 kGy. However, gamma irradiation accelerated the increase of lipid oxidation and therefore, decreased the sensory characteristics of MCP as irradiation dose increased. to improve the sensory qualities of gamma irradiated MCP, combination treatment (vacuum packaging, 0.1% vitamin c) were applied. there was no significant difference in the overall acceptance scores between the combined-treatment sample (5.6 points) and the non-irradiated samples (6.0). the results indicate that combination treatment (vacuum packaging, 0.1% vitamin c) may help to maintain the quality of MCP. therefore, it considered that irradiation of MCP with combined treatment and this is an effective method for the consumption as a special purpose food such as for space travel or immuno-compromised patients

Cerebral hematocrit decreases with hemodynamic compromise in carotid artery occlusion: a PET study.

Science.gov (United States)

Yamauchi, H; Fukuyama, H; Nagahama, Y; Katsumi, Y; Okazawa, H

1998-01-01

This study investigated whether in patients with internal carotid artery occlusion the regional cerebral hematocrit correlates with cerebral hemodynamics or metabolic state and, if so, how the regional cerebral hematocrit changes in the hemodynamically compromised region. We used positron emission tomography to study seven patients with unilateral internal carotid artery occlusion and no cortical infarction in the chronic stage. The distributions of red blood cell and plasma volumes were assessed using oxygen-15-labeled carbon monoxide and copper-62-labeled human serum albumin-dithiosemicarbazone tracers, respectively. The calculated hematocrit value was compared with the hemodynamic and metabolic parameters measured with the oxygen-15 steady-state technique. In the cerebral cortex, the value of the cerebral hematocrit varied but was correlated with the hemodynamic and metabolic status. Stepwise regression analysis revealed that the large vessel hematocrit, the cerebral metabolic rate of oxygen, and the cerebral blood flow or the oxygen extraction fraction accounted for a significant proportion of variance of the cerebral hematocrit. The oxygen extraction fraction and the cerebral metabolic rate of oxygen negatively correlated with the cerebral hematocrit, whereas the cerebral blood flow correlated positively: patients with reduced blood supply relative to metabolic demand (decreased blood flow with increased oxygen extraction fraction) showed low hematocrit values. In carotid artery occlusion in the chronic stage, regional cerebral hematocrit may vary according to cerebral hemodynamics and metabolic status. Regional cerebral hematocrit may decrease with hemodynamic compromise unless oxygen metabolism concomitantly decreases.

Localization and regulation of mouse pantothenate kinase 2 [The PanK2 Genes of Mouse and Human Specify Proteins with Distinct Subcellular Locations

Energy Technology Data Exchange (ETDEWEB)

Leonardi, Roberta [St. Jude Children' s Research Hospital, Memphis, TN (United States); Zhang, Yong-Mei [St. Jude Children' s Research Hospital, Memphis, TN (United States); Lykidis, Athanasios [DOE Joint Genome Inst., Walnut Creek, CA (United States); Rock, Charles O. [St. Jude Children' s Research Hospital, Memphis, TN (United States); Jackowski, Suzanne [St. Jude Children' s Research Hospital, Memphis, TN (United States)

2007-09-07

Coenzyme A (CoA) biosynthesis is initiated by pantothenatekinase (PanK) and CoA levels are controlled through differentialexpression and feedback regulation of PanK isoforms. PanK2 is amitochondrial protein in humans, but comparative genomics revealed thatacquisition of a mitochondrial targeting signal was limited to primates.Human and mouse PanK2 possessed similar biochemical properties, withinhibition by acetylCoA and activation by palmitoylcarnitine. Mouse PanK2localized in the cytosol, and the expression of PanK2 was higher in humanbrain compared to mouse brain. Differences in expression and subcellularlocalization should be considered in developing a mouse model for humanPanK2 deficiency.

Interactions of mouse pinworms and trichomonads

OpenAIRE

Choutková, Jana

2012-01-01

Oxyurid nematodes Aspiculuris tetraptera and Syphacia obvelata are both common mouse intestinal parasites; in the same location several species of trichomonads occur. Tritrichomonas muris is the most often found, but there are also some others: Tritrichomonas minuta, Pentatrichomonas hominis or Hexamastix muris. It is known that, under some circumstances, trichomonads can be found in the intestine of mouse pinworms, as reported by Theiler and Farber (1936) for T. muris in A. tetraptera and S....

Accesion number Protein name ENOA_MOUSE Alpha-enolase ...

Indian Academy of Sciences (India)

Sandra Feijoo Bandin

Mitochondrial inner membrane protein. CMC1_MOUSE. Calcium-binding mitochondrial carrier protein Aralar1. CMC2_MOUSE. Calcium-binding mitochondrial carrier protein Aralar2. Biological process. Metabolic process. Glycolysis. Lipid metabolism. Respiratory electron transport chain. Others. Calcium ion homeostasis.

[A multi-measure analysis of the similarity, attraction, and compromise effects in multi-attribute decision making].

Science.gov (United States)

Tsuzuki, Takashi; Matsui, Hiroshi; Kikuchi, Manabu

2012-12-01

In multi-attribute decision making, the similarity, attraction, and compromise effects warrant specific investigation as they cause violations of principles in rational choice. In order to investigate these three effects simultaneously, we assigned 145 undergraduates to three context effect conditions. We requested them to solve the same 20 hypothetical purchase problems, each of which had three alternatives described along two attributes. We measured their choices, confidence ratings, and response times. We found that manipulating the third alternative had significant context effects for choice proportions and confidence ratings in all three conditions. Furthermore, the attraction effect was the most prominent with regard to choice proportions. In the compromise effect condition, although the choice proportion of the third alternative was high, the confidence rating was low and the response time was long. These results indicate that the relationship between choice proportions and confidence ratings requires further theoretical investigation. They also suggest that a combination of experimental and modeling studies is imperative to reveal the mechanisms underlying the context effects in multi-attribute, multi-alternative decision making.

Characterization and mapping of the mouse NDP (Norrie disease) locus (Ndp).

Science.gov (United States)

Battinelli, E M; Boyd, Y; Craig, I W; Breakefield, X O; Chen, Z Y

1996-02-01

Norrie disease is a severe X-linked recessive neurological disorder characterized by congenital blindness with progressive loss of hearing. Over half of Norrie patients also manifest different degrees of mental retardation. The gene for Norrie disease (NDP) has recently been cloned and characterized. With the human NDP cDNA, mouse genomic phage libraries were screened for the homolog of the gene. Comparison between mouse and human genomic DNA blots hybridized with the NDP cDNA, as well as analysis of phage clones, shows that the mouse NDP gene is 29 kb in size (28 kb for the human gene). The organization in the two species is very similar. Both have three exons with similar-sized introns and identical exon-intron boundaries between exon 2 and 3. The mouse open reading frame is 393 bp and, like the human coding sequence, is encoded in exons 2 and 3. The absence of six nucleotides in the second mouse exon results in the encoded protein being two amino acids smaller than its human counterpart. The overall homology between the human and mouse NDP protein is 95% and is particularly high (99%) in exon 3, consistent with the apparent functional importance of this region. Analysis of transcription initiation sites suggests the presence of multiple start sites associated with expression of the mouse NDP gene. Pedigree analysis of an interspecific mouse backcross localizes the mouse NDP gene close to Maoa in the conserved segment, which runs from CYBB to PFC in both human and mouse.

Arsenic promotes centrosome abnormalities and cell colony formation in p53 compromised human lung cells

International Nuclear Information System (INIS)

Liao Weiting; Lin Pinpin; Cheng, T.-S.; Yu, H.-S.; Chang, Louis W.

2007-01-01

Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus, an interaction between arsenic and cigarette smoking in lung carcinogenesis was suspected. p53 dysfunction or mutation in lung epithelial cells was frequently observed in cigarette smokers. Our present study was to explore the differential effects by arsenic on H1355 cells (human lung adenocarcinoma cell line with mutation in p53), BEAS-2B (immortalized lung epithelial cell with functional p53) and pifithrin-α-treated BEAS-2B cells (p53-inhibited cells). These cells were treated with different doses of sodium arsenite (0, 0.1, 1, 5 and 10 μM) for 48 h. A greater reduction in cell viability was observed in the BEAS-2B cells vs. p53 compromised cells (H1355 or p53-inhibited BEAS-2B). Similar observation was also made on 7-day cell survival (growth) study. TUNEL analysis confirmed that there was indeed a significantly reduced arsenite-induced apoptosis found in p53-compromised cells. Centrosomal abnormality has been attributed to eventual chromosomal missegregation, aneuploidy and tumorigenesis. In our present study, reduced p21 and Gadd45a expressions and increased centrosomal abnormality (atopic and multiple centrosomes) were observed in both arsenite-treated H1355 and p53-inhibited BEAS-2B cells as compared with similarly treated BEAS-2B cells. Increased anchorage-independent growth (colony formation) of BEAS-2B cells co-treated with pifithrin-α and 5 μM sodium arsenite was also observed in soft agar. Our present investigation demonstrated that arsenic would act specifically on p53 compromised cells (either with p53 dysfunction or inhibited) to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenic, especially under the condition of p53 dysfunction

Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes

NARCIS (Netherlands)

van der Geld, Ymke M.; Hellmark, Thomas; Selga, Daina; Heeringa, Peter; Huitema, Minke G.; Limburg, Pieter C.; Kallenberg, Cees G. M.

2007-01-01

Aim: In this study, we employed chimeric human/ mouse Proteinase 3 ( PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice. Method: Rats and mice were immunised with recombinant human PR3 ( HPR3), recombinant murine PR3 ( mPR3), single chimeric human/ mouse PR3 ( HHm,

Mouse Genome Informatics (MGI)

Data.gov (United States)

U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

Mouse Phenome Database (MPD)

Data.gov (United States)

U.S. Department of Health & Human Services — The Mouse Phenome Database (MPD) has characterizations of hundreds of strains of laboratory mice to facilitate translational discoveries and to assist in selection...

Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects

NARCIS (Netherlands)

Korstanje, Ron; Desai, Jigar; Lazar, Gloria; King, Benjamin; Rollins, Jarod; Spurr, Melissa; Joseph, Jamie; Kadambi, Sindhuja; Li, Yang; Cherry, Allison; Matteson, Paul G.; Paigen, Beverly; Millonig, James H.

Korstanje R, Desai J, Lazar G, King B, Rollins J, Spurr M, Joseph J, Kadambi S, Li Y, Cherry A, Matteson PG, Paigen B, Millonig JH. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol Genomics 35:

Behavioral phenotypes of genetic mouse models of autism.

Science.gov (United States)

Kazdoba, T M; Leach, P T; Crawley, J N

2016-01-01

More than a hundred de novo single gene mutations and copy-number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

International Nuclear Information System (INIS)

Kukat, Alexandra; Edgar, Daniel; Bratic, Ivana; Maiti, Priyanka; Trifunovic, Aleksandra

2011-01-01

Highlights: → Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. → This process is independent of endogenous ROS production. → Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O 2 ) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

Endonucleases : new tools to edit the mouse genome

NARCIS (Netherlands)

Wijshake, Tobias; Baker, Darren J.; van de Sluis, Bart

2014-01-01

Mouse transgenesis has been instrumental in determining the function of genes in the pathophysiology of human diseases and modification of genes by homologous recombination in mouse embryonic stem cells remains a widely used technology. However, this approach harbors a number of disadvantages, as it

Rational Design of Mouse Models for Cancer Research

NARCIS (Netherlands)

Landgraf, M.; McGovern, J.A.; Friedl, P.; Hutmacher, D.W.

2018-01-01

The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models.

Disrupted hippocampal sharp‐wave ripple‐associated spike dynamics in a transgenic mouse model of dementia

Science.gov (United States)

Witton, Jonathan; Staniaszek, Lydia E.; Bartsch, Ullrich; Randall, Andrew D.; Jones, Matthew W.

2015-01-01

Key points High frequency (100–250 Hz) neuronal oscillations in the hippocampus, known as sharp‐wave ripples (SWRs), synchronise the firing behaviour of groups of neurons and play a key role in memory consolidation.Learning and memory are severely compromised in dementias such as Alzheimer's disease; however, the effects of dementia‐related pathology on SWRs are unknown.The frequency and temporal structure of SWRs was disrupted in a transgenic mouse model of tauopathy (one of the major hallmarks of several dementias).Excitatory pyramidal neurons were more likely to fire action potentials in a phase‐locked manner during SWRs in the mouse model of tauopathy; conversely, inhibitory interneurons were less likely to fire phase‐locked spikes during SWRs.These findings indicate there is reduced inhibitory control of hippocampal network events and point to a novel mechanism which may underlie the cognitive impairments in this model of dementia. Abstract Neurons within the CA1 region of the hippocampus are co‐activated during high frequency (100–250 Hz) sharp‐wave ripple (SWR) activity in a manner that probably drives synaptic plasticity and promotes memory consolidation. In this study we have used a transgenic mouse model of dementia (rTg4510 mice), which overexpresses a mutant form of tau protein, to examine the effects of tauopathy on hippocampal SWRs and associated neuronal firing. Tetrodes were used to record simultaneous extracellular action potentials and local field potentials from the dorsal CA1 pyramidal cell layer of 7‐ to 8‐month‐old wild‐type and rTg4510 mice at rest in their home cage. At this age point these mice exhibit neurofibrillary tangles, neurodegeneration and cognitive deficits. Epochs of sleep or quiet restfulness were characterised by minimal locomotor activity and a low theta/delta ratio in the local field potential power spectrum. SWRs detected off‐line were significantly lower in amplitude and had an altered temporal

Tracheostomy in neurologically compromised paediatric patients: role of starplasty.

Science.gov (United States)

Gupta, A; Stokken, J; Krakovitz, P; Malhotra, P; Anne, S

2015-10-01

Starplasty tracheostomy is an alternative to traditional tracheostomy. This paper reviews neurologically compromised paediatric patients with tracheostomies and discusses the role of starplasty tracheostomy. A retrospective review was conducted of paediatric patients with a neurological disorder who underwent tracheostomy between 1997 and 2011. Forty-eight patients, with an average age of 7.3 years, were identified. The most common indications for tracheostomy were: ventilator dependence (39.6 per cent), an inability to tolerate secretions or recurrent aspiration pneumonia (33.3 per cent), and upper respiratory obstruction or hypotonia (12.5 per cent). The most common underlying neurological diagnosis was cerebral palsy. There were no early complications. Eighteen (43 per cent) of 42 patients with follow up experienced at least 1 delayed complication. Only 12 patients (28.6 per cent) were decannulated. Patients with primary neurological diagnoses have low rates of decannulation; starplasty tracheostomy should be considered for these patients. Patients with seizure disorder or acute neurological injury tended to have a higher short-term decannulation rate; traditional tracheostomy is recommended in these patients.

Communication Framework For the Mionix Naos QG Mouse

DEFF Research Database (Denmark)

Wulff-Jensen, Andreas

2017-01-01

The Mionix Naos QG mouse has multiple sensors integrated. It can record all the metrics native to mice: being scroll, clicks and mouse movements. Moreover, this mouse has heart rate (HR) and Galvanic Skin Response (GSR) sensors embedded. Through Mionics API [1] WebSocket can be used to access all...... or be recorded. Another Unity implementation have been developed as well. This was directly connected to the WebSocket, and has the same properties as the first Unity development. Since two nearly identical implementations were made, the quality of their recordings and data communication were tested. Based...

A Comprehensive Atlas of the Adult Mouse Penis

Science.gov (United States)

Phillips, Tiffany R.; Wright, David K.; Gradie, Paul E.; Johnston, Leigh A.; Pask, Andrew J.

2016-01-01

Mice are routinely used to study the development of the external genitalia and, in particular, the process of male urethral closure. This is because misplacement of the male penile urethra, or hypospadias, is amongst the most common birth defects reported in humans. While mice present a tractable model to study penile development, several structures differ between mice and humans, and there is a lack of consensus in the literature on their annotation and developmental origins. Defining the ontology of the mouse prepuce is especially important for the relevance and interpretation of mouse models of hypospadias to human conditions. We have developed a detailed annotation of the adult mouse penis that addresses these differences and enables an accurate comparison of murine and human hypospadias phenotypes. Through MRI data, gross morphology and section histology, we define the origin of the mouse external and internal prepuces, their relationship to the single human foreskin as well as provide a comprehensive view of the various structures of the mouse penis and their associated muscle attachments within the body. These data are combined to annotate structures in a novel 3D adult penis atlas that can be downloaded, viewed at any angle, and manipulated to examine the relationship of various structures. PMID:26112156

The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009.

Science.gov (United States)

Russell, Liane B

2013-01-01

The large mouse genetics program at the Oak Ridge National Laboratory (ORNL) is often remembered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-chromosome's importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a

Effect of computer mouse gain and visual demand on mouse clicking performance and muscle activation in a young and elderly group of experienced computer users

DEFF Research Database (Denmark)

Sandfeld, Jesper; Jensen, Bente R.

2005-01-01

and three levels of target size were used. All subjects demonstrated a reduced working speed and hit rate at the highest mouse gain (1:8) when the target size was small. The young group had an optimum at mouse gain 1:4. The elderly group was most sensitive to the combination of high mouse gain and small...

Mouse endometrial stromal cells produce basement-membrane components

DEFF Research Database (Denmark)

Wewer, U M; Damjanov, A; Weiss, J

1986-01-01

During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations. The dec......During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations....... Mouse decidual cells isolated from 6- to 7-day pregnant uteri explanted in vitro continue to synthesize basement-membrane-like extracellular matrix. Using immunohistochemistry and metabolic labeling followed by immunoprecipitation, SDS-PAGE, and fluorography, it was shown that the decidual cells...... to undergo pseudodecidualization. We thus showed that stromal cells from pregnant and nonpregnant mouse uteri synthesize significant amounts of basement-membrane components in vitro, and hence could serve as a good model for the study of normal basement-membrane components....

Autophagy Deficiency Compromises Alternative Pathways of Respiration following Energy Deprivation in Arabidopsis thaliana.

Science.gov (United States)

Barros, Jessica A S; Cavalcanti, João Henrique F; Medeiros, David B; Nunes-Nesi, Adriano; Avin-Wittenberg, Tamar; Fernie, Alisdair R; Araújo, Wagner L

2017-09-01

Under heterotrophic conditions, carbohydrate oxidation inside the mitochondrion is the primary energy source for cellular metabolism. However, during energy-limited conditions, alternative substrates are required to support respiration. Amino acid oxidation in plant cells plays a key role in this by generating electrons that can be transferred to the mitochondrial electron transport chain via the electron transfer flavoprotein/ubiquinone oxidoreductase system. Autophagy, a catabolic mechanism for macromolecule and protein recycling, allows the maintenance of amino acid pools and nutrient remobilization. Although the association between autophagy and alternative respiratory substrates has been suggested, the extent to which autophagy and primary metabolism interact to support plant respiration remains unclear. To investigate the metabolic importance of autophagy during development and under extended darkness, Arabidopsis ( Arabidopsis thaliana ) mutants with disruption of autophagy ( atg mutants) were used. Under normal growth conditions, atg mutants showed lower growth and seed production with no impact on photosynthesis. Following extended darkness, atg mutants were characterized by signatures of early senescence, including decreased chlorophyll content and maximum photochemical efficiency of photosystem II coupled with increases in dark respiration. Transcript levels of genes involved in alternative pathways of respiration and amino acid catabolism were up-regulated in atg mutants. The metabolite profiles of dark-treated leaves revealed an extensive metabolic reprogramming in which increases in amino acid levels were partially compromised in atg mutants. Although an enhanced respiration in atg mutants was observed during extended darkness, autophagy deficiency compromises protein degradation and the generation of amino acids used as alternative substrates to the respiration. © 2017 American Society of Plant Biologists. All Rights Reserved.

Resistance of human and mouse myeloid leukemia cells to UV radiation

International Nuclear Information System (INIS)

Poljak-Blazi, M.; Osmak, M.; Hadzija, M.

1989-01-01

Sensitivity of mouse bone marrow and myeloid leukemia cells and sensitivity of human myeloid leukemia cells to UV light was tested. Criteria were the in vivo colony-forming ability of UV exposed cells and the inhibition of DNA synthesis during post-irradiation incubation for 24 h in vitro. Mouse bone marrow cells irradiated with a small dose of UV light (5 J/m 2 ) and injected into x-irradiated animals did not form hemopoietic colonies on recipient's spleens, and recipients died. However, mouse leukemia cells, after irradiation with higher doses of UV light, retained the ability to form colonies on the spleens, and all recipient mice died with typical symptoms of leukemia. In vitro, mouse bone marrow cells exhibited high sensitivity to UV light compared to mouse myeloid leukemia cells. Human leukemia cells were also resistant to UV light, but more sensitive than mouse leukemia cells. (author)

Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha

Science.gov (United States)

DOKI, Tomoyoshi; TAKANO, Tomomi; HOHDATSU, Tsutomu

2016-01-01

Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2–4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2–4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2–4) by fusing the variable region of mouse mAb 2–4 to the constant region of feline antibody. The chimeric mAb 2–4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2–4 and chimeric mAb 2–4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2–4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2–4 was reduced. In contrast, in cats treated with chimeric mAb 2–4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2–4-treated cats. PMID:27264736

Single-mass mutations associated with mouse lymphomas

International Nuclear Information System (INIS)

Guerrero, I.; Berman, J.W.; Diamond, L.E.; Newcomb, E.W.; Villasante, A.

1986-01-01

The authors study the induction of mouse lymphomas after treatment with a chemical carcinogen, nitrosomethyl urea (NMU), or with gamma irradiation. The koplan fractionated gamma radiation scheme and an established protocol for NMU tumor formation were chosen as protocols for induction of mouse lymphomas. In both cases, the mice developed thymic lymphomas with up to 90% incidence. In NMU induction, the latency period is shorter than irradiation

Safety and Efficacy of Alginate Adhesion Barrier Gel in Compromised Intestinal Anastomosis.

Science.gov (United States)

Chaturvedi, Ankit A; Yauw, Simon T K; Lomme, Roger M L M; Hendriks, Thijs; van Goor, Harry

For any anti-adhesive barrier developed for abdominal surgery, the use under conditions in which anastomotic healing is compromised needs to be investigated. The current study evaluates the effect of a new ultrapure alginate gel on early healing of high-risk anastomoses in the ileum and compares this with the gold standard used in clinical practice. In 75 adult male Wistar rats, a 5 mm ileal segment was resected and continuity was restored by construction of an inverted anastomosis. Rats were divided randomly into a control group and groups receiving either alginate gel or a sodium hyaluronate carboxymethylcellulose (HA/CMC) film around the anastomosis (n = 25 each). Carprofen, given in a daily dose of 1.25 mg/kg, was used to compromise anastomotic healing. At day three, animals were killed and scored for signs of anastomotic leakage and the presence of adhesions. The incidence of adhesion formation was 95% in the HA/CMC film group, which was significantly higher than in the controls (64%, p = 0.010) and the alginate gel group (52%, p = 0.004). The adhesion score was nearly 40% lower in the alginate gel group compared with the HA/CMC film group. The incidence of ileal leakage in the HA/CMC film group (92%) was significantly higher than in the controls (68%, p = 0.016). Leakage rate did not differ between the alginate gel and control groups. There was no significant difference between groups in either incision bursting pressure or incision breaking strength. Ultrapure alginate gel does not interfere with repair of ileal anastomoses constructed under conditions in which chances of anastomotic dehiscence are high. The alginate gel performs better than the HA/CMC film.

SENP3 grants tight junction integrity and cytoskeleton architecture in mouse Sertoli cells.

Science.gov (United States)

Wu, Di; Huang, Chun-Jie; Khan, Faheem Ahmed; Jiao, Xiao-Fei; Liu, Xiao-Ming; Pandupuspitasari, Nuruliarizki Shinta; Brohi, Rahim Dad; Huo, Li-Jun

2017-08-29

Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation. SENP3 is predominantly expressed in the nucleus of Sertoli and spermatocyte cells in adult mouse testis, and knockdown of SENP3 compromises tight junction in Sertoli cells by destructing the permeability function with a concomitant decline in trans-epithelial electrical resistance in primary Sertoli cells, which could attribute to the conspicuous dysfunction of tight junction (TJ) proteins (e.g., ZO-1, occludin) at the cell-cell interface due to the inactivation of STAT3. Moreover, SENP3 knockdown disrupts F-actin architecture in Sertoli cells through intervening Rac1/CDC42-N-WASP-Arp2/3 signaling pathway and Profilin-1 abundance. Our study pinpoints SENP3 might be a novel determinant of multiple pathways governing BTB dynamics in testis to support germ cells development in mammals.

Spallanzani's mouse: a model of restoration and regeneration.

Science.gov (United States)

Heber-Katz, E; Leferovich, J M; Bedelbaeva, K; Gourevitch, D

2004-01-01

The ability to regenerate is thought to be a lost phenotype in mammals, though there are certainly sporadic examples of mammalian regeneration. Our laboratory has identified a strain of mouse, the MRL mouse, which has a unique capacity to heal complex tissue in an epimorphic fashion, i.e., to restore a damaged limb or organ to its normal structure and function. Initial studies using through-and-through ear punches showed rapid full closure of the ear holes with cartilage growth, new hair follicles, and normal tissue architecture reminiscent of regeneration seen in amphibians as opposed to the scarring usually seen in mammals. Since the ear hole closure phenotype is a quantitative trait, this has been used to show-through extensive breeding and backcrossing--that the trait is heritable. Such analysis reveals that there is a complex genetic basis for this trait with multiple loci. One of the major phenotypes of the MRL mouse is a potent remodeling response with the absence or a reduced level of scarring. MRL healing is associated with the upregulation of the metalloproteinases MMP-2 and MMP-9 and the downregulation of their inhibitors TIMP-2 and TIMP-3, both present in inflammatory cells such as neutrophils and macrophages. This model has more recently been extended to the heart. In this case, a cryoinjury to the right ventricle leads to near complete scarless healing in the MRL mouse whereas scarring is seen in the control mouse. In the MRL heart, bromodeoxyuridine uptake by cardiomyocytes filling the wound site can be seen 60 days after injury. This does not occur in the control mouse. Function in the MRL heart, as measured by echocardiography, returns to normal.

Phenotypic compromises in a long-distance migrant during the transition from migration to reproduction in the High Arctic

NARCIS (Netherlands)

Vezina, Francois; Williams, Tony D.; Piersma, Theunis; Morrison, R. I. Guy; Dawson, Alistair

1. Seasonal carry-over effects may be important structuring components of avian life-history cycles. However, little is known on physiological transitions between stages and on phenotypic compromises that may be made at such time to improve fitness. 2. We studied postmigratory body remodelling in

First trimester serum placental growth factor and hyperglycosylated human chorionic gonadotropin are associated with pre-eclampsia: a case control study.

Science.gov (United States)

Keikkala, Elina; Koskinen, Sini; Vuorela, Piia; Laivuori, Hannele; Romppanen, Jarkko; Heinonen, Seppo; Stenman, Ulf-Håkan

2016-11-25

To study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors. Gestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8-13 weeks of gestation. The case-control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls. Of 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis factors.

Meeting Report: The Twelfth International Mouse Genome Conference

Energy Technology Data Exchange (ETDEWEB)

Manolakou, Katerina; Cross, Sally H.; Simpson, Eleanor H.; Jackson, Ian J.

1998-10-01

The annual International Mouse Genome Conference (IMGC) is where, scientifically speaking, classical mouse genetics meets the relative newcomer of genomics. The 12th meeting took place last October in the delightful Bavarian village of Garmisch-Partenkirchen, and we were greeted by the sight on the mountains of the first snowfall of the season. However the discussions left little time for exploration. Minds of participants in Garmisch were focused by a recent document produced by the NIH and by discussions within other funding agencies worldwide. If implemented, the proposals will further enhance the status of the mouse as the principal model for study of the function of the human genome.

Methods of in-vivo mouse lung micro-CT

Science.gov (United States)

Recheis, Wolfgang A.; Nixon, Earl; Thiesse, Jacqueline; McLennan, Geoffrey; Ross, Alan; Hoffman, Eric

2005-04-01

Micro-CT will have a profound influence on the accumulation of anatomical and physiological phenotypic changes in natural and transgenetic mouse models. Longitudinal studies will be greatly facilitated, allowing for a more complete and accurate description of events if in-vivo studies are accomplished. The purpose of the ongoing project is to establish a feasible and reproducible setup for in-vivo mouse lung micro-computed tomography (μCT). We seek to use in-vivo respiratory-gated μCT to follow mouse models of lung disease with subsequent recovery of the mouse. Methodologies for optimizing scanning parameters and gating for the in-vivo mouse lung are presented. A Scireq flexiVent ventilated the gas-anesthetized mice at 60 breaths/minute, 30 cm H20 PEEP, 30 ml/kg tidal volume and provided a respiratory signal to gate a Skyscan 1076 μCT. Physiologic monitoring allowed the control of vital functions and quality of anesthesia, e.g. via ECG monitoring. In contrary to longer exposure times with ex-vivo scans, scan times for in-vivo were reduced using 35μm pixel size, 158ms exposure time and 18μm pixel size, 316ms exposure time to reduce motion artifacts. Gating via spontaneous breathing was also tested. Optimal contrast resolution was achieved at 50kVp, 200μA, applying an aluminum filter (0.5mm). There were minimal non-cardiac related motion artifacts. Both 35μm and 1μm voxel size images were suitable for evaluation of the airway lumen and parenchymal density. Total scan times were 30 and 65 minutes respectively. The mice recovered following scanning protocols. In-vivo lung scanning with recovery of the mouse delivered reasonable image quality for longitudinal studies, e.g. mouse asthma models. After examining 10 mice, we conclude μCT is a feasible tool evaluating mouse models of lung pathology in longitudinal studies with increasing anatomic detail available for evaluation as one moves from in-vivo to ex-vivo studies. Further developments include automated

Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection

Directory of Open Access Journals (Sweden)

Elena Ufimtseva

2015-01-01

Full Text Available Tuberculosis (TB is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.

Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection

Science.gov (United States)

2015-01-01

Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals. PMID:26064970

Identifying compromised systems through correlation of suspicious traffic from malware behavioral analysis

Science.gov (United States)

Camilo, Ana E. F.; Grégio, André; Santos, Rafael D. C.

2016-05-01

Malware detection may be accomplished through the analysis of their infection behavior. To do so, dynamic analysis systems run malware samples and extract their operating system activities and network traffic. This traffic may represent malware accessing external systems, either to steal sensitive data from victims or to fetch other malicious artifacts (configuration files, additional modules, commands). In this work, we propose the use of visualization as a tool to identify compromised systems based on correlating malware communications in the form of graphs and finding isomorphisms between them. We produced graphs from over 6 thousand distinct network traffic files captured during malware execution and analyzed the existing relationships among malware samples and IP addresses.

The Mouse SAGE Site: database of public mouse SAGE libraries

Czech Academy of Sciences Publication Activity Database

Divina, Petr; Forejt, Jiří

2004-01-01

Roč. 32, - (2004), s. D482-D483 ISSN 0305-1048 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015 Grant - others:HHMI(US) 555000306 Institutional research plan: CEZ:AV0Z5052915 Keywords : mouse SAGE libraries * web -based database Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.260, year: 2004

Mouse manipulation through single-switch scanning.

Science.gov (United States)

Blackstien-Adler, Susie; Shein, Fraser; Quintal, Janet; Birch, Shae; Weiss, Patrice L Tamar

2004-01-01

Given the current extensive reliance on the graphical user interface, independent access to computer software requires that users be able to manipulate a pointing device of some type (e.g., mouse, trackball) or be able to emulate a mouse by some other means (e.g., scanning). The purpose of the present study was to identify one or more optimal single-switch scanning mouse emulation strategies. Four alternative scanning strategies (continuous Cartesian, discrete Cartesian, rotational, and hybrid quadrant/continuous Cartesian) were selected for testing based on current market availability as well as on theoretical considerations of their potential speed and accuracy. Each strategy was evaluated using a repeated measures study design by means of a test program that permitted mouse emulation via any one of four scanning strategies in a motivating environment; response speed and accuracy could be automatically recorded and considered in view of the motor, cognitive, and perceptual demands of each scanning strategy. Ten individuals whose disabilities required them to operate a computer via single-switch scanning participated in the study. Results indicated that Cartesian scanning was the preferred and most effective scanning strategy. There were no significant differences between results from the Continuous Cartesian and Discrete Cartesian scanning strategies. Rotational scanning was quite slow with respect to the other strategies, although it was equally accurate. Hybrid Quadrant scanning improved access time but at the cost of fewer correct selections. These results demonstrated the importance of testing and comparing alternate single-switch scanning strategies.

Effect of potassium channel modulators in mouse forced swimming test

Science.gov (United States)

Galeotti, Nicoletta; Ghelardini, Carla; Caldari, Bernardetta; Bartolini, Alessandro

1999-01-01

The effect of intracerebroventricular (i.c.v.) administration of different potassium channel blockers (tetraethylammonium, apamin, charybdotoxin, gliquidone), potassium channel openers (pinacidil, minoxidil, cromakalim) and aODN to mKv1.1 on immobility time was evaluated in the mouse forced swimming test, an animal model of depression. Tetraethylammonium (TEA; 5 μg per mouse i.c.v.), apamin (3 ng per mouse i.c.v.), charybdotoxin (1 μg per mouse i.c.v.) and gliquidone (6 μg per mouse i.c.v.) administered 20 min before the test produced anti-immobility comparable to that induced by the tricyclic antidepressants amitriptyline (15 mg kg−1 s.c.) and imipramine (30 mg kg−1 s.c.). By contrast pinacidil (10–20 μg per mouse i.c.v.), minoxidil (10–20 μg per mouse i.c.v.) and cromakalim (20–30 μg per mouse i.c.v.) increased immobility time when administered in the same experimental conditions. Repeated administration of an antisense oligonucleotide (aODN) to the mKv1.1 gene (1 and 3 nmol per single i.c.v. injection) produced a dose-dependent increase in immobility time of mice 72 h after the last injection. At day 7, the increasing effect produced by aODN disappeared. A degenerate mKv1.1 oligonucleotide (dODN), used as control, did not produce any effect in comparison with saline- and vector-treated mice. At the highest effective dose, potassium channels modulators and the mKv1.1 aODN did not impair motor coordination, as revealed by the rota rod test, nor did they modify spontaneous motility as revealed by the Animex apparatus. These results suggest that modulation of potassium channels plays an important role in the regulation of immobility time in the mouse forced swimming test. PMID:10323599

Protecting Privacy of Shared Epidemiologic Data without Compromising Analysis Potential

Directory of Open Access Journals (Sweden)

John Cologne

2012-01-01

Full Text Available Objective. Ensuring privacy of research subjects when epidemiologic data are shared with outside collaborators involves masking (modifying the data, but overmasking can compromise utility (analysis potential. Methods of statistical disclosure control for protecting privacy may be impractical for individual researchers involved in small-scale collaborations. Methods. We investigated a simple approach based on measures of disclosure risk and analytical utility that are straightforward for epidemiologic researchers to derive. The method is illustrated using data from the Japanese Atomic-bomb Survivor population. Results. Masking by modest rounding did not adequately enhance security but rounding to remove several digits of relative accuracy effectively reduced the risk of identification without substantially reducing utility. Grouping or adding random noise led to noticeable bias. Conclusions. When sharing epidemiologic data, it is recommended that masking be performed using rounding. Specific treatment should be determined separately in individual situations after consideration of the disclosure risks and analysis needs.

Protecting Privacy of Shared Epidemiologic Data without Compromising Analysis Potential

International Nuclear Information System (INIS)

Cologne, J.; Nakashima, E.; Funamoto, S.; Grant, E.J.; Chen, Y.; Hiroaki Katayama, H.

2012-01-01

Objective. Ensuring privacy of research subjects when epidemiologic data are shared with outside collaborators involves masking (modifying) the data, but over masking can compromise utility (analysis potential). Methods of statistical disclosure control for protecting privacy may be impractical for individual researchers involved in small-scale collaborations. Methods. We investigated a simple approach based on measures of disclosure risk and analytical utility that are straightforward for epidemiologic researchers to derive. The method is illustrated using data from the Japanese Atomic-bomb Survivor population. Results. Masking by modest rounding did not adequately enhance security but rounding to remove several digits of relative accuracy effectively reduced the risk of identification without substantially reducing utility. Grouping or adding random noise led to noticeable bias. Conclusions. When sharing epidemiologic data, it is recommended that masking be performed using rounding. Specific treatment should be determined separately in individual situations after consideration of the disclosure risks and analysis needs

Chromosomal localization of the human and mouse hyaluronan synthase genes

Energy Technology Data Exchange (ETDEWEB)

Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Seldin, M.F. [Univ. of California Davis, CA (United States)] [and others

1997-05-01

We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17. HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome. 33 refs., 2 figs.

Comparison of three mouse strains by radiosensitivity of hemato-immune system

International Nuclear Information System (INIS)

Li, Deguan; Wu, Hongying; Wang, Yong; Zhang, Junling; Wang, Yueying; Lu, Lu; Meng, Aimin

2008-01-01

IRM-2, developed in our Lab, is an inbred strain mouse created by cross of a ICR/JCL female and 615 male mouse. Compared to the parent strains, the IRM-2 mouse exhibit increased resistance to radiation. We examine the damage of hemato-immune system induced by radiation in IRM-2, ICR and 615 mice in order to elucidate the radiation resistant mechanism of IRM-2 mouse. The hemato-immune function and radiosensitivities of three mouse strains (IRM-2, ICR/JCL, 615) have been compared using the following parameters: the white blood cells (WBC) in peripheral blood (PB), the bone marrow nucleated cells (BMC) per femur. Percent of phagocytosis of peritoneal macrophage (PM) was checked by chicken red blood cells. Lymphocyte phenotype in PB were analyzed by flow cytometry. Damage induced by radiation were analysed in the bone marrows cells, splenocytes and thymocyte exposed to irradiation in vitro by cell viability assay (ATP Bioluminescence assay) and apoptosis assay (Annexin V/PI). The WBC and BMC of IRM-2 mice were significantly higher than those in ICR mice and 615 mice, respectively (P<0.01). The ratio of CD4/CD8 in PB of IRM-2 mouse was lower than those in ICR and 615, P<0.01. Cell viability showed difference after 18 hs incubation post radiation in three mouse strains. The results of our primary study suggest that the hemato-immune function in IRM-2 mouse is different to its parent strains. The IRM-2 mouse provides an animal model to conducted further investigation to explore the role of hemato-immune system in radiation resistance. (author)

Immunohistochemical visualization of mouse interneuron subtypes

DEFF Research Database (Denmark)

Jensen, Simon Mølgaard; Ulrichsen, Maj; Boggild, Simon

2014-01-01

, and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies...... of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, stainings with high signal-to-noise ratios and location...

Phenotypic compromises in a long-distance migrant during the transition from migration to reproduction in the High Arctic

NARCIS (Netherlands)

Vézina, F.; Williams, T.D.; Piersma, T.; Morrison, R.I.G.

2012-01-01

1. Seasonal carry-over effects may be important structuring components of avian life-history cycles. However, little is known on physiological transitions between stages and on phenotypic compromises that may be made at such time to improve fitness.
2. We studied postmigratory body remodelling in

A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

Directory of Open Access Journals (Sweden)

Matthew E. Brown

2018-04-01

Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

Astonishing advances in mouse genetic tools for biomedical research.

Science.gov (United States)

Kaczmarczyk, Lech; Jackson, Walker S

2015-01-01

The humble house mouse has long been a workhorse model system in biomedical research. The technology for introducing site-specific genome modifications led to Nobel Prizes for its pioneers and opened a new era of mouse genetics. However, this technology was very time-consuming and technically demanding. As a result, many investigators continued to employ easier genome manipulation methods, though resulting models can suffer from overlooked or underestimated consequences. Another breakthrough, invaluable for the molecular dissection of disease mechanisms, was the invention of high-throughput methods to measure the expression of a plethora of genes in parallel. However, the use of samples containing material from multiple cell types could obfuscate data, and thus interpretations. In this review we highlight some important issues in experimental approaches using mouse models for biomedical research. We then discuss recent technological advances in mouse genetics that are revolutionising human disease research. Mouse genomes are now easily manipulated at precise locations thanks to guided endonucleases, such as transcription activator-like effector nucleases (TALENs) or the CRISPR/Cas9 system, both also having the potential to turn the dream of human gene therapy into reality. Newly developed methods of cell type-specific isolation of transcriptomes from crude tissue homogenates, followed by detection with next generation sequencing (NGS), are vastly improving gene regulation studies. Taken together, these amazing tools simplify the creation of much more accurate mouse models of human disease, and enable the extraction of hitherto unobtainable data.

Growth and production kinetics of human x mouse and mouse hybridoma cells at reduced temperature and serum content.

Science.gov (United States)

Borth, N; Heider, R; Assadian, A; Katinger, H

1992-09-01

The growth and production kinetics of a mouse hybridoma cell line and a human-mouse heterohybridoma were analyzed under conditions of reduced temperature and serum content. The mouse hybridoma P24 had a constant cell specific production rate and RNA content, while the heterohybridoma 3D6-LC4 showed growth associated production kinetics and an increased RNA content at higher growth rates. This behaviour of 3D6-LC4 cells can be explained by the unusual cell cycle kinetics of this line, which can be arrested in any phase under growth limiting conditions, so that a low growth rate does not result in a greater portion of high producing G1-phase cells. Substrate limitation changes the cell cycle distribution of this cell line to a greater extent than low temperature or serum content, which indicates that this stress factor exerts a greater physiological control than assumed.

Simple and efficient expression of codon-optimized mouse leukemia ...

African Journals Online (AJOL)

Purpose: To obtain a higher yield of mouse leukemia inhibitory factor to maintain the proliferation potential of pluripotent ... It induces mouse myeloid leukemic M1 cells of terminal ... induces the production of acute phase proteins by lipocyte ...

Identifying and Embedding Common Indicators of Compromise in Virtual Machines for Lab-Based Incident Response Education

Science.gov (United States)

2015-09-01

as an ever more popular method of exploiting hosts. Because the Internet is used for things like ecommerce , trading, voting, government, services...HTTP hypertext transfer protocol IE Internet Explorer IMAP Internet message access protocol IOC indicators of compromise IP Internet protocol MD5...notification of detection. These questions not only deal with how an incident is detected, but with the detection system itself. Things like whether

An update on the mouse liver proteome

Directory of Open Access Journals (Sweden)

Borlak Jürgen

2009-09-01

Full Text Available Abstract Background Decoding of the liver proteome is subject of intense research, but hampered by methodological constraints. We recently developed an improved protocol for studying rat liver proteins based on 2-DE-MALDI-TOF-MS peptide mass finger printing. This methodology was now applied to develop a mouse liver protein database. Results Liver proteins were extracted by two different lysis buffers in sequence followed by a liquid-phase IEF pre-fractionation and separation of proteins by 2 DE at two different pH ranges, notably 5-8 and 7-10. Based on 9600 in gel digests a total of 643 mouse liver proteins with high sequence coverage (> 20 peptides per protein could be identified by MALDI-TOF-MS peptide mass finger printing. Notably, 255 proteins are novel and have not been reported so far by conventional two-dimensional electrophoresis proteome mapping. Additionally, the results of the present findings for mouse liver were compared to published data of the rat proteome to compile as many proteins as possible in a rodent liver database. Conclusion Based on 2-DE MALDI-TOF-MS a significantly improved proteome map of mouse liver was obtained. We discuss some prominent members of newly identified proteins for a better understanding of liver biology.

Colonization, mouse-style

Directory of Open Access Journals (Sweden)

Searle Jeremy B

2010-10-01

Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

Characteristics of the mouse genomic histamine H1 receptor gene

Energy Technology Data Exchange (ETDEWEB)

Inoue, Isao; Taniuchi, Ichiro; Kitamura, Daisuke [Kyushu Univ., Fukuoka (Japan)] [and others

1996-08-15

We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. 12 refs., 3 figs.

The Mouse House: A brief history of the ORNL mouse-genetics program, 1947–2009

Energy Technology Data Exchange (ETDEWEB)

Russell, Liane B.

2013-10-01

The large mouse genetics program at the Oak Ridge National Lab is often re-membered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-Chromosome s importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a valuable

Downregulation of mouse CCR3 by lentiviral shRNA inhibits proliferation and induces apoptosis of mouse eosinophils.

Science.gov (United States)

Zhu, Xin-Hua; Liao, Bing; Xu, Yi; Liu, Ke; Huang, Yun; Huang, Quan-Long; Liu, Yue-Hui

2017-02-01

RNA interference has been considered as an effective gene silencing method in basic and preclinical investigations. The aims of the present study were to construct a lentiviral vector expressing a short hairpin RNA (shRNA) targeting the murine CC chemokine receptor 3 (mCCR3), and to investigate its effects on the proliferation and apoptosis of mouse eosinophils. A recombinant lentiviral vector expressing four fragments of mouse CCR3 shRNA (pLVX‑mCCR3‑1+2+3+4‑shRNA) was constructed using subcloning techniques. This novel lentivirus was then packaged into 293T cells by co‑transduction with plasmids, including Baculo p35, pCMV R8.2 and VSV. The interference effects of the vector were verified using polymerase chain reaction (PCR) and western blot analyses. The effects of the interference on the proliferation and apoptosis of mouse eosinophils were investigated using 3‑(4,5‑dimethylthiazol‑2‑yl)‑5‑(3‑carboxymethoxyphenyl)‑2‑(4‑sulfophenyl)‑2H‑tetrazolium and terminal deoxynucleotidyl transferase dUTP nick end labeling methods, respectively. The results of the PCR and western blot analyses confirmed that the novel recombinant vector, pLVX‑mCCR3‑1+2+3+4‑shRNA, had high efficiency in inhibiting the mRNA and protein expression levels of mCCR3 in mouse eosinophils. The downregulation of mCCR3 significantly inhibited proliferation of the eosinophils. Furthermore, the present study found that the downregulation of mCCR3 significantly promoted apoptosis of the eosinophils. Therefore, the downregulation of mCCR3 led to the inhibition of proliferation and induction of apoptosis in mouse eosinophils. The predominant characteristics of allergic rhinitis are eosinophil infiltration and release of inflammatory mediators, which appear in a variety of clinical manifestations. The results of the present study indicate that mCCR3 silencing may serve as a putative approach for the treatment of allergic rhinitis.

Suppression of mouse-killing in rats following irradiation

International Nuclear Information System (INIS)

O'Boyle, M.

1976-01-01

Suppression of mouse-killing was produced following pairings of mouse-presentations (CS) with 96 roentgens of ionizing radiation (US) at 0 (less than 2 min.) and 30 min. US-CS interstimulus intervals. No suppression was found at CS-US intervals of 30 min., 1 hr., and 2 hr., or at US-CS intervals of 1 hr. and 2 hr

Compromised careers: the occupational transition of immigration and resettlement.

Science.gov (United States)

Suto, Melinda

2009-01-01

Work is a significant occupational transition that occurs with immigration and resettlement. Problems finding work and regaining economic capital are multi-factorial, differentiated by gender and mediated by specific contexts. Surprisingly, past education and work experience are unreliable predictors of successful employment outcomes. Critical theory and ethnographic concepts informed the methodological approach. Data were generated primarily through in-depth interviews, conducted in English, with 14 well-educated women who immigrated to Canada as adults and sought employment in their professions. The thematic findings were analyzed using Bourdieu's [7] concepts of capital, field and habitus. The theme Compromised Careers describes the downward occupational (work) mobility that occurs despite expectations that education, credentials and work experience are transferable to desirable employment. A devaluation of foreign qualifications and no relevant Canadian work experience function with gendered responsibilities, less social support, and time spent in resettlement activities to create negative work trajectories. The role that federal policies and professional organizations play is examined to reveal the tension between individuals' efforts to find employment and institutional barriers that impede these actions. A critical inquiry approach examined the ruling relations to show how power and privilege function in relation to migrants' occupational transitions.

Gene expression and functional annotation of the human and mouse choroid plexus epithelium.

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Sarah F Janssen

Full Text Available BACKGROUND: The choroid plexus epithelium (CPE is a lobed neuro-epithelial structure that forms the outer blood-brain barrier. The CPE protrudes into the brain ventricles and produces the cerebrospinal fluid (CSF, which is crucial for brain homeostasis. Malfunction of the CPE is possibly implicated in disorders like Alzheimer disease, hydrocephalus or glaucoma. To study human genetic diseases and potential new therapies, mouse models are widely used. This requires a detailed knowledge of similarities and differences in gene expression and functional annotation between the species. The aim of this study is to analyze and compare gene expression and functional annotation of healthy human and mouse CPE. METHODS: We performed 44k Agilent microarray hybridizations with RNA derived from laser dissected healthy human and mouse CPE cells. We functionally annotated and compared the gene expression data of human and mouse CPE using the knowledge database Ingenuity. We searched for common and species specific gene expression patterns and function between human and mouse CPE. We also made a comparison with previously published CPE human and mouse gene expression data. RESULTS: Overall, the human and mouse CPE transcriptomes are very similar. Their major functionalities included epithelial junctions, transport, energy production, neuro-endocrine signaling, as well as immunological, neurological and hematological functions and disorders. The mouse CPE presented two additional functions not found in the human CPE: carbohydrate metabolism and a more extensive list of (neural developmental functions. We found three genes specifically expressed in the mouse CPE compared to human CPE, being ACE, PON1 and TRIM3 and no human specifically expressed CPE genes compared to mouse CPE. CONCLUSION: Human and mouse CPE transcriptomes are very similar, and display many common functionalities. Nonetheless, we also identified a few genes and pathways which suggest that the CPE

The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines.

Science.gov (United States)

Stanley, Joanna L; Lincoln, Rachael J; Brown, Terry A; McDonald, Louise M; Dawson, Gerard R; Reynolds, David S

2005-05-01

The mouse rotarod test of motor coordination/sedation is commonly used to predict clinical sedation caused by novel drugs. However, past experience suggests that it lacks the desired degree of sensitivity to be predictive of effects in humans. For example, the benzodiazepine, bretazenil, showed little impairment of mouse rotarod performance, but marked sedation in humans. The aim of the present study was to assess whether the mouse beam walking assay demonstrates: (i) an increased sensitivity over the rotarod and (ii) an increased ability to predict clinically sedative doses of benzodiazepines. The study compared the effects of the full benzodiazepine agonists, diazepam and lorazepam, and the partial agonist, bretazenil, on the mouse rotarod and beam walking assays. Diazepam and lorazepam significantly impaired rotarod performance, although relatively high GABA-A receptor occupancy was required (72% and 93%, respectively), whereas beam walking performance was significantly affected at approximately 30% receptor occupancy. Bretazenil produced significant deficits at 90% and 53% receptor occupancy on the rotarod and beam walking assays, respectively. The results suggest that the mouse beam walking assay is a more sensitive tool for determining benzodiazepine-induced motor coordination deficits than the rotarod. Furthermore, the GABA-A receptor occupancy values at which significant deficits were determined in the beam walking assay are comparable with those observed in clinical positron emission tomography studies using sedative doses of benzodiazepines. These data suggest that the beam walking assay may be able to more accurately predict the clinically sedative doses of novel benzodiazepine-like drugs.

Enhancement of mouse sperm motility by trophinin-binding peptide

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Park Seong

2012-11-01

Full Text Available Abstract Background Trophinin is an intrinsic membrane protein that forms a complex in the cytoplasm with bystin and tastin, linking it microtubule-associated motor dynein (ATPase in some cell types. Previously, we found that human sperm tails contain trophinin, bystin and tastin proteins, and that trophinin-binding GWRQ (glycine, tryptophan, arginine, glutamine peptide enhanced motility of human sperm. Methods Immunohistochemistry was employed to determine trophinin protein in mouse spermatozoa from wild type mouse, by using spermatozoa from trophinin null mutant mice as a negative control. Multivalent 8-branched GWRQ (glycine, tryptophan, arginine, glutamine peptide or GWRQ-MAPS, was chemically synthesized, purified by HPLC and its structure was confirmed by MALDI-TOF mass spectrometry. Effect of GWRQ-MAPS on mouse spermatozoa from wild type and trophinin null mutant was assessed by a computer-assisted semen analyzer (CASA. Results Anti-trophinin antibody stained the principal (central piece of the tail of wild type mouse sperm, whereas the antibody showed no staining on trophinin null sperm. Phage particles displaying GWRQ bound to the principal piece of sperm tail from wild type but not trophinin null mice. GWRQ-MAPS enhanced motility of spermatozoa from wild type but not trophinin null mice. CASA showed that GWRQ-MAPS enhanced both progressive motility and rapid motility in wild type mouse sperm. Conclusions Present study established the expression of trophinin in the mouse sperm tail and trophinin-dependent effect of GWRQ-MAPS on sperm motility. GWRQ causes a significant increase in sperm motility.

Mouse ATP-Binding Cassette (ABC) Transporters Conferring Multi-Drug Resistance

Science.gov (United States)

Shuaizhang, L I; Zhang, Wen; Yin, Xuejiao; Xing, Shilai; Xie, Qunhui; Cao, Zhengyu; Zhao, Bin

2015-04-28

The ABC (ATP-binding cassette) transporter is one of the largest and most ancient protein families with members functioning from protozoa to human. The resistance of cancer and tumor cells to anticancer drugs is due to the over-expression of some ABC transporters, which may finally lead to chemotherapy failure. The mouse ABC transporters are classified into seven subfamilies by phylogenetic analysis. The mouse ABC transporter gene, alias, chromosomal location and function have been determined. Within the ABC super-family, the MDR transporters (Abcb1, Abcc1, Abcg2) in mouse models have been proved to be valuable to investigate the biochemistry and physiological functions. This review concentrates on the multidrug resistance of mouse ABC transporters in cancer and tumor cells.

Infra Red 3D Computer Mouse

DEFF Research Database (Denmark)

Harbo, Anders La-Cour; Stoustrup, Jakob

2000-01-01

The infra red 3D mouse is a three dimensional input device to a computer. It works by determining the position of an arbitrary object (like a hand) by emitting infra red signals from a number of locations and measuring the reflected intensities. To maximize stability, robustness, and use of bandw......The infra red 3D mouse is a three dimensional input device to a computer. It works by determining the position of an arbitrary object (like a hand) by emitting infra red signals from a number of locations and measuring the reflected intensities. To maximize stability, robustness, and use...

High-throughput mouse genotyping using robotics automation.

Science.gov (United States)

Linask, Kaari L; Lo, Cecilia W

2005-02-01

The use of mouse models is rapidly expanding in biomedical research. This has dictated the need for the rapid genotyping of mutant mouse colonies for more efficient utilization of animal holding space. We have established a high-throughput protocol for mouse genotyping using two robotics workstations: a liquid-handling robot to assemble PCR and a microfluidics electrophoresis robot for PCR product analysis. This dual-robotics setup incurs lower start-up costs than a fully automated system while still minimizing human intervention. Essential to this automation scheme is the construction of a database containing customized scripts for programming the robotics workstations. Using these scripts and the robotics systems, multiple combinations of genotyping reactions can be assembled simultaneously, allowing even complex genotyping data to be generated rapidly with consistency and accuracy. A detailed protocol, database, scripts, and additional background information are available at http://dir.nhlbi.nih.gov/labs/ldb-chd/autogene/.

Providing training enhances the biomechanical improvements of an alternative computer mouse design

NARCIS (Netherlands)

Houwink, A.; Oude Hengel, K.M.; Odell, D.; Dennerlein, J.T.

2009-01-01

To determine if an alternative mouse promotes more neutral postures and decreases forearm muscle activity and if training enhances these biomechanical benefits is the purpose of the study. Computer mouse use is a risk factor for developing musculoskeletal disorders; alternative mouse designs can

Mouse Vocal Communication System: Are Ultrasounds Learned or Innate?

Science.gov (United States)

Arriaga, Gustavo; Jarvis, Erich D.

2013-01-01

Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production.…

The effect of minimal concentration of ethylene glycol (EG) combined with polyvinylpyrrolidone (PVP) on mouse oocyte survival and subsequent embryonic development following vitrification.

Science.gov (United States)

Wang, Yao; Okitsu, Osamu; Zhao, Xiao-Ming; Sun, Yun; Di, Wen; Chian, Ri-Cheng

2014-01-01

Vitrification techniques employ a relatively high concentration of cryoprotectant in vitrification solutions. Exposure of oocytes to high concentrations of cryoprotectant is known to damage the oocytes via both cytotoxic and osmotic effects. Therefore, the key to successful vitrification of oocytes is to strike a balance between the usage of minimal concentration of cryoprotectant without compromising their cryoprotective actions. The minimal concentration of ethylene glycol (EG) on mouse oocyte survival and subsequent embryonic development was evaluated following vitrification-warming and parthenogenetic activation. Polyvinylpyrrolidone (PVP) combined with EG on mouse oocyte survival and subsequent embryonic development as well as morphology of the spindle and chromosome alignment were also evaluated. Vitrification system was adapted with JY Straw and the cooling rate was approximately 442-500 °C/min. In contrast, the warming rate was approximately 2,210-2,652 °C/min. Survival rate of oocytes increased significantly when 15 % EG was combined with 2 % PVP in vitrification solution (VS). The effect of combination of EG and PVP was not significant when the concentration of EG was 20 % and higher. Although there were no significant differences in embryonic development, the percentage of abnormal spindle and chromosome alignment was significantly higher in the oocytes without 2 % PVP in VS. Our data provide a proof of principle for oocyte vitrification that may not require a high concentration of cryoprotectant. There are synergic effects of EG combined with PVP for oocyte vitrification, which may provide important information to the field in developing less cytotoxic VS.

Accomplishments and Compromises in Prediction Research for World Records and Best Performances in Track and Field and Swimming

Science.gov (United States)

Liu, Yuanlong; Paul, Stanley; Fu, Frank H.

2012-01-01

The conductors of this study reviewed prediction research and studied the accomplishments and compromises in predicting world records and best performances in track and field and swimming. The results of the study showed that prediction research only promises to describe the historical trends in track and field and swimming performances, to study…

Tamoxifen-independent recombination in the RIP-CreER mouse.

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Yanmei Liu

Full Text Available BACKGROUND: The inducible Cre-lox system is a valuable tool to study gene function in a spatial and time restricted fashion in mouse models. This strategy relies on the limited background activity of the modified Cre recombinase (CreER in the absence of its inducer, the competitive estrogen receptor ligand, tamoxifen. The RIP-CreER mouse (Tg (Ins2-cre/Esr1 1Dam is among the few available β-cell specific CreER mouse lines and thus it has been often used to manipulate gene expression in the insulin-producing cells of the endocrine pancreas. PRINCIPAL FINDINGS: Here, we report the detection of tamoxifen-independent Cre activity as early as 2 months of age in RIP-CreER mice crossed with three distinct reporter strains. SIGNIFICANCE: Evidence of Cre-mediated recombination of floxed alleles even in the absence of tamoxifen administration should warrant cautious use of this mouse for the study of pancreatic β-cells.

A Mouse Model of Chronic West Nile Virus Disease.

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Jessica B Graham

2016-11-01

Full Text Available Infection with West Nile virus (WNV leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans.

4D atlas of the mouse embryo for precise morphological staging.

Science.gov (United States)

Wong, Michael D; van Eede, Matthijs C; Spring, Shoshana; Jevtic, Stefan; Boughner, Julia C; Lerch, Jason P; Henkelman, R Mark

2015-10-15

After more than a century of research, the mouse remains the gold-standard model system, for it recapitulates human development and disease and is quickly and highly tractable to genetic manipulations. Fundamental to the power and success of using a mouse model is the ability to stage embryonic mouse development accurately. Past staging systems were limited by the technologies of the day, such that only surface features, visible with a light microscope, could be recognized and used to define stages. With the advent of high-throughput 3D imaging tools that capture embryo morphology in microscopic detail, we now present the first 4D atlas staging system for mouse embryonic development using optical projection tomography and image registration methods. By tracking 3D trajectories of every anatomical point in the mouse embryo from E11.5 to E14.0, we established the first 4D atlas compiled from ex vivo 3D mouse embryo reference images. The resulting 4D atlas comprises 51 interpolated 3D images in this gestational range, resulting in a temporal resolution of 72 min. From this 4D atlas, any mouse embryo image can be subsequently compared and staged at the global, voxel and/or structural level. Assigning an embryonic stage to each point in anatomy allows for unprecedented quantitative analysis of developmental asynchrony among different anatomical structures in the same mouse embryo. This comprehensive developmental data set offers developmental biologists a new, powerful staging system that can identify and compare differences in developmental timing in wild-type embryos and shows promise for localizing deviations in mutant development. © 2015. Published by The Company of Biologists Ltd.

Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein.

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Christian Much

2016-06-01

Full Text Available Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse.

Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein.

Science.gov (United States)

Much, Christian; Auchynnikava, Tania; Pavlinic, Dinko; Buness, Andreas; Rappsilber, Juri; Benes, Vladimir; Allshire, Robin; O'Carroll, Dónal

2016-06-01

Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse.

Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes

Science.gov (United States)

Rowley, Jesse W.; Oler, Andrew J.; Tolley, Neal D.; Hunter, Benjamin N.; Low, Elizabeth N.; Nix, David A.; Yost, Christian C.; Zimmerman, Guy A.

2011-01-01

Inbred mice are a useful tool for studying the in vivo functions of platelets. Nonetheless, the mRNA signature of mouse platelets is not known. Here, we use paired-end next-generation RNA sequencing (RNA-seq) to characterize the polyadenylated transcriptomes of human and mouse platelets. We report that RNA-seq provides unprecedented resolution of mRNAs that are expressed across the entire human and mouse genomes. Transcript expression and abundance are often conserved between the 2 species. Several mRNAs, however, are differentially expressed in human and mouse platelets. Moreover, previously described functional disparities between mouse and human platelets are reflected in differences at the transcript level, including protease activated receptor-1, protease activated receptor-3, platelet activating factor receptor, and factor V. This suggests that RNA-seq is a useful tool for predicting differences in platelet function between mice and humans. Our next-generation sequencing analysis provides new insights into the human and murine platelet transcriptomes. The sequencing dataset will be useful in the design of mouse models of hemostasis and a catalyst for discovery of new functions of platelets. Access to the dataset is found in the “Introduction.” PMID:21596849

Dissection of the Mouse Pancreas for Histological Analysis and Metabolic Profiling.

Science.gov (United States)

Veite-Schmahl, Michelle J; Regan, Daniel P; Rivers, Adam C; Nowatzke, Joseph F; Kennedy, Michael A

2017-08-19

We have been investigating the pancreas specific transcription factor, 1a cre-recombinase; lox-stop-lox- Kristen rat sarcoma, glycine to aspartic acid at the 12 codon (Ptf1a cre/+ ;LSL-Kras G12D/+ ) mouse strain as a model of human pancreatic cancer. The goal of our current studies is to identify novel metabolic biomarkers of pancreatic cancer progression. We have performed metabolic profiling of urine, feces, blood, and pancreas tissue extracts, as well as histological analyses of the pancreas to stage the cancer progression. The mouse pancreas is not a well-defined solid organ like in humans, but rather is a diffusely distributed soft tissue that is not easily identified by individuals unfamiliar with mouse internal anatomy or by individuals that have little or no experience performing mouse organ dissections. The purpose of this article is to provide a detailed step-wise visual demonstration to guide novices in the removal of the mouse pancreas by dissection. This article should be especially valuable to students and investigators new to research that requires harvesting of the mouse pancreas by dissection for metabolic profiling or histological analyses.

Using the mouse to model human disease: increasing validity and reproducibility

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Monica J. Justice

2016-02-01

Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.

An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man

KAUST Repository

Ravasi, Timothy; Suzuki, Harukazu; Cannistraci, Carlo; Katayama, Shintaro; Bajic, Vladimir B.; Tan, Kai; Akalin, Altuna; Schmeier, Sebastian; Kanamori-Katayama, Mutsumi; Bertin, Nicolas; Carninci, Piero; Daub, Carsten O.; Forrest, Alistair R.R.; Gough, Julian; Grimmond, Sean; Han, Jung-Hoon; Hashimoto, Takehiro; Hide, Winston; Hofmann, Oliver; Kamburov, Atanas; Kaur, Mandeep; Kawaji, Hideya; Kubosaki, Atsutaka; Lassmann, Timo; van Nimwegen, Erik; MacPherson, Cameron Ross; Ogawa, Chihiro; Radovanovic, Aleksandar; Schwartz, Ariel; Teasdale, Rohan D.; Tegné r, Jesper; Lenhard, Boris; Teichmann, Sarah A.; Arakawa, Takahiro; Ninomiya, Noriko; Murakami, Kayoko; Tagami, Michihira; Fukuda, Shiro; Imamura, Kengo; Kai, Chikatoshi; Ishihara, Ryoko; Kitazume, Yayoi; Kawai, Jun; Hume, David A.; Ideker, Trey; Hayashizaki, Yoshihide

2010-01-01

Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man

KAUST Repository

Ravasi, Timothy

2010-03-01

Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

Mouse tetranectin: cDNA sequence, tissue-specific expression, and chromosomal mapping

DEFF Research Database (Denmark)

Ibaraki, K; Kozak, C A; Wewer, U M

1995-01-01

regulation, mouse tetranectin cDNA was cloned from a 16-day-old mouse embryo library. Sequence analysis revealed a 992-bp cDNA with an open reading frame of 606 bp, which is identical in length to the human tetranectin cDNA. The deduced amino acid sequence showed high homology to the human cDNA with 76......(s) of tetranectin. The sequence analysis revealed a difference in both sequence and size of the noncoding regions between mouse and human cDNAs. Northern analysis of the various tissues from mouse, rat, and cow showed the major transcript(s) to be approximately 1 kb, which is similar in size to that observed...

ACCOUNTING – THE REZULT OF A COMPROMISE BETWEEN EXPECTATIONS AND EXIGENCIES

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Mihaela TULVINSCHI

2017-12-01

Full Text Available Current concerns in the field of accounting are circumscribed to the need to perfect a unanimously accepted accounting language to be included in the application, as uniformly as possible, of the principles and accounting treatments as a basis in making financial statements. This approach is complicated and implies an extraordinary dynamics. The objective of the article is to investigate whether, in the current economic environment, accounting is able to issue an objective message to meet the expectations and exigencies of all users of financial information. Accounting can provide only a single representation of reality, and the information produced by accounting can only be a compromise between the respect for accounting principles and the care for reflecting economic reality. Accounting is an information system that quantifies, processes and transmits financial information about an economic entity. It establishes the link between economic activities and decision-makers.

Inhibition of Wnt/β-catenin signaling by IWR1 induces expression of Foxd3 to promote mouse epiblast stem cell self-renewal.

Science.gov (United States)

Liu, Kuisheng; Sun, Yuanyuan; Liu, Dahai; Ye, Shoudong

2017-08-26

Inhibition of Wnt/β-catenin signaling facilitates the derivation of mouse epiblast stem cells (EpiSCs), as well as dramatically promotes EpiSC self-renewal. The specific mechanism, however, is still unclear. Here, we showed that IWR1, a Wnt/β-catenin signaling inhibitor, allowed long-term self-renewal of EpiSCs in serum medium in combination with ROCK inhibitor Y27632. Through transcriptome data analysis, we arrived at a set of candidate transcription factors induced by IWR1. Among these, Forkhead box D3 (Foxd3) was most abundant. Forced expression of Foxd3 could recapitulate the self-renewal-promoting effect of IWR1 in EpiSCs. Conversely, knockdown of Foxd3 profoundly compromised responsiveness to IWR1, causing extinction of pluripotency markers and emergence of differentiation phenotype. Foxd3 thus is necessary and sufficient to mediate self-renewal downstream of Wnt/β-catenin signaling inhibitor. These findings highlight an important role for Foxd3 in regulating EpiSCs and will expand current understanding of the primed pluripotency. Copyright © 2017 Elsevier Inc. All rights reserved.

Automated classification of mouse pup isolation syllables: from cluster analysis to an Excel based ‘mouse pup syllable classification calculator’

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Jasmine eGrimsley

2013-01-01

Full Text Available Mouse pups vocalize at high rates when they are cold or isolated from the nest. The proportions of each syllable type produced carry information about disease state and are being used as behavioral markers for the internal state of animals. Manual classifications of these vocalizations identified ten syllable types based on their spectro-temporal features. However, manual classification of mouse syllables is time consuming and vulnerable to experimenter bias. This study uses an automated cluster analysis to identify acoustically distinct syllable types produced by CBA/CaJ mouse pups, and then compares the results to prior manual classification methods. The cluster analysis identified two syllable types, based on their frequency bands, that have continuous frequency-time structure, and two syllable types featuring abrupt frequency transitions. Although cluster analysis computed fewer syllable types than manual classification, the clusters represented well the probability distributions of the acoustic features within syllables. These probability distributions indicate that some of the manually classified syllable types are not statistically distinct. The characteristics of the four classified clusters were used to generate a Microsoft Excel-based mouse syllable classifier that rapidly categorizes syllables, with over a 90% match, into the syllable types determined by cluster analysis.

Genome-wide Analysis of RARβ Transcriptional Targets in Mouse Striatum Links Retinoic Acid Signaling with Huntington's Disease and Other Neurodegenerative Disorders.

Science.gov (United States)

Niewiadomska-Cimicka, Anna; Krzyżosiak, Agnieszka; Ye, Tao; Podleśny-Drabiniok, Anna; Dembélé, Doulaye; Dollé, Pascal; Krężel, Wojciech

2017-07-01

Retinoic acid (RA) signaling through retinoic acid receptors (RARs), known for its multiple developmental functions, emerged more recently as an important regulator of adult brain physiology. How RAR-mediated regulation is achieved is poorly known, partly due to the paucity of information on critical target genes in the brain. Also, it is not clear how reduced RA signaling may contribute to pathophysiology of diverse neuropsychiatric disorders. We report the first genome-wide analysis of RAR transcriptional targets in the brain. Using chromatin immunoprecipitation followed by high-throughput sequencing and transcriptomic analysis of RARβ-null mutant mice, we identified genomic targets of RARβ in the striatum. Characterization of RARβ transcriptional targets in the mouse striatum points to mechanisms through which RAR may control brain functions and display neuroprotective activity. Namely, our data indicate with statistical significance (FDR 0.1) a strong contribution of RARβ in controlling neurotransmission, energy metabolism, and transcription, with a particular involvement of G-protein coupled receptor (p = 5.0e -5 ), cAMP (p = 4.5e -4 ), and calcium signaling (p = 3.4e -3 ). Many identified RARβ target genes related to these pathways have been implicated in Alzheimer's, Parkinson's, and Huntington's disease (HD), raising the possibility that compromised RA signaling in the striatum may be a mechanistic link explaining the similar affective and cognitive symptoms in these diseases. The RARβ transcriptional targets were particularly enriched for transcripts affected in HD. Using the R6/2 transgenic mouse model of HD, we show that partial sequestration of RARβ in huntingtin protein aggregates may account for reduced RA signaling reported in HD.

Macronutrient manipulations of cheese resulted in lower energy content without compromising its satiating capacity

DEFF Research Database (Denmark)

Hansen, Thea Toft; Sjödin, Anders Mikael; Ritz, Christian

2018-01-01

Manipulation of food’s macronutrient composition in order to reduce energy content without compromising satiating capacity may be helpful in body weight control. For cheeses, substituting fat with protein may provide such opportunity. We aimed at examining the acute effect of cheeses with different...... macronutrient compositions on accumulated energy intake and subjective appetite sensation. A total of thirty-nine normal-weight (average BMI 24·4 kg/m2) men and women completed the partly double-blind, randomised crossover study with high-protein/low-fat (HP/LF, 696 kJ), high-protein/high-fat (HP/HF, 976 k...

CT-morphological characterization of respiratory syncytial virus (RSV) pneumonia in immune-compromised adults

International Nuclear Information System (INIS)

Mayer, J.L.; Kauczor, H.U.; Lehners, N.; Egerer, G.; Heussel, C.P.

2014-01-01

Characterization and follow-up evaluation of chest CT of RSV pneumonia in immune-compromised adults during a seasonal epidemic. Retrospective analysis of 132 chest CT examinations of 51 adult immune-compromised patients (29 m/22f, diameter 58 years) with clinical signs of pneumonia and positive RSV test in winter 2011/2012. Two experienced chest radiologists evaluated the morphology (bronchial wall thickening, tree-in-bud, nodules, halo, ground-glass opacities, consolidations, pleural fluid) of the CT scans by consensus. Pathological findings were in 86 % of the chest CT scans: Areas of ground-glass attenuation in 64 %, consolidations in 56 %, nodules in 55 % (diameter 8 mm in maximal diameter, with halo in 71 %), pleural fluid in 44 % (diameter 2 cm), tree-in-bud in 36 %, bronchial wall thickening in 27 % and more than one morphological finding in 72 %. There were no pathological CT findings in 14 % of patients with clinical symptoms of pneumonia because these patients did not undergo follow-up. Radiological progression was found in 45 % of patients and regression in 33 % in follow-up examinations. In 37 % an additional examination of the paranasal sinuses was performed and showed sinusitis in 63 % of cases. 90 % of the patients had sinusitis as well as pneumonia. In addition to RSV, a further pathogenic agent was found in bronchoalveolar lavage of five patients (Aspergillus spec., herpes simplex virus, Pseudomonas aeruginosa). The most characteristic signs in chest CT scans were at the beginning of pneumonia with nodules and tree-in-bud often combined with bronchial wall thickening. The following CT scans showed characteristic but not pathognomonic chest CT findings of RSV pneumonia. These morphological findings should be recognized seasonally (winter) especially at the beginning of the case of pneumonia. RSV-associated additional sinusitis is probably common and should be noticed.

Staurosporine induces necroptotic cell death under caspase-compromised conditions in U937 cells.

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Zsuzsanna A Dunai

Full Text Available For a long time necrosis was thought to be an uncontrolled process but evidences recently have revealed that necrosis can also occur in a regulated manner. Necroptosis, a type of programmed necrosis is defined as a death receptor-initiated process under caspase-compromised conditions. The process requires the kinase activity of receptor-interacting protein kinase 1 and 3 (RIPK1 and RIPK3 and mixed lineage kinase domain-like protein (MLKL, as a substrate of RIPK3. The further downstream events remain elusive. We applied known inhibitors to characterize the contributing enzymes in necroptosis and their effect on cell viability and different cellular functions were detected mainly by flow cytometry. Here we report that staurosporine, the classical inducer of intrinsic apoptotic pathway can induce necroptosis under caspase-compromised conditions in U937 cell line. This process could be hampered at least partially by the RIPK1 inhibitor necrotstin-1 and by the heat shock protein 90 kDa inhibitor geldanamycin. Moreover both the staurosporine-triggered and the classical death ligand-induced necroptotic pathway can be effectively arrested by a lysosomal enzyme inhibitor CA-074-OMe and the recently discovered MLKL inhibitor necrosulfonamide. We also confirmed that the enzymatic role of poly(ADP-ribosepolymerase (PARP is dispensable in necroptosis but it contributes to membrane disruption in secondary necrosis. In conclusion, we identified a novel way of necroptosis induction that can facilitate our understanding of the molecular mechanisms of necroptosis. Our results shed light on alternative application of staurosporine, as a possible anticancer therapeutic agent. Furthermore, we showed that the CA-074-OMe has a target in the signaling pathway leading to necroptosis. Finally, we could differentiate necroptotic and secondary necrotic processes based on participation of PARP enzyme.

Regulatory Forum commentary: alternative mouse models for future cancer risk assessment.

Science.gov (United States)

Morton, Daniel; Sistare, Frank D; Nambiar, Prashant R; Turner, Oliver C; Radi, Zaher; Bower, Nancy

2014-07-01

International regulatory and pharmaceutical industry scientists are discussing revision of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S1 guidance on rodent carcinogenicity assessment of small molecule pharmaceuticals. A weight-of-evidence approach is proposed to determine the need for rodent carcinogenicity studies. For compounds with high human cancer risk, the product may be labeled appropriately without conducting rodent carcinogenicity studies. For compounds with minimal cancer risk, only a 6-month transgenic mouse study (rasH2 mouse or p53+/- mouse) or a 2-year mouse study would be needed. If rodent carcinogenicity testing may add significant value to cancer risk assessment, a 2-year rat study and either a 6-month transgenic mouse or a 2-year mouse study is appropriate. In many cases, therefore, one rodent carcinogenicity study could be sufficient. The rasH2 model predicts neoplastic findings relevant to human cancer risk assessment as well as 2-year rodent models, produces fewer irrelevant neoplastic outcomes, and often will be preferable to a 2-year rodent study. Before revising ICH S1 guidance, a prospective evaluation will be conducted to test the proposed weight-of-evidence approach. This evaluation offers an opportunity for a secondary analysis comparing the value of alternative mouse models and 2-year rodent studies in the proposed ICH S1 weight-of-evidence approach for human cancer risk assessment. © 2014 by The Author(s).

HIV treatment as prevention: debate and commentary--will early infection compromise treatment-as-prevention strategies?

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Myron S Cohen

Full Text Available Universal HIV testing and immediate antiretroviral therapy for infected individuals has been proposed as a way of reducing the transmission of HIV and thereby bringing the HIV epidemic under control. It is unclear whether transmission during early HIV infection--before individuals are likely to have been diagnosed with HIV and started on antiretroviral therapy--will compromise the effectiveness of treatment as prevention. This article presents two opposing viewpoints by Powers, Miller, and Cohen, and Williams and Dye, followed by a commentary by Fraser.

Introduction of the human proα1(I) collagen gene into proα1(I)-deficient Mov-13 mouse cells leads to formation of functional mouse-human hybrid type I collagen

International Nuclear Information System (INIS)

Schnieke, A.; Dziadek, M.; Bateman, J.; Mascara, T.; Harbers, K.; Gelinas, R.; Jaenisch, R.

1987-01-01

The Mov-13 mouse strain carries a retroviral insertion in the proα1(I) collagen gene that prevents transcription of the gene. Cell lines derived from homozygous embryos do not express type I collagen although normal amounts of proα2 mRNA are synthesized. The authors have introduced genomic clones of either the human or mouse proα1(I) collagen gene into homozygous cell lines to assess whether the human or mouse proα1(I) chains can associate with the endogenous mouse proα2(I) chain to form stable type I collagen. The human gene under control of the simian virus 40 promoter was efficiently transcribed in the transfected cells. Protein analyses revealed that stable heterotrimers consisting of two human α1 chains and one mouse α2 chain were formed and that type I collagen was secreted by the transfected cells at normal rates. However, the electrophoretic migration of both α1(I) and α2(I) chains in the human-mouse hybrid molecules were retarded, compared to the α(I) chains in control mouse cells. Inhibition of the posttranslational hydroxylation of lysine and proline resulted in comigration of human and mouse α1 and α2 chains, suggesting that increased posttranslational modification caused the altered electrophoretic migration in the human-mouse hybrid molecules. Amino acid sequence differences between the mouse and human α chains may interfere with the normal rate of helix formation and increase the degree of posttranslational modifications similar to those observed in patients with lethal perinatal osteogenesis imperfecta. The Mov-13 mouse system should allow the authors to study the effect specific mutations introduced in transfected proα1(I) genes have on the synthesis, assembly, and function of collagen I

Immunohistochemical Examination of Novel Rat Monoclonal Antibodies against Mouse and Human Podoplanin

International Nuclear Information System (INIS)

Kaji, Chiaki; Tsujimoto, Yuta; Kato Kaneko, Mika; Kato, Yukinari; Sawa, Yoshihiko

2012-01-01

This study aims to develop new monoclonal antibodies (mAbs) against mouse and human podoplanin. Rats were immunized with synthetic peptides, corresponding to amino acids 38–51 of mouse podoplanin or human podoplanin which is 100% homologous to the same site of monkey podoplanin; anti-mouse podoplanin mAb PMab-1 (IgG 2a ) and anti-human mAb NZ-1.2 (IgG 2a ) were established. In immunocytochemistry, the mouse melanoma B16-F10 and mouse podoplanin (mPDPN)-expressed CHO transfectant were stained by PMab-1; human lymphatic endothelial cells (LEC) and human podoplanin (hPDPN)-expressed squamous cell carcinoma HSC3 transfectant, were stained by NZ-1.2. Western-blot analysis detected an about 40-kDa protein in CHO-mPDPN and B16-F10 by PMab-1, and in HSC3-hPDPN and LEC by NZ-1.2. In frozen sections, PMab-1 reacted with mouse kidney, pulmonary alveoli, pulmonary pleura, and salivary gland myoepithelial cells while NZ-1.2 reacted to the human salivary gland myoepithelial cells. The immunostaining of paraffin-embedded sections also showed the reaction of PMab-1 or NZ-1.2 to the mouse or monkey kidney glomerulus, pulmonary alveoli, and lung lymphatic vessels. These results indicate that the two novel rat mAbs to the mouse and human/monkey podoplanin are useful for Western-blot and immunostaining of somatic tissues on paraffin-embedded sections as well as frozen sections

Mass spectrometry analysis of hepcidin peptides in experimental mouse models.

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Harold Tjalsma

Full Text Available The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1 and its paralogue Hepcidin-2 (Hep-2 at the peptide level. To this purpose, Fourier transform ion cyclotron resonance (FTICR and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i 3 mouse strains (C57Bl/6; DBA/2 and BABL/c upon stimulation with intravenous iron and LPS, ii homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X mutated mice and double affected mice, and iii mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics.

A surgical approach appropriate for targeted cochlear gene therapy in the mouse.

Science.gov (United States)

Jero, J; Tseng, C J; Mhatre, A N; Lalwani, A K

2001-01-01

Therapeutic manipulations of the mammalian cochlea, including cochlear gene transfer, have been predominantly studied using the guinea pig as the experimental model. With the significant developments in mouse genomics and the availability of mutant strains of mice with well-characterized hearing loss, the mouse justifiably will be the preferred animal model for therapeutic manipulations. However, the potential advantages of the mouse model have not been fully realized due to the surgical difficulty of accessing its small cochlea. This study describes a ventral approach, instead of the routinely used postauricular approach in other rodents, for accessing the mouse middle and inner ear, and its application in cochlear gene transfer. This ventral approach enabled rapid and direct delivery of liposome-transgene complex to the mouse inner ear while avoiding blood loss, facial nerve morbidity, and mortality. Transgene expression at 3 days was detected in Reissner's membrane, spiral limbus, spiral ligament, and spiral ganglion cells, in a pattern similar to that previously described in the guinea pig. The successful access and delivery of material to the mouse cochlea and the replication of gene expression seen in the guinea pig demonstrated in this study should promote the use of the mouse in future studies investigating targeted cochlear therapy.

20 CFR 408.950 - Will we accept a compromise settlement of an overpayment debt or suspend or terminate collection...

Science.gov (United States)

2010-04-01

...' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Underpayments... (31 CFR 900.3 and parts 902 and 903). (c) Effect of compromise, suspension or termination. When we... accordance with provisions of the Social Security Act, other laws, and the standards set forth in 31 CFR...

Protein degradation in preimplantation mouse embryos and the lethality of tritiated amino acids

International Nuclear Information System (INIS)

Wielbold, J.L.

1982-01-01

The role of protein degradation in preimplantation development in the mouse was studied. Proteins of morulae and blastocysts (M and B) cultured in vitro after labeling for 1 hour (h) in 3 H-leucine exhibit a mean half-life (t 1 / 2 ) of 8.1 h. The t 1 / 2 tends to increase (9.5 h) when 10% fetal calf serum is added to the chase medium. This decrease in protein degradation in the presence of serum is associated with an increase in the percentage of B that are hatching (P 3 H-leucine in their proteins than did Day 4 embryos remaining in culture (P<0.02), while Day 4 embryos in a Day 3 uterus retained the same amount of radioactivity as did Day 4 embryos in culture. This differential effect of uterine environment was also seen when Day 4 embryos were transferred to recipients. More fetuses developed to term when the recipient was in Day 3 of PSP (50.8%) than when the recipient was in Day 4 PSP (25.9%, P<0.001), regardless of the age of the recipient. Age of the recipient does affect the percentage of transferred embryos developing to term. Thus, protein degradation may vary with the stage of embryo development and the conditions to which the embryos are exposed. However, even low levels of incorporated tritiated leucine can have lethal effects on the embryos and compromise the validity of the protein half-lives determined

Treatment of chest burn contracture causing respiratory compromise with island release and grafting using cross-link collagen and Integra™ bilayer dressing

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Neil Doctor

2014-04-01

Full Text Available Post-burn skin contractures of the anterior and lateral abdomen and chest may result in respiratory compromise due to limitation of rib excursion. This case report describes a young man with respiratory compromise limiting his daily activity and function, as a result of a 90% burn sustained 6 years previously. Release of his chest and upper abdomen was achieved using “island” scar releases and a cross-linked bovine tendon collagen and glycosaminoglycan and a semi-permeable polysiloxane bilayer matrix dressing (Integra™ followed by subsequent split thickness skin graft. An immediate increase in maximal inspiratory volume was obtained intra-operatively and in the im­mediate post-operative period, and this improvement was sustained after healing of all wounds with subjective relief of the patient’s symptoms.

Nrl-Cre transgenic mouse mediates loxP recombination in developing rod photoreceptors.

Science.gov (United States)

Brightman, Diana S; Razafsky, David; Potter, Chloe; Hodzic, Didier; Chen, Shiming

2016-03-01

The developing mouse retina is a tractable model for studying neurogenesis and differentiation. Although transgenic Cre mouse lines exist to mediate conditional genetic manipulations in developing mouse retinas, none of them act specifically in early developing rods. For conditional genetic manipulations of developing retinas, a Nrl-Cre mouse line in which the Nrl promoter drives expression of Cre in rod precursors was created. The results showed that Nrl-Cre expression was specific to the retina where it drives rod-specific recombination with a temporal pattern similar to endogenous Nrl expression during retinal development. This Nrl-Cre transgene does not negatively impact retinal structure and function. Taken together, the data suggested that the Nrl-Cre mouse line was a valuable tool to drive Cre-mediated recombination specifically in developing rods. © 2016 Wiley Periodicals, Inc.

The alpha-spectrin gene is on chromosome 1 in mouse and man.

Science.gov (United States)

Huebner, K; Palumbo, A P; Isobe, M; Kozak, C A; Monaco, S; Rovera, G; Croce, C M; Curtis, P J

1985-06-01

By using alpha-spectrin cDNA clones of murine and human origin and somatic cell hybrids segregating either mouse or human chromosomes, the gene for alpha-spectrin has been mapped to chromosome 1 in both species. This assignment of the mouse alpha-spectrin gene to mouse chromosome 1 by DNA hybridization strengthens the previous identification of the alpha-spectrin locus in mouse with the sph locus, which previously was mapped by linkage analysis to mouse chromosome 1, distal to the Pep-3 locus. By in situ hybridization to human metaphase chromosomes, the human alpha-spectrin gene has been localized to 1q22-1q25; interestingly, the locus for a non-Rh-linked form of elliptocytosis has been provisionally mapped to band 1q2 by family linkage studies.

SU-F-T-668: Irradiating Mouse Brain with a Clinical Linear Accelerator

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Perez-Torres, C [N Rancilio Purdue University, West Lafayette, IN (United States)

2016-06-15

Purpose: To design and construct a “mouse jig” device that would allow for irradiation of the mouse brain with a clinical Varian 6 MeV Linear Accelerator. This device must serve as a head immobilizer, gaseous anesthesia delivery, and radiation bolus concurrently. Methods: The mouse jig was machined out of nylon given that it is inexpensive, easy to machine, and has similar electron density to water. A cylindrical opening with diameter of 16 mm and 40 mm depth was drilled into a nylon block sized 56×56×50 mm (width, length, depth). Additional slots were included in the block for ear bars and a tooth bar to serve as a three-point immobilization device as well as for anesthesia delivery and scavenging. For ease of access when loading the mouse into the holder, there is a removable piece at the top of the block that is 15 mm in depth. This serves a dual purpose, as with the proper extra shielding, the mouse jig could be used with lower linear energy transfer photons with this piece removed. A baseplate was then constructed with five square slots where the mouse jig can securely be inserted plus additional slots that would allow the baseplate to be mounted on a standard lock bar in the treatment couch. This maximizes the reproducibility of placement between imaging and treatment and between treatment sessions. Results: CT imaging and radiation treatment planning was performed that showed acceptable coverage and uniformity of radiation dose in the mouse brain while sparing the throat and eyes. Conclusion: We have designed and manufactured a device that fulfills our criteria allowing us to selectively irradiate the mouse brain with a clinical linear accelerator. This setup will be used for generating mouse models of radiation-induced brain injury.

Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

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Ivanna Ihnatovych

Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

Cloning, characterization and targeting of the mouse HEXA gene

Energy Technology Data Exchange (ETDEWEB)

Wakamatsu, N.; Trasler, J.M.; Gravel, R.A. [McGill Univ., Quebec (Canada)] [and others

1994-09-01

The HEXA gene, encoding the {alpha} subunit of {beta}-hexosaminidase A, is essential for the metabolism of ganglioside G{sub M2}, and defects in this gene cause Tay-Sachs disease in humans. To elucidate the role of the gene in the nervous system of the mouse and to establish a mouse model of Tay-Sachs disease, we have cloned and characterized the HEXA gene and targeted a disruption of the gene in mouse ES cells. The mouse HEXA gene spans {approximately}26 kb and consists of 14 exons, similar to the human gene. A heterogeneous transcription initiation site was identified 21-42 bp 5{prime} of the initiator ATG, with two of the sites fitting the consensus CTCA (A = start) as seen for some weak initiator systems. Promoter analysis showed that the first 150 bp 5{prime} of the ATG contained 85% of promoter activity observed in constructs containing up to 1050 bp of 5{prime} sequence. The active region contained a sequence matching that of the adenovirus major late promoter upstream element factor. A survey of mouse tissues showed that the highest mRNA levels were in (max to min): testis (5.5 x brain cortex), adrenal, epididymis, heart, brain, lung, kidney, and liver (0.3 x brain cortex). A 12 kb BstI/SalI fragment containing nine exons was disrupted with the insertion of the bacterial neo{sup r} gene in exon 11 and was targeted into 129/Sv ES cells by homologous recombination. Nine of 153 G418 resistant clones were correctly targeted as confirmed by Southern blotting. The heterozygous ES cells were microinjected into mouse blastocysts and implanted into pseudo-pregnant mice. Nine male chimeric mice, showing that 40-95% chimerism for the 129/Sv agouti coat color marker, are being bred in an effort to generate germline transmission of the disrupted HEXA gene.

First-Trimester Serum Acylcarnitine Levels to Predict Preeclampsia: A Metabolomics Approach

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Maria P. H. Koster

2015-01-01

Full Text Available Objective. To expand the search for preeclampsia (PE metabolomics biomarkers through the analysis of acylcarnitines in first-trimester maternal serum. Methods. This was a nested case-control study using serum from pregnant women, drawn between 8 and 14 weeks of gestational age. Metabolites were measured using an UPLC-MS/MS based method. Concentrations were compared between controls (n=500 and early-onset- (EO- PE (n=68 or late-onset- (LO- PE (n=99 women. Metabolites with a false discovery rate <10% for both EO-PE and LO-PE were selected and added to prediction models based on maternal characteristics (MC, mean arterial pressure (MAP, and previously established biomarkers (PAPPA, PLGF, and taurine. Results. Twelve metabolites were significantly different between EO-PE women and controls, with effect levels between −18% and 29%. For LO-PE, 11 metabolites were significantly different with effect sizes between −8% and 24%. Nine metabolites were significantly different for both comparisons. The best prediction model for EO-PE consisted of MC, MAP, PAPPA, PLGF, taurine, and stearoylcarnitine (AUC = 0.784. The best prediction model for LO-PE consisted of MC, MAP, PAPPA, PLGF, and stearoylcarnitine (AUC = 0.700. Conclusion. This study identified stearoylcarnitine as a novel metabolomics biomarker for EO-PE and LO-PE. Nevertheless, metabolomics-based assays for predicting PE are not yet suitable for clinical implementation.

Evaluation of Some Inflammatory and Biochemical Markers in Acute Coronary Syndrome

International Nuclear Information System (INIS)

Abdel-Messeih, PH.L.; Nossier, N.M.; Mansour, H.H.

2012-01-01

The term acute coronary syndrome (ACS) encompasses a range of thrombotic coronary artery diseases, including unstable angina (UA) and both ST-segment elevation (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). Bio markers play an important role in the diagnosis of non-ST-elevation ACS (NSTE-ACS) including unstable angina and non-STEMI. Among these, cardiac troponin and creatine phosphokinase myocardial band appeared to be the most sensitive and specific markers of myocardial injury. The important role of inflammatory processes in the development and progression of atherosclerosis has been clearly established. Different circulating inflammatory bio markers indicating the instability of atherosclerotic plaque have been identified and serve as diagnostic tools for the identification of patients with unstable angina or acute myocardial infarction and to identify risk patients. The present study was carried out on twenty patients with (NSTE-ACS). The level of serum troponin I (cTnI), creatine phosphokinase-total (CPK-T), myocardial band of creatine phosphokinase (CPK-MB), pregnancy associated plasma protein-A (PAPP-A) and highly sensitive C-reactive protein (hsCRP) were determined. The results showed increase in the level of cardiac bio markers (cTnI, CPK-MB, CPK-T) and inflammatory markers (PAPP-A, hsCRP). It could be concluded that the increase in inflammatory markers correlate especially PAPP-A in NSTE-ACS with the increase of cardiac bio markers

Humanized mouse models: Application to human diseases.

Science.gov (United States)

Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

2018-05-01

Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

Three-Dimensional Reconstruction of the Mouse Nephron

DEFF Research Database (Denmark)

Zhai, Xiao-Yue; Thomsen, Jesper Skovhus; Birn, Henrik

2006-01-01

Renal function is crucially dependent on renal microstructure which provides the basis for the regulatory mechanisms that control the transport of water and solutes between filtrate and plasma and the urinary concentration. This study provides new, detailed information on mouse renal architecture...... and collecting ducts was performed on aligned digital images, obtained from 2.5-µm-thick serial sections of mouse kidneys. Important new findings were highlighted: (1) A tortuous course of the descending thin limbs of long-looped nephrons and a winding course of the thick ascending limbs of short-looped nephrons...

Mouse Model of Burn Wound and Infection

DEFF Research Database (Denmark)

Calum, Henrik; Høiby, Niels; Moser, Claus

2017-01-01

The immunosuppression induced by thermal injury renders the burned victim susceptible to infection. A mouse model was developed to examine the immunosuppression, which was possible to induce even at a minor thermal insult of 6% total body surface area. After induction of the burn (48 hr) a depres......The immunosuppression induced by thermal injury renders the burned victim susceptible to infection. A mouse model was developed to examine the immunosuppression, which was possible to induce even at a minor thermal insult of 6% total body surface area. After induction of the burn (48 hr...

Genetic analysis of radiation-induced mouse thymic lymphomas

International Nuclear Information System (INIS)

Kominami, R.; Wakabayashi, Y.; Niwa, O.

2003-01-01

Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies, and the model has been used for the study of genes involved in carcinogenesis. ras oncogenes are the first isolate which undergoes mutations in 10 to 30 % of lymphomas, and p16INK4a and p19ARF in the INK4a-ARF locus are also frequently inactivated. In our previous study, the inactivation of Ikaros, a key regurator of lymphoid system, was found in those lymphomas, and it was suggested that there are other responsible genes yet to be discovered. On the other hand, genetic predisposition to radiation-induced lymphoma often differs in different strains, and this reflects the presence of low penetrance genes that can modify the impact of a given mutation. Little study of such modifiers or susceptibility genes has been performed, either. Recent availability of databases on mouse genome information and the power of mouse genetic system underline usefulness of the lymphoma model in search for novel genes involved, which may provide clues to molecular mechanisms of development of the radiogenic lymphoma and also genes involved in human lymphomas and other malignancies. Accordingly, we have carried out positional cloning for the two different types of tumor-related genes. In this symposium, our current progress is presented that includes genetic mapping of susceptibility/ resistance loci on mouse chromosomes 4, 5 and 19, and also functional analysis of a novel tumor suppressor gene, Rit1/Bcl11b, that has been isolated from allelic loss (LOH) mapping and sequence analysis for γ -ray induced mouse thymic lymphomas

Conditional Expression of Human 15-Lipoxygenase-1 in Mouse Prostate Induces Prostatic Intraepithelial Neoplasia: The FLiMP Mouse Model

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Uddhav P. Kelavkar

2006-06-01

Full Text Available The incidence and mortality of prostate cancer (PCa vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1, which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN, and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt, FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC, and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN. In summary, targeted overexpression of h

Modulation of hepatocyte growth factor gene expression by estrogen in mouse ovary.

Science.gov (United States)

Liu, Y; Lin, L; Zarnegar, R

1994-09-01

Hepatocyte growth factor (HGF) is expressed in a variety of tissues and cell types under normal conditions and in response to various stimuli such as tissue injury. In the present study, we demonstrate that the transcription of the HGF gene is stimulated by estrogen in mouse ovary. A single injection of 17 beta-estradiol results in a dramatic and transient elevation of the levels of mouse HGF mRNA. Sequence analysis has found that two putative estrogen responsive elements (ERE) reside at -872 in the 5'-flanking region and at +511 in the first intron, respectively, of the mouse HGF gene. To test whether these ERE elements are responsible for estrogen induction of HGF gene expression, chimeric plasmids containing variable regions of the 5'-flanking sequence of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT) gene were transiently transfected into both human endometrial carcinoma RL 95-2 cells and mouse fibroblast NIH 3T3 cells to assess hormone responsiveness. Transfection results indicate that the ERE elements of the mouse HGF gene can confer estrogen action to either homologous or heterologous promoters. Nuclear protein extracts either from RL95-2 cells transfected with the estrogen receptor expression vector or from mouse liver bound in vitro to ERE elements specifically, as shown by band shift assay. Therefore, our results demonstrate that the HGF gene is transcriptionally regulated by estrogen in mouse ovary; and such regulation is mediated via a direct interaction of the estrogen receptor complex with cis-acting ERE elements identified in the mouse HGF gene.

Wrist Hypothermia Related to Continuous Work with a Computer Mouse: A Digital Infrared Imaging Pilot Study

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Jelena Reste

2015-08-01

Full Text Available Computer work is characterized by sedentary static workload with low-intensity energy metabolism. The aim of our study was to evaluate the dynamics of skin surface temperature in the hand during prolonged computer mouse work under different ergonomic setups. Digital infrared imaging of the right forearm and wrist was performed during three hours of continuous computer work (measured at the start and every 15 minutes thereafter in a laboratory with controlled ambient conditions. Four people participated in the study. Three different ergonomic computer mouse setups were tested on three different days (horizontal computer mouse without mouse pad; horizontal computer mouse with mouse pad and padded wrist support; vertical computer mouse without mouse pad. The study revealed a significantly strong negative correlation between the temperature of the dorsal surface of the wrist and time spent working with a computer mouse. Hand skin temperature decreased markedly after one hour of continuous computer mouse work. Vertical computer mouse work preserved more stable and higher temperatures of the wrist (>30 °C, while continuous use of a horizontal mouse for more than two hours caused an extremely low temperature (<28 °C in distal parts of the hand. The preliminary observational findings indicate the significant effect of the duration and ergonomics of computer mouse work on the development of hand hypothermia.

Trb2, a mouse homolog of tribbles, is dispensable for kidney and mouse development

International Nuclear Information System (INIS)

Takasato, Minoru; Kobayashi, Chiyoko; Okabayashi, Koji; Kiyonari, Hiroshi; Oshima, Naoko; Asashima, Makoto; Nishinakamura, Ryuichi

2008-01-01

Glomeruli comprise an important filtering apparatus in the kidney and are derived from the metanephric mesenchyme. A nuclear protein, Sall1, is expressed in this mesenchyme, and we previously reported that Trb2, a mouse homolog of Drosophila tribbles, is expressed in the mesenchyme-derived tissues of the kidney by microarray analyses using Sall1-GFP knock-in mice. In the present report, we detected Trb2 expression in a variety of organs during gestation, including the kidneys, mesonephros, testes, heart, eyes, thymus, blood vessels, muscle, bones, tongue, spinal cord, and ganglions. In the developing kidney, Trb2 signals were detected in podocytes and the prospective mesangium of the glomeruli, as well as in ureteric bud tips. However, Trb2 mutant mice did not display any apparent phenotypes and no proteinuria was observed, indicating normal glomerular functions. These results suggest that Trb2 plays minimal roles during kidney and mouse development

Controlling the fluoride dosage in a patient with compromised salivary function.

Science.gov (United States)

Eichmiller, Frederick C; Eidelman, Naomi; Carey, Clifton M

2005-01-01

High-concentration topical fluorides are used commonly to with compromised salivary function due to irradiation and chemotherapy. The authors describe a 50-year-old man with previously treated cancer who was using tray-applied topical fluoride gel. He complained of gastric symptoms, difficulty in swallowing, leg muscle soreness and knee joint soreness. A computed tomographic scan revealed thickening of the esophageal walls. An upper endoscopy revealed abnormal motility. The motility test indicated high-amplitude peristalsis and hypertensive lower esophageal sphincter, and urine testing indicated high levels of systemic fluoride. The patient's fluoride regimen was altered, and within a short period his urinary fluoride levels returned to normal and his symptoms resolved. Clinicians prescribing home-applied high-concentration fluorides need to be cognizant of the symptoms of fluoride toxicity, carefully monitor the patient's compliance with the treatment regimen, and adjust the dosage or mode of application to control the total ingested dose of fluoride.

Risk-Controlled Multiobjective Portfolio Selection Problem Using a Principle of Compromise

Directory of Open Access Journals (Sweden)

Takashi Hasuike

2014-01-01

Full Text Available This paper proposes a multiobjective portfolio selection problem with most probable random distribution derived from current market data and other random distributions of boom and recession under the risk-controlled parameters determined by an investor. The current market data and information include not only historical data but also interpretations of economists’ oral and linguistic information, and hence, the boom and recession are often caused by these nonnumeric data. Therefore, investors need to consider several situations from most probable condition to boom and recession and to avoid the risk less than the target return in each situation. Furthermore, it is generally difficult to set random distributions of these cases exactly. Therefore, a robust-based approach for portfolio selection problems using the only mean values and variances of securities is proposed as a multiobjective programming problem. In addition, an exact algorithm is developed to obtain an explicit optimal portfolio using a principle of compromise.

Mouse Activity across Time Scales: Fractal Scenarios

Science.gov (United States)

Lima, G. Z. dos Santos; Lobão-Soares, B.; do Nascimento, G. C.; França, Arthur S. C.; Muratori, L.; Ribeiro, S.; Corso, G.

2014-01-01

In this work we devise a classification of mouse activity patterns based on accelerometer data using Detrended Fluctuation Analysis. We use two characteristic mouse behavioural states as benchmarks in this study: waking in free activity and slow-wave sleep (SWS). In both situations we find roughly the same pattern: for short time intervals we observe high correlation in activity - a typical 1/f complex pattern - while for large time intervals there is anti-correlation. High correlation of short intervals ( to : waking state and to : SWS) is related to highly coordinated muscle activity. In the waking state we associate high correlation both to muscle activity and to mouse stereotyped movements (grooming, waking, etc.). On the other side, the observed anti-correlation over large time scales ( to : waking state and to : SWS) during SWS appears related to a feedback autonomic response. The transition from correlated regime at short scales to an anti-correlated regime at large scales during SWS is given by the respiratory cycle interval, while during the waking state this transition occurs at the time scale corresponding to the duration of the stereotyped mouse movements. Furthermore, we find that the waking state is characterized by longer time scales than SWS and by a softer transition from correlation to anti-correlation. Moreover, this soft transition in the waking state encompass a behavioural time scale window that gives rise to a multifractal pattern. We believe that the observed multifractality in mouse activity is formed by the integration of several stereotyped movements each one with a characteristic time correlation. Finally, we compare scaling properties of body acceleration fluctuation time series during sleep and wake periods for healthy mice. Interestingly, differences between sleep and wake in the scaling exponents are comparable to previous works regarding human heartbeat. Complementarily, the nature of these sleep-wake dynamics could lead to a better

Diffusion of [2-14C]diazepam across hairless mouse skin and human skin

International Nuclear Information System (INIS)

Koch, R.L.; Palicharla, P.; Groves, M.J.

1987-01-01

The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. [ 14 C]Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the 14 C-label applied being recovered in urine and feces. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties. In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber

Mouse Models of the Skin: Models to Define Mechanisms of Skin Carcinogenesis

International Nuclear Information System (INIS)

Wheeler, D. L.; Verma, A. K.; Denning, M. F.

2013-01-01

The multistep model of mouse skin carcinogenesis has facilitated identification of irreversible genetic events of initiation and progression, and epigenetic events of tumor promotion. Mouse skin tumor initiation can be accomplished by a single exposure to a sufficiently small dose of a carcinogen, and this step is rapid and irreversible. However, promotion of skin tumor formation requires a repeated and prolonged exposure to a promoter, and that tumor promotion is reversible. Investigations focused on the mechanisms of mouse carcinogenesis have resulted in the identifications of potential molecular targets of cancer induction and progression useful in planning strategies for human cancer prevention trials. This special issue contains eight papers that focus on mouse models used to study individual proteins expressed in the mouse skin and the role they play in differentiation, tissue homeostasis, skin carcinogenesis, and chemo prevention of skin cancer.

Immunologic applications of conditional gene modification technology in the mouse.

Science.gov (United States)

Sharma, Suveena; Zhu, Jinfang

2014-04-02

Since the success of homologous recombination in altering mouse genome and the discovery of Cre-loxP system, the combination of these two breakthroughs has created important applications for studying the immune system in the mouse. Here, we briefly summarize the general principles of this technology and its applications in studying immune cell development and responses; such implications include conditional gene knockout and inducible and/or tissue-specific gene over-expression, as well as lineage fate mapping. We then discuss the pros and cons of a few commonly used Cre-expressing mouse lines for studying lymphocyte development and functions. We also raise several general issues, such as efficiency of gene deletion, leaky activity of Cre, and Cre toxicity, all of which may have profound impacts on data interpretation. Finally, we selectively list some useful links to the Web sites as valuable mouse resources. Copyright © 2014 John Wiley & Sons, Inc.

Effect of low dose radiation on apoptosis in mouse spleen

International Nuclear Information System (INIS)

Chen Dong; Liu Jiamei; Chen Aijun; Liu Shuzheng

1999-01-01

Objective: To study the effect of whole body irradiation (WBI) with different doses of X-ray on apoptosis in mouse spleen. Methods: Time course changes and dose-effect relationship of apoptosis in mouse spleen induced by WBI were observed with transmission electron microscopy (TEM) qualitatively and TUNEL method semi-quantitatively. Results: Many typical apoptotic lymphocytes were found by TEM in mouse spleen after WBI with 2 Gy. No marked alterations of ultrastructure were found following WBI with 0.075 Gy. It was observed by TUNEL that the apoptosis of splenocytes increased after high dose radiation and decreased following low dose radiation (LDR). The dose-effect relationship of radiation-induced apoptosis showed a J-shaped curve. Conclusion: The effect of different doses of ionizing radiation on apoptosis in mouse spleen was distinct. And the decrease of apoptosis after LDR is considered a manifestation of radiation hormesis

Reduction of Cone-Beam CT scan time without compromising the accuracy of the image registration in IGRT

DEFF Research Database (Denmark)

Westberg, Jonas; Jensen, Henrik R; Bertelsen, Anders

2010-01-01

In modern radiotherapy accelerators are equipped with 3D cone-beam CT (CBCT) which is used to verify patient position before treatment. The verification is based on an image registration between the CBCT acquired just before treatment and the CT scan made for the treatment planning. The purpose...... of this study is to minimise the scan time of the CBCT without compromising the accuracy of the image registration in IGRT....

Genomic association for sexual precocity in beef heifers using pre-selection of genes and haplotype reconstruction.

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Luciana Takada

Full Text Available Reproductive traits are of the utmost importance for any livestock farming, but are difficult to measure and to interpret since they are influenced by various factors. The objective of this study was to detect associations between known polymorphisms in candidate genes related to sexual precocity in Nellore heifers, which could be used in breeding programs. Records of 1,689 precocious and non-precocious heifers from farms participating in the Conexão Delta G breeding program were analyzed. A subset of single nucleotide polymorphisms (SNP located in the region of the candidate genes at a distance of up to 5 kb from the boundaries of each gene, were selected from the panel of 777,000 SNPs of the High-Density Bovine SNP BeadChip. Linear mixed models were used for statistical analysis of early heifer pregnancy, relating the trait with isolated SNPs or with haplotype groups. The model included the contemporary group (year and month of birth as fixed effect and parent of the animal (sire effect as random effect. The fastPHASE® and GenomeStudio® were used for reconstruction of the haplotypes and for analysis of linkage disequilibrium based on r2 statistics. A total of 125 candidate genes and 2,024 SNPs forming haplotypes were analyzed. Statistical analysis after Bonferroni correction showed that nine haplotypes exerted a significant effect (p<0.05 on sexual precocity. Four of these haplotypes were located in the Pregnancy-associated plasma protein-A2 gene (PAPP-A2, two in the Estrogen-related receptor gamma gene (ESRRG, and one each in the Pregnancy-associated plasma protein-A gene (PAPP-A, Kell blood group complex subunit-related family (XKR4 and mannose-binding lectin genes (MBL-1 genes. Although the present results indicate that the PAPP-A2, PAPP-A, XKR4, MBL-1 and ESRRG genes influence sexual precocity in Nellore heifers, further studies are needed to evaluate their possible use in breeding programs.

Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer’s disease patients

Science.gov (United States)

Mihelčić, Matej; Šimić, Goran; Babić Leko, Mirjana; Lavrač, Nada; Džeroski, Sašo; Šmuc, Tomislav

2017-01-01

Based on a set of subjects and a collection of attributes obtained from the Alzheimer’s Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer’s disease (AD). We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM) setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A), which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01) were found between PAPP-A and clinical tests: Alzheimer’s Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP) in the non-amyloidogenic pathway, it could

Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.

Science.gov (United States)

Mihelčić, Matej; Šimić, Goran; Babić Leko, Mirjana; Lavrač, Nada; Džeroski, Sašo; Šmuc, Tomislav

2017-01-01

Based on a set of subjects and a collection of attributes obtained from the Alzheimer's Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer's disease (AD). We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM) setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A), which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01) were found between PAPP-A and clinical tests: Alzheimer's Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP) in the non-amyloidogenic pathway, it could be

Screening for aneuploidies by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-13+6 gestational weeks

Directory of Open Access Journals (Sweden)

Karadžov-Orlić Nataša

2012-01-01

Full Text Available Introduction. Aneuploidies are the major cause of perinatal death and early psychophysical disorders. Objective. In this study, we analyzed detection and false-positive rates of screening for aneuploidies in the first trimester by the combination of maternal age, fetal nuchal translucency (NT thickness and maternal serum free beta-human chorionic gonadotrophin (β-hCG, and pregnancy-associated plasma protein-A (PAPP-A at 11-13+6 weeks of gestation, using the appropriate software developed by the Fetal Medicine Foundation. Methods. Our screening study for aneuploidies analyzed 4172 singleton pregnancies from January 2006 to December 2010. The sensitivities and false-positive rates using the combined aneuploidies determination for the risk cut-off of 1:275 were evaluated. Results. In the trisomy 21 pregnancies, the fetal NT was higher than 95th centile, in 72.8%, serum free b-hCG concentration it was above the 95th centile in 55% and serum PAPP-A was below the 5th centile in 47% of the cases. In the trisomy 18 and 13, the fetal NT was above 95th centile in 66.6% and 44.4% of the cases, respectively. The serum free b-hCG concentration was above the 95th centile in 0 and 10%, but serum PAPP-A was below 5th centile in 80.9% and 88.8% of pregnancies. In the trisomy 21 pregnancies the median free beta-hCG was 2.3 MoM and the median PAPP-A was 0.45 MoM. Chromosomal abnormalities were detected in 169 fetuses: trisomy 21 (97, Turner syndrome (19, trisomy 18 (28, trisomy 13 (11 and others (14. Detection rate of combined screening for aneuploides were 86.0% with false positive rate of 5.3% (mean age 33±4.9 years, >35 years in 35% of pregnancies. Conclusion. Our study suggests that the strategy of first-trimester combined screening of biochemical values and ultrasonographic parameters at 12 gestational weeks identifies higher percentage of aneuploidies with a lower false-positive rate than a single parameter strategy.

Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.

Directory of Open Access Journals (Sweden)

Matej Mihelčić

Full Text Available Based on a set of subjects and a collection of attributes obtained from the Alzheimer's Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer's disease (AD. We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A, which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01 were found between PAPP-A and clinical tests: Alzheimer's Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP in the non-amyloidogenic pathway

Using the Scroll Wheel on a Wireless Mouse as a Motion Sensor

Science.gov (United States)

Taylor, Richard S.; Wilson, William R.

2010-01-01

Since its inception in the mid-80s, the computer mouse has undergone several design changes. As the mouse has evolved, physicists have found new ways to utilize it as a motion sensor. For example, the rollers in a mechanical mouse have been used as pulleys to study the motion of a magnet moving through a copper tube as a quantitative demonstration…

Experimental photoallergic contact dermatitis: a mouse model

International Nuclear Information System (INIS)

Maguire, H.C. Jr.; Kaidbey, K.

1982-01-01

We have induced photoallergic contact dermatitis in mice to 3,3',4',5 tetrachlorosalicylanilide (TCSA), chlorpromazine and 6-methylcoumarin. These compounds are known to produce photoallergic contact dermatitis in humans. The photoallergic contact dermatitis reaction in the mouse is immunologically specific viz. mice photosensitized to TCSA react, by photochallenge, to that compound and not to chlorpromazine, and conversely. The reaction requires UVA at both sensitization and challenge. It appears to be T-cell mediated in that it can be passively transferred to syngeneic mice by lymph node cells from actively sensitized mice, the histology of the reactions resembles that of classic allergic contact dermatitis in mice, challenge reactions are seen at 24 but not at 4 hr, and photoallergic contact dermatitis can be induced in B-cell deficient mice. The availability of a mouse model for the study of photo-ACD will facilitate the identification of pertinent control mechanisms and may aid in the management of the disease. It is likely that a bioassay for photoallergens of humans can be based on this mouse model

Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test sensitivity

NARCIS (Netherlands)

Matsui, E. C.; Diette, G. B.; Krop, E. J. M.; Aalberse, R. C.; Smith, A. L.; Eggleston, P. A.

2006-01-01

High serum levels of cat-specific IgG and IgG4 are associated with protection against allergic sensitization to cat, but whether this association applies to other animal allergens remains unclear. To determine if high levels of mouse-specific IgG and IgG4 are associated with a decreased risk of

Testing the effect of time pressure on asymmetric dominance and compromise decoys in choice

Directory of Open Access Journals (Sweden)

Jonathan Pettibone

2012-07-01

Full Text Available Dynamic, connectionist models of decision making, such as decision field theory (Roe, Busemeyer, and Townsend, 2001, propose that the effect of context on choice arises from a series of pairwise comparisons between attributes of alternatives across time. As such, they predict that limiting the amount of time to make a decision should decrease rather than increase the size of contextual effects. This prediction was tested across four levels of time pressure on both the asymmetric dominance (Huber, Payne, and Puto, 1982 and compromise (Simonson, 1989 decoy effects in choice. Overall, results supported this prediction, with both types of decoy effects found to be larger as time pressure decreased.

Cholangiocarcinoma

Science.gov (United States)

... of the ducts that carries bile from the liver to the small intestine. ... Updated December 9, 2015. www.cancer.gov/types/liver/hp/bile-duct-treatment-pdq . Accessed July 8, 2016. Zani S, Pappas ...

Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx(-/-) ) and the 129sv wild type mouse

DEFF Research Database (Denmark)

Rovsing, Louise; Rath, Martin Fredensborg; Møller, Morten

2013-01-01

circadian AVP-rhythm. We have in this study of the brown 129sv mouse and the visual blind cone-rod homeobox gene knock out mouse (Crx(-/-) ) with degeneration of the retinal rods and cones, but a preserved non-image forming optic system, studied the temporal Avp-expression in both the neurosecretory...

Low-cost computer mouse for the elderly or disabled in Taiwan.

Science.gov (United States)

Chen, C-C; Chen, W-L; Chen, B-N; Shih, Y-Y; Lai, J-S; Chen, Y-L

2014-01-01

A mouse is an important communication interface between a human and a computer, but it is still difficult to use for the elderly or disabled. To develop a low-cost computer mouse auxiliary tool. The principal structure of the low-cost mouse auxiliary tool is the IR (infrared ray) array module and the Wii icon sensor module, which combine with reflective tape and the SQL Server database. This has several benefits including cheap hardware cost, fluent control, prompt response, adaptive adjustment and portability. Also, it carries the game module with the function of training and evaluation; to the trainee, it is really helpful to upgrade the sensitivity of consciousness/sense and the centralization of attention. The intervention phase/maintenance phase, with regard to clicking accuracy and use of time, p value (p< 0.05) reach the level of significance. The development of the low cost adaptive computer mouse auxiliary tool was completed during the study and was also verified as having the characteristics of low cost, easy operation and the adaptability. To patients with physical disabilities, if they have independent control action parts of their limbs, the mouse auxiliary tool is suitable for them to use, i.e. the user only needs to paste the reflective tape by the independent control action parts of the body to operate the mouse auxiliary tool.

The value of predicting restriction of fetal growth and compromise of its wellbeing: Systematic quantitative overviews (meta-analysis) of test accuracy literature.

Science.gov (United States)

Morris, Rachel K; Khan, Khalid S; Coomarasamy, Aravinthan; Robson, Stephen C; Kleijnen, Jos

2007-03-08

Restriction of fetal growth and compromise of fetal wellbeing remain significant causes of perinatal death and childhood disability. At present, there is a lack of scientific consensus about the best strategies for predicting these conditions before birth. Therefore, there is uncertainty about the best management of pregnant women who might have a growth restricted baby. This is likely to be due to a dearth of clear collated information from individual research studies drawn from different sources on this subject. A series of systematic reviews and meta-analyses will be undertaken to determine, among pregnant women, the accuracy of various tests to predict and/or diagnose fetal growth restriction and compromise of fetal wellbeing. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Independent reviewers will select studies, extract data and assess study quality according to established criteria. Language restrictions will not be applied. Data synthesis will involve meta-analysis (where appropriate), exploration of heterogeneity and publication bias. The project will collate and synthesise the available evidence regarding the value of the tests for predicting restriction of fetal growth and compromise of fetal wellbeing. The systematic overviews will assess the quality of the available evidence, estimate the magnitude of potential benefits, identify those tests with good predictive value and help formulate practice recommendations.

Olfaction in three genetic and two MPTP-induced Parkinson's disease mouse models.

Directory of Open Access Journals (Sweden)

Stefan Kurtenbach

Full Text Available Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson's disease (PD mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs and an olfactory behavior test (cookie-finding test. We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.

Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

Science.gov (United States)

Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

2014-02-01

Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

Development of the mouse cochlea database (MCD).

Science.gov (United States)

Santi, Peter A; Rapson, Ian; Voie, Arne

2008-09-01

The mouse cochlea database (MCD) provides an interactive, image database of the mouse cochlea for learning its anatomy and data mining of its resources. The MCD website is hosted on a centrally maintained, high-speed server at the following URL: (http://mousecochlea.umn.edu). The MCD contains two types of image resources, serial 2D image stacks and 3D reconstructions of cochlear structures. Complete image stacks of the cochlea from two different mouse strains were obtained using orthogonal plane fluorescence optical microscopy (OPFOS). 2D images of the cochlea are presented on the MCD website as: viewable images within a stack, 2D atlas of the cochlea, orthogonal sections, and direct volume renderings combined with isosurface reconstructions. In order to assess cochlear structures quantitatively, "true" cross-sections of the scala media along the length of the basilar membrane were generated by virtual resectioning of a cochlea orthogonal to a cochlear structure, such as the centroid of the basilar membrane or the scala media. 3D images are presented on the MCD website as: direct volume renderings, movies, interactive QuickTime VRs, flythrough, and isosurface 3D reconstructions of different cochlear structures. 3D computer models can also be used for solid model fabrication by rapid prototyping and models from different cochleas can be combined to produce an average 3D model. The MCD is the first comprehensive image resource on the mouse cochlea and is a new paradigm for understanding the anatomy of the cochlea, and establishing morphometric parameters of cochlear structures in normal and mutant mice.

Generation of Knock-in Mouse by Genome Editing.

Science.gov (United States)

Fujii, Wataru

2017-01-01

Knock-in mice are useful for evaluating endogenous gene expressions and functions in vivo. Instead of the conventional gene-targeting method using embryonic stem cells, an exogenous DNA sequence can be inserted into the target locus in the zygote using genome editing technology. In this chapter, I describe the generation of epitope-tagged mice using engineered endonuclease and single-stranded oligodeoxynucleotide through the mouse zygote as an example of how to generate a knock-in mouse by genome editing.

Genotoxicity of 3-nitrobenzanthrone and 3-aminobenzanthrone in MutaMouse and lung epithelial cells derived from MutaMouse.

Science.gov (United States)

Arlt, Volker M; Gingerich, John; Schmeiser, Heinz H; Phillips, David H; Douglas, George R; White, Paul A

2008-11-01

FE1 lung epithelial cells derived from MutaMouse are a new model system to provide in vitro mutagenicity data with the potential to predict the outcome of an in vivo MutaMouse test. 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and urban air pollution. We investigated the mutagenicity and DNA binding of 3-NBA and its main metabolite 3-aminobenzanthrone (3-ABA) in vitro and in vivo in the MutaMouse assay. Mice were treated with 3-NBA or 3-ABA (0, 2 or 5 mg/kg body weight/day) by gavage for 28 days and 28 days later lacZ mutant frequency (MF) was determined in liver, lung and bone marrow. For both compounds, dose-related increases in MF were seen in liver and bone marrow, but not in lung; mutagenic activity was approximately 2-fold lower for 3-ABA than for 3-NBA. With 3-NBA, highest DNA adduct levels (measured by (32)P-post-labelling) were found in liver (approximately 230 adducts per 10(8) nucleotides) with levels 20- to 40-fold lower in bone marrow and lung. With 3-ABA, DNA adduct levels were again highest in the liver, but approximately 4-fold lower than for 3-NBA. FE1 cells were exposed to up to 10 microg/ml 3-NBA or 3-ABA for 6 h with or without exogenous activation (S9) and harvested after 3 days. For 3-NBA, there was a dose-related increase in MF both with and without S9 mix, which was >10 times higher than observed in vivo. At the highest concentration of 3-ABA (10 microg/ml), we found only around a 2-fold increase in MF relative to controls. DNA adduct formation in FE1 cells was dose-dependent for both compounds, but 10- to 20-fold higher for 3-NBA compared to 3-ABA. Collectively, our data indicate that MutaMouse FE1 cells are well suited for cost-effective testing of suspected mutagens with different metabolic activation pathways as a guide for subsequent in vivo MutaMouse testing.

Expression of HSG is essential for mouse blastocyst formation

International Nuclear Information System (INIS)

Jiang Guangjian; Pan Lei; Huang Xiuying; Han Mei; Wen Jinkun; Sun Fangzhen

2005-01-01

It has been shown recently that hyperplasia suppressor gene (HSG) is a powerful regulator for cell proliferation and has a critical role in mitochondrial fusion in many cells. However, little is known about its expression, localization, and function during oocyte maturation and early embryogenesis. In this study, with indirect immunofluorescent staining and Western blotting, we found that HSG was expressed in mouse oocytes and preimplantation embryos which primarily exhibited a submembrane distribution pattern in the cytoplasm. Moreover, HSG mainly associated with β-tubulin during oocyte maturation and early embryonic development. When mouse zygotes were injected with HSG antisense plasmid and cultured in vitro, their capacity to form blastocysts was severely impaired. Our results indicate that HSG plays an essential role in mouse preimplantation development

Genome-wide identification of estrogen receptor alpha-binding sites in mouse liver

DEFF Research Database (Denmark)

Gao, Hui; Fält, Susann; Sandelin, Albin

2007-01-01

We report the genome-wide identification of estrogen receptor alpha (ERalpha)-binding regions in mouse liver using a combination of chromatin immunoprecipitation and tiled microarrays that cover all nonrepetitive sequences in the mouse genome. This analysis identified 5568 ERalpha-binding regions...... genes. The majority of ERalpha-binding regions lie in regions that are evolutionarily conserved between human and mouse. Motif-finding algorithms identified the estrogen response element, and variants thereof, together with binding sites for activator protein 1, basic-helix-loop-helix proteins, ETS...... signaling in mouse liver, by characterizing the first step in this signaling cascade, the binding of ERalpha to DNA in intact chromatin....

New Insights on the Morphology of Adult Mouse Penis1

Science.gov (United States)

Rodriguez, Esequiel; Weiss, Dana A.; Yang, Jennifer H.; Menshenina, Julia; Ferretti, Max; Cunha, Tristan J.; Barcellos, Dale; Chan, Lok Yun; Risbridger, Gail; Cunha, Gerald R.; Baskin, Laurence S.

2011-01-01

ABSTRACT The adult mouse penis represents the end point of masculine sex differentiation of the embryonic genital tubercle and contains bone, cartilage, the urethra, erectile bodies, several types of epithelium, and many individual cell types arrayed into specific anatomical structures. Using contemporary high-resolution imaging techniques, we sought to provide new insights to the current description of adult mouse penile morphology to enable understanding of penile abnormalities, including hypospadias. Examination of serial transverse and longitudinal sections, scanning electron microscopy, and three-dimensional (3D) reconstruction provided a new appreciation of the individual structures in the adult mouse penis and their 3D interrelationships. In so doing, we discovered novel paired erectile bodies, the male urogenital mating protuberance (MUMP), and more accurately described the urethral meatus. These morphological observations were quantified by morphometric analysis and now provide accurate morphological end points of sex differentiation of mouse penis that will be the foundation of future studies to identify normal and abnormal penile development. PMID:21918128

Comparison of the metabolic activation of environmental carcinogens in mouse embryonic stem cells and mouse embryonic fibroblasts

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Krais, Annette M.; Mühlbauer, Karl-Rudolf; Kucab, Jill E.; Chinbuah, Helena; Cornelius, Michael G.; Wei, Quan-Xiang; Hollstein, Monica; Phillips, David H.; Arlt, Volker M.; Schmeiser, Heinz H.

2015-01-01

We compared mouse embryonic stem (ES) cells and fibroblasts (MEFs) for their ability to metabolically activate the environmental carcinogens benzo[a]pyrene (BaP), 3-nitrobenzanthrone (3-NBA) and aristolochic acid I (AAI), measuring DNA adduct formation by 32P-postlabelling and expression of xenobiotic-metabolism genes by quantitative real-time PCR. At 2 μM, BaP induced Cyp1a1 expression in MEFs to a much greater extent than in ES cells and formed 45 times more adducts. Nqo1 mRNA expression was increased by 3-NBA in both cell types but induction was higher in MEFs, as was adduct formation. For AAI, DNA binding was over 450 times higher in MEFs than in ES cells, although Nqo1 and Cyp1a1 transcriptional levels did not explain this difference. We found higher global methylation of DNA in ES cells than in MEFs, which suggests higher chromatin density and lower accessibility of the DNA to DNA damaging agents in ES cells. However, AAI treatment did not alter DNA methylation. Thus mouse ES cells and MEFs have the metabolic competence to activate a number of environmental carcinogens, but MEFs have lower global DNA methylation and higher metabolic capacity than mouse ES cells. PMID:25230394

Regenerative Needs Following Alveolar Ridge Preservation Procedures in Compromised and Noncompromised Extraction Sockets: A Cone Beam Computed Tomography Study.

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Koutouzis, Theofilos; Lipton, David

2016-01-01

The aim of this study was to evaluate the necessity for additional regenerative procedures following healing of compromised and noncompromised extraction sockets with alveolar ridge preservation procedures through the use of virtual implant imaging software. The cohort was comprised of 87 consecutive patients subjected to a single maxillary tooth extraction with an alveolar ridge preservation procedure for subsequent implant placement. Patients were divided into two main groups based on the integrity of the buccal bone plate following teeth extraction. Patients in the compromised socket (CS) group (n = 52) had partial or complete buccal bone plate loss, and patients in the noncompromised socket (NCS) group (n = 35) exhibited no bone loss of their socket walls following tooth extraction. Following 4 to 6 months of healing, all patients had a cone beam computed tomography (CBCT) study. Root-formed implants were placed virtually in an ideal prosthetic position. The number of implants per group and location (anterior, premolar, molar) exhibiting exposed buccal implant surface was calculated. In the CS group, 5 out of 19 anterior implants (26.3%), 4 out of 14 premolar implants (28.5%), and 7 out of 19 molar implants (36.8%) had exposed buccal surfaces. In the NCS group, 4 out of 9 anterior implants (44.4%), 2 out of 9 premolar implants (22.2%), and 4 out of 17 molar implants (23.5%) had exposed buccal surfaces. There were no statistically significant differences for intragroup and intergroup comparisons (χ² test, P > .05). This study failed to find statistically significant differences in the frequency of implants with exposed buccal surfaces placed virtually, following treatment of compromised and noncompromised sockets. A high proportion (22% to 44%) of sites had implants that potentially needed additional regenerative procedures.

Fracture resistance of structurally compromised and normal endodontically treated teeth restored with different post systems: An in vitro study

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Vajihesadat Mortazavi

2012-01-01

Full Text Available Background: With the aim of developing methods that could increase the fracture resistance of structurally compromised endodontically treated teeth, this study was conducted to compare the effect of three esthetic post systems on the fracture resistance and failure modes of structurally compromised and normal roots. Materials and Methods: Forty five extracted and endodontically treated maxillary central teeth were assigned to 5 experimental groups (n=9. In two groups, the post spaces were prepared with the corresponding drills of the post systems to be restored with double taper light posts (DT.Light-Post (group DT.N and zirconia posts (Cosmopost (group Zr.N. In other 3 groups thin wall canals were simulated to be restored with Double taper Light posts (DT.W, double taper Light posts and Ribbond fibers (DT+R.W and Zirconia posts (Zr.W. After access cavity restoration and thermocycling, compressive load was applied and the fracture strength values and failure modes were evaluated. Data were analyzed using two-way ANOVA, Tukey and Fisher exact tests (P<0.05. Results: The mean failure loads (N were 678.56, 638.22, 732.44, 603.44 and 573.67 for groups DT.N, Zr.N, DT.W, DT+R.W and Zr.w respectively. Group DT+R.W exhibited significantly higher resistance to fracture compared to groups Zr.N, DT.W and Zr.w (P<0.05. A significant difference was detected between groups DT.N and Zr.W (P=0.027. Zirconia posts showed significantly higher root fracture compared to fiber posts (P=0.004. Conclusion: The structurally compromised teeth restored with double taper light posts and Ribbond fibers showed the most fracture resistance and their strengths were comparable to those of normal roots restored with double taper light posts. More desirable fracture patterns were observed in teeth restored with fiber posts.

Protein catabolism in pregnant snakes (Epicrates cenchria maurus Boidae) compromises musculature and performance after reproduction.

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Lourdais, O; Brischoux, F; DeNardo, D; Shine, R

2004-07-01

In many species the high energetic demands of reproduction induce a negative energy balance, and thus females must rely on tissue catabolism to complete the reproductive process. Previous works have shown that both fat and protein are energy resources during prolonged fasting in vertebrates. While many ecological studies on energy costs of reproduction have focused on variations in fat stores, the impact of protein investment on the female has not been thoroughly investigated. Notably, as there is no specialized storage form for proteins, intense catabolism is likely to entail structural (musculature) loss that may compromise maternal physical performance after reproduction. Measurements on captive rainbow boas ( Epicrates cenchria maurus) confirm that reproducing females undergo significant protein catabolism (as indicated by elevated plasma uric acid levels) and show considerable musculature loss during gestation (as detected by reduced width of the epaxial muscles). Protein mobilization entailed a significant functional loss that was illustrated by decrements in tests of strength and constriction after parturition. In wild situations, such effects are likely to decrease the snakes' ability to forage and apprehend prey. Hence, the time period needed to recover from reproduction can be extended not only because the female must compensate losses of both fat stores and functional muscle, but also because the ability to do so may be compromised. Performance alteration is likely to be of equal or greater importance than reduced energy stores in the physiological mediation of elevated post-reproduction mortality rates and infrequent reproductive bouts (e.g. biannual or triannual), two common ecological traits of female snakes.

Conjoined lumbosacral nerve roots compromised by disk herniation: sagittal shoulder sign for the preoperative diagnosis

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Kang, Chang Ho [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea); Korea University College of Medicine, Department of Radiology, Anam Hospital, Seoul (Korea); Shin, Myung Jin; Kim, Sung Moon; Lee, Sang Hoon; Kim, Hee Kyung; Ryu, Jeong Ah [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea); Lee, Choon-Sung [University of Ulsan College of Medicine, Asan Medical Center, Department of Orthopedic Surgery, Seoul (Korea); Kim, Sam Soo [Kangwon National University College of Medicine, Department of Radiology, Kangwon (Korea)

2008-03-15

The objective was to determine the importance of the ''sagittal shoulder sign'' on magnetic resonance (MR) images for the diagnosis of conjoined lumbosacral nerve roots (CLNR) that are compromised by herniated disks. Magnetic resonance images of 11 patients (6 men and 5 women; age range, 25-71 years; average age, 48.7 years) with surgically proven CLNR, which was compromised by herniated disks, were retrospectively evaluated by two musculoskeletal radiologists. MR images were evaluated for the presence or absence of the sagittal shoulder sign - a vertical structure connecting two consecutive nerve roots and overlying disk on the sagittal MR images. The radiologists noted the type of accompanying disk herniation and bony spinal canal changes, as well as other characteristic MR features of CLNR, the common passage of two consecutive nerve roots through the neural foramen on axial MR images. The sagittal shoulder sign was identified with a mean frequency of 90.9% by the two observers (in 10 of 11 patients). The common passage of two consecutive nerve roots through the neural foramen on axial MR images was identified with a mean frequency of 59.1% (in 7 and 6 out of 11 patients, by observers 1 and 2, respectively). Good interobserver agreement for the sagittal shoulder sign was present (k = 0.621, p < 0.05). Observation of the sagittal shoulder sign may prove helpful for diagnosing CLNR in patients with disk herniation. In particular, this sign appears to be useful when there is no evidence of CLNR on axial MR images. (orig.)

Absence of Rybp Compromises Neural Differentiation of Embryonic Stem Cells

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Gergo Kovacs

2016-01-01

Full Text Available Rybp (Ring1 and Yy1 Binding Protein is a transcriptional regulator and member of the noncanonical polycomb repressive complex 1 with essential role in early embryonic development. We have previously described that alteration of Rybp dosage in mouse models induced striking neural tube defects (NTDs, exencephaly, and disorganized neurocortex. In this study we further investigated the role of Rybp in neural differentiation by utilising wild type (rybp+/+ and rybp null mutant (rybp-/- embryonic stem cells (ESCs and tried to uncover underlying molecular events that are responsible for the observed phenotypic changes. We found that rybp null mutant ESCs formed less matured neurons, astrocytes, and oligodendrocytes from existing progenitors than wild type cells. Furthermore, lack of rybp coincided with altered gene expression of key neural markers including Pax6 and Plagl1 pinpointing a possible transcriptional circuit among these genes.

Mechanisms of Hyperhomocysteinemia Induced Skeletal Muscle Myopathy after Ischemia in the CBS−/+ Mouse Model

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Sudhakar Veeranki

2015-01-01

Full Text Available Although hyperhomocysteinemia (HHcy elicits lower than normal body weights and skeletal muscle weakness, the mechanisms remain unclear. Despite the fact that HHcy-mediated enhancement in ROS and consequent damage to regulators of different cellular processes is relatively well established in other organs, the nature of such events is unknown in skeletal muscles. Previously, we reported that HHcy attenuation of PGC-1α and HIF-1α levels enhanced the likelihood of muscle atrophy and declined function after ischemia. In the current study, we examined muscle levels of homocysteine (Hcy metabolizing enzymes, anti-oxidant capacity and focused on protein modifications that might compromise PGC-1α function during ischemic angiogenesis. Although skeletal muscles express the key enzyme (MTHFR that participates in re-methylation of Hcy into methionine, lack of trans-sulfuration enzymes (CBS and CSE make skeletal muscles more susceptible to the HHcy-induced myopathy. Our study indicates that elevated Hcy levels in the CBS−/+ mouse skeletal muscles caused diminished anti-oxidant capacity and contributed to enhanced total protein as well as PGC-1α specific nitrotyrosylation after ischemia. Furthermore, in the presence of NO donor SNP, either homocysteine (Hcy or its cyclized version, Hcy thiolactone, not only increased PGC-1α specific protein nitrotyrosylation but also reduced its association with PPARγ in C2C12 cells. Altogether these results suggest that HHcy exerts its myopathic effects via reduction of the PGC-1/PPARγ axis after ischemia.